The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Objective To obtain the occurrence and clinical characteristics of central nervous system adverse drug reactions(CNS-ADR)associated with three kinds of carbapenems,and to provide reference for clinical drug safety.Methods Based on adverse drug event active surveillance and assessment system-Ⅱ(ADE-ASAS-Ⅱ),retrospective automated monitoring of inpatients using imipenem,meropenem,and biapenem in a tertiary hospital from January 2022 to December 2022 was conducted.The incidence of carbapenem related CNS-ADR was calculated,and the basic conditions,disease conditions,drug use,occurrence time of ADR and symptoms of patients with CNS-ADR were analyzed by descriptive statistics.Results A total of 2 482 patients with 2 709 times of medication were included in this study,and a total of 93 positive cases of CNS-ADR occurred,with an overall incidence of 3.43％for all three medications,3.98％for imipenem,3.51％for meropenem,and 2.78％for biapenem.The indications for the 93 positive cases of CNS-ADR were mainly pulmonary infections(59.13％)and abdominal infections(25.80％);they occurred mostly within 7 days of the administration of the medication;with a variety of clinical manifestations,with anxiety/irritability being the most common,and epilepsy appearing most frequently in severe cases.Co-administration of proton pump inhibitors and cephalosporins accounted for a greater proportion of positive cases,50.54％of positive cases had a history of surgery,and 69.89％of positive cases were associated with electrolyte disturbances.Conclusion Clinical use of carbapenems should be based on the actual situation of the patient to develop an individualised drug regimen,and special attention should be paid to patients with comorbidities of renal disease,electrolyte disorders,and a history of previous surgery and neurological disorders,in order to reduce the risk of the occurrence of CNS-ADR.

This study was aimed at analyzing the genomic characteristics of Salmonella typhimurium(1,4,[5],12:i:1,2)in Urumqi from 2018 to 2021,to provide evidence for the monitoring of this serotype and handling of public health emergen-cies.A total of 26 Salmonella typhimurium isolates were obtained from the feces of people with diarrhea in Urumqi.Whole-genome sequencing(WGS)combined with bioinformatic analysis was used to predict serovars,MLST types,plasmid repli-cons,antimicrobial resistance genes,and virulence genes;in addition phylogenomic analysis based on genome-wide single nucleotide polymorphisms(wgSNPs)was conducted to determine the epidemiological relatedness among isolates.A total of 47 resistance genes representing ten categories were de-tected with a high prevalence,including aac(6')-Iaa(100％),blaTEM-1B(30.8％),tet(A)(42.3％),qnrS1(30.8％),and sul3(23.1％),encoding resistance to aminoglycosides,β-lac-tams,tetracyclines,quinolones,and sulfa,in addition to chro-mosomic mutations affecting the gyrA gene.Moreover,12 plasmids were detected,among which IncFIB(S)and IncFII(S)(34.6％)were dominant.The differences in virulence genes a-mong strains isolated in different periods were reflected primarily in the typical virulence genes associated with Salmonella vir-ulence mechanisms.In addition,cgMLST indicated that the dominant type of Salmonella typhimurium was cgST36414,con-tainning 10 strains.Moreover,wgSNP analysis indicated that Salmonella typhimurium isolates in Urumqi were consistent with the epidemic trends in 15 provinces and cities in China and also showed local evolution.Salmonella typhimurium isolates in Urumqi frequently carried a variety of resistance genes and plasmid replicons,which are key in the dissemination and evolution of drug resistance.Close communication links may exist with various sources of flora in the food chain,thus posing severe chal-lenges in public health monitoring and prevention.Therefore,the construction of the laboratory routine monitoring network based on internet information systems should be strengthened to improve the timeliness of monitoring and limit the spread of multidrug-resistant strains.

