Objective To explore the relationship between PANoptosis and hepatic ischemia-reperfusion injury (HIRI), and to screen the key genes of PANoptosis in HIRI. Methods PANoptosis-related differentially expressed genes (PDG) were obtained through the Gene Expression Omnibus database and GeneCards database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore the biological pathways related to PDG. A protein-protein interaction network was constructed. Key genes were selected, and their diagnostic value was assessed and validated in the HIRI mice. Immune cell infiltration analysis was performed based on the cell-type identification by estimating relative subsets of RNA transcripts. Results A total of 16 PDG were identified. GO analysis showed that PDG were closely related to cellular metabolism. KEGG analysis indicated that PDG were mainly enriched in cellular death pathways such as apoptosis and immune-related signaling pathways such as the tumor necrosis factor signaling pathway. GSEA results showed that key genes were mainly enriched in immune-related signaling pathways such as the mitogen-activated protein kinase (MAPK) signaling pathway. Two key genes, DFFB and TNFSF10, were identified with high accuracy in diagnosing HIRI, with areas under the curve of 0.964 and 1.000, respectively. Immune infiltration analysis showed that the control group had more infiltration of resting natural killer cells, M2 macrophages, etc., while the HIRI group had more infiltration of M0 macrophages, neutrophils, and naive B cells. Real-time quantitative polymerase chain reaction results showed that compared with the Sham group, the relative expression of DFFB messenger RNA in liver tissue of HIRI group mice increased, and the relative expression of TNFSF10 messenger RNA decreased. Cibersort analysis showed that the infiltration abundance of naive B cells was positively correlated with DFFB expression (r=0.70, P=0.035), and the infiltration abundance of M2 macrophages was positively correlated with TNFSF10 expression (r=0.68, P=0.045). Conclusions PANoptosis-related genes DFFB and TNFSF10 may be potential biomarkers and therapeutic targets for HIRI.

OBJECTIVE To investigate the clinical efficacy of integrating pharmacists into family health teams （FHTs） for long-term medication therapeutical management （MTM） in stroke patients， and empirically evaluate the service model. METHODS A pharmacist team， jointly established by clinical and community pharmacists from the Affiliated Suzhou Hospital of Nanjing Medical University （hereinafter referred to as “our hospital”）， developed a pharmacist-supported MTM model integrated into FHTs. Using a prospective randomized controlled design， 170 stroke patients discharged from our hospital （July 2022-December 2023） and enrolled in FHTs at Suzhou Runda Community Hospital were randomly divided into trial group （88 cases） and control group （82 cases） according to random number table. The control group received routine FHTs care （without pharmacist involvement in the team collaboration）， while the trial group xhz8405@126.com received 12-month MTM services supported by pharmacists via an information platform. These services specifically included innovative interventions such as personalized medication regimen optimization based on the MTM framework， dynamic medication adherence management， medication safety monitoring， a home medication assessment system， and distinctive service offerings. Outcomes of the 2 grousp were compared before and after intervention， involving medication adherence （adherence rate， adherence score）， compliance rates for stroke recurrence risk factors [blood pressure， low-density lipoprotein cholesterol （LDL-C）]， and incidence of adverse drug reactions （ADR）. RESULTS After 12 months， the trial group exhibited significantly higher medication adherence rates， improved adherence scores， higher compliance rates for blood pressure and LDL-C targets compared to the control group （P＜0.05）. The incidence of ADR in the trial group （4.55%） was significantly lower than that in the control group （8.11%）， though the difference was not statistically significant （P＞ 0.05）. CONCLUSIONS Pharmacist involvement in FHTs to deliver MTM services significantly enhances medication adherence and optimizes risk factor for stroke recurrence， offering practical evidence for advancing pharmaceutical care in chronic disease management under the family doctor system.

Approach-avoidance conflict(AAC)refers to the internal conflict that individuals experi-ence when faced with conflicting approach or avoidance thoughts.It reveals some characteristics of mental disorders,such as anxiety,depression,and addiction represented by excessive tendencies of approach or avoidance.The function of the cortico-limbic-striatal system influences behavioral choices at the neural level during the onset of AAC,and the development of related behavioral paradigms that can better represent AAC behaviors is critical to evaluating the efficacy of drugs and guiding the development of new drugs.This paper summarizes the neural mechanisms,behavioral paradigms,and applications in behavioral pharmacology related to AAC behaviors from the perspective of psychopharmacology with a view to providing new perspectives and methods for the diagnosis and treatment of related neuro-psychiatric disorders.

