Objective To investigate the multi-target mechanisms of quercetin in treating endometriosis(EMT)through integrative network pharmacology analysis.Methods Active targets of quercetin were collected from the TCMSP database,while EMT-related differentially expressed genes(DEGs)were identified through the Gene Expression Omnibus(GEO)dataset.A comparative analysis was conducted to pinpoint potential therapeutic targets of quercetin for EMT treatment.Functional enrichment analyses were employed to investigate the biological functions associated with these targets,and a protein-protein interaction(PPI)network was conducted to identify core targets.Molecular docking and dynamics simulations were performed to validate the binding characteristics between quercetin and the core targets.The top 2 target protein pairs,HSP90AB1 and AR,exhibiting the lowest binding energy,were selected for subsequent cellular experimental validation.Human EMT-immortalized ectopic endometrial epithelial cell line 12Z(n=6,independent replicates)was subjected,and CCK-8 assay was used to determine ehe effects of quercetin on cell viability and proliferation,and the half-maximal inhibitory concentration(IC50)was calculated at 48 h after treatment.Then the 12Z cells were treated with quercetin at a concentration gradient of 0,30,60 and 90 μmol/L,the migration and invasion abilities were assessed with cell scratch and cell invasion assays.Western blotting was conducted to detect the changes in the expression of HSP90AB1 and AR proteins after different doses of treatment.Results There were 49 potential EMT-related therapeutic targets and 10 core targets identified.Functional enrichment analyses revealed that these targets were significant enriched in inflammation-related signaling pathways,including AGE-RAGE,ErbB and TNF;immune-related pathways,such as Th17 cell differentiation,T/B cell receptor signaling;angiogenesis-related pathways like VEGF;and hormonal regulatory pathways involving estrogen and GnRH.Molecular docking demonstrated that quercetin exhibited favorable binding activity(binding energy<-5 kcal/mol)with all core target proteins,with particularly strong binding energies(<-7 kcal/mol)observed for AR,EGFR,FOS,ERBB2,and HSP90AB1.Molecular dynamics simulations revealed that quercetin forms sustained hydrogen bond interactions with AR and HSP90AB1,facilitating the formation of stable complexes.CCK-8 assay,cell scratch assay,and transwell invasion assay indicated that quercetin inhibited the proliferative activity,and migrative and invasive abilities of 12Z cells in a concentration-dependent manner,with more pronounced inhibitory effects observed at 60 and 90 μmol/L quercetin(P<0.001);Western blotting revealed that treatment of 12Z cells with varying quercetin concentrations for 48 h up-regulated the expression of HSP90AB1 and AR,with the most significant increase observed at 90 μmol/L quercetin(HSP90AB1,P<0.05;AR,P<0.001).The restored expression levels of HSP90AB1 and AR showed positive correlations with the proliferative activity,migrative and invasive abilities of ectopic endometrial cells.Conclusion Quercetin effectively addresses endometriosis through multiple molecular targets and signaling pathways,and stabilization of the HSP90AB1/AR complex and subsequent protein upregulation represents a key therapeutic mechanism.

Background and Aims:Obstructive jaundice(OJ)caused by common bile duct stones(CBDS)is a major risk factor for acute cholangitis(AC).Early identification of high-risk patients is essential for improving prognosis.Soluble CD163(sCD163)and milk fat globule epidermal growth factor 8(MFG-E8)are associated with inflammatory diseases,but their predictive value for AC in CBDS-related OJ remains unclear.This study aimed to evaluate the predictive significance of serum sCD163 and MFG-E8 levels for AC in patients with CBDS-OJ.Methods:A total of 142 patients with CBDS-OJ admitted from January 2022 to June 2024 were included as the observation group,and 145 healthy individuals undergoing physical examination served as controls.Serum sCD163 and MFG-E8 levels were measured using ELISA.Based on the occurrence of AC within 24 hours after admission,patients with CBDS-OJ were divided into an AC group(n=48)and a non-AC group(n=94).Clinical variables and serological indicators were compared between groups.Multivariate logistic regression was used to identify independent factors associated with AC.Receiver operating characteristic(ROC)curves were generated to assess the predictive performance of sCD163,MFG-E8,and their combination.Results:Compared with the control group,patients with CBDS-OJ showed significantly elevated serum sCD163 levels and decreased MFG-E8 levels(both P<0.05).Within the observation group,the AC group had higher AST,ALT and sCD163 levels and lower MFG-E8 levels than the non-AC group(all P<0.05).Logistic regression identified elevated sCD163 as an independent risk factor(OR=3.478,P<0.001)and reduced MFG-E8 as a protective factor(OR=0.526,P=0.020)for AC.ROC analysis showed AUC values of 0.759 for sCD163,0.787 for MFG-E8,and 0.920 for their combined detection,with the combined model outperforming either marker alone(P<0.001).Conclusion:Serum sCD163 elevation and MFG-E8 reduction are closely associated with the development of AC in patients with CBDS-OJ.Combined detection of sCD163 and MFG-E8 provides superior predictive value and may serve as a useful tool for early risk stratification in clinical practice.

