Objective: To investigate the association between uric acid level and elevated blood pressure among children and adolescents in Guangzhou, so as to provide a scientific basis for prevention and control of hypertension in the pediatric population. Methods: From March to December 2019, using stratified cluster random sampling, 3 626 children and adolescents aged 6-17 years without elevated blood pressure at baseline were recruited from 6 primary and secondary schools in Guangzhou. Serum uric acid levels were measured at baseline, and divided into four groups ( Q1-Q 4) based on age and sex specific quartiles for analyses. Two waves of follow up were carried out from October 2020 to May 2021 and from October 2021 to May 2022, respectively. Multilevel robust Poisson regression was used to evaluate the association between uric acid level and elevated blood pressure among children and adolescents. The additive interaction between high uric acid level and sugar sweetened beverage (SSB) intake on elevated blood pressure was assessed by stratification analysis and calculation of the relative excess risk due to interaction (RERI). Results: A total of 1 131 new cases of elevated blood pressure were identified during the two follow ups, with an incidence density of 130.5 cases 1 000 person years. Multilevel robust Poisson regression analysis showed that after adjusting for confounders such as gender, age and annual family income, compared with those in the uric acid Q 1 level, the risk of elevated blood pressure in individuals in the Q 4 level increased by 25% ( RR=1.25, 95%CI =1.08-1.44), and the risk of elevated systolic blood pressure increased by 20% ( RR=1.20, 95%CI =1.05-1.36) (both P <0.05); no statistical association was observed between uric acid and elevated diastolic blood pressure (all P >0.05). In the stratified analysis, the statistical associations of uric acid Q 4 level with elevated blood pressure ( RR=1.34, 95%CI =1.13-1.58) and elevated systolic blood pressure ( RR=1.33, 95%CI =1.14-1.55) were only observed in the group with SSB intake ≥ 250 mL/week (both P <0.05). The RERI values for the effect of uric acid Q 4 and Q 3 levels with SSB intake ≥ 250 mL/week on elevated systolic and diastolic blood pressure were 0.29 and 0.44 (both P <0.05). Conclusions High uric acid level is a risk factor for elevated blood pressure among children and adolescents, with a predominant effect on systolic blood pressure. High uric acid level and SSB intake synergistically promote the increase of blood pressure of children and adolescents.

Objective To establish a stable in vitro model of CD8+T cell exhaustion.Methods CD8+T cells were isolated and purified from the spleens of ovalbumin-specific CD8+T cell receptor(OT-I)transgenic mice and subjected to chronic antigen stimulation to induce exhaustion in vitro.Flow cytometry was employed to evaluate the expressions of exhaustion markers,secretion of effector cytokines,and transcription factor profiles in CD8+T cells.Exhausted and effector(non-exhausted)CD8+T cells were co-cultured with tumor cells before tumor cell viability was measured to assess the cytotoxic potential of CD8+T cells.Additionally,N-acetyl-L-cysteine(N-AC)was used as a positive control during exhaustion induction to validate the model.Results Chronic stimulation resulted in a significant upregulation of inhibitory receptors,including programmed cell death protein 1(PD-1),T cell immunoglobulin and mucin domain-containing protein 3(TIM-3),T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motifdomain(TIGIT),and lymphocyte activation gene 3(LAG-3).Concurrently,the secretion of key effector cytokines such as tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ)was markedly reduced.Exhausted CD8+T cells exhibited diminished cytotoxicity against tumor cells compared to effector CD8+T cells.Notably,treatment with N-AC effectively restored the function of exhausted CD8+T cells and enhanced their anti-tumor activity.Conclusion This study has established an effective in vitro model for CD8+T cell exhaustion.The use of N-AC demonstrates its potential to restore functionality in exhausted CD8+T cells,underscoring the reliability and utility of this model for investigating the anti-tumor potential of exhausted T cells.

Objective: To investigate the iodine nutrition status of children aged 8-10 in Guangming, Longhua and Yantian District of Shenzhen in 2023, and to explore the influencing factors of thyroid volume. To evaluate prevention strategies and to provide a scientific basis for the elimination of iodine deficiency disorders. Methods: Urine and household salt samples were randomly collected from 580 non-boarding students aged 8-10 years foriodine content detection. Thyroid volume was measured using a fully digital ultrasound imaging system, and goiter prevalence was calculated. Results: A total of 580 samples was tested. The median salt iodine concentration was 23.86 mg/kg, with 93.62% qualified iodized salt and 94.48% coverage rate. The median of urinary iodine was 265.00 μg/L, mainly distributed between 200 - < 300 μg/L and ≥300 μg/L. The proportion of children with ap⁃ propriate iodine was 20. 86% , and the proportion of children with insufficient or excessive urinary iodine levels was 10. 86% and 68. 28% of the total surveyed population , respectively. The median thyroid volume was 3. 27 mL , and the goiter rate was 1. 72% . Multiple linear regression analysis showed that age was the risk factor for thyroid volume (8=0 328, P<0.05). while urinary iodine was the protective factor for thyroid volume(B=-4.134x10-4,P<0.05). Conclusion The qualified iodized salt rate, median of urinary iodine,and goiter prevalence of 580 children aged 8 - 10 meet the elimination criteria for iodine deficiency disorders. Age and urinary iodine are closely related to thyroid volume change. The urinary iodine level of children is generally high and requires serious attention.

