To analyze the clinical efficacy and safety of polyenophosphatidylcholine (PPC) in combination with tenofovir tablets in the treatment of patients with hepatitis B combined with nonalcoholic steatohepatitis (NASH).

The patients with hepatitis B complicated with NASH in our hospital were divided into treatment group and control group by random number table method. The control group was treated with tenofovir tablets, 25 mg qd, taken during meals. The treatment group was treated with PPC on the basis of the control group. The initial dose was 456 mg tid, taken with warm boiled water, and the daily dose could not exceed 1 368 mg. After 12 weeks of treatment, the dose was reduced to 228 mg tid, according to the immune response, and the dose was maintained. Both groups were treated for 24 weeks, and the treatment group was followed up to 48 weeks after stopping PPC. The negative conversion rates of hepatitis B virus surface antigen (HBsAg) and hepatitis B virus e antigen (HBeAg), hepatitis B virus DNA (HBV-DNA) load, the levels of costimulatory molecule B7 homolog 1 (B7-H1), transforming growth factor β1 (TGFβ1), Golgi transmembrane glycoprotein 73 (GP73), chitinase 3-like protein 1 (CHI3L1) and prothrombin activity (PTA) were compared between the two groups, and the safety was evaluated.

A total of 95 cases were enrolled and 92 cases were included in statistical analysis, including 46 cases in the treatment group and 46 cases in the control group. After treatment, the total effective rates of the treatment group and the control group were 97.83% (45 cases / 46 cases) and 84.78% (39 cases / 46 cases), respectively, and the difference was statistically significant (P<0.05). After 24 weeks of treatment, the HBV-DNA load of the treatment group and the control group were 80.43% and 60.87%, respectively; the HBsAg negative conversion rates were 28.26% and 10.87%, respectively; and the HBeAg negative conversion rates were 30.43% and 13.04%, respectively. The above indicators in the treatment group were statistically significantly different from those in the control group (all P<0.05). After 48 weeks of treatment, the HBV-DNA load of the treatment group and the control group were 89.13% and 69.57%, respectively; the HBsAg negative conversion rates were 50.00% and 28.26%, respectively; and the HBeAg negative conversion rates were 50.00% and 26.09%, respectively. The above indicators in the treatment group were statistically significantlly different from those in the control group (all P<0.05 ). After treatment, the levels of B7-H1 in the treatment group and the control group were 0.40 (0.30, 0.40) and 0.60 (0.50, 0.70) ng·mL^-1, the levels of TGFβ1 were (269.02±24.36) and (287.64±27.39) ng·mL^-1, respectively; and the levels of GP73 were (76.24±8.95) and (87.22±10.03) ng·mL^-1, respectively; PTA were (80.02 ± 12.55)% and (65.24±10.24)%, respectively. The treatment group compared with the control group, the differences were statistically significant (all P<0.05). The main adverse drug reactions during treatment in the treatment group and the control group were nausea and vomiting, headache, rash and abdominal distension. The total incidence of adverse drug reactions in the treatment group was 10.87% (5 cases / 46 cases), which was 13.04% (6 cases / 46 cases) in the control group, and the difference had no statistically significant (P>0.05).

The combined application of PPC and tenofovir tablets in the treatment of hepatitis B patients with NASH can reduce the levels of B7-H1 and TGFβ1, improve the liver function of the body, and has good safety.

To develop and validate a simple scoring system for predicting the risk of infection after acute myocardial infarction (AMI) in patients undergoing percutaneous coronary intervention (PCI).

Continuous patients with ST-segment elevation myocardial infarction (STEMI) who received PCI in our hospital were divided into training set and validation set using a cohort approach. All patients received oral rosuvastatin calcium tablets 10-20 mg per day combined with evolocumab injection therapy 140 mg. The primary endpoint was post-AMI infection during hospitalization, while all-cause mortality and major adverse cardiovascular events (MACE) were considered secondary endpoints. The area under the curve (AUC) and the calibration between predicted and observed infection risks were calculated. A backward stepwise logistic regression model was selected to develop the risk score.

A total of 359 patients were included, with 217 in the training set and 142 in the validation set, and no patient dropout occurred during the study. A 24-point risk scoring system was developed, with infection risks ranging from 0.70% to 99.60% in patients with the lowest and highest scores, respectively. Seven variables including age, Killip class, insulin use, white blood cell count, serum albumin, diuretics and transfemoral approach were incorporated into the model. The model achieved equally high discrimination in both the development and validation cohorts (C-statistic: 0.85) and demonstrated good calibration in both datasets. In both development and validation cohorts, the incidence of post-myocardial infarction infection increased steadily across risk score groups. Additionally, this risk score exhibited good predictive ability for infection, in-hospital all-cause mortality.

This study established a simple bedside tool, a risk scoring system for assessing the risk of infection and other in-hospital outcomes in STEMI patients undergoing PCI. Clinicians can utilize this risk scoring system to evaluate infection risk and make evidence-based decisions accordingly.

To investigate the association between drug resistant epilepsy (DRE) and single nucleotide polymorphisms (SNPs) in whole-exome sequencing (WES).

Patients with epilepsy, who visited in our hospital, were enrolled in this study and divided into a drug-resistant group and a monotherapy-effective group based on treatment outcomes. Baseline demographic characteristics, medical history and laboratory test results were collected. Seizure outcomes were observed after more than 12 months under adequate treatment. WES was performed on 12 extreme cases (6 patients with resistant to three antiepileptic drugs vs. 6 patients effectively treated with monotherapy and undergoing dose reduction) to identify candidate SNPs. These candidate SNPs were then validated in the larger cohort to explore the association with DRE.

A tota of 560 patients were enrolled, 153 were DRE group and 407 were monotherapy-effective group. The median age in the monotherapy-effective group and the drug-resistant group was 19 years old and 25 years old, respectively; the median weight were 50 kg and 55 kg, respectively. All these differences between the two groups were statistically significant (all P<0.05); the proportion of structural etiology was 55.56% in the drug-resistant group and 45.46% in the monotherapy-effective group; the proportion of infectious etiology were 3.92% and 2.21%; the proportion of immune etiology were 3.27% and 1.23%; the proportion of metabolic and genetic etiology were 5.88% and 11.30%; the proportion of dual etiologies were 1.96% and 1.23%; the proportion of patients with impaired consciousness were 56.21% and 39.07%; the proportion of second-generation antiseizure medication as initial medication regimen were 50.98% and 65.46%; the proportion of malformation of cortical development were 10.46% and 2.95%; the proportion of hippocampal sclerosis were 15.03% and 9.58%; the proportion of hypoxic-ischemic encephalopathy were 3.92% and 1.47%; the proportion of vascular malformation were 4.58% and 3.93%; the proportion of traumatic brain injury were 1.31% and 3.44%; the proportion with brain tumor were 3.92% and 2.21%; the proportion with dual pathologies were 1.96% and 0.98%; the proportion of abnormal nonepileptogenic were 23.53% and 29.48%. Baseline information showed statistically significant differences in age, weight, etiology, presence of impaired awareness, initial medication regimen and neuroimaging results (P<0.05, P<0.001). 102 candidate SNPs were selected for genotyping and association analysis in larger cohort including 560 patients. 5 SNPs were identified to be significantly associated with DRE. Multivariate logistic regression incorporating both clinical and genetic factors revealed that hippocampal sclerosis, malformation of cortical development, hypoxic-ischemic, presence of impaired awareness, as well as the SCN2A rs17183814 GG and SPATA31 rs1919128 GA genotypes were risk factors for drug resistance (SCN2A rs17183814 GG: P=0.027; SPATA31 rs1919128 GA: P=0.014).

