Objective: To explore the bidirectional associations among body mass index Z scores (BMI Z scores) and weight stigma with depressive symptoms in adolescents, thereby providing evidence for targeted intervention strategies. Methods: A stratified cluster random sampling method was employed to select 18 301 adolescents aged 12-18 years from all 12 prefectures (103 counties) in the Inner Mongolia Autonomous Region, and two waves of longitudinal surveys were conducted in September 2023 (T1) and September 2024 (T2) among the adolescents. Weight stigma was assessed by using a self developed questionnaire, depressive symptom was measured with the Center for Epidemiologic Studies Depression Scale (CES-D), and BMI Z scores were calculated according to the World Health Organization standards. Pearson correlation analysis was used to examine associations among variables, and cross lagged panel models were constructed to investigate the dynamic bidirectional relationships among the three variables. Results: Adolescents BMI Z scores and weight stigma with depressive symptoms all exhibited autoregressive stability across the two time points (autoregressive paths, all P <0.01). Cross lagged model comparisons indicated that the bidirectional path model achieved the best fit ( χ 2=12.65, RMSEA =0.017, CFI =1.000; △ χ 2=193.39, P <0.01), supporting dynamic bidirectional associations among the three variables. After adjusting for gender, age, subjective social status and only child status, T1 BMI Z scores among adolescents positively predicted T2 weight stigma ( β =0.061), and T1 weight stigma positively predicted T2 depressive symptoms ( β =0.608); in the reverse direction, T1 depressive symptoms predicted T2 weight stigma ( β =0.003), and T1 weight stigma predicted T2 BMI Z scores ( β =0.081) (all P <0.01). Conclusions There is a bidirectional cross lagged relationship among adolescents BMI Z scores and weight stigma with depressive symptoms, suggesting that weight stigma may serve as a key psychological variable linking obesity and depressive symptoms. Greater attention should be paid to the potential threat of weight stigma to adolescents mental health, with intervention strategies expanded from a solely physiological focus to encompass psychosocial dimensions.

Objective To analyze the medication rule of Traditional Chinese Medicine(TCM)in treating diabetes nephropathy(DN)and to explore the interaction between core components and key targets.Methods Based on the ancient and modern medical case cloud platform,the medication rules of TCMs and the drug pairs with the highest frequency in treating DN were summarized.Then the network pharmacology approach was utilized to analyze the pharmacodynamic material basis and mechanisms of the highest frequency-drug pairs.The potential targets were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)databases.TTD,DISGENET,and GENECARD databases were used to obtain the related targets of DN and screen out the potential targets for DN.In order to clarify the relationships between the active ingredients,the core targets,and pathways,STRING and Cytoscape 3.7.1 software were used to construct the protein-protein interaction(PPI)network and core drugs-ingredients-targets-disease interaction network,DAVID database was screened for Kyoto Encyclopedia of Genes and Gnomes(KEGG)enrichment analysis of core targets.Sybyl 2.1 software and biofilm interference verify the combined capacity between the core ingredients and key targets.Results Among 183 prescriptions,Astragali Radix had the highest use frequency and average dose,43 times and 37 g,respectively,followed by Salviae miltiorrhizae Radix and Poria cocos.To find the core combined with the highest confidence in association analysis was astragalus,salvia miltiorrhiza,and tuckahoe.Correlation analysis indicates that the core combination with the highest confidence was Astragali Radix-Salviae miltiorrhizae Radix-Poria cocos.Network pharmacologic showed 89 potential targets and 15 key signaling pathways for the treatment of DN by the drug pair.TNF signaling pathway,Nod-like receptor signaling pathway,and MAPK signaling pathway were disease-related pathways,and IL-6,TNF,and vascular endothelial growth factor A(VEGFA)were core targets.Isorhamnetin and quercetin of the drug pair had high binding ability with IL6,the scores were 8.2 and 7.4,respectively,and the dissociation constants(KD)were 5.6×10-5 mol·L-1 and 6.8×10-5 mol·L-1,respectively.Conclusion This study preliminarily finds the prescription rule of treating DN with Astragali Radix-Salviae miltiorrhizae Radix-Poria cocos as the core drug pair,isorhamnetin,and quercetin are probably the main active compounds of this drug pair in DN treatment,which provides a basis for clinical treatment and drug discovery of DN.