Objective:To investigate the brain iron status in the sensorimotor cortex of patients with chronic low back pain (CLBP) and its relationship with changes in resting-state functional connectivity (RS-FC).Methods:This was a cross-sectional study. Thirty-two patients with CLBP (CLBP group) who were treated at Wuxi People′s Hospital Affiliated to Nanjing Medical University from July 2023 to March 2024 and 30 age-and gender-matched healthy volunteers (control group) were prospectively included. All subjects underwent pain and neuropsychological assessments and head MRI examinations, including conventional sequences, quantitative susceptibility mapping (QSM), and blood oxygen level-dependent (BOLD) functional MRI. QSM values of the sensorimotor cortex and the left middle frontal gyrus, right inferior temporal gyrus, right olfactory cortex, and right posterior cingulate gyrus were extracted using the ANTs toolkit. The bilateral postcentral gyrus and posterior portion of the bilateral precentral gyrus in the sensorimotor cortex were selected as seed points using SPM software to extract the average time series of BOLD signals and evaluate the changes in RS-FC values with other brain regions. Two-sample t-tests were used to compare the differences in QSM values and RS-FC values between the two groups. Pearson correlation analysis was used to analyze the correlation between iron deposition in key brain regions and RS-FC values and clinical scale scores. Results:The QSM values in the posterior portion of the bilateral precentral gyrus and the left postcentral gyrus in the CLBP group were significantly higher than those in the control group ( t=2.17, P=0.009; t=4.44, P<0.001), and the QSM value in the left postcentral gyrus was positively correlated with pain-related scale scores ( P<0.05). Compared with the control group, the QSM values in the left orbital part of the middle frontal gyrus ( t=2.22, P=0.031) and the right inferior temporal gyrus ( t=2.98, P=0.004) were increased, while the QSM values in the right olfactory cortex ( t=2.54, P=0.014) and the right posterior cingulate gyrus ( t=2.70, P=0.009) were decreased in the CLBP group. Compared with the control group, the RS-FC values between the left postcentral gyrus, the posterior part of the bilateral precentral gyrus, and the left superior frontal gyrus were increased in the CLBP group ( P<0.001), the RS-FC value between the right postcentral gyrus and the right precuneus was increased ( P<0.001). The RS-FC of the bilateral motor cortex and the left dorsolateral superior frontal gyrus was positively correlated with the QSM values of the bilateral motor cortex ( r=0.444, P=0.015). Conclusion:Iron deposition in the sensorimotor cortex (posterior portion of the bilateral precentral gyrus and the left postcentral gyrus) is increased in CLBP patients and is correlated with abnormal functional connectivity within and between brain regions.

[Objective]To explore the relationships between the specifications of pills and medication and syndrome treatment in Jingui Yaolue,summarize ZHANG Zhongjing's academic thoughts of flexibly using pills.[Methods]Through studying Jingui Yaolue,combining the annotations of past generations and modern researches,this study summarized the specifications of the pills involved in the whole book based on the"quantity",interpreted the meaning of the specifications,analyzed the selection basis of different pill specifications from the two dimensions of medication and syndrome treatment,and summarized the academic thoughts of pills and its modern clinical significance.[Results]ZHANG Zhongjing established a two-dimensional specification system of"size-amount"of pills.The size of the pill was standardized by the quantitative unit and the amount of medicine was determined according to the single dosage and the frequency of medication.He emphasized that the amount of medicine was led through medication,paid attention to the unification of"medicinal properties-medicine quantity"and the balance of efficacy and poison.Moreover,he advocated clarifying the amount according to the syndrome treatment,flexibly adjusted the specifications of pills in terms of medicinal methods,objects and time of taking,and built a dynamic balance system of"specifications-medicine efficacy".This academic thoughts of using pills was based on specifications and deeply guided modern clinical practice.[Conclusion]ZHANG Zhongjing's academic thoughts of using pills takes"amount"as the core realized the unification of individualized medication and maximum therapeutic effect through specification selection.Based on the specifications of pills,focusing on"amount-effect"research,and integrating modern research results,it was expected to provide more accurate guidance for the clinical application of pills and promote its modern application.

