Aim To explore the effect of serum contai-ning Duhuo Jisheng Decoction on the proliferation,ap-optosis and inflammation of fibroblast-like synoviocytes(FLS)induced by tumor necrosis factor-α(TNF-α)in rheumatoid arthritis(RA)and to reveal the under-lying mechanism.Methods The MH7A cells were divided into five groups:normal group(10％blank se-rum),model group(10 μg·L-1 TNF-α+10％blank serum),Duhuo Jisheng Decoction low(10 μg·L-1 TNF-α+2.5％drug-containing serum+7.5％blank serum),medium(10 pg·L-1 TNF-α+5％drug-con-taining serum+5％blank serum),high(10 μg·L-1 TNF-α+10％drug-containing serum)dose group.The concentration of serum containing Duhuo Jisheng Decoction was screened by MTT method.Cell prolifer-ation was detected using EdU staining.The expression of proliferation marker Ki67 was detected using immu-nofluorescence staining.The apoptosis rate was meas-ured by flow cytometry.The contents of IFN-γ,IL-4,IL-6 and IL-10 in each group were detected by ELISA.The mRNA and protein expression of Bax,Bcl-2,caspase-3 and TLR4/MyD88/NF-κB signaling pathway were detected by RT-qPCR and Western blot.Results Compared with the normal group,the cell prolifera-tion activity of the model group significantly increased,and the level of apoptosis decreased.The content of IFN-γ and IL-6 increased,and the content of IL-4 and IL-10 decreased.The TLR4/MyD88/NF-κB signaling pathway was activated.After the intervention of low,medium and high dose groups of serum containing Du-huo Jisheng Decoction,it could effectively improve the abnormal proliferation of cells and enhance apoptosis.At the same time,it inhibited the inflammatory re-sponse and the activation of TLR4/MyD88/NF-κB sig-naling pathway.Conclusions The serum containing Duhuo Jisheng Decoction can inhibit the abnormal pro-liferation of RA-FLS induced by TNF-α and the secre-tion of pro-inflammatory factors,and enhance apoptosis and anti-inflammatory levels.The mechanism may be related to the regulation of TLR4/MyD88/NF-κB sig-naling pathway.

This study was aimed at analyzing the effectiveness of vector control efforts at the 19th Asian Games in Hang-zhou,to provide a reference for future vector control at similar large-scale events.We collected and analyzed vector organism monitoring data for various venues at Asian Games(branch)villages and designated reception hotels(hotels and guesthouses)associated with the Asian Games in Hangzhou from April to October of 2023.Excel 2019 software and SPSS 20.0 software were used to organize the data.Paired t tests(for normally distributed data)or Wilcoxon signed rank tests(for data not nor-mally distributed)were performed,and count data were analyzed statistically with x2 tests.The larva mosquito path index at Asian Games venues peaked in June and then declined month by month.The first circle area of the adult mosquito human trapping index peaked in June,and the second circle area peaked in July.The mosquito indicators reached the corre-sponding control standards before the Asian Games.Moreo-ver,the differences in mosquito density before and after the Asian Games were statistically significant(all P＜0.05).Both the positivity rate and density of flies in rooms reached level A in the first and second circle areas from April to October.The proportion of indoor fly-proof facilities meeting the standards was lowest in May,then gradually increased.The corresponding control standards were reached in the first round in the fourth week of September,and in the second round in the first week of October.The difference in the density of positivity for room flies before and after the Asian Games was statistically significant(all P＜0.05).Rodent density reached the corre-sponding control standards in the second week of September.The proportion of anti-rodent facilities meeting the standards was lowest in June,and then gradually increased.The first round began to meet the corresponding control standards in the fourth week of September,and the second round began to meet the corresponding control standards in the first week of October.Ex-cept for the outdoor rat density path index,which was statistically significant before and after the Asian Games,the other indi-cators showed no statistical significance(P＞0.05).The cockroach density in the first circle area reached level A in all months,and that in the second circle area reached level B in mid-August.Vector control in the Hangzhou Asian Games achieved the ex-pected results,with no vector infringement or local vector-borne infectious diseases occurring.In future vector control for large-scale events,vector density monitoring should be performed as early as possible,and comprehensive prevention and control measures should be taken to maintain low vector density and prevent vector infringement incidents.

