Background: Condyloma acuminatum (CA) is a common sexually transmitted disease caused by human papillomavirus (HPV). In recent years, research on anal CA has primarily focused on treatment rather than underlying mechanisms. The mechanism of HPV persistence and recurrence in CA require further exploration. It needs multiple researches in mechanisms to focalize treatment targets. Objective: To investigate the relationship between intestinal mucosal immunity and the relapse of anal CA and persistent infection. Methods: Levels of interferon gamma (IFN-γ) and secretory immunoglobulin A (sIgA) were measured using enzyme-linked immunosorbnent assay in anal mucosal cells obtained from patients treated at Tianjin Union Medical Center from September 2022 to December 2024. All the participants signed Informed Consent and the whole plan was approved by Institutional Review Board in Tianjin Union Medical Center (No. B155). Results: The levels of IFN-γ and sIgA significantly decreased after infection, and persistent infection exhibited even lower levels. These two factors increased following treatment, reaching peak concentrations at 4 weeks before decreasing again. Conclusion These findings demonstrate a significant association between persistent anal CA infection and dysregulation of intestinal mucosal immunity.

Objective:To analyze the impact of serum alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19-9) on the prognosis of patients with combined hepatocellular-cholangiocarcinoma (CHC) after radical surgery.Methods:Clinical data of 100 patients diagnosed with CHC by postoperative pathology in Hunan Provincial People's Hospital from January 2009 to January 2019 were retrospectively analyzed, including 73 males and 27 females, aged (52.0±10.9) years. Univariate and multivariate Cox regression analysis were conducted to try to find out the effects of AFP and CA19-9 on postoperative disease-free survival (DFS) of patients with CHC. Subgroup analysis was also performed to analyze the DFS among patients with different levels of AFP and CA19-9. Kaplan-Meier method and log-rank test were used to plot and compare the survival curves between groups.Results:Univariate analysis showed that levels of AFP, CA19-9, alanine transaminase, aspartate transaminase, American Joint Committee on Cancer (AJCC) TNM staging, portal vein invasion, tumor number are associated with postoperative DFS in CHC patients (all P<0.05). The multivariate Cox analysis showed that AFP≥20.6 μg/L ( HR=6.686, 95% CI: 1.985-9.582), CA19-9≥35.2 U/L ( HR=5.790, 95% CI: 1.197-8.855), AJCC tumor TNM staging stage Ⅱ( HR=6.384, 95% CI: 2.069-11.532), and portal vein invasion ( HR=2.384, 95% CI: 1.100-10.125) were risk factors for a shortened DFS in CHC patients after surgery (all P<0.05). Subgroup analysis showed that patients with AFP≥20.6 μg/L and CA19-9≥35.2 U/L ( n=14) had a lower DFS compared to patients with AFP<20.6 μg/L and CA19-9≥35.2 U/L ( n=32), and patients with AFP≥20.6 μg/L and CA19-9<35.2 U/L ( n=20) ( χ2=6.23, 4.98, P=0.014, 0.043). Conclusion:AFP and CA19-9 are risk factors for DFS in CHC patients. Patients with AFP≥20.6 μg/L and CA19-9≥35.2 U/L showed a worse prognosis.

Objective To investigate the mechanism by which angiotensin Ⅱ type 1 receptor autoantibody(AT1-AA)promotes phenotypic switch of vascular smooth muscle cells(VSMCs)and vascular fibrosis through abnormal expression of circadian clock protein BMAL1.Methods Twelve male SD rats(6～8 weeks old,weighing 180～220 g)were randomly divided into(n=6)a control group and an AT1-AA-positive group[established by active immunization of SD rats with AT1R extracellular loop Ⅱ peptide(AT1R-ECLⅡ)].HE and Masson stainings were used to observe structural changes and fibrosis in the thoracic aorta(n=3).Western blotting was performed to detect the expression of Collagen I,phenotypic switch-related proteins(SM22,α-SMA,OPN and MMP2)in vascular tissues and primary VSMCs(n=4),as well as the expression of BMAL1 at CT0,CT4,CT8,CT12,CT16,and CT20.Transwell and scratch assays were used to assess the proliferation and migration of VSMCs(n=3).si-RNA was employed to knock down Bmal1,followed by detection of BMAL1,Collagen I,and phenotypic conversion-related protein expression(n=3).Additionally,AT1-AA-positive AT1R-knockout(AT1R-KO)rats were constructed to measure BMAL1 expression in thoracic aortic tissues(n=4).Results The AT1-AA-positive rats had significantly thickened thoracic aortic vessel wall[(140±9)%vs(120±5)%,P<0.05],badly arranged VSMCs,obvious blue Masson staining,and up-regulated Collagen I expression(P<0.05).In the thoracic aorta of AT1-AA-positive rats and AT1-AA-treated VSMCs,the expression of contractile phenotype-related proteins(α-SMA,SM22)was decreased(P<0.05),while the expression of synthetic phenotype-related proteins(OPN,MMP2)was increased(P<0.05).AT1-AA enhanced the scratch healing ability and migration ability of VSMCs.Furthermore,both mRNA and protein levels of Bmal1 were significantly up-regulated at CT12(P<0.05),and the rhythmicity of Bmal1 was lost.Knockdown of Bmal1 partially ameliorated AT1-AA-induced phenotypic switch of VSMCs.Compared with AT1-AA-positive WT rats,AT1-AA-positive AT1R-KO rats showed significantly reduced BMAL1 expression in the thoracic aorta(1.35±0.06 vs 0.86±0.07,P<0.001).At the cellular level,AT1-AA-induced phenotypic switch and high Collagen I expression in VSMCs were partially improved in AT1R-KO VSMCs.Conclusion AT1-AA promotes VSMCs phenotypic conversion and vascular fibrosis through the AT1R-Bmal1 axis.

