Caspase-8 is a cysteine-aspartate protease widely dis-tributed in cells.As a molecular"switch",caspase-8 is involved in the regulation of various modes of cell death,including apopto-sis,necroptosis and pyroptosis.During cerebral ischemia/reper-fusion,caspase-8 activation is one of the key factors inducing neuronal cell death.Currently there are both specific inhibitors of caspase-8,such as Z-IETD-FMK and Ac-IETD-CHO,as well as a variety of pan-caspase inhibitors,such as z-VAD,Q-VD-OPH,and enricosan.Both animal and cellular experiments have demonstrated that all of these inhibitors attenuate cerebral ische-mia/reperfusion injury,an effect that involves inhibition of caspase-8 activity and reduction of neuronal apoptosis.Clinical-ly,certain drugs for ischemic stroke reduce plasma caspase-8 ac-tivity,suggesting that caspase-8 may be a biomarker for the diag-nosis and prognosis of ischemic stroke.Finding and developing clinically valuable inhibitors around caspase-8 is expected to provide new ideas for new drug development in ischemic stroke.

Objective:To investigate potential factors associated with nephrocalcinosis in children with X-linked hypophosphatemic rickets (XLH).Methods:A case-control study was conducted involving XLH children who were regularly followed up at Children′s Hospital of Nanjing Medical University, from January 2016 to January 2024.Patients diagnosed with nephrocalcinosis were assigned to the case group, and those without nephrocalcinosis served as controls.A retrospective analysis was performed to examine the correlation between nephrocalcinosis and laboratory parameters, as well as the diagnostic value of relevant factors.Multivariable Logistic regression was used to identify factors associated with nephrocalcinosis in children with XLH.Receiver operating characteristic (ROC) curves were plotted for the significant factors, and the areas under the curve (AUC) were compared using Delong′s test to evaluate differences in predictive performance.Results:Univariate analysis revealed significant differences between the case and control groups in serum calcium, urinary calcium, urinary calcium/creatinine ratio, urinary phosphorus, and renal tubular maximum reabsorption rate of phosphate/glomerular filtration rate (TmPi/GFR) (all P<0.05).However, multivariate logistic regression analysis identified only urinary calcium ( B=0.489, P=0.001) and TmPi/GFR ( B=-0.886, P=0.007) as independent predictors, while the urinary calcium/creatinine ratio was not statistically significant.The sensitivity, specificity, optimal cutoff value, and AUC for urinary calcium in predicting nephrocalcinosis were 0.842, 0.833, 0.614 mmol/L, and 0.851 ( P<0.01), respectively.For TmPi/GFR, the corresponding values were 0.900, 0.877, 0.573 mmol/L, and 0.875 ( P<0.01).The Delong test showed no significant difference in AUC between the combined indicator and TmPi/GFR ( Z=-1.555, P=0.120) or urinary calcium alone ( Z=-1.598, P=0.110). Conclusions:Urinary calcium and TmPi/GFR are significantly associated with nephrocalcinosis in children with XLH and demonstrate good predictive performance for early detection.The combination of these two indicators does not outperform either individual marker in diagnostic accuracy.

The evaluation of blood compatibility of biomaterials is crucial for ensuring the clinical safety of implantable medical devices. To address the limitations of traditional testing methods in real-time monitoring and electrical property analysis, this study developed a portable electrical impedance tomography (EIT) system. The system uses a 16-electrode design, operates within a frequency range of 1 to 500 kHz, achieves a signal to noise ratio (SNR) of 69.54 dB at 50 kHz, and has a data collection speed of 20 frames per second. Experimental results show that the EIT system developed in this study is highly consistent with a microplate reader ( R ²=0.97) in detecting the hemolytic behavior of industrial-grade titanium (TA3) and titanium alloy-titanium 6 aluminum 4 vanadium (TC4) in anticoagulated bovine blood. Additionally, with the support of a multimodal image fusion Gauss-Newton one-step iterative algorithm, the system can accurately locate and monitor in real-time the dynamic changes in blood permeation and coagulation caused by TC4 in vivo. In conclusion, the EIT system developed in this study provides a new and effective method for evaluating the blood compatibility of biomaterials.
Electric Impedance ; Animals ; Tomography/instrumentation* ; Biocompatible Materials ; Materials Testing/instrumentation* ; Cattle ; Titanium ; Alloys ; Prostheses and Implants