Objective: To explore the current status and progress of regional school health work to provide policy reference for school health improvement. Methods: Survey data on school health work in Tianjin from 2019, 2021 and 2023 was used. School health staff allocation and expenditure of the health administrative department, CDC and education department, as well as the annual implementation of health education, prevention and control of common diseases and infectious diseases, sports activities and food nutrition in primary and secondary schools were analyzed. Statistical analysis was conducted using KruskalWallis test, Chisquare test, and Fishers exact test. Results: The number of school health staff in the health commissions and education departments from 2019, 2021 and 2023 was relatively stable. Parttime staffs were often employed by health commissions while fulltime staffs were mainly employed by education departments. The number of school health staff at CDCs increased gradually (H=12.65, P<0.01). School health expenditure of administrative departments and schools in 2021 and 2023 increased significantly compared with that in 2019 (H=22.28, 23.75, P<0.05). More than 95% of schools set up clinics or health care rooms, and about 97% of schools had school health technicians or health teachers. More than 90% of schools had health education courses over 4 hours per semester. The rate of mental health education increased by year (86.87%, 89.91%, 96.30%, Z=2.40，P<0.05). Lack of courses regarded safety emergency and risk avoidance, growth and development, and adolescent health education. The provision rate of psychological counseling services (89.00%, 97.25%, 100.00%) and psychological problem prevention and control (56.12%, 71.56%, 81.48%) also increased by year (Z=3.83, 3.96, P<0.01). The implementation rates of prevention and control of poor vision, dental caries, overweight and obesity were all higher than 80%, and the prevention and control rate of abnormal spinal curvature showed an increasing trend (38.78%, 77.06%, 72.22%, Z=4.87, P<0.01). More than 90% of schools met the standard for physical education class hours, and the proportion of schools conducting at least 30 minutes of recess physical activities every day increased year by year (65.00%, 80.73%, 85.98%, Z=3.59, P<0.01). All schools did not have shops. Conclusions School health work in Tianjin is effective and constantly developing. It is necessary to continue to increase the investment of human resources and expenditure in school health, explore the approaches of cooccurrence and prevention of common diseases, and improve the school sports and nutrition environment.

Objective:To investigate the risk factors and cumulative risk of myopia in children and adolescents, providing a basis for identifying cumulative risk factors in preventing and controlling myopia.Methods:Baseline data from the mental and physical health cohort of children and adolescents established in Inner Mongolia Autonomous Region were used. A stratified random cluster sampling method was adopted to select 138 974 students from fourth to twelfth grade as participants. Distance visual exams, refractive assessments, and questionnaires were conducted on the included students. Logistic regression analysis was used to evaluate each risk factor's impact on myopia's prevalence. The number of risk factors was summed to form a cumulative risk score, and logistic regression analysis was conducted to examine the association between the cumulative risk score and the prevalence of myopia. Additionally, the association between the cumulative risk score of myopic students and their degree of refractivity was analyzed using a generalized estimating equation.Results:The study found a high prevalence of myopia among children and adolescents at baseline (70.2%). Girls exhibited a higher prevalence (74.8%) than boys (65.6%), urban areas (74.3%) surpassed suburban ones (68.6%), and the incidence was greater in high schools (80.3%) compared to middle schools (75.3%), which, in turn, was higher than in elementary schools (57.7%) (all P<0.05). Analysis of risk factors revealed that children and adolescents experiencing improper reading and writing distances ( OR=1.10, 95% CI: 1.07-1.13), excessive homework ( OR=1.09, 95% CI: 1.06-1.12), insufficient sleep ( OR=1.10, 95% CI: 1.07-1.13), having myopic father ( OR=1.98, 95% CI: 1.91-2.05), having myopic mother ( OR=2.04, 95% CI: 1.97-2.10), or using classroom chairs not matched to their height faced ( OR=1.04, 95% CI: 1.01-1.07) increased myopia risks. Additionally, the prevalence and significant odds ratio of myopia increased with the increase in cumulative risk score, with every additional unit of cumulative risk score increasing the right eye's refractive error by -0.10 D. Conclusion:The presence of multiple factors and their comprehensive score increases the prevalence of myopia in children and adolescents.