This study was aimed at analyzing the genomic characteristics of Salmonella typhimurium(1,4,[5],12:i:1,2)in Urumqi from 2018 to 2021,to provide evidence for the monitoring of this serotype and handling of public health emergen-cies.A total of 26 Salmonella typhimurium isolates were obtained from the feces of people with diarrhea in Urumqi.Whole-genome sequencing(WGS)combined with bioinformatic analysis was used to predict serovars,MLST types,plasmid repli-cons,antimicrobial resistance genes,and virulence genes;in addition phylogenomic analysis based on genome-wide single nucleotide polymorphisms(wgSNPs)was conducted to determine the epidemiological relatedness among isolates.A total of 47 resistance genes representing ten categories were de-tected with a high prevalence,including aac(6')-Iaa(100％),blaTEM-1B(30.8％),tet(A)(42.3％),qnrS1(30.8％),and sul3(23.1％),encoding resistance to aminoglycosides,β-lac-tams,tetracyclines,quinolones,and sulfa,in addition to chro-mosomic mutations affecting the gyrA gene.Moreover,12 plasmids were detected,among which IncFIB(S)and IncFII(S)(34.6％)were dominant.The differences in virulence genes a-mong strains isolated in different periods were reflected primarily in the typical virulence genes associated with Salmonella vir-ulence mechanisms.In addition,cgMLST indicated that the dominant type of Salmonella typhimurium was cgST36414,con-tainning 10 strains.Moreover,wgSNP analysis indicated that Salmonella typhimurium isolates in Urumqi were consistent with the epidemic trends in 15 provinces and cities in China and also showed local evolution.Salmonella typhimurium isolates in Urumqi frequently carried a variety of resistance genes and plasmid replicons,which are key in the dissemination and evolution of drug resistance.Close communication links may exist with various sources of flora in the food chain,thus posing severe chal-lenges in public health monitoring and prevention.Therefore,the construction of the laboratory routine monitoring network based on internet information systems should be strengthened to improve the timeliness of monitoring and limit the spread of multidrug-resistant strains.

Objective: To analyze the drug resistance and genomic characteristics of a strain of serogroup O139 Vibrio cholerae producing cholera toxin isolated from the bloodstream of a person with bacteremia. Methods: The broth dilution method and automatic drug sensitivity analyzer were used to determine the antibiotic sensitivity of the strain. The complete genome sequence of the strain was obtained by using second-generation gene sequencing and nanopore sequencing. BLAST software was used for comparison and analysis with CARD, Resfinder, ISfinder, VFDB, and other databases. The drug-resistant genes, insertion sequences and virulence genes carried by the strain were identified. MEGA 5.1 software was used to construct a genetic phylogenetic tree based on the core genomic single nucleotide polymorphisms. Results: V. cholerae SH400, as the toxigenic strain, carried multiple virulence-related genes and four virulence islands. The strain was resistant to streptomycin, tetracycline and cotrimoxazole, carrying corresponding drug-resistant genes. The strain also carried IncA/C plasmid with the size of 172914 bp and contained 10 drug-resistant genes. Combined with the genomic evolutionary relationship, this study found that the drug-resistant genes and drug-resistant plasmids carried among strains showed certain aggregation. The traditional ST type of strain SH400 was ST69, and the cgMLST type was a new type highly similar to cgST-252. Conclusion: This strain of serogroup O139 V. cholerae carries the ctxAB gene, multiple drug-resistant genes and IncA/C plasmid, and there are multiple drug-resistant islands.

