Objective:To investigate the effect of the virtual simulation system-based teaching method for the experimental course of oral local nerve block anesthesia in improving the effect of traditional teaching methods.Methods:One hundred and eighteen undergraduate dental students were randomly divided into two groups, the experimental group was taught using a virtual simulation-based system, and the control group was taught using traditional teaching. The results of the teaching were comprehensively evaluated through course feedback questionnaires, analysis of theoretical test scores, evaluations of the trainees administering and receiving anesthesia on the current anesthesia, and faculty evaluations of the success of the anesthesia, and t-tests and chi-square tests were performed using SPSS 23.0.Results:There was no significant difference in baseline level between the two groups. The students in the experimental group thought that the learning was more vivid ( t=4.24, P=0.005) and had more self-confidence in local anesthesia ( t=4.99, P<0.001). The students in the experimental group felt less needle tip jitter during injection ( t=2.22, P=0.048) and better contact with the medial surface of the mandible ( t=2.22, P=0.020). The students who received anesthesia reported less pain during injection ( t=1.99, P=0.029) and better anesthesia of the inferior alveolar nerve ( t=3.36, P=0.039) in the experimental group. Teacher assessment revealed that the experimental group had a significantly lower failure rate of inferior alveolar nerve block than the control group ( χ2=4.40, P=0.036). Conclusions:The virtual simulation system can optimize the experimental teaching of oral local nerve block anesthesia and can achieve a satisfactory teaching effect.

Objective To analyze the postmarketing safety characteristics of three immunomodulatory drugs(IMiDs)(thalidomide,lenalidomide and pomalidomide)in order to provide reference for clinical rational drug use.Methods The Open Vigil 2.0 tool was used to collect adverse drug event(ADE)reporting data from the U.S.Food and Drug Administration's(FDA)Adverse Event Reporting System(FAERS)between the first quarter of 2013 and the second quarter of 2022 for three IMiDs as primary suspect drugs.High frequency ADE was analyzed by mapping according to Medical Dictionary for Regulatory Activities(MedDRA terminology)25.0.The effective signals of adverse drug reactions(ADR)were screened according to the reporting odds ratio(ROR)and proportional reporting ratio(PRR)methods,and the high-intensity signals were analyzed.Results Among the top 20 ADEs,peripheral neuropathy,decreased blood count,thrombosis,skin squamous cell carcinoma and other ADEs occurred in all three drugs,but the distribution of the involved tissues and organs was different.Among the top 20 ADR signals,nearly half of the ADR signals of the 3 drugs were also in the high-frequency ADE range,among which 3 drugs showed increased human chorionic gonadotrophin,thalidomide and lenalidomide showed false positives in pregnancy tests,rectal adenocarcinoma and colorectal adenocarcinoma,and pomalidomide and lenalidomide showed decreased complete blood counts.Conclusion The overall ADE distribution of the three diamines is consistent,but there are some differences in the specific ADR signal characteristics.In clinical application,more attention should be paid to hemocytopenia,peripheral neuropathy,thrombus and second primary malignant tumors.

OBJECTIVE To assess the efficacy， safety and cost-effectiveness of tenecteplase in the treatment of acute ischemic stroke， and to provide a basis for clinical rational drug use and related decision-making. METHODS The related literature in the PubMed， the Cochrane Library， CNKI， Wanfang data and health technology assessment （HTA） databases were searched from the establishment of the database to June 30th， 2024. Systematic reviews/meta-analyses， pharmacoeconomic studies and HTA reports on tenecteplase in the treatment of acute ischemic stroke were collected. After data extraction and quality assessment， descriptive analysis of the included studies was carried out. RESULTS A total of 31 articles were included， involving 28 systematic reviews/ meta-analysis and 3 pharmacoeconomic studies. In terms of effectiveness， compared with alteplase， tenecteplase （0.25 mg/kg） could significantly increase the early neurological improvement； the 90 d excellent neurological recovery rate， 90 d good neurological recovery rate， and recanalization were not inferior to alteplase. For safety， compared with alteplase， tenecteplase did not increase the incidence of hemorrhage， symptomatic intracranial hemorrhage， 3-month mortality， or intracranial hemorrhage. In terms of cost-effectiveness， foreign research results showed that tenecteplase had economic advantages over alteplase. CONCLUSIONS Compared with alteplase， tenecteplase is effective and safe in the treatment of acute ischemic stroke， and it is cost-effective.

