ObjectiveTo investigate the influence of empagliflozin combined with donafenib or lenvatinib on the pharmacokinetic parameters of each drug， and to provide a reference for combined medication in clinical practice. MethodsA total of 48 healthy male Sprague-Dawley rats were divided into 8 groups： empagliflozin group 1 and 2， donafenib group， lenvatinib group， donafenib pretreatment+empagliflozin group， lenvatinib pretreatment + empagliflozin group， empagliflozin pretreatment+donafenib group， and empagliflozin pretreatment+lenvatinib group， with 6 rats in each group. The doses of empagliflozin， donafenib， and lenvatinib were 2.5 mg/kg， 40 mg/kg， and 1.2 mg/kg， respectively. The rats in the empagliflozin group， donafenib group， and lenvatinib group were given a blank solvent by gavage for 7 consecutive days， followed by a single dose of empagliflozin， donafenib， or lenvatinib on day 7 after the administration of the blank solvent； the rats in the pretreatment groups were given the pretreatment drug by gavage for 7 consecutive days， followed by a single dose of drug combination on day 7 after administration of the pretreatment drug. Blood samples were collected at different time points， and plasma was separated to measure the concentration of each drug. A validated ultra-performance liquid chromatography-tandem mass spectrometry method was used to measure the plasma concentrations of donafenib， lenvatinib， and empagliflozin， and a non-compartmental model was used to calculate the main pharmacokinetic parameters of each drug （area under the plasma concentration-time curve ［AUC］， time to peak ［T_max］， peak concentration ［C_max］， and half-life time ［t_1/2］）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. ResultsCompared with the empagliflozin group， the donafenib pretreatment+empagliflozin group had significant increases in the AUC_0-t and AUC_0-∞ of empagliflozin （P=0.011 and 0.008）， while the lenvatinib pretreatment+empagliflozin group had no significant change in the AUC of empagliflozin， with a slightly shorter T_max （P=0.019）. Compared with the donafenib group， the empagliflozin pretreatment+donafenib group had significant increases in the AUC_0-t and AUC_0-∞ of donafenib （P=0.027 and 0.025）， as well as a significant increase in C_max （P=0.015） and significant reductions in CLz/F and Vz/F （P=0.005 and 0.004）； compared with the lenvatinib group， the empagliflozin pretreatment+lenvatinib group had a reduction in the t_1/2 of lenvatinib by approximately 5 hours （P=0.002）， with a trend of reduction in AUC_0-t （P0.05）. ConclusionEmpagliflozin combined with donafenib may alter the pharmacokinetic parameters of both drugs， leading to a significant increase in the exposure levels of both drugs， and efficacy and adverse reactions should be monitored during co-administration. There are no significant changes in the exposure levels of empagliflozin and lenvatinib during co-administration.

Antibody drug conjugates(ADCs)are a new class of anti-tumor drugs in which linkers in the structure link cytotoxic drugs to monoclonal an-tibodies and release cytotoxic drugs to tumors.Disi-tamab vedotin(RC48)is a new antibody-drug con-jugate independently developed in China.It targets the HER2 protein on the surface of tumors,it has both antibody targeting and small molecule drug killing,and can accurately recognize and kill tumor cells.Compared with traditional HER2-targeted drugs,disitamab vedotin has a wider therapeutic window and less toxicity to normal tissues.Current-ly,disitamab vedotin for injection has been ap-proved by the National Medical Products Adminis-tration(NMPA)for use in patients with HER2 over-expression(HER2 immunohistochemical results of 2+or 3+)who have locally advanced or metastatic gastric cancer(including gastroesophageal junction adenocarcinoma)and have received at least two types of systemic chemotherapy.Additionally,it is indicated for patients with locally advanced or met-astatic urothelial carcinoma who have previously undergone platinum-containing chemotherapy and exhibit HER2 overexpression,specifically 2+or 3+immunohistochemical results.In this paper,we will review the structural characteristics,mechanism of action and clinical trials of disitamab vedotin and look forward to the clinical application prospects of this drug.

