ArchiveTo evaluate the differences in clinical efficacy between continued azithromycin therapy and switching to tetracycline antibiotics (doxycycline/minocycline) in children with macrolide-unresponsive Mycoplasma pneumoniae pneumonia (MUMPP).
Children with MUMPP hospitalized in our hospital were divided into treatment group and control group according to the secondary antibiotic selection after ineffective initial macrolide treatment for 72 hours. The control group continued to receive azithromycin for injection at a dose of 10 mg·kg-1 once a day for a 7-day course of treatment. The treatment group was switched to oral tetracycline antibiotics: minocycline capsules at 2 mg·kg-1 twice a day, or doxycycline enteric-coated capsules at 2.2 mg·kg-1 twice a day, with a total course of 10 days. The time to defervescence, treatment effectiveness rate, and changes in white blood cell count (WBC), neutrophil percentage (NE%) and C-reactive protein (CRP) levels were compared between the two groups, and a safety evaluation was performed.
A total of 107 cases were included in this study, with 87 cases in the treatment group and 20 cases in the control group. The total clinical effective rates of the treatment group and the control group were 90.80% (79 cases /87 cases) and 85.00% (17 cases /20 cases), respectively, and the difference was not statistically significant (P>0.05). The antipyretic time of the treatment group and the control group was (6.82±1.71) and (7.75±2.12) days, respectively, with statistically significant difference (P<0.05). Before conversion therapy, the white blood cell counts of the control group and the treatment group were (8.58±3.67) and (6.77±2.59) ×109·L-1, respectively, and the CRP levels were (14.44±8.58) and (26.43±26.53) mg·L-1, respectively; both differences were statistically significant (all P<0.05). The neutrophil percentages of the control group and the treatment group were (57.93±9.39)% and (62.43±10.79)%, respectively, the lymphocyte percentages were (32.43±8.46)% and (28.60±9.57)%, respectively, the monocyte percentages were (7.63±2.01)% and (7.43±2.53)%, respectively, none of these differences were statistically significant (all P>0.05). The total incidence of adverse drug reactions in the treatment group and the control group was 1.15% and 0, respectively, with no statistically significant difference (P>0.05).
For children with MUMPP, tetracycline antibiotics provide faster fever resolution, but the overall efficacy of both regimens is comparable. Clinical decisions should consider the child’s age (tetracyclines preferred for those ≥8 years) and parental informed consent. Continued azithromycin therapy is recommended in combination with glucocorticoids to control excessive inflammatory responses.
To compare the efficacy and safety of ticagrelor combined with nicorandil versus clopidogrel combined with nicorandil in elderly coronary heart disease (CHD) patients experiencing angina pectoris following percutaneous coronary intervention (PCI).
Patients with post-PCI angina admitted to our hospital were divided into treatment group and control group based on treatment protocols. The control group received clopidogrel bisulfate tablets (75 mg, qd), and nicotardil tablets (5 mg, tid) based on standard post-PCI therapy including aspirin enteric-coated tablets (100 mg, qd), atorvastatin calcium tablets (20 mg, qd). The treatment group received ticagrelor tablets (90 mg, bid), and nicotardil tablets (5 mg, tid) based on the same standard post-PCI therapy. Both groups underwent continuous treatment for 24 weeks. Sublingual nitroglycerin tablets were allowed for acute angina attacks. Primary outcomes included therapeutic efficacy, cardiac function indices, lipid profiles, lipoprotein-associated phospholipase A2 (Lp-PLA2) levels, antiplatelet reactivity and coagulation parameters, Seattle angina questionnaire (SAQ) scores, and incidence of major adverse cardiovascular events (MACE) were compared between the two groups.
A total of 123 patients were enrolled with 59 patients in treatment group and 64 patients in control group. After treatment, the overall response rates in treatment group and control group were 91.53% (54 cases /59 cases) and 78.12% (50 cases/64 cases), respectively. Left ventricular end-diastolic diameter (LVEDD) in treatment group and control group were (44.76±4.23) mm and (46.63±4.13) mm, respectively; left ventricular end-systolic diameter (LVESD) were (30.16±4.22) and (32.57±5.13) mm, respectively; left ventricular ejection fraction (LVEF) were (61.49±6.24)% and (58.49±6.13)%, respectively; cardiac index (CI) were (2.80±0.29) and (2.67±0.27) L·min-1·m-2, respectively; triglycerides (TG) were (1.70±0.21) and (1.82±0.35) mmol·L-1, respectively; total cholesterol (TC) were (5.12±0.56) and (5.41±0.60) mmol·L-1, respectively; low-density lipoprotein cholesterol (LDL-C) were (3.28±0.64) and (3.57±0.58) mmol·L-1, respectively; high-density lipoprotein cholesterol (HDL-C) were (2.74±0.54) and (2.53±0.51) mmol·L-1, respectively; Lp-PLA2 were (231.63±32.47) and (244.89±35.62) ng·mL-1, respectively. Regarding antiplatelet and coagulation parameters, the arachidonic acid inhibition rate (AA-IR) in treatment group and control group were (81.26±15.11)% and (74.52±15.13)%, respectively; adenosine diphosphate inhibition rate (ADP-IR) were (78.56±15.96)% and (70.95±14.57)%, respectively; lower maximum platelet aggregation rate (MPAR) were (26.78±4.82)% and (28.52±4.18)%, respectively; coagulation rate (CR) were (18.04±2.04) and (19.28±2.71) sig·min-1, respectively; SAQ scores were significantly higher in the treatment group across all dimensions: angina stability were (82.80±9.10) and (78.53±8.91) points, respectively; attack frequency were (80.17±12.24) and (75.63±10.22) points, respectively; physical activity limitation were (82.10±10.26) and (77.77±9.99) points, respectively; disease awareness were (74.49±11.25) and (69.13±10.96) points, respectively; and satisfaction were (83.41±10.35) and (78.56±11.49) points, respectively; the difference of the above indexes were all statistically significant (all P<0.05). The total incidence rates of MACE in treatment group and control group were 6.78% (4 cases/59 cases) and 20.31% (13 cases /64 cases), respectively, with statistically significant difference (P<0.05).