OBJECTIVE To investigate the expression levels of nucleotide-binding oligomerization domain-like recep-tor pyrin domain-associated protein 3(NLRP3)inflammasome pathway and toll-like receptors(TLRs)pathway in serofast patients with syphilis infection,and their correlation with helper T lymphocytes(Th)1/Th2.METHODS A total of 549 patients with syphilis admitted to Tianjin Chest Hospital and Tianjin Medical University General Hospital from Jan.2021 to Dec.2022 were selected.Among them,62 patients who had not received anti-syphilis treatment were assigned to the syphilis group,238 patients whose serum remained positive after anti-syphilis treatment were selected as the fixed group,249 patients whose serum turned negative after anti-syphilis treatment were selected as the negative conversion group,and another 565 healthy people who underwent medical examina-tion in the hospital during the same period were selected as the control group.TLR2,TLR4,nuclear factor(NF)-κB,NLRP3,apoptosis-associated speck-like protein(ASC),cysteinyl aspartate proteolytic enzyme 1(Caspase-1),in-terleukin(IL)-1β mRNA and interferon-γ(IFN-γ),IL-12,IL-13 and IL-10 levels were compared between each group.Pearson's analysis was used to analyze the correlation between the mRNA expression of TLR2,TLR4,NF-κB,NLRP3,ASC,Caspase-1,and IL-1β and the levels of IFN-γ,IL-12,IL-13,and IL-10 in serologically fixed patients with syphilis.RESULTS Compared with the control group,the mRNA expression of TLR2,TLR4,NF-κB,NLRP3,ASC,Caspase-1 and IL-1β was elevated in the negative conversion and the syphilis groups,and the expres-sion of the above indicators was decreased in the fixed group(P＜0.05).Compared with negative conversion group,mR-NA expressions of TLR2,TLR4,NF-κB,NLRP3,ASC,Caspase-1 and IL-1β were increased in syphilis group,while the expression of the above indicators was decreased in fixed group(P＜0.05).Compared with fixed group,mRNA ex-pressions of TLR2,TLR4,NF-κB,NLRP3,ASC,Caspase-1 and IL-1β in syphilis group were increased in the syphilis group(P＜0.05).Compared with the control group,IFN-γ and IL-12 levels were decreased in the negative conversion group,syphilis group and fixed group,and IL-13 and IL-10 levels were increased(P＜0.05).Compared with the nega-tive conversion group,IFN-γ and IL-12 levels in the syphilis group and fixed group were decreased,while IL-13 and IL-10 levels were increased(P＜0.05).Compared with the fixed group,the levels of IFN-γ and IL-12 in syphilis group were increased,while the levels of IL-13 and IL-10 were decreased(P＜0.05).The mRNA levels of TLR2,TLR4,NF-κB,NLRP3,ASC,Caspase-1 and IL-1β were positively correlated with the levels of IFN-γ and IL-12 in serum fixed patients with syphilis infection(r=0.698,0.602,0.636,0.702,0.645,0.617,0.583 and 0.669,and 0.693,0.641,0.702,0.623,0.618 and 0.647,respectively,all P＜0.05),and negatively correlated with the levels of IL-13 and IL-10(r=-0.639,-0.705,-0.614,-0.590,-0.598,-0.651 and-0.628,and-0.704,-0.649,-0.606,-0.655,-0.650,-0.641 and-0.539,respectively,all P＜0.05).CONCLUSION The NLRP3 inflammasome pathway and TLRs pathway are abnormally expressed in sero-fast patients with syphilis infection,positively correlated with the expression of Th1 cytokines IFN-γ and IL-12,and negatively correlated with the expression of Th2 cytokines IL-13 and IL-10.

