ArchiveTo investigate the clinical efficacy and safety of budesonide/formoterol/glycopyrronium inhalation aerosol combined with bacterial lysate capsules in the treatment of patients with moderate-to-severe stable chronic obstructive pulmonary disease (COPD) complicated with bronchiectasis.
The patients with moderate-to-severe stable COPD complicated with bronchiectasis admitted to our hospital were divided into control group and treatment group based on their treatment regimens. Patients in control group were administered budesonide/formoterol/glycopyrronium inhalation aerosol (1 inhalation per time, twice daily), while treatment group additionally received oral bacterial lysate capsules (7 mg once daily on an empty stomach, 10 consecutive days followed by a 20-day break as one cycle). Patients in both groups were treated for 6 months. Differences in clinical efficacy, acute exacerbation, airway inflammation indicators, immune function indicators and pulmonary function were compared, and safety evaluation was performed.
A total of 116 participants were enrolled, with 57 cases in control group and 59 cases in treatment group. The treatment group achieved an overall effective rate of 91.53% (54 cases/59 cases), which was statistically significantly higher to 77.19% (44 cases/57 cases) observed in control group(P<0.05). After treatment, the number of acute exacerbations in treatment and control group were (1.53±0.50) and (1.74±0.48) episodes, respectively; the duration of acute exacerbations were (9.80±2.75) and (11.16±3.06) days, respectively; the soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) levels were (33.89±7.47) and (38.34±8.35) pg·mL-1, respectively; the endothelin (ET) levels were (27.75±4.68) and (30.25±6.12) pg·mL-1, respectively; the soluble urokinase-type plasminogen activator receptor (suPAR) levels were (244.01±44.13) and (264.13±52.27) pg·mL-1, respectively; the immunoglobulin (Ig) A levels were (2.97±0.51) and (2.75±0.52) g·L-1, respectively; the IgG levels were (12.05±2.55) and (10.89±2.34) g·L-1, respectively; the IgM levels were (1.95±0.40) and (1.76±0.32) g·L-1, respectively; the IgE levels were (87.67±10.26) and (93.61±13.58) IU·mL-1, respectively; the diffusing capacity for carbon monoxide (DLCO) were (67.80±8.43)% and (64.38±7.81)%, respectively; the residual volume/total lung capacity ratio (RV/TLC) were (41.57±4.25)% and (43.61±4.11)%, respectively; the maximum minute ventilation during exercise (VEmax) were (54.24±5.61) and (51.96±5.58) L·min-1, respectively. Intergroup comparisons revealed statistically significant differences in the aforementioned indicators (P<0.05, P<0.01). Adverse drug reactions in treatment group included nausea, dizziness, mild elevated transaminase, dry mouth and hoarseness; those in control group included nausea and retching, rash, pharyngeal discomfort and elevated bilirubin. The total incidence of adverse reactions in treatment group and control group were 11.86% (7 cases/59 cases) and 8.77% (5 cases/57 cases), respectively, with no statistically significant difference (P>0.05).
Budesonide/formoterol/glycopyrronium inhalation aerosol combined with bacterial lysate capsules can reduce the risk of acute exacerbations and effectively improve pulmonary function in patients with moderate-to-severe stable COPD complicated with bronchiectasis. The underlying mechanism may be associated with the alleviation of airway inflammation and the enhancement of immune function
To explore the clinical therapeutic effect of inclisiran injection combined with rosuvastatin tablets in the treatment of patients with extremely high-risk atherosclerotic cardiovascular disease (ASCVD).
The patients with extremely high-risk ASCVD were divided into the treatment group and the control group according to the actual clinical medication regimens they received. The control group was given rosuvastatin calcium tablets 10 mg, po, qd, while the treatment group was given inclisiran sodium injection 284 mg, ih, for the first time, and 284 mg, ih, again after 3 months on the basis of control group. The treatment duration for both groups was 6 months. The clinical efficacy, lipid profile, low-density lipoprotein cholesterol (LDL-C) target attainment rate, proprotein convertase subtilisin/kexin type 9 (PCSK9) levels, cardiac function, plaque stability, safety evaluation, and cardiovascular benefits were compared between the two groups.
A total of 98 patients were enrolled, with 51 in the control group and 47 in the treatment group. After treatment, the overall response rates in the control group and the treatment group and were 68.63% (35 cases/51 cases) and 87.23% (41 cases/47 cases), respectively; the LDL-C levels were (1.42±0.27) and (1.26±0.22) mmol·L-1, respectively; the LDL-C goal attainment rates at 3 months were 41.18% (21 cases/51 cases) and 61.70% (29 cases/47 cases), respectively; LDL-C goal attainment rates at 6 months were 52.94% (27 cases/51 cases) and 74.47% (35 cases/47 cases), respectively; PCSK9 levels at 3 months were (313.66±41.35) and (295.63±39.43) ng·mL-1, respectively; PCSK9 levels at 6 months were (203.71±33.39) and (184.29±31.54) ng·mL-1, respectively; carotid intima-media thickness were (1.01±0.27) and (0.91±0.11) mm, respectively; plaque areas were (18.52±3.76) and (16.31±3.63) mm2, respectively; proportions of unstable plaques were 39.22% (20 cases/51cases) and 19.15% (9 cases/47 cases), respectively; high-density lipoprotein cholesterol (HDL-C) levels were (1.46±0.55) and (1.47±0.33) mmol·L-1, respectively; apolipoprotein A (ApoA) levels were (1.11±0.25) and (1.10±0.29) g·L-1, respectively. Except HDL-C level and ApoA level, comparisons of other indexes between the two groups showed statistically significant differences (P<0.05, P<0.01). No significant difference in the incidence of adverse events was observed between the control group (5.88%, 3 cases/51 cases) and treatment group (8.51%, 4 cases/47 cases) (P>0.05).
The combination of inclisiran injection and rosuvastatin tablet is effective in the treatment of extremely high-risk ASCVD, significantly improving the total effective rate and the early and sustained LDL-C target attainment rate, and more effectively reducing LDL-C levels and stabilizing plaques. The mechanism may be related to significantly inhibiting PCSK9 levels and further enhancing lipid-lowering and plaque-stabilizing effects.
To observe the clinical efficacy and safety of allylestrenol tablet combined with ritodrine hydrochloride tablet in the treatment of patients with gestational diabetes mellitus and threatened premature labor.
The patients with gestational diabetes mellitus threatened premature delivery were divided into treatment group and control group according to the treatment method. The control group received conventional treatment+ritodrine hydrochloride injection (100 mg, intravenous drip, continuous infusion after stopping uterine contraction for 12 h)+ritodrine hydrochloride tablets (10 mg, oral, q2 h on the first day, q4 h on the second day, q6 h on the day 3-7); on the basis of control group, the treatment group was added with allylestradiol tablets (5 mg, orally, 3-4 times a day). The course of treatment for both groups was 7 days. The clinical efficacy, blood glucose-related indicators, inflammatory-related indicators, pregnancy outcomes and neonatal outcomes were compared between the two groups, and safety was evaluated.