Compared with clopidogrel combined with nicorandil, ticagrelor combined with nicorandil exhibits superior efficacy in treating angina pectoris after CHD-PCI in elderly patients, with significant improvements in cardiac function and angina symptoms, as well as favorable safety profiles.
To explore the clinical efficacy and safety of thoracolumbar fascia plane block with ropivacaine hydrochloride injection combined with compound betamethasone injection in elderly patients undergoing lumbar spine surgery during the perioperative period.
The elderly patients admitted to our hospital who underwent posterolateral approach lumbar fusion (PLIF) under general anesthesia due to lumbar degenerative diseases were divided into control group and treatment group according to different anesthesia methods. Both groups of patients received thoracolumbar fascia plane (TLIP) block. Control group was injected with a single dose of 20 mL of 0.375% ropivacaine hydrochloride injection, while treatment group was injected with a single dose of a mixture of 20 mL of 0.375% ropivacaine hydrochloride injection and 5 mg of compound betamethasone injection for TLIP block. The remaining operations were same. The hemodynamic indicators, rehabilitation process indicators, opioid dosage and remedial analgesia conditions, visual analogue scale (VAS) scores at rest and turning over at different time points, stress and immune indicators of the two groups of patients were compared, and safety evaluations were conducted.
A total of 115 cases were screened in this study, with 102 cases enrolled. Among them, 50 cases were enrolled in control group and 52 cases in treatment group. The heart rate (HR) of the control group and the treatment group at T4 were (82.13±10.68) and (74.81±10.19) times·min-1, respectively; and the mean arterial pressure (MAP) were (92.33±9.87) and (88.27±8.92) mmHg, respectively; the recovery time were (36.41±6.97) and (31.87±6.53) min, respectively; and the resting VAS scores at 48 hours after the operation were (2.71±0.88) and (2.56±0.82) points, respectively; the VAS scores at turning over 48 hours after the operation were (3.42±0.97) and (2.88±0.84) points, respectively; the first PCIA time were (20.04±5.67) and (16.79±4.32) hours, respectively; the effective compression times of PCIA were (14.19±4.36) and (11.64±3.52) times, respectively; and the β-Endorphin (β -endorphin) 24 hours after the operation were (160.31±19.68) and (146.83±18.49) pg·mL-1, respectively; CC Chemokine ligand 2 (CCL2) were (109.39±19.78) and (97.86±17.88) pg·mL-1, respectively; angiotensin Ⅱ (Ang Ⅱ) were (79.14±12.53) and (70.65±11.71) pg·mL-1, respectively. The above indicators of treatment group were compared with those of control group, and the differences were all statistically significant (all P<0.05). The incidence rates of adverse reactions to anesthetic drugs during the perioperative period in the two groups of patients were 9.62%(5 cases/52 cases) and 16.00%(8 cases/50 cases), respectively, and there was no statistically significant difference (P>0.05).
The TLIP block with ropivacaine combined with betamethasone can enhance the analgesic effect during the perioperative period of patients undergoing PLIF, reduce the dosage of opioid drugs, alleviate early pain symptoms and the level of postoperative stress responses, and has a relatively high level of safety.
To investigate the changes of intestinal flora in patients with Helicobacter pylori (HP) positive gastric ulcer treated with rabeprazole capsule combined with aluminum phosphate gel based on metagenomics.
Patients with HP-positive gastric ulcers were selected who were admitted from January 2022 to December 2024. They were randomly divided into the combined group and the control group. The control group only received rabeprazole treatment, while the combined group received combined treatment with rabeprazole and aluminum phosphate gel. The model efficacy and key biomarkers for distinguishing patients in different treatment groups were detected using a linear kernel-based support vector classification (SVC) model and recursive feature elimination (RFE). The association between microbial abundance and clinical continuous indicators was detected using a support vector regression factor model (SVR). The Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis was used to detect the metabolic and signaling pathways enriched by the differentially expressed genes in the intestinal microbiota. The clinical efficacy of the two groups was compared, and the safety was evaluated.
A total of 130 patients were enrolled in the study, with 65 patients in each of the combined group and the control group. The intestinal microbial diversity in the combined group was significantly higher than that in the control group (P<0.05). Using RFE to further distinguish between the two groups, the area under the curve (AUC) was 0.80. Among the patients in the combined group, the levels of 10 metabolites were elevated. Through multi-omics integrated analysis of the fecal samples of the two groups of patients, it was found that the AUC of combining specific microbial communities and fecal metabolites analysis was 0.85, with higher accuracy than using microbial community or metabolite analysis alone, and the statistical difference was statistically significant (P<0.05). SVC and SVR analysis showed that the intestinal inflammation of patients was related to the composition of specific microbial communities. A metabolic reaction network diagram was constructed based on KEGG. The results showed that the levels of arginase, protein phosphatase, and tyrosine phosphatase were higher in patients with positive HP gastric ulcers. The ulcer healing rates in the combined group and the control group were 95.38% (62 cases/65 cases) and 83.08% (54 cases/65 cases), respectively. There was statistically significant difference between the two groups (P<0.05). The incidence of adverse drug reactions was 10.77% (7 cases/65 cases) in the combined group and 16.92% (11 cases/65 cases) in the control group. There was no statistically significant difference between the two groups (P>0.05).