Background and Aims:Obstructive jaundice(OJ)caused by common bile duct stones(CBDS)is a major risk factor for acute cholangitis(AC).Early identification of high-risk patients is essential for improving prognosis.Soluble CD163(sCD163)and milk fat globule epidermal growth factor 8(MFG-E8)are associated with inflammatory diseases,but their predictive value for AC in CBDS-related OJ remains unclear.This study aimed to evaluate the predictive significance of serum sCD163 and MFG-E8 levels for AC in patients with CBDS-OJ.Methods:A total of 142 patients with CBDS-OJ admitted from January 2022 to June 2024 were included as the observation group,and 145 healthy individuals undergoing physical examination served as controls.Serum sCD163 and MFG-E8 levels were measured using ELISA.Based on the occurrence of AC within 24 hours after admission,patients with CBDS-OJ were divided into an AC group(n=48)and a non-AC group(n=94).Clinical variables and serological indicators were compared between groups.Multivariate logistic regression was used to identify independent factors associated with AC.Receiver operating characteristic(ROC)curves were generated to assess the predictive performance of sCD163,MFG-E8,and their combination.Results:Compared with the control group,patients with CBDS-OJ showed significantly elevated serum sCD163 levels and decreased MFG-E8 levels(both P<0.05).Within the observation group,the AC group had higher AST,ALT and sCD163 levels and lower MFG-E8 levels than the non-AC group(all P<0.05).Logistic regression identified elevated sCD163 as an independent risk factor(OR=3.478,P<0.001)and reduced MFG-E8 as a protective factor(OR=0.526,P=0.020)for AC.ROC analysis showed AUC values of 0.759 for sCD163,0.787 for MFG-E8,and 0.920 for their combined detection,with the combined model outperforming either marker alone(P<0.001).Conclusion:Serum sCD163 elevation and MFG-E8 reduction are closely associated with the development of AC in patients with CBDS-OJ.Combined detection of sCD163 and MFG-E8 provides superior predictive value and may serve as a useful tool for early risk stratification in clinical practice.

OBJECTIVE To investigate the expression levels of nucleotide-binding oligomerization domain-like recep-tor pyrin domain-associated protein 3(NLRP3)inflammasome pathway and toll-like receptors(TLRs)pathway in serofast patients with syphilis infection,and their correlation with helper T lymphocytes(Th)1/Th2.METHODS A total of 549 patients with syphilis admitted to Tianjin Chest Hospital and Tianjin Medical University General Hospital from Jan.2021 to Dec.2022 were selected.Among them,62 patients who had not received anti-syphilis treatment were assigned to the syphilis group,238 patients whose serum remained positive after anti-syphilis treatment were selected as the fixed group,249 patients whose serum turned negative after anti-syphilis treatment were selected as the negative conversion group,and another 565 healthy people who underwent medical examina-tion in the hospital during the same period were selected as the control group.TLR2,TLR4,nuclear factor(NF)-κB,NLRP3,apoptosis-associated speck-like protein(ASC),cysteinyl aspartate proteolytic enzyme 1(Caspase-1),in-terleukin(IL)-1β mRNA and interferon-γ(IFN-γ),IL-12,IL-13 and IL-10 levels were compared between each group.Pearson's analysis was used to analyze the correlation between the mRNA expression of TLR2,TLR4,NF-κB,NLRP3,ASC,Caspase-1,and IL-1β and the levels of IFN-γ,IL-12,IL-13,and IL-10 in serologically fixed patients with syphilis.RESULTS Compared with the control group,the mRNA expression of TLR2,TLR4,NF-κB,NLRP3,ASC,Caspase-1 and IL-1β was elevated in the negative conversion and the syphilis groups,and the expres-sion of the above indicators was decreased in the fixed group(P＜0.05).Compared with negative conversion group,mR-NA expressions of TLR2,TLR4,NF-κB,NLRP3,ASC,Caspase-1 and IL-1β were increased in syphilis group,while the expression of the above indicators was decreased in fixed group(P＜0.05).Compared with fixed group,mRNA ex-pressions of TLR2,TLR4,NF-κB,NLRP3,ASC,Caspase-1 and IL-1β in syphilis group were increased in the syphilis group(P＜0.05).Compared with the control group,IFN-γ and IL-12 levels were decreased in the negative conversion group,syphilis group and fixed group,and IL-13 and IL-10 levels were increased(P＜0.05).Compared with the nega-tive conversion group,IFN-γ and IL-12 levels in the syphilis group and fixed group were decreased,while IL-13 and IL-10 levels were increased(P＜0.05).Compared with the fixed group,the levels of IFN-γ and IL-12 in syphilis group were increased,while the levels of IL-13 and IL-10 were decreased(P＜0.05).The mRNA levels of TLR2,TLR4,NF-κB,NLRP3,ASC,Caspase-1 and IL-1β were positively correlated with the levels of IFN-γ and IL-12 in serum fixed patients with syphilis infection(r=0.698,0.602,0.636,0.702,0.645,0.617,0.583 and 0.669,and 0.693,0.641,0.702,0.623,0.618 and 0.647,respectively,all P＜0.05),and negatively correlated with the levels of IL-13 and IL-10(r=-0.639,-0.705,-0.614,-0.590,-0.598,-0.651 and-0.628,and-0.704,-0.649,-0.606,-0.655,-0.650,-0.641 and-0.539,respectively,all P＜0.05).CONCLUSION The NLRP3 inflammasome pathway and TLRs pathway are abnormally expressed in sero-fast patients with syphilis infection,positively correlated with the expression of Th1 cytokines IFN-γ and IL-12,and negatively correlated with the expression of Th2 cytokines IL-13 and IL-10.

