Objective: To analyze epidemiological trends and changing characteristics of syphilis among students in Yunnan Province from 2005 to 2023, so as to provide evidence for the comprehensive prevention and control of syphilis in schools. Methods: The case data of syphilis among students in Yunnan Province from 2005 to 2023 were obtained from the China Information System for Disease Control and Prevention. The Joinpoint regression model was used to conduct a time trend analysis of the reported incidence rate of syphilis. Results: From 2005 to 2023, a cumulative total of 3 191 cases of syphilis were reported in schools in Yunnan Province(1 248 male cases and 1 943 female cases). The reported incidence rate rose continuously from 0.17/100 000 in 2005 to 8.26/100 000 in 2023, with an average annual percent change (AAPC) of 24.89%( Z =13.18, P <0.01). The reported incidence rate was higher in female students than in male students ( χ 2=229.48, P <0.05). The incidence rates in the primary school, junior high school, senior high school and higher education were 0.21/100 000, 2.42/100 000, 4.45/100 000 and 6.29/100 000 respectively, and the difference was statistically significant (χ 2=3 432.84, P <0.05). The average annual growth rate was the highest in the junior high school stage(AAPC= 30.68% , Z =7.57, P <0.05),followed by the senior high school stage (AAPC=24.28%, Z = 5.70 , P <0.05).The reported incidence rate of primary and secondary syphilis increased from 0.12/100 000 in 2005 to 2.06/ 100 000 in 2023, with an AAPC of 16.86% ( Z = 4.57, P <0.05). Conclusions The overall reported incidence rate of syphilis among students in schools in Yunnan Province shows a sustained upward trend, with the most rapid annual increase observed in junior high schools. Schools should prioritize syphilis education and expand awareness campaigns to curb transmission.

Objective To investigate the effect of basic helix-loop-helix family member E40 (BHLHE40) on the invasion and migration of osteosarcoma (OS) cells, and to explore the role of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway in the biological behavior of OS mediated by BHLHE40, providing a scientific basis for targeted therapy of OS. Methods On the basis of clinical OS samples and OS cell lines, the expression differences of BHLHE40 between OS and adjacent tissues, as well as those between OS cells and normal osteoblast cell lines, were analyzed. BHLHE40 knockdown OS cells were obtained through shRNA transfection. The effects of BHLHE40 on OS cell proliferation, migration, and invasion were examined using CCK-8, EdU staining, wound healing, and Transwell assays. The involvement of the PI3K/AKT signaling pathway was assessed by Western blotting. Further validation was conducted in vivo experiments. Results The expression of BHLHE40 was significantly higher in OS tissues compared to adjacent tissues. In OS cell lines, BHLHE40 protein expression levels were increased compared to normal osteoblasts, and the cell line with the highest BHLHE40 expression was selected for subsequent knockdown experiments. Compared with the knockdown control group, the BHLHE40 knockdown group exhibited reduced cell viability, EdU-positive cell count, colony number, cell migration, and invasion abilities, along with downregulation of phosphorylated PI3K(p-PI3K)/PI3K and p-AKT/AKT protein expression. The aforementioned functions of BHLHE40 were also reproduced in in vivo experiments. Conclusion BHLHE40 is highly expressed in OS tissues, and its knockdown can significantly inhibit OS cell proliferation, migration, and invasion, while reducing PI3K/AKT signaling pathway activity. This suggests that BHLHE40 could serve as a novel therapeutic target for OS.
Osteosarcoma/metabolism* ; Humans ; Proto-Oncogene Proteins c-akt/genetics* ; Cell Proliferation/genetics* ; Cell Movement/genetics* ; Signal Transduction/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Cell Line, Tumor ; Animals ; Neoplasm Invasiveness ; Basic Helix-Loop-Helix Transcription Factors/metabolism* ; Bone Neoplasms/metabolism* ; Mice ; Gene Knockdown Techniques ; Male ; Female ; Mice, Nude