The treatment plan of rabeprazole combined with aluminum phosphate gel can enhance the diversity of intestinal microorganisms, promote the secretion of microbial metabolites, effectively improve the intestinal flora, and facilitate the recovery of patients.
To observe the clinical efficacy of dulaglutide injection combined with letrozole tablets in the treatment of obese polycystic ovary syndrome (PCOS) infertility patients.
Obese infertility patients with PCOS were divided into control group and treatment group according to medication regimen. The control group was given letrozole tablets 5 mg orally, once a day for 3 months on the basis of conventional treatment; the treatment group was given dulaglutide injection 1.5 mg, subcutaneous injection once a week, and letrozole tablets were treated with the same method as the control group for 3 months. The clinical efficacy, glucose metabolism characteristics, visceral fat, body composition and the occurrence of adverse drug reactions were compared between the two groups.
42 patients were included in the treatment group and 38 in the control group. After treatment, the total effective rate of treatment group and control group was 90.48% (38 cases /42 cases) and 73.68% (28 cases /38 cases), the difference was statistically significant (P<0.05). After treatment, the fasting plasma glucose (FPG) of the treatment group and the control group were (4.37±0.85) and (4.84±0.81) mmol·L-1, respectively; glycosylated hemoglobin (HbA1c) were (4.84±0.82)% and (5.25±0.88)%, respectively; homeostasis model assessment for insulin resistance (HOMA-IR) were 2.45±0.41 and 2.73±0.48, respectively; visceral fat mass were (687.19±97.29) and (739.37±105.24) g, respectively; visceral fat volume were (751.21±106.34) and (821.82±112.64) cm3, respectively; visceral fat area were (143.29±27.88) and (156.39±25.26) cm2, respectively; body mass index (BMI) were (32.04±3.65) and (34.33±3.56) kg·m-2, respectively; waist-hip ratio (WHR) were 0.96±0.22 and 1.10±0.25, respectively; body fat percentage were (31.43±4.87)% and (34.37±4.54)%, respectively. The differences of the above indexes between the two groups were statistically significant (P<0.05, P<0.01). The main adverse drug reactions in the treatment group were nausea, vomiting, and loss of appetite, while no obvious adverse reactions occurred in the control group. There was no statistically significant difference in the total incidence of adverse reactions between the two groups (P>0.05).
Dulaglutide injection combined with letrozole tablets has significant clinical efficacy in the treatment of obese PCOS infertility patients, which can regulate the level of glucose and lipid metabolism, visceral fat content and body composition, reduce insulin resistance, and has certain safety.
To analyze the effect of conbercept ophthalmic injection on aqueous humor glucose (AHG) and vascular endothelial growth factor (VEGF) in elderly patients with diabetes retinopathy (DR) and vitreous hemorrhage, and the correlation with blood glucose.
A total of 80 elderly patients with DR and vitreous hemorrhage were selected as the study subjects. All of them received intravitreal injection of 0.05 mL of conbercept ophthalmic injection for 7 consecutive days, and then underwent vitrectomy. They were divided into the standard reaching group and the non-standard reaching group according to whether blood glucose control met the standard. The changes in ocular signs and visual recovery indicators [central macular thickness (CMT), hemorrhagic spot area and best corrected visual acuity (BCVA)], aqueous humor AHG, VEGF, inflammatory factors [interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)] and blood glucose before and after conbercept ophthalmic injection treatment were compared between groups. Pearson method was used to analyze the correlation between AHG, VEGF and blood glucose level. Logistic regression method was used to identify the independent influencing factors of inadequate blood glucose control.
49 patients were included in the standard reaching group, and 31 patients were included in the non-standard reaching group. After treatment, the CMT values of standard reaching and the non-standard reaching groups were (215.63±22.45) and (254.68±26.73) μm, respectively; the bleeding spot areas were (1.18±0.14) and (1.46±0.17) mm2, respectively; the BCVA values were 0.85±0.07 and 0.71±0.08, respectively; the AHG values for aqueous humor were (4.68±0.54) and (6.27±0.65) mmol·L-1, respectively; VEGF levels were (121.46±13.65) and (158.72±16.39) pg·mL-1, respectively; IL-6 levels were (18.13±1.89) and (19.44±2.31) pg·mL-1, respectively; TNF-α levels were (6.73±0.75) and (7.16±0.73) pg·mL-1, respectively; the blood glucose levels were (5.16±0.57) and (7.22±0.78) mmol·L-1, respectively; the above indicators of standard reaching group were compared with those of the non-standard reaching group, and the differences were statistically significant (all P<0.05). Correlation analysis found that the levels of aqueous humor AHG, VEGF, IL-6 and TNF-α were positively correlated with blood glucose levels in elderly patients with DR and vitreous hemorrhage (P<0.05). Logistic regression analysis showed that aqueous humor AHG, VEGF, and IL-6 were independent risk factors for inadequate blood glucose control in elderly patients with DR and vitreous hemorrhage (P<0.05).
After conbercept ophthalmic injection treatment, there are significant differences in the levels of AHG and VEGF in elderly patients with DR and vitreous hemorrhage, and visual acuity is restored. Moreover, AHG and VEGF are positively correlated with blood glucose. Monitoring them can assist in efficacy evaluation.
