Correlation between Combined Urinary Metal Exposure and Grip Strength under Three Statistical Models: A Cross-sectional Study in Rural Guangxi / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength.@*METHODS@#We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.@*RESULTS@#In the multimetal linear regression, Cu (β = -2.119), As (β = -1.318), Sr (β = -2.480), Ba (β = 0.781), Fe (β = 1.130) and Mn (β = -0.404) were significantly correlated with grip strength ( P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95% confidence interval: -1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn ( P interactions of 0.003 and 0.018, respectively).@*CONCLUSION@#In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Factors Associated With Coronary Heart Disease Among Adult Residents in Jinjiang District,Chengdu City / 中国医学科学院学报

Objective To analyze the prevalence of coronary heart disease among community residents over 18 years old in Jinjiang district of Chengdu city,Sichuan province,and explore its associated factors,so as to provide a reference for the prevention and control of coronary heart disease in communities.Methods From October 15 to November 10 in 2021,a total of 5220 adult residents from 33 communities in Jinjiang were selected by multi-stage stratified random sampling for face-to-face questionnaire survey,physical examination,and laboratory blood test.Binary Logistic regression was employed to predict the factors associated with coronary heart disease among adult residents in Jinjiang.Results The crude and standard prevalence rates of coronary heart disease among 5220 adult residents were 3.39% and 2.11%,respectively.Logistic regression analysis showed that age (OR=1.068,95%CI=1.051-1.086,P<0.001),depressive symptoms (OR=1.639,95%CI=1.037-2.591,P=0.034),regular exercise (OR=0.584,95%CI=0.378-0.902,P=0.015),elevated blood pressure (OR=3.529,95%CI=2.344-5.312,P<0.001),dyslipidemia (OR=2.152,95%CI=1.291-3.587,P=0.003),and core knowledge score of chronic diseases (OR=1.144,95%CI=1.066-1.228,P<0.001) were associated with coronary heart disease among adult residents in Jinjiang.Conclusions The prevalence of coronary heart disease is high among adult residents in Jinjiang district of Chengdu.The urban residents who are older,have depressive symptoms,lack of exercise,elevated blood pressure,dyslipidemia,and score higher on core knowledge of chronic diseases are prone to coronary heart disease.

Research progress of the regulation of orphan nuclear receptors on chronic liver diseases / 生理学报

The development of chronic liver disease can be promoted by excessive fat accumulation, dysbiosis, viral infections and persistent inflammatory responses, which can lead to liver inflammation, fibrosis and carcinogenesis. An in-depth understanding of the etiology leading to chronic liver disease and the underlying mechanisms influencing its development can help identify potential therapeutic targets for targeted treatment. Orphan nuclear receptors (ONRs) are receptors that have no corresponding endogenous ligands to bind to them. The study of these ONRs and their biological properties has facilitated the development of synthetic ligands, which are important for investigating the effective targets for the treatment of a wide range of diseases. In recent years, it has been found that ONRs are essential for maintaining normal liver function and their dysfunction can affect a variety of liver diseases. ONRs can influence pathophysiological activities such as liver lipid metabolism, inflammatory response and cancer cell proliferation by regulating hormones/transcription factors and affecting the biological clock, oxidative stress, etc. This review focuses on the regulation of ONRs, mainly including retinoid related orphan nuclear receptors (RORs), pregnane X receptor (PXR), leukocyte cell derived chemotaxin 2 (LECT2), Nur77, and hepatocyte nuclear factor 4α (HNF4α), on the development of different types of chronic liver diseases in different ways, in order to provide useful references for the therapeutic strategies of chronic liver diseases based on the regulation of ONRs.