Objective To explore the time cross-lagged effect between carotid intima-media thickness(CIMT)and bone mineral density(BMD)and to assess whether CIMT can be used as an early predictor of osteoporosis.Methods Based on the retrospective cohort study involved,people who underwent health checkups at The First Affiliated Hospital of Xi'an Jiaotong University from January 2019 to December 2023 were selected,and data related to CIMT and BMD were collected.The time-series relationship between CIMT and BMD was explored by cross-lagged modeling.Meanwhile,the effects of CIMT on BMD and its dose-response relationship were assessed using multiple linear regression and restricted cubic spline regression models.Results Analysis of 2 453 study subjects revealed a significant negative relationship between prior physical examination CIMT and subsequent BMD,and this relationship remained significant after controlling for confounders.For every 1-unit increase in CIMT,there was a mean decrease in second-stage BMD T-values of 0.113.Restricted cubic spline regression analysis showed a maximum decrease in BMD T-values of 0.121 for every 1.00 mm increase in CIMT.Conclusion The present study found that there was a significant negative cross-lag effect between CIMT and BMD,and that there was a dose-response between an increase in CIMT and a decrease in BMD.CIMT,as an easy-to-measure indicator,may be a potential marker for early prediction of osteoporosis,especially in the elderly population.

Objective To explore the time cross-lagged effect between carotid intima-media thickness(CIMT)and bone mineral density(BMD)and to assess whether CIMT can be used as an early predictor of osteoporosis.Methods Based on the retrospective cohort study involved,people who underwent health checkups at The First Affiliated Hospital of Xi'an Jiaotong University from January 2019 to December 2023 were selected,and data related to CIMT and BMD were collected.The time-series relationship between CIMT and BMD was explored by cross-lagged modeling.Meanwhile,the effects of CIMT on BMD and its dose-response relationship were assessed using multiple linear regression and restricted cubic spline regression models.Results Analysis of 2 453 study subjects revealed a significant negative relationship between prior physical examination CIMT and subsequent BMD,and this relationship remained significant after controlling for confounders.For every 1-unit increase in CIMT,there was a mean decrease in second-stage BMD T-values of 0.113.Restricted cubic spline regression analysis showed a maximum decrease in BMD T-values of 0.121 for every 1.00 mm increase in CIMT.Conclusion The present study found that there was a significant negative cross-lag effect between CIMT and BMD,and that there was a dose-response between an increase in CIMT and a decrease in BMD.CIMT,as an easy-to-measure indicator,may be a potential marker for early prediction of osteoporosis,especially in the elderly population.

To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.

To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.

