Objective To study the bioequivalence of test and reference olmesartan tablet in Chinese healthy subjects after single dose under fasting and fed conditions.Methods A single-center,random,open,single-dose,two-preparations,double-period,crossover study was adopted.A total of 48 healthy adult male and female subjects(24 cases of fasting test and 24 cases of fed test)were included in the random crossover administration.Single oral dose 20 mg of test and reference were taken under fasting and postprandial conditions,respectively.Plasma concentration of olmesartan in plasma were determined by liquid chromatography tandem mass spectrometry.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.0 software.Results The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the fasting group were as follows:Cmax were(653.06±133.53)and(617.37±151.16)ng·mL-1,AUC0-t were(4 201.18±1 035.21)and(4 087.38±889.99)ng·mL-1·h,AUC0-∞ were(4 254.30±1 058.90)and(4 135.69±905.29)ng·mL-1·h.The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the postprandial group were as follows:Cmax were(574.78±177.05)and(579.98±107.74)ng·mL-1,AUC0-t were(3 288.37±866.06)and(3 181.51±801.06)ng·mL-1·h,AUC0-∞ were(3 326.11±874.26)and(3 242.01±823.09)ng·mL-1·h.Under fasting and postprandial conditions,the 90％confidence intervals of the main pharmacokinetic parameters of the test and reference preparations are both 80.00％-125.00％.Conclusion Under fasting and postprandial conditions,a single oral dose of test and reference preparations olmesartan tablets in Chinese healthy adult volunteers showed bioequivalence.

Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.
Humans ; Polymyxin B/adverse effects* ; Retrospective Studies ; Gram-Negative Bacterial Infections/complications* ; Fever/drug therapy* ; Sepsis/drug therapy* ; Anti-Bacterial Agents/therapeutic use* ; Bacteremia/complications*

OBJECTIVE: To identify traditional Chinese drugs that contain active ingredients for treatment of myocardial infarction (MI) and explore their therapeutic mechanisms using network pharmacology and molecular docking technology. METHODS: The TCMSP database was used for screening the traditional Chinese drugs containing active ingredients for treating MI, and the related targets of MI and the candidate drugs were obtained from Genecards, OMIM, PharmGkb and PharmMapper databases. The common target network of the drug targets and disease targets was established using Venny2.1.0 software. GO and KEGG signal pathway enrichment analysis of the common targets was performed, and the protein-protein interaction (PPI) network was constructed for the targets. The targets in the PPI network were analyzed to identify the key targets, for which GO and KEGG pathway enrichment analyses were performed. Molecular docking was performed for the candidate ingredients and the key targets, and a total score ≥6 was used as the criteria for screening the therapeutic ingredients and their docking binding with key targets was verified. A human umbilical vein endothelial cell (HUVEC) model of oxygen-glucose deprivation (OGD) was used to validate the candidate ingredients and the key therapeutic targets for MI by Western blotting. RESULTS: Our analysis identified Salvia miltiorrhiza and Dalbergiae odoriferae as the candidate drugs rich in active ingredients for treatment of MI. These ingredients involved 16 key therapeutic targets for MI, which participated in such biological processes as inflammatory response, angiogenesis, energy metabolism and oxidative stress and the pathways including HIF-1, VEGF, and TNF pathways. Sclareol and PTGS2 in Salvia miltiorrhiza and formononetin and KDR in Dalbergiae odoriferae all had high docking total scores. Western blotting showed that at medium and high doses, sclareol significantly inhibited PTGS2 expression and formononetin promoted KDR expressions in the cell models in a dose-dependent manner (P < 0.05). CONCLUSION Both Salvia miltiorrhiza and Dalbergiae odoriferae have good therapeutic effects on MI. Sclareol in Salvia miltiorrhiza and formononetin in Dalbergiae odoriferae regulate the expressions of KDR and PTGS2, respectively, to modulate the inflammatory response, angiogenesis, oxidative stress and energy metabolism and thus produce myocardial protective effects.
China ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Myocardial Infarction/drug therapy* ; Network Pharmacology

Animals ; Ehrlichia/isolation & purification* ; Ehrlichiosis/veterinary* ; Prevalence ; Rodent Diseases/microbiology* ; Rodentia ; Species Specificity

BACKGROUND: Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment. METHODS: This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR. RESULTS: A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities. CONCLUSION: Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; Bendamustine Hydrochloride/therapeutic use* ; China ; Humans ; Lymphoma, Non-Hodgkin/drug therapy* ; Neoplasm Recurrence, Local/drug therapy* ; Prospective Studies ; Rituximab/therapeutic use*

Humans ; Mutation ; Myelodysplastic Syndromes/genetics* ; Prognosis ; Splicing Factor U2AF/genetics*