Objective:To analyze the biological characteristics, phylogeny and the taxonomic status of strain 7712 (=CGMCC 1.17031=NBRC 113783=KCTC 15766) isolated from a clinical blood sample.Methods:Strain 7712 was identified by the cultural properties, cellular and colonial morphology, physiological and biochemical reactions, matrix-assisted laser desorption ionization time-of-flight mass spectrometry system, and genome correlation index analysis. The genomic phylogenetic tree was construct to analyze the taxonomic position. The virulence factors and resistance genes of strain 7712 and related strains were then compared by the online virulence factor database and online comprehensive antibiotic research database respectively.Results:Strain 7712 was urease negative, gram-negative nonfermenters, which was identified as Ochrobactrum anthropi by VITEK GN card. The 16S rRNA gene analysis showed that the strain was closely related to the members of genera Ochrobactrum and Brucella. The phylogenetic tree showed that strain 7712 was clustered together with Ochrobactrum teleogrylli LCB8 T and Ochrobactrum haematophilum CCUG 38531 T, along with genus Brucella and other Ochrobactrum species. The genome relatedness indexes analysis showed that the average nucleotide identity between strain 7712 and Ochrobactrum teleogrylli LCB8 T was 98.16%, which was higher than the threshold for prokaryotic species. Genetic prediction showed that strain 7712 carried several virulence-related genes and resistance-related genes, of which the existence of OCH gene might be responsible to the resistance to cephalosporin. Conclusions:A case of human infection caused by Ochrobactrum teleogrylli is identified, which would help promote the understanding of biodiversity of genus Ochrobactrum.

Humans ; Vascular Stiffness ; Coal Mining ; Occupational Diseases/epidemiology* ; Risk Factors ; Coal ; Miners

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To observe the application effect of intra-arterial tirofiban during mechanical thrombectomy for acute anterior circulation cerebral infarction.Methods The clinical data of patients with acute anterior circulation cerebral infarction were retrospectively analyzed.According to cohort method,they were divided into control group and treatment group.The control group was treated with mechanical thrombectomy,while the treatment group was additionally given intra-arterial therapy with tirofiban 0.25-0.5 mg on the basis of the control group.The perioperative indicators(surgical time,number of thrombectomy,vascular recanalization time,vascular recanalization rate),National Institutes of Health Stroke Scale(NIHSS)score before treatment and at 24 hours and 7 days after treatment,platelet indicators[mean platelet distribution width(PDW),mean platelet volume(MPV),plateletcrit(PCT)],hemorheological indicators[plasma viscosity(PV),low whole blood viscosity(LWBV),high whole blood viscosity(HWBV)],serum indicators[high-sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α),vascular endothelial growth factor(VEGF)]and clinical efficacy were compared,and the safety of the treatment regimen was assessed.Results There were 92 patients were finally included in this study,including 49 cases in control group and 43 cases in treatment group.The effective rates in treatment group and control group were 75.51％(37 cases/49 cases)and 93.02％(40 cases/43 cases),with significant difference(P＜0.05).The surgical times in treatment group and control group were(93.53±9.86)and(91.59±8.36)min;the vascular recanalization times were(78.46±9.69)and(77.40±10.32)min;the vascular recanalization rates were 93.02％and 83.67％;the NIHSS scores were(10.32±2.90)and(9.59±2.84)points at 24 hours after treatment,all with no significant difference(all P＞0.05).At 7 days after treatment,the NIHSS scores in treatment group and control group were(3.34±1.25)and(4.12±1.48)points;the PDW values were(12.58±1.81)％and(14.15±1.95)％;MPV values were(9.16±1.24)and(11.26±1.86)fL;PCT levels were(0.33±0.05)％and(0.29±0.04)％;PV values were(1.64±0.27)and(1.99±0.24)mPa·s-1;LWBV values were(4.16±0.48)and(5.01±0.49)mPa·s-1;HWBV values were(8.12±0.54)and(9.27±0.68)mPa·s-1;serum hs-CRP levels were(3.57±0.45)and(4.48±0.83)mg·L-1;TNF-α levels were(20.42±4.55)and(27.34±4.95)ng·L-1;VEGF levels were(738.80±52.41)and(664.72±41.68)ng·L-1,all with significant difference(all P＜0.05).Incidence rates of adverse drug reactions in treatment group and control group were 8.16％(4 cases/49 cases)and 4.65％(2 cases/43 cases)respectively,with no significant difference(P＞0.05).Conclusion Intra-arterial tirofiban therapy during thrombectomy for acute anterior circulation cerebral infarction has good neurological function and prognosis,and it may be related to the improvement of platelet function and cerebral tissue blood flow and relief of inflammatory response.

