Objective:To compare the drug release of nifedipine sustained-release tablets from four manufacturers to evaluate the intrinsic quality. Methods:The drug release rate was determined by UV respectively with pH 1. 2 HCl solution, pH 4. 0 sodium ace-tate buffer, pH 6. 8 phosphate buffer and water as the dissolution medium. The dissolution curves were compared by f2 factor. Results:The drug release rate of nifedipine sustained-release tablets from the four manufacturers all met quality standard of our country, al-though the dissolution curves in the different dissolution medium was various. Conclusion:There are differences in intrinsic quality a-mong the nifedipine sustained-release tablets from the four manufacturers. The dissolution examination standard should be improved fur-ther.

OBJECTIVETo observe the influence of heat shock preconditioning on the expressions of heat shock protein (HSP) 60 and HSP 70 and on the activities of cytochrome oxidase (CCO) and superoxide dismutase (SOD) in mitochondria in gastric mucosa of severely scalded rats, and to investigate its protective mechanism on acute gastric mucosal lesion in rats with severe scald.

METHODSOne hundred and forty-four Wistar rats were randomized into three groups, i. e. scald group ( n = 40, acute gastric mucosal lesion was made after scald, other 8 normal rats without scald were employed as blank control); HS group ( n =40, with heat shock preconditioning 20 h before scald), and other 8 rats preconditioned with heat shock but without scald were employed as experimental control I; actinomycin D group ( n = 40, with intraperitoneal injection of 0. 1 mg/kg actinomycin D 30 min before heat shock preconditioning and other treatment as HS group), and other 8 rats with merely actinomycin D injection were employed as experimental control II. Eight rats in each group were sacrificed and laparotomized at 3, 6, 12, 24 and 48 post-scald hours (PSH) , respectively to determine the index of gastric mucosal lesions (UI ) , the mRNA expressions of HSP70 and protein expression of HSP60 and HSP70, and the changes in the activities of SOD and CCO.

RESULTSUI of the scalded rats increased as the time elapses, reaching the peak (12. 8 +/- 1.9) at 24 PSH. In addition, UI in HS group was significantly lower than that in scald group at each time-point except that at 3 PSH ( P < 0. 05 or 0. 01). The extent of gastric mucosal lesion in rats in actinomycin D group was obviously aggravated compared with that in scald and HS groups ( P <0. 05). The HSP70 mRNA expression in both scald and HS groups was increased at each time-points except for 48PBH, while that in actinomycin D group was increased at 24 PBH and 48PBH. The expressions of HSP70 and HSP60 were greatly increased in HS group compared with those in scald group ( P < 0. 05 or 0. 01) , while those in actinomycin D group were significantly inhibited ( P < 0. 05). The activities of CCO and SOD were gradually decreased in gastric mucosa in scald group, but it was greatly improved by HS preconditioning at 6, 12, 24 PSH ( P < 0. 05 or 0. 01).

CONCLUSIONHeat shock preconditioning is beneficial for the protection of acute gastric mucosal lesion of rats after severe scald, due to increase of HPS60 and HSP70 expression, and increase of CCO and SOD activities in mitochondria.

Animals ; Burns ; metabolism ; pathology ; Chaperonin 60 ; metabolism ; Electron Transport Complex IV ; metabolism ; Female ; Gastric Mucosa ; metabolism ; pathology ; HSP70 Heat-Shock Proteins ; metabolism ; Heat-Shock Response ; Male ; Mitochondrial Proteins ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Superoxide Dismutase ; metabolism

OBJECTIVETo investigate the therapeutic effect of Qingyi Decoction (QYD) and tetrandrine (Tet), used singly or combind, in treating miniature pigs with severe acute pancreatitis (SAP) and its mechanism.

METHODSThirty-two Guizhou miniature pigs were made into SAP model by pancreatic duct retrograde injection of 5% sodium taurocholate. They were randomly divided into 4 groups: the control group, the QYD group, the Tet group and the combined treated group. The serum amylase activity and interleukin-1 and 6 (IL-1, IL-6) contents in serum from vena cava and portal vein were tested by biochemistry and radioimmunoassay (RIA). Serum emodin and plasma Tet levels were measured by high performance liquid chromatography (HPLC) 24, 48 and 72 hrs after treatment. And the pathological changes of pancreas, lung and liver were observed under microscope.

RESULTSThe mortality of SAP pigs was reduced significantly and the inflammatory injury of the organs was ameliorated obviously in all treated groups, and the increased amylase activity and IL-1, IL-6 levels was attenuated. The therapeutic effect was much more obvious, and the plasma Tet level at different time points were much higher in the combined treated group than those in the other two groups treated by single drug (P < 0.01).

CONCLUSIONBoth QYD and Tet could treat effectively SAP through multiple pathways, combination of them reveals an elevation of serum drug concentration and shows a synergistic effect.