SCN2A rs17183814 and SPATA31 rs1919128 were found to be associated with drug resistance. Carriers of the GG genotypes of SCN2A rs17183814 and GA genotype of SPATA31 rs1919128 are more likely to develop DRE.

To observe the effects of empagliflozin tablets-assisted therapy on end-diastolic volume and major cardiovascular adverse events in patients with mild reduced EF heart failure (HFmrEF).

Patients with HFmrEF were divided into control group and treatment group by queue method. The control group received conventional treatment. The treatment group was given empagliflozin tablets in addition to control group, 10 mg each time (starting dose and target dose were both 10 mg), orally on an empty stomach in the morning, once a day. Both groups of patients were treated for 6 months. The clinical efficacy, end-diastolic volume including left ventricular end-diastolic area (LVEDA) and left ventricular end-diastolic volume (LVEDV), left ventricular ejection fraction (LVEF), myocardial markers including cardiac troponin I (cTnI) and N-terminal B-type natriuretic peptide (NT-proBNP), major adverse cardiovascular events and safety were compared between the two groups.

Both groups had no cases dropped out, with 60 cases in control group and 60 cases in treatment group. After treatment, the total effective rates of treatment group and control group were 95.00% (57 cases/60 cases) and 81.67% (49 cases/60 cases), respectively, with statistically significant difference (P<0.05). After treatment, the LVEF of treatment group and control group were (56.20±5.12)% and (50.25±4.26)%, LVEDV were (142.58±15.58) and (165.28±18.59) mL, LVEDA were (36.28±3.41) and (39.62±3.56) cm², serum NT-proBNP levels were (869.48±135.29) and (1 459.87±158.69) pg·mL^-1, cTnI levels were (7.02±1.65) and (9.28±1.74) ng·L^-1, respectively, and the incidence of major cardiovascular adverse events in treatment group and control group were 5.00% and 16.67%. The above indexes in treatment group had statistical significant differences compared with control group (all P<0.05). The adverse drug reactions of treatment group mainly include headache, hyperkalemia, hypotension and gastrointestinal reactions, while the adverse drug reactions of control group mainly include hyperkalemia, headache and hypotension. During the treatment, the incidence of adverse drug reactions in treatment group and control group were 8.33% and 5.00%, respectively (P>0.05).

Adjuvant treatment with empagliflozin tablets can improve the overall therapeutic effect of HFmrEF, improve the end diastolic volume index and LVEF of patients, regulate myocardial marker indicators, reduce the incidence of major cardiovascular adverse events, and has good safety.

To explore the clinical efficacy and safety of beraprost sodium tablets combined with alprostadil injection in patients with stage Ⅲ diabetic nephropathy.

According to queuing method, inpatients with stage Ⅲ diabetic nephropathy treated in the hospital were divided into treatment group and control group. Treatment group was treated with beraprost sodium tablets + alprostadil injection (the first 2 weeks: intravenous drip of alprostadil injection 10 μg qd. the last 2 weeks: oral beraprost sodium tables 40 μg tid), while control group was treated with alprostadil injection (the same administration method as treatment group for 4 weeks). The clinical efficacy, β2 microglobulin (β2-MG), cystatin C (Cys-C), blood urea nitrogen (BUN), serum creatinine (SCr), urinary albumin to creatinine ratio (UACR), transforming growth factor β1 (TGF-β1), tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), hemoglobin Alc (HbAlc), fasting blood glucose (FBG), 2 h postprandial blood glucose (2 h PBG), homeostasis model assessment for insulin resistance (HOMA-IR), hypersensitive C-reactive protein (hs-CRP), tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) were compared between the two groups, and the safety was evaluated.

Among the 103 patients, there were 52 cases in treatment group and 51 cases in control group. The efficiency rate in treatment group was higher than that in control group [92.31% (48 cases/52 cases) vs. 78.43% (40 cases/51 cases), P<0.05]. After treatment, levels of serum β2-MG in treatment group and control group were (0.25±0.06) and (0.31±0.07) mg·L^-1, BUN levels were (5.70±0.91) and (6.89±1.01) mmol·L^-1, SCr levels were (85.46±8.89) and (93.88±9.77) μmol·L^-1, Cys-C levels were (1.38±0.26) and (1.64±0.30) mg·L^-1, UACR levels were (140.24±31.04) and (176.40±36.19) mg·g^-1, respectively; levels of serum TIMP-1 were (88.34±12.36) and (97.62±15.44) ng·mL^-1, TGF-β1 levels were (112.49±17.24) and (138.50±19.84) ng·mL^-1, MMP-9 levels were (130.69±21.30) and (114.79±19.77) μg·L^-1, respectively; levels of serum IL-6 were (141.49±28.85) and (173.49±32.36) pg·mL^-1, hs-CRP levels were (7.64±1.16) and (9.29±1.54) mg·L^-1, TNF-α levels were (23.65±4.34) and (29.12±3.86) pg·mL^-1, and differences in the above indexes between treatment group and control group were all statistically significant (all P<0.05). During treatment, there was 1 case with diarrhea, 1 case with rash and 1 case with nausea and vomiting in treatment group, while there was 1 case with rash and 1 case with diarrhea in control group. There was no statistically significant difference in incidence of adverse drug reactions between treatment group and control group (5.77% vs. 3.92%, P>0.05).

Alprostadil injection combined with beraprost sodium tablets can effectively improve renal function, regulate metabolism of extracellular matrixes in renal tissues, relieve inflammatory response and improve clinical curative effect in patients with stage Ⅲ diabetic nephropathy.

To investigate the clinical efficacy and safety of midazolam injection combined with propofol medium/long-chain fat emulsion target-controlled infusion (TCI) in severely obese patients undergoing laparoscopic sleeve gastrectomy with double-tract anastomosis (LSG-DJB).

Severely obese patients treated in our hospital were randomly assigned by a random number table method to the control group or the treatment group. The control group received propofol medium/long-chain fat emulsion TCI (effect-site concentration 1.2–2.0 μg·mL^-1), while the treatment group additionally received midazolam injection (0.03 mg·kg^-1 for induction, 0.02 mg·kg^-1·h^-1 for maintenance). Pain indicators, recovery quality, inflammatory markers, oxidative stress parameters and safety outcomes were compared between the two groups.

