Objective:To investigate the relationship between body mass index(BMI) and osteoporosis using Mendelian randomization analysis.Methods:The genetic variation strongly related to BMI was selected as the instrumental variables in the collection data set of the genome-wide association study(GWAS). The MR-Egger regression, weighted median estimator(WME), inverse variance weighted(IVW), simple mode and weighted mode were used for Mendelian randomization(MR) analysis. The causal association between BMI and osteoporosis was evaluated by odds ratio and 95% confidence interval. The MR-APSS method was applied to make the causal inference results based on MR more reliable. The Linkage disequilibrium score regression was applied to evaluate the genetic correlation, and the horizontal pleiotropy test, heterogeneity test, and leave-one-out method were used to evaluate whether the results were reliable, The influence of heterogeneity and horizontal pleiotropy were reduced by the MR-PRESSO outlier test.Results:A total of 421 SNPs were included, with inverse variance-weighted method as the main analysis approach. The calculated OR value and 95% CI were 0.994(95% CI 0.992-0.997), indicating a protective effect of BMI on osteoporosis. The MR-APSS method showed that the effect of BMI on osteoporosis was statistically significant. Linkage disequilibrium score regression demonstrated a genetic correlation between BMI and osteoporosis. MR-Egger regression intercept showed no horizontal pleiotropy of instrumental variables, and the funnel plot showed no bias in instrumental variables. Leave-one-out analysis confirmed robust results. Conclusion:There may be a negative causal relationship between BMI and osteoporosis and BMI is a protective factor for osteoporosis.

Background::Limited information exists regarding the impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on psoriasis patients. The objective of this study was to identify clinical factors associated with the prognosis of psoriasis following SARS-CoV-2 infection.Methods::A retrospective, multicenter study was conducted between March and May 2023. Univariable and multivariable logistic regression analyses were employed to identify factors associated with coronavirus disease 2019 (COVID-19)-related psoriasis outcomes. The study included 2371 psoriasis patients from 12 clinical centers, with 2049 of them having been infected with SARS-CoV-2.Results::Among the infected groups, lower exacerbation rates were observed in individuals treated with biologics compared to those receiving traditional systemic or nonsystemic treatments (22.3% [236/1058] vs. 39.8% [92/231] vs. 37.5% [140/373], P <0.001). Psoriasis progression with lesions (adjusted odds ratio [OR] = 8.197, 95% confidence interval [95% CI] = 5.685–11.820, compared to no lesions), hypertension (adjusted OR = 1.582, 95% CI = 1.068–2.343), traditional systemic (adjusted OR = 1.887, 95% CI= 1.263–2.818), and nonsystemic treatment (adjusted OR= 1.602, 95% CI= 1.117–2.297) were found to be associated with exacerbation of psoriasis after SARS-CoV-2 infection, but not biologics (adjusted OR = 0.931, 95% CI = 0.680–1.274, compared to no treatment), according to multivariable logistic regression analysis. Conclusions::A reduced risk of psoriasis exacerbation after SARS-CoV-2 infection was observed with biologics compared to traditional systemic and nonsystemic treatments. Significant risk factors for exacerbation after infection were identified as existing psoriatic lesions and hypertension.