A total of 98 cases were included in this study, including 50 cases in control group and 48 cases in treatment group. After treatment, the total clinical effective rates in treatment group and control group were 93.75% (45 cases/48 cases) and 80.00% (40 cases/50 cases), respectively, with statistically significant difference (P<0.05). After treatment, the fasting blood glucose (FBG) levels in treatment group and control group were (5.26±0.11) and (5.28±0.17) mmol·L-1, respectively; the 2-hour postprandial blood glucose (2 h PG) levels were (6.35±0.25) and (6.42±0.24) mmol·L-1, respectively; interleukin-6 (IL-6) levels were (6.49±1.06) and (7.13±1.43) pg·mL-1, respectively; IL-8 levels were (12.59±2.17) and (13.94±2.60) pg·mL-1, respectively; IL-10 levels were (12.30±2.49) and (11.09±1.95) pg·mL-1, respectively; prolonged pregnancy duration were (11.67±3.84) and (9.82±2.96) days, respectively; the proportions of vaginal delivery was 66.67% (32 cases/48 cases) and 46.00% (23 cases/50 cases), respectively; postpartum blood loss levels were (185.21±21.49) and (196.58±24.75) mL, respectively; the 1-minute Apgar scores of newborns were (9.04±0.20) and (8.86±0.35) points, respectively; the live birth rates were 97.92% (47 cases/48 cases) and 90.00% (45 cases/50 cases), respectively; the incidences of neonatal respiratory distress syndrome (NRDS) were 4.17% (2 cases/48 cases) and 20.00% (10 cases/50 cases), respectively; the incidences of apnea in premature infants were 4.17% (2 cases/48 cases) and 18.00% (9 cases/50 cases), respectively; the incidences of hematosepsis were 6.25% (3 cases/48 cases) and 14.00% (7 cases/50 cases), respectively; the incidences of neonatal pneumonia were 2.08% (1 cases/48 cases) and 6.00% (3 cases/50 cases), respectively. Except for FBG, 2 h PG, live birth rate, incidences of neonatal sepsis and neonatal pneumonia, the differences in the above indicators between treatment group and control group were all statistically significant (P<0.05, P<0.01). The adverse drug reactions in treatment group were primarily palpitations, nausea and vomiting, and headache, while those in control group mainly included palpitations, constipation, nausea and vomiting. The incidences of adverse drug reactions in treatment group and control group were 6.25% (3 cases/48 cases) and 8.00% (4 cases/50 cases), respectively, with no statistically significant difference (P>0.05).
Allylestrenol tablet combined with ritodrine hydrochloride tablet can effectively treat threatened preterm labor in gestational diabetes mellitus, significantly prolong gestational age, improve inflammatory responses, and optimize pregnancy and neonatal outcomes without increasing the risk of adverse drug reactions.
To observe the efficacy of polyethylene glycol recombinant human growth hormone (PEG-rhGH) injection combined with vitamin D drops and lysine hydrochloride and calcium hydrogen phosphate granules in the treatment of children with idiopathic short stature (ISS).
Based on treatment regimen, children with ISS were categorized into treatment and control groups. Both groups received basic treatment of vitamin D drops (400-800 U daily) and lysine hydrochloride and calcium hydrogen phosphate granules (5 g, twice daily). The control group was given human somatropin injection at a dose of 0.10-0.20 IU·kg-1·d-1 by subcutaneous injection, while the treatment group was given PEG-rhGH injection at a dose of 0.20-0.40 mg·kg-1·w-1 by subcutaneous injection. Both groups received continuous medication for 12 months. The clinical efficacy, evaluation indicators of GH-insulin-like growth factor (IGF) axis function, bone metabolism indicators and safety were compared between the two groups.
The study enrolled 79 cases, comprising 41 cases in the treatment group and 38 cases in the control group. After treatment, the effective rates of the treatment group and the control group were 95.12% (39 cases/41 cases) and 92.11% (35 cases/38 cases), respectively, with no statistically significant difference (P>0.05). After treatment, the levels of insulin-like growth factor-1/insulin-like growth factor binding protein-3 (IGF-1/IGFBP-3) in the treatment group and the control group were 0.08±0.02 and 0.07±0.02, respectively; the levels of liver-expressed antimicrobial peptide-2 (LEAP-2) were (1 395.69±187.26) pg·mL-1 and (1 487.58±195.48) pg·mL-1, respectively; the levels of osteocalcin (BGP) were (22.18±3.67) and (20.43±3.48) μg·L-1, respectively; procollagen I N-terminal peptide (PINP) were (602.68±63.41) and (574.08±61.83) μg·L-1, respectively; bone-specific alkaline phosphatase (BALP) was (192.68±23.64) and (203.41±22.18) U·L-1, respectively; vitamin D (Vit-D) were (20.39±3.47) and (18.65±3.62) ng·mL-1, respectively. Both indicators showed statistically significant differences between the two groups (all P<0.05). The incidences of adverse drug reactions of treatment group and the control group were 7.32% (3 cases/41 cases) and 10.53% (4 cases/38 case), with no statistically significant difference (P>0.05).
PEG-rhGH injection at a dose of 0.20-0.40 mg·kg-1·w-1 combined with vitamin D drops and lysine hydrochlodride and calcium hydrogen phosphate granules in the treatment of children with ISS can ensure efficacy and safety, while potentially achieving better long-term growth improvement effects. It can also improve the function of the GH-IGF axis and bone metabolism levels.
To investigate the clinical efficacy and safety of medroxyprogesterone acetate tablets in the treatment of ovulatory dysfunction-related abnormal uterine bleeding.
Patients with ovulatory dysfunction-related abnormal uterine bleeding were allocated into control group and treatment group based on their treatment regimen. The control group received dydrogesterone tablets (10 mg, twice daily) for 10 days starting from the 14th day of the menstrual cycle. The treatment group received medroxyprogesterone acetate tablets (2 mg, three times daily) for 10 days, also starting from the 14th day of the menstrual cycle. Both groups were treated for three menstrual cycles. The clinical efficacy, recovery indicators, angiogenesis and inflammatory response markers, and safety were compared between the two groups.
A total of 135 cases were included in the analysis, with 64 in the control group and 71 in the treatment group. The overall response rate of treatment group and control group were 88.73% (63 cases/71 cases) and 82.81% (53 cases/64 cases), respectively (P>0.05). After treatment, endometrial thickness of treatment group and control group were (6.78±1.23) and. (7.36±1.48) mm, respectively; menstrual blood loss were (60.83±9.78) and (64.61±9.25) mL, respectively; hemostasis time were (3.55±1.85) and (3.95±1.82) d, respectively; follicle stimulating hormone (FSH) levels were (6.07±0.96) and (6.51±1.05) U·L-1, respectively; prolactin (PRL) levels were (8.92±1.37) and (9.65±1.49) μg·L-1, respectively; progesterone (P) levels were (0.87±0.13) and (0.94±0.16) pg·mL-1, respectively; matrix metalloproteinase 9 (MMP-9) levels were (22.16±3.58) and (23.93±3.71) pg·mL-1, respectively; activator protein-1 (AP-1) levels were (36.82±4.76) and (39.57±5.37) pg·mL-1, respectively; prostaglandin I2 (PGI2) levels were (21.39±3.84) and (23.18±4.06) pg·mL-1, respectively; angiotensin-Ⅱ (Ang-Ⅱ) levels were (164.47±22.58) and (175.81±35.94) pg·mL-1, respectively; basic fibroblast growth factor (bFGF) levels were (21.15±3.42) and (19.63±3.08) pg·mL-1, respectively. Except for hemostasis time, all the above indicators showed statistically significant differences between the two groups (all P<0.05). The incidence of adverse reactions in the treatment group and control group was 8.45% (6 cases/71 cases) and 12.50% (8 cases/64 cases), respectively, with no statistical significance (P>0.05).
Compared with dydrogesterone, medroxyprogesterone acetate tablets demonstrates comparable efficacy and safety in treating ovulatory dysfunction-related abnormal uterine bleeding. However, medroxyprogesterone acetate tablets shows superior effects in improving endometrial thickness, reducing menstrual blood loss, regulating sex hormone levels, modulating angiogenesis-related markers.
To evaluate the clinical efficacy and safety of palbociclib capsules combined with trastuzumab injection in the treatment of hormone receptor positive (HR+)/human epidermal growth factor receptor 2 positive (HER-2+) breast cancer patients who had progressed after prior trastuzumab therapy.
Patients with HR+/HER-2+ breast cancer were divided into control group and treatment group. The control group was treated with intravenous infusion of trastuzumab injection [the initial dose was 8 mg·kg-1, administered slowly intravenously on the first day of treatment (infusion time ≥90 min); thereafter, the maintenance dose was 6 mg·kg-1, with 28 days as one treatment cycle, and intravenous infusion was administered on the first day of each cycle (infusion time ≥30 min)]. The treatment group was treated with trastuzumab injection combined with palbociclib capsules, the administration of trastuzumab was the same as that of the control group, and palbociclib capsules was administered orally. The initial dose was determined based on the patient’s condition, ranging from 125 mg to 100 mg (if the adverse reactions were severe, the dose would be reduced), and the treatment was continued for 21 days, followed by a 7-day withdrawal, with a total of 28 days as one treatment cycle. Both groups were treated for three courses and followed up. The clinical efficacy, tumor markers, serological indicators, immune function, expression of phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) pathway-related proteins, quality of life, safety evaluation and prognosis of the two groups of patients were compared.
