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.

To observe the clinical efficacy and safety of preoperative medication with lidocaine hydrochloride injection ultrasonic atomization combined with low-dose dexmedetomidine hydrochloride injection for fiberoptic bronchoscopy under general anesthesia in patients with pulmonary tuberculosis.

Patients with pulmonary tuberculosis scheduled for general anesthesia fiberoptic bronchoscopy were randomly divided into treatment group and control group. Both groups were given intravenous infusions of fentanyl citrate injection 0.05 mg and 1.5 mg·kg^-1 propofol medium and long chain fat emulsion injection for induction of anesthesia. During the procedure, 2-3 mg·kg^-1·h^-1 propofol medium and long chain fat emulsion injection was used to maintain anesthesia. Control group received no additional treatment, while treatment group received an additional intravenous infusion of 0.2 μg·kg^-1 dexmedetomidine hydrochloride injection through micro-pump over 15 min, combined with nebulized inhalation of lidocaine hydrochloride injection 3-4 mL, before induction of anesthesia. The postoperative anesthesia status, recovery quality, inflammation-related indicators and safety were compared between the two groups.

Among the 95 patients with pulmonary tuberculosis who underwent fiberoptic bronchoscopy under general anesthesia, 3 cases dropped out during the treatment and finally 46 cases were included in each group. After treatment, the loss of consciousness time in control group and treatment group were (172.65±36.81) and (146.67±26.46)s, respectively; the recovery time were (18.67±1.06) and (15.50±0.75) min, respectively; the orientation recovery time were (16.63±1.76) and (9.57±1.70) min and the dosage of propofol were (130.21±13.41) and (124.02±15.43) mg, respectively; the Ramsay scores of 10 minutes after awakening were (3.09±0.51) and (2.57±0.62) points, respectively; the Ramsay scores of 20 minutes after awakening were (3.52±0.55) and (3.00±0.67) points, respectively; the levels of death-associated protein kinase 1 (DAPK1) were (88.08±9.85) and (81.88±11.55) ng·L^-1, respectively; the levels of NOD-like receptor family pyrin domain-containing 3 (NLRP3) were (78.63±9.35) and (73.96±7.52) ng·L^-1, respectively; the levels of interleukin-1β (IL-1β) were (46.02±4.59) and (41.04±6.62) ng·L^-1, respectively and the levels of IL-18 were (5.71±1.64) and (4.78±1.23) ng·L^-1, respectively. The differences of the above indexes between treatment group and control group were statistically significant (all P<0.05). The main adverse drug reactions of control group were tinnitus, dizziness, nausea, agitation and convulsion; in treatment group were dizziness, nausea, agitation and convulsion, the total incidence of adverse drug reactions in control group was 13.04% (6 cases/46 cases), while that in treatment group was 8.70% (4 cases/46 cases). There was no statistically significant difference between the two groups (P>0.05).

Lidocaine hydrochloride injection combined with low-dose dexmedetomidine hydrochloride injection has significant advantages in patients with pulmonary tuberculosis undergoing fiberoptic bronchoscopy under general anesthesia. It can effectively improve the anesthetic effect and recovery quality of patients, reduce the dosage of propofol and reduce the levels of inflammatory factors with with good safety.

To study the efficacy and safety of allisartan isoproxil tablet combined with indapamide tablet in the treatment of patients with mild to moderate essential hypertension and coronary heart disease.

Patients with mild to moderate essential hypertension and coronary heart disease were divided into treatment group and control group using the cohort method. The control group was given oral indapamide tablets 2.5 mg once a day based on the conventional treatment regimen. The treatment group was given allisartan isoproxil tablets 240 mg once a day in addition to the control group’s regimen for a total of 12 weeks. The clinical efficacy, 24-hour blood pressure variability, cardiac function, vascular endothelial function and safety evaluation of the two groups were compared.