Background and Aims:Accurate early pathogen diagnosis is a breakthrough for improving the prognosis of infectious pancreatic necrosis(IPN)patients.However,there is currently a lack of efficient methods for early identification of IPN in clinical settings.This study was performed to assess the application value of next-generation sequencing technology based on metagenomic capture(MetaCAP)in the pathogen diagnosis of IPN. Methods:A prospective study was conducted on 29 patients suspected of having acute necrotizing pancreatitis at Xiangya Hospital of Central South University between January and July 2024.Blood samples were tested using MetaCAP and conventional pathogen culture.The results of peritoneal fluid pathogen culture were used as the gold standard to compare the diagnostic efficacy of the two methods. Results:Due to three cases lacking peritoneal fluid culture results,a total of 26 cases were included in the final analysis.The overall mortality rate was 23.1％(6/26).During hospitalization,9 cases(34.6％)were diagnosed with IPN.The sensitivity and negative predictive value of MetaCAP for diagnosing IPN were significantly higher than those of conventional pathogen culture(77.8％vs.11.1％,P=0.031;86.7％vs.65.2％,P=0.032),while the differences in specificity(76.5％vs.88.2％,P=0.689)and positive predictive value(63.6％vs.33.3％,P=0.347)between the two methods were not statistically significant.The average detection time for MetaCAP was 33(20-49)h,while microbial culture took 125(45-142)h,with a significant difference(P＜0.001).The average cost for blood MetaCAP testing was 2 500 yuan per case,but it accounted for only 1.19％of the average hospitalization cost. Conclusion:MetaCAP has significant value in the early pathogen diagnosis of IPN,with a shorter detection time,good testing efficacy,and health-economic value,demonstrating a promising clinical application prospect.

Antibody drug conjugates(ADCs)are a new class of anti-tumor drugs in which linkers in the structure link cytotoxic drugs to monoclonal an-tibodies and release cytotoxic drugs to tumors.Disi-tamab vedotin(RC48)is a new antibody-drug con-jugate independently developed in China.It targets the HER2 protein on the surface of tumors,it has both antibody targeting and small molecule drug killing,and can accurately recognize and kill tumor cells.Compared with traditional HER2-targeted drugs,disitamab vedotin has a wider therapeutic window and less toxicity to normal tissues.Current-ly,disitamab vedotin for injection has been ap-proved by the National Medical Products Adminis-tration(NMPA)for use in patients with HER2 over-expression(HER2 immunohistochemical results of 2+or 3+)who have locally advanced or metastatic gastric cancer(including gastroesophageal junction adenocarcinoma)and have received at least two types of systemic chemotherapy.Additionally,it is indicated for patients with locally advanced or met-astatic urothelial carcinoma who have previously undergone platinum-containing chemotherapy and exhibit HER2 overexpression,specifically 2+or 3+immunohistochemical results.In this paper,we will review the structural characteristics,mechanism of action and clinical trials of disitamab vedotin and look forward to the clinical application prospects of this drug.

Antidepressants are mainly used to treat mental illnesses. Traditional antidepressants mainly target monoamine neurotransmitters, but these drugs are slow to be effective and cannot meet clinical needs. Recently, therapeutics have been developed that depart from the traditional monoamine hypothesis and focus on the glutamatergic, GABAergic, opioidergic, and inflammatory systems. In recent years, great progress has been made in the development of new antidepressants, some of which have been applied in clinical practice. This article mainly summarizes the research mechanisms and treatment programs of new antidepressants, and briefly reviews common rapid-acting antidepressants.

Objective:To determine and investigate the stability of ginkgo biloba extract injection from three different manufactur-ers respectively in 0.9% NaCl infusion and 5% glucose infusion under different conditions (room temperature, high temperature and light). Methods:Ginkgo biloba extract injection was mixed with the two kinds of infusions,and then divided into the normal tempera-ture group,the high temperature group and the light group. The appearance,insoluble particles,pH and content of flavonoids after the relevant treatment were investigated. The appearance and insoluble particles were tested according to the characteristics of the inspec-tion method described in Chinese Pharmacopoeia(2015 edition,volume IV,the general rule),and the content of flavonoids was detec-ted by HPLC-UV. Results:All the mixed solutions were yellow. No significant changes were found in the appearance,pH value,in-soluble particles and contents of quercetin and isorhamnetin in all the mixed solutions in 24 h. The pH value of the mixed solution with 5% glucose infusion was lower than that with 0.9% NaCl infusion,and all the pH values met the standard in Chinese Pharmacopeias. The kaemphenol content in the injection from Shenwei pharmaceutical company was higher than that from the other manufacturers, while the content of kaemphenol in all the injections was within the standard range. Conclusion:The quality of Ginkgo biloba extract injection from the three different manufacturers is stable under different conditions.