A total of 78 patients were enrolled, with 41 cases in the control group and 37 cases in the treatment group. After treatment, the total effective rate of the treatment group and the control group were 40.54% (15 cases/37 cases) and 17.07% (7 cases/41 cases), (P<0.05). The median progression free survival (PFS) of the treatment group and the control group were 24.5 and 14.3 months, respectively; the cancer antigen 15-3 (CA15-3) levels were (36.72±5.64) and (40.92±6.73) IU·mL-1, respectively; the levles of vascular endothelial growth factor (VEGF) were (86.22±12.32) and (95.26±12.15) pg·mL-1, respectively; the cluster of differentiation 3 positive (CD3+) percentages were (50.16±7.12)% and (46.30±7.16)%, respectively; the relative expression levels of p-AKT protein were 0.58±0.12 and 0.64±0.11, respectively; the short form 36 health survey questionnaire (SF-36) scores werr (72.29±9.49) and (67.18±8.93,) points, respectively. The differences of above indexes were all statistically significant (P<0.05, P<0.01, P<0.001). The overall incidence of drug adverse reactions (including thrombocytopenia, leukopenia, neutropenia, nausea and vomiting, and abnormal liver function) was 72.97% (27 cases/37 cases) in the treatment group and 70.73% (29 cases/41 cases) in the control group, with no statistically significant difference (P>0.05).
Palbociclib capsules combined with trastuzumab injection has a definite therapeutic effect in HR+/HER-2+ breast cancer patients. It can more effectively reduce tumor marker levels, significantly prolong PFS, improve quality of life, and does not increase overall adverse reactions.
To investigate the clinical efficacy of vedolizumab injection combined with mesalazine enteric-coated tablets in the treatment of patients with ulcerative colitis(UC).
Patients with ulcerative colitis (UC) were randomly divided into control group and treatment group using a random number table. The control group received mesalazine enteric-coated tablets: 1 g four times daily during the induction phase (weeks 0-14), and 1 g two to three times daily during the maintenance phase (from week 14 until the end of the study). The treatment group received vedolizumab injection in addition to the same mesalazine regimen as the control group. Vedolizumab was administered via intravenous infusion at a dose of 300 mg at weeks 0, 2, 6, and 14 of treatment. Clinical efficacy, levels of inflammatory factors [C-reactive protein(CRP)], fecal calprotectin], immune microenvironment indicators[T helper 17 (Th17) cells, regulatory T (Treg) cells], intestinal barrier function markers (D-lactate, endotoxin), and serum albumin were compared between the two groups at 6 months of treatment. Safety evaluations were also performed.
A total of 108 patients were screened, with 54 enrolled in each group. In the control group, 5 dropped out, leaving 49 for statistical analysis; in the treatment group, 3 dropped out, leaving 51 for statistical analysis. After 6 months of treatment, the total effective rates in the treatment and control groups were 94.12% (48/51) and 77.55% (38/49) respectively, with the treatment group significantly higher (P<0.05). The CRP levels in the treatment and control groups were (6.75±1.86) and (11.71±2.12) mg·L-1, respectively; fecal calprotectin levels were (36.93±4.54) and (60.15±7.04) μg·g-1, respectively; albumin levels in the experimental and control groups were (44.29±5.31) and (37.41±4.62) g·L-1, respectively; the proportions of Th17 were (2.07±0.26)% and (2.54±0.36)%, respectively; the proportions of Treg were (4.20±0.61)% and (3.58±0.49)%, respectively; the levels of D-lactate were (4.62±0.98) and (6.99±1.42)μg·L-1, respectively; the levels of endotoxin were (2.97±0.39) and(4.03±0.94)U·mL-1, respectively. The differences of above indexes were all statistically significant (all P<0.05). Adverse drug reactions (ADRs) in the treatment group included nausea (2 cases), diarrhea (1 case), liver dysfunction (elevated alanine aminotransferase, 2 cases), and rash (2 cases), totaling 7 cases. ADRs in the control group included nausea (1 case), abdominal pain (1 case), kidney dysfunction (mildly elevated serum creatinine, 1 case), and rash (2 cases), totaling 5 cases. The total incidence of ADRs was 13.73% (7cases/51cases) in the treatment group and 10.20% (5cases/49cases) in the control group, with no statistically significant difference (P>0.05).
The combination of vedolizumab injection and mesalazine enteric-coated tablet improves clinical outcomes for ulcerative colitis patients without raising the incidence of adverse drug reactions.
To observe the clinical efficacy of short-term intensive insulin therapy combined with blood purification in the treatment of hypertriglyceridemic severe acute pancreatitis (HTG-SAP).
HTG-SAP patients were divided into control group and treatment group based on the treatment method. The control group received continuous blood purification (CBP) treatment for 24 to 48 hours, and the next treatment was performed after a 24-hour interval for a total of 2 treatments. The treatment group received continuous intravenous pumping of CBP combined with 0.1-0.3 U·kg-1·h-1 insulin injection. The course of treatment in both groups was 7 days. The clinical efficacy, clinical symptom relief time, prognostic indicators, clinical scores, blood lipid levels, inflammation and biochemical factor levels were compared between the two groups, and safety was evaluated.
A total of 78 patients were enrolled, with 41 cases in control group and 37 cases in treatment group. The total effective rates of treatment in the treatment group and the control group were 89.19% (33 cases/37 cases) and 70.73% (29 cases/41 cases), respectively, with statistical significance differences between the two groups (P<0.05). After treatment, the disappearance times of abdominal distension in the treatment and control groups were (6.27±1.10) and (6.93±1.27) days, respectively; the disappearance times of abdominal pain were (4.97±0.80) and (5.46±1.10) days, respectively; the recovery times of bowel sounds were (3.14±0.63) and (3.56±0.71) days, respectively; the first defecation times were (4.08±0.86) and (4.66±1.33) days, respectively; the total hospitalization times were (17.78±3.29) and (19.54±4.15) days, respectively. the recovery times of organ failure were (6.32±1.62) and (7.24±2.13) days, respectively; the incidences of local complications were 8.11% (3 cases/37 cases) and 26.83% (11 cases/41 cases), respectively; the incidences of systemic complications were 10.81% (4 cases/37 cases) and 29.27% (12 cases/41 cases), respectively; the Bedside Index for Severity in Acute Pancreatitis (BISAP) scores were (1.51±0.51) and (1.83±0.38) points, respectively; the Acute physiology and chronic health evaluation scoring system (APACHE II) scores were (6.05±1.13) points and (6.88±1.44) points, respectively; triglyceride (TG) levels were (4.63±1.07) mmol·L-1 and (5.41±1.26) mmol·L-1, respectively; total cholesterol (TC) were (4.95±1.01) and (5.73±1.27) mmol·L-1, respectively; low-density lipoprotein cholesterol (LDL-C) were (2.87±0.43) and (3.15±0.56) mmol·L-1, respectively; serum amylase (AMY) levels were (138.46±25.49) and (159.85±33.43) U·L-1, respectively; interleukin-8 (IL-8) levels were (28.65±5.15) and (32.18±6.42) pg·mL-1, respectively; C-reactive protein (CRP) levels were (29.88±4.81) and (33.12±6.01) mg·L-1, respectively; the differences of above indexes were all statistically significant (all P<0.05). The incidence of drug adverse reactions of the treatment group and the control group were 5.41% (2 cases/37 cases) and 2.44% (1 case/41 cases), respectively and there was no statistical significance between the two groups (P>0.05).
Short-term intensive insulin therapy combined with blood purification can effectively improve the clinical efficacy of HTG-SAP patients, significantly improve clinical symptoms, organ function recovery, clinical scores, blood lipids, inflammation and biochemical indicators, and does not increase the risk of adverse reactions, which has clinical application value.