The neuroprotective effect of salidroside prophylactic administration on MCAO model rats / 中国药理学通报

Aim To investigate the neuroprotective effect of prophylactic administration of salidroside (Sal) on MCAO rats. Methods A total of 52 SD adult male rats were randomly divided into sham operation group (Sham), model group (MCAO) and salidroside pre-administration group (MCAO + Sal). The dose of Sal was 50 mg·kg

The synergistic effect of withaferin A combined with cisplatin on cervical cancer and its mechanism / 中国药理学通报

Aim To study the synergistic effect of withaferin A (WA) combined with cisplatin (DDP) on cervical cancer and its mechanism. Methods MTT assay was employed to detect the synergistic effect of WA on DDP in cervical cancer cell lines. Annexin V-FITC/PI staining, TUNEL assay and immunoblotting were used to investigate the effect of WA combined with DDP on apoptosis of cervical cancer cells. Immunofluorescence and immunoblotting were used to detect NF-kB/MDR1 pathway related proteins. DCFH-DA and MitoSOX were applied to determine the intracellular reactive oxygen species (ROS) levels. A xenograft model was also used to evaluate the synergistic effect of WA on DDP. Results The combination of WA and DDP could inhibit the survival of cervical cancer cells, promote apoptosis, and inhibit the growth of tumor in mice. WA could inhibit DDP-induced NF-kB/MDR1 signaling pathway and promote ROS production. Conclusions WA plays a synergistic role in anti-cervical cancer by inhibiting DDP-induced NF-kB/MDR1 pathway activation and enhancing DDP induced ROS production.

Peptide P3 ameliorates foam cell formation in RAW264.7 cells and its molecular mechanisms / 中国药理学通报

Aim To examine the effect of peptide P3 on lipid accumulation in RAW264.7 cells and the underlying molecular mechanism. Methods MTT method was used to screen the concentration of peptide P3 and oxidized low density lipoprotein(ox-LDL),and RAW.264.7 cells were induced to form foam cells by ox-LDL with 80 mg·L

Clinical Characteristics and Risk Factors in Children with Acute Leukemia Complicated with Multiple Drug Resistant Bacterial Septicemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics and risk factors of acute leukemia complicated with multi-drug resistant bacterial septicemia in children.@*METHODS@#The clinical data of children with acute leukemia complicated with septicemia admitted to the Affiliated Hospital of Guangdong Medical University from January 2013 to May 2021 were retrospectively analyzed. Their flora composition and drug resistance were also analyzed. The children were divided into multi-drug resistant bacteria (MDRB) group and non-multi-drug resistant bacteria (non-MDRB) group according to the drug sensitivity results, and the differences in clinical data between the two group were compared.@*RESULTS@#A total of 108 children had drug sensitivity results, 47 cases in the MDRB group, including 26 strians of Gram-positive bacteria (G+), the most common multi-drug resistant G+ bacteria were coagulase-negative staphylococci (CoNS) and Staphylococcus aureus, and the most common multi-drug resistant Gram-negative bacteria G- bacteria were Escherichia coli and Klebsiella pneumoniae subspecies pneumoniae. Compared with non-MDRB group, children in MDRB group had higher C-reactive protein (CRP) level and mortality rate (P <0.001, P =0.009), lower initial empirical anti-infection efficiency (P <0.001), and were more likely to have septic shock (P =0.003). Logistic analysis showed that the risk factors of acute leukemia complicated with MDRB septicemia in children were previous MDRB infection (OR =6.763, 95% CI: 1.141-40.092, P =0.035), duration of agranulocytosis before infection≥7 days (OR =3.071, 95% CI: 1.139-8.282, P =0.027), and previous use of antimicrobial drugs within 90 days before infection (OR =7.675, 95% CI: 1.581-37.261, P =0.011).@*CONCLUSIONS@#The clinical features of acute leukemia complicated with MDRB septicemia in children include a heavy inflammatory response, significantly elevated CRP, susceptibility to secondary septic shock, low efficiency of initial empirical anti-infective therapy, and high mortality rate. Previous MDRB infection, duration of agranulocytosis before infection≥7 days, and previous use of antimicrobial drugs within 90 days before infection are risk factors of acute leukemia complicated with MDRB septicemia in children.