Objective: To compare the safety and efficacy of transmesenteric vein extrahepatic portosystemic shunt (TEPS) and transjugular intrahepatic portosystemic shunt (TIPS) in the treatment of cavernous transformation of the portal vein (CTPV). Methods: The clinical data of CTPV patients with patency or partial patency of the superior mesenteric vein treated with TIPS or TEPS treatment in the Department of Vascular Surgery of Henan Provincial People's Hospital from January 2019 to December 2021 were selected. The differences in baseline data, surgical success rate, complication rate, incidence rate of hepatic encephalopathy, and other related indicators between TIPS and TEPS group were statistically analyzed by independent sample t-test, Mann-Whitney U test, and Chi-square test. Kaplan-Meier survival curve was used to calculate the cumulative patency rate of the shunt and the recurrence rate of postoperative portal hypertension symptoms in both groups. Results: The surgical success rate (100% vs. 65.52%), surgical complication rate (6.67% vs. 36.84%), cumulative shunt patency rate (100% vs. 70.70%), and cumulative symptom recurrence rate (0% vs. 25.71%) of the TEPS group and TIPS group were statistically significantly different (P < 0.05). The time of establishing the shunt [28 (2141) min vs. 82 (51206) min], the number of stents used [1 (12) vs. 2 (15)], and the length of the shunt [10 (912) cm vs. 16 (1220) cm] were statistically significant between the two groups (t = -3.764, -4.059, -1.765, P < 0.05). The incidence of postoperative hepatic encephalopathy in the TEPS group and TIPS group was 6.67% and 15.79% respectively, with no statistically significant difference (Fisher's exact probability method, P = 0.613). The pressure of superior mesenteric vein decreased from (29.33 ± 1.99) mmHg to (14.60 ± 2.80) mmHg in the TEPS group and from (29.68 ± 2.31) mmHg to (15.79 ± 3.01) mmHg in TIPS group after surgery, and the difference was statistically significant (t = 16.625, 15.959, P < 0.01). Conclusion: The best indication of TEPS is in CTPV patients with patency or partial patency of the superior mesenteric vein. TEPS improves the accuracy and success rate of surgery and reduces the incidence of complications.
Humans ; Portal Vein/surgery* ; Portasystemic Shunt, Transjugular Intrahepatic/methods* ; Hepatic Encephalopathy/etiology* ; Treatment Outcome ; Hypertension, Portal/complications* ; Retrospective Studies ; Gastrointestinal Hemorrhage/etiology*

This study analyzed the effects of male age and abstinence time on semen quality and explored the best abstinence time for Chinese males among different age groups. Semen parameters, including sperm kinetics, morphology, and DNA fragmentation index (DFI), were reviewed from 2952 men. Samples were divided into six age groups (≤25 years, 26-30 years, 31-35 years, 36-40 years, 41-45 years, and >45 years) and were divided into six groups according to different abstinence time (2 days, 3 days, 4 days, 5 days, 6 days, and 7 days). The differences in semen quality between the groups were compared, and the effect of age and abstinence time on semen quality was analyzed. Significant differences were observed in semen volume, progressive motility (PR), and DFI among the age groups (all P < 0.05), and no significant differences were observed in sperm morphological parameters (all P > 0.05). There were significant differences in semen volume, PR, and DFI among different abstinence time groups (all P < 0.05) and no significant differences in sperm morphological parameters (all P > 0.05). Pearson analysis showed that male age and abstinence time were both significantly correlated with sperm kinetics and DFI (both P < 0.05), while no significant correlation was found with sperm morphological parameters (all P > 0.05). The box plots and histograms of men's age, abstinence time, and semen quality show that most semen quality parameters differ significantly between the 2 days and 7 days abstinence groups and other groups at different ages. Except for the sperm morphology parameters, sperm kinetic parameters and sperm DFI are linearly related to male age and abstinence time.
Adult ; DNA Fragmentation ; Humans ; Male ; Retrospective Studies ; Semen ; Semen Analysis ; Sperm Count ; Sperm Motility ; Spermatozoa

Preoperative detection of biomarkers that can predict postoperative survival of gastric cancer patients has important implications for surgical procedures, postoperative chemoradiotherapy and followup. Using multi-center cancer database and online analysis and verifying by qRT-PCR and Western blotting, we found that Osteomodulin (OMD) was highly expressed in gastric cancer tissues (P =0. 015) and could affect the survival of gastric cancer patients (P < 0. 001) and can be detected preoperatively to evaluate the prognosis of gastric cancer patients. The mRNA expression of OMD was significantly correlated with age (P = 0. 034), Lauren typing (P < 0. 001) and clinical stage (P =0. 001) of gastric cancer patients. It also associated with a variety of immune cells (dendritic cellsresting, eosinophils) and the immune checkpoint regulator ENTPD1 (rho = 0. 634, P < 0. 001) and chemokine CXCL12 (rho = 0. 625, P < 0. 001), which affects the occurrence and development of gastriccancer through the immune microenvironment. Therefore, OMD may become a clinically feasible prognostic biomarker of gastric cancer and a new target for immunotherapy.

