Objective: To investigate the relationship between pubertal timing and depressive symptoms among high school students in Suzhou, so as to provide scientific evidence for promoting adolescents mental health. Methods: From October 2023 to January 2024, 3 369 students were selected from 20 high schools in Suzhou using stratified cluster random sampling method. Physical examinations and questionnaire surveys were conducted. The Preece & Baines growth Model 1 was used to calculate the age at take off of height velocity (ATO) and age at peak height velocity (APHV), categorizing students into three groups: early pubertal timing group (< P 15 ), ontime group ( P 15 - P 85 ), and delayed group (> P 85 ). Binary Logistic regression was used to analyze its association with depressive symptoms. Results: The ATO for male and female high school students in Suzhou was (9.35±1.23) and ( 8.12 ±1.52) years old, respectively. The mean APHV was (12.35±0.74) years old for boys and (10.91±0.82) years old for girls. The overall prevalence of depressive symptoms was 34.22%, with no statistically significant gender difference ( χ 2=0.42, P =0.52). Significant differences in depressive symptom prevalence were observed across grade levels, breakfast frequency, weekly days of moderate to vigorous physical activity, daily sleep duration, history of school bullying, and the presence of Internet addiction ( χ 2=5.03-69.21, all P < 0.05 ). After adjusting for age, body mass index, region, boarding status, breakfast frequency, weekly moderate to vigorous physical activity days, sleep duration, campus bullying, and presence of Internet addiction, Logistic regression analysis revealed that when ATO was used to evaluate pubertal timing, the risk of depressive symptoms in the delayed group of boys was 1.65 times that of the on time group (95% CI =1.24-2.19); when APHV was used to evaluate pubertal timing, the risks of depressive symptoms in the early pubertal timing group and delayed group of boys were 1.43 times (95% CI =1.07-1.91) and 1.41 times (95% CI =1.05-1.88) of that of the on time group, respectively (all P <0.05). No statistically significant associations were found among females (all P > 0.05 ). Conclusion The prevalence of depressive symptoms among high school students in Suzhou is relatively high, and both early and delayed puberty timing in boys are associated with depressive symptoms.

Objective: To analyze the changes in classroom lighting environment of schools in Suzhou and their impact on refractive progression among primary and secondary school students, so as to provide the basis for accurate provention and control of myopia. Methods: A baseline investigation was conducted in October 2022 by using a stratified cluster random sampling method to recruit primary and secondary school students from Suzhou. A follow up visit was performed in October 2023. A total of 12 302 students and 360 classrooms that participated in both surveys were included analysis. The visual acuity progression over one year and classroom lighting conditions were assessed. Group comparisons were performed by using the Wilcoxon or Kruskal-Wallis rank-sum, and Chi-square tests. Multivariate Logistic regression was employed to identify the major factors influencing refractive changes. Results: The compliance rate of average illuminance on classroom blackboard surface increased from 72.22% to 75.28%, while the compliance rate of average illuminance on desks decreased from 89.44% to 87.22%, the overall myopia rate among students rose from 59.63% to 66.99% from 2022 to 2023. The average annual progression of equivalent spherical power(SE) in the right eye of students was -0.25(-0.75,0.06)D. Significant statistical differences were observed in the annual mean changes across different school levels, regions, baseline refractive statuses, and classroom lighting environment change groups ( Z/H =316.59, -8.27, 38.80 , 51.01, all P <0.05). Multivariate Logistic regression analysis showed that pre myopia, low myopia, junior high school, senior high school, vocational high school, and improved classroom lighting environment were protective factors of reducing the risk of rapid progression in refractive error ( OR =0.58, 0.69, 0.81, 0.50, 0.28, 0.82, all P <0.05). Conversely, female students and rural students had higher risks of rapid myopia progression ( OR =1.09, 1.42, both P <0.05). Conclusions Over one year follow up, the complance rate of classroom lighting indicators in Suzhou remaines stable, while students refractive status shows a trend toward myopia. Improving classroom lighting environment can reduce the risk of rapid myopia progression.