Construction of an epileptic seizure prediction model using a semi-supervised method of generative adversarial and long short term memory network combined with Stockwell transform / 南方医科大学学报

OBJECTIVE@#To propose a semi-supervised epileptic seizure prediction model (ST-WGAN-GP-Bi-LSTM) to enhance the prediction performance by improving time-frequency analysis of electroencephalogram (EEG) signals, enhancing the stability of the unsupervised feature learning model and improving the design of back-end classifier.@*METHODS@#Stockwell transform (ST) of the epileptic EEG signals was performed to locate the time-frequency information by adaptive adjustment of the resolution and retaining the absolute phase to obtain the time-frequency inputs. When there was no overlap between the generated data distribution and the real EEG data distribution, to avoid failure of feature learning due to a constant JS divergence, Wasserstein GAN was used as a feature learning model, and the cost function based on EM distance and gradient penalty strategy was adopted to constrain the unsupervised training process to allow the generation of a high-order feature extractor. A temporal prediction model was finally constructed based on a bi-directional long short term memory network (Bi-LSTM), and the classification performance was improved by obtaining the temporal correlation between high-order time-frequency features. The CHB-MIT scalp EEG dataset was used to validate the proposed patient-specific seizure prediction method.@*RESULTS@#The AUC, sensitivity, and specificity of the proposed method reached 90.40%, 83.62%, and 86.69%, respectively. Compared with the existing semi-supervised methods, the propose method improved the original performance by 17.77%, 15.41%, and 53.66%. The performance of this method was comparable to that of a supervised prediction model based on CNN.@*CONCLUSION@#The utilization of ST, WGAN-GP, and Bi-LSTM effectively improves the prediction performance of the semi-supervised deep learning model, which can be used for optimization of unsupervised feature extraction in epileptic seizure prediction.

The past, present and future of sleep medicine in China / 北京大学学报(医学版)

Sleep is a highly conserved phenomenon in endotherms, and has a universal physiological function across all species. In mammals, sleep can be divided into two stages: rapid eye movement (REM) sleep and non-REM (NREM) sleep, which alternate in a cyclic manner. Humans spend about one-third of their lives asleep. Sufficient sleep is necessary for humans to sustain everyday functioning. Sleep plays an important role in regulating energy metabolism, immune defense, endocrine function, and the consolidation of memory process. With the development of social economy and the change of life style, sleep duration of the residents has gradually decreased and the incidence of sleep disturbances has increased. Sleep disturbances can lead to severe mental disorders, such as depression, anxiety disorders, dementia, and other mental diseases, and may increase the risk of physical diseases, such as chronic inflammation, heart disease, diabetes, hypertension, atherosclerosis and others. Maintaining good sleep is of great significance for developing social productive forces, promoting sustainable development of economic society, and is a necessary condition for carrying out the "Healthy China Strategy". The sleep research in China started in 1950s. After decades of development, researchers have made great progress in the molecular mechanisms of sleep and wakefulness, the pathogenesis of sleep disorders and the development of new therapies. With the advancement of science and technology and the public's attention to sleep, the level of clinical diagnosis and therapy of sleep disorders in China is gradually brought in line with international standards. The publication of diagnosis and treatment guidelines in the field of sleep medicine will promote the standardization of the construction. In the future, it is still necessary to promote the development of sleep medicine in the following aspects: Strengthening the professional training and discipline construction, improving the cooperation of sleep research, promoting the intelligent diagnosis and treatment of sleep disorders, and developing the new intervention strategies. Therefore, this review will comprehensively summarize the origin, current situation, and future expectations of sleep medicine in China, including discipline construction of sleep medicine, the number of sleep project grants, research findings, the status and progress of diagnosis and treatment of sleep disorders, and the development direction of sleep medicine.