A total of 179 patients were screened in this study, with 67 cases enrolled in the control group and 68 cases in the treatment group. Three cases dropped out in the control group and four cases dropped out in the treatment group; ultimately, 64 cases in each group completed the study. The pain scores (NRS) at discharge from the operating room were (0.76±0.42) and (0.93±0.28) points for the treatment group and control group, respectively; at 6 hours postoperatively, they were (1.94±0.46) and (2.37±0.82) points, respectively; at 12 hours postoperatively, they were (2.24±0.51) and (2.92±0.71) points, respectively. Compared with the control group, the differences in the above indicators in the treatment group were statistically significant (all P<0.05). The total intraoperative dosage of sufentanil injection were (0.75±0.12) and (0.92±0.15) μg·kg^-1 for the treatment group and control group, respectively; the eye-opening time was (10.77±1.48) and (8.39±1.23) min, respectively; the extubation time was (18.68±2.91) and (13.21±2.48) min, respectively; the respiratory recovery time was (16.87±2.25) and (11.93±2.03) min, respectively. Compared with the control group, the differences in the above indicators in the treatment group were statistically significant (all P<0.05). At 24 hours postoperatively, the serum interleukin-6 (IL-6) levels were (72.16±10.28) and (88.32±11.14) ng·L^-1 for the treatment group and control group, respectively; tumor necrosis factor-α (TNF-α) levels were (152.47±21.95) and (176.84±25.67) ng·L^-1, respectively; C-reactive protein (CRP) levels were (5.63±0.88) and (7.74±0.86) mg·L^-1, respectively; malondialdehyde (MDA) levels were (4.82±1.19) and (7.03±1.22) mmol·mL^-1, respectively; cortisol (Cor) levels were (31.42±3.27) and (37.75±4.16) μg·dL^-1, respectively; superoxide dismutase (SOD) levels were (37.38±5.82) and (23.67±3.59) mmol·mL^-1, respectively. Compared with the control group, the differences in the above indicators in the treatment group were statistically significant (all P<0.05). The main adverse drug reactions in the treatment group were hypoxemia, hypotension, delayed recovery, nausea and vomiting; the main adverse reactions in the control group were nausea and vomiting, hypoxemia, and hypotension. The total incidence rates of adverse drug reactions were 54.69% and 42.19% in the treatment group and control group, respectively, with no statistically significant difference (P>0.05).

Midazolam injection combined with propofol medium/long-chain fat emulsion TCI provides optimized sedation depth, reduces inflammatory and stress responses, and demonstrates good safety in severely obese patients undergoing LSG-DJB.

To compare the clinical efficacy and safety of labetalol injection and nifedipine controlled-release tablets combined with magnesium sulfate injection and calcium carbonate D3 tablets in the treatment of preeclampsia.

The patients with preeclampsia who were hospitalized in the obstetrics department of our hospital were included as the research objects, and the patients were divided into group A, group B and group C according to the medication plan. Group A was treated with labetalol hydrochloride injection 100-200 mg, intravenous drip, 1.5-3.5 mg per minute, once a day combined with 25% magnesium sulfate injection 60 mL, intravenous drip, 1.55-2.0 g per hour, 25 g per day and calcium carbonate D3 tablets, take orally, 300 mg each time, twice a day; Group B was treated with nifedipine controlled-release tablets orally, 30 mg each time, once a day, and the administration methods of magnesium sulfate injection, calcium carbonate D3 tablets were the same as those in group A; Group C was treated with labetalol hydrochloride injection, nifedipine controlled-release tablets, magnesium sulfate injection and calcium carbonate D3 tablets, and the administration methods of them were the same as those in group A and group B. The clinical efficacy, blood pressure condition, heart and kidney function, psychological status, fetal hemodynamics, maternal and pregnancy outcome of patients in 3 groups were compared, and the safety was evaluated.

A total of 170 patients were enrolled, 90 patients in group A, 39 patiets in group B and 41 patients in group C. After treatment, the total effective rates of group A, Group B and Group C were 58.89% (53 cases/90 cases), 53.85% (21 cases / 39 cases) and 85.37% (35 cases / 41 cases), respectively, and the blood pressure recovery time were 3.00 (3.00,5.00), 3.00 (3.00,5.00), and 7.00 (3.00,9.00) d, respectively. The total effective rate of group C was statistically significantly higher than that of group A and group B (all P<0.05), and the recovery time of blood pressure was statistically significantly shorter than that of group A and group B (all P<0.05). After treatment, the systolic blood pressures of group A, group B and group C were (145.60±5.15), (143.72±4.86) and (137.24±5.07) mmHg, respectively; the diastolic blood pressures were (97.83±6.56), (96.72±7.00) and (86.80±4.87) mmHg, respectively; Hamilton anxiety scale scores were 15.00 (13.00,17.00), 15.00 (13.50,17.50) and 12.00 (11.00,14.00) points, respectively; the Hamilton depression scale scores were 14.00 (12.00,15.00), 14.00 (12.00,15.00) and 10.00 (9.00,12.00) points, respectively; and the above indicators in group C were all lower than those of group A and group B (all P<0.05). After treatment, the B-type natriuretic peptide levels in group A, group B and group C were 35.00 (21.00,56.00), 42.00 (22.50,90.50) and 24.00 (13.00,60.00) pg·L^-1, respectively; the the urinary protein levels were 0.35 (0.14,0.57), 0.24 (0.15, 0.39) and 0.14 (0.06,0.34) g, respectively; and the B-type natriuretic peptide level of group C was statistically significantly lower than that of group B (P<0.05), and the urinary protein level was statistically significantly lower than that of group A (P<0.05). After treatment, the diastolic flow velocity ratio in group A, Group B and group C were 2.15 (1.92, 2.24), 2.04 (1.86, 2.23), 2.16 (2.02, 2.25), respectively; the flow resistance index were 0.53 (0.48, 0.55), 0.51 (0.46, 0.56), 0.54 (0.51, 0.58), respectively; the flow pulse index were 0.77 (0.66, 0.83), 0.69 (0.63, 0.80), 0.77 (0.67, 0.81), respectively; the incidence rates of adverse drug reactions were 13.33% (12 cases / 90 cases), 12.82% (5 cases / 39 cases) and 12.20% (5 cases / 41 cases), respectively; and there were no statistically significant differences in the above indicators and pregnancy outcome among the three groups (all P>0.05).

The therapy with labetalol, nifedipine, magnesium sulfate and calcium in PE is better, which can improve the blood pressure level, psychological status, heart and kidney function, maternal and infant outcomes, regulate fetal hemodynamics, and will not cause serious adverse reactions.

To investigate the off-label drug use of escitalopram in children and adolescents, and to provide a reference for rational clinical medication.

Collected prescription data of children and adolescents (<18 years) receiving antidepressant treatment, including gender, age, clinical diagnosis, drug name, dosage, frequency and route of administration. Based on domestic drug labeling, we assessed whether escitalopram was used off-label, and further conducted evidence-based searches regarding its off-label drug use. A literature search was conducted using the keywords escitalopram, off-label use, evidence-based medicine, children and adolescents across multiple electronic databases, including PubMed, Embase, The Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang and VIP.

This study included a total of 156 504 outpatients, with escitalopram prescribed to 9 798, the off-label use rate was 6.26%. An analysis of the off-label use of escitalopram was conducted based on 22 articles, including the original drug instructions, evidence-based databases and related medical literature, the results demonstrated that escitalopram was supported by evidence for the use of both depression and generalized anxiety disorder in children and adolescents.

Escitalopram has preliminary evidence-based support for its use in children and adolescent patients, it is an off-label application. Therefore, clinical practice should strengthen the supervision and management of off-label use of escitalopram to ensure medication safety for patients.