Metastasis serves as an indicator of malignancy and is a biological characteristic of carcinomas. Epithelial-mesenchymal transition (EMT) plays a key role in the promotion of tumor invasion and metastasis and in the enhancement of tumor cell aggressiveness. Prostaglandin E synthase 3 (p23) is a cochaperone for heat shock protein 90 (HSP90). Our previous study showed that p23 is an HSP90-independent transcription factor in cancer-associated inflammation. The effect and mechanism of action of p23 on lung cancer metastasis are tested in this study. By utilizing cell models in vitro and mouse tail vein metastasis models in vivo, the results provide solid evidence that p23 is critical for promoting lung cancer metastases by regulating downstream CXCL1 expression. Rather than acting independently, p23 forms a complex with RNA-binding motif protein 14 (RBM14) to facilitate EMT progression in lung cancer. Therefore, our study provides evidence for the potential role of the RBM14-p23-CXCL1-EMT axis in the metastasis of lung cancer.

Objective:To analyze the correlation between mental health status and metabolic syndrome (MetS) in health checkup people.Methods:It was a cross-sectional study, 2 920 participants who received health checkup in the Health Examination Center of Peking University Third Hospital from January 2019 to December 2023 were selected using cluster sampling method. Their general information, physical examination, biochemical indicators, body composition, and self-evaluation scores on the Symptom Checklist-90 (SCL-90) were collected. According to the inclusion and exclusion criteria, a total of 2 813 study subjects were included, and divided into the MetS group and the non-MetS group based on whether they had MetS. The differences in general demographic information, body composition, blood biochemistry, and SCL-90 scores between the two groups were compared. Binary Logistic regression analysis was used to explore the correlation between mental health status and MetS.Results:Of the 2 813 subjects included, 1 576 were males (56.0%) and 1 237 were females (44.0%), with an average age of (41.7±11.0) years, the MetS group had 586 cases (20.8%) and the non-MetS group had 2 227 cases (79.2%). The MetS group had higher levels of age, body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, total cholesterol, triglycerides, low density lipoprotein cholesterol (LDL-C), fasting blood glucose, glycosylated hemoglobin (HbA 1c), free thyroxine(FT4), total triiodothyronine (TT3), free triiodothyronine (FT3), waist-to-hip ratio, visceral fat area, body fat percentage, uric acid/creatinine, homocysteine (Hcy), aspartate aminotransferases (AST), and alanine transaminase (ALT) levels, as well as higher scores for somatization, hostility, paranoia, and other factor compared to the non-MetS group (all P<0.05), while high density lipoprotein cholesterol (HDL-C) and estimated glomerular filtration rate (eGFR) levels were lower than those in the non-MetS group (all P<0.05). The proportion of male, and the positive rates of SCL-90, somatization, interpersonal sensitivity, hostility, paranoia and other factor in the MetS group were higher than those in the non-MetS group (all P<0.05). Multifactorial analysis showed that individuals with a positive SCL-90 assessment had a 1.34 times higher risk of MetS than those with a negative assessment ( OR=1.34, 95% CI: 1.06-1.68; P=0.014). Among them, individuals with positive somatization ( OR=2.02, 95% CI: 1.25-3.28; P=0.004) and hostility ( OR=1.61, 95% CI: 1.02-2.56; P=0.042) had increased risk of MetS. Conclusion:Poor mental health status increases the risk of MetS.