Objective To analyze the expression level of YEATS2 in hepatocellular carcinoma(HCC)about its clinical prognosis and therapeutic value based on biological information from the cancer genome atlas(TCGA)and human protein atlas(HPA)databases.Methods The mRNA expression data and clinical information of HCC were downloaded from the TCGA database,the expression of YEATS2 between HCC tissues and normal tissues was analyzed by using the R software,and the protein expression differences were preliminary verified by the HPA database.The expression differences of YEATS2 between various clinical features of HCC were compared,and their effects on the survival of HCC patients by Kaplan-Meier method and COX regression analysis were then evaluated.Receiver operating characteristic(ROC)curves were plotted to evaluate their diagnostic values.The biological functions of YEATS2 in HCC were analyzed using gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis.The relationship between YEATS2 expression and tumor microenvironment(TME)was analyzed by the"ESTIMATE"algorithm,and its relationship with tumor-infiltrating immune cells(TIICs)was assessed by CIBERSORT.Analysis of YEATS2 expression levels to immune checkpoints and drug sensitivity was performed using the R package.Results The expression of YEATS2 was increased in HCC tissues(P=4.96e-21),and its expression level was correlated with age,clinical stage,pathological grade and T stage(all P＜0.05).Overall survival(OS)(P＜0.001)and progression-free survival(FPS)(P=0.016)were decreased in HCC patients with high expression of YEATS2,COX regression results showed that the expression level ofYEATS2 was associated with poor prognosis in HCC patients(OS:HR=2.167,95％CI:1.441～3.261,P=2.06e-04),and it was an independent risk factor for predicting poor prognosis in HCC patients(OS:HR=1.891,95％CI:1.243～2.877,P=0.003).The ROC curve suggested the AUCs for 1,3 and 5 years were 0.677,0.622 and 0.612,respectively,indicating good predictive ability.The TCGA database screened a total of 6 764 differential genes in the YEATS2 high and low expression groups,of which 4 094 genes were up-regulated and 2 670 genes were down-regulated in the YEATS2 high expression group.The results of GO and KEGG enrichment analyses showed that the differentially differentiated genes in the YEATS2 high expression group were mainly enriched in immunoregulation,and cell cycle regulation drug resistance pathway.The results of the TME score showed that the YEATS2 high expression group caused a decrease in immunity score(P＜0.01).The correlation between YEATS2 and TIICs showed that YEATS2 expression was positively correlated with the level of M0-type macrophage infiltration levels(r=0.48,P＜0.001)and 23 immune checkpoint genes(r=0.20～0.46,all P＜0.05),and was negatively correlated with the CD8+T-cells,plasma cells and monocyte(r=-0.26,-0.29,-0.30,P=0.021,0.011,0.008).Drug sensitivity analysis showed that the half maximal inhibitory concentration(IC50)of cabozantinib,lincitinib,doxorubicin,and cyclobenzaprine in patients with high expression of YEATS2 was higher than those in patients with low expression(all P＜0.01).Conclusion YEATS2 was highly expressed in HCC,and the expression level was associated with poor prognosis in HCC patients.YEATS2 can be used as a biomarker for the clinical early diagnosis,prognosis and immunotherapy of HCC,which may provide new ideas for clinical diagnosis and treatment.

Animal models are powerful tools for studying the mechanism of depressive disorders and screening antidepressants,but so far there is no model which can stimulate the clinical status of patients ideally.Here,we briefly introduced the research advances in classic animal models of depres-sive disorders,and focused on stress-related animal models,especially those induced by physical and social psychological stressors.The tests for evaluating animal depression behavior were reviewed.In this article,the strengths and weaknesses of each model were analyzed,and the precautions in its application were recommended.Finally,given the high heterogeneity of depressive disorders,this article elaborated on the research progress in models for subtypes of depressive disorders,such as treatment resistant depression,bipolar disorder,peripartum depression,and premenstrual syndrome.