To observe the clinical efficacy and safety of retroauricular injection of dexamethasone sodium phosphate injection in the treatment of sudden deafness.
Patients with sudden deafness were divided into control group and treatment group according to actual treatment method. Both groups were given conventional treatment (neurotrophy and microcirculation improvement) according to guidelines. The control group received additional intravenous drip of methylprednisolone sodium succinate (80 mg once daily for 4 d, reduced to 40 mg for 4 d, then further reduced to 20 mg for 2 d). The treatment group was given retroauricular injection of dexamethasone (5 mg every other day) in addition to the control group’s regimen. Both groups were treated for 10 d. The efficacy, metabolomic differences, hearing recovery status, hemorheological indexes, and immune function indexes were compared between the two groups. Meanwhile, the safety was evaluated.
38 cases and 42 cases were included in the control group and the treatment group, respectively. After treatment, the effective rates in the treatment group and the control group were 80.95% (34 cases/42 cases) and 57.89% (22 cases/38 cases), with statistically significant difference (P<0.05). There were significant increases in 11 metabolites and significant decreases in 18 metabolites before treatment for sudden deafness. The four metabolites showing the most significant increases were ascorbic acid, tauroursodeoxycholic acid, D-pantothenic acid, and glucaric acid. The most significantly decreased metabolites were lysophosphatidylethanolamine and vanillic acid. After treatment, patients with sudden deafness in the effective group showed significant increases in 37 metabolites and significant decreases in 8 metabolites compared to the ineffective group. The three metabolites showing the most significant increases were L-leucine, undecanoylcarnitine, and lauroylcarnitine, while the three with the most notable decreases were L-histidine, 2-pyridylacetic acid, and D-pantothenic acid. After treatment, hearing thresholds under 0.5, kHz in the control group and the treatment group were (49.82±7.03) and (43.69±5.38) dB, respectively; hearing thresholds under 1.0 kHz were (58.14±7.39) and (46.33±6.25) dB, respectively; hearing thresholds under 2.0 kHz were (60.05±8.23) and (49.51±5.30) dB, respectively; hearing thresholds under 4.0 kHz were (62.29±8.14) and (51.36±5.87) dB, respectively, with statistically significant differences between two groups (P<0.05). After treatment, superoxide dismutase (SOD) levels in the control group and the treatment group were (94.65±14.06) and (99.72±13.56) μg·L-1; malondialdehyde (MDA) levels were (4.36±0.51) and (3.94±0.40) μmol·L-1, with statistically significant differences between groups (P<0.05). After treatment, plasma viscosity in the control group and the treatment group was (2.12±0.30) and (1.55±0.26) mPa·s; erythrocyte aggregation index was 3.38±0.30 and 2.97±0.19; low-shear viscosity was (10.13±1.60) and (9.06±1.19) mPa·s; high-shear viscosity was (5.96±0.39) and (5.33±0.31) mPa·s, with statistically significant differences between groups (P<0.05). After treatment, CD3+ in the control group and the treatment group was 57.76±4.70 and 63.52±5.46; CD4+ was 33.29±3.38 and 37.42±3.68; CD4+/CD8+ was 1.43±0.22 and 1.70±0.30; immunoglobulin (Ig) G levels were (12.16±1.12) and (10.23±0.93) g·L-1; IgA levels were (2.36±0.23) and (2.11±0.15) g·L-1, with statistically significant differences between groups (all P<0.05). No significant adverse reactions occurred in either group during the treatment.
Retroauricular injection of dexamethasone sodium phosphate injection is markedly effective in the treatment of sudden deafness, and it has advantages in improving metabolomic differences, hemorheology and immune function.
To comparatively analyze the molecular characteristics of linear plasmids in Enterococcus avium, clarify the global transmission trajectory of linear plasmids in Enterococcus, and explore the genetic stability of linear plasmids in different host strains through subculture of transconjugants, thereby providing a theoretical basis for the prevention and control of clinically drug-resistant bacteria.
The minimum inhibitory concentrations (MICs) of vancomycin against Enterococcus avium ZB195, three recipient strains (Enterococcus avium 07H170, Enterococcus faecalis FA2-2, and Enterococcus faecium BM4105RF), and their corresponding transconjugants were determined using the broth microdilution method. Whole-genome sequencing of strain ZB195 was performed to characterize its plasmid features. Linear plasmid sequences from 18 global Enterococcus faecium strains isolated between 2000 and 2019 were collected, and phylogenetic trees and Bayesian evolutionary trees were constructed using MAFFT, IQtree, and BEAST software. The global transmission trajectory was simulated with SpreaD3 software. The genetic stability of linear plasmids in different host strains was evaluated through a 15-day subculture experiment without antibiotic selection pressure.
For the first time, this study identified a linear plasmid in the genome of Enterococcus avium ZB195, which harbors the vancomycin resistance vanA gene and was capable of horizontal transfer to three recipient strains. Sequence alignment showed that the linear plasmid of ZB195 had the highest sequence identity with that of Enterococcus faecium AA708 from Japan, and phylogenetic analysis confirmed that they were most closely related. Simulation of global transmission trajectories revealed that the linear plasmid in Enterococcus was first detected in Japan in 2000, and then gradually spreaded to China, the United States, Norway, Denmark, India and other countries. Passage experiments indicated that the linear plasmid exhibited the highest stability in Enterococcus avium hosts.
The linear plasmids detected in Enterococcus strains in China may have originated from the horizontal transmission of Enterococcus faecium from Japan. Moreover, after transferring to Enterococcus avium, these plasmids can form better host adaptability. This suggests that it is necessary to strengthen cross-regional monitoring of linear plasmids in Enterococcus to curb the global spread of drug-resistant genes.