Vascular calcification is a highly regulated process of ectopic calcification in cardiovascular system while no effective intervention can be clinically performed up to date.As vascular calcification undergoes a common regulatory mechanism within bone formation,bone morphogenetic protein 7(BMP-7)main-tains contractile phenotype of vascular smooth muscle cells and further inhibits vascular calcification via promoting the process of osteoblast differentiation,reducing ectopic calcification pressure by increasing bone formation and reducing bone resorption.This work systematically reviews the role of BMP-7 in vascular calcifi-cation and the possible mechanism,and their current clinical application as well.The current proceedings may help develope early diagnostic strategy and therapeutic treatment with BMP-7 as a new molecular marker and potential drug target.The expec-tation could achieve early prevention and intervention of vascular calcification and improve poor prognosis on patients.

Aim To investigate the effect and role of neuronal restriction silencing factor(REST/NRSF)in epilepsy disorder.Methods Immunohistochemistry,immunofluorescence,Western blot and qPCR tech-niques were used to detect REST/NRSF expression levels in hippocampal tissues of mice induced by kainic acid and human brain tissue.Viral injections,EEG re-cordings and behavioral methods were used to test the effects on epileptic mice after knockdown and overex-pression of REST/NRSF in the hippocampal CA1 re-gion,respectively.Results The positive rate of REST/NRSF in the lesions of epileptic patients was significantly higher compared with that in the control group.The levels of REST/NRSF protein and mRNA in the CA1 region of the hippocampus of mice in the KA model group were significantly higher.Kv7.2 and Kv7.3 potassium channel mRNA expression levels were significantly down-regulated.Significant up-regu-lation of REST/NRSF expression levels was observed in mouse hippocampus after NMDA injection.Knock-down of REST/NRSF in the CA1 region of hippocam-pus significantly elevated the expression levels of Kv7.2 and Kv7.3 potassium channel mRNAs.The fre-quency of EEG spiking and sharp-wave issuance and epileptic seizure grade were significantly lower.Over-expression of REST/NRSF in the CA1 region of hippo-campus significantly reduced the mRNA expression lev-els of Kv7.2 and Kv7.3 potassium channels.The fre-quency of EEG spiking and sharp-wave issuance was significantly higher and epileptic symptoms were exac-erbated.Conclusion REST/NRSF in mouse hipp-ocampal brain regions is involved in epileptic disease development through transcriptional regulation of Kv7.2 and Kv7.3 potassium channels.

Flavonoids are a class of compounds with a variety of biological activities widely found in nature,mainly including an-tioxidant,anti-inflammatory,antibacterial,anti-tumor,anti-al-lergic,hypoglycemic,cardiovascular protection and other phar-macological effects.In recent years,the anti-neuroinflammatory effects of flavonoids have received widespread attention,and studies have found that they can improve neuroinflammation and exert neuroprotective effects through multiple pathways and chan-nels.Neuroinflammation,as one of the important etiological and predisposing factors of neurodegenerative diseases,suppression of neuroinflammation is considered an important tool for the pre-vention and treatment of neurodegenerative diseases.This paper reviews the relationship between neuroinflammation and neurode-generative diseases,and summarizes the possible mechanisms of action of flavonoids intervening in neuroinflammation to treat neurodegenerative diseases,with a view to providing references for further basic research on flavonoid components and new re-search ideas and methods for the development of drugs for the treatment of neurodegenerative diseases.