Objective:To investigate the expression of soluble T cell immunoglobulin and mucin domain-3 (Tim-3) in peripheral blood of patients with pancreatic cancer and its diagnostic value in combination with serum Carbohydrate antigen 19-9 (CA19-9) .Methods:106 newly diagnosed pancreatic cancer patients and 65 age and sex matched healthy individuals were enrolled. Tim-3 concentration was quantitatively determined by enzyme-linked immunosorbent assay (ELISA). According to the expression levels of soluble Tim-3 and serum CA19-9, a binary logistic regression model of receiver operating characteristic (ROC) curve was established to compare the diagnostic effects of serum CA19-9 and soluble Tim-3 alone or combined with the two tests.Results:The levels of soluble Tim-3 in the pancreatic cancer group were significantly higher than those in the healthy control group ( P<0.001). The expression level of soluble Tim-3 was significantly higher in patients with stage III-IV pancreatic cancer than in patients with stage I-II ( P=0.003). The AUC of soluble Tim-3 diagnosis for stage I-II pancreatic cancer was 0.856 (95%CI: 0.765 to 0.992 P<0.001), Serum CA19-9 The AUC used for the stage I-II pancreatic cancer diagnosis was 0.862 (95%CI: 0.772 to 0.926 P<0.001), The AUC for the combined diagnosis was 0.949 (95%CI: 0.880 - 0.985 P<0.001) ; In a healthy population and in patients with stage III-IV pancreatic cancer, the AUC of soluble T I I-IV pancreatic cancer in stage III was 0.927 (95%CI: 0.873 to 0.963 P<0.001), the AUC of serum CA19-9 used for the diagnosis of stage III-IV pancreatic cancer was 0.933 (95%CI: 0.881 to 0.968 P<0.001), the AUC for the combined diagnosis was 0.989 (95%CI: 0.956 to 0.999 P<0.001) . Conclusions:The combination of soluble Tim-3 and serum CA19-9 can improve the diagnostic rate of pancreatic cancer patients.

Background::Ubiquitination plays an essential role in many biological processes, including viral infection, and can be reversed by deubiquitinating enzymes (DUBs). Although some studies discovered that DUBs inhibit or enhance viral infection by various mechanisms, there is lack of information on the role of DUBs in virus regulation, which needs to be further investigated.Methods::Immunoblotting, real-time polymerase chain reaction, in vivo/ in vitro deubiquitination, protein immunoprecipitation, immunofluorescence, and co-localization biological techniques were employed to examine the effect of ubiquitin-specific protease 3 (USP3) on APOBEC3G (A3G) stability and human immunodeficiency virus (HIV) replication. To analyse the relationship between USP3 and HIV disease progression, we recruited 20 HIV-infected patients to detect the levels of USP3 and A3G in peripheral blood and analysed their correlation with CD4 + T-cell counts. Correlation was estimated by Pearson correlation coefficients (for parametric data). Results::The results demonstrated that USP3 specifically inhibits HIV-1 replication in an A3G-dependent manner. Further investigation found that USP3 stabilized 90% to 95% of A3G expression by deubiquitinating Vif-mediated polyubiquitination and blocking its degradation in an enzyme-dependent manner. It also enhances the A3G messenger RNA (mRNA) level by binding to A3G mRNA and stabilizing it in an enzyme-independent manner. Moreover, USP3 expression was positively correlated with A3G expression ( r= 0.5110) and CD4 + T-cell counts ( r= 0.5083) in HIV-1-infected patients. Conclusions::USP3 restricts HIV-1 viral infections by increasing the expression of the antiviral factor A3G. Therefore, USP3 may be an important target for drug development and serve as a novel therapeutic strategy against viral infections.