OBJECTIVE: To observe the therapeutic effect of pre-acupuncture at Neiguan (PC 6) and Zusanli (ST 36) on exercise-induced fatigue. METHODS: A total of 50 subjects were divided into an observation group and a control group by random number table method, 25 cases in each one. In the observation group, acupuncture was applied at Neiguan (PC 6) and Zusanli (ST 36) before exercise, once a day, consecutive 5-day treatment was required. In the control group, there was no intervention. The subjective fatigue perception score, serum levels of lactate and lactate dehydrogenase, heart rate and oxygen saturation before and after exercise were observed in the two groups. RESULTS: Compared before exercise, the subjective fatigue perception scores, serum levels of lactate and lactate dehydrogenase and heart rates after exercise were increased in the two groups (<0.05, <0.01), and the subjective fatigue perception score, serum levels of lactate and lactate dehydrogenase and heart rate after exercise in the observation group were lower than the control group (<0.05, <0.01). There was no significant difference in oxygen saturation before and after exercise in the two groups，there was no significant difference in oxygen saturation after exercise between the two groups (>0.05). CONCLUSION Pre-acupuncture at Neiguan (PC 6) and Zusanli (ST 36) can effectively reduce the subjective fatigue perception score，serum levels of lactate and lactate dehydrogenase and heart rate to improve exercise-induced fatigue.
Acupuncture Points ; Acupuncture Therapy ; Case-Control Studies ; Exercise ; physiology ; Fatigue ; therapy ; Heart Rate ; Humans

Objective: To evaluate the effects of CYP2C19 genetic polymorphism on the plasma concentration of voriconazole in patients with hematological disease and the value of serial monitoring plasma concentrations in the treatment and prevention of invasive fungal disease (IFD). Methods: From January 2016 to December 2016, 65 hematological patients who received voriconazole intravenous administration for the treatment of invasive fungal disease were enrolled in this study. The population CYP2C19 polymorphism of voriconazole were performed using PCR-Pyrosequencing. The trough plasma concentrations of vriconazole (C_trough) was detected by ultra performance liquid chromatography tandem mass spectrometry. Results: Based on the genotype analysis, 65 subjects were identified as extensive metabolizers' group (30 cases) and poor metabolizers' group (35 cases). The C_trough of the 65 patients were detected for 169 times totally, and there was a significant difference of C_trough values between the two groups [0.98(0.38-2.08) mg/L vs 2.19(1.53-4.27) mg/L, z=10.286, P<0.001]. The medium of C_trough in 65 hematological patients were described. Lack of response to therapy was more frequent in patients with voriconazole levels <1.5 mg/L (50.0%) than in those with voriconazole levels >1.5 mg/L (20.5%) (P=0.052). And the risk of adverse events was more frequent in patients with voriconazole levels >5.5 mg/L (80.0%) than in those with voriconazole levels ≤5.5 mg/L (8.3%) (χ²=11.689, P=0.020). Conclusion: Patients with CYP2C19 wild-type phenotype are extensive metabolizers, their C_trough of voriconazole are significantly lower than patients with CYP2C19 non-wild-type phenotype (poor metabolizers). Appropriate concentrations of vriconazole can improve the efficacy and safety during treatment.
Antifungal Agents ; Cytochrome P-450 CYP2C19/genetics* ; Genotype ; Hematologic Diseases/genetics* ; Humans ; Mycoses ; Phenotype ; Polymorphism, Genetic ; Voriconazole

Though evaluation and analysis on the relevant literatures at home and abroad in recent years, the total number of retrieved literature was 2 664. According to the inclusion criteria and exclusion criteria,the literatures were screened out, and the results were as follows：374 literatures. To analyse the advantages and evidence of Chinese medicine in the prevention and treatment of adult acute tonsillitis. It is found to be effective, convenient and practical for the treatment of acute tonsillitis by traditional Chinese medicine (TCM) like treatment according to syndrome differentiation, Chinese patent drug, self Chinese medicine prescription and external treatment. TCM has obvious advantages in the prevention and treatment of acute tonsillitis, has the function of supplementing or substituting antibiotics, and has the function of regulating the defense function of organism.

Objective To establish a HPLC-MS/MS method to simultaneously determinate R-warfarin and S-warfarin concentrations in human plasma.Methods Warfarin enantiomers were extracted with ethylacetate,ibuprofen was used as internal standard (IS).R-warfarin and S-warfarin were separated on column Lux cellulose-4 (4.6 mm× 250 mm,5 μm) with mobile phase 5 mmol ammonium acetate solution containing 0.4％ formic acid acetonitrile =45 ∶ 55,at flow rate of 0.5 mL · min-1.Warfarin enantiomers were protonated with electroapry ionization (ESI),the multiple reaction monitoring (MRM) transitions were preformed at m/z 307.0→m/z 161.0 for R-warfarin,m/z 306.9→m/z 106.9 for S-warfarin and m/z 204.8--→m/z 161.0 for internal standard,the specificity,lower limit of quantitation and standard curve,precision and accuracy and recovery rate as well as stability were investigated.Results The standard curves of R-warfarin and S-warfarin were Y=2.57 ×10-3X+3.84 ×10-3(R2 =0.997 6),Y=2.46 × 10-3X+ 4.60 × 10-3(R2 =0.996 8),had a good linear relationship in 10.00-500.0 μg · L-1,the limit of quantification was 10.00 μg · L-1.The method was validated by recovery,precision,accuracy,matrix effect and sample stability.Conclusion The developed HPLC-MS/MS method in our study was sensitive and accurate,and the method was able to determinate the R-warfarin and S-warfarin concentrations in human plasma.