OBJECTIVE To provide technical support for improving recognition rate of adverse drug events （ADEs） related to traditional Chinese medicine （TCM） formula granules and decoction pieces among inpatient patients. METHODS By referencing the global trigger tool （GTT） whitepaper， literature on adverse reactions to TCM， and expert review opinions， ADE trigger items for TCM formula granules and decoction pieces used in the inpatients were established. GTT was applied to analyze ADEs in inpatients who had used TCM formula granules and decoction pieces in our hospital from August 2013 to August 2023， utilizing the Chinese Hospital Pharmacovigilance System. The effectiveness of GTT and the characteristics of these ADEs were analyzed. RESULTS A total of forty-eight triggers were established， including thirty-two laboratory test indexes， thirteen clinical symptoms， and three antidotes. Among the 1 682 patients included， GTT identified 652 potential ADEs， 284 true positive ADEs，with a trigger rate of 38.76% and a positive predictive value of 43.56%. After review by the auditor， 278 cases of ADEs were finally confirmed， with an incidence rate of 16.53%， significantly higher than the number of spontaneously reported ADEs during the same period （0）. The 278 cases of ADEs were mostly grade 1 （223 cases）， mainly involving hepatobiliary system， gastrointestinal system， blood- lymphatic system， etc；a total of 219 types of TCMs are involved，and the top five suspected TCMs used at a frequency higher than 1% were Poria cocos， Codonopsis pilosula， Atractylodes macrocephala， fried Glycyrrhiza uralensis， and Scutellaria baicalensis. CONCLUSIONS The established GTT can improve the recognition rate of ADEs for hospitalized patients using traditional Chinese medicine formula granules and decoction pieces.

To investigate the therapeutic effect and related mechanisms of hordenine on ovalbumin (OVA)-induced allergic rhinitis (AR) in rats, HE and AB-PAS staining were used to detect the improvement of pathological damage to the nasal mucosa induced by hordenine. ELISA was employed to detect the effect of hordenine on OVA-sIgE in serum and IL-4 in the nasal mucosa supernatant of rats. IHC and Western blot experiments were undertaken to examine the effect of hordenine on Th1/Th2 cell balance. Bioinformatics analysis was performed to predict pathways, which were verified by in vivo and in vitro experiments. The experimental results showed that hordenine could alleviate the behavioral manifestations of OVA-induced AR rats, alleviate nasal mucosal pathological damage caused by AR, and reduce the secretion of OVA-sIgE and IL-4. In addition, hordenine could regulate the Th1/Th2 balance. Bioinformatics analysis results showed that the potential pathway of action of hordenine on AR was the phosphoinositide 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway. The in vivo experimental results showed that the expression of PI3K and p-Akt proteins in the nasal mucosa of the model group rats was significantly increased (P < 0.01), and that the protein expression level was significantly decreased after the administration of hordenine, which was also confirmed by an in vitro experiment. This study suggests that hordenine may regulate Th1/Th2 cell balance through the PI3K/Akt signaling pathway, thereby exerting an alleviating effect on OVA-induced AR.

OBJECTIVE To improve the diagnosis and treatment level of critically ill infectious diseases， standardize the clinical application of nanopore sequencing and promote the sound development of the technology. METHODS Division of Therapeutic Drug Monitoring of Chinese Pharmacological Society and Expert Committee of Precision Medicine for Clinical Treatment of Guangdong Pharmaceutical Association initiated and organized multidisciplinary experts to discuss and determine the consensus writing outline by using the nominal group method， forming a preliminary consensus draft； expert consultation was performed by using Delphi method， and then experts’ opinions were analyzed and revised to form consensus. RESULTS & CONCLUSIONS Consensuses of Experts on the Application of Nanopore Sequencing Technology in the Detection of Pathogenic Microorganisms covers targeted sequencing， metagenomic sequencing and whole genome sequencing， and is standardized in terms of sample collection and storage， detection process， bioinformatics analysis and report interpretation； the recommendations are provided for the key issues.

Objective:To assess the predictive value of a combined multiclassification model for computed tomography(CT)in the patholo-gical analysis of ground-glass nodules(GGN).Methods:Pulmonary GGN lesions that were pathologically confirmed as invasive adenocar-cinoma(IAC),minimally invasive adenocarcinoma(MIA),adenocarcinoma in situ(AIS),and preinvasive lesions(PILs),were collected from pa-tients who were treated at The First Affiliated Hospital of Xinxiang Medical University between February 2019 and March 2023.A total of 324 nodules were retrospectively collected from 285 patients,and divided into three groups:infiltrating IAC,MIA,and PILs.Radiomics and clinical-CT features were selected through recursive feature elimination and univariate Logistic regression.Seven models were constructed using Logistic regression(LR),support vector machine(SVM),random forest(RF),and integrative learning(stacking).Results:The hybrid model combining clinical-CT-radiomics features and an integrative strategy showed superior predictive performance,with an accuracy of 0.791,precision of 0.788,specificity of 0.857,recall of 0.790,and F1-Score of 0.789.Conclusions:The multiclassification joint model based on CT-radiomics is effective in predicting pathological classification of pulmonary GGNs.This model aids in accurate imaging diagnosis and can provide a basis for optimizing treatment plans.