Objective:To investigate the differences in programmed death-ligand 1 (PD-L1) expression and immune cell infiltration characteristics in different molecular subtypes of endometrial cancer.Methods:A retrospective case series study was conducted. Ninety primary treated EC patients who underwent surgery without preoperative neoadjuvant therapy at the Second Hospital of Tianjin Medical University from November 2016 to May 2022 were collected. The surgical paraffin-embedded tissues were selected, and the molecular subtypes of endometrial cancer were classified according to 2020 World Health Organization (WHO) molecular subtypes using POLE gene Sanger sequencing and immunohistochemical staining. The expression of PD-L1, CD3, CD4, CD8, CD68, and CD20 proteins were detected by immunohistochemistry. Stained slides were digitally scanned for quantitative analysis of PD-L1 and immune cell infiltration density. The PD-L1-related scores were evaluated, including tumor cell score (TCS, the percentage of PD-L1 positive tumor cells among total tumor cells ≥1% was TCS positive, <1% was TCS negative), immune cell score (ICS, the percentage of PD-L1 positive tumor-associated lymphocytes and macrophages among total tumor-associated lymphocytes and macrophages ≥1% was ICS positive, <1% was ICS negative) and combined positive score [CPS, PD-L1 positive stained cells (including tumor cells, lymphocytes and macrophages)/total number of viable tumor cells ×100 ≥ 1 was CPS positive, < 1 was CPS negative]. Clinicopathological characteristics, PD-L1 scores and immune cell infiltration densities among different molecular subtypes were analyzed. Kaplan-Meier method was used to plot disease-free survival (DFS) curves for molecular subtypes, PD-L1 scores and immune cell infiltration densities, with subgroup comparisons using log-rank test. Cox proportional hazards models were used for univariate and multivariate analyses of poor DFS in endometrial cancer patients.Results:The median age of 90 patients was 58 years old (range: 33-72 years old); endometrioid carcinoma was present in 78 cases (86.7%), and non-endometrioid carcinoma was present in 12 cases (13.3%). Molecular subtyping identified POLE-mutated subtype in 6 cases (6.7%), mismatch repair deficient (MMRd) subtype in 23 cases (25.6%), p53 abnormal subtype in 14 cases (15.6%), and non-specific molecular profile (NSMP) subtype in 47 cases (52.2%). Significant differences were observed among the 4 molecular subtypes in International Federation of Gynecology and Obstetrics (FIGO) stage, histological grade, morphological subtype, tertiary lymphoid structures, estrogen receptor expression, and progesterone receptor expression (all P < 0.05). Among the 90 cases, 18 cases (20.0%) were positive for TCS, 31 cases (34.4%) were positive for ICS, and 39 cases (43.3%) were positive for CPS. Significant differences were found among the 4 molecular subtypes in PD-L1 + cell density, distribution of patients with ICS positivity, and distribution of patients with CPS positivity (all P < 0.01), but not in distribution of patients with TCS positivity ( P = 0.090); compared to NSMP subtype, the proportions of ICS-positive patients in POLE-mutated and MMRd subtypes were higher, the proportion of CPS-positive patients and PD-L1 + cell density in MMRd and p53 abnormal subtypes were higher, and the differences were statistically significant (all P < 0.05). Significant differences in immune cell densities were observed among the 4 molecular subtypes (all P < 0.01); compared to NSMP subtype, POLE-mutated, MMRd and p53 abnormal subtypes had higher densities of CD3 + and CD8 + cells, MMRd subtype had higher CD4 + cell density, and POLE-mutated and MMRd subtypes had higher CD68 + and CD20 + cell densities (all P < 0.05). The median follow-up was 43 months (range: 7-75 months). Among the molecular subtypes, p53 abnormal patients had the worst DFS, and POLE-mutated patients had the best DFS, and the difference in DFS among the 4 subtypes was statistically significant ( P = 0.046). Grouping according to the median density of immune cells in the entire group, patients with high CD8 + cell density (45 cases) had better DFS than those with low density (45 cases) ( P = 0.010), PD-L1 ICS-positive patients had worse DFS than negative patients ( P = 0.019), and NSMP subtype patients with high CD4 + cell density (24 cases) had better DFS than those with low density (23 cases) ( P < 0.001). There was no statistically significant difference in DFS among patients grouping with other PD-L1 scoring modes and other immune cell infiltration density (all P > 0.05). Cox regression analysis indicated that high CD8 + cell density ( HR = 0.335, 95% CI: 0.113-0.990, P = 0.048) was an independent protective factor for poor DFS in endometrial cancer patients, and high CD4 + cell density was an independent protective factor for poor DFS in NSMP subtype patients ( HR = 0.035, 95% CI: 0.003-0.345, P = 0.004). Conclusions:There are significant differences in PD-L1 expression and immune cell infiltration density among the different molecular subtypes of endometrial cancer, which are correlated with the prognosis of patients, and may provide reference for the selection of immunotherapy strategies and prognosis judgment.

