Objective To investigate the effects of the gene expression of carbohydrate response element binding protein(ChREBP)on human retinal microvascular endothelial cell(hRMEC)injury and angiogenesis under high-glucose conditions.Methods The hRMECs after 4-6 passages were added to a serum-free medium and cultured for 6 hours.Then,these hRMECs were treated by a normal concentration of glucose(5.6 mmol·L-1),a normal concentration of glu-cose+mannitol(24.4 mmol·L-1),a high concentration of glucose(30.0 mmol·L-1),blank siRNA+a high concentra-tion of glucose,and ChREBP siRNA+a high concentration of glucose,which were designed as the control group,hyperos-motic group,high-glucose alone group,blank siRNA group,and ChREBP knockdown group,respectively.Subsequently,these hRMECs were transfected with Lipofectamine RNAiMAX for 24 hours.Western blot was used to analyze the expression of ChREBP in hRMECs under high-glucose conditions.The terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assay,cell scratch assay,Transwell migration assay,and tube formation assay were conducted to analyze the apoptosis and migration of these cells and capillary angiogenesis.Normal ChREBP-expressing wild-type mice and ChREBP-knockout mutant mice were selected to construct corresponding animal models,and the number of retinal angiogenic sprouts was counted under a microscope.Results The relative protein expression level of ChREBP in hRMECs after 30 minutes of high-glucose stimulation was significantly higher than that after 15 minutes,1 hour,2 hours,and 3 hours of stimulation(all P＜0.05).Meanwhile,the relative protein expression level of TXNIP in hRMECs after 2 hours of high-glu-cose stimulation was significantly higher than that after 15 minutes,30 minutes,1 hour,and 3 hours of stimulation(all P＜0.05).Under high-glucose conditions,the relative protein expression level of TXNIP and NLRP3 in hRMECs of the ChREBP knockdown group was significantly lower than that of the blank siRNA group and the high-glucose alone group(all P＜0.05).The results of TUNEL assay,cell scratch assay,and capillary tube formation assay showed that the relative apopto-sis rate,relative cell coverage area percentage,and relative migrating cell number percentage of the ChREBP knockdown group were significantly lower than those of the blank siRNA group and the high-glucose alone group,whereas the number of ring structures was significantly lower than that of the blank siRNA group,the high-glucose alone group,and the hyper-osmotic group(all P＜0.05).The relative expression level of p-AKT/AKT and p-mTOR/mTOR in the ChREBP knockdown group was significantly lower than that in the blank siRNA group and the high glucose alone group(all P＜0.05).The num-ber of retinal angiogenic sprouts in ChREBP-knockout mutant mice was(22.81±4.03),which was significantly lower than that of normal ChREBP-expressing wild-type mice(64.35±11.69)(P＜0.05).Conclusion ChREBP can affect the oc-currence and development of diabetic retinopathy by regulating the apoptosis,migration,and tubulogenesis of hRMECs and the development of retinal neovascularization under high-glucose conditions,and hence it can be regarded as a potential target for the treatment of this disease.