Interferon regulatory factor 4 (IRF4) is a critical transcription factor that governs the differentiation of cluster of differentiation 4⁺ (CD4⁺) T cells. The pathogenesis and progression of psoriasis are primarily attributed to an immune imbalance stemming from the overproduction of interleukin-17A (IL-17A) by T lymphocytes. However, the role of IRF4 in psoriasis remains unexplored. In this study, we found that IRF4 activity is increased in the cutaneous lesions of patients with psoriasis in response to stimulation by IL-23A and IL-1β. This IRF4 elevation heightens its binding to the E1A binding protein p300 (EP300) promoter, triggering the transcription of downstream retinoic acid receptor-related orphan receptor-γt (RORγt) and increasing the secretion of IL-17A, thereby establishing the IL-1β/IL-23A-IRF4-EP300-RORC-IL-17A inflammatory cascade in psoriasis. The alleviation of imiquimod (IMQ)-induced psoriatic-like symptoms was achieved through the creation of a Irf4 ^-/- gene deletion mouse model and pharmacological inhibition using antisense oligonucleotides targeted for Irf4. This amelioration was accompanied by a decreased number of IL-17A-producing CD4⁺ T cells in the skin. The findings of this study suggest that IRF4 plays a crucial role in the promotion of inflammation and exacerbation of IMQ-induced psoriasiform dermatitis. Consequently, IRF4 targeting could be a promising therapeutic strategy.

Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis. However, mechanisms associated with stem cell senescence require further investigation. In this study, we conducted a proteomic analysis of human dental pulp stem cells (HDPSCs) obtained from individuals of various ages. Our findings showed that the expression of NUP62 was decreased in aged HDPSCs. We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo. Conversely, the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs. Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression, we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1. This, in turn, stimulates the transcription of the epigenetic enzyme NSD2. Finally, the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes (HMGA1, HMGA2, and SIRT6). Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming.
Humans ; Dental Pulp/cytology* ; Nuclear Pore Complex Proteins/genetics* ; Cellular Senescence/genetics* ; Stem Cells/metabolism* ; Epigenesis, Genetic ; Cell Proliferation ; Cell Differentiation ; Histone-Lysine N-Methyltransferase/metabolism* ; Cells, Cultured ; Cellular Reprogramming ; Cell Movement ; Proteomics

Objective:To investigate the association between blood selenium levels and sex hormones in Chinese men aged 18-79 years.Methods:Data were derived from the China National Human Biomonitoring survey conducted in 2017-2018, with a final sample size of 5 414 men. General demographic characteristics, behavioral habits, and dietary frequency were collected through questionnaires and physical examinations. Fasting blood samples were collected to measure blood lead, serum testosterone, and estradiol levels. Complex sampling linear regression models were used to analyze the associations between blood selenium levels and testosterone, estradiol, and the testosterone/estradiol ratio, adjusting for confounding factors including age, education level, marital status, smoking status, alcohol consumption, seafood intake, soy product intake, protein supplement intake, BMI, and diabetes status.Results:The mean age of the 5 414 participants was (46.85±27.91) years; 4 774 (91.65%) were of Han ethnicity and 4 505 (86.68%) were married. The median ( Q1, Q3) blood selenium concentration in men was 97.80 (80.64, 116.99) μg/L. After adjusting for confounding factors, the complex sampling linear regression model revealed negative associations between blood selenium levels and both testosterone levels and the testosterone/estradiol ratio, with a significant linear trend ( Ptrend<0.05). Compared with the Q1 group, the β (95% CI) values for testosterone in the Q2, Q3, and Q4 groups were -0.02 (-0.06 to 0.02), -0.03 (-0.08 to 0.01), and -0.06 (-0.09 to -0.02), respectively. Similarly, the β (95% CI) values for the testosterone/estradiol ratio in the Q2, Q3, and Q4 groups were -0.01 (-0.03 to 0.02), -0.01 (-0.04 to 0.04), and -0.03 (-0.06 to -0.01), respectively. Subgroup analysis indicated stronger associations between blood selenium levels and testosterone/estradiol levels in non-smoking and obese men (BMI≥28 kg/m2). Conclusion:Blood selenium levels are negatively associated with testosterone levels and the testosterone/estradiol ratio in Chinese adult males.

