Background As one of the key populations in the prevention and treatment of iodine deficiency disorders, it is important to continuously monitor the iodine nutritional level of school-age children. The current reference interval for thyroid volume in China is based on age only, without taking into account differences in individual developmental levels, and the distribution of thyroid volume may vary regionally due to economic, demographic, and environmental factors. The current reference cut-off points for thyroid volume proposed by the World Health Organization are not based on the Chinese population. Objective To understand the iodine nutritional status and distribution of thyroid volume (Tvol) among children aged 8-10 years in Huangpu District, Shanghai, China, to identify impact factors of Tvol, and to propose a reference range upper limit for local thyroid health surveillance, so as to provide a basis for goiter control and prevention. Methods Six hundred children aged 8-10 years in Huangpu District were recruited in 2017, 2020, and 2023, and body height, weight, thyroid volume, urinary iodine, and iodine content of household edible salt were determined. A multilevel model was constructed using population density and area as regional variables, and age, body surface area (BSA), and body mass index (BMI) as potential impact factors for at the individual level, to assess their effects on thyroid volume. Quantile regression of thyroid volume was performed, and the 98th percentile (P₉₈) of thyroid volume was predicted based on age and BSA. Results The iodized salt coverage in the households of surveyed children in 2017, 2020, and 2023 was 72.0%, 57.0%, and 48.0%, respectively, and the iodized salt coverage decreased by year (χ²=24.31, P<0.001). The urinary iodine level of children in 2017 was higher than that in 2020 and 2023 (χ²=18.77, P<0.001). The Tvol medians of children in 2017, 2020, and 2023 were 2.29, 2.49, and 2.97 mL, respectively, and the Tvol increased by year (χ²=60.04, P<0.001). The proportion of goiter was higher in children in 2023 than in 2017 and 2020 (χ²=6.57, P<0.05). Sex differences were not statistically significant for urinary iodine levels, thyroid volume, and goiter. The median Tvol was 2.26, 2.58, and 2.76 mL in children of 8, 9, and 10 years old respectively, and the Tvol increased with age (χ²=49.02, P <0.001). Tvol was positively correlated with age, BSA, and BMI with correlation coefficients of 0.2846, 0.3723, and 0.2950, respectively. The final quantile regression model showed that the strongest effect of BSA was associated with the 98th percentile of Tvol. Multilevel models considering population density or area as regional variables failed to achieve convergence. Conclusion To establish the upper limit of the reference interval for thyroid volume of healthy children in Huangpu District, the effects of age and BSA should be considered at the individual level, and the upper limit of the normal interval for goiter screening is suggested to be the 98th percentile value of BSA at the same age. In addition, the adaptability of population density and regional area as indicators of regional aggregation of thyroid volume distribution still needs to be further explored.

OBJECTIVE To investigate the effects of multiple doses of Shugan jieyu capsules on the pharmacokinetics of voriconazole， rivaroxaban and apixaban in rats. METHODS Male SD rats were randomly divided into voriconazole group （30 mg/kg）， rivaroxaban group （2 mg/kg）， apixaban group （0.5 mg/kg）， Shugan jieyu capsules+voriconazole group （145 mg/kg+30 mg/kg）， Shugan jieyu capsules+rivaroxaban group （145 mg/kg+2 mg/kg）， Shugan jieyu capsules+apixaban group （145 mg/kg+0.5 mg/kg）， with 6 rats in each group. After the rats in each group were consecutively administered solvent （0.5% sodium carboxymethyl cellulose solution） or Shugan jieyu capsules by intragastric gavage for 8 days， they were respectively given voriconazole， rivaroxaban and apixaban solution by intragastric gavage on the 8th day. Blood samples were then collected at different time points （in voriconazole group， rivaroxaban group and corresponding drug combination groups， blood was collected before administration and at 0.17， 0.34， 0.5， 0.75， 1， 1.5， 2， 3， 4， 5， 6， 8， 10 and 12 hours post-administration； in apixaban group and corresponding drug combination group， blood was collected before administration and at 0.08， 0.17， 0.25， 0.34， 0.5， 0.75， 1， 3， 5， 7， 10 and 12 hours post-administration）. Ultra-high performance liquid chromatography-tandem mass spectrometry method was employed to determine the mass concentrations of voriconazole， rivaroxaban and apixaban in rat plasma. The main pharmacokinetic parameters of these drugs were calculated using a non-compartmental model， and the comparisons were made between groups. RESULTS Compared with single drug group， after multiple administrations of Shugan jieyu capsules， AUC0－t， AUC0－∞ and cmax of voriconazole were significantly decreased， while CLz/F was significantly increased， and tmax was also significantly prolonged （P＜0.05）. For rivaroxaban and apixaban， their tmax values were both significantly prolonged （P＜0.05）. However， there were no statistically significant differences in the other pharmacokinetic parameters between the two groups （P＞0.05）. CONCLUSIONS The combination of Shugan jieyu capsules can decrease the exposure， increase the clearance， and delay the peak concentration of oral voriconazole. However， it does not affect the exposure levels of rivaroxaban and apixaban， but it does delay the time to reach peak concentration for both drugs.