Objective To investigate the effects of the gene expression of carbohydrate response element binding protein(ChREBP)on human retinal microvascular endothelial cell(hRMEC)injury and angiogenesis under high-glucose conditions.Methods The hRMECs after 4-6 passages were added to a serum-free medium and cultured for 6 hours.Then,these hRMECs were treated by a normal concentration of glucose(5.6 mmol·L-1),a normal concentration of glu-cose+mannitol(24.4 mmol·L-1),a high concentration of glucose(30.0 mmol·L-1),blank siRNA+a high concentra-tion of glucose,and ChREBP siRNA+a high concentration of glucose,which were designed as the control group,hyperos-motic group,high-glucose alone group,blank siRNA group,and ChREBP knockdown group,respectively.Subsequently,these hRMECs were transfected with Lipofectamine RNAiMAX for 24 hours.Western blot was used to analyze the expression of ChREBP in hRMECs under high-glucose conditions.The terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assay,cell scratch assay,Transwell migration assay,and tube formation assay were conducted to analyze the apoptosis and migration of these cells and capillary angiogenesis.Normal ChREBP-expressing wild-type mice and ChREBP-knockout mutant mice were selected to construct corresponding animal models,and the number of retinal angiogenic sprouts was counted under a microscope.Results The relative protein expression level of ChREBP in hRMECs after 30 minutes of high-glucose stimulation was significantly higher than that after 15 minutes,1 hour,2 hours,and 3 hours of stimulation(all P＜0.05).Meanwhile,the relative protein expression level of TXNIP in hRMECs after 2 hours of high-glu-cose stimulation was significantly higher than that after 15 minutes,30 minutes,1 hour,and 3 hours of stimulation(all P＜0.05).Under high-glucose conditions,the relative protein expression level of TXNIP and NLRP3 in hRMECs of the ChREBP knockdown group was significantly lower than that of the blank siRNA group and the high-glucose alone group(all P＜0.05).The results of TUNEL assay,cell scratch assay,and capillary tube formation assay showed that the relative apopto-sis rate,relative cell coverage area percentage,and relative migrating cell number percentage of the ChREBP knockdown group were significantly lower than those of the blank siRNA group and the high-glucose alone group,whereas the number of ring structures was significantly lower than that of the blank siRNA group,the high-glucose alone group,and the hyper-osmotic group(all P＜0.05).The relative expression level of p-AKT/AKT and p-mTOR/mTOR in the ChREBP knockdown group was significantly lower than that in the blank siRNA group and the high glucose alone group(all P＜0.05).The num-ber of retinal angiogenic sprouts in ChREBP-knockout mutant mice was(22.81±4.03),which was significantly lower than that of normal ChREBP-expressing wild-type mice(64.35±11.69)(P＜0.05).Conclusion ChREBP can affect the oc-currence and development of diabetic retinopathy by regulating the apoptosis,migration,and tubulogenesis of hRMECs and the development of retinal neovascularization under high-glucose conditions,and hence it can be regarded as a potential target for the treatment of this disease.

Background::Breast cancer (BC) risk-stratification tools for Asian women that are highly accurate and can provide improved interpretation ability are lacking. We aimed to develop risk-stratification models to predict long- and short-term BC risk among Chinese women and to simultaneously rank potential non-experimental risk factors.Methods::The Breast Cancer Cohort Study in Chinese Women, a large ongoing prospective dynamic cohort study, includes 122,058 women aged 25-70 years old from the eastern part of China. We developed multiple machine-learning risk prediction models using parametric models (penalized logistic regression, bootstrap, and ensemble learning), which were the short-term ensemble penalized logistic regression (EPLR) risk prediction model and the ensemble penalized long-term (EPLT) risk prediction model to estimate BC risk. The models were assessed based on calibration and discrimination, and following this assessment, they were externally validated in new study participants from 2017 to 2020.Results::The AUC values of the short-term EPLR risk prediction model were 0.800 for the internal validation and 0.751 for the external validation set. For the long-term EPLT risk prediction model, the area under the receiver operating characteristic curve was 0.692 and 0.760 in internal and external validations, respectively. The net reclassification improvement index of the EPLT relative to the Gail and the Han Chinese Breast Cancer Prediction Model (HCBCP) models for external validation was 0.193 and 0.233, respectively, indicating that the EPLT model has higher classification accuracy.Conclusions::We developed the EPLR and EPLT models to screen populations with a high risk of developing BC. These can serve as useful tools to aid in risk-stratified screening and BC prevention.