Objective:To evaluate the role of miR-124-3p in reduction of oxygen-glucose deprivation and restoration (OGD/R) injury by electrostimulation preconditioning in microglia and its relationship with microglial polarization.Methods:The well-growing BV2 cells were divided into 4 groups ( n=30 each) by the random number table method: control group (group C), OGD/R group, electrostimulation preconditioning group (group E) and miR-124-3p inhibitor group (group I). Group C was cultured under normal conditions, and group OGD/R was deprived of oxygen and glucose for 2 h followed by restoration of oxygen and glucose supply for 24 h to develop the OGD/R injury model. In group E, cells were stimulated with 100 mV/mm direct current for 4 h before oxygen-glucose deprivation, and the other treatments were similar to those previously described in group OGD/R. Group I was transfected with micrOFF? mmu-miR-124-3p inhibitor at 48 h before oxygen-glucose deprivation, and the other treatments were similar to those previously described in group E. The cell survival rate was determined by CCK-8 assay, the concentrations of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and IL-10 in the cell supernatant were measured by enzyme-linked immunosorbent assay. The expression of a surface marker of M1 microglia inducible nitric oxide synthase (iNOS) and a surface marker of M2 microglia arginase 1 (Arg-1) was detected by immunofluorescence and Western blot, respectively. The expression of iNOS and Arg-1 mRNA and miR-124-3p was detected by quantitative polymerase chain reaction. Results:Compared with group C, the cell survival rate was significantly decreased, the concentrations of TNF-α, IL-1β and IL-10 in the supernatant were increased, and the expression of iNOS and Arg-1 protein and mRNA and miR-124-3p was up-regulated in the remaining three groups ( P<0.05). Compared with group OGD/R, the cell survival rate was significantly increased, the concentrations of TNF-α and IL-1β in the supernatant were decreased, the IL-10 concentration was increased, the expression of iNOS protein and mRNA was down-regulated, and the expression of Arg-1 protein and mRNA and miR-124-3p was up-regulated in E and I groups ( P<0.05). Compared with group E, the cell survival rate was significantly decreased, the concentrations of TNF-α and IL-1β in the supernatant were increased, the IL-10 concentration was decreased, the expression of iNOS protein and mRNA was up-regulated, and the expression of Arg-1 protein and mRNA and miR-124-3p was down-regulated in group I ( P<0.05). Conclusions:The mechanism by which electrostimulation preconditioning reduces OGD/R injury in microglia is related to up-regulation of the expression of miR-124-3p, promotion of M2 microglia polarization, inhibition of M1 microglia polarization, and thus inhibiting the inflammatory responses.

Objective:To analyze the non-enterovirus A71 (non-EVA71) and non-coxsackievirus A16 (non-CVA16) enteroviruses causing hand, foot and mouth disease (HFMD) in Kunming and Qujing of Yunnan Province in 2021 by sequencing the VP4/VP2 and VP1 genes and to analyze the phylogenetic characteristics of the VP1 gene of CVA2, aiming to provide reference for the prevention and control of CVA2.Methods:The samples were made and extracted strictly according to the Laboratory Manual for Hand, Foot and Mouth Disease (China Center for Disease Control and Prevention, 2018 Edition). VP4/VP2 junction regions were firstly amplified and sequenced by MD91/OL68-1 primers. These sequences were firstly edited and then "blasted" on the GenBank to determine the virus serotype. To analyze the phylogenetic characteristics of CVA2, the entire VP1 gene sequences were amplified in two segments using enterovirus species A primers. Virus serotype was again confirmed online by "Enterovirus Genotyping Tool Version 0.1". The sequences of the reference virus genotypes/sub-genotypes were downloaded according to the reference. The phylogenetic trees were constructed by Mega5.2 software and the genetic characteristics were analyzed.Results:A total of 749 non-EVA71 and non-CVA16 enteroviruses were detected in the two areas in 2021. Group A enteroviruses were the main pathogens, with CVA16 as the predominant virus, and a small number of group B enteroviruses were reported. Only five strains of CVA2 were detected with a detection rate of 0.67% (5/749), indicating that CVA2 was a rare pathogen for HFMD in the two areas. The sequencing and serotyping results were consistent using the two genomic regions of VP4/VP2 junction region and VP1 region. Phylogenetic analysis showed that three Kunming strains belonged to genotype A, while two Qujing strains belonged to genotype D.Conclusions:The detection rate of CVA2 in Kunming and Qujing was 0.67% in 2021. CVA2 was a rare pathogen for HFMD in the two regions. Phylogenetic analysis showed genotypes A and D spread in Kunming and Qujing, respectively, but had not caused epidemics. To our knowledge, this was the first report of genotype A of CVA2 in China. Strengthening the laboratory surveillance especially molecular epidemiological surveillance is valuable for the monitor and analysis of transmission source for CVA2.

