Objective: To construct a hypertension risk prediction model for residents aged 18-79 years, so as to provide an assessment tool for early screening and prevention of hypertension in high-risk groups. Methods: The permanent residents aged 18-79 years from 6 townships (streets) in Fangshan District of Beijing Municipality were selected as the study subjects using a multi-stage stratified random sampling method from March to June 2023. Demographic information, lifestyle, body mass index (BMI), blood pressure, fasting blood glucose, and blood lipid were collected through questionnaire survey, physical examination, and laboratory tests. Subjects were randomly divided into training and validation sets at a 7∶3 ratio. The logistic regression model was used to screen the risk factors of hypertension, and a hypertension risk prediction nomogram was constructed. Receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis were used to verify the discrimination, fit, and clinical application value of the model. Results: A total of 4 438 subjects were included, including 2 365 males (53.29%) and 2 073 females (46.71%), with a mean age of (44.99±14.90) years. The prevalence of hypertension was 35.29% (1 566 cases), and the standardized prevalence was 24.74%. The logistic regression model screened out 9 influencing factors of hypertension. The nomogram was established as ln[p/ (1-p)]= -2.873 + 0.935×40-<50 years + 1.463×50-<60 years + 1.908×60-<70 years + 2.346×70-79 years + 0.298×male-0.675×college degree or above + 0.384×smoking + 0.227×drinking + 0.572×overweight + 1.449×obesity + 0.557×heart rate ≥80 beats/min + 0.428×diabetes + 0.484×dyslipidemia. The area under the ROC curve of the validation set was 0.821 (95%CI: 0.798-0.843), and the calibration curve results showed that the calibration curve fitted the actual curve well. Decision curve analysis showed that the threshold probability was in the range of 0.10 to 0.70, and the model had good predictive value and clinical application value. Conclusion The nomogram based on age, gender, educational level, smoking, drinking, body mass index, heart rate, diabetes, and dyslipidemia can be used to predict the risk of hypertension among residents aged 18-79 years.

Objective: To investigate the prevalence, awareness, treatment and control rates of diabetes among residents in Fangshan District, Bejing Municipality, so as to provide reference for strengthening the prevention and control of diabetes. Methods: The residents aged 18 to 79 years were selected in Fangshan District using multistage stratified cluster sampling method from March to June 2023. Demographic information, lifestyle, body mass index, fasting blood glucose, and blood lipid were collected through questionnaire surveys, physical examinations and laboratory tests. The prevalence, awareness, treatment and control rates of diabetes among residents were analyzed and their influencing factors were identified using a multivariable logistic regression model. Results: A total of 4 438 residents were enrolled, including 2 367 males (53.33%) and 2 071 females (46.67%), and had a mean age of (44.99±14.90) years. The prevalence, awareness, treatment and control rates of diabetes were 15.75%, 57.37%, 56.22% and 22.90%, respectively. Multivariable logistic regression analysis showed that age (aged 30 to 39 years, OR=1.624, 95%CI: 1.011-2.609; aged 40 to 49 years, OR=3.469, 95%CI: 2.163-5.561; aged 50 to 59 years, OR=4.202, 95%CI: 2.595-6.803; aged 60 to 69 years, OR=7.229, 95%CI: 4.406-11.862; aged 70 to 79 years, OR=7.929, 95%CI: 4.665-13.479), obesity (OR=1.368, 95%CI: 1.071-1.748), hypertension (OR=1.943, 95%CI: 1.601-2.359) and dyslipidemia (OR=2.754, 95%CI: 2.287-3.317) were the factors affecting the prevalence of diabetes. Sex (women, OR=1.529, 95%CI: 1.019-2.293), age (aged 40 to 49 years, OR=4.971, 95%CI: 1.681-14.698; aged 50 to 59 years, OR=6.070, 95%CI: 2.045-18.020; aged 60 to 69 years, OR=6.902, 95%CI: 2.287-20.832; aged 70 to 79 years, OR=6.954, 95%CI: 2.191-22.070) and hypertension (OR=1.906, 95%CI: 1.337-2.718) were the factors affecting the awareness of diabetes. Age (aged 40 to 49 years, OR=4.699, 95%CI: 1.594-13.855; aged 50 to 59 years, OR=5.990, 95%CI: 2.023-17.732; aged 60 to 69 years, OR=7.134, 95%CI: 2.370-21.470; aged 70 to 79 years, OR=6.639, 95%CI: 2.102-20.964) and hypertension (OR=1.857, 95%CI: 1.304-2.645) were the factors affecting the treatment of diabetes. Age (aged 40 to 49 years, OR=2.948, 95%CI: 1.349-6.438; aged 60 to 69 years, OR=2.344, 95%CI: 1.049-5.234) was the factor affecting the control of diabetes. Conclusions The prevalence rate of diabetes among residents in Fangshan District was high, and the improvements of awareness rate, treatment rate and control rate were not obvious. Health education and management of diabetes should be strengthened for elderly, hypertensive and dyslipidemic residents.