Objective:To explore the association of blood and urinary cadmium levels with lipid profile levels and dyslipidemia in Chinese adults aged 18 to 79 years.Methods:Based on the China National Human Biomonitoring (CNHBM) program, a cross-sectional survey was conducted from 2017 to 2018 using a multi-stage stratified random sampling method, including a total of 10 713 adults aged 18 to 79 years. Data was obtained through questionnaires, physical examinations, biological sample collection, and laboratory testing. Multiple linear mixed effect model (MLMM) and generalized linear mixed effect model (GLMM) were used to analyze the association of blood and creatinine-corrected urinary cadmium levels with lipid profile levels as well as dyslipidemia among adults.Results:The age of 10 713 participants was (47.23±0.24) years, with 5 372 males accounting for 61.3% of the national population. The weighted mean±standard error (SE) of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) was (5.21±0.03), (1.86±0.03), (2.96±0.03), and (1.43±0.01) mmol/L, respectively. The prevalence rate of hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, low HDL-C, and high LDL-C was 16.0%, 21.6%, 6.6%, 13.5%, and 10.0%, respectively. MLMM showed that, after adjusting for relevant confounders, log-transformed blood cadmium levels were positively associated with increased levels of TC, TG and LDL-C ( P<0.05). When blood cadmium levels were categorized into quartiles, compared to the lowest exposure group ( Q1), participants in the highest blood cadmium exposure group ( Q4) had increases of 0.19 (95% CI: 0.06, 0.32) mmol/L in TC and 0.25 (95% CI: 0.08, 0.43) mmol/L in TG. GLMM indicated that, after adjusting for confounders, higher blood cadmium exposure levels were associated with increased risks of hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, and high LDL-C ( P<0.05). Further analysis by quartiles showed that, compared to the blood cadmium Q1 exposure group, the OR value (95% CI) for the Q4 group was 1.53 (1.12, 2.08) for hypercholesterolemia, 1.54 (1.09, 2.17) for hypertriglyceridemia, 2.24 (1.47, 3.40) for mixed hyperlipidemia, and 1.49 (1.07, 2.09) for high LDL-C. Conclusion:The cadmium internal exposure levels are associated with blood lipid profile levels as well as the incidence of dyslipidemia in Chinese adults aged 18 to 79.

Objective:To investigate the application of blended team-based learning (BTBL) in improving the clinical reasoning ability of general practitioners from different sources.Methods:From September to December in 2021, 52 postgraduates of general practice in Tongji University School of Medicine were selected as subjects, and according to their study background and practice experience, they were divided into residency training group, community group, and specialist group. BTBL was adopted for all students in the course of clinical reasoning in general practice, and a 4-station objective structured clinical examination (OSCE) test was conducted before and after the course to evaluate teaching effectiveness from the aspects of medical history collection, physical examination, doctor-patient communication, and medical record writing. SPSS 22.0 was used to perform a statistical analysis of data. Continuous data were expressed as mean±standard deviation, and an analysis of variance or the Kruskal-Wallis test was used for comparison between groups; the paired samples t-test or the Wilcoxon signed rank sum test was used for comparison of normally distributed or non-normally distributed data within each group. Categorical data were expressed as frequency and percentage. Results:There was a significant change in the score of physical examination after the course in the community group (44.88±9.17 vs. 78.06±12.11, t=-12.49, P<0.001), the specialist group (45.85±8.18 vs. 68.65±13.10, t=-6.43, P<0.001), and the residency training group (42.38±15.30 vs. 76.44±16.46, t=-5.98, P<0.001). There was a significant change in the score of doctor-patient communication after the course in the community group (63.00±13.84 vs. 78.69±7.10, t/Z=-4.33, P<0.05) and the residency training group (60.00±15.50 vs. 70.88±6.44, t/Z=-2.12, P<0.05). There was also a significant change in the score of medical record writing after the course in the community group (60.19±17.96 vs. 79.69±14.25, t=-2.96, P<0.05), the specialist group (47.77±12.59 vs. 80.31±12.93, t=-6.26, P<0.05), and the residency training group (37.00±15.50 vs. 75.88±15.88, t=-7.25, P<0.05). The score of medical record writing before the course was 60.19±17.96 in the community group, 47.77±12.59 in the specialist group, and 37.00±15.50 in the residency training group, with a significant difference between the three groups ( χ2=13.04, P=0.001); after the course, the score of medical record writing was 78.69±7.10 in the community group, 63.46±19.40 in the specialist group, and 70.88±6.44 in the residency training group, with a significant difference between the three groups ( χ2=10.13, P=0.006). Conclusions:In the course of clinical reasoning in general practice, BTBL can improve teaching efficiency, save teaching resources, and play the role of promoting strengths and avoiding weaknesses.