Cross-Sectional Studies ; Urodynamics ; China

Objective:To explore the clinical characteristics of pneumocystis carinii pneumonia (PCP) after kidney transplantation.Methods:From January 2020 to January 2022, clinical data were retrospectively reviewed for 13 renal transplant recipients with pneumocystis pneumonia diagnosed by metagenomics next generation sequencing (mNGS). There were 3 females and 10 males with an age range of (46±10) years.The median time of postoperative onset was 10(2-21) months; The major clinical manifestations included fever ( n=11), cough ( n=7), expectoration ( n=6) and dyspnea ( n=11). Paired t-test was employed for analyzing the laboratory results at admission and discharge. Results:The diagnosis was confirmed by the detection of NGS in alveolar lavage fluid or venous blood.The levels of G test, LDH test, total T lymphocyte absolute count (CD3+ Abs), inhibitory/cytotoxic T lymphocyte count (CD3+ CD8+ Abs) and auxiliary/induced T lymphocyte absolute count (CD3+ CD4+ Abs) were (543.27±440.49) pg/ml, (529.98±222.43)U/L and (191.92±119.42)/μl, (87.33±50.59)/μl and (106.92±87.42)/μl at admission and (69.58±50.21) pg/ml, (285.38±46.62 U/L), (888.58±672.99)/μl, (336.83±305.21)/μl and (520.08±388.76)/μl at discharge.The differences were statistically significant ( P<0.001, P=0.002, 0.006, 0.017, 0.005). All of them received compound sulfamethoxazole and caspofungin.Except for one death due to septic shock after 21-day treatment, 12 cases were cured. Conclusions:mNGS test is one of the important tool for an early diagnosis of PCP.Combined use of compound sulfamethoxazole and caspofungin is an effective anti-infective regimen.And immune function monitoring is vital for adjusting antibiotic and immunosuppressive regimens.

Objective To investigate the efficacy of switching to co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/c/F/TAF) combined with sofosbuvir/velpatasvir (SOF/VEL) in the treatment of previously untreated chronic hepatitis C patients with HIV/HCV co-infection and the changes in blood lipid levels. Methods This prospective cohort study was conducted among 10 previously untreated chronic hepatitis C patients with HIV/HCV co-infection who attended Department of Infectious Diseases in Tangdu Hospital from July 2019 to May 2021 and achieved continuous HIV suppression after antiretroviral treatment (ART). As for anti-HIV therapy, the ART regimen was switched to the E/c/F/TAF regimen for 32 weeks, and for anti-HCV therapy, the SOF/VEL regimen was started since week 4 after switching and lasted for 12 weeks. Related indices were monitored before and after switching to E/c/F/TAF for anti-HCV therapy and SOF/VEL for anti-HCV therapy, including body weight, body mass index, HCV genotype, alpha-fetoprotein, liver stiffness measurement, CD4 + T cell count, CD4 + T/CD8 + T ratio, hepatic and renal function parameters, blood lipids, HIV RNA, HCV RNA, SVR12, SVR24, and adverse reactions. The Mann-Whitney U test was used for comparison of continuous data between two groups, and a Spearman correlation analysis was performed. Results After 4 weeks of treatment with E/c/F/TAF, 10 patients (HCV genotypes 2a and 1b) had HIV RNA below the lower limit of detection (20 IU/ml) and a significant reduction in albumin ( Z =-2.801, P =0.003 7), with the other indices remaining stable, and the patients reported significant improvements in the adverse events of anti-HIV therapy with the former ART regimen. After 4 weeks of E/c/F/TAF combined with SOF/VEL, the patients had HCV RNA below the lower limit of detection (15 IU/ml), and both SVR12 and SVR24 reached 100%; after 12 weeks of anti-HCV therapy, there were significant reductions in alanine aminotransferase ( Z =-2.732, P =0.004 8) and aspartate aminotransferase ( Z =-2.501, P =0.010 7) and significant increases in total cholesterol (TC) ( Z =-2.797, P =0.003 9) and low-density lipoprotein cholesterol (LDL-C) ( Z =-2.343, P =0.018 5), with a significantly positive correlation between them ( r =0.87, P < 0.001), and all the other indices were normal. Conclusion For previously untreated chronic hepatitis C patients with HIV/HCV co-infection, switching to E/c/F/TAF combined with SOF/VEL has good efficacy, tolerability, and safety, and the combination of the two regimens can avoid drug interaction, achieve a high HCV cure rate, and maintain HIV suppression. Transient increases in TC and LDL-C are observed during combination treatment, which suggests dyslipidemia caused by HCV infection and the pharmacological action of this regimen.