Objective:To summarize the experience of transthoracic epicardial insertion pacemaker for isolated congenital third-degree atrioventricular block (CAVB), and explore the necessity and feasibility of permanent pacemaker in the treatment of CAVB in neonates and infants.Methods:The clinical data and follow-up of four children with CAVB admitted to the Senior Department of Pediatrics, the Seventh Medical Center of PLA General Hospital from September 2010 to February 2022 were analyzed retrospectively.Two patients were implanted with permanent cardiac pacemakers during an early stage (less than one year old), and two patients were implanted during the non-early stage (one year old and above). All patients were diagnosed based on clinical symptoms, electrocardiogram and echocardiographic examination.After treatment, the pacing threshold, atrial sensing function, clinical symptoms, electrocardiogram and echocardiography examination of four patients were followed up.Results:All patients were successfully implanted with permanent cardiac pacemakers.One patient of non-early implantation was died of severe pneumonia and sepsis.During the follow-up period, pacing threshold, amplitude, impedance, minute ventilation and sensor function indicated pacemakers worked well in other three patients.Heart rates in these patients were significantly recovered, and showed growth trends in line with percentile curves for Chinese children and good movement skills.Conclusion:A pacemaker implantation performed by an experienced operator is a safe and feasible treatment for children with CAVB diagnosed in neonates and infants period with good prognosis.

To study and establish a set technology systems of sampling, investigation, quality control, and data analysis of complex sampling for chronic diseases and risk factor surveillance in China based on the requirements of the WHO and China's national conditions, and provide evidence for the policy making and prevention and control evaluation of chronic diseases and technical support for the research of chronic diseases. Through the study of complex sampling technique, adjustment of surveillance points and evaluation of their representatives, a national and provincial representative surveillance system and a complex weighted data analysis were established. According to the relevant plans, actions, and policies in China and other countries, the surveillance content and index system were studied and constructed, which was in line with China's national conditions, "1 + X" steps surveillance, covering the content of questionnaire , physical measurement, and laboratory testing. Based on modern information technology, a three-level platform of information collection and a multi-center laboratory quality control technology system were established, including sampling, information collection, biological sample management, quality control, and result display. Relying on the above research techniques, a national epidemiological investigation was conducted in China, which covered cerebrovascular disease, mental disorders, digestive system disease, and diabetes complications, to obtain the national representative data. This study reflected the innovation of "combination of medicine and prevention" and multi department cooperation in the fields of clinical medicine and public health and provided some big data for the health policy making and the evaluation of the effects of chronic disease prevention and control.

The application of tooth whitening technology in oral clinical diagnosis and treatment is becoming increasing widespread. Non-invasive tooth whitening based on bleaching technology has become the choice of many patients with tooth discoloration because of its unique advantage of not destroying the hard tissue of the tooth. The whitening effects differ according to the causes and degrees of tooth discoloration The effect of bleaching on tetracycline teeth is not as good as that of fluorosis teeth. The bleaching effect of hydrogen peroxide bleaching agents is similar to that of urea peroxide bleaching agents with the same concentration of hydrogen peroxide. The addition of non-peroxide agents such as bromelain to peroxide bleaching agents can improve the whitening effect on teeth. The whitening effect of a high-concentration bleaching agent can be achieved by using a low-concentration bleaching agent for a prolonged the working time. The effect of pH on tooth whitening is still controversial; the combination of lasers and traditional peroxide bleaching agents can effectively improve the whitening effect of teeth. The combination of enamel micro-grinding and peroxide tooth bleaching agents can improve the whitening effect in cases of dental fluorosis. This review analyzes the causes of tooth staining, the properties of bleaching agents, the application of laser microgrinding and the changes in tooth tissue after bleaching to discuss the influencing factors of the non-invasive tooth whitening effect mainly based on bleaching techniques.