Objective: To explore the potential application of PAK4-PROTAC targeted degradation drug (PpD) in renal cancer immunotherapy. Methods: TIMER 2.0 and TISIDB databases were used to analyze the relationship among PAK4 expression, tumor purity and abundance of immune cell infiltration in renal tumor microenvironment (TEM).Renal cancer cell lines OS-RC-2, 786-O and ACHN were treated with 0, 125 and 250 nmol/L PpD, and the effects of Jurkat cell co-culture on the results were investigated.The cell apoptosis was detected with flow cytometry, and the expression of programmed cell death 1 ligand 1 (PD-L1) in renal cancer cells was detected with immunoblotting. Results: The high expression of PAK4 was positively related to immune purity, and inhibited the abundance of immune killer cells in TEM, such as CD8 T cells, CD4 T cells, natural killer cells and dendritic cells.With 250 nmol/L PpD treatment, there were 21.02% apoptotic cells in OS-RC-2, 29.67% apoptotic cells in 786-O, and 15.39% apoptotic cells in ACHN, respectively.However, with the same concentration of 250 nmol/L PpD treatment, cell apoptotic rate was sharply increased to 70.13% in OS-RC-2/Jurkat, 70.68% in 780-O/Jurkat, and 60.27% in ACHN/Jurkat co-culture models, respectively. Conclusion: PpD can promote apoptosis of renal cancer cells by reducing the expression of PAK4 protein, and enhance the killing effects of immune cells on tumor cells.

Objective To explore the mediating role of activities of daily living (ADL) in pain and depressive symptoms in the elderly in China. Methods Utilizing the data from 2020 China Health and Retirement Longitudinal Study, 4403 Chinese elderly individuals aged ≥ 60 years old were selected as the research subjects. Depression Scale (CES-D 10) of the Center for Epidemiological Survey and ADL scale were used in the study. The PROCESS4.1 macro was used to test the mediating effect of daily living activities between pain and depressive symptoms, and the Bootstrap method was applied for verification of the mediating variables. Results A total of 2368 cases of depressive symptoms were detected in the elderly in China, with a detection rate of 53.78%. Pain was positively correlated with depressive symptoms (r=0.27, P<0.01), and activities of daily living were negatively correlated with pain and depressive symptoms (r=-0.27, -0.337, P<0.01). The results showed that the total effect value of pain on depressive symptoms was 0.33, the direct effect value was 0.24, and the mediating effect value of daily living activities was 0.09, accounting for 27.27%. Conclusion Pain and activities of daily living are important factors influencing depressive symptoms in the elderly, and activities of daily living play a partial mediating role in the relationship between pain and depressive symptoms in the elderly.