Objective To study the differences and mechanisms of damage to the reproductive organs of male rats by single and compound exposure to microwaves at 2.856 and 9.375 GHz.Methods A total of 40 male Wistar rats were randomly divided into sham group,S10 group,X10 group and SX5 group.Microwavesat 2.856 and 9.375 GHz were used to expose the rats for 6 min in the S10 and X10 groups with an average power density of 10 mW/cm2,respectively.The SX5 group was sequentiallyexposed to 2.856 and 9.375 GHz microwaves with an average power density of 5 mW/cm2 for 6 min.At 1 and 7 d after exposure,the sperm viability and serum sex hormones were detected by light microscopy and electron microscopy,and testicular tissue structure and oxidative stress and energy metabolism levels were examined.Results The sperm viability,testosterone(T),follicle stimulating hormone(FSH),and inhibin B(INHB)decreased in the S10 and X10 groups at 1 and 7 d after exposure(P＜0.01),and in the SX5 group at 7 d after exposure(P＜0.05).The LH decreased in all the exposure groups at 1 d after exposure(P＜0.01),and increased in the S10 and X10 groups at 7 d after exposure(P＜0.05).The spermatogenic epithelium of testicular tissue was lax,spermatogenic cells were edematous and vacuolated,chromatin condensed and shifted side by side,and the damage was significant in the S10 and X10 groups as compared with the SX5 group.The superoxide dismutase(SOD)activity in testis tissue decreased and malondialdehyde(MDA)content increased at 1 and 7 d after exposure in the S10 group(P＜0.01).In the X10 group,the SOD decreased at 1 d after exposure(P＜0.01).The lactate dehydrogenase(LDH)and succinate dehydrogenase(SDH)activity and adenosine triphosphate(ATP)content in testis tissue decreased at 1 and 7 d after exposure in the S10 and X10 groups(P＜0.05).In the SX5 group,the LDH and SDH decreased at 1 d after exposure(P＜0.05).Conclusion Single and combined exposure to S-band and X-band microwaves can cause damage to male reproductive organs.The S-band causes damage more significantly than that of X-band.Single-frequency microwave high-intensity exposure causes damage more significantly than that of multi-frequency microwave prolonged combined exposure.The damage is closely related to oxidative stress and energy metabolism.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

AIM:To evaluate and analyze the post-marketing adverse drug reaction(ADR)signals of polatuzumab vedotin,so as to provide reference for clinical safety management.METHODS:Using the FDA adverse drug event reporting system(FAERS)database and OpenVigil data platform,the ADR reports of polatuzumab vedotin were collect-ed from June 10,2019(FDA approval for market-ing)to the March 31,2023.The ADR signals were detected by using the reporting odds ratio(ROR)and proportional reporting ratio(PRR)in the pro-portional imbalance method.To increase the threshold and obtain stronger and more frequently occurring ADRs,a second screening of signals was performed.RESULTS:A total of 2 408 ADR reports related to polatuzumab vedotin were collected,and 83 ADR signals were detected after secondary screening.26 ADR signals were not mentioned in the drug instructions such as abnormal spinal mag-netic resonance imaging,increased bone resorp-tion,osteolysis,decreased aspartate aminotransfer-ase,decreased alanine aminotransferase,hypofibri-nogenemia,and pulmonary embolism.The system organ classes with a high signal counts or cumula-tive number of cases included infections and inva-sive diseases(24 signals,632 cases),various exami-nations(17 signals,675 cases),blood and lymphat-ic system diseases(11 signals,734 cases),various nervous system diseases(7 signals,153 cases),im-mune system diseases(3 signals,95 cases),system-ic diseases and various reactions at the site of ad-ministration(2 signals,145 cases),and systemic dis-eases and various reactions at the site of adminis-tration(2 signals,87 cases),etc.CONCLUSION:In addition to the common ADRs suggested by the in-structions,this study identified new ADR risk sig-nals for polatuzumab vedotin.In the clinical appli-cation of polatuzumab vedotin,in addition to the ADR mentioned in the instructions such as infec-tions,myelosuppression,peripheral neuropathies,infusion-related reactions,and abnormal liver func-tion,attention should also be paid to the risk sig-nals not mentioned such as abnormal spinal mag-netic resonance imaging,and increased bone re-sorption.