To observe the clinical efficacy and safety of azelastine hydrochloride eye drops combined with polyvinyl alcohol eye drops in the treatment of allergic conjunctivitis in children aged 4-6 years.
Children with allergic conjunctivitis were divided into control group and treatment group based on the medication regimen. The control group received azelastine hydrochloride eye drops,1 drop each time, tid; while the treatment group received additional polyvinyl alcohol eye drops, 1 drop each time, tid. The treatment duration was 2 weeks. The two groups were compared in terms of clinical efficacy, comprehensive ocular symptom scores, tear film stability indicators, inflammatory factor levels, tear meniscus parameters and the incidence of adverse drug reactions were eveluated.
A total of 99 children were enrolled, including 48 cases in the control group and 51 cases in the treatment group. After treatment, the total effective rates in the treatment group and control group were 92.16% (47 cases/51 cases) and 89.58% (43 cases/48 cases), respectively, with no statistically significant difference between the two groups (P>0.05). After treatment, the scores for eye itching of the treatment group and the control group were (0.65±0.56) and (0.92±0.45) points, respectively; scores for foreign body sensation were (0.35±0.56) and (0.65±0.56) points, respectively; scores for tearing were (0.35±0.52) and (0.65±0.53) points, respectively; scores for photophobia were (0.37±0.49) and (0.63±0.57) points, respectively; the levels of hyaluronic acid (HA) were (85.58±9.36) and (90.69±10.58) μg·L-1, respectively; the levels of eosinophil cationic protein (ECP) were (6.36±0.89) and (6.82±0.95) μg·L-1, respectively; the levels of thymic stromal lymphopoietin (TSLP) were (7.57±1.59) and (8.43±1.48) pg·mL-1, respectively; the tear film breakup time (TBUT) were (11.49±1.37) and (10.83±1.19) s, respectively; the corneal fluorescein staining (CFS) score were (1.93±0.55) and (2.17±0.41) points, respectively; the lipid layer thickness (LLT) were (58.46±5.84) and (55.52±5.63) nm, respectively; the incomplete blink ratio (PBR) were (56.49±5.21) and (58.95±5.71)%, respectively; the meibomian gland dropout rate (MGDR) of the upper eyelids were (14.49±2.06)% and (15.36±1.88)%, respectively; MGDR of lower eyelids were (21.25±3.07)% and (22.87±2.79)%, respectively; the tear meniscus depth (TMD) were (219.64±24.56) and (208.65±23.57) μm, respectively; tear meniscus height (TMH) were (237.61±26.82) and (223.49±27.48)μm, respectively; tear meniscus area (TMA) were (58.49±8.33) and (55.07±8.11) μm2, respectively. For all the above parameters, the differences between the two groups were all statistically significant (all P<0.05). The total incidence of adverse drug reactions in the treatment group and control group was 5.88% (3 cases/51 cases) and 8.33% (4 cases/48 cases), respectively, with no statistically significant difference (P>0.05).
The combination of azelastine hydrochloride eye drops and polyvinyl alcohol eye drops demonstrates good efficacy in treating allergic conjunctivitis in children aged 4-6 years, significantly improving ocular symptoms and tear film stability, reducing inflammatory markers, and without increasing adverse drug reactions.
To observe the clinical efficacy and safety of low molecular weight heparin (LMWH) calcium injection combined with cimetidine (CIM) injection in the treatment of children with recurrent Henoch-Schönlein purpura (HSP).
Children with recurrent HSP were randomly divided into control group and treatment group. Both groups received conventional comprehensive treatment. The control group was administered 10 mg·kg-1 of CIM injection for intravenous infusion, bid. The treatment group received subcutaneous injection of 100 IU·kg-1 LMWH calcium injection in addition to control group’s regimen, qd. Both groups underwent continuous treatment for 14 days. Clinical efficacy, renal injury indicators, coagulation function parameters, immunoglobulin levels, T lymphocyte counts and inflammatory response markers were compared between the two groups, along with safety evaluation.
This clinical trial enrolled a total of 92 pediatric patients, with 46 cases each group. After treatment, the overall response rates were 78.26% (36 case/46 case) in control group and 93.48% (43 case /46 case) in treatment group; the urinary microalbumin (mALB) levels were (26.43±2.37) and (25.31±1.82) mg·L-1, respectively; urinary α1-microglobulin (α1-MG) levels were (10.23±1.22) and (9.58±1.25) mg·L-1, respectively; N-acetyl-β-D-glucosaminidase (NAG) levels were (16.32±1.12) and (15.70±1.18) U·L-1, respectively; cystatin C (CysC) levels were (0.77±0.19) and (0.69±0.13) mg·L-1, respectively; plasma D-dimer (D-Dimer) levels were (167.49±25.27) and (157.35±22.80) ng·mL-1, respectively; fibrinogen (FIB) levels were (3.19±0.87) and (2.81±0.48) g·L-1, respectively; prothrombin time (PT) were (11.44±1.19) and (12.17±1.52) s, respectively; the activated partial thromboplastin time (APTT) were (28.76±4.49) and (30.90±3.62) s, respectively; immunoglobulin A (IgA) levels were (2.35±0.56) and (2.08±0.59) g·L-1, respectively; IgE levels were (74.74±9.64) and (71.04±7.78) IU·L-1, respectively; IgG levels were (10.61±1.77) and (10.63±1.61) g·L-1, respectively; IgM levels were (1.31±0.28) and (1.29±0.26) g·L-1, respectively; CD4-positive T lymphocyte (CD4+) percentage were (37.89±4.92)% and (40.86±6.02)%, respectively; CD8+ percentage were (26.22±3.28)% and (24.55±3.01)%, respectively; CD4+/CD8+ ratio were 1.54±0.50 and 1.77±0.55, respectively; interferon-γ (IFN-γ) levels were (15.33±3.81) and (13.48±3.60) pg·mL-1, respectively; interleukin-4 (IL-4) levels were (27.38±4.07) and (25.33±3.47) pg·mL-1, respectively; interleukin-17 (IL-17) levels were (80.98±8.12) and (76.60±8.06) ng·L-1, respectively. All these parameters in treatment group showed statistically significant differences compared to control group (P<0.05, P<0.01). The main adverse drug reactions in treatment group included injection site redness and swelling, fatigue and vomiting, while those in control group included nausea, dizziness and vomiting. The overall incidence of adverse drug reactions was 6.52% (3 cases/46 cases) in control group and 8.70% (4 cases/46 cases) in treatment group, with no statistically significant difference between the two groups (P>0.05).
The combination of LMWH calcium injections and CIM injections demonstrates superior efficacy in treating recurrent HSP in children, alleviating immune stress, exerting anti-inflammatory effects, and exhibiting safety profiles.
To explore the potential mechanism of morin in improving airway inflammation in asthma.
In animal experiments, rats were randomly divided into four groups, with 10 rats in each group: animal control group, animal model group [ovalbumins (OVA)-induced], animal experimental-L group (OVA-induced + 10 mg·kg-1 morin), animal experimental-M (OVA-induced+30 mg·kg-1 morin) and the experimental-H group (OVA-induced+100 mg·kg-1 morin). After 4 weeks of treatment, bronchoalveolar lavage fluid (BALF) and serum were collected for subsequent use, and lung tissues were harvested. Western blot assay was used to detect the expression of murine double minute 2(MDM2) protein; enzyme-linked immunosorbent assay (ELISA) assay was employed to determine the expression of inflammatory factors in BALF; and real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) assay was applied to measure the mRNA expressions of tumor protein 53 (p53) and BCL-2 associated X protein (Bax). In cell experiments, 16HBE cells were randomly assigned to four groups: cell blank group, cell model group [treated with 50 μg·L-1 interleukin(IL)-13], cell experimental group (treated with 65 μmol·L-1 morin+IL-13), si-NC group(transfected with si-NC, then treated with 65 μmol·L-1 morin+IL-13) and si-MDM2 group (transfected with si-MDM2, then treated with 65 μmol·L-1 morin+IL-13). After 48 hours of treatment, TdT mediated dUDP nick end labeling(Tunel) assay was used to detect the cell apoptosis rate; Western blot assay was performed to determine protein expression and P53 ubiquitination level.