To investigate the effect and of hydrogen sulfide (H₂S) on the osteogenic differentiation of osteoblast precursor cells (MC3T3-E1) by regulating the polarization of macrophages (RAW264.7).

RAW264.7 cells were divided into four groups (n=10 in each group), including control group (untreated), M1 induction group [added with 100 ng·mL^-1 lipopolysaccharide (LPS)], M2 induction group (added with 20 ng·mL^-1 interleukin-4+20 ng·mL^-1 interleukin-10, IL-4+IL-10), GYY4137 intervention group (H₂S donor GYY4137 100 μmol·L^-1). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to detect the mRNA and protein expression levels of M1 macrophage related factors including tumor necrosis factor-α (TNF-α), interleukin-1 β (IL-1β) and inducible nitric oxide synthase (i-NOS) and M2 macrophage related factors including interleukin-10 (IL-10), arginase-1 (Arg-1) and mannose receptor (CD206), and to verify the effect of polarization induction and the intervention of GYY4137; cell counting kit-8 (CCK-8) was used to detect the activity of RAW264.7 cells treated with GYY4137 at different concentrations for 24 h and 72 h (6 wells in each group). The expression levels of Arg-1 and CD206 in control group and GYY4137 group (100 μmol·L^-1) were detected by flow cytometry (n=10 in each group). MC3T3-E1 cells were divided into four groups (n=10), which were blank group (without osteogenic induction medium), osteogenic control group (with osteogenic induction medium), co-culture group (co-cultured with RAW264.7 cells Transwell) and GYY4137 pretreatment co-culture group (co-cultured with 100 μmol·L^-1 GYY4137 pretreated RAW264.7 cells). The mRNA expression levels of osteogenic related genes including Runt-related transcription factor 2 (Runx-2), osteopontin (OPN), bone morphogenetic protein-2 (BMP-2) and bone sialoprotein (BSP) mRNA were detected by RT-qPCR; alkaline phosphatase (ALP) staining and alizarin red staining were used to detect osteogenic differentiation.

The relative expression levels of TNF-α mRNA in control group, M1 induction group and GYY4137 intervention group were 1.56±0.22, 16.49±3.56 and 0.57±0.11, respectively; the relative expression levels of IL-1β mRNA were 1.06±0.24, 3.37±0.76 and 1.43±0.34, respectively. The above indexes in M1 induced group were significantly higher than those in control group, and the above indexes in GYY4137 intervention group were significantly lower than those in M1 induced group (all P<0.001). The relative expression levels of Arg-1 mRNA in GYY4137 group and control group were 1.38±0.36 and 0.91±0.12, respectively; the relative expression levels of CD206 mRNA were 17.43±2.84 and 1.14±0.21, respectively; the relative expression levels of CD206 protein were 0.89±0.25 and 0.20±0.04, respectively; the relative expression levels of i-NOS protein were 0.72±0.19 and 0.25±0.07, respectively; the relative expression levels of Arg-1 were 28.65±3.21 and 12.31±2.15, respectively; the relative expression levels of CD206 were 31.24±2.89 and 10.8±1.98, respectively. The above indexes in GYY4137 intervention group were significantly higher than those in control group, and the differences were statistically significant (P<0.05, P<0.001). The relative expression levels of Runx-2 mRNA in GYY4137 pretreatment and co-culture groups were 3.21±0.45 and 1.56±0.22, respectively; the relative expression levels of OPN mRNA were 2.89±0.38 and 1.43±0.19, respectively; the relative expression levels of BMP-2 mRNA were 3.56±0.52 and 1.67±0.25, respectively; the relative expression levels of BSP mRNA were 2.98±0.41 and 1.51±0.20, respectively. The above indexes in GYY4137 pretreatment co-culture group were significantly higher than those in co-culture group, and the differences were statistically significant (all P<0.05). The OD values of ALP in GYY4137 pretreatment co-culture group and osteogenic control group were (0.89±0.12) and (0.56±0.08) μm², respectively; the areas of alizarin red stained calcium nodules were (2 865.32±215.67) and (1 568.45±189.32) μm², respectively; the above indexes of GYY4137 pretreatment co-culture group were significantly higher than those of osteogenic control group, and the differences were statistically significant (all P<0.05).

100 μmol·L^-1 GYY4137 can enhance the osteogenic differentiation of MC3T3-E1 cells by promoting the polarization of RAW264.7 cells to M2 macrophages, up regulating the expression of osteogenic related genes.

To investigate the effects of baicalein combined with 5-fluorouracil (5-FU) on the proliferation, apoptosis and migration of H446 cells, and to explore the sensitization mechanism.

Lung cancer H466 cells were allocated into blank, control, experimental and combination groups. The blank group was treated with 10 μmol·L^-1 dimethyl sulfoxide, the control group with 20 μmol·L^-1 baicalein, the experimental group with 20 μmol·L^-1 5-FU, and the combination group with 10 μmol·L^-1 baicalein plus 10 μmol·L^-1 5-FU. Cell viability was determined using the cell counting kit-8 assay. Apoptosis and reactive oxygen species (ROS) levels were analyzed by flow cytometry. Cell migration was evaluated with Transwell assays, and alterations in mitogen-activated protein kinase (MAPK) pathway protein expression were examined by Western blotting.

After 24 h of incubation, cell viability in blank, control, experimental and combination groups were (114.34±2.88)%, (79.87±3.48)%, (57.66±1.82)% and (40.31±2.73)%, respectively; the corresponding apoptosis rates were (14.47±1.36)%, (33.94±4.33)%, (49.20±3.82)% and (49.17±2.13)%; and cell migration rates were (8.43±1.94)%, (11.25±1.55)%, (26.74±3.31)% and (68.83±4.32)%. Compared with control group, the above indexes of experimental group and combined group were significantly increased, and combined group were significantly higher than experimental group (all P<0.01). After adding ROS scavenger NAC to combination group, the apoptosis rates of blank group, control group, experimental group, combination group and combination group+NAC were (7.82±0.94)%, (12.31±2.13)%, (33.48±4.92)%, (52.42±3.17)% and (30.39±2.72)%, respectively; the cell migration rates were (4.36±0.54)%, (4.92±0.71)%, (31.43±3.14)%, (52.64±5.26)% and (27.61±3.52)%, respectively. Compared with combined group, the above indexes of combined group+NAC were significantly decreased (all P<0.01). The relative expression levels of p-JNK protein in blank, experimental, control, combination and combination group+NAC were 0.78±0.05, 0.70±0.04, 0.73±0.03, 0.98±0.02 and 0.73±0.05, respectively; the relative expression levels of p-p38 were 0.56±0.02, 0.51±0.03, 0.60±0.04, 0.76±0.06 and 0.54±0.03, respectively; the relative expression levels of p-ERK were 0.34±0.03, 0.30±0.04, 0.28±0.04, 0.18±0.03 and 0.33±0.05, respectively. The relative expression levels of p-JNK and p-p38 protein in combination group were significantly higher than those in control group, and the relative expression levels of p-ERK protein were significantly lower (all P<0.01); the relative expression levels of p-JNK and p-p38 low protein in combined group+NAC were significantly decreased, while the relative expression levels of p-ERK protein were significantly increased (all P<0.01).