OBJECTIVE: To investigate risk factors of acute cerebrovascular events and effects on the prognosis within 1 year after hip fracture surgery. METHODS: A retrospective analysis was performed on 320 elderly patients with hip fracture treated from July 2017 to December 2020, including 111 males and 209 females, aged from 60 to 101 years old with an average of (79.05±8.48) years old. According to whether acute cerebrovascular events occurred within 1 year after surgery, patients were divided into cerebrovascular events and non-cerebrovascular events group. Clinical data of patients were collected, including age, sex, comorbidities, fracture type, white blood cell count, hemoglobin, albumin, activities of daily living (ADL) score, walking ability, type of anesthesia, type of surgery, and length of hospital stay, Univariate analysis and multivariate Logistic regression were used to analyze the independent risk factors of acute cerebrovascular events within 1 year after hip fracture in elderly patients. ADL, walking ability and mortality were compared between the two groups 1 year after surgery. RESULTS: Acute cerebrovascular events occurred in 38 patients (11.9%) within 1 year after surgery. In the cerebrovascular events group, there were 20 males and 18 females, aged (82.53±7.91) years. In the non-cerebrovascular event group, there were 91 males and 191 females, aged with an average of (78.59±8.46) years old . Univariate analysis showed that acute cerebrovascular events were associated with age (t=2.712, P=0.007), male (χ²=6.129, P=0.013), hypertension (χ²=8.449, P=0.004), arrhythmia (χ²=6.360, P=0.012), stroke history (χ²=34.887, P=0.000), diabetes mellitus (χ²=4.574, P=0.032) and length of hospital stay (t=2.249, P=0.025) were closely related. Multivariate Logistic regression analysis showed age (OR=1.068, P=0.018), male (OR=2.875, P=0.008), arrhythmia (OR=2.722, P=0.017) and stroke history (OR=7.382, P=0.000) was an independent risk factor for acute cerebrovascular events 1 year after surgery. The patients with cerebrovascular events died at 1 year after surgery (11 cases) compared with those without cerebrovascular events (41 cases), and the difference was statistically significant(χ²=5.108, P=0.024). ADL scores of patients with cerebrovascular events at 1 year after operation were (58.70±14.45) points compared with those without cerebrovascular events (67.83±10.45) points, and the difference was statistically significant(t=4.122, P=0.000). Independent walking, assisted walking and bed rest were 3, 17 and 7 cases in cerebrovascular event group, and 54, 174 and 13 cases in non-cerebrovascular event group, respectively;and the difference was statistically significant(χ²=11.030, P=0.003). CONCLUSION Acute cerebrovascular events were common in elderly patients 1 year after hip fracture. Age, male, arrhythmia and stroke history were independent risk factors for acute stroke. The patients in the cerebrovascular event group had higher mortality and worse self-care ability and walking ability one year after operation.
Female ; Humans ; Male ; Aged ; Middle Aged ; Aged, 80 and over ; Retrospective Studies ; Activities of Daily Living ; Hip Fractures ; Risk Factors ; Prognosis ; Stroke ; Arrhythmias, Cardiac