Objective:To analyze the current situation of cardiovascular diseases and the exposure as well as control level of their risk factors in the Chinese residents.Methods:Based on the 2017 China Cardiovascular Health Index (hereafter referred to as CHI) study, data on the 29 indicators from three dimensions named as prevalence of cardiovascular disease, exposure to relevant risk factors, and prevention and control of risk factors of the 31 provinces in China (excluding Hong Kong, Macao and Taiwan) were obtained. To make a higher CHI score indicate better cardiovascular health levels, all the reverse metrics were firstly converted into positive metrics. Thenstandard normal conversion were adopted and a percentage score was assigned to each value according to its area proportion under the standard normal conversion distribution curve. Finally the scores of the three dimensions and the total CHI were calculated by weighted sum of these scores. Scores and ranks in each dimension were used to compare the performance in different provinces.Results:Heilongjiang, Tibet, Jilin, Henan, Xinjiang had the lowest scores in the prevalence of cardiovascular disease. Tianjin, Hebei, Liaoning, Shanxi and Beijing had the lowest scores in the exposure to relevant risk factors. Hainan, Guizhou, Yunnan, Shaanxi and Guangxi had the lowest in the prevention and control of risk factors. In terms of behavioral risk factors, smoking rates, rate of insufficient physical activity, obesity rate of adults aged 18 in the 31 provinces in China excluding Hong Kong, Macao, Taiwan were 26.80% (25.15%, 29.25%), 17.80% (11.60%, 19.45%) and 12.00% (8.90%, 17.95%), respectively. The daily per capital salt intake level was 8.6 (8.2, 9.3) g. As for metabolic risk factors, the prevalence of dyslipidemia (33.7%) exceeded hypertension (26.0%) and diabetes (9.7%), while its awareness rate (14.5%), treatment rate (7.9%) and control rate (5.4%) were all below the corresponding levels of hypertension and diabetes.Conclusion:Risk factors of cardiovascular disease in China is relatively severe and the prevention and control of dyslipidemia needs to be further strengthened.

Objective:To analyze the current situation of cardiovascular diseases and the exposure as well as control level of their risk factors in the Chinese residents.Methods:Based on the 2017 China Cardiovascular Health Index (hereafter referred to as CHI) study, data on the 29 indicators from three dimensions named as prevalence of cardiovascular disease, exposure to relevant risk factors, and prevention and control of risk factors of the 31 provinces in China (excluding Hong Kong, Macao and Taiwan) were obtained. To make a higher CHI score indicate better cardiovascular health levels, all the reverse metrics were firstly converted into positive metrics. Thenstandard normal conversion were adopted and a percentage score was assigned to each value according to its area proportion under the standard normal conversion distribution curve. Finally the scores of the three dimensions and the total CHI were calculated by weighted sum of these scores. Scores and ranks in each dimension were used to compare the performance in different provinces.Results:Heilongjiang, Tibet, Jilin, Henan, Xinjiang had the lowest scores in the prevalence of cardiovascular disease. Tianjin, Hebei, Liaoning, Shanxi and Beijing had the lowest scores in the exposure to relevant risk factors. Hainan, Guizhou, Yunnan, Shaanxi and Guangxi had the lowest in the prevention and control of risk factors. In terms of behavioral risk factors, smoking rates, rate of insufficient physical activity, obesity rate of adults aged 18 in the 31 provinces in China excluding Hong Kong, Macao, Taiwan were 26.80% (25.15%, 29.25%), 17.80% (11.60%, 19.45%) and 12.00% (8.90%, 17.95%), respectively. The daily per capital salt intake level was 8.6 (8.2, 9.3) g. As for metabolic risk factors, the prevalence of dyslipidemia (33.7%) exceeded hypertension (26.0%) and diabetes (9.7%), while its awareness rate (14.5%), treatment rate (7.9%) and control rate (5.4%) were all below the corresponding levels of hypertension and diabetes.Conclusion:Risk factors of cardiovascular disease in China is relatively severe and the prevention and control of dyslipidemia needs to be further strengthened.