The combination of baicalein and 5-FU can enhance the inhibitory effect on proliferation, induce apoptosis, and suppress migration in H446 cells by upregulating ROS levels, activating the JNK and p38 pathways, and inhibiting the ERK pathway.

To explore the effects of ropivacaine on the cyclic guanosine monophosphate synthase interferon gene stimulating factor (cGAS/STING) pathway in glial cells of septic encephalopathy (SAE) model mice, and its related mechanisms of action.

Mice were randomly divided into blank group, model group, experimental group and control group, with 15 mice in each group. Except for the blank group and control group, the other two groups were used to establish sepsis mouse models by intraperitoneal injection of lipopolysaccharide. The experimental group and control group were intraperitoneally injected with 0.3 mg·kg^-1·d^-1 ropivacaine, while the blank group and model group were intraperitoneally injected with an equal volume of 0.9% NaCl. The four groups of mice were administered once a day for 7 consecutive days. The Morris water maze was used to detect the cognitive function of the mouse brain, real-time fluorescent quantitative polymerase chain reaction was used to detect the mRNA levels of brain inflammatory factors, Western blot was used to detect the expression levels of brain cGAS and STING proteins, and immunofluorescence staining was used to detect the expression of apoptosis-related proteins.

The exploration time proportions of the blank group, model group, experimental group and control group were (0.48±0.10)%, (0.23±0.05)%, (0.37±0.04)% and (0.46±0.07)%, respectively; the platform crossing times were (4.67±0.48), (1.03±0.11), (2.50±0.65) and (4.99±0.52) times, respectively; the escape latency time was (11.92±0.98), (12.49±1.22), (11.17±1.43) and (12.21±1.52) min, respectively; the relative expression levels of interleukin-1β (IL-1β) mRNA were 1.00±0.10, 3.80±0.28, 1.87±0.13 and 1.06±0.29, respectively; the relative expression levels of IL-18 mRNA were 1.00±0.12, 1.61±0.27, 1.06±0.08 and 0.97±0.05, respectively; the relative expression levels of tumor necrosis factor (TNF)-α mRNA were 1.00±0.13, 2.02±0.18, 1.05±0.09 and 1.13±0.11, respectively; the relative expression levels of IL-6 mRNA were 1.00±0.08, 1.56±0.11, 1.05±0.09 and 0.93±0.06, respectively; the relative expression levels of cGAS protein were 1.00±0.08, 1.92±0.19, 1.42±0.11 and 1.03±0.10, respectively; the relative expression levels of STING protein were 1.00±0.12, 2.01±0.22, 1.18±0.09 and 1.08±0.16, respectively; the relative fluorescence intensities of cGAS protein were 1.00±0.18, 1.88±0.15, 1.57±0.09 and 1.03±0.11, respectively; the relative fluorescence intensities of STING were 1.00±0.16, 1.79±0.26, 1.14±0.06 and 1.20±0.29, respectively; the relative fluorescence intensities of caspase-3 protein were 1.00±0.12, 1.51±0.08, 1.23±0.10, and 1.11±0.15, respectively. The above indexes of the experimental group and the control group were statistically different from the model group (all P<0.05).

Ropivacaine can alleviate apoptosis of glial cells in the hippocampus of SAE mice by inhibiting the cGAS/STING pathway, and has a protective effect on the brain of SAE mice.

To explore the antidepressant effect and its mechanism of effective components of Lilium brownii based on brain-derived neurotrophic factor/protein kinase B/mammalian target of rapamycin (BDNF/AKT/mTOR) pathway.

In cellular experiments, the experiments were divided into control group (cell culture solution), model group (corticosterone 400 μmol·L^-1), lily saponin low dose group (corticosterone 400 μmol·L^-1+0.2 mg·L^-1 liliy saponin), lily saponin high dose group (corticosterone 400 μmol·L^-1+0.6 mg·L^-1 liliy saponin), lily polysaccharide low dose group (corticosterone 400 μmol·L^-1+0.2 mg·L^-1 liliy polysaccharide), and lily polysaccharide high dose group (corticosterone 400 μmol·L^-1+0.6 mg·L^-1 liliy polysaccharide). Except for the blank group, the remaining groups were modeled with corticosterone to establish human neuroblastoma cells (SH-SY5Y) injury, and cell survival was detected. In the animal experiments, 48 male ICR mice were randomly divided into 6 groups: model group (drinking water with the same amount), low dose of lily saponin (50 mg·kg^-1), high dose of lily saponin (100 mg·kg^-1), low dose of lily polysaccharide (50 mg·kg^-1), high dose of lily polysaccharide (100 mg·kg^-1) and positive drug control group (fluoxetine,10 mg·kg^-1). Each group was given acute stress modeling in mice, and changes in behavioral indexes were observed. Serum corticosterone levels were measured by enzyme-linked immunosorbent assay. The relative expression levels of proteins such as postsynaptic densifier 95 (PSD95) and synapsin in the prefrontal cortex of mice were detected by protein immunoblot analysis.

In the cellular experiments, the cell survival rates of each subgroup were (71.46±1.92)%, (95.97±1.11)%, (105.51±1.80)%, (107.48±0.27)% and (107.66±3.61)%, respectively. The differences between the administered groups and the model group were all statistically significant (all P<0.01). In the animal experiments, the cumulative immobilization time of mice with suspended tails in model group, low and high dose of lily saponin groups, low and high dose of lily polysaccharide group and positive drug group was (122.75±4.77), (90.75±2.09), (66.13±3.23), (79.75±2.84), (54.38±4.40), and (42.00±6.34) s, respectively; the levels of corticosterone in the serum of mice were (236.94±6.17), (213.88±3.95), (165.52±2.19), (203.40±3.27), (170.18±2.18) and (104.96±3.87) ng·mL^-1, respectively; the relative expression levels of brain-derived neurotrophic factor (BDNF) were 0.26±0.03, 0.74±0.25, 0.86±0.03, 0.97±0.11, 0.92±0.13 and 1.05±0.23, respectively; the relative expression levels of phosphorylated protein kinase B/protein kinase B (p-AKT/AKT) were 0.26±0.03, 0.60±0.19, 0.75±0.09, 0.82±0.05, 0.94±0.23 and 0.58±0.07, respectively; the relative expression levels of phosphorylated mammalian target of rapamycin/mammalian target of rapamycin protein (p-mTOR/mTOR) were 0.46±0.04, 0.52±0.19, 0.60±0.18, 1.01±0.01, 0.98±0.06 and 0.93±0.10, respectively; the relative expression levels of postsynaptic density protein-95 (PSD95) were 0.36±0.05, 0.50±0.08, 0.60±0.09, 0.73±0.09, 0.84±0.18 and 1.00±0.12, respectively; the relative expression levels of synapsin protein were 0.13±0.04, 1.03±0.02, 1.16±0.06, 1.02±0.00, 1.00±0.04 and 0.65±0.15, respectively. Except the p-mTOR/mTOR and PSD95 in high dose of lily saponin, the differences of the above indexes between the model group and the high dose groups were all statistically significant (P<0.05, P<0.01).

Lily saponins and polysaccharides may improve synaptic plasticity in prefrontal cortex by modulating the BDNF/AKT/mTOR signaling pathway, which improves depressive-like behavior and suppresses serum corticosterone levels in behavioral despair mice. Among them, lily polysaccharides were slightly better than lily saponins in improving synaptic plasticity.