To investigate the effects of lycorine (LYC) on the proliferation and apoptosis of acute promyelocytic leukemia (APL) cells by regulating the phosphatase and tensin homolog deleted on chromosome ten (PTEN)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway.
Human APL cells (NB4) were treated with 1.0-32.0 μmol·L-1 LYC, the cell viability was detected, and the LYC experimental concentration was screened. NB4 cells were divided into group A (control group), group B, group C, group D (lycorine low concentration group, medium concentration group, high concentration group), group E (high concentration lycorine+PI3K activator 740 Y-P group). Except for the control group, groups B, C, and D were treated with 4.0, 8.0 and 16.0 μmol·L-1 lycorine, respectively, for 24 hours. Group E was treated with 16.0 μmol·L-1 lycorine combined with 25.0 μmol·L-1 740 Y-P for 24 hours. Cell proliferation, apoptosis, invasion, migration, and cell cycle status were detected, and the expression of related proteins was detected.
After treatment with concentrations of 4.0, 8.0 and 16.0 μmol·L-1 of lycorine, the survival rate of NB4 cells prominently decreased, therefore, they were used for subsequent experiments. The colony formation numbers of NB4 cells in group A, group B, group C, group D and group E were 151.38±16.42, 117.15±12.78, 81.04±8.36, 56.17±6.05 and 105.02±10.64, respectively. The scratch healing rates were (89.62±9.15) %, (72.57±7.45)%, (55.34±5.83)%, (36.78±3.72)% and (65.59±6.58)%, respectively. The number of cell invasion was (168.27±17.82), (132.69±14.39), (90.58±9.25), (61.64±6.37) and (110.59±12.27), respectively. The proportion of cells in S phase was (46.17±4.71)%, (35.18±3.56)%, (28.20±3.13)%, (20.52±2.16)% and (32.01±3.32)%, respectively. The percentages of cells in G2/M phase were (24.68±2.56)%, (19.34±1.97)%, (15.62±1.55)%, (11.15±1.23)% and (17.03±1.89)%, respectively. The levels of cyclin dependent kinase 1 (CDK1) were 0.95±0.09, 0.74±0.07, 0.50±0.05, 0.32±0.03 and 0.63±0.06, respectively. The levels of matrix metalloproteinase 2 (MMP-2) were 1.14±0.11, 0.83±0.08, 0.56±0.05, 0.37±0.03 and 0.69±0.06, respectively. The levels of matrix metalloproteinase 9 (MMP-9) were 0.94±0.09, 0.70±0.07, 0.47±0.04, 0.26±0.02 and 0.55±0.05, respectively. The phosphorylated phosphatidylinositol 3-kinase (p-PI3K)/PI3K were 0.86±0.08, 0.71±0.07, 0.45±0.04, 0.26±0.02 and 0.55±0.05, respectively. The expression levels of phosphorylated protein kinase B (p-AKT)/AKT were 0.91±0.09, 0.78±0.07, 0.53±0.05, 0.31±0.03 and 0.69±0.06, respectively. The apoptosis rates were (2.23±0.26)%, (17.41±1.82)%, (26.34±2.75)%, (39.62±4.05)% and (21.58±2.27)%, respectively. The proportion of cells in G0/G1 phase was (29.15±3.06)%, (45.48±4.67)%, (56.18±5.73)%, (68.33±6.88)% and (50.96±5.01)%, respectively. The levels of Bcl-2 associated X protein (Bax) were 0.26±0.02, 0.41±0.04, 0.72±0.07, 0.98±0.09 and 0.66±0.06, respectively. The levels of PTEN were 0.32±0.03, 0.45±0.04, 0.74±0.07, 0.96±0.09 and 0.61±0.06, respectively. Group B, group C, group D compared with group A, group E compared with group D, the above indicators were statistically significant (P<0.05). After NK cells were co-cultured with NB4 cells, compared with the A group, the cell killing rate of B, C and D groups increased (P<0.001). Compared with the D group, the cell killing rate of E group decreased (P<0.001).
Lycorine inhibited APL cells with up-regulation of PTEN expression and inhibition of PI3K/AKT pathway, and its effect is dependent on PI3K/AKT pathway.
To explore the mechanism by which hedysarum polybotrys polysaccharide (HPS) improves iron death of steatotic hepatocytes through the protein kinase RNA-like endoplasmic reticulum kinase- nuclear factor-erythroid 2-related factor 2 (PERK-Nrf2) signaling pathway.
The cells were cultured with 0.6 mmol·L-1 fatty acids to replicate the non-alcoholic fatty liver disease cell model. The LO-2 cell were divided into normal group (complete medium), model group (0.6 mmol·L-1 fatty acid solution), positive control group (0.6 mmol·L-1 fatty acid solution+24 μmol·L-1 liproxstain-1) and experimental group (0.6 mmol·L-1 fatty acid solution + 50 mg·L-1 HPS), culture for 24 h. Stain with Oil Red O was used to analyze the positive area (%Area) of cell lipid deposition; the content of lipid peroxide(LPO), 4-hydroxynonenal(4-HNE), glutathione(GSH) and superoxide dismutase(SOD) was detected by enzyme-linked immunosorbent assay(Elisa) method; the relative expressions levels of PERK-Nrf2 signaling pathway protein in hepatocytes were detected by Western blot; immunofluorescence assay was used to detect the relative expression levels of GPX4 and SLC7A11 proteins.