Salivary gland cancer includes a group of heterogeneous malignant tumors. The latest WHO classification of head and neck tumors divides salivary gland cancer into 22 histopathological subtypes. The most common clinical subtypes include mucoepidermoid carcinoma, adenoid cystic carcinoma, salivary duct carcinoma, acinar cell carcinoma and secretory carcinoma, etc. The histomorphology of the subtypes of salivary gland cancer overlaps, making diagnosis and differential diagnosis difficult. The main treatment for salivary gland cancer is tumor resection and postoperative radiotherapy as appropriate. Even in cases of local progression, recurrence and metastasis, the treatment options available are limited, mainly palliative treatment. Accurate determination of tumor receptor expression, genome and pathway changes is the key to changing the prognosis of patients with local progression or distant metastasis. In this paper, the known genetic mutations, amplifications and protein expression profiles of common salivary gland cancer histological subtypes was summarized, and the significance of the above-mentioned molecular genetic changes for disease diagnosis, future research and personalized targeted therapy was analyzed.

Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic inflammation and aggressive arthritis. The basic pathological changes of RA include intra-articular hyperplasia synovitis and extra-articular vasculitis, symmetrical joint cavity effusion and stenosis, and the formation of pannus leading to the destruction of articular cartilage or joint accessory structures. In the course of RA, swelling and pain of the affected joints occur, causing joint deformities, joint stiffness, and joint dysfunction, and eventually disability. In recent years, significant progress has been made in the study of the relationship between nerve growth factor (NGF) and RA immunopathology. The results of existing studies have shown that the level of NGF in the synovial fluid of RA patients is elevated, suggesting that NGF plays an important role in immune inflammation-mediated pain behavior. In addition, nerve growth factor precursors (including proNGF and proBDNF, etc.) can promote cell apoptosis and inflammation. Among them, the levels of proBDNF and its receptors have significant changes in the blood of RA patients. Therefore, it can be inferred that proNGF and proBDNF may become new targets for RA treatment. According to the latest international domestic research results, in this paper the research progress of NGF and RA in immunopathology, immune inflammatory response, pain behavior, etc. were briefly introduced, and the potential application value of NGF in the treatment of RA was summarized.

Objective To explore the qualitative evaluation of contrast-enhanced ultrasound (CEUS) in the differential diagnosis between benign and malignant thyroid nodules (TNs).Methods Totally 110 outpatients with 132 TNs underwent CEUS were enrolled in this study in Jinling Hospitall Medical School of Nanjing University (Nanjing General Hospital of Nanjing Military).Nanjing General Hospital of Nanjing Military All the nodules underwent ultrasound guided fine needle aspiration biopsy (FNAB).113 TNs were histologically diagnosed,the characteristics of enhancement for each noudle were scored.The characteristicsof enhancement between benign and malignant TNs were compared by chi-square test.The receiver operating characteristic (ROC) curve analysis were conducted to determine the diagnostic values of thyroid CEUS.Results Contrast-enhanced patterns were significantly different between benign and malignant TNs in the degree,homogeneity of enhancement,enhanced ring and boundary,shape and size of the enhanced lesions (x2=23.85,P ＜ 0.001;x2=7.43,P=0.04;x2=34.54,P ＜ 0.001;x2=25.7,P ＜ 0.001;x2=53.10,P ＜ 0.001;x2=22.78,P ＜ 0.001;x2=30.90,P ＜ 0.001).Contrast-enhanced patterns were not significantly different between benign and malignant TNs in the process and completeness of enhancement.Malignant lesions had concentric (79.5％),inhomogeneous (89.0％) and low (71.1％) enhanced with irregular (79.5％) and unclear (64.4％) boundary and bigger size (63.0％).The typical CEUS feature of benign nodules was peripheral ring hyperenhancement (34.7％).According to ROC curve,the cut off value was 3.5 points.The area under the ROC curve (AUC) for CEUS was 0.862 (95％CI:0.797-0.927).The sensitivity,specificity and accuracy for CEUS were 80.8％,79.6％,80.3％ respectively.Conclusion The pattem of CEUS may assist in differential diagnosis of benign and malignant TNs.