In animal experiments, the levels of MDM2 protein in the animal control group, animal model group, animal experimental-L group, animal experimental-M and animal experimental-H group were 0.65±0.05, 0.32±0.03, 0.41±0.06, 0.46±0.04 and 0.51±0.05, respectively; the levels of BALF-IL-13 were (15.44±1.19), (55.43±3.90), (48.79±4.88), (37.25±4.59) and (25.64±1.64) pg·mL-1, respectively; the relative expression levels of p53 mRNA were 1.00±0.14, 1.75±0.13, 1.51±0.12, 1.44±0.09 and 1.24±0.14, respectively; the relative expression levels of Bax mRNA were 1.00±0.14, 1.94±0.16, 1.75±0.17, 1.62±0.17 and 1.39±0.09, respectively; when comparing the animal model group with the animal control group, and the animal experimental-L, -M, -H groups with the animal model group respectively, the differences of the above indicators were all statistically significant (P<0.05, P<0.01). In cell experiment, the apoptosis rates of cells in cell blank group, cell model group, cell experimental group, si-NC group and si-MDM2 group were (3.94±0.27), (31.76±2.39), (19.93±1.91), (18.14±2.50) and (25.97±1.74)%, respectively; the realtive expression levels of MDM2 protein were 0.91±0.09, 0.44±0.05, 0.66±0.08, 0.68±0.05 and 0.21±0.04, respectively; when comparing the cell model group with the cell blank group, the cell experimental group with the cell model group, the si-MDM2 group with the si-NC group, the differences of the above indicators were all statistically significant (all P<0.01).
Morin may alleviate asthmatic airway inflammation and cell apoptosis by upregulating MDM2 ubiquitination to regulate p53.
To discuss the effects of apatinib (APa) on proliferation, apoptosis, and immune escape of gastric cancer cells by adjusting the high mobility group box 1 (HMGB1)/receptor for advanced glycosylation end products (RAGE) pathway.
SGC-7901 cells were randomly separated into blank control group, low-dose experimental group (intervention with 20 μmol·L-1 Apa for 48 hours), medium-dose experimental group (intervention with 40 μmol·L-1 Apa for 48 hours), high-dose experimental group (intervention with 60 μmol·L-1 Apa for 48 hours) and HMGB1 group (intervention with 60 μmol·L-1 Apa combined with 100 ng·mL-1 HMGB1 recombinant factor for 48 hours). After intervention with APa and human HMGB1 recombinant factor, cell counting kit-8 (CCK-8) method, 5-Ethynyl-2’- deoxyuridine (Edu) staining, and immunofluorescence staining Ki67 were used to measure the proliferation of SGC-7901 cells in each group. Flow cytometry, Hoechst 33342/PI double staining, and immunofluorescence were performed to measure apoptosis of SGC-7901 cells in each group. Western blot was performed to detect the expression of HMGB1/RAGE signaling pathway proteins of SGC-7901 cells in various groups. A co-culture system of activated peripheral blood mononuclear cells (PBMCs) or NK cells with SGC-7901 cells was constructed. After grouping and drug intervention, the CCK-8 method was performed to detect the killing rates of T cells and NK cells against SGC-7901 cells in each group. Flow cytometry was used to measure the proportion of activated CD8+T cells in the co culture system of PBMCs and SGC-7901 cells in each group. Immunofluorescence staining was performed to measure the expression of programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in the co culture system of PBMC and SGC-7901 cells in various groups. In addition, enzyme linked immunosorbent assay (ELISA) method was used to measure the levels of immune cytokines interleukin (IL)-6, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and IL-2 production in the co culture system of PBMC and SGC-7901 cells.
The Edu positive rates in blank control group, the low-dose experimental group, medium-dose experimental group, high-dose experimental group and HMGB1 group were (86.23±5.30)%, (65.81±4.65)%, (43.16±4.52)%, (20.19±3.79)% and (82.45±5.27)%, respectively; the apoptosis rates were (4.37±1.19)%, (23.05±2.14)%, (41.87±2.69)%, (62.04±3.12)% and (5.91±1.28)%, respectively; the relative expression levels of HMGB1 protein were 1.15±0.07, 0.79±0.05, 0.43±0.04, 0.10±0.02 and 1.13±0.06, respectively; the RAGE protein expression levels were 1.23±0.08, 0.85±0.06, 0.47±0.05, 0.14±0.03 and 1.21±0.07, respectively; the PD-1 positive expression rates were (58.13±3.70)%, (45.37±2.84)%, (32.06±3.01)%, (21.47±2.31)% and (54.87±3.53)%, respectively; the T cell killing rates were (10.12±1.34)%, (23.45±1.62)%, (37.06±2.08)%, (51.29±2.73)% and (12.01±1.61)%, respectively; the proportions of activated CD8+T cells were (7.21±0.53)%, (12.42±0.81)%, (17.93±0.75)%, (23.07±0.64)% and (7.93±0.56)%, respectively; the IL-6 production levels were (28.31±3.26), (46.02±4.18), (65.43±3.70), (86.15±4.39) and (31.04±3.48) ng·L-1, respectively. Compared the blank control group with the low-dose experimental group, medium-dose experimental group and high-dose experimental group, compared the HMGB1 group with the high-dose experimental group, the differences of above indexes were all statistically significant (all P<0.05).
APa can inhibit the proliferation and immune escape of gastric cancer cells, promote their apoptosis, possibly by blocking the activation of the HMGB1/RAGE signaling pathway.
To explore the potential mechanism of rosmarinic acid in reducing sepsis related kidney injury.
In the animal experiment, BALB/c mice were randomly divided into animal control group, animal model group [10 mg·kg-1 lipopolysaccharide (LPS) modeling], animal low-dose experimental group (modeling+10 mg·kg-1 rosmarinic acid) and animal high-dose experimental group (modeling+20 mg·kg-1 rosmarinic acid), with 10 mice in each group. In the cell experiment part, RAW264.7 cells were randomly divided into cell blank group, cell model group (1 μg·mL-1 LPS), cell low-dose experimental group (modeling+20.00 μmol·mL-1 rosmarinic acid) and cell high-dose experimental group (modeling+40.00 μmol·mL-1 rosmarinic acid). Serum and renal tissue inflammatory related indicators were analyzed by enzyme linked immunosorbent assay (ELISA) kit and real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). Renal tissue differentiation cluster 86 (CD86)+cells and F4/80+cells were co-located by immunohistochemistry.
In the animal experiment part, the serum creatinine (Scr) levels of animal control group, animal model group, low-dose experimental group and high-dose experimental group were (14.80±0.73), (59.73±6.79), (50.06±5.12) and (43.62±3.73) mmol·L-1, respectively; the levels of inducible nitric oxide synthase (iNOS) were (1.26±0.11), (4.74±0.11), (3.86±0.23) and (2.48±0.28) U·L-1, respectively; the levels of tumor necrosis factor-alpha (TNF-α) were (14.00±1.47), (85.90±6.66), (64.97±5.62) and (46.84±1.95) pg·mL-1, respectively; the levels of interleukin (IL)-6 were (6.93±0.47), (50.05±3.84), (39.93±3.50) and (27.26±2.09) pg·mL-1, respectively; the levels of IL-1 β were (22.17±2.27), (122.42±12.77), (91.54±6.84) and (61.23±6.31) pg·mL-1, respectively; the CD86+/F4/80+ co-located cells were (100.00±4.85)%, (476.99±39.89)%, (322.15±24.15)% and (219.90±19.81)%, respectively. There were statistically significant differences in the above indexes between animal model and animal control group, between low-dose, high-dose experimental groups and animal model group, and between high-dose experimental group and low-dose experimental group (P<0.05, P<0.01, P<0.001). In the cell experiment, the relative expression levels of iNOS mRNA in the cell blank group, cell model group, cell low-dose experimental group and cell high-dose experimental group were 1.00±0.10, 3.26±0.31, 2.51±0.27 and 1.94±0.19, respectively; the relative expression levels of TNF - α mRNA were 1.00±0.14, 2.54±0.26, 2.07±0.22 and 1.77±0.18, respectively; the relative expression levels of IL-1β mRNA were 1.00±0.12, 2.24±0.30, 1.83±0.22 and 1.52±0.17, respectively; the relative expression levels of IL-6 mRNA were 1.00±0.08, 2.43±0.17, 1.85±0.21 and 1.54±0.16, respectively. There were statistically significant differences in the above indexes between cell model group and cell blank group, between low-dose and high-dose experimental groups and cell model group, and between high-dose experimental group and low-dose experimental group (P<0.01, P<0.001).