Alkaloids ; blood ; pharmacokinetics ; therapeutic use ; Animals ; Benzylisoquinolines ; blood ; pharmacokinetics ; therapeutic use ; Drug Synergism ; Drugs, Chinese Herbal ; pharmacokinetics ; therapeutic use ; Emodin ; blood ; Female ; Interleukin-1 ; blood ; Interleukin-6 ; blood ; Male ; Pancreatitis, Acute Necrotizing ; blood ; drug therapy ; Phytotherapy ; Random Allocation ; Swine, Miniature

OBJECTIVETo observe the effect of Feiyanning Granule (FYN) on tumor growth and cell cycle distribution in mice with Lewis lung cancer, as well as its influence on G1/S cell cycle checkpoint dominating signaling RB-E2F1 bio-axis.

METHODSModeled C57BL/6 mice were randomly divided into 6 groups: the model group (A), the DDP treated group (B) peritoneally injected with cisplatin 0.1 mg on d1, d3 and d5 after modeling, and the 4 FYN treated groups (C-F), administered via gastrogavage with FYN Decoction, and FYN Granule in small-, median- and high- dose respectively for 14 days. The tumour inhibiting rate, tumour weight, and body weight of mice were observed after treatment; cell cycle distribution was detected by flow cytometry (FCM), RB-E2F1mRNA expressions in tumour tissue were analyzed by RT-PCR, and their protein expressions by Western blot.

RESULTSTumour weight in the 5 treated groups was lower than that in the model group (P < 0.05, P < 0.01). Body weight in group E was significantly higher than that in group A and B (P < 0.05, P < 0.01). FCM analysis showed the proportion of G0/G1 phase was higher in group E than in group A, B and C (P < 0.01), and cancer cell proliferation index (PI) in group E was lower than in group B (P < 0.05, P < 0.01). RT-PCR showed mRNA level of E2F1 was lower, but that of RB was significantly higher in group E than those in group A, B and C respectively (P < 0.01). Westem blot analysis showed the protein expression of E2F1 was lower in group E and B than that in group A (P < 0.05), while the protein expression of Rb in group E was higher than that in group A, B and C (P < 0.05).

CONCLUSIONThe effect of FYN in inhibiting Lewis lung cancer growth was related to its intervention on cancer cell cycle distribution which blocks most tumor cells in G0/G1 phase. Moreover, FYN can reduce MDM2 expression, enhance P53 expression to influence cell cycle G1/S checkpoint dominating signaling, so as to achieve the effect of antagonizing lung cancer cell proliferation.

Animals ; Carcinoma, Lewis Lung ; metabolism ; pathology ; Cell Cycle Checkpoints ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Signal Transduction ; drug effects

OBJECTIVETo observe the clinical efficacy of Xiaoshui decoction (XSD) combined with intrapleural perfusion of cisplatin in the treatment of malignant pleural effusion.

METHODSFifty-one patients with malignant pleural effusion were randomly assigned to two groups. The treated group (26 patients) received oral administration of XSD combined with intrapleural perfusion of cisplatin, and the control group (25 patients) was only treated with intrapleural perfusion of cisplatin. The effects of the short-term efficacy, quality of life scores and clinical symptom scores of malignant pleural effusion were evaluated.

RESULTSThe short-term efficacy in the treated group and the control group was 72.0% and 58.3%, respectively, and no significant difference was found (P>0.05). In contrast, the quality of life in the treated group was significantly improved compared to that of the control group (P<0.05), and so was the symptom remission (P<0.05).

CONCLUSIONSThe combined therapy of XSD and intrapleural perfusion of cisplatin did not show obvious improvement in short-term efficacy, but the therapy remarkably alleviated the symptoms and improved the quality of life of patients.

Aged ; Aged, 80 and over ; Antineoplastic Agents, Phytogenic ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cisplatin ; administration & dosage ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Male ; Middle Aged ; Perfusion ; Pleural Cavity ; Pleural Effusion, Malignant ; drug therapy ; Treatment Outcome

COVID-19 epidemic continues to spread around the world till these days, and it is urgent to develop more safe and effective new drugs. Due to the limited P3 biosafety laboratories for directly screening inhibitors of virulent viruses with high infectivity, it is necessary to develop rapid and efficient screening methods for viral proteases and other related targets. The main protease (M^pro), which plays a key role in the replication cycle of SARS-CoV-2, is highly conserved and has no homologous proteases in humans, making it an ideal target for drug development. From two different levels, namely, molecular level and cellular level, this paper summarizes the reported screening methods of SARS-CoV-2 M^pro inhibitors through a variety of representative examples, expecting to provide references for further development of SARS-CoV-2 M^pro inhibitors.

As a common protease with high similarity among coronavirus species, the main protease (M^pro) of SARS-CoV-2 is responsible for the catalytic hydrolysis of viral precursor proteins into functional proteins, which is essential for coronavirus replication and is one of the ideal targets for the development of broad-spectrum antiviral drugs. This paper reviews the main protease inhibitors of SARS-CoV-2, including their molecular structures, potencies and drug-like profiles, binding modes and structure-activity relationships, etc.

OBJECTIVETo investigate the risk factors of benazepril related cough.