To investigate the effects of fucoxanthin on endothelial cell function in coronary heart disease (CHD) and its mechanism.

The cell experiment section divided the human coronary artery endothelial cells (HCAEC) into blank group, ox-LDL group (40 μg·mL^-1), fucoxanthin group (ox-LDL+25 μmol·L^-1 fucoxanthin) and miR-483-3p inhibitor group (transfected with miR-483-3p inhibitor+ox-LDL+25 μmol·L^-1 fucoxanthin). The expression levels of miR-483-3p and pyroptosis related proteins NLR family pyrin domain containing 3 (NLRP3) were detected by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting (WB), respectively. The animal experiment section divided the rats into control group, model group (constructed CHD model), experimental group (modeling +30 mg·kg^-1 fucoxanthin) and inhibitor group (modeling+transfection of miR-483-3p inhibitor+30 mg·kg^-1 fucoxanthin). The relative expression levels of miR-483-3p, endothelium-related factors and pyroptosis related proteins NLRP3 were detected by RT-qPCR, enzyme-linked immunosorbent assay (ELISA) and Western blot, respectively.

In cell experiment, the relative expression levels of miRNA-483-3p in cells of blank group, ox-LDL group, fucoxanthin group and miR-483-3p inhibitor group were 1.00±0.11, 0.39±0.07, 0.74±0.06 and 0.22±0.03, respectively; NLRP3 protein relative expression levels were 0.39±0.02, 1.03±0.07, 0.52±0.04 and 0.85±0.10, respectively. ox-LDL group was compared with blank group, fucoxanthin group was compared with ox-LDL group, miR-483-3p inhibitor group was compared with fucoxanthin group, the above indicators all showed statistically significant differences. (all P<0.001). In animal experiments, the relative expression levels of miR-483-3p in control group, model group, experimental group and inhibitor group were 1.00±0.12, 0.51±0.06, 0.70±0.08 and 0.31±0.04, respectively; nitric oxide (NO) levels were (46.93±3.18), (20.21±2.43), (36.13±4.87) and (24.43±1.60) μmol·L^-1, respectively; the NLRP3 protein relative expression levels were 0.29±0.04, 0.97±0.09, 0.56±0.09 and 0.86±0.08, model group was compared with control group, experimental group was compared with model group, inhibitor group was compared with experimental group, the above indicators all showed statistically significant differences. (all P<0.001).

Fucoxanthin can up-regulate miR-483-3p to improve endothelial cell pyroptosis and relieve CHD inflammatory response.

To investigate the effects of total alkaloids of Aconitum carmichaelii on myocardial function in rats and its underlying mechanisms.

SPF-grade Wistar rats were randomly assigned into five groups (n=10 each): blank group (0.9% NaCl), control group (isoproterenol 10 mg·kg^-1), experimental-L group (2.72 g·kg^-1 total alkaloids of A. carmichaelii), experimental-M group (3.68 g·kg^-1), and experimental-H group (4.98 g·kg^-1). All groups were gavaged once daily for 5 consecutive days. Thirty minutes after the last injection, T-wave amplitude on electrocardiogram was recorded. An isolated heart perfusion model was established to evaluate cardiac function and myocardial contractility. Myocardial cell activity and malondialdehyde content were measured, and real-time quantitative PCR was used to detect mRNA expression levels of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (Pgc-1α), B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax).

The T-wave amplitudes for the experimental -L, -M, -H groups, blank group and control group were (0.17±0.07), (0.29±0.05), (0.37±0.04), (0.30±0.07) and (0.36±0.04) mV, respectively; the myocardial cell activities were (0.46±0.05), (0.44±0.08), (0.35±0.07), (0.45±0.06) and (0.33±0.05) Abs, respectively; the while malondialdehyde contents were (2.56±0.28), (2.55±0.26), (2.86±0.28), (2.49±0.34) and (2.83±0.25) mmol·mL^-1, respectively; the relative mRNA expression levels of Pgc-1α were 0.49±0.05, 0.41±0.07, 0.27±0.05, 0.48±0.06 and 0.35±0.05, respectively; the relative mRNA expression levels of Bax were 1.10±0.08, 1.25±0.09, 1.36±0.07, 1.09±0.09 and 1.33±0.07, respectively; the relative mRNA expression levels of Bcl-2 were 0.58±0.06, 0.51±0.05, 0.44±0.04, 0.56±0.08 and 0.45±0.03, respectively. Compared with the experimental -M, -H groups and blank group, the above indexes of the experimental -L group were statistically significant (all P<0.05).

Lower doses of Aconitum carmichaelii total alkaloids positively influence ECG T-wave amplitude, cardiac function, and myocardial contractility, improve myocardial cell activity, and reduce oxidative stress, whereas high doses exert cardiotoxic effects.

To explore the effect and potential mechanism of hyperuricemia (HUA) on acetaminophen (APAP)-induced liver injury.

Male mice were randomly divided into four groups: group A (control), group B [establishment of a hyperuricemia (HUA) model], group C (administered by oral gavage at a dose of 300 mg·kg^-1 APAP), and group D (establishment of a HUA model combined with administered by oral gavage at a dose of 300 mg·kg^-1 APAP). The HUA model was established by intraperitoneal injection of potassium oxonate (350 mg·kg^-1) and gavage of xanthine (450 mg·kg^-1) for 14 consecutive days. On day 13, mice in group C and group D received APAP via gavage. All mice were sacrificed 24 h later. Serum levels of uric acid (UA), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined by biochemical analyzer. Liver histopathology was evaluated by hematoxylin-eosin (H&E) staining. Levels of malondialdehyde (MDA), reactive oxygen species (ROS), glutathione (GSH), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in liver tissues were measured using commercial kits. Immunofluorescence was used to detect the relative expression of nuclear factor erythroid 2-related factor 2 (Nrf2).

The serum uric acid levels in the group A, group B, group C and group D were (186.20±15.61), (521.50±56.81), (325.20±31.74) and (682.00±49.51) μmol·L^-1, respectively; the liver coefficients were (4.51±0.14)%, (4.77±0.23)%, (4.98±0.21)%, and (5.51±0.30)%, respectively; the serum ALT levels were (55.80±15.86), (78.09±10.92), (27 688.81±7 166.01), and (34 571.89±7 793.74) U·L^-1, respectively; the AST levels were (159.90±29.72), (143.70±26.46), (10 880.00±4 291.01), and (19 824.84±7 874.64) U·L^-1, respectively; the hepatic MDA contents were (5.42±0.38), (7.77±0.32), (6.07±0.31), and (9.08±0.36) mol·g^-1·prot^-1, respectively; the ROS contents were (28.09±3.52), (39.67±2.70), (32.22±4.71), and (45.67±2.71) μg·g^-1·prot^-1, respectively; the GSH levels were (2.47±0.27), (1.72±0.16), (2.24±0.16), and (1.37±0.11) μg·g^-1·prot^-1, respectively; the IL-1β contents were (22.16±0.88), (31.74±1.82), (25.35±1.07), and (38.82±1.68) μg·g^-1·prot^-1, respectively; the TNF-α contents were (114.90±10.60), (180.20±3.72), (142.20±4.69), and (228.10±17.33) μg·g^-1·prot^-1, respectively; the relative protein expression of Nrf2 were 218.30±5.16, 63.60±29.02, 100.80±23.60, and 9.31±8.83, respectively. The indices in groups B and C were significantly different from those in group A, and the indices in group D were significantly different from those in group C, with all differences showing statistical significance (P<0.05).