The chimeric antigen receptor T cell(CAR-T)therapy products approved for market and under development mainly targets the B-cell receptor-related protein CD19.This paper relies on the pharmacovigilance database during clinical trials of the Center for Drug Evaluation National Medical Products Administration.We retrospectively analyzed the 113 individual case safety expedited reports of suspected unexpected serious adverse reactions of CAR-T cell therapy products containing B-cell receptor-rolated protein CD19 from domestic clinical trials received from January 1,2021 to May 20,2024.Strengthen risk management according to product characteristics.It is expected that through this paper,the sponsors can improve the pharmacovigilance regime and system,timely report according to the requirements,strengthen the risk communication with the regulatory authorities,form a joint force with the regulatory authorities,and jointly do a good job in risk management during clinical trials.

Objective To study the pharmacokinetics and bioequivalence of two formulations of rasagiline mesylate tablets in healthy subjects under fasting and fed conditions.Methods The two-period,two-sequence,crossover study design was adopted in the fasting study.Thirty-six subjects were enrolled and given either test preparation or reference preparation 1 mg respectively in two periods.After collecting plasma samples,the plasma concentration of rasagiline was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)and the bioequivalence was evaluated using the average bioequivalence(ABE)method.The four-period,two-sequence,fully replicate crossover study design was adopted in the fed study.Forty-eight subjects were enrolled and given the test preparation or the reference preparation at a dose of 1 mg twice respectively in four periods.According to the degree of intra-individual variation of Cmax,AUC0-t and AUC0-∞,the equivalence was evaluated using the reference-scaled average bioequivalence and ABE method,respectively.Results In the fasting study,the pharmacokinetic parameters of rasagiline of the test and reference preparation were as follow:Cmax were(9.70±3.14)and(9.62±3.85)ng·mL-1,AUC0-t were(6.03±1.47)and(6.02±1.95)ng·h·mL-1,AUC0-∞ were(6.13±1.51)and(6.12±1.97)ng·h·mL-1.The 90％confidence interval(CI)of the geometric mean ratio(GMR)were 94.11％-118.06％,99.22％-107.74％and 99.16％-107.44％for Cmax,AUC0-t and AUC0-∞,respectively,which were within the acceptance criteria of 80.00％-125.00％.In the fed study,the pharmacokinetic parameters of rasagiline of the test and reference preparation were as follow:Cmax were(3.00±1.92)and(3.52±1.77)ng·mL-1,AUC0_t were(5.02±1.20)and(5.06±1.20)ng·h·mL-1,AUC0-∞ were(5.11±1.23)and(5.14±1.22)ng·h·mL-1.The 90％CI of GMR were 96.99％-101.19％and 97.17％-101.41％for AUC0-t and AUC0-∞,which were within the acceptance criteria of 80.00％-125.00％.The 95％upper confidence bound of Cmax for were less than"0",and the point estimate of GMR were within the acceptance criteria of 80.00％-125.00％.The incidence of adverse events in fasting and fed studies was 22.86％and 22.92％,respectively,and all adverse events were moderate to mild.Conclusion The two rasagiline mesylate tablets were bioequivalent,and both the formulations were well tolerated.

In recent years,chimeric antigen receptor T cell(CAR-T)therapeutic products have shown good efficacy in the treatment of blood tumors,and breakthroughs have also been made in the treatment of solid tumors and autoimmune diseases.In order to further understand the clinical research and development progress of CAR-T products,this paper mainly uses the drug clinical trial registration and information publication platform of the Center for Drug Evaluation National Medical Products Administration as the information source,and focuses on the statistical analysis of the clinical trial progress of domestic CAR-T cell therapy products containing the targeted B-cell receptor-related protein CD19.It is hoped to further improve the quality and efficiency of clinical research and development of CAR-T cell therapy products,strengthen the sponsor's awareness of main responsibility,and timely update trial information to protect the rights and interests of subjects during clinical trials.

Eleven compounds were isolated from the twigs and leaves of Xylopia vielana Pierre by various chromatographic techniques such as silica gel, ODS and the semi-preparative HPLC. Their chemical structures were identified by HR-ESI-MS, NMR, ECD and other spectroscopic methods as vielana A (1), vielana B (2), vielana C (3), 10-oxo-isodauc-3-en-15-al (4), 1α-hydroxyisodauc-4-en-15-al (5), mokko lactone (6), 11β,13-dihydrocostunolide (7), eurylosesquiterpenol E (8), epi-α-cadinol (9), mustakone (10), 7-epi-amiteo (11). Among them, compounds 1-3 were new compounds, and the rest compounds were isolated from this plant for the first time. Compounds 1 and 2 increased the transcriptional activity of the farnesoid X receptor (FXR) downstream target gene BSEP promoter, indicating that they have potential of FXR activation.