Objective:To investigate the early recognition of coronary artery lesions(CAL)in Kawasaki disease(KD)and its relationship with monocyte/high-density lipoprotein cholesterol(HDL-C)ratio(MHR).Methods:A total of 216 children with KD who were hospitalized in Affiliated Hospital of Nantong University from June 2019 to June 2022 were selected as the research subjects,and divided into training set(162 cases)and test set(54 cases).The clinical data of the children were collected,and the children in the training set were divided into the CAL group(45 cases)and the NCAL group(117 cases)according to the diagnostic results of echo-cardiography,and the differences in clinical data and laboratory test results were compared between the two groups;Logistic regres-sion analysis was used to analyze the risk factors of CAL in children with KD;Pearson was used to analyze the correlation between MHR and CAL in children with KD.According to the MHR quantile,the children in the CAL group were divided into low MHR group(≤0.28),medium MHR group(0.29～0.42)and high MHR group(≥0.43),and they were analyzed and compared.Cox regression model was used to analyze the relationship between MHR and CAL risk in children with KD,and a predictive model was constructed based on the independent risk factors of CAL in children with KD.Results:There were 162 KD children with fever,and summer was a high incidence period;compared with the NCAL group,the CAL group had statistically significant differences in age,gender,fever time,KD type,MHR,WBC,PLT,NLR,and CRP(all P<0.05);Pearson correlation analysis showed that MHR was positively cor-related with the degree of coronary artery dilatation in children with CAL(r=0.743,P=0.001).and the risk of CAL in the KD children in the high MHR group was significantly higher than that in the low MHR group(HR=2.857,95%CI:1.329～6.431,P=0.003);Logis-tic regression analysis showed that gender,fever time,MHR,WBC,NLR and CRP were independent risk factors for CAL in children with KD.A prediction model was constructed based on the independent risk factors of CAL:Logit(P)=1.342+0.359×gender+0.181×ever time+1.064×MHR+0.459×WBC+0.146×NLR+0.211×CRP,P=e logit(P)/1+e logit(P),the AUC of this model was 0.874(95%CI:0.799～0.892),compared with the test set(AUC was 0.881,95%CI:0.785～0.913),the difference was not statistically sig-nificant(P>0.05);the AUC of MHR for predicting CAL in children with KD was 0.796,the sensitivity was 0.896,and the specificity was 0.824,which could be used as an early predictor of CAL in children with KD.Conclusion:MHR has a certain predictive value in the diagnosis of CAL in children with KD,and can reflect the degree of CAL in children with KD to a certain extent.Therefore,it is necessary to pay attention to the changes of MHR in children with KD in clinical practice.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*