Objective:To explore the effect of medical alliance combined with video recording guidance on the out-of-hospital rehabilitation of elderly patients undergoing hip replacement.Methods:Using the convenient sampling method, a total of 58 aged patients who were hospitalized in the Department of Orthopedics and underwent hip replacement in the First Affiliated Hospital of Zhengzhou University from March 2018 to June 2019 were selected as research objects. They were randomly divided into the observation group and the control group, with 29 cases in each group. The control group was given conventional out-of-hospital rehabilitation management while the observation group was given medical alliance combined with video recording guidance. The serum albumin, Harris score, total body skeletal muscle mass, skeletal muscle mass of the affected limb, incidence of deep venous thrombosis (DVT) and incidence of artificial hip dislocation were compared between the two groups before and after the intervention.Results:After intervention, the serum albumin of the observation group was (36.73±1.95) g/L, the Harris score was (89.29±5.25) , the total body skeletal muscle mass was (17.91±1.18) kg and the skeletal muscle mass of the affected limb was (5.38±0.79) kg, which were all higher than those of the control group, and the differences were statistically significant ( t=3.524, 7.231, 4.584, 4.252; P<0.05) . After intervention, the incidence of DVT in the observation group was 3.45% (1/29) , and the difference was not statistically significant when compared with 13.79% (4/29) in the control group (χ 2=1.970, P>0.05) . After the intervention, the incidence of artificial hip dislocation in the observation group was 0 (0/29) , which was lower than 20.69% (6/29) in the control group, and the difference was statistically significant ( P<0.05) . Conclusions:Medical consortium combined with video guidance can effectively improve the out-of-hospital rehabilitation effect of elderly patients undergoing hip replacement surgery and reduce the occurrence of complications. Medical alliance combined with video recording guidance can effectively improve the out-of-hospital rehabilitation effect of elderly patients with artificial hip replacement and reduce the incidence of complications.

Objective To study the enhanced performance of contrast-enhanced ultrasouond( CEUS) parametric imaging , and to explore the diagnostic value of CEUS parametric imaging in predicting extracapsular invasion and cervical lymph node metastasis of papillary thyroid cancer( PTC) . Methods One hundred and fifty-eight PTCs in 136 patients pathologically proven papillary thyroid carcinoma between January 2016 and January 2017 were enrolled in this study . According to the pathological results of extracapsular invasion and cervical lymph node metastasis respectively ,the PTCs were grouped into the negative group and the positive group . The parametric imaging features of the two groups were summarized to explore the risk factors of extracapsular invasion and cervical lymph node metastasis of PTCs respectively . Results The parametric imaging suggested that centripetal enhancement had a significant effect on extracapsular invasion ( P =0 .001) . While there was no difference in the perfusion start time of extracapsular invasion between the negative and positive group ( P > 0 .05 ) . Besides , there was no statistical significance in the perfusion start time and perfusion pattern of cervical lymph node metastasis between the negative and positive group (all P >0 .05) .Conclusions The parametric imaging features help predicting extracapsular invasion in PTCs . And the ones with centripetal enhancement patterns are more often with extracapsular invasion .

Objective To explore the diagnostic value of conventional ultrasound(US) and contrast enhanced ultrasound(CEUS) in predicting extrathyroidal extension of papillary thyroid cancer(PTC).Methods Eighty-five PTCs in 75 patients were selected for thyroid surgery underwent ultrasound and contrast-enhanced ultrasound.The degrees of contact between PTCs and capsule were observed by US and CEUS respectively(0,0-25％,25％-50％,≥50％),and the diagnostic efficiency in different degree of contact (＞0 ％,≥25 ％,≥50％) as preoperative diagnostic criteria were analyzed.The diagnostic efficiency between US and CEUS in predicting extrathyroidal extension of PTC were compared.Results Of the 85 PTCs,extrathyroidal extension was presented in 57 (67.06％) based on pathologic results.When the degree of contact (＞ 0 ％,＜ 25 ％,25 ％-50 ％,≥ 50 ％) was gradually increased,the incidence of extrathyroidal extension of the thyroid cancer was also gradually risen (P ＜0.001).Comparing the sensitivity,accuracy,odds ratio,and Az value of three groups(＞0％,≥25％,≥50％),it showed that the general diagnostic efficiency between two groups(＞0％,≥25％) was similar by US and CEUS.However,the sensitivity and accuracy of ＞0％ contact with the adjacent capsule were markedly higher than those of the other two groups(P ＜0.001).Selecting ＞0％ contact with the adjacent capsule as preoperative criteria,the Az value of CEUS was markedly higher than that of US (Z =2.208,P =0.027).Conclusions The preoperative imaging feature of more than 0％ contact with the adjacent capsule is more sensitive and accurate degree in predicting extrathyroidal extension of PTC.Compared with US,CEUS may serve as a better useful tool to predict extrathyroidal extension of PTC.