Objective:To explore the correlation between normalized grip strength (NGS) and normal weight obesity (NWO) in the population undergoing health check-ups.Methods:It was a cross-sectional study. A cluster sampling method was adopted to consecutively select 4 104 subjects who completed general health check-ups, body composition tests, and grip strength tests at the Medical Examination Center of Peking University Third Hospital from January 2019 to December 2023. The general information, physical examination results, biochemical indicators, body composition, and grip strength test results were collected. The subjects were grouped by gender and whether they had NWO (male: NWO group 314 cases, normal control group 690 cases; female: NWO group 834 cases, normal control group 2 266 cases). The differences in various indicators between the NWO group and the normal control group were compared by using t-tests, χ 2 tests, or Mann-Whitney U tests. The subjects were divided into four groups with the quartiles of NGS (Q 1-Q 4 groups), and binary logistic regression analysis was used to explore the correlation between the NGS and NWO. The receiver operating characteristic (ROC) curve was used to evaluate the optimal cut-off point of the NGS for diagnosing NWO. Results:Among the 4 104 subjects included in the analysis, 1 148 (28.0%) had NWO. The risk of NWO in both males and females increased with the decrease of NGS. Compared with the Q 4 group, the risk of NWO in the Q 2 and Q 1 groups of males increased by 2.600 times ( OR=2.600, 95% CI:1.556-4.343) and 4.350 times ( OR=4.350, 95% CI: 2.618-7.229), respectively; the risk of NWO in the Q 3, Q 2, and Q 1 groups of females increased by 2.024 times ( OR=2.024, 95% CI: 1.322-3.099), 4.265 times ( OR=4.265, 95% CI: 2.856-6.371), and 7.395 times ( OR=7.395, 95% CI: 4.991-10.956), respectively (all P<0.05). The optimal cut-off point of the NGS for diagnosing NWO in males and females was 0.636 2 and 0.472 2, respectively. Conclusions:The NGS is negatively correlated with the risk of NWO. Evaluation of the NGS can provide a reference for the early diagnosis and prevention of NWO.