Objective: To explore the association between mental health and muscle strength among Chinese adolescents aged 13- 18, providing a theoretical foundation and intervention strategies for mental health promotion. Methods: Data were obtained from the 2019 Chinese National Survey on Students Constitution and Health, including 98 631 Chinese adolescents aged 13- 18. Psychological distress was assessed by using the Kessler Psychological Distress Scale (K10), and mental well being was measured with the Warwick-Edinburgh Mental Well being Scale (WEMWBS). Based on the gender and age specific Z scores of various test items [grip strength, standing long jump, pull ups (for males), and sit ups (for females)], muscle strength index (MSI) was constructed to evaluate the comprehensive level of muscle strength in adolescents. According to the Dual factor Model (DFM) of mental health, participants were categorized into four groups:troubled, symptomatic but content, vulnerable, and complete mental health. Gender differences were analyzed by using Chi-square tests, trends were tested with Cochran-Armitage tests, and multinomial Logistic regression models were applied to assess associations between muscle strength and mental health among adolescents. Results: In 2019, 37.4% of Chinese adolescents aged 13-18 were reported of high mental distress, and 59.9% were reported of low mental well being. Boys had significantly lower rates of high mental distress (35.3%) and low mental well being (55.6%) compared to girls (39.4%, 64.3%), and the differences were of statistical significance ( χ 2=176.13, 780.42, both P <0.05). In 2019, the rate of complete mental health among adolescents showed a downward trend with increasing age ( χ 2 trend = 258.47) and a gradual upward trend with increasing muscle strength levels ( χ 2 trend =123.14)，and both boys and girls exhibited similar trends ( χ 2 trend =103.83, 168.46; 57.00 , 67.34) (all P <0.05). The results of the unordered multiclass Logistic regression model showed that after controlling for confounding factors such as age and gender, when the completely pathological group as a reference, for every 1 unit increase in MSI in adolescents, the likelihood of being in a completely mental health state increased by 29% ( OR = 1.29); for every unit increase in the Z-score for pull ups, the likelihood of being in a completely mental health state increased by 6% ( OR =1.06) among boys; for every 1 unit increase in sit up Z score, the likelihood of being in a completely mental health state increased by 19% ( OR =1.19) among girls (all P <0.05). Conclusions The mental health status of Chinese adolescents is not good enough. Muscle strength is positively associated with mental health.

Objective To analyze the prognosis of elderly patients with community-acquired pneumonia (CAP) and its correlation with serum angiopoietin 2 (Ang-2), activated protein C (APC) and pentraxin 3 (PTX3) levels. Methods A total of 508 elderly patients with CAP in the hospital from March 2021 to March 2024 were divided into death group (n=104) and survival group (n=404) according to the survival status at 28 days after admission. Another 110 healthy subjects with physical examination were included in the control group. The levels of serum Ang-2, APC and PTX3 were compared, and their correlation with prognosis was explored by Pearson correlation analysis. Results In this study, 404 cases survived after 28 days and 104 cases died. The levels of C-reactive protein, procalcitonin and interleukin-8 and the proportion of severe condition in the survival group were lower than those in the death group (P<0.05). The level of serum APC in the case group and the death group was lower than that in the control group and the survival group (P<0.05), while the levels of Ang-2 and PTX3 were higher than those in the control group and the survival group (P<0.05), respectively. Serum APC level was negatively correlated with community-acquired pneumonia in the elderly CAP (r=-0.476, P<0.05), while Ang-2 and PTX3 were positively correlated with prognosis (r=0.489, 0.502, P<0.05). Conclusion Serum levels of Ang-2 and APC in elderly patients with CAP are decreased and the level of PTX3 is increased. Serum Ang-2 and APC levels are negatively correlated with elderly CAP, and PTX3 is positively correlated with prognosis.

Background::Total human immunodeficiency virus (HIV) DNA and integrated HIV DNA are widely used markers of HIV persistence. Droplet digital polymerase chain reaction (ddPCR) can be used for absolute quantification without needing a standard curve. Here, we developed duplex ddPCR assays to detect and quantify total HIV DNA and integrated HIV DNA.Methods::The limit of detection, dynamic ranges, sensitivity, and reproducibility were evaluated by plasmid constructs containing both the HIV long terminal repeat (LTR) and human CD3 gene (for total HIV DNA) and ACH-2 cells (for integrated HIV DNA). Forty-two cases on stable suppressive antiretroviral therapy (ART) were assayed in total HIV DNA and integrated HIV DNA. Correlation coefficient analysis was performed on the data related to DNA copies and cluster of differentiation 4 positive (CD4 +) T-cell counts, CD8 + T-cell counts and CD4/CD8 T-cell ratio, respectively. The assay linear dynamic range and lower limit of detection (LLOD) were also assessed. Results::The assay could detect the presence of HIV-1 copies 100% at concentrations of 6.3 copies/reaction, and the estimated LLOD of the ddPCR assay was 4.4 HIV DNA copies/reaction (95% confidence intervals [CI]: 3.6-6.5 copies/reaction) with linearity over a 5-log 10-unit range in total HIV DNA assay. For the integrated HIV DNA assay, the LLOD was 8.0 copies/reaction (95% CI: 5.8-16.6 copies/reaction) with linearity over a 3-log 10-unit range. Total HIV DNA in CD4 + T cells was positively associated with integrated HIV DNA ( r = 0.76, P <0.0001). Meanwhile, both total HIV DNA and integrated HIV DNA in CD4 + T cells were inversely correlated with the ratio of CD4/CD8 but positively correlated with the CD8 + T-cell counts. Conclusions::This ddPCR assay can quantify total HIV DNA and integrated HIV DNA efficiently with robustness and sensitivity. It can be readily adapted for measuring HIV DNA with non-B clades, and it could be beneficial for testing in clinical trials.