Medicine, Chinese Traditional ; Drugs, Chinese Herbal ; China

The dysregulation of transcription factors is widely associated with tumorigenesis. As the most well-defined transcription factor in multiple types of cancer, c-Myc can transform cells by transactivating various downstream genes. Given that there is no effective way to directly inhibit c-Myc, c-Myc targeting strategies hold great potential for cancer therapy. In this study, we found that WSB1, which has a highly positive correlation with c-Myc in 10 cancer cell lines and clinical samples, is a direct target gene of c-Myc, and can positively regulate c-Myc expression, which forms a feedforward circuit promoting cancer development. RNA sequencing results from Bel-7402 cells confirmed that WSB1 promoted c-Myc expression through the β-catenin pathway. Mechanistically, WSB1 affected β-catenin destruction complex-PPP2CA assembly and E3 ubiquitin ligase adaptor β-TRCP recruitment, which inhibited the ubiquitination of β-catenin and transactivated c-Myc. Of interest, the effect of WSB1 on c-Myc was independent of its E3 ligase activity. Moreover, overexpressing WSB1 in the Bel-7402 xenograft model could further strengthen the tumor-driven effect of c-Myc overexpression. Thus, our findings revealed a novel mechanism involved in tumorigenesis in which the WSB1/c-Myc feedforward circuit played an essential role, highlighting a potential c-Myc intervention strategy in cancer treatment.

Objective:To investigate the normal reference values of spinal bone mineral density measured by quantitative computed tomography (QCT) and the differences of bone mineral density (BMD) in different regions of in Chinese adult males.Methods:Men who underwent low-dose CT lung scan for cancer screening in regions of Northeast, North, East, South, Central and Southwest of China from January 2018 to December 2019 were selected. And the lumbar vertebrae BMD values in the male subjects were measured by the QCT system (Mindways Software, Inc.). The mean BMD values and their decline rates were calculated at an age interval of 10 years, and the prevalence of osteoporosis was calculated according to the American College of Radiology spine QCT osteoporosis diagnostic criteria.Results:A total of 50 682 males with a mean age of (50.22±12.79) years (ranged 20 to 98 years) were included in this study. The peak BMD of (173.11±28.56) mg/cm 3 in the healthy Chinese adult male population appeared in the age group of 20 to 29 years and then declined with age. Before the age of 70 years, the BMD was relatively higher in males in South China, and it was lower in Central China and Southwest China, and it was intermediate in Northeast, North and East of China, with statistically significant differences. There was no significant differences in BMD in the males in the two age groups of 70 to 79 years and 80 and older among the regions in China. The overall decline rate of spinal BMD in Chinese males under QCT was about 46.92% over the lifetime, and it declined obviouslyin the 40-49 age group. The overall prevalence of osteoporosis in Chinese male population aged 50 years and above was approximately 11.42%, with the highest prevalence in Southwest China and Central China (14.72% and 13.87%, respectively) and the lowest in North China and South China (8.53% and 7.71%, respectively). Conclusions:A reference of lumbar spine BMD values for healthy males in China based on QCT is established. BMD values were highest in South China and Lowest in Central China.

Objective:To investigate the association of metabolic syndrome(MS) with cardiovascular disease(CVD) mortality and all-cause mortality in peritoneal dialysis patients.Methods:A retrospective analysis was performed on patients who underwent peritoneal dialysis from January 1, 2013 to July 31, 2021 in the Shaoxing People′s Hospital. Patients were divided into MS group and non-MS group. The differences in baseline biochemical variables, comorbidities, and clinical outcomes between the two groups were compared. Kaplan-Meier method was used to obtain survival curves, the Cox regression model was used to evaluate the influence of MS for survival rates, and the inverse probability of treatment weighting(IPTW) was used to eliminate influence of the confounders in the groups.Results:A total of 494 peritoneal dialysis patients were enrolled in this study, which were divided into MS group( n=266) and non-MS group( n=228). The total median follow-up time was(31±22) months. At baseline, the standard mean difference( SMD) in smoking history, drinking history, CVD history, prevalence of chronic glomerulonephritis, left ventricular ejection fraction, B-type natriuretic peptides, hemoglobin, blood calcium, hypersensitive C-reactive-protein, intact parathyroid hormone, ultrafiltration and 4 h dialysate/plasma creatinine in the two groups were greater than 0.1. Their SMD decreased to under 0.1 after IPTW, showing a good balance between the two groups. The analysis of the survival curve of Kaplan Meier showed that the cumulative survival rate and cumulative CVD survival rate in MS group were significantly lower than those in non-MS group before and after IPTW( P<0.05). After IPTW was used to eliminate the effect of confounders, multivariate Cox regression analysis still displayed that MS was an independent risk factor for all-cause mortality( HR=1.824, 95% CI 1.121-2.968, P=0.015) and CVD mortality( HR=2.470, 95% CI 1.324-4.609, P=0.004)in peritoneal dialysis patients. Conclusion:The prevalence of metabolic syndrome is high in peritoneal dialysis patients. MS is an independent risk factor for all-cause mortality and CVD mortality in peritoneal dialysis patients.