The % Area of cell lipid deposition in hepatocytes of normal group, model group, control group and experimental group were 0.02±0.01, 0.26±0.08, 0.09±0.02 and 0.15±0.04; the contents of LPO were (2.62±0.17), (13.47±1.55), (6.31±1.12) and (5.71±1.50) nmol·mL-1; the contents of 4-HNE were (8.06±0.40), (14.60±2.02), (9.40±0.81) and (12.94±0.56) ng·L-1; the contents of GSH were (120.73±7.75), (34.60±2.98), (67.86±2.08) and (59.33±7.46) mg·L-1; the contents of SOD were (7.25±0.61), (3.77±0.44), (5.22±0.76) and (8.12±0.78) U·mL-1; the levels of Grp78 mRNA were 1.01±0.15, 1.47±0.11, 1.41±0.08 and 1.02±0.05; the levels of PERK mRNA were 1.00±0.09, 1.85±0.16, 1.02±0.27 and 1.16±0.01; the levels of Nrf2 mRNA were 1.01±0.12, 0.26±0.07, 0.68±0.09 and 0.66±0.05; the levels of GPX4 mRNA were 1.00±0.05, 0.79±0.02, 0.87±0.17 and 0.83±0.10; the levels of SLC7A11 mRNA were 1.01±0.17, 0.50±0.14, 0.91±0.09 and 0.98±0.05; the relative expression levels of Grp78 protein were 1.00±0.11, 2.72±0.07, 1.83±0.04 and 2.24±0.06; the relative expression levels of PERK protein were 1.00±0.06, 1.21±0.08, 1.03±0.07 and 0.95±0.06; the relative expression levels of p-PERK protein were 1.00±0.04, 2.70±0.08, 1.40±0.07 and 1.76±0.06; the relative levels of PERK protein phosphorylation were 1.00±0.09, 2.24±0.21, 1.36±0.03 and 1.85±0.09; the relative expression levels of Nrf2 protein were 1.00±0.03, 0.52±0.01, 0.73±0.02 and 0.84±0.02; the protein fluorescence intensity of GPX4 were 24.34±0.86, 13.86±1.65, 18.01±2.03 and 16.20±1.55; the protein fluorescence intensity of SLC7A11 were 69.58±4.13, 34.24±6.73, 60.75±9.35 and 45.18±6.46. Compared with the normal group, there were significant differences in the above indexes of model group (all P<0.05) ; compared with the model group, there were significant differences in the above indexes of experimental group (all P<0.05).
HPS may protect liver cells by regulating the PERK-Nrf2 signaling pathway, reducing lipid peroxidation and iron death in liver cells.
To study the mechanism of mangiferin alleviating liver injury induced by high-fat and high-sugar diet in obese rats based on oxidative stress signaling pathway.
Forty SD rats were divided into blank control group (NC) (raised normally and given the same amount of normal saline), model group (fed with high-fat and high-sugar diet and given the same amount of normal saline), the mangiferin administration group (MGF) (fed with high-fat and high-sugar diet), and mangiferin administration+miR-195-3p mimics group (MGF+miR-195-3p mimics) (fed with high-fat and high-sugar diet and administered 40 mg·kg-1 mangiferin suspension, in addition, recombinant lentiviruses containing miR-195-3p mimics were injected into the tail vein), with 10 rats in each group. After treatment, body mass, visceral fat mass and liver coefficient were measured, blood glucose, blood lipid, aminotransferase, liver glycogen and oxidative stress related factors were detected by kit, and histopathological status of liver was detected by hematoxylin-eosin (HE) staining. Real-time quantitative fluorescence polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization (FISH) were used to detect the levels of miR-195-3p, and protein Western blot (WB) was used to detect the expression levels of nuclear factor erythroidderived 2-like 2 (Nrf2) and heme oxygenase-1 (HO-1).
After different treatment, the liver coefficients of NC group, Model group and MGF group were (2.20±0.29)%, (3.11±0.40)% and (2.75±0.32)%, respectively. Insulin was (310.63±38.06), (426.59±55.35) and (378.57±42.81) ng·L-1; glutamic pyruvic transaminase was (55.17±6.11), (137.57±17.45) and (106.85±12.66) U·L-1, respectively. The liver glycogen was (21.64±2.98), (7.96±1.03) and (15.52±2.16) mg·g-1, respectively. The malondialdehyde levels in Model group, MGF group and MGF+miR-195-3p mimics group were (9.63±1.22), (7.79±0.91) and (9.11±1.16) mmol·g-1, respectively, super oxide dismutase was (110.42±14.57), (251.36±36.26) and (181.45±20.95) U·g-1, and Nrf2 mRNA was 1.00±0.12, 1.97±0.20, 1.29±0.15, respectively. The mRNA of HO-1 was 1.00±0.14, 2.84±0.35 and 1.81±0.29, respectively. Comparison of Model group with NC group, MGF group with Model group and MGF+miR-195-3p mimics group with MGF group showed statistically significant differences in the above indexes (all P<0.05).
Mangiferin can reduce liver injury and regulate glucose and lipid metabolism in obese rats, and its mechanism may be related to the down-regulation of miR-195-3p expression and activation of Nrf2/HO-1 signaling pathway.
To establish an ultra-high performance liquid chromatography-tandem mass spectrometry method (UPLC-MS/MS) for the determination of the contents of cholic acid, imperatorin, quercetin, isoquercetin, ferulic acid, chlorogenic acid, rutin, and cryptochlorogenic acid in the Huoxuexiaozhong capsule.