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective: To determine the latent class of dietary patterns and their association with depressive symptoms among first grade students from multi ethnic middle schools in Yunnan Province, so as to provide a reference basis for promoting mental health among border middle school students. Methods: A cluster random sampling involving 8 500 first grade middle school students from 11 counties in Yunnan Province was conducted by a questionnaire survey between October to December 2022. The Children s Depression Inventory (CDI) was used to assess the depressive symptoms and the Food Frequency Questionnaire was used to collect eating behavior data. The latent profile analysis model was used to fit the latent class of dietary patterns among students. The association between the dietary pattern latent class and depressive symptoms was analyzed by Logistic regression. Results: The depressive symptom detection rate among firstgrade middle school students was 28.3%. Prevalence of depressive symptom in girls (30.9%) was higher than boys (25.5%) with a statistically significant difference ( χ 2=29.83, P <0.01). The dietary patterns among first grade middle school students were classified into four latent classes, as follows:class 1 (low consumption of all dietary components), class 2 (high consumption of fruit, milk and dairy products), class 3 (high consumption of vegetables and meat, and low consumption of processed foods) and class 4 (low consumption of milk, dairy products and eggs, and high consumption of processed foods). After adjusting for confounding variables, the class 3 dietary pattern was negatively correlated with depressive symptoms ( OR=0.62, 95%CI =0.52-0.74) and the class 4 dietary pattern was positively correlated with depressive symptoms ( OR= 1.28 , 95%CI =1.05-1.57) ( P <0.05), compared with the class 1 dietary pattern. Conclusions Multi ethnic first grade middle school students in Yunnan Province follow various dietary patterns. Unhealthy dietary patterns increase the risk of depressive symptoms. The dietary patterns of multi ethnic middle school students in Yunnan Province should be adjusted to promote the establishment of healthy dietary patterns and reduce the risk of depression symptoms in middle school students.

Objective To investigate the influencing factors of adverse pregnancy outcomes in patients with preeclampsia and the predictive value of serum trace elements in the second trimester.Methods A total of 98 patients with preeclampsia admitted to Qujing First People's Hospital from January 2019 to June 2022 were enrolled in the study.Patients were divided into poor outcome group and good outcome group according to whether they had adverse pregnancy outcomes.The clinical data of all patients enrolled in the study were col-lected and the serum levels of trace elements calcium,copper,zinc and iron were detected in the second trimes-ter.Univariate analysis and multivariate Logistic regression were used to analyze the influencing factors of ad-verse pregnancy outcomes in patients with preeclampsia.The levels of serum trace elements in the second tri-mester of pregnancy were compared between the poor outcome group and the good outcome group.The re-ceiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum trace elements calcium,copper,zinc and iron for adverse pregnancy outcomes in patients with preeclampsia.Results Univari-ate analysis showed that compared with the good outcome group,the poor outcome group had significantly higher systolic blood pressure,24 h urinary protein quantitation,and D-dimer level(P＜0.05)and significantly less gestational age and platelet count at admission(P＜0.05).Multivariate Logistic regression analysis showed that 24 h urinary protein quantification,D-dimer and platelet count were the influencing factors of ad-verse pregnancy outcomes in patients with preeclampsia(P＜0.05).The levels of serum trace elements calci-um,copper,and zinc in the poor outcome group were significantly lower than those in the good outcome group(P＜0.05),and the level of iron was significantly higher than that in the good outcome group(P＜0.05).ROC curve analysis showed that the areas under the curves(AUCs)of serum calcium,copper,zinc,and iron in the second trimester of pregnancy for predicting adverse pregnancy outcomes in preeclampsia patients were 0.830(95％CI:0.780-0.880),0.855(95％CI:0.805-0.905),0.847(0.797-0.897)and 0.861(95％CI:0.811-0.911),respectively.Conclusion Adverse pregnancy outcomes in patients with preeclampsia are re-lated to 24 h urine protein,D-dimer and platelet count.The levels of serum trace elements calcium,copper,zinc and iron in the second trimester of pregnancy change significantly in patients with adverse pregnancy out-comes,which may become predictive markers of adverse pregnancy outcomes.