Objective: To investigate the clinicopathological and radiological features of benign fibro-osseous lesion (BFOL). Methods: Sixty-five cases of craniofacial BFOL, eight cases of peripheral ossifying fibroma (POF) and one case of low-grade central osteosarcoma diagnosed at Sichuan Provincial People′s Hospital between January 2010 and March 2019 were collected. The clinicopathologic features, hematoxylin-eosin and immunohistochemical (IHC) staining and radiographic features were analyzed. MDM2 gene amplification was detected by FISH in difficult borderline cases. Results: This cohort of BFOLs included 50 cases of fibrous dysplasia (FD), 12 cases of ossifying fibroma (OF), and three cases of juvenile psammomatoid ossifying fibroma (JPOF). The average ages of patients with FD,OF and JPOF were 31.7, 39.2 and 26.0 years respectively. The male to female ratio was 1.0∶1.8.The average age of POF was 47.0 years, with male to female ratio of 1∶7. Patient of low-grade central osteosarcoma was a 48-year-old man. Twenty-seven cases of FD were located in the jaw, and 23 cases were in other craniofacial bones. Nine cases of OF were located in the jaw, and three cases were in the nasal cavity. Two cases of JPOF were in the nasal sinus, and one was in the jaw. All POF were located in the gingiva, and low-grade central osteosarcoma was located in the mandible. The imaging features of FD were luffa-like or ground-glass like signal shadows with poorly defined borders with expansion. OF had clear borders or sclerosing margins. Both JOF and low-grade central osteosarcoma were expansile intraosseously and with focally invasive nodular masses with ground-glass like signal shadows; and POF showed soft tissue mass with bone formation. Histological features of BFOLs showed mixed fibrous and irregular osteoid lesions. FD had no clear relationship with the host bone and no osteoblasts surrounded the bone trabeculae. Osteoblasts rimming was found in OF, and the boundaries of the host bone were clear. JPOF and low-grade central osteosarcoma infiltrated the host bone focally, and the latter showed mild cellular atypia. MDM2 amplification was detected in low-grade central osteosarcoma. Conclusions BFOLs are a group of fibro-osseous lesions with similar morphology in the head and neck and face, but their clinical features and prognosis are different; and their imaging and histological characteristics are also slightly different. Attentions should be given to the combination of clinical, imaging and pathologic features of BFOLs, especially the differential diagnosis between BFOLs and low-grade central osteosarcoma. Molecular detection could be used to assist the diagnosis in difficult cases.

Objective To establish a prokaryotic expression system of interstitial lung disease associated autoantigen human bactericidal/permeability-increasing fold-containing B1 (BPIFB1), providing tools for the study on its function in immune responese. Methods The coding region of BPIFB1 gene was amplified with specific primers from recombinant pGEM-C20ORF114 plasmid and cloned into the pET28a-MBP-His and pGEX-5X-1 vectors. The recombinant pET-BPIFB1-MBP-His and pGEX-BPIFB1-GST plasmids were transfected into Top10 cells. The positive clones were selected and sequenced. The correct clones of pET-BPIFB1-MBP-His and pGEX-BPIFB1-GST were transfected into prokaryotic expression strain Rosetta (DE3) and induced by Isopropyl β-D-Thiogalactoside (IPTG). The expression of recombinant BPIFB1 fusion protein was analyzed by SDS-PAGE and Western blotting, and purified by urea modified and renaturation and affinity chromatography of nickel NTA-resin. Results The polymerase chain reaction (PCR) produced specific product with the molecular weight equivalent to that of BPIFB1. The recombinant pET-BPIFB1-MBP-His and pGEX-BPIFB1-GST plasmids were cloned by double restriction enzyme digestion and ligation and confirmed by sequencing. The SDS-PAGE result showed that both BPIFB1-MBP and BPIFB1-GST fusion proteins were mainly expressed in the form of inclusion bodies. The Western blotting result revealed that the recombinant BPIFB1-MBP-His protein could be recognized by Anti-6 ×His antibody. The purified soluble BPIFB1-MBP fusion protein was obtained by urea denaturation, affinity chromatography of nickel NTA-resin and then renaturation after purification. Conclusion The BPIFB1 prokaryotic expression system is established by construct recombinant plasmid pET-BPIFB1-MBP-His, and an approach of renaturation after nickel resin affinity purification in denatured condition.