The analysis was performed by UPLC-MS/MS. Chromatographic conditions: separation was achieved on an Agilent Poroshell 120 EC-C18 column (2.1×150 mm, 1.9 μm). The mobile phase consisted of acetonitrile (A) and 0.1% formic acid in water (B) with gradient elution, at a flow rate of 0.3 mL·min-1 and a column temperature of 35 ℃. Mass spectrometry conditions: multiple reaction monitoring (MRM) with positive/negative ion switching mode was used electrospray ionization source. The ion source voltage was set at +5.5 kV and -4.5 kV, with the ion source temperature maintained at 550 ℃. The gas settings were as follows: GS1 344.74 kPa, GS2 344.74 kPa, and CUR 241.32 kPa. The specificity, standard curves and limits of detection and quantification, precision and recovery, and stability were investigated.
The analytical method demonstrated good linearities for cholic acid, quercetin, isoquercitrin, ferulic acid, chlorogenic acid, cryptochlorogenic acid, rutin and imperatorin over the concentration ranges of (0.26-25.70), (0.03-1.68), (0.03-1.51), (0.03-1.47), (0.40-10.34), (0.56-27.05), (0.03-1.37), and (2.50-759.65) μg·mL-1, respectively (R2 ≥ 0.9911). The relative standard deviations (RSD) of peak areas for reference standards and test samples were ≤ 2.44% and ≤ 2.87%, respectively. Recoveries for all components ranged from 96.54% to 107.86%, with RSD values between 0.47% and 5.41%, indicating good precision and accuracy. The stability of the method showed an RSD of ≤ 2.77%.
The UPLC-MS/MS method was established to determine the concentration of eight components in Huoxuexiaozhong capsule simultaneously. This method has high sensitivity, specificity and stability, which can be used as a reliable reference for the quality control of the capsule.
To investigate the prevalence and associated influencing factors of potentially inappropriate medications (PIM) in elderly hospitalized patients with ischemic stroke, and to construct a risk prediction model for this population. This study aimed to provide decision support for identifying high-risk patients and ensuring rational clinical medication use.
Retrospective analysis was performed on the medical records of elderly hospitalized patients with ischemic stroke admitted to our hospital from January 2021 to December 2023. The 2023 version of the Beers Criteria was adopted to assess PIM. Univariate and multivariate Logistic regression analyses were applied to identify risk factors associated with PIM, and the optimal model was ascertained via the Akaike information criterion (AIC) followed by nomogram development. The discriminative ability, calibration, and clinical utility of the model were evaluated systematically.
A total of 1 797 patients were included, among whom 866 (48.19%) had PIM, involving 1 756 PIM episodes. Multivariate Logistic regression analysis revealed that female gender, number of medications≥10 types, National Institutes of Health Stroke Scale (NIHSS) score of >5 points, personal history of cerebral infarction, type 2 diabetes mellitus, coronary heart disease, and atrial fibrillation were independent risk factors for PIM (P<0.05, P<0.001). Validation of the nomogram model showed an area under curve (AUC) of the receiver operating characteristic of 0.73. The Hosmer-Lemeshow goodness-of-fit test showed a P-value >0.05, meaning the model fit well, and there was good agreement between the calibration curve and the ideal curve. Clinical decision curve analysis (DCA) demonstrated that when the threshold probability ranged from 15% to 87%, the model achieved a high net benefit, confirming its clinical practical value.
The constructed nomogram model exhibits good discriminative ability, calibration, and clinical applicability. It can accurately predict the risk of PIM in elderly patients with ischemic stroke, facilitating early clinical risk identification and targeted intervention implementation.
Cardiac fibrosis is a common pathological basis for a variety of cardiovascular diseases, and its core feature is cardiac fibroblast overactivation and extracellular matrix deposition, which ultimately leads to cardiac structural remodeling. Studies have shown that mitochondrial dysfunction is an important driver of the occurrence and development of cardiac fibrosis. Mitochondrial quality control is a set of precise dynamic regulatory systems in cells, involving mitochondrial dynamics, mitochondrial biogenesis and mitochondrial autophagy, which are responsible for maintaining mitochondrial homeostasis. Traditional Chinese medicine has the advantages of multiple pathways, multiple targets and small toxic side effects, and shows great potential in regulating mitochondrial quality control and treating cardiac fibrosis. Based on this, this paper systematically reviews the relationship between mitochondrial quality control and cardiac fibrosis and the mechanism of traditional Chinese medicine to regulate mitochondrial quality control in the treatment of cardiac fibrosis, aiming to provide a theoretical basis and new targets for the clinical treatment of cardiovascular diseases.
Sepsis-induced cardiomyopathy is a common cardiovascular complication among septic patients, which significantly increases mortality rates. Ferroptosis is an iron-dependent form of regulated cell death characterized by increased lipid reactive oxygen species (ROS), which causes lipid peroxidation and cell membrane damage. Increasing evidence has highlighted a significant link between ferroptosis and sepsis-induced cardiomyopathy, in which traditional Chinese medicine (TCM) exhibits promising therapeutic potential. This article reviews the mechanism of ferroptosis and current advances in the use of TCM active ingredients and formulated preparations to target ferroptosis in treating sepsis-induced cardiomyopathy, aiming to offer new perspectives for clinical management.