Objective:To analyze the clinical features and genetic etiology of 17 Chinese pedigrees affected with X-linked intellectual disability (XLID).Methods:Seventeen pedigrees affected with unexplained intellectual disability which had presented at Henan Provincial People′s Hospital from May 2021 to May 2023 were selected as the study subjects. Clinical data of the probands and their pedigree members were collected. Trio-whole exome sequencing (Trio-WES), Sanger sequencing and X chromosome inactivation (XCI) analysis were carried out. Pathogenicity of candidate variants was predicted based on the guidelines from the American College of Medical Genetics and Genomics and co-segregation analysis.Results:The 17 probands, including 9 males and 8 females with an age ranging from 0.6 to 8 years old, had all shown mental retardation and developmental delay. Fourteen variants were detected by genetic testing, which included 4 pathogenic variants ( MECP2: c. 502C>T, MECP2: c. 916C>T/c.806delG, IQSEC2: c.1417G>T), 4 likely pathogenic variants ( MECP2: c. 1157_1197del/c.925C>T, KDM5C: c. 2128A>T, SLC6A8: c. 1631C>T) and 6 variants of uncertain significance ( KLHL15: c. 26G>C, PAK3: c. 970A>G/c.1520G>A, GRIA3: c. 2153C>G, TAF1: c. 2233T>G, HUWE1: c. 10301T>A). The PAK3: c.970A>G, GRIA3: c. 2153C>G and TAF1: c. 2233T>G variants were considered as the genetic etiology for pedigrees 12, 14 and 15 by co-segregation analysis, respectively. The proband of pedigree 13 was found to have non-random XCI (81: 19). Therefore, the PAK3: c. 1520G>A variant may underlie its pathogenesis. Conclusion:Trio-WES has attained genetic diagnosis for the 17 XLID pedigrees. Sanger sequencing and XCI assay can provide auxiliary tests for the diagnosis of XLID.

Objective:To explore the genetic etiology of a pedigree with intellectual disability and explore its pathogenesis.Methods:A Chinese pedigree which had presented at the Henan Provincial People′s Hospital in March 2023 was selected as the study subject. Clinical data of the pedigree were collected, along with peripheral venous blood samples from its members. Whole exome sequencing (WES) was carried out, and candidate variants were verified by Sanger sequencing. Amniotic fluid was collected for prenatal diagnosis. This study was approved by the Medical Ethics Committee of the Henan Provincial People′s Hospital (No. 2019-134).Results:Both the proband (a 6-year-old male) and his mother (30 years old) had various degrees of intellectual and motor impairment. WES revealed that the proband has harbored a de novo heterozygous c. 2563_2567dup (p.Lys856fs) variant of the UBE3A gene, while his mother, maternal grandmother and fetus had all harbored a novel heterozygous c. 409+ 1G>A variant of the RNF13 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS1+ PS1+ PM2_Supporting; PVS1+ PM2_Supporting+ PP3). Conclusion:Based on the clinical manifestations and the result of genetic testing, the heterozygous c.2563_2567dup (p.Lys856fs) variant of the UBE3A gene probably underlay the intellectual disability and developmental delay in the proband, whilst the heterozygous c. 409+ 1G>A variant of the RNF13 gene may underlie the intellectual disability in the proband′s mother and grandmother. Above results have enabled genetic counseling and prenatal diagnosis for this pedigree.

Objective To investigate the therapeutic effect and mechanism of NLRP3 inflammasome inhibitor-dapansutrile(OLT1177)-against acute radiation lung injury.Methods Mice were divided into the control group,OLT1177 injection group,irradiation group,and irradiation+OLT1177 injection group.A single dose of 22 Gy whole-lung 60Co radiation was used to establish a model of acute radiation lung injury.After 6 h of radiation,OLT1177(100mg/kg,once daily)was administered intraperitoneally.After 14 consecutive days of administration,lung tissues were collected and weighed while the lung coefficient was calculated.Hematoxylin-eosin(HE)staining and F4/80 immuno-histochemical staining were used to observe the pathological changes and inflammatory cell infiltration in lung tissues.Real-time quantitative PCR(qPCR)was used to detect the transcription levels of NLRP3,IL-1β,and other mRNAs in lung tissues.Serum cytokines such as TNF-α and IL-6 were measured by cytometric bead array(CBA).The activation of Caspase-1 and IL-18 was detected by Western blotting.Results Radiation caused acute inflammation in the lung tissues of mice,manifested as edema in the lung tissues and destruction of the alveolar structure,increased macrophage infiltration,and elevated expressions of inflammatory genes NLRP3,IL-1β,TNF-α,and IL-6 in the lung tissues and higher serum levels of TNF-α,IL-6.Treatment with OLT1177 significantly improved the above symptoms induced by radiation.OLT1177 inhibited the activation of NLRP3 inflammasome downstream Caspase-1 and IL-18 induced by radiation.Conclusion OLT1177 can significantly alleviate acute radiation lung injury in mice,which may be due to its inhibition of NLRP3 inflammasome activation induced by radiation.