Rosmarinic acid plays a protective role in LPS-induced acute kidney injury by inhibit macrophage activation and inhibition of their transformation into M1-type macrophages.
To explore the mechanism of theaflavin improving the inflammatory response of intestinal epithelial cells in ulcerative colitis (UC) through regulating NOD-like receptor thermal protein domain associated protein 3 (NLRP3) / Caspase-1 signaling pathway mediated by astrocyte elevated gene 1 (AEG-1).
NCM460 cells were divided into control group (conventional culture of NCM460 cells without any intervention treatment, model group (treated with 1 mg·L-1 lipopolysaccharide in NCM460 cells for 24 hours), experimental group (treated with 64 μmol·L-1 theaflavin and 1 mg·L-1 lipopolysaccharide in NCM460 cells for 24 h), pcDNA3.1-NC group (after NCM460 cells were transfected with the pcDNA3.1-NC plasmid, treated with 64 μmol·L-1 theaflavin and 1 mg·L-1 lipopolysaccharide for 24 h) and pcDNA3.1-AEG-1 group (after NCM460 cells were transfected with the pcDNA3.1-AEG-1 plasmid, treated with 64 μmol·L-1 theaflavin and 1 mg·L-1 lipopolysaccharide for 24 h). Cell viability was detected by cell counting kit-8 method, cell invasion ability was detected by Transwell assay, cell migration ability was detected by cell scratch assay, and mRNA levels of AEG-1 and barrier damage-related proteins were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction. Western blotting was used to detect the expressions of AEG-1, apoptosis, barrier injury and NLRP3/Caspase-1 signaling pathway-related proteins and enzyme-linked immunosorbent assay was used to detect the contents of inflammatory factors.
The cell migration rate of the control group, model group, experimental group were (78.85±13.47)%, (19.32±3.15)% and (54.97±9.03)%, respectively. The levels of interleukin-6 (IL-6) in the control group, model group, experimental group, pcDNA3.1-NC group and pcDNA3.1-AEG-1 group were (0.49±0.07), (1.36±0.21), (0.64±0.09), (0.68±0.10) and (1.21±0.18) pg·L-1, respectively; the apoptosis rates were (8.26±1.47)%, (27.09±4.62)%, (14.51±2.18)%, (16.75±2.83)% and (22.68±3.56)%, respectively; the relative expression levels of B-cell lymphoma-2 (Bcl-2) protein were 1.00±0.16, 0.39±0.07, 0.71±0.12, 0.67±0.09 and 0.54±0.08, respectively; the relative expression levels of Bcl-2-associated X (Bax) protein were 1.00±0.19, 6.45±1.12, 3.90±0.64, 3.79±0.58 and 6.07±0.96, respectively; the mRNA levels of AEG-1 were 1.00±0.13, 4.35±0.76, 1.92±0.33, 2.08±0.32 and 3.26±0.57, respectively; the relative expression levels of AEG-1 protein were 1.00±0.17, 4.82±0.79, 2.07±0.34, 2.25±0.36 and 3.94±0.71, respectively; the mRNA levels of Zonula Occludens-1 (ZO-1) were 1.00±0.15, 0.37±0.06, 0.76±0.13, 0.79±0.14 and 0.51±0.09, respectively, while the mRNA levels of Occludin were 1.00±0.16, 0.29±0.05, 0.58±0.10, 0.52±0.09 and 0.37±0.06, respectively; the relative protein expression levels of NLRP3 were 1.00±0.19, 6.58±1.06, 2.71±0.43, 2.59±0.42 and 5.16±0.94, respectively; the relative protein expression levels of cleaved caspase-1 were 1.00±0.16, 5.26±0.93, 3.42±0.59, 3.65±0.64 and 5.09±0.87, respectively. When comparing the model group with the control group and the experimental group, and the pcDNA3.1-NC group with the pcDNA3.1-AEG-1 group, the differences in the above indicators were all statistically significant (P<0.01, P<0.001).
Theaflavin can improve the inflammatory response of LPS-induced UC intestinal epithelial cells and inhibit cell apoptosis, and has a protective effect on epithelial barrier function. The mechanism may be related to the down-regulation of AEG-1 expression and the inhibition of the NLRP3/Caspase-1 signaling pathway.
To investigate the inhibitory effect of curcumol on the growth of hepatocellular carcinoma(HCC)cells through sialic acid-binding immunoglobulin-like lectin 15(Siglec-15)and its underlying mechanism.
Bel-7402 and HepG2 cells were randomly divided into control group(normal culture), low-dose experimental group (treated with 50 μmol·L-1 curcumol for 48 hours), and a high-dose experimental group (treated with 100 μmol·L-1 curcumol for 48 hours). The proliferative, invasive, and migratory capacities of cells were evaluated through a combination of functional assays, including the methyl thiazolyl tetrazolium (MTT) method for cell viability, Transwell and wound healing assays for migration and invasion, and flow cytometry for additional cellular characteristics. The expression levels of Siglec-15, along with key molecules involved in the phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) signaling cascade, were examined at both the messenger RNA(mRNA) and protein levels. For this purpose, real-time quantitative polymerase chain reaction (RT-qPCR) was employed to assess transcript abundance, while Western blotting was used to determine protein expression.
The cell viability rates in the control, low-dose, and high-dose experimental groups of Bel-7402 cells and HepG2 cells were (100.00±0)%, (72.09±1.07)%, (55.65±2.99)% and (100.00±0)%, (57.38±6.97)%, (44.63±6.04)%, respectively; the apoptosis rates in the corresponding groups of Bel-7402 cells and HepG2 cells were (1.87±0.05)%, (2.77±0.08)%, (4.19±0.11)% and (3.52±0.17)%, (5.46±0.11)%, (6.63±0.16)%, respectively; the wound healing rates (horizontal migration rates) in the corresponding groups of Bel-7402 cells and HepG2 cells were (39.06±0.81)%, (19.20±0.59)%, (8.34±0.89)% and (52.25±1.43)%, (21.10±1.95)%, (15.31±0.80)%, respectively; the vertical migration rates in the corresponding groups of Bel-7402 cells and HepG2 cells were (100.00±0)%, (72.40±4.34)%, (62.47±3.08)% and (100.00±0)%, (60.51±2.62)%, (40.47±2.76)%, respectively. In the control group, low-dose experimental group, and high-dose experimental group of Bel-7402 cells and HepG2 cells, the relative mRNA expression levels of Siglec-15 were 1.00±0.18, 0.89±0.01, 0.69±0.07 and 1.00±0.09, 0.90±0.04, 0.88±0.03, respectively; the relative mRNA expression levels of PI3K were 1.00±0.16, 0.80±0.12, 0.75±0.11 and 1.00±0.16, 0.93±0.08, 0.93±0.04, respectively; the relative mRNA expression levels of AKT were 1.00±0.15, 0.73±0.17, 0.52±0.11 and 1.00±0.21, 0.69±0.06, 0.27±0.05, respectively; the relative protein expression levels of Siglec-15 were 1.05±0.07, 0.91±0.09,0.84±0.07 and 0.99±0.05, 0.80±0.02, 0.64±0.04, respectively; the relative protein expression levels of PI3K were 0.96±0.09, 0.49±0.10, 0.17±0.10 and 1.01±0.03, 0.73±0.03, 0.49±0.03, respectively. The relative protein expression levels of AKT were 0.98±0.04, 0.88±0.08, 0.63±0.04 and 1.06±0.04, 0.92±0.02, 0.67±0.03, respectively. In both cell lines, compared with the control group, the differences in the above indicators between each experimental group and the control group were all statistically significant (all P<0.001).