As a multi-target tyrosine kinase inhibitor, sorafenib is the core therapeutic drug for advanced hepatocellular carcinoma, renal cell carcinoma and differentiated thyroid cancer. However, its cardiotoxicity significantly limits clinical application, mainly manifests in hypertension, myocardial ischemia, heart failure, arrhythmia, and thrombosis/hemorrhage events, which seriously affect the patient’s prognosis. This paper deeply explores the molecular mechanisms of sorafenib inducing cardiotoxicity, including key pathways such as oxidative stress and mitochondrial dysfunction, autophagy imbalance, ribonucleic acid binding motif protein 20 (RBM20) mediated gene splicing abnormalities, calcium homeostasis imbalance and myocardial electrophysiological abnormalities; at the same time, a systematic summary of clinical prevention and treatment strategies, covering monitoring and intervention measures for adverse reactions such as hypertension and heart failure, as well as research progress in experimental therapeutic drugs.
The high-altitude environment is characterized by hypoxia, low temperatures, strong radiation, and low humidity, with hypoxia exerting profound effects on human physiological functions. Cardiovascular disease, a prevalent chronic condition in plateau regions, poses a serious threat to health. While pharmacotherapy is the primary intervention, the hypoxic environment significantly alters the pharmacokinetic processes of cardiovascular drugs in vivo, thereby compromising their safety and efficacy. Consequently, investigating the pharmacokinetic characteristics of cardiovascular drugs under high-altitude hypoxia is crucial. Given the current scarcity of research in this area, this review summarizes the impact of high-altitude hypoxia on key pharmacokinetic parameters of cardiovascular drugs and explores potential mechanisms of action, aiming to provide a theoretical basis for the rational clinical use of these drugs in plateau areas.
Elderly patients with hip fracture have a high incidence of perioperative neurocognitive disorders (PND), poor prognosis and high resource consumption. Remazolam has the pharmacokinetic advantages of esterase metabolism, predictable recovery and hemodynamic friendliness, and can be quickly reversed by flumazenil, making it suitable for people with advanced age, insufficient organ reserve or high risk of cognitive complications. Recent studies have shown that remazolam can reduce the level of postoperative inflammatory markers, improve early cognitive function and reduce the incidence of delirium, while retaining good hemodynamic stability and controllable recovery characteristics. The underlying mechanism involves the inhibition of excessive activation of microglia and neuroinflammatory response, reduction of systemic inflammatory response, reduction of stress and pain intensity, and reduction of cerebral hypoperfusion events and other pathways to produce neuroprotective effects. Therefore, this paper integrates the latest evidence of the molecular mechanism, pharmacological characteristics and clinical application of remazolam in the prevention and treatment of perioperative neurocognitive disorders in elderly patients with hip fracture, and emphasizes its potential value in optimizing perioperative anesthesia management of elderly hip fracture. It is expected to provide a theoretical basis for future high-quality, multi-center, long-term follow-up clinical research, and provide reference for individualized perioperative strategy formulation and PND prevention and treatment.
Polymyxin’s clinical application is limited by its significant nephrotoxicity, complex pharmacokinetic and pharmacodynamic characteristics, and the growing issue of bacterial resistance. This systematic review summarizes research progress on three novel polymyxin derivatives: SPR206, QPX9003, and MRX-8. Through structural design, these compounds retain potent antimicrobial activity while reducing nephrotoxicity and improving PK/PD profiles. Preclinical studies and preliminary clinical trials demonstrate broad-spectrum antimicrobial activity against multidrug-resistant Gram-negative bacteria, along with promising efficacy in models such as pulmonary infections. Although these candidate drugs are still undergoing clinical trials, they show potential to become alternatives to existing polymyxin therapies.
Dystrophic epidermolysis bullosa (DEB) is a mechanobullous disorder caused by mutations in the COL7A1 gene encoding type VII collagen. It has been included in China’s Rare Disease List, with clinical management primarily focused on preventing mechanical trauma and infections. In recent years, significant progress has been made in the development of advanced therapy medicinal products (ATMPs) for DEB, with two products already approved for marketing and multiple others undergoing clinical trials. This article reviews the fundamental characteristics of both approved and investigational ATMPs for DEB and discusses key considerations in clinical trial design, aiming to provide valuable insights for the clinical development of advanced therapies for this condition.
As a representative of the new generation of nucleic acid vaccine technology, messenger ribonucleic acid (mRNA) vaccines have demonstrated advantages such as rapid manufacture, high efficacy, and good safety since Coronavirus Disease 2019(COVID-19), becoming an important direction in global vaccine research and development. Many mRNA vaccines have been approved or in clinical trials. This article systematically reviews and summarizes the current research and development of mRNA vaccines, discussing the current state of mRNA vaccine development and evaluation strategies in China, with the aim of providing scientific basis for the development of mRNA vaccines.
To examine issues in sample management within drug clinical trials, their implications on subject rights, data integrity, and propose targeted enhancements.
A retrospective analysis was conducted on 69 clinical trial projects, encompassing bioequivalence and innovative drug phase I-IV trials, processed by the phase I clinical trial laboratory at our institution from April 2018 to December 2024. Problems in biological sample management were identified through monitoring records maintained by quality control professionals, institutional quality control personnel, and clinical research monitors. The distribution patterns of issues were analyzed, and non-standard problems were assessed and categorized using the protocol deviation (PD) evaluation system.
A total of 68 issues were identified in biological sample management, primarily centered around sample collection (27.94%), processing (19.12%), and preservation (36.76%). PD evaluations indicated that deficiencies in operational processes (e.g., non-compliance with standard operating procedures), insufficient personnel training, and irregular documentation were the primary underlying causes.
Comprehensive standardized management strategies, including enhancing standardized procedures in critical stages, improving personnel training, quality control frameworks, and implementing intelligent information systems, are essential to ensure the provision of dependable sample support for high-caliber clinical research.