Objective The extensive use of high-resolution thyroid ultrasonography has markedly improved the detection rate of thyroid nodules ( TNs) .However, the ultrasonographic features of benign and malignant TNs usually overlap and have yet to be de-fined.This study aimed to investigate the ultrasonographic features and risk factors of malignant TNs by comparing their ultrasonograph-ic manifestations with those of benign TNs. Methods A total of 119 TNs (63 benign and 56 malignant) in 64 patients were includ-ed in this retrospective study.The gender, age, location of the TNs, and other variables were subjected to univariate analysis, the risk factors of malignant TNs were screened by multivariate logistic regression analysis, and the predictive value of the logistic regression model was assessed using the ROC curve. Results Multivariate logistic regression analysis indicated that the risk factors of malig-nant TNs in ultrasonography were irregular shape (OR:6.166, 95%CI:1.681-22.617), micro calcification (OR:3.593, 95%CI:1.800-7.169), and A/T ratio≥1 (OR:17.577, 95%CI:1.739-166.468).ROC curve analysis showed the area under the curve (AUC) to be 0.922 (95%CI:0.868-0.976). Conclusion Such ultrasonographic manifestations as irregular shape, micro-calcification, and A/T ratio≥1 are valuable in identifying the nature of TNs.

Objective The increased use of high-resolution ultrasound (US) for thyroid disease has markedly increased the detection rate of nonpalpable thyroid nodules .The objective of this study was to investigate the diagnostic value of conventional ultrasonography, ultrasonic elastography(UE) and combined application of both in the differential diagnosis of thyroid nodules. Methods A retrospective analysis was made on 105 patients with 160 histologically proved thyroid nodules from September 2014 and August 2015 in our hospital.The receiver operating characteristic ( ROC) curve analysis was made on Thyroid Imaging Repor-ting and Data System ( TI-RADS) score, elastography score and the score of combined application.The area under curve ( AUC) was calculated and compared to select the best cut-off value in order to work out the respective diagnostic efficacy of 3 methods and Kappa consistence check with pathologic results . Results In ROC curve analysis, AUC of combination score(0.930, 95%CI:0.890-0.969) was higher than those of TI-RADS score(0.855, 95%CI:0.794-0.915) and elasticity score(0.845, 95%CI:0.780-0.909), and the difference was statistically significant (Z=2.20, 2.03, P<0.05) .Taking TI-RADS score≥4, elastography score≥3, and combination score≥7 as the limitation to diagnose ma-lignant thyroid nodules, the specificity and PPV of combination score(94.3%, 95%CI:0.867-0.979;91.7%, 95%CI:0.809-0.969) were higher than those of TI-RADS score(78.4%, 95%CI:0.681-0.862;84.7%, 95%CI:0.692-0.886) and e-lasticity score(81.8%, 95%CI:0.719-0.889;78.7%,95%CI:0.674-0.870).Kappa value of combination score(0.718, 95%CI:0.610-0.826) was higher than that of TI-RADS score(0.586, 95%CI:0.461-0.711) and elasticity score(0.635, 95%CI:0.515-0.755). Conclusion Conventional ultrasonography and UE are mutual complementation, and the application of conventional ultrasonography combined with UE has higher value than single examination in the differential diagnosis of thyroid nodules.