Effect of respiratory filter on pulmonary function in occupational health examination / 中华劳动卫生职业病杂志

Objective: To explore the influence and significance of respiratory filter on the judgment of pulmonary function and the conclusion of occupational health examination in occupational health examination. Methods: From August to November 2020, 252 occupational health examinees were randomly selected as the research objects, and the lung function was examined with the respiratory filter bite and the straight cylinder bite without filter, respectively. The lung function examination indexes and the qualification rate of lung function examination were analyzed and compared between the two groups, and the diagnostic criteria of lung function examination was corrected. Results: 252 subjects were 36 (30, 42) years old. The qualified rate of lung function examination with respiratory filter bite (28.17%, 71/252) was lower than that with straight cylinder bite (34.92%, 88/252) , the difference was statistically significant (P<0.05) . The percentage of forced vital capacity in normal predicted value (FVC%) , percentage of forced expiratory volume in the first second in normal predicted value (FEV(1)%) , and percentage of forced expiratory volume in the first second in forced vital capacity (FEV(1)/FVC%) of subjects using respiratory filter bite were lower than those using the straight cylinder bite (P<0.05) . The corrected diagnostic criteria of pulmonary function were FVC%>78%, FEV(1)%>77%, FEV(1)/FVC%>68%. There was no significant difference between the qualified rate of the respiratory filter bite lung function test calculated according to the corrected diagnostic criteria (35.71%, 90/252) and the qualified rate of the straight cylinder bite lung function test calculated according to the original diagnostic criteria (34.92%, 88/252) (P>0.05) . Conclusion: In occupational health examination, the use of respiratory filter may affect the results of pulmonary function examination. The diagnostic criteria of pulmonary function can be corrected according to different filtering effects to ensure the accuracy of the conclusions of occupational health examination.

The distribution of blood pressure and associated factors of the elderly with type 2 diabetes in Jiangsu Province / 中华预防医学杂志

Objective: To investigate the distribution of blood pressure and analyze the associated factors of blood pressure of the elderly with type 2 diabetes in Jiangsu Province. Methods: The elderly over 60 years old participants with type 2 diabetes in the communities of Huai'an City and Changshu City, Jiangsu Province were selected in this study. They were divided into two groups: taking antihypertensive drugs and not taking antihypertensive drugs. The demographic characteristics, such as age and sex, and relevant factors were collected by questionnaire. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by physical examination. The percentile of SBP and DBP in each age group of men and women were described. The kernel density estimation curve was used to show the blood pressure distribution. The trend of blood pressure with age was fitted by locally weighted regression. The logistic regression model was used to analyze relevant factors of blood pressure. Results: A total of 12 949 participants were included in this study, including 7 775 patients in the antihypertensive drug group and 5 174 patients in the group without antihypertensive drugs. The SBP of participants was concentrated at 140-160 mmHg, and their DBP was concentrated at 75-85 mmHg. There were significant differences in the distribution of blood pressure among the subgroups of body mass index (BMI) and rural areas whether taking antihypertensive drugs and not. For participants aged under 80 years old, the SBP showed an increasing trend with age and the DBP showed a decreasing trend with age. Age, BMI ≥24 kg/m2, fasting blood glucose ≥7.0 mmol/L, living in rural areas and no smoking were influencing factors of the elevated SBP; BMI ≥24 kg/m2, male, living in rural areas, no smoking, drinking alcohol and not receiving drug hypoglycemic treatment were influencing factors of the elevated DBP. Conclusion: The SBP of older diabetic adults in Jiangsu Province is at a high level, and the distribution of blood pressure is significantly different between men and women in taking antihypertensive drugs group. The SBP presents a rising trend and the DBP is decreasing at the age of 60-80 years. The blood pressure level of this population are mainly affected by age, BMI, urban and rural areas, smoking.