OBJECTIVES: To reconstruct the cases of acceleration craniocerebral injury caused by blunt in forensic cases by finite element method (FEM), and to study the biomechanical mechanism and quantitative evaluation method of blunt craniocerebral injury. METHODS: Based on the established and validated finite element head model of Chinese people, the finite element model of common injury tool was established with reference to practical cases in the forensic identification, and the blunt craniocerebral injury cases were reconstructed by simulation software. The cases were evaluated quantitatively by analyzing the biomechanical parameters such as intracranial pressure, von Mises stress and the maximum principal strain of brain tissue. RESULTS: In case 1, when the left temporal parietal was hit with a round wooden stick for the first time, the maximum intracranial pressure was 359 kPa; the maximum von Mises stress of brain tissue was 3.03 kPa at the left temporal parietal; the maximum principal strain of brain tissue was 0.016 at the left temporal parietal. When the right temporal was hit with a square wooden stick for the second time, the maximum intracranial pressure was 890 kPa; the maximum von Mises stress of brain tissue was 14.79 kPa at the bottom of right temporal lobe; the maximum principal strain of brain tissue was 0.103 at the bottom of the right temporal lobe. The linear fractures occurred at the right temporal parietal skull and the right middle cranial fossa. In case 2, when the forehead and left temporal parietal were hit with a round wooden stick, the maximum intracranial pressure was 370 kPa and 1 241 kPa respectively, the maximum von Mises stress of brain tissue was 3.66 kPa and 26.73 kPa respectively at the frontal lobe and left temporal parietal lobe, and the maximum principal strain of brain tissue was 0.021 and 0.116 respectively at the frontal lobe and left temporal parietal lobe. The linear fracture occurred at the left posterior skull of the coronary suture. The damage evaluation indicators of the simulation results of the two cases exceeded their damage threshold, and the predicted craniocerebral injury sites and fractures were basically consistent with the results of the autopsy. CONCLUSIONS The FEM can quantitatively evaluate the degree of blunt craniocerebral injury. The FEM combined with traditional method will become a powerful tool in forensic craniocerebral injury identification and will also become an effective means to realize the visualization of forensic evidence in court.
Humans ; Finite Element Analysis ; Biomechanical Phenomena ; Wounds, Nonpenetrating ; Head ; Craniocerebral Trauma

Nonalcoholic fatty liver disease (NAFLD) is regarded as the most common liver disease with no approved therapeutic drug currently. Silymarin, an extract from the seeds of Silybum marianum, has been used for centuries for the treatment of various liver diseases. Although the hepatoprotective effect of silybin against NAFLD is widely accepted, the underlying mechanism and therapeutic target remain unclear. In this study, NAFLD mice caused by methionine-choline deficient (MCD) diet were orally administrated with silybin to explore the possible mechanism and target. To clarify the contribution of peroxisome proliferator-activated receptor α (PPARα), PPARα antagonist GW6471 was co-administrated with silybin to NAFLD mice. Since silybin was proven as a PPARα partial agonist, the combined effect of silybin with PPARα agonist, fenofibrate, was then evaluated in NAFLD mice. Serum and liver samples were collected to analyze the pharmacological efficacy and expression of PPARα and its targets. As expected, silybin significantly protected mice from MCD-induced NAFLD. Furthermore, silybin reduced lipid accumulation via activating PPARα, inducing the expression of liver cytosolic fatty acid-binding protein, carnitine palmitoyltransferase (Cpt)-1a, Cpt-2, medium chain acyl-CoA dehydrogenase and stearoyl-CoA desaturase-1, and suppressing fatty acid synthase and acetyl-CoA carboxylase α. GW6471 abolished the effect of silybin on PPARα signal and hepatoprotective effect against NAFLD. Moreover, as a partial agonist for PPARα, silybin impaired the powerful lipid-lowering effect of fenofibrate when used together. Taken together, silybin protected mice against NAFLD via activating PPARα to diminish lipid accumulation and it is not suggested to simultaneously take silybin and classical PPARα agonists for NAFLD therapy.