Objective:To investigate the role of serum adenosine deaminase(ADA)combined with globulin(GLB),creatinine(CREA),β2-microglobulin(β2-MG)and hemoglobin(HGB)in the initial screening of multiple myeloma(MM),in order to reduce missed diagnosis and misdiagnosis of MM.Methods:A retrospective analysis was performed on 62 newly diagnosed multiple myeloma(NDMM)patients who were admitted to the Department of Hematology of the First Affiliated Hospital of Chengdu Medical College from April 2018 to December 2021,and 33 patients with benign hematologic diseases and 30 healthy subjects were selected as the control group.The expression of ADA in pan-cancer was analyzed using TCGA and GTEx databases.The general data and laboratory indicators of the subjects were collected,and the differences of ADA activity and other laboratory indicators in each group were compared.The relationship between serum ADA activity and clinical data of NDMM patients was analyzed.The changes of ADA activity before and after chemotherapy in NDMM patients and the differences of ADA activity in NDMM patients with different DS and ISS stages were compared.Multivariate logistic regression was used to analyze the risk factors of NDMM.The receiver operating characteristic(ROC)curve was used to evaluate the diagnostic efficacy of ADA and other laboratory indicators in MM.Bioinformatics method was used to analyze the co-expression networks and enrichment pathways of ADA.Results:ADA level was significantly upregulated in tissues of 14 types of cancer in TCGA database,and ADA was highly expressed in 11 types of cancer in TCGA combined with GTEx databases.The serum levels of ADA,GLB,uric acid(UA),cystatin C(CysC)and β2-MG in the NDMM group were significantly higher than those in benign hematologic disease group and healthy control group(P＜0.05),while the levels of ALB and the value of albumin to globulin ratio(A:G)in the NDMM group were significantly lower than those in the other two groups(P＜0.001).There were significant differences in DS stage(P=0.036),ISS stage(P=0.019)and the levels of CREA(P=0.036),UA(P=0.034),β2-MG(P=0.019)in NDMM patients with different ADA activity levels.After primary chemotherapy,ADA activity and(32-MG concentration were decreased in NDMM patients(P＜0.01).The comparison results of patients in different stages showed that ADA activity of patients in DS stage I+11 was significantly lower than that of patients in DS stage Ⅲ(P＜0.05),and ADA activity of patiens in ISS stage Ⅰ+Ⅱ was significantly lower than that of patients in ISS stage Ⅲ(P＜0.01).Multivariate logistic regression analysis showed that increased GLB,increased ADA activity,increased CREA,increased β2-MG and decreased HGB were independent risk factors for NDMM.The area under the curve(AUC)of ADA in the diagnosis of MM was 0.847,and the AUC of ADA combined with GLB,CREA,(32-MG and HGB in the diagnosis of MM was 0.940.The results of co-expression network and enrichment pathway analysis showed that ADA bounded to 20 proteins and it was significantly associated with the metabolic pathways of purine,pyrimidine,nicotinate and nicotinamide.Conclusion:The detection of ADA activity in serum is of positive significance for the auxiliary diagnosis,therapeutic evaluation and monitoring the progress of NDMM patients.ADA combined with GLB,CREA,β2-MG and HGB can improve the detection rate of MM,and reduce missed diagnosis and misdiagnosis to a certain extent.

Objective:To screen interleukin(IL)-1β secretion-related membrane transporters by macrophage experiment in vitro and conventional knockout mice.Methods:THP-1 cell line was differentiated to obtain human THP-1-derived macrophages,and the primary macrophages were obtained from human peripheral blood.FVB wild-type mice with the same sex and age were used as the controls of MRP1 knockout mice.The macrophages in abdominal cavity and bone marrow of mice were cultivated.The cells were treated with ABCC1/MRP1,ABCG2/BCRP,ABCB1/P-gp,OATP1B1,and MATE transporter inhibitors,then stimulated by lipopolysaccharide and adenosine triphosphate.The secretion level of IL-iβ was detected by ELISA,Western blot,and immunofluorescence.Results:After inhibiting ABCC1/MRP1 transporter,the secretion of IL-1β decreased significantly,while inhibition of the other 4 transporters had no effect.In animal experiment,the level of IL-1 β secreted by macrophages in bone marrow of MRP1 knockout mice was significantly lower than control group(P＜0.05).Conclusion:ABCC1/MRP1 transporter is a newly discovered IL-1β secretion pathway,which is expected to become a new target for solving clinical problems such as cytokine release syndrome.