In the hyperuricemia (HUA) mouse model, the liver damage induced by acetaminophen (APAP) is aggravated, and this effect may be related to the downregulation of NRF2 expression.

To establish a rat model of renal fibrosis induced by unilateral ureteral obstruction (UUO), and investigate the mechanism of the Yishen Qufeng Formula (YQF) improves renal fibrosis through regulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) axis to mediate ferroptosis.

Eight-week-old SD rats were randomly divided into the sham-operation group, model group, positive control group (dapagliflozin at 20 mg·kg^-1·d^-1), and experimental -L,-M,-H groups (Yishen Qufeng Formula at 15.21, 22.82 and 30.42 g·kg^-1·d^-1). Except for the sham operation group, rats in the other groups were subjected to left ureteral ligation to establish a renal interstitial fibrosis (RIF) model. After successful modeling, the positive control group and the -L, -M, and -H dose experimental groups were given the corresponding drugs by gavage, while the sham operation group and model group were given an equal volume of 0.9% NaCl by gavage. All rats in the 6 groups were administered once a day for 14 consecutive days. Serum creatinine, urea nitrogen and urine protein levels were detected using a fully automatic integrated biochemical analyzer. The content of transforming growth factor-β1 (TGF-β1) was measured by enzyme-linked immunosorbent assay (ELISA). The changes in the relative expression levels of fibrosis-related, oxidative stress-related and ferroptosis-related proteins in renal tissues were determined by Western blotting.

The levels of serum creatinine in the experimental -M, -H groups, sham operation group, model group and positive control group were (50.24±7.81), (49.15±8.87), (41.96±5.25), (59.44±11.93) and (52.14±8.38)μmol·L^-1, respectively; the levels of urea nitrogen were (4.58±0.56), (4.45±0.55), (4.32±0.60), (6.00±1.03) and (6.55±1.02)mmol·L^-1, respectively; the levels of urine protein were (640.59±205.70), (538.74±237.98), (526.51±192.62), (982.91±349.13) and (964.26±456.84)mg·d^-1, respectively; the relative protein expression levels of glutathione peroxidase 4 (GPX4) were 1.62±0.15, 3.01±0.41, 2.25±0.27, 1.01±0.51 and 2.15±0.63, respectively; the relative protein expression levels of cystine/glutamate antiporter (xCT) were 0.62±0.10, 1.02±0.06, 1.65±0.13, 0.52±0.20 and 1.18±0.13, respectively; the relative protein expression levels of Nrf2 were 0.66±0.12, 1.04±0.16, 1.20±0.10, 0.54±0.03 and 1.19±0.14, respectively; the relative protein expression levels of HO-1 were 1.13±0.15, 1.21±0.18, 2.21±0.17, 0.64±0.44 and 1.57±0.26, respectively; the relative protein expression levels of α-smooth muscle actin (α-SMA) were 1.63±0.47, 1.13±0.57, 0.49±0.91, 2.88±0.97 and 1.05±0.60, respectively. There were statistically significant differences in the above indicators between the high-dose experimental group and the model group (all P<0.05).

Yishen Qufeng Formula may inhibit ferroptosis by activating the Nrf2/HO-1 signaling pathway, thereby effectively alleviating renal interstitial fibrosis in UUO rats. This provides important theoretical evidence for the mechanism by which the Yishen Qufeng Formula improves renal fibrosis through regulation of ferroptosis.

To investigate the effect of Gardenia jasminoides Ellis (Zhi-zi) in alleviating the hepatotoxicity induced by its constituent, genipin, which is called the "self-detoxification" effect, and to explore its mechanism through targeted metabolomics and integrated network pharmacology.

Male mice of the Kunming breed were randomly divided into three groups (n=8) including blank group, control group and experimental group. Blank group was administered a blank solvent 0.5% carboxymethyl cellulose (CMC-Na) by gavage; control group was administered genipin by gavage at a dose of 100 mg·kg^-1·d^-1, and experimental group was administered 100 mg·kg^-1·d^-1 genipin and 520 mg·kg^-1·d^-1 Zhi-zi aqueous extract powder by gavage. After 28 days of continuous administration, serum biochemical indicators were measured using an automated biochemical analyzer, liver tissue pathology was examined using hematoxylin and eosin (HE) staining, and differential metabolites were quantified and analyzed using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for targeted metabolomics analysis. The targets associated with active compounds in Zhi-zi, genipin, and liver damage were predicted separately. Finally, the results of metabolomics and network pharmacology were integrated to screen the potential targets related to the self-detoxification effect of Zhi-zi.

The alanine transaminase (ALT) levels in experimental group, control group and blank group were (35.75±8.50), (53.00±14.43) and (37.38±3.11) U·L^-1, respectively; the aspartate transaminase (AST) levels were (123.38±31.40), (146.50±19.73) and (115.75±17.44) U·L^-1, respectively. Compared with control group, experimental group showed significant decrease in ALT levels, with statistically significant difference (P<0.05). Compared with control group, the AST levels in experimental group showed no statistically significant difference (P>0.05). Targeted metabolomics identified 8 characteristic endogenous metabolites including fumaric acid, isocitric acid, maleic acid, ornithine, aminocaproic acid, isoLCA, pipecolic acid and pyrrole-2-carboxylic acid, and the metabolic pathways induced by these 8 differentially expressed metabolites were primarily associated with arginine biosynthesis and the tricarboxylic acidcycle (TCA) metabolic pathways.

Zhi-zi can improve the metabolic disorders of endogenous metabolites in the liver caused by genipin by affecting the arginine biosynthesis and the TCA metabolic pathway, and improve inflammation and oxidative stress by acting on the corresponding targets to alleviate the hepatic injuries caused by genipin and exerting the self-detoxification effect.

To establish and validate a high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method for simultaneously determining the serum concentration of lamotrigine(LTG), levetiracetam(LEV), oxcarbazepine(OXC) and monohydroxycarbazepine(MHD), which is applied for clinical blood concentration detection.

A simple one-step precipitation method was used for the serum sample pretreatment, and stable isotopes of two antiepileptic drugs (OXC-D4, LEV-D6) as the internal standard. The mobile phases were aqueous solution of 0.1% formic acid and 5 mM ammonium acetate(A) and methyl alcohol(B), and the gradient elution was performed at the speed of 0.6 mL·min^-1 for 6 min on Phenomenex C₁₈(100.0 mm×4.6 mm, 3.0 μm). The column temperature was 40 ℃. Positive ion scan analysis was carried out in multi-reaction monitoring mode, using electrospray ion source. The specificity, standard curve and lower limit of quantification (LLOQ), accuracy and precision, extraction recovery, matrix effect and stability were evaluated. The patients treated with LRG, LEV or OXC in hospital were included as the research object. Blood samples were collected after the blood concentration reached a steady state and the serum concentration was detected by the method developed in this study.