Oxalate is an organic dicarboxylic acid that is a common component of plant foods.The kidneys are essential organs for oxalate excretion,but excessive oxalates may induce kidney stones.Jupiter micro-tubule associated homolog 2(JPT2)is a critical molecule in Ca2+mobilization,and its intrinsic mecha-nism in oxalate exposure and kidney stones remains unclear.This study aimed to reveal the mechanism of JPT2 in oxalate exposure and kidney stones.Genetic approaches were used to control JPT2 expression in cells and mice,and theJPT2 mechanism of action was analyzed using transcriptomics and untargeted metabolomics.The results showed that oxalate exposure triggered the upregulation of JPT2,which is involved in nicotinic acid adenine dinucleotide phosphate(NAADP)-mediated Ca2+mobilization.Tran-scriptomic analysis revealed that cell adhesion and macrophage inflammatory polarization were inhibited by JPT2 knockdown,and these were dominated by phosphatidylinositol 3-kinase(PI3K)/AKT signaling,respectively.Untargeted metabolomics indicated that JPT2 knockdown inhibited the produc-tion of succinic acid semialdehyde(SSA)in macrophages.Furthermore,JPT2 deficiency in mice inhibited kidney stones mineralization.In conclusion,this study demonstrates that oxalate exposure facilitates kidney stones by promoting crystal-cell adhesion,and modulating macrophage metabolism and in-flammatory polarization via JPT2/PI3K/AKT signaling.

Clinical data of 3 pregnant women with primary hyperparathyroidism admitted in Jinan Maternal and Child Health Hospital from 2013 to 2021 were retrospectively reviewed. Hyperparathyroidism was diagnosed during pregnancy in all 3 cases. The clinical manifestations were non-specific, such as nausea, vomiting, anorexia, and fatigue. Patients also had gallbladder stones (1 case), gallbladder polyps (1 case), and renal parenchyma changes (2 cases). The hypercalcemia crisis occurred in all 3 cases, the blood Ca 2+ levels were 4.11 mmol/L, 2.92-3.82 mmol/L and 3.49-4.10 mmol/L, respectively; and preeclampsia developed in 2 cases. Sudden death occurred in case 1 who did not receive effective treatment during pregnancy; blood calcium was well controlled during pregnancy in case 2, and her neonate had hypocalcemia with good prognosis; case 3 underwent surgical treatment in early pregnancy, and then had missed abortion. Pathological examination revealed parathyroid tumors in all 3 cases.

Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models.

Objective:To investigate the therapeutic effect of artesunate on mice with acute Toxoplasma gondii ( T. gondii) infection. Methods:Based on body weight (16 - 18 g), sixty-four C57BL/6 female mice aged 6 - 8 weeks were divided into 4 groups by random number table method: uninfected control group without treatment; T. gondii-infected group (Tg group), each mouse was intraperitoneally (i.p.) infected with 100 tachyzoites of T. gondii RH strain; T. gondii-infected + artesunate treatment group (Tg + ART group), 3 hours after each mouse i.p. infected with 100 tachyzoites of T. gondii RH strain, artesunate solution was i.p. injected at a dose of 30 mg/kg, once a day for a total of 7 consecutive days; T. gondii-infected + sulfadiazine treatment group (Tg + SDZ group), 3 hours after each mouse i.p. infected with 100 tachyzoites of T. gondii RH strain, sulfadiazine solution was orally administrated at a dose of 100 mg/kg, once a day for a total of 7 consecutive days. There were 16 mice in each group, in which 10 mice were used to observe survival time and 6 mice were used to monitor body weight and collect tissue samples. Mice were weighed every day from day 1 post infection (p.i.); mice were sacrificed at day 7 p.i., the liver weights of mice were weighed and the liver indexes were calculated; liver tissues were paraffin-embedded, sectioned, and stained with hematoxylin-eosin (HE), and the pathological changes of liver tissues of mice in each group were observed under a light microscope. The expression levels of T. gondii major surface antigen 1 (SAG1) in the liver tissues of mice in each group were detected by real-time quantitative PCR for evaluating parasite load. Results:All mice in the uninfected control group were survived. The survival time was 7 - 9 days in Tg group, 8 - 11 days in Tg + ART group, and 9 - 13 days in Tg + SDZ group. Compared with Tg group, the survival times of mice in Tg + ART group and Tg + SDZ group were significantly longer ( P < 0.05). On day 7 p.i., compared with uninfected control group, Tg + ART group or Tg + SDZ group, the body weight of mice in Tg group was lower ( P < 0.05); however, there was no significant difference of body weight in Tg + ART group and Tg + SDZ group compared with uninfected control group ( P > 0.05). Compared with Tg group, Tg + ART group and Tg + SDZ group had lower liver indexes and SAG1 mRNA expression levels in the liver tissues ( P < 0.05 or < 0.001), and liver histopathological changes were milder. Compared with Tg + SDZ group, there was no significant difference in both liver index and SAG1 mRNA expression level in the liver tissue of Tg + ART group ( P > 0.05). Conclusion:Artesunate solution i.p. injection can prolong the survival time, reduce parasite load in the liver, and attenuate hepatic pathological damage, to a certain extent, of mice with acute T. gondii infection.