AIM:To explore the mechanisms underlying contraction induced by extracelluar acidosis (pHex6.8) in rat isolated coronary artery (RCA).METHODS:Using the microvessel tension recorder system, the effects of acid-base transporters on RCA contraction induced by pHex6.8 were explored by applying the selective pharmacological inhibitors of Na+-H+ exchanger 1 (NHE-1) and Na+-HCO-3 cotransporter (NBC), HOE-642 and S0859, respectively.The effects of chloride channel on RCA contraction induced by pHex6.8 were explored by applying the inhibitors of chloride channel (NPPB and NFA), and by replacing the extracellular NaCl with equimolar NaBr.RESULTS:pHex6.8 augmented the resting tension of RCA, and the maximum contraction was (3.90±0.95) mN.HOE-642 at 30 μmol/L and S0859 at 100 μmol/L both inhibited the contraction of RCA induced by pHex6.8 (P<0.01).NPPB and NFA both inhibited the contraction of RCA induced by pHex6.8 or KCl (60 mmol/L) in a concentration-dependent manner.NPPB and NFA (100 μmol/L) both inhibited the contraction of RCA induced by U46619 (1 μmol/L).Replacing the extracellular NaCl with equimolar NaBr almost completely inhibited RCA contraction induced by pHex6.8 (P<0.01), but had no obvious effect on the contraction induced by KCl (60 mmol/L) or U46619 (1 μmol/L).CONCLUSION:Extracellular acidosis-induced contraction in RCA may be related to the activated NHE-1 and NBC, and it may be also related to the enhanced chloride transport across the membrane.

Objective To profile the omp1 genotypes of Chlamydia trachomatis (Ct) in patients with nongonococcal urethritis (cervicitis) in Guangzhou region. Methods Swab samples were obtained from the urethra of males and cervix of females in clinical settings of venereology and gynecology as well as at outreach sites for the prevention and control of sexually transmitted diseases (STDs). DNA was extracted from the swabs and nested PCR was performed to amplify the variable domain (VD) 1 - 3 of omp1 gene of Ct followed by gene sequencing. The genotypes of Ct were determined based on the amino acid mutation in VD 1 - 2 of omp1 gene. Results Totally, 1208 swabs were collected. Of them, 132 were Ct positive, and 130 positive samples underwent genotyping. Ten ompl genotypes were determined in total, including serotype E (38, 29.23%), D (25, 19.23%), J(24, 18.46%), F(21, 16.15%), G(7, 5.38%), H(5, 3.85%), K(5, 3.85%), B(2, 1.54%), Ja (2, 1.54%), I (1, 0.77%). E, D, J and F were the dominant type of Ct in this region, and amounted to 83% of all the Ct isolates. Mutations were observed within VD 1 and 2 of omp1 gene in serotype D, B and K.Serotypes were undetermined for Ct in 2 patients with mixed infection. Conclusions In Guangzhou region, E,D, F and J are the predominant genotypes of Ct, and amount to 83% of all the Ct isolates. Ct serotype B is also observed in the urethra of males and cervix of females in this region.

OBJECTIVETo study the distribution of poly(ADP-ribose) polymerase(PARP) pseudogene polymorphism and the association with susceptibility to lung cancer in Chinese people.

METHODSThe subjects of this study included 63 patients with lung cancer and 82 healthy controls matched in gender and age. Genome DNA was extracted from white blood cells. Products from PCR with a pair of specific primer were electrophoresized in agarose including EB. Under ultraviolet, observation and imaging were performed.

RESULTSThere was no significant difference in genotype between the cases and controls. The frequencies of B allele in cases and controls were 0.095 and 0.116 respectively. Whether there was B allele or not, smoking was a risk factor of lung cancer (P<0.05). As the genotype was AA and AB or BB, smoking OR was 2.28 and 4.83 respectively. Among non-smokers, the risk at lung cancer did not increase in AB or BB genotypes(P=0.202).

CONCLUSIONFrequency of B allele is relatively lower in Chinese people than in other races. In smokers, B allele may be a susceptible marker of lung cancer, and there is synergistic function between B allele and smoking.

Adult ; Aged ; Alleles ; China ; DNA, Neoplasm ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Lung Neoplasms ; enzymology ; genetics ; Male ; Middle Aged ; Poly(ADP-ribose) Polymerases ; genetics ; Polymorphism, Genetic ; Pseudogenes ; genetics