METHODSCase-control study nested in a community-based postmarketing surveillance was carried out. One thousand eight hundred and thirty-one hypertensive patients screened from a Chinese community were recruited to take benazepril for 3 years. Demographic characteristics and behavior risks were investigated and the level of uric acid and creatinine were tested at baseline. Episodes of benazepril related cough during follow period were recorded.

RESULTSWithin half a year of administration, the incidence rates of cough were as high as 18.35% in women and 12.11% in men. Incidence decreased significantly when time went by. Two years later of administration, first occurrences of cough were still seen. Based on logistic regression analysis, women were more likely to develop cough (OR = 2.193, 95% CI: 1.500 - 3.206). The association between decompensated kidney function and cough occurrence was only detected in women (OR = 3.432, 95% CI: 1.954 - 6.028). Women aged 65 or more had 1.672 (95% CI: 1.040 - 2.688) times risk than women aged 35 to 64 years. In men, the OR of developing cough was 1.689 (95% CI: 0.976 - 2.924) for daily drinking alcohol less than 100 g but increased to 2.478 (95% CI: 1.148 - 5.347) when drinking 100 g or more, but not the determinant ones.

CONCLUSIONWomen, older age, drinking alcohol and decompensated kidney function were the possible risk factors for benazepril related cough, but not the determinant ones.

Adult ; Age Factors ; Aged ; Alcohol Drinking ; adverse effects ; Angiotensin-Converting Enzyme Inhibitors ; adverse effects ; Benzazepines ; adverse effects ; Case-Control Studies ; China ; epidemiology ; Cough ; chemically induced ; epidemiology ; Female ; Follow-Up Studies ; Humans ; Hypertension ; drug therapy ; Incidence ; Kidney Function Tests ; Logistic Models ; Male ; Middle Aged ; Product Surveillance, Postmarketing ; Risk Factors ; Sex Factors

OBJECTIVETo investigate the long-term effect, safety and tolerability of benazepril in general hypertensive patients.

METHODSWe conducted a three-year community-based postmarketing surveillance on benazepril among 1831 essential hypertensive patients (age range from 35 to 88 years) in Shanghai.

RESULTS74.3% of patients persisted in medication taking and were with optimal compliance in a 3-year-follow-up program. Among those taking medication as prescribed after 3 years, 75.7% of them attained systolic blood pressure (SBP) target level of 140 mm Hg (1 mm Hg = 0.133 kPa), 87.4% attained diastolic blood pressure (DBP) target level of 90 mm Hg, and 71.5% attained total target level of 140/90 mm Hg. The reductions were approaching 15 mm Hg for SBP, 10 mm Hg for DBP, and 5 mm Hg for pulse pressure (PP) during the 3 year period. No serious adverse drug reactions (ADRs) were detected during the 3 years follow-up. Cough was the most common ADR. The cumulative incidence of benazepril related cough was 23.6% in women, significant higher than in men (18.8%).

CONCLUSIONBenazepril was safe and tolerable when applied in hypertensive patients.

Adult ; Aged ; Aged, 80 and over ; Antihypertensive Agents ; adverse effects ; therapeutic use ; Benzazepines ; adverse effects ; therapeutic use ; China ; epidemiology ; Cough ; chemically induced ; epidemiology ; Female ; Humans ; Hypertension ; drug therapy ; epidemiology ; Male ; Middle Aged ; Product Surveillance, Postmarketing

OBJECTIVETo investigate the effect of omega-3 polyunsaturated fatty acids(omega-3PUFAs) on the apoptosis of human gastric cancer cell line SGC-7901 and to explore the potential mechanisms.

METHODSCells were treated with eicosapentaenoic acid (20:5 omega-3,EPA) or docosahexaenoic acid (22:6 omega-3, DHA) at concentrations of 10, 20 and 40 microg/ml. Cell growth and apoptosis were analyzed with MTT assay, cell morphology, DNA electrophoresis and flow cytometry. Mitochondrial membrane potential ( triangle right psi mt) was measured by fluorescent probe rhodamine 123. The distribution of cytochrome C in mitochondria and cytosol was determined by enzyme-linked immunoadsorbent assay. The composition of mitochondrial membrane phospholipid(MMP)was examined by gas chromatography.

RESULTSBoth EPA and DHA markedly inhibited the SGC-7901 cell growth and induced apoptosis in a time- and dose-dependent manner. After incubation of the cells with 40 microg/ml EPA or DHA for 24 hours, the level of Deltapsimt siginificantly decreased (P<0.001), and cytochrome C largely released into cytosol from mitochondria. The proportions of EPA and DHA in MMP rapidly elevated while that of arachidonic acid sharply decreased.

CONCLUSIONSomega-3PUFAs inhibit the growth of gastric cancer cells through promoting apoptosis. Compositional and functional alterations in mitochondrial membrane may be an important initiator of apoptosis induced by omega-3PUFAs.

Apoptosis ; drug effects ; Cell Line, Tumor ; Cytochromes c ; metabolism ; Fatty Acids, Omega-3 ; pharmacology ; Humans ; Membrane Potential, Mitochondrial ; Mitochondria ; metabolism ; pathology ; Stomach Neoplasms ; metabolism