Purpose: Reduced quality of life after cystectomy has made bladder preservation a popular research topic for muscle-invasive bladder cancer (MIBC). Previous research has indicated significant tumor downstaging after neoadjuvant chemotherapy (NAC). However, maximal transurethral resection of bladder tumor (TURBT) was performed before NAC to define the pathology, impacting the real evaluation of NAC. This research aimed to assess real NAC efficacy without interference from TURBT and apply combined modality therapies guided by NAC efficacy. Materials and Methods: Patients with cT2-4aN0M0 MIBC were confirmed by cystoscopic biopsy and imaging. NAC efficacy was assessed by imaging, urine cytology, and cystoscopy with multidisciplinary team discussion. Definite responders (≤ T1) underwent TURBT plus concurrent chemoradiotherapy. Incomplete responders underwent radical cystectomy or partial cystectomy if feasible. The primary endpoint was the bladder preservation rate. Results: Fifty-nine patients were enrolled, and the median age was 63 years. Patients with cT3-4 accounted for 75%. The median number of NAC cycles was three. Definite responders were 52.5%. The complete response (CR) was 10.2%, and 59.3% of patients received bladder-sparing treatments. With a median follow-up of 44.6 months, the 3-year overall survival (OS) was 72.8%. Three-year OS and relapse-free survival were 88.4% and 60.0% in the bladder-sparing group but only 74.3% and 37.5% in the cystectomy group. The evaluations of preserved bladder function were satisfactory. Conclusion After stratifying MIBC patients by NAC efficacy, definite responders achieved a satisfactory bladder-sparing rate, prognosis, and bladder function. The CR rate reflected the real NAC efficacy for MIBC. This therapy is worth verifying through multicenter research.