Curcumol exerts anti-hepatocellular carcinoma effects by downregulating Siglec-15 expression and inhibiting the proliferation and migration of Bel-7402 and HepG2 hepatoma cells.
To investigate the effects of ginsenoside Rb1 on hypoxia/reoxygenation (H/R)-induced injury in human pulmonary endothelial cells (HPECs) and its underlying mechanism.
HPECs were randomly divided into control group(normal culture), model group(subjected to 3 h of hypoxia followed by 7 h of reoxygenation), and experimental group(pretreated with 0.1 μmol·L-1, 1.0 μmol·L-1, 10.0 μmol·L-1 and 100.0 μmol·L-1 ginsenoside Rb1 for 1 h prior to H/R). Cell viability was assessed using the CCK-8 assay. The levels of inflammatory factors including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). The intracellular adenosine triphosphate(ATP) content and the activities of mitochondrial respiratory chain complex Ⅰ (complex Ⅰ) and ATP synthase were detected by ELISA . The protein relative expression levels of glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), zonula occludens-1 (ZO-1), vascular endothelial cadherin (VE-cadherin) and ATP synthase F1 subunit delta (ATP5D) were measured by Western blot.
The cell viability of the control group, model group and experimental group(0.1, 1.0, 10.0 and 100.0 μmol·L-1)were 1.07±0.04, 0.61±0.06, 0.68±0.07, 0.80±0.06, 0.96±0.08 and 0.95±0.09, respectively, among which 10.0 μmol·L-1 showed the optimal protective effect and this concentration was therefore used for subsequent experimental group. The levels of IL-1β in the control group, model group and experimental group were (136.25±3.61), (200.12±8.56) and (149.50±9.20) ng·L-1, respectively; the levels of IL-6 were (4.95±0.26), (8.96±0.60) and (6.23±0.34)ng·L-1, respectively; the levels of TNF-α were (328.66±19.14), (461.54±26.39) and (391.77±17.22) ng·L-1, respectively; the relative expression levels of GRP78 were 0.84±0.15, 1.45±0.13 and 0.82±0.15, respectively; the relative expression levels of CHOP were 0.66±0.11, 1.20±0.41 and 0.76±0.14, respectively; the relative expression levels of ZO-1 were 0.81±0.11, 0.25±0.07 and 0.84±0.13, respectively; the relative expression levels of VE-cadherin were 0.75±0.12, 0.32±0.09 and 0.73±0.14, respectively; the relative expression levels of ATP5D were 0.88±0.16, 0.26±0.08 and 0.83±0.17, respectively; the activities of mitochondrial respiratory chain complex Ⅰ were 2.12±0.26, 1.40±0.17 and 1.82±0.15, respectively; the activities of ATP synthase were 2.14±0.25, 1.32±0.17 and 1.81±0.18, respectively; the contents of ATP were (86.32±8.50), (52.21±5.62) and (91.12±6.10) μmol·ug-1 protein, respectively; there were statistically significant differences in the above indicators between the model group and the control group, between the experimental group and the model group (all P<0.05).
Ginsenoside Rb1 may alleviate H/R-induced HPECs injury, inflammatory response, and endoplasmic reticulum stress by improving mitochondrial function and increasing intracellular ATP content, thereby restoring normal cellular function.
To investigate the potential mechanism of lycopene mediating iron autophagy in improving the inflammatory response in endometriosis (EMs).
Fifty rats were randomly divided into sham group, model group (EMs model was constructed), experiment-L group (10.0 mg·kg-1 lycopene after modeled), experiment-H group (20.0 mg·kg-1 lycopene after modeled) and positive group (1.05 mg·kg-1 mifepristone after modeled), with 10 rats in each group. At the end of drug treatment, the volume of ectopic endometrial tissue were detected, and detected free iron content with a corresponding detection kit. The expressions of vascular endothelial growth factor A (VEGFA), interleukin (IL) -8, nuclear receptor coactivator 4 (NCOA4) and microtubule-associated protein 1 light chain 3B (LC3B) were detected by immunofluorescence, or Western blot.
The volumes of ectopic endometrial lesion tissues in the sham group, the model group, the experiment-L group, the experiment-H group and the positive group of rats were (0.00±0.00), (130.92±12.45), (97.55±10.56), (71.96±6.46), and (54.22±2.72) mm3, respectively; the levels of free iron were (262.89±23.51), (636.97±58.75), (523.63±46.13), (383.30±38.92) and (603.15±69.98) μmol·kg-1, respectively; the immunofluorescence intensities of VEGFA were (1 034.45±102.39), (3 628.16±104.65), (3 100.73±231.67), (2 193.07±293.16) and (3 418.68±377.98) a.u., respectively; the relative expression levels of IL-8 protein were 0.22±0.05, 0.79±0.10, 0.62±0.10, 0.49±0.06 and 0.71±0.07, respectively; the relative expression levels of NCOA4 protein were 0.33±0.04, 1.12±0.13, 0.85±0.10, 0.61±0.09 and 1.05±0.08, respectively; the relative expression levels of LC3Ⅱ/Ⅰ protein were 0.36±0.04, 1.02±0.12, 0.78±0.08, 0.51±0.05 and 0.94±0.07, respectively. Compared the sham operation group with the model group, compared experiment-L and experiment-H groups with the model group, the differences of above indicators were all statistically significant (all P<0.05).
Lycopene significantly inhibits inflammation and angiogenesis in EMs rats, thereby reducing the volume of ectopic lesions, which may be related to the inhibition of iron autophagy signaling.
To investigate the effects of curcumin on ferroptosis and neurological deficit in mice with intracerebral hemorrhage (ICH) and to clarify its potential molecular mechanism.
A total of 40 mice were divided into sham group, model group, experimental group and inhibitor group, with 10 mice in each group. Intracerebral hemorrhage model in mice was established by tail vein autologous blood injection. The sham group was injected with the same amount of normal saline; in the model group, the model group was established and injected with the same amount of normal saline; the experimental group was intragastrically administered with 200 mg·kg-1 curcumin, and the inhibitor group was intraperitoneally injected with 5 mg·kg-1 secretory phosphoprotein 1 (SPP1) inhibitor solution on the basis of 200 mg·kg-1 curcumin. At the end of the treatment, Longa score was used to evaluate the neurological deficit; the serum levels of Fe2+, malondialdehyde (MDA) and superoxide dismutase (SOD) were detected by enzyme-linked immunosorbent assay (ELISA); the relative fluorescence intensity of reactive oxygen species (ROS) in brain tissue was detected by immunofluorescence method; the relative expression levels of B-cell lymphoma 2 (BCL-2), BCL-2-associated X protein (Bax), nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione peroxidase (GPX4) were detected by Western blot; the relative positive level of SPP1 in brain tissue was detected by immunohistochemistry.
The neurological deficit scores of sham group, model group, experimental group and inhibitor group were (0±0), (3.20±0.42), (1.40±0.52) and (2.10±0.57) scores, respectively; the serum Fe2+levels were (220.35±26.17), (432.40±65.28), (276.52±33.20) and (329.15±45.71) μmol·kg-1, respectively; the serum MDA levels were (53.75±7.62), (120.36±18.22), (72.68±11.23) and (89.44±13.16) nmol·mg-1, respectively; the serum SOD levels were (63.78±9.80), (20.86±3.41), (51.18±7.30) and (37.35±5.08) U·mg-1, respectively; the relative fluorescence intensities of ROS were 1.00±0.09, 3.87±0.56, 1.52±0.22 and 2.43±0.38, respectively; the relative expression levels of Bax in brain tissue were 1.00±0.11, 2.95±0.33, 1.58±0.26 and 2.37±0.29, respectively; the relative expression levels of Bcl-2 were 1.00±0.15, 0.20±0.04, 0.65±0.12 and 0.43±0.07, respectively; the relative expression levels of Nrf2 were 1.00±0.13, 0.33±0.05, 0.65±0.10 and 0.54±0.09, respectively; the relative expression levels of GPX4 were 1.00±0.14, 0.21±0.04, 0.58±0.09 and 0.45±0.06, respectively; the relative positive levels of SPP1 were 1.00±0.13, 0.30±0.05, 0.76±0.12 and 0.43±0.07, respectively. There were statistically significant differences in the above indicators between the model group and the sham operation group, between the experimental group and the model group, and between the inhibitor group and the experimental group (P<0.05, P<0.01, P<0.001).