Objective:To construct a health management mode for functional community groups and evaluate its health management effect.Methods:This study was a non-randomized controlled trial. A cluster sampling method was adopted to select 3 352 subjects who completed three health examinations at the Physical Examination Center of Peking University Third Hospital from January 2022 to October 2024 and received health management for two consecutive years from a certain functional community (an enterprise) in Beijing as the research subjects. A health management mode for functional community groups was constructed, and a cohort of the population was established. A health management platform was built, and the research subjects were included in the health management system. Comprehensive interventions were carried out using multiple methods, including disease risk assessment, daily monitoring and reminders, exercise and nutrition assessment and intervention, personal health consultation, and health science popularization knowledge push. The subjects were classified and analyzed based on general information such as age and gender. The changes in systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were assessed using One-way Repeated Measures Analysis of Variance before the intervention and at 1 and 2 years after the intervention. The changes in triglycerides were assessed using Generalized Estimating Equations before the intervention and at 1 and 2 years after the intervention.Results:The systolic blood pressure, total cholesterol, and LDL-C levels of the total population showed a linear decreasing trend after the intervention (all P0.001). The HDL-C level showed an overall upward trend after the intervention [(1.45±0.32) vs (1.39±0.30) vs (1.47±0.33) mmol/L, F=12.746, P0.001]. However, there was no linear change trend in diastolic blood pressure, fasting blood glucose, and triglycerides after the intervention (all P0.05). The systolic blood pressure, total cholesterol and LDL-C levels of both men and women showed a linear decreasing trend after the intervention. For men, systolic blood pressure [(128.6±16.1) vs (127.6±16.3) vs (126.5±15.5) mmHg (1 mmHg=0.133 kPa); F=33.488, P0.001], total cholesterol [(5.29±1.02) vs (5.07±1.00) vs (4.94±1.03) mmol/L; F=286.525, P0.001], and LDL-C [(3.45±0.86) vs (3.43±0.84) vs (3.33±0.83) mmol/L; F=55.419, P0.001] all decreased. For women, systolic blood pressure [(118.9±15.6) vs (117.5±15.6) vs (117.2±15.8) mmHg; F=34.188, P0.001], total cholesterol [(5.13±0.94) vs (4.96±0.90) vs (4.85±0.90) mmol/L; F=274.080, P0.001], and LDL-C [(3.13±0.79) vs (3.10±0.76) vs (3.10±0.75) mmol/L; F=6.861, P=0.009] also decreased. The HDL-C level of men showed an overall upward trend after the intervention [(1.30±0.26) vs (1.25±0.25) vs (1.32±0.28) mmol/L; F=6.866, P0.05]. For men and women, diastolic blood pressure, fasting blood glucose and triglyceride levels showed no linear change trend after the intervention (all P0.05). The systolic blood pressure and total cholesterol levels of all age groups showed a linear decreasing trend after the intervention(all P0.001). In the 50-59 age group, diastolic blood pressure showed a linear decreasing trend after intervention [(81.6±11.6) vs (80.1±11.6) vs (79.9±11.6) mmHg; F=7.043, P0.05]. In the 40-49 age group, triglyceride showed an overall decreasing trend after intervention [1.29(0.91-2.01) vs 1.27(0.88-1.91) vs 1.27(0.92-1.89) mmol/L; Wald χ 2=10.062, P0.05]. In the 30-39 age group, LDL-C showed a linear decreasing trend after intervention [(3.23±0.80) vs (3.20±0.79) vs (3.19±0.77) mmol/L; F=7.702, P0.05]. In the 40-49 age group, LDL-C also showed a linear decreasing trend after intervention [(3.39±0.84) vs (3.36±0.82) vs (3.30±0.80) mmol/L; F=22.801, P0.001]. In the 50-59 age group, LDL-C showed a linear decreasing trend after intervention [(3.38±0.92) vs (3.32±0.91) vs (3.15±0.88) mmol/L; F=27.920, P0.001]. In the 30-39 age group, HDL-C showed an overall increasing trend after intervention [(1.46±0.33) vs (1.39±0.31) vs (1.48±0.34) mmol/L; F=10.047, P0.05]. In the 40-49 age group, HDL-C also showed an overall increasing trend after intervention [(1.45±0.30) vs (1.40±0.30) vs (1.47±0.32) mmol/L; F=10.118, P0.05]. However, there was no linear change trend in fasting blood glucose and triglyceride levels in all age groups after intervention ( F=1.169, 2.643, 0.663, 0.001, all P0.05). Conclusion:The functional community group health management mode constructed in this study has a good effect.

Objective:To investigate the role of ubiquitin-specific protease 21 (USP21) in enterovirus group A type 71 (EV-A71) infection.Methods:Peripheral blood mononuclear cells (PBMC) were obtained from a cohort of 24 children infected with EV-A71 and 24 healthy children. Expression of USP21 was determined by real-time fluorescence quantitative PCR (qPCR). Additionally, the impact of USP21 overexpression or knockout on EV-A71 replication was evaluated using a combination of qPCR and western blot (WB) analysis. Furthermore, WB was employed to measure the levels of EV-A71 structural protein VP1, phosphorylated interferon regulatory factor 3 (IRF3) and other key molecules in the RIG-I-like receptor (RLR) signaling pathway. Co-immunoprecipitation (Co-IP) was utilized to investigate the effects of USP21 on the ubiquitin levels of EV-A71 nonstructural protein 2A protease (2A pro). Results:In comparison to healthy children, the expression of USP21 mRNA in PBMC of children infected with EV-A71 was notably elevated. The overexpression of USP21 significantly enhanced the cytopathic effects induced by EV-A71, upregulated levels of VP1 mRNA and protein, and facilitated EV-A71 replication, leading to a decrease in cell activity with increasing levels of USP21 transfection. Following the knockout of the USP21 gene, the VP1 mRNA levels were significantly declined in comparison to the control group. Furthermore, the overexpression of USP21 was found to have no impact on the transcriptional activity of EV-A71 2A pro. However, it was observed to enhance the expression of 2A pro protein, reduce the ubiquitination of 2A pro, suppress the protein levels of mitochondrial antiviral signaling protein (MAVS) and melanoma differentiation-associated gene 5 (MDA5), as well as decrease the phosphorylation of IRF3. Additionally, the induction of IFN-β mRNA by EV-A71 infection was downregulated. Conclusions:USP21 has been shown to enhance the replication of EV-A71 through the downregulation of 2A pro ubiquitination, suppression of MAVS and MDA5 protein expression, and inhibition of the interferon signaling pathway.