Objective:To investigate the effect of feeder layer cells expressing interleukin(IL)-21 on the amplification of NK cells in vitro.Methods:The K562 cell line with IL-21 expression on its membrane was constructed by electroporation,and co-cultured with NK cells after inactivation.The proliferation of NK cells was observed.The killing function of the amplified NK cells in vitro was evaluated by the lactate dehydrogenase(LDH)and interferon-γ(IFN-y)release assay.A colorectal cancer xenograft model in NOD/SCID mice was established,and a blank control group,a NK cell group and an amplified NK cell group were set up to detect the tumor killing effect of amplified NK cells in vivo.Results:K562 cells expressing IL-21 on the membrane were successfully constructed by electroporation.After co-culturing with K562 cells expressing IL-21 on the membrane for 17 days,the NK cells increased to 700 times,which showed an enhanced amplification ability compared with control group(P＜0.001).In the tumor cell killing experiment in vitro,there was no significant difference in the killing activity on tumor cells between NK cells and amplified NK cells,and there was also no significant difference in mice in vivo.Conclusion:K562 cells expressing IL-21 on the membrane can significantly increase the amplification ability of NK cells in vitro,but do not affect the killing function of NK cells in vitro and in vivo.It can be used for the subsequent large-scale production of NK cells in vitro.

Objective To investigate the correlation between aCAS and the location and volume of cerebral WMH in the elderly people.Methods A total of 188 elderly WMH patients admitted to our hospital from September 2022 to September 2023 were enrolled and divided into no or mild(stenosis≤49％,137 cases),moderate(50％-69％,25 cases),and severe aCAS groups(≥70％,26 cases)according to the degree of carotid stenosis.All of the patients underwent cranial MRI scanning to assess total,periventricular,deep,and juxtacortical WMH volumes.Univariate and multivariate generalized linear model analyses were used.Results The moderate and severe aCAS groups had significantly older age,larger proportions of coronary heart disease and smoking,and higher total,peri ventricular,and juxtacortical WMH volumes than the no or mild aCAS group,and the deep WMH in the severe aCAS group was higher than that in the no or mild aCAS group(P＜0.05).Multivariate generalized linear model analysis showed that both moderate and severe aCAS were independent risk factors for total WMH volume(OR=325.629,95％CI:24.255-4371.608;OR=51.088,95％CI:4.135-631.128),periventricular WMH volume(OR=27.655,95％CI:5.168-147.976;OR=8.988,95％CI:1.754-46.051),deep WMH volume(OR=3.641,95％CI:1.511-8.774;OR=2.589,95％CI:1.105-6.064)and juxtacortical WMH volume(OR=3.005,95％CI:1.831-4.933;OR=2.199,95％CI:1.36-3.566)(P＜0.05,P＜0.01).Conclusion aCAS is an independent risk factor for WMH in the elderly population,and stenosis＞50％has a greater correlation with WMH volume.

Objective:To understand the molecular epidemiological characteristics of unique recombinant forms (URFs) in newly reported HIV-1 patients in Hangzhou, and provide theoretical support for prevention and control of AIDS.Methods:The blood samples of newly-diagnosed HIV-1 infected cases who received no antiviral therapy from 2019 to 2023 were collected, pol gene was amplified by RT-PCR and nested PCR, followed by sequencing. The URFs were screened using phylogenetic tree, followed by recombinant analysis. Genetic distances between URFs sequences were calculated and molecular transmission networks were constructed. The calibrated population resistance program (CPR) was used to analyze transmissible drug-resistant mutations. Results:A total of 222(5.0%, 222/4 471) URFs pol gene sequence were obtained, and the recombination types were CRF01_AE/CRF07_BC (60.4%, 134/222), CRF01_AE/C (11.7%, 26/222), CRF01_AE/B (9.5%, 21/222), CRF01_AE/B/C (8.1%, 18/222), B/C (7.6%, 17/222) and CRF55_01B/CRF07_BC (2.7%, 6/222), respectively. 78.8% (175/222) were infected by men who have sex with man(MSM), whoes mean age was 31.3±10.5. The proportion of URFs increased from 4.0% (34/843) to 7.4% (60/807) from 2019 to 2023. Under the optimal gene distance threshold of 1.5%, the molecular network access rate was 49.5% (110/222), included 23 clusters. We found a large active transmission cluster with 39 cases mixed homosexual and heterosexual, the recombination types was CRF01_AE/CRF07_BC, and the average gene distance was 0.005. Prevalence of URFs transmissible resistance was 3.2% (7/222). Conclusions:URFs are mainly produced and transmitted in young MSM, which shows an increasing trend year by year. There is a large active transmission cluster required major attention and effective intervention to prevent further expansion. At the same time, the occurrence and transmission of URFs should be continuously monitored to understand the clusters and drug resistance dynamics.