Objective: To observe the effect of Tuina (Chinese therapeutic massage) on creatine kinase (CK), mitochondrial Ca2+ concentration, and ultrastructure of skeletal muscle in delayed onset muscle soreness (DOMS) model rats.Methods: A total of 130 healthy male Sprague-Dawley rats were randomly divided into a blank group, an exercise control group, a pre-exercise Tuina group, and a post-exercise Tuina group. According to the time points for sample collection, the exercise control group was divided into a 0 h exercise control group, a 24 h exercise control group, a 48 h exercise control group, and a 72 h exercise control group; the pre-exercise Tuina group was further divided into a 0 h pre-exercise Tuina group, a 24 h pre-exercise Tuina group, a 48 h pre-exercise Tuina group, and a 72 h pre-exercise Tuina group; and the post-exercise Tuina group was divided into a 0 h post-exercise Tuina group, a 24 h post-exercise Tuina group, a 48 h post-exercise Tuina group, and a 72 h post-exercise Tuina group. Rats in all groups except for the blank group received DOMS modeling. Professionals performed Nie-Pinching manipulation and finger Nian-Twisting manipulation on the lower limbs of the rats. The samples were collected at 0 h, 24 h, 48 h, or 72 h after exhaustive exercise for each pre-exercise Tuina group. The samples were collected at 0 h, 24 h, 48 h, or 72 h after Tuina for each post-exercise Tuina group. The changes in serum CK, skeletal muscle mitochondrial Ca2+ concentration, and Ca2+-adenosine triphosphatase (ATPase) were determined. The ultrastructure changes of skeletal muscles in each group were observed by a transmission electron microscope. Results: The electron microscope showed that compared with the exercise control group, the skeletal muscle structures of the pre-exercise Tuina group and the post-exercise Tuina group were significantly improved, and the overall performance of skeletal muscle in the pre-exercise Tuina group was more similar to that of the blank group. The level of serum CK in the pre-exercise Tuina group and the post-exercise Tuina group was significantly lower than that in the exercise control group (P<0.01). The Ca2+ concentration of skeletal muscle in the 24 h, 48 h, and 72 h pre-exercise Tuina groups was lower than that in the post-exercise Tuina group at the same time point (P<0.01). The Ca2+-ATPase concentration of skeletal muscle in the 24 h and 72 h pre-exercise Tuina groups was lower than that in the post-exercise Tuina group at the same time point (P<0.05).Conclusion: Tuina effectively prevents muscle damage caused by heavy exercise and long-term exercise, which may be related to the increase of skeletal muscle Ca2+-ATPase activity and mitochondrial Ca2+ transport.

Background::Keratinocytes play an important role in wound healing; however, less is known about skin keratinocytes in patients with type 2 diabetes mellitus (T2DM). Therefore, this study aimed to search for the transcriptional characteristics of keratinocytes at the single-cell level from T2DM patients, and to provide experimental data for identifying the pathological mechanisms of keratinocytes under pathological conditions.Methods::We performed single-cell RNA sequencing on the skin tissue from two T2DM patients and one patient without diabetes-induced trauma using the BD Rhapsody TM Single-Cell Analysis System. With the help of bioinformatics R-based single-cell analysis software, we analyzed the results of single-cell sequencing to identify the single-cell subsets and transcriptional characteristics of keratinocytes at the single-cell level, including Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyzes. Results::In this study, we found specific highly expressed signature keratinocyte-related genes. We analyzed the transcriptome of keratinocytes from experimental and control groups and screened a total of 356 differential genes, which were subject to bioinformatics analysis. Enriched pathways included oxidative phosphorylation, antigen processing and presentation, prion and Huntingtons’ diseases, bacterial invasion of epithelial cells, thermogenesis, vasopressin-regulated water reabsorption, and protein processing in the endoplasmic reticulum.Conclusions::This study revealed the characteristics of keratinocytes at the single-cell level and screened a group of differentially expressed genes related to T2DM-associated keratinocytes, oxidative phosphorylation, cytokine receptor interactions, prion diseases, and other signaling pathways.