A total of 105 patients were enrolled, including 54 patients in treatment group and 51 patients in control group. After treatment, the total clinical effective rate of the treatment group was 90.74% (49 cases/54 cases), and that of control group was 72.55% (37 cases/51 cases), which was significantly higher in treatment group than in control group (P<0.05). After treatment, the daytime (d) systolic blood pressure variability (SBPV) levels in treatment group and control group were (11.32±2.13) and (12.48±2.26) mmHg, respectively; the nighttime (n) SBPV levels were (10.03±1.79) and (10.82±2.10) mmHg, respectively; the d diastolic blood pressure variability (DBPV) levels were (8.66±1.51) and (9.36±1.57) mmHg, respectively; the nDBPV levels were (8.05±1.32) and (8.68±1.62) mmHg, respectively; the 24 h SBPV levels were (10.85±2.20) and (11.96±2.05) mmHg, respectively; the 24 h DBPV levels were (9.67±1.93) and (10.66±1.92) mmHg, respectively; the brain natriuretic peptide (BNP) levels were (83.47±10.53) and (89.41±13.19) ng·L^-1, respectively; the endothelin-1 (ET-1) levels were (55.44±9.27) and (60.36±10.86) ng·L^-1, respectively; and the Apelin levels were (36.44±6.41) and (34.22±4.37) ng·mL^-1, respectively. The above metrics showed significant differences between the two groups (P<0.05，P<0.01). The adverse drug reactions in treatment group included diarrhea, fever, fatigue, palpitations, soreness in both knee joints, cough, insomnia, decreased appetite and orthostatic hypotension. The adverse drug reactions in control group included diarrhea, headache, decreased appetite, insomnia and orthostatic hypotension. The total incidence of adverse drug reactions in treatment group was 22.22% (12 cases /54 cases), and that in control group was 17.65% (9 cases /51 cases). There was no statistically significant difference (P>0.05).

The application of allisartan isoproxil combined with indapamide in treatment of patients with mild to moderate essential hypertension and coronary heart disease can achieve significant therapeutic effects, regulate 24-hour blood pressure variability, improve cardiac function, vascular endothelial function, and quality of life, also demonstrate good safety.

To observe the clinical efficacy and safety of finerenone tablets combined with dapagliflozin tablets in the treatment of elderly diabetic nephropathy (DN).

Elderly patients with DN in hospital were divided into treatment group and control group. The patients in control group were treated with oral dapagliflozin tablets once a day in the morning, with a dose of 5 mg each time, while the patients in the treatment group were combined with finerenone tablets on the basis of control group, and adjusted according to the estimated glomerular filtration rate (eGFR) levels of patients. Serum creatinine (SCr), blood urea nitrogen (BUN), 24 h urine protein quantification, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hs-cRP), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and clinical efficacy were compared between groups of patients, and the safety was evaluated.

A total 90 patients were enrolced; 45 in treatment group and 45 in control group. After treatment, the SCr levels in treatment group and control group were (127.63±10.28) and (140.27±11.95) μmol·L^-1, BUN levels were (11.45±3.57) and (18.62±3.29) mmol·L^-1, 24 h urine protein quantification levels were (99.28±11.42) and (117.92±12.00) mg·24 h^-1, IL-6 levels were (12.32±2.15) and (16.41±3.50) ng·L^-1, TNF-α levels were (31.68±10.52) and (43.09±11.83) ng·L^-1, hs-cRP levels were (6.08±1.20) and (9.56±1.57) ng·L^-1, TC levels were (4.49±0.55) and (4.83±0.72) mmol·L^-1, TG levels were (2.57±0.63) and (2.79±0.48) mmol·L^-1, LDL-C levels were (2.71±0.63) and (3.06±0.45) mmol·L^-1 respectively, and the above indicators in treatment group were significantly lower than those in control group, with statistically significant differences (all P<0.05). The total clinical effective rate in treatment group was 93.34% (42 cases/45 cases), and that in control group was 75.56% (34 cases/45 cases), with statistically significant difference (P<0.05). The adverse drug reactions in treatment group were hypotension, hypoglycemia, acute kidney injury, hyperkalemia and pruritus, and the adverse drug reactions in control group included hypoglycemia, acute kidney injury and hyperkalemia. The total incidence rates of adverse drug reactions in treatment group and control group were 22.22% (10 cases/45 cases) and 8.89% (4 cases /45 cases) respectively, without statistically significant difference (P>0.05).

Compared with dapagliflozin tablets, the combined use of finerenone tablets for elderly DN can better improve the renal function, and regulate the lipid metabolism, with good safety.