Curcumin can alleviate neuronal apoptosis and ferroptosis after ICH, and improve neurological function injury in mice. The underlying mechanism may be associated with the up-regulation of SPP1 expression, which in turn activates the Nrf2/GPX4 signaling pathway.
To assess the tablet effect of a high-fat diet on the pharmacokinetics of oral FM888 tablet in healthy Chinese participants. FM888 tablet is a novel highly selective adenylyl cyclase 1 (AC1) antagonist potentially involved in chronic pain treatment by modulation of central plasticity.
A single-center, open-label, randomized, single-dose, two-period crossover trial was conducted. Subjects were randomized 1∶1 to receive 400 mg FM888 tablet under fasting or high-fat meal conditions, then crossed over after a 7-day washout. Plasma FM888 concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and analyzed by non-compartmental methods using Phoenix WinNonlin 8.3.1.
The Cmax of FM888 tablet in the fasting state and after a highfat meal were (175.57±89.51) and (63.74±38.74) ng·mL-1, respectively; AUC0-last were (645.84±355.50) and (416.28±245.83) h·ng·mL-1, respectively; AUC0-∞ were (698.22±373.46) and (455.36±290.66) h·ng·mL-1, respectively. Exposure to FM888 tablet was lower under fed conditions than under fasting conditions, with Cmax and AUC0-last reduced to approximately 36.00% and 65.00% of the fasting values, respectively. The geometric mean ratios (fed/fasting) for Cmax、AUC0-last and AUC0-∞ were 36.86% [90% confidence interval (CI): 28.94%-46.95%], 66.01% (90% CI: 55.72%-78.20%), and 67.39% (90% CI: 55.70%-81.53%), respectively. Mixed-effects modeling confirmed a significant effect of feeding status on key parameters (P<0.05). FM888 tablet was well tolerated; all adverse events were grade 1, with no serious events.
A high-fat meal significantly reduced FM888 bioavailability, indicating a marked food effect. Despite lower exposure, FM888 tablet demonstrated favorable safety and tolerability.
To study the bioequivalence of test preparation and reference preparation of pregabalin capsule in Chinese healthy subjects under fasting and fed conditions.
Using a single center, randomized, open, two cycle crossover design, 52 healthy subjects were divided into fasting group and fed group, with 26 cases in each group. The test or reference preparation of pregabalin capsules was orally administered 150 mg once. The blood concentration was determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and pharmacokinetic (PK) parameters were calculated to evaluate the bioequivalence.
The main PK parameters Cmax of pregabalin capsule test preparation and reference preparation in the fasting group were (6 722.00±1 390.00) and (6 065.00±1 218.00) ng·mL-1, respectively; AUC0-t were (32 570.52±3 877.48) and (32 721.93±4 270.54) ng·h·mL-1, respectively; AUC0-∞ were (32 941.98±4 040.07) and (33 097.11±4 428.89) ng·h·mL-1, respectively; tmax was 0.75 (0.50, 1.75) and 1.00 (0.50, 1.75) h, respectively; the t1/2 were (5.58±0.74) and (5.55±0.80) h, respectively. The main PK parameters Cmax of the test preparation and reference preparation of pregabalin capsules in the fed group were (3 786.00±513.90) and (3 786.00±437.50) ng·ml-1, respectively; AUC0-t were (32 760.51±4 250.79) and (31 923.83±3 842.92) ng·h·mL-1, respectively; AUC0-∞ were (33 371.21±4 406.02) and (32 519.87±4 050.39) ng·h·mL-1, respec tively; tmax was 3.50 (2.50, 4.50) and 3.00 (2.50, 4.51) h, respectively; the t1/2 was (5.95±0.79) and (5.89±0.91) h, respectively. Under fasting or fed conditions, the 90% confidence intervals of the main PK parameters of the test preparation and the reference preparation were both 80.00%-125.00%.
The test preparation and reference preparation of pregabalin capsules are bioequivalent under fasting and fed conditions.
Polycystic ovary syndrome (PCOS), a prevalent endocrine-metabolic disorder, is characterized by hyperandrogenemia, ovulatory dysfunction, and polycystic ovarian morphology. The nucleotide-binding leucine-rich repeat (NLR) family pyrin domain containing 3 (NLRP3) inflammasome, an intracellular complex composed of active-NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC) and pro-cysteine aspartate specific proteinase 1 (Pro-Caspase-1), is activated by stimuli such as pathogen invasion, oxidative stress, and metabolic disorders, regulating the release of pro-inflammatory cytokines including interleukin-1β (IL-1β) and IL-18 to mediate inflammatory responses. PCOS is intricately linked to NLRP3 inflammasome activation: it triggers NLRP3 via mechanisms including ion imbalance, mitochondrial dysfunction, and metabolic product accumulation, leading to the release of pro-inflammatory factors that exacerbate ovarian inflammatory microenvironment, inhibit follicular development, and induce granulosa cell apoptosis. Concurrently, NLRP3 inflammasome activation exacerbates metabolic disorders and reproductive endocrine abnormalities by disrupting insulin signaling and promoting androgen synthesis, forming a "metabolism-inflammation-reproduction" vicious cycle. This paper systematically reviews the basic research progress of traditional Chinese medicine (TCM) in regulating NLRP3 inflammasome and deeply explores the synergistic mechanisms of TCM in anti-inflammatory and metabolic regulation within PCOS models, aiming to provide novel therapeutic strategies for PCOS.
Pharmacological treatment of bladder cancer (BC), including intravesical chemotherapy, systemic chemotherapy, chemoradiotherapy, and immunotherapy, still faces major challenges such as high recurrence rates, drug resistance, and treatment-related toxicities. As an important adaptive response under therapeutic stress, autophagy exerts a dual role in BC; it may cooperate with apoptosis and other pathways to mediate tumor cell death, or function as protective autophagy to promote cell survival and drive drug resistance. Therefore, strategies aimed at inducing lethal autophagy or inhibiting therapy-induced protective autophagy/autophagic flux blockade have emerged as potential approaches to optimize treatment response. Active components and compound formulas of traditional Chinese medicine can modulate autophagy through signaling pathways such as AMP-activated protein kinase/mechanistic target of rapamycin (AMPK/mTOR), and have shown potential to suppress tumor growth, enhance therapeutic sensitivity, and reduce toxicity. However, current evidence is still largely limited to in vitro and animal studies, criteria for autophagic flux evaluation remain inconsistent, and systematic studies on pharmacokinetics/pharmacodynamics (PK/PD), drug-drug interactions, and safety are lacking. Based on a systematic review of previous basic and preclinical studies, this article focuses on the representative molecular mechanisms by which active components and compound formulas of traditional Chinese medicine regulate autophagy, as well as their potential benefits and major limitations in the pharmacological treatment of BC, and further proposes possible directions for subsequent combination therapy and optimization of therapeutic strategies from the perspective of clinical pharmacology.
Ursodeoxycholic acid (UDCA) is an endogenous substance. After oral administration of UDCA preparations, conjugated UDCA is formed, and its metabolism in the body is more complex than that of exogenous substances. This article based on the pharmacokinetic (PK) characteristics of UDCA, summarized the technical key points in the current bioequivalence (BE) studies of UDCA preparations. It analyzed from various aspects, including trial design, methodological validation, biological sample analysis, and bioequivalence result evaluation. This provides a certain reference for the bioequivalence studies of endogenous drugs such as ursodeoxycholic acid preparations.