Objective:To observe the effect of interleukin-6 (IL-6) on the phenotype and function of human umbilical vein endothelial cells (HUVECs) and explore the role of IL-6 in the process of endothelial-to-mesenchymal transition (EndMT).Methods:The experimental research method was used. Fresh umbilical cord discarded after normal maternal delivery was collected. On the second day of the primary cell isolation and cultivation, the cell morphology was observed under inverted phase contrast microscope. HUVECs of the 4th passage were identified by immunofluorescence method, and 2 batches of HUVECs ofthe 3rd to 5th passages were used for the subsequent experiments. The first batch of cells were divided into 6 groups according to the random number table (the same below): blank control group, 5 ng/mL IL-6 group, 10 ng/mL IL-6 group, 25 ng/mL IL-6 group, 50 ng/mL IL-6 group, and 100 ng/mL IL-6 group. The second batch of cells were divided into 4 groups: blank control group, 10 ng/mL IL-6 group, 25 ng/mL IL-6 group,and 50 ng/mL IL-6 group; the cells in blank control group was cultured with complete culture medium only, while the cells in the other groups were added with IL-6 of the corresponding final mass concentrations.Cells from the 1st batch were cultured for 72 hours after grouping, the morphology of HUVECS in the 6 groups was observed under inverted phase contrast microscope. At 72 h after grouping culture, the positive expressions of coagulation factor Ⅷ and α vascular smooth muscle actin (α-SMA) in HUVECs in the 6 groups were detected by immunofluorescence method, and the ratio of the number of double positive cells to the number of coagulation factor Ⅷ positive cells (the ratio of double positive cells for short) was calculated, with 6 samples per group; mRNA expression levels of vascular endothelial cadherin and α-SMA of HUVECs in 6 groups were detected by reverse transcription-polymerase chain reaction, with 3 samples per group.Cells from the 2nd batch were cultured 72 hours after grouping, the protein expression levels of vascular endothelial cadherin, α-SMA, and type Ⅰ collagen in the 4 groups were detected by Western blotting, with 3 samples per group. Data were statistically analyzed with one-way analysis of variance and Bonferroni correction.Results:On the 2nd day after isolation and cultivation, the primary cells were in short spindle shape or polygon, cells of the 4th passage were identified as HUVECs by immunofluorescence method. At 72 hours of culture after grouping, the cells from the 1st batch in the 6 groups changed to long spindle shape morphologically along with the increase of IL-6 concentration, the intercellular connections decreased or disappeared with the gap between cells becoming larger. At 72 h after grouping culture, compared with that inblank control group, the ratio of double positive cells in 25 ng/mL IL-6 group, 50 ng/mL IL-6 group, and 100 ng/mL IL-6 group were significantly increased ( P<0.01); compared with that in 5 ng/mL IL-6 group, the ratio of double positive cells in 25 ng/mL IL-6 group, 50 ng/mL IL-6 group, and 100 ng/mL IL-6 group were significantly increased ( P<0.01); compared with that in 10 ng/mL IL-6 group, the ratio of double positive cells in 50 ng/mL IL-6 group and 100 ng/mL IL-6 group were significantly increased ( P<0.01); the ratio of double positive cells in 100 ng/mL IL-6 group was significantly increased compared with those in 25 ng/mL IL-6 group and 50 ng/mL IL-6 group ( P<0.01). At 72 h after grouping culture, compared with that in blank control group, the mRNA expression levels of vascular endothelial cadherin of cells in 25 ng/mL IL-6 group, 50 ng/mL IL-6 group, and 100 ng/mL IL-6 group were significantly decreased ( P<0.01 or P<0.05); compared with that in 5 ng/mL IL-6 group, the mRNA expression levels of vascular endothelial cadherin of cells in 50 ng/mL IL-6 group and 100 ng/mL IL-6 group were significantly decreased ( P<0.01); compared with that in 10 ng/mL IL-6 group, the mRNA expression levels of vascular endothelial cadherin of cells in 50 ng/mL IL-6 group and 100 ng/mL IL-6 group were significantly decreased ( P<0.01); compared with that in 25 ng/mL IL-6 group, the mRNA expression levels of vascular endothelial cadherin of cells in 50 ng/mL IL-6 group and 100 ng/mL IL-6 group were significantly decreased ( P<0.01). At 72 h after grouping culture, compared with that in blank control group, the mRNA expression levels of α-SMA of cells in 5 ng/mL IL-6 group, 10 ng/mL IL-6 group, 25 ng/mL IL-6 group, 50 ng/mL IL-6, group, and 100 ng/mL IL-6 group were significantly increased ( P<0.05 or P<0.01). Cells from the 2nd batch were cultured for 72 hours after grouping. Compared with 1.391±0.026 in blank control group, the protein expressions of vascular endothelial cadherin of cells in 10 ng/mL IL-6 group (1.185±0.063), in 25 ng/mL IL-6 group (0.717±0.078), and in 50 ng/mL IL-6 group (0.239±0.064) were significantly decreased ( P<0.05); compared with that in 10 ng/mL IL-6 group, the protein expressions of vascular endothelial cadherin of cells in 25 ng/mL IL-6 group and 50 ng/mL IL-6 group were significantly decreased ( P<0.01); compared with that in 25 ng/mL IL-6 group, the protein expression of vascular endothelial cadherin of cells in 50 ng/mL IL-6 group was significantly decreased ( P<0.01). At 72 h after grouping culture, compared with that in blank control group, the protein expression levels of α-SMA of cells in 10 ng/mL IL-6 group, 25 ng/mL IL-6 group, and 50 ng/mL IL-6 group were significantly increased ( P<0.01); compared with that in 10 ng/mL IL-6 group, the protein expression levels of α-SMA of cells in 25 ng/mL IL-6 group and 50 ng/mL IL-6 group were significantly increased ( P<0.01). At 72 h after grouping culture, compared with that in blank control group, the protein expressions of type Ⅰ collagen of cells in 25 ng/mL IL-6 group and 50 ng/mL IL-6 group were significantly increased ( P<0.05). Conclusions:After IL-6 treatment, the phenotype and function of HUVECS showed the characteristics of mesenchymal cells in a concentration-dependent manner. The inflammatory factor can promote the process of EndMT, and become one of the important factors regulating the mechanism of tissue fibrosis.