Objective To investigate the relationship between (serum neutrophil gelatinase-associated lipocalin,sNGAL) and cardiovascular events in patients with chronic kidney disease(CKD).Methods 300 patients with CKD were divided into two groups according to the level of sNGAL:high sNGAL group (n=158) and low sNGAL group (n=142).The incidence of cardiovascular events and cumulative survival rate were analyzed by ROC curve,and the correlation between sNGAL and cardiovascular risk factors,cardiovascular events in patients with chronic renal disease was analyzed.Influencing factors of cardiovascular events in CKD patients was analyzed.Results There were significant differences in the data about BMI,diabetes proportion,CKD staging,eGFR,hsCRP,24h proteinuria,HDL,iPTH,phosphate and blood calcium between the two groups (P＜0.05).The 3-year cumulative survival rate of high sNGAL group(77.2％) was significantly lower than that of low sNGAL group(96.5％),and the 3-year incidence of cardiovascular events (37.9％) was significantly higher than that of low sNGAL group (9.8％) (P＜ 0.05).AUC in diagnosing cardiovascular events in high sNGAL group (0.746) was significantly higher than that in eGFR(0.636),age (0.504),serum calcium (0.545),HDL(0.594) and LDL (0.508,all P＜0.05).There was a significant correlation between sNGAL and eGFR,HDL,BMI,hs-CRP,iPTH and phosphate (P＜ 0.05).Both univariate and multivariate fact ors COX showed that sNGAL was a risk factor of cardiovascular events in patients with CKD (P＜0.05),((HR=1.976 and 1.588,95％ CI=1.443-2.724 and 1.144-2.143,respectively,P=0.O00 and 0.000)).Conclusions The incidence of cardiovascular events in patients with CKD with high sNGAL is significantly increased.sNGAL is an independent factor of cardiovascular events in patients with chronic renal disease.

Objective To investigate the clinical,endoscopic and pathological features of gastritis cystica profunda (GCP).Methods A total of 40 patients with GCP confirmed by pathology who received endoscopic or surgical treatment at Renji Hospital,School of Medicine,Shanghai Jiaotong University from May 2013 to May 2018,were included in the retrospective analysis.The clinical data such as population composition,clinical manifestations,endoscopic findings and pathological results were summarized and analyzed.Results Among the 40 patients were predominantly males (75.0％,30/40),and the mean age of onset was 61.2 years.The most common sites were cardia (32.5％,13/40) and gastric antrum (30.0％,12/40).The clinical symptoms of the patients were atypical and it was difficult to diagnose GCP with routine endoscopy examination.The endoscopic findings were mostly type 0-Ⅱ (50.0％,20/40).GCP with neoplastic lesions accounted for 55％ (22/40).Unconditional logistic regression analysis showed that male (P =0.013,OR =31.093,95％ CI:2.079-464.976) and Helicobacter pylori infection (P =0.041,OR =10.225,95％ CI:1.096-95.411) were risk factors for GCP with neoplastic lesions.Conclusion GCP commonly occurs in middle-aged and elderly men,and varies in different manifestations under white light endoscopy.GCP is not a benign lesion,but can also coexist with neoplastic lesions,which are mostly differentiated intramucosal cancer.