This study aimed to evaluate the ability of rete testis thickness (RTT) and testicular shear wave elastography (SWE) to differentiate obstructive azoospermia (OA) from nonobstructive azoospermia (NOA). We assessed 290 testes of 145 infertile males with azoospermia and 94 testes of 47 healthy volunteers at Shanghai General Hospital (Shanghai, China) between August 2019 and October 2021. The testicular volume (TV), SWE, and RTT were compared among patients with OA and NOA and healthy controls. The diagnostic performances of the three variables were evaluated using the receiver operating characteristic curve. The TV, SWE, and RTT in OA differed significantly from those in NOA (all P ≤ 0.001) but were similar to those in healthy controls. Males with OA and NOA were similar at TVs of 9-11 cm 3 ( P = 0.838), with sensitivity, specificity, Youden index, and area under the curve of 50.0%, 84.2%, 0.34, and 0.662 (95% confidence interval [CI]: 0.502-0.799), respectively, for SWE cut-off of 3.1 kPa; and 94.1%, 79.2%, 0.74, and 0.904 (95% CI: 0.811-0.996), respectively, for RTT cut-off of 1.6 mm. The results showed that RTT performed significantly better than SWE in differentiating OA from NOA in the TV overlap range. In conclusion, ultrasonographic RTT evaluation proved a promising diagnostic approach to differentiate OA from NOA, particularly in the TV overlap range.
Male ; Humans ; Azoospermia ; Rete Testis ; China ; Testis

Klinefelter syndrome (KS) is the most common genetic cause of human male infertility. However, the effect of the extra X chromosome on different testicular cell types remains poorly understood. Here, we profiled testicular single-cell transcriptomes from three KS patients and normal karyotype control individuals. Among the different somatic cells, Sertoli cells showed the greatest transcriptome changes in KS patients. Further analysis showed that X-inactive-specific transcript ( XIST ), a key factor that inactivates one X chromosome in female mammals, was widely expressed in each testicular somatic cell type but not in Sertoli cells. The loss of XIST in Sertoli cells leads to an increased level of X chromosome genes, and further disrupts their transcription pattern and cellular function. This phenomenon was not detected in other somatic cells such as Leydig cells and vascular endothelial cells. These results proposed a new mechanism to explain why testicular atrophy in KS patients is heterogeneous with loss of seminiferous tubules but interstitial hyperplasia. Our study provides a theoretical basis for subsequent research and related treatment of KS by identifying Sertoli cell-specific X chromosome inactivation failure.
Animals ; Humans ; Male ; Female ; Sertoli Cells/metabolism* ; Klinefelter Syndrome/genetics* ; Endothelial Cells ; Testis/metabolism* ; X Chromosome/metabolism* ; Mammals/genetics*

The regulation of spermatogonial proliferation and apoptosis is of great significance for maintaining spermatogenesis. The single-cell RNA sequencing (scRNA-seq) analysis of the testis was performed to identify genes upregulated in spermatogonia. Using scRNA-seq analysis, we identified the spermatogonia upregulated gene origin recognition complex subunit 6 (Orc6), which is involved in DNA replication and cell cycle regulation; its protein expression in the human and mouse testis was detected by western blot and immunofluorescence. To explore the potential function of Orc6 in spermatogonia, the C18-4 cell line was transfected with control or Orc6 siRNA. Subsequently, 5-ethynyl-2-deoxyuridine (EdU) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, flow cytometry, and western blot were used to evaluate its effects on proliferation and apoptosis. It was revealed that ORC6 could promote proliferation and inhibit apoptosis of C18-4 cells. Bulk RNA sequencing and bioinformatics analysis indicated that Orc6 was involved in the activation of wingless/integrated (Wnt)/ β-catenin signaling. Western blot revealed that the expression of β-catenin protein and its phosphorylation (Ser675) were significantly decreased when silencing the expression of ORC6. Our findings indicated that Orc6 was upregulated in spermatogonia, whereby it regulated proliferation and apoptosis by activating Wnt/β-catenin signaling.