Objective To investigate the mechanism underlying the Jiaji electroacupuncture(EA)-induced improvement in neuronal apoptosis among rats with spinal cord injury(SCI).Methods Sprague-Dawley rats were randomly divided into sham,SCI,EA,and EA+colivelin groups(n=10 each).Allen's modified heavy-fall method was used to prepare the animal model of SCI.The clamped-spine EA group was treated with EA at the paraspinal clamped spine points at the vertebral bodies of T7_9 at the upper and lower ends of the spinal cord injury on the backs of the rats.The Basso-Beattie-Bresnahan score and slope test were used to evaluate the rats'locomotor abilities;TUNEL staining was used to detect changes in neuronal apoptosis in the spinal cord;immunofluorescence was used to detect changes in glial fibrillary acidic protein(GFAP)expression in the rats'spinal cord tissues;and Western blotting was used to detect the relative expressions of GFAP,phospho-signal transducer and activator of transcription 3(p-STAT3),STAT3,and cleaved caspase-3 pro-tein expression in spinal cord tissues.Results The mean Basso-Beattie-Bresnahan score was higher in the EA compared with SCI group(P＜0.01).The mean angle on the slant plate test was smaller in the EA compared with sham group(P＜0.001).The mean angle was slightly larger in the EA compared with SCI group(P＜0.01).GFAP-positive,p-STAT3,cleaved caspase-3 protein,and inflammatory cytokine expressions were significantly increased(P＜0.05)and the number of neuronal apoptotic cells was increased(P＜0.01)in the SCI compared with sham group.However,the opposite trend was observed in the EA group.In addition,the therapeutic effect of spinal EA on spinal cord injury was reversed after colivelin administration(P＜0.05).Conclusion EA reduces neuronal apoptosis and improves motor and balance functions in the spinal cord tissues of rats with SCI,possibly via GFAP/STAT3 pathway inhibition.

Objective To investigate the effects and molecular mechanisms of decorin(DCN),imatinib mesylate,and sunitinib malate on the malignant phenotype of gastrointestinal stromal tumor cells.Methods Western blotting was used to detect changes in the expres-sion of DCN and its downstream proteins after DCN overexpression and treatment with imatinib mesylate and sunitinib malate alone or in combination in gastrointestinal stromal tumor cells(GIST-882).Cell counting kit-8,scratch,and Transwell assays were performed to validate the changes in cell proliferation,migration,and invasion abilities after DCN overexpression and treatment with imatinib mesylate and sunitinib malate alone or in combination in GIST-882 cells.Results Compared with the control group,DCN overexpression and treatment with imatinib mesylate and sunitinib malate alone or in combination in GIST-882 cells increased the expression levels of DCN protein,decreased the expression levels of epidermal growth factor receptor(EGFR),phosphorylated EGFR(p-EGFR),extracellular signal-regulated kinase 1/2(ERK1/2),and phosphorylated ERK1/2(p-ERK1/2)proteins,and significantly reduced cell proliferation,migration,and invasion abilities.Conclusion DCN overexpression and treatment with imatinib mesylate and sunitinib malate alone or in combination affect the MAPK signaling pathway by downregulating the expression of EGFR,thereby regulating the proliferation,migra-tion,and invasion abilities of gastrointestinal stromal tumor cells.

Thrombolytic therapy plays a vital role in reperfusion strategy for ST-segment elevation myocardial infarction(STEMI)patients.Previous Chinese expert consensus focused on pre-hospital thrombolysis therapy in STEMI patients was published in 2018 which tremendously promoted pre-hospital thrombolysis therapy.In recent years,plenty of research progress and results of clinical trials have been released in following areas such as STEMI reperfusion strategy,anti-platelet/anti-coagulants therapy,contemporary facilitated percutaneous coronary intervention,and so on.Meanwhile,the COVID-19 pandemic makes timely reperfusion for STEMI patients even more challenging.Therefore,this consensus has been proposed aiming to summarize recent progress in STEMI thrombolysis therapy and to provide practical & evidence-based instructions conforming to national conditions.We hope this consensus will contribute to the emergency management and long-term prognosis of STEMI patients.