Caspase-8 is a cysteine-aspartate protease widely dis-tributed in cells.As a molecular"switch",caspase-8 is involved in the regulation of various modes of cell death,including apopto-sis,necroptosis and pyroptosis.During cerebral ischemia/reper-fusion,caspase-8 activation is one of the key factors inducing neuronal cell death.Currently there are both specific inhibitors of caspase-8,such as Z-IETD-FMK and Ac-IETD-CHO,as well as a variety of pan-caspase inhibitors,such as z-VAD,Q-VD-OPH,and enricosan.Both animal and cellular experiments have demonstrated that all of these inhibitors attenuate cerebral ische-mia/reperfusion injury,an effect that involves inhibition of caspase-8 activity and reduction of neuronal apoptosis.Clinical-ly,certain drugs for ischemic stroke reduce plasma caspase-8 ac-tivity,suggesting that caspase-8 may be a biomarker for the diag-nosis and prognosis of ischemic stroke.Finding and developing clinically valuable inhibitors around caspase-8 is expected to provide new ideas for new drug development in ischemic stroke.

Objective:To investigate potential factors associated with nephrocalcinosis in children with X-linked hypophosphatemic rickets (XLH).Methods:A case-control study was conducted involving XLH children who were regularly followed up at Children′s Hospital of Nanjing Medical University, from January 2016 to January 2024.Patients diagnosed with nephrocalcinosis were assigned to the case group, and those without nephrocalcinosis served as controls.A retrospective analysis was performed to examine the correlation between nephrocalcinosis and laboratory parameters, as well as the diagnostic value of relevant factors.Multivariable Logistic regression was used to identify factors associated with nephrocalcinosis in children with XLH.Receiver operating characteristic (ROC) curves were plotted for the significant factors, and the areas under the curve (AUC) were compared using Delong′s test to evaluate differences in predictive performance.Results:Univariate analysis revealed significant differences between the case and control groups in serum calcium, urinary calcium, urinary calcium/creatinine ratio, urinary phosphorus, and renal tubular maximum reabsorption rate of phosphate/glomerular filtration rate (TmPi/GFR) (all P<0.05).However, multivariate logistic regression analysis identified only urinary calcium ( B=0.489, P=0.001) and TmPi/GFR ( B=-0.886, P=0.007) as independent predictors, while the urinary calcium/creatinine ratio was not statistically significant.The sensitivity, specificity, optimal cutoff value, and AUC for urinary calcium in predicting nephrocalcinosis were 0.842, 0.833, 0.614 mmol/L, and 0.851 ( P<0.01), respectively.For TmPi/GFR, the corresponding values were 0.900, 0.877, 0.573 mmol/L, and 0.875 ( P<0.01).The Delong test showed no significant difference in AUC between the combined indicator and TmPi/GFR ( Z=-1.555, P=0.120) or urinary calcium alone ( Z=-1.598, P=0.110). Conclusions:Urinary calcium and TmPi/GFR are significantly associated with nephrocalcinosis in children with XLH and demonstrate good predictive performance for early detection.The combination of these two indicators does not outperform either individual marker in diagnostic accuracy.