Objective:To explore the application value of two-dimensional speckle tracking imaging (2D-STI) in evaluating diaphragm function, and to compare the ability of 2D-STI and conventional diaphragm ultrasonography in diagnosing diaphragmatic dysfunction and evaluating disease severity in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Methods:A total of 58 AECOPD patients admitted to the First Affiliated Hospital of Xi′an Jiaotong University from January to October 2021 were retrospectively enrolled as AECOPD group, and 34 healthy subjects were recruited as control group during the same period. Repeatability test of diaphragmatic 2D-STI was performed. According to modified Medical Research Council (mMRC) dyspnea scores system and COPD Assessment Test (CAT), mMRC 0-1 and CAT<10 was classified as group A, mMRC≥2 and CAT≥10 was classified as group B. The baseline characteristics, conventional diaphragm ultrasonography parameters(thickening fraction and excursion) and 2D-STI parameters (longitudinal and radial strains) were compared between the AECOPD group and the control group, and the Spearman correlation between parameters of AECOPD group and forced expiratory volume in one second (FEV1) was analyzed. The differences of these parameters between group A and B were also compared. The ROC curve of conventional diaphragm ultrasonography parameters and 2D-STI parameters was plotted to differentiate group A from group B, and the diagnostic efficacy was evaluated.Results:Great intra- and inter-observer reproducibility was found for all diaphragmatic 2D-STI parameters, with ICCs above 0.80 for all measurements. The control group and the AECOPD group did not differ in age, sex and body mass index( P>0.05), whereas there were significant differences in smoking history, lung function, bilateral thickening fraction, excursion, longitudinal and radial strains( P<0.05). Compared with control group, patients in group A had a significant increase in diaphragm thickness ( P<0.05), while there was no significant difference in that between group B and control group ( P>0.05). The bilateral longitudinal strains, radial strains and thickening fraction of diaphragm were linearly correlated with FEV1 (right side rs=0.828, 0.794, 0.843, respectively; all P<0.001; left side rs=0.757, 0.704, 0.752, respectively; all P<0.001 ), while the correlation between excursion and FEV1 was not significant(right side rs=0.247, left side rs=0.253; all P>0.05). There were significant differences in bilateral longitudinal strains, radial strains and thickening fraction between group A and group B(all P<0.05), whereas there was no significant difference in excursion between the two groups ( P>0.05). ROC analysis showed bilateral longitudinal and radial strains had higher accuracy in distinguishing group A from group B than thickening fraction and excursion(right side AUCs 0.90, 0.84, 0.78 and 0.62, respectively; left side AUCs 0.85, 0.83, 0.77 and 0.62, respectively). Conclusions:2D-STI is a real-time noninvasive technique for diaphragm function assessment, which has high clinical value. Compared with conventional ultrasonography, 2D-STI shows more accuracy and effectiveness in diagnosing diaphragmatic dysfunction and evaluating disease severity of patients with AECOPD.

After the promulgation and implementation of the Vaccine Administration Law of the People’s Republic of China， the compensation of suspected adverse reactions in China is to be reformed and innovated. There have been attempts at compensation through government finance and insurance， but there has been no precedent for a fund of vaccine-related compensation in China， which means that this could be a new method of solving disputes of compensation for vaccine-related incidences and enhancing public confidence in vaccination. It is suggested that under the current system， we can select a province as a pilot to explore the fund compensation mechanism. The fund comes from special financial allocation， special taxation of vaccine enterprises， fund investment income， charitable donation and other channels. Through a special fund management organization， the independent identification and compensation process can be realized， so as to shorten the current compensation procedure， improve the amount of compensation， ultimately protect the interests of all parties， and promote the steady development of vaccination.