Objective:To investigate the impact of small extracellular vesicles(sEVs) derived from perirenal adipose cells on the biological behavior of renal tubular epithelial cells under diabetic conditions and the underlying molecular mechanisms.Methods:Primary perirenal adipose cells were extracted from db/m and db/db mice for in vitro culture. The culture supernatant was collected and sEVs(NDM-sEVs PRAT-Adipo, DM-sEVs PRAT-Adipo) were extracted by ultracentrifugation. The sEVs were incubated with human renal tubular epithelial cell line(HK-2) to observe changes in their proliferation, apoptosis, autophagy, and epithelial-mesenchymal transition(EMT) levels. The protein composition of sEVs was analyzed using mass spectrometry to explore the molecular mechanisms. Results:CCK8 results showed that the proliferation level of HK-2 cells after DM-sEVs PRAT-Adipo intervention did not change significantly compared with the two control groups(Ctrl group and NDM-sEVs PRAT-Adipo intervention group). Western Blot(WB) results indicated that there were no significant changes in apoptosis levels(Bcl-2, Cleaved-caspase 3, Caspase 3) and autophagy levels(p62, LC3BⅠ, LC3BⅡ) in the DM-sEVs PRAT-Adipo intervention group compared with the two control groups. WB and immunofluorescence results demonstrated that DM-sEVs PRAT-Adipo intervention upregulated the expression levels of mesenchymal cell marker proteins(Vimentin, α-SMA, Snail2) and downregulated the expression level of epithelial cell marker protein ZO-1 in HK-2 cells compared with the two control groups. Mass spectrometry analysis of sEVs revealed that the differential proteins between DM-sEVs PRAT-Adipo and NDM-sEVs PRAT-Adipo were enriched in EMT-related pathways. Among them, the enrichment of thrombospondin(THBS1) in DM-sEVs PRAT-Adipo might be involved in the regulation of EMT in HK-2 cells. Conclusion:Under diabetic conditions, sEVs secreted by PRAT-derived adipocytes promote the upregulation of EMT in renal tubular epithelial cells, a process that may be mediated by the enrichment of THBS1 in sEVs.

BACKGROUND: T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), an inhibitory receptor expressed on T cells, plays a dysfunctional role in antiviral infection and antitumor activity. However, it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccines. METHODS: Forty-five people living with HIV (PLWH) on antiretroviral therapy (ART) for more than two years and 31 healthy controls (HCs), all received a third dose of a SARS-CoV-2 inactivated vaccine, were enrolled in this study. The amounts, activation, proportion of cell subsets, and magnitude of the SARS-CoV-2-specific immune response of TIGIT + CD4 + and TIGIT + CD8 + T cells were investigated before the third dose but 6 months after the second vaccine dose (0W), 4 weeks (4W) and 12 weeks (12W) after the third dose. RESULTS: Compared to that in HCs, the frequency of TIGIT + CD8 + T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine, and the immune activation of TIGIT + CD8 + T cells also increased. A decrease in the ratio of both T naïve (T N ) and central memory (T CM ) cells among TIGIT + CD8 + T cells and an increase in the ratio of the effector memory (T EM ) subpopulation were observed at 12W in PLWH. Interestingly, particularly at 12W, a higher proportion of TIGIT + CD8 + T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay. Compared with 0W, SARS-CoV-2-specific TIGIT + CD8 + T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs. Additionally, at all time points, the SARS-CoV-2-specific responses of TIGIT + CD8 + T cells in PLWH were significantly weaker than those of TIGIT - CD8 + T cells. However, in HCs, the difference in the SARS-CoV-2-specific responses induced between TIGIT + CD8 + T cells and TIGIT - CD8 + T cells was insignificant at 4W and 12W, except at 0W. CONCLUSIONS TIGIT expression on CD8 + T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine, suggesting weakened resistance to SARS-CoV-2 infection, especially in PLWH. Furthermore, TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8 + T cells, thereby enhancing the effectiveness of vaccination.
Humans ; Antibodies, Viral ; CD8-Positive T-Lymphocytes ; COVID-19/complications* ; COVID-19 Vaccines/immunology* ; HIV Infections/complications* ; Receptors, Immunologic ; SARS-CoV-2

Taking medical statistics major in Binzhou Medical University as an example, based on the outcome-based education theory, in order to enhance the innovation ability of university students, we put forward the systematic second classroom training system, including improving the personnel training system, implementing education, experiment teaching reform, and practice teaching reform. It has achieved outstanding results in the discipline competition, improved social service ability and high degree of employer satisfaction. The systematic second-class talent training system based on the outcome-based education theory can provide reference for other medical colleges and related applied majors.