The method demonstrated good specificity. For LTG, LEV, OXC and MHD, outstanding linearity was observed in the ranges of (0.20-25.00), (0.39-50.00), (0.04-5.00), (0.31-40.00) μg·mL^-1, respectively. The linear equation of LTG was y=0.99x+0.02 (r=0.999 2), LEV was y=0.55x+0.01 (r=0.999 4), OXC was y=4.35x+0.04 (r=0.998 9), and MHD was y=0.56x+0.01 (r=0.998 7). The LLOQs were 0.20, 0.39, 0.04, 0.31 μg·mL^-1, respectively. Acceptable accuracy as well as intra-batch and inter-batch precision were achieved; relative error (RE) and relative standard deviation (RSD) were all <15.00%. The extraction recoveries reached the standard (88.56%~112.18%, RSD<15.00%), without significant matrix effects and carryover effects. The serum samples of LTG, LEV, OXC, and MHD exhibited stability under the following conditions: storage at -20 ℃ for 14 days, three freeze-thaw cycles (-20 ℃ to room temperature), room temperature exposure for 3 hours, and post-treatment storage in the autosampler (4 ℃) for 24 hours, with all RSDs ≤10.72%. The analysis of 145 clinical samples showed that the linear range could meet the clinical needs.

This study successfully established a HPLC-MS/MS method to simultaneously quantify the serum concentration of LTG, LEV, OXC and MHD. The method is simple, economical accurate and efficient, which has promotional value.

Evaluate whether the test formulation and reference formulation of bisoprolol amlodipine tablets are bioequivalent after a single oral administration in healthy subjects under fasting and postprandial conditions.

A single-dose, randomized, open-label, two-period, self-crossover trial design was adopted. Fasting and postprandial tests were randomly divided into 2 administration sequence groups according to 1∶1 ratio, the subjects were administered orally one tablet of either the test or reference formulation of the bisoprolol-amlodipine tablet, containing 5 mg bisoprolol fumarate and 5 mg amlodipine besylate (equivalent to 5 mg amlodipine). Liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) was applied to determine the concentration of bisoprolol and amlodipine in plasma of healthy subjects after fasting or fed administration, while Phoenix WinNonlin 8.1 software were used for pharmacokinetics (PK) parameters calculation and bioequivalence analysis.

Healthy subjects took one tablet of test product (T) and the reference product (R), under fasting condition. The main pharmacokinetic parameters of bisoprolol were as follows: C_max were (26.94±5.93) and (27.85±6.06) ng·mL^-1, respectively; AUC_0-t were (325.81±59.30) and (345.77±87.04) ng·mL^-1·h^-1, respectively; AUC_0→∞ were (337.94±63.91) and (360.03±95.94) ng·mL^-1·h^-1, respectively; the main pharmacokinetic parameters of amlodipine were as follows: C_max were (3.56±0.89) and (3.63±0.93) ng·mL^-1, respectively; AUC_0-t were (165.78±47.60) and (170.76±48.63) ng·mL^-1·h^-1, respectively; AUC_0→∞ were (188.76±67.62) and (188.40±54.85) ng·mL^-1·h^-1, respectively; the 90% confidence intervals of C_max、AUC_0-t and AUC_0-∞ after logarithmic conversion of bisoprolol and amlodipine of the two products were all within 80.00%-125.00%. Healthy subjects took the test and reference product under fed condition. The main pharmacokinetic parameters of bisoprolol were as follows: C_max were (22.66±2.91) and (22.68±3.85) ng·mL^-1, respectively; AUC_0-t were (310.42±59.44) and (303.39±53.21) ng·mL^-1·h^-1, respectively; AUC_0→∞ were (320.68±67.30) and (313.31±60.15) ng·mL^-1·h^-1, respectively; the main pharmacokinetic parameters of amlodipine were as follows: C_max were (3.24±0.53) and (3.15±0.55) ng·mL^-1, respectively; AUC_0-t were (180.74±40.77) and (178.27±33.53) ng·mL^-1·h^-1, respectively; AUC_0→∞ were (199.02±50.12) and (197.77±39.64) ng·mL^-1·h^-1, respectively. The 90% confidence intervals of C_max、AUC_0-t and AUC_0-∞ after logarithmic conversion of bisoprolol and amlodipine of the two products were all within 80.00%-125.00%.

Healthy adult subjects demonstrate bioequivalence between the test formulation and reference formulation of bisoprolol amlodipine tablets following a single oral administration under both fasting and postprandial conditions.

To analyze the anticoagulant treatment of patients with low molecular weight heparin-induced severe type II thrombocytopenia complicated by multi-site embolism, and to provide reference for rational use of anticoagulant drugs in clinic.

Clinical pharmacists participated in the diagnosis and treatment of a patient with heparin-induced thrombocytopenia(HIT) with multiple thrombus. According to the patient’s pathophysiology, auxiliary examination and other conditions, combined with literature review and individualized medication monitoring, they assisted in formulating and optimizing the anticoagulant treatment plan, improving the quality of pharmaceutical care, and promoting clinical rational drug use.

The clinical pharmacist assisted in identifying the cause of thrombocytopenia, with a 4T’s HIT score of 7 (indicating high probability of HIT) and positive HIT antibody(HIT-Ab) (6.2 U·mL^-1). Following argatroban anticoagulation therapy, the patient’s blood platelet count (PLT) improved from 11 to 87 ×10 ·L^-1, while D-dimer levels peaked at 60.08 mg·L^-1 FEU before declining to 30.60 mg·L^-1 FEU. Activated partial thromboplastin time (APTT) remained stable at approximately 50 seconds. No new thrombotic or hemorrhagic events occurred, and the clinical outcome was favorable.

Although low molecular weight heparin-induced thrombocytopenia is rare, it still needs clinical attention. Clinical pharmacists can assist physicians in formulating individualized treatment plans for patients from the perspective of pharmaceutical professionals to ensure the rationality of clinical drug use.

To explore the potential role of platelet factor 4 (PF4) in Alzheimer’s disease (AD) by network pharmacology and bioinformatics analysis.

PubChem and SwissTargetPrediction databases were used to collect PF4 related targets, GeneCards and DisGeNET databases were used to collect AD targets; the protein-protein interaction (PPI) network was constructed by using STRING database to obtain the protein-protein interaction of common genes. Gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis of common targets were performed using DAVID database. The VascularSingleCells database was used to query the expression of PF4 in mouse cerebrovascular-related cells, and the AlzData database was used to analyze the verification of PF4 in the data set of known AD patients.

A total of 102 PF4-related targets, 2 403 AD targets and 51 common targets were obtained. Enrichment analysis showed that the common argets were mainly involved in cancer pathways, neutrophil extracellular trap formation, Interleukin-17 (IL-17) signaling pathway, platelet activation and relaxin signaling pathway. Analysis of cerebrovascular single cell data showed that PF4 was only expressed in microglia. The results of HPA database analysis showed that PF4 was mainly expressed in the cerebral cortex, and a small part was expressed in the amygdala.

PF4 may interfere with AD by improving neuronal viability, oxidative stress and reducing inflammatory response through neutrophil extracellular trapping network formation, IL-17 signaling and other pathways.