Objective:To analyze the impact of serum alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19-9) on the prognosis of patients with combined hepatocellular-cholangiocarcinoma (CHC) after radical surgery.Methods:Clinical data of 100 patients diagnosed with CHC by postoperative pathology in Hunan Provincial People's Hospital from January 2009 to January 2019 were retrospectively analyzed, including 73 males and 27 females, aged (52.0±10.9) years. Univariate and multivariate Cox regression analysis were conducted to try to find out the effects of AFP and CA19-9 on postoperative disease-free survival (DFS) of patients with CHC. Subgroup analysis was also performed to analyze the DFS among patients with different levels of AFP and CA19-9. Kaplan-Meier method and log-rank test were used to plot and compare the survival curves between groups.Results:Univariate analysis showed that levels of AFP, CA19-9, alanine transaminase, aspartate transaminase, American Joint Committee on Cancer (AJCC) TNM staging, portal vein invasion, tumor number are associated with postoperative DFS in CHC patients (all P<0.05). The multivariate Cox analysis showed that AFP≥20.6 μg/L ( HR=6.686, 95% CI: 1.985-9.582), CA19-9≥35.2 U/L ( HR=5.790, 95% CI: 1.197-8.855), AJCC tumor TNM staging stage Ⅱ( HR=6.384, 95% CI: 2.069-11.532), and portal vein invasion ( HR=2.384, 95% CI: 1.100-10.125) were risk factors for a shortened DFS in CHC patients after surgery (all P<0.05). Subgroup analysis showed that patients with AFP≥20.6 μg/L and CA19-9≥35.2 U/L ( n=14) had a lower DFS compared to patients with AFP<20.6 μg/L and CA19-9≥35.2 U/L ( n=32), and patients with AFP≥20.6 μg/L and CA19-9<35.2 U/L ( n=20) ( χ2=6.23, 4.98, P=0.014, 0.043). Conclusion:AFP and CA19-9 are risk factors for DFS in CHC patients. Patients with AFP≥20.6 μg/L and CA19-9≥35.2 U/L showed a worse prognosis.

Objective: To investigate the causal relationship between gut microbiota and polycystic ovary syndrome (PCOS) using a Mendelian randomization (MR) study, so as to provide insights into the pathogenesis of PCOS and the formulation of prevention and treatment strategies. Methods: The genetic data on gut microbiota was derived from a meta-analysis of genome-wide association studies (GWAS) involving 18 340 participants. The genetic data on PCOS was sourced from two GWAS meta-analyses in European populations, serving as the discovery set and the validation set, respectively. A two-sample MR analysis was conducted using the discovery set, with the inverse variance weighted (IVW) method as the primary approach. Sensitivity analyses employed the weighted median method, MR-Egger regression, and the MR-PRESSO test. The validation set was utilized for verification, and a meta-analysis was performed to combine the results from the two datasets. Results: Forward MR analysis results showed that nine types of gut microbiota were statistically associated with PCOS (all P<0.05). Specifically, the association of family Streptococcaceae (OR=1.442, 95%CI: 1.097-1.895), genus Actinomyces (OR=1.359, 95%CI: 1.036-1.784), genus Ruminococcaceae UCG 011 (OR=0.755, 95%CI: 0.619-0.921), genus Sellimonas (OR=0.766, 95%CI: 0.657-0.893) and genus Streptococcus with PCOS (OR=1.496, 95%CI: 1.136-1.972) remained consistent in the sensitivity analysis. Reverse MR analysis showed no evidence for the causal association between PCOS and the aforementioned five types of gut microbiota (all P>0.05). The MR analysis results of the validation set showed that there was no statistical association between the aforementioned five types of gut microbiota and PCOS (all P>0.05). However, the associations remained significant for genus Actinomyces (OR=1.226,95%CI：1.010-1.503) and genus Streptococcus (OR=1.266,95%CI：1.042-1.452) in the meta-analysis (both P<0.05). Conclusion This study provides the evidence that genus Actinomyces and genus Streptococcus are causally associated with PCOS.

Objective: To examine the association between sleep and frailty using the bidirectional two-sample Mendelian randomization (MR) approach, so as to provide the basis for the prevention and intervention of frailty. Methods: The data on single nucleotide polymorphisms (SNP) related to sleep duration, insomnia and morning chronotype were collected from genome-wide association studies (GWAS) and meta-analysis of GWAS, involving 446 118, 1 331 010 and 697 828 participants, respectively. The frailty was evaluated using the frailty index, and the relevant SNP data were collected from a meta-analysis of GWAS involving 175 226 participants. A bidirectional MR analysis was performed using the inverse-variance weighted method. Sensitivity analyses employed the weighted median method, the maximum likelihood-based method, the MR-Egger regression, and the MR-PRESSO test. Results: Forward MR analysis showed that longer sleep duration (β=-0.170, 95%CI: -0.255 to -0.085) and morning chronotype (β=-0.036, 95%CI: -0.058 to -0.014) decreased the risk of frailty, while insomnia increased the risk of frailty (β=0.167, 95%CI: 0.149-0.184). Reverse MR analysis showed that frailty increased the risk of insomnia (OR=1.645, 95%CI: 1.278-2.117). Both bidirectional MR results were robust, which excluded the impact of heterogeneity and horizontal pleiotropy. Conclusion Sleep duration, insomnia, and morning chronotype are associated with frailty.