Objective To explore the efficacy and prognostic independent factors of modified island flap(OIF)and urethroplasty(tip)in the treatment of hypospadias in children.Methods The 164 children with hypospadias analyzed retrospectively were treated from February,2013 to February,2021.They were divided into two groups according to the operation method.82 patients in tip group were treated with tip and 82 patients in OIF group were treated with OIF.The treatment effects of the two groups were compared.Then they were divided into two groups according to the cure condition,namely,the good prognosis group(cured by operation,151 case)and the poor prognosis group(not cured by operation,13 case).Independent factors affecting the prognosis of children were analyzed by binary logistic regression.Results The cure rate of OIF group was 96.34％,which was higher than that of the tip group(87.8％),and the incidence of postoperative complications in OIF group was 7.32％,which was lower than that of the tip group(23.17％,P＜0.05).The operation time in tip group(95.95±12.35)min,which was shorter than that of the OIF group(P＜0.05).At the same time,the binary logistic regression analysis showed that the degree of hypospadias and the classification of barcat were the prognostic factors of children with hypospadias.The degree of penis bending,the width of penis head and the method of operation were suspicious factors.Conclusion OIF and tip have good effects in the treatment of hypospadias in children.OIF has a higher success rate,tip has a shorter operation time and fewer postoperative complications.However,the independent factors affecting the prognosis of children are preoperative hypospadias classification and barcat classification.This operation method is not an independent factor affecting the prognosis.

Background::It is controversial whether the apolipoprotein E epsilon 4 allele ( APOE ε4) is a risk gene for human immunodeficiency virus (HIV)-related neurocognitive impairment. This meta-analysis aimed to summarize evidence of the associations between APOE ε4 and cognitive impairment in people living with HIV (PLWH). Methods::Our study conducted a systematic literature search of PubMed, Web of Science, Embase, Google Scholar, and ProQuest for studies published before April 11, 2022 that evaluated associations between APOE ε4 and cognitive impairment in adult PLWH (aged ≥18 years). We calculated pooled odds ratios (ORs) of global cognitive impairment and 95% confidence intervals (CIs) and standardized mean differences (SMDs) for specific cognitive domains between APOE ε4 carriers and non-carriers. Subgroup meta-analyses were used to evaluate the result profiles across different categorical variables. Results::Twenty studies met the inclusion criteria, including 19 that evaluated global cognitive impairment. APOE ε4 was significantly associated with global cognitive impairment in PLWH (OR = 1.36, 95% CI = [1.05, 1.78], number of estimates [ k] = 19, P = 0.02, random effects). Subgroup meta-analysis based percentage of females showed evident intergroup differences in global cognitive performance between ε4 carriers and non-carriers ( P = 0.015). APOE ε4 carriers had lower cognitive test scores than non-carriers in all seven cognitive domains, including fluency (SMD = -0.51, 95% CI = [-0.76, -0.25], P < 0.001, k = 4, I2= 0%), learning (SMD = -0.52, 95% CI = [-0.75, -0.28], P < 0.001, k = 5, I2 = 0%), executive function (SMD = -0.41, 95% CI= [-0.59, -0.23], P < 0.001, k= 8, I2= 0%), memory (SMD=-0.41, 95% CI= [-0.61, -0.20], P < 0.001, k= 10, I2= 36%), attention/working memory (SMD=-0.34, 95% CI= [-0.54, -0.14], P= 0.001, k= 6, I2= 0%), speed of information processing (SMD = -0.34, 95% CI = [-0.53, -0.16], P < 0.001, k = 8, I2 = 0%), and motor function (SMD = -0.19, 95% CI = [-0.38, -0.01], P = 0.04, k = 7, I2 = 0%). Conclusions::Our meta-analysis provides significant evidence that APOE ε4 is a risk genotype for HIV-associated cognitive impairment, especially in cognitive domains of fluency, learning, executive function, and memory. Moreover, the impairment is sex specific. Meta analysis registration::PROSPERO, CRD 42021257775.

Purpose: The aim of the study was to evaluate the status of psychological resilience among women in their second pregnancy and to investigate the possible influencing factors. Methods: A total of 275 women in their second pregnancy and who met the criteria were surveyed from two public hospitals in China from July 2018 to January 2019. The instruments included the General Self-designed Questionnaire, Connor–Davidson Resilience Scale, Social Support Rate Scale, and 36-item Pregnancy Stress Rating Scale. Results: The total psychological resilience score of second-pregnancy women was relatively low. Multivariate regression analysis identified five factors associated with psychological resilience: intimacy with husbands, social support utilization, gender of the first child, high-risk pregnancy of the first child, and the stress caused by worrying about the health and safety of the mother and fetus. Conclusion Women in their second pregnancy represent a unique population, and their low psychological resilience score deserves attention. Identification of factors contributing to decreased psychological resilience may enable us to design prevention and intervention strategies and to deliver specific psychological supports to pregnant women at high risk of developing negative psychology.