New progress and challenges in the diagnosis and treatment of cosmetic allergy-related adverse reactions / 中华预防医学杂志

In China, the current standard for cosmetic adverse reactions related skin disease (GB/T 17149.1-1997) was jointly issued by the Ministry of Health and the State Bureau of Technical Supervision in 1997, cosmetic-allergic adverse reactions include allergic contact dermatitis and photo-allergic contact dermatitis according to this standard. The increasing use and changes in cosmetic ingredients or formula lead to a significant increase for the incidence of adverse reactions as the cosmetics industry is developing rapidly in the last 20 years. In the meantime, the clinical manifestations have become more diverse. In recent years, there have been many reports on the special manifestations for cosmetic allergy and allergen test, which provide a reference for the subsequent improvement of the diagnosis and prevention.

Analysis of dyslipidemia management status in atrial fibrillation patients with very high and high risk of atherosclerotic cardiovascular disease / 中华心血管病杂志

Objective: To analyze the status of statins use and low-density lipoprotein cholesterol (LDL-C) management in patients with atrial fibrillation (AF) and very high/high risk of atherosclerotic cardiovascular disease (ASCVD) from Chinese Atrial Fibrillation Registry (CAFR). Methods: A total of 9 119 patients with AF were recruited in CAFR between January 1, 2015 to December 31, 2018, patients at very high and high risk of ASCVD were included in this study. Demographics, medical history, cardiovascular risk factors, and laboratory test results were collected. In patients with very high-risk, a threshold of 1.8 mmol/L was used as LDL-C management target and in patients with high risk, a threshold of 2.6 mmol/L was used as LDL-C management target. Statins use and LDL-C compliance rate were analyzed, multiple regression analysis was performed to explore the influencing factors of statins use. Results: 3 833 patients were selected (1 912 (21.0%) in very high risk of ASCVD group and 1 921 (21.1%) in high risk of ASCVD group). The proportion of patients with very high and high risk of ASCVD taking statins was 60.2% (1 151/1 912) and 38.6% (741/1 921), respectively. Attainment rate of LDL-C management target in patients with very high and high risk were 26.7% (511/1 912) and 36.4% (700/1 921), respectively. Conclusion: The proportion of statins use and attainment rate of LDL-C management target are low in AF patients with very high and high risk of ASCVD in this cohort. The comprehensive management in AF patients should be further strengthened, especially the primary prevention of cardiovascular disease in AF patients with very high and high risk of ASCVD.

Current use of oral anticoagulation therapy and influencing factors among coronary artery disease patients with nonvalvular atrial fibrillation in China / 中华心血管病杂志

Objective: To investigate current use of oral anticoagulant (OAC) therapy and influencing factors among coronary artery disease (CAD) patients with nonvalvular atrial fibrillation (NVAF) in China. Methods: Results of this study derived from "China Atrial Fibrillation Registry Study", the study prospectively enrolled atrial fibrillation (AF) patients from 31 hospitals, and patients with valvular AF or treated with catheter ablation were excluded. Baseline data such as age, sex and type of atrial fibrillation were collected, and drug history, history of concomitant diseases, laboratory results and echocardiography results were recorded. CHA2DS2-VASc score and HAS-BLED score were calculated. The patients were followed up at the 3rd and 6th months after enrollment and every 6 months thereafter. Patients were divided according to whether they had coronary artery disease and whether they took OAC. Results: 11 067 NVAF patients fulfilling guideline criteria for OAC treatment were included in this study, including 1 837 patients with CAD. 95.4% of NVAF patients with CAD had CHA2DS2-VASc score≥2, and 59.7% of patients had HAS-BLED≥3, which was significantly higher than NVAF patients without CAD (P<0.001). Only 34.6% of NVAF patients with CAD were treated with OAC at enrollment. The proportion of HAS-BLED≥3 in the OAC group was significantly lower than in the no-OAC group (36.7% vs. 71.8%, P<0.001). After adjustment with multivariable logistic regression analysis, thromboembolism(OR=2.48,95%CI 1.50-4.10,P<0.001), left atrial diameter≥40 mm(OR=1.89,95%CI 1.23-2.91,P=0.004), stain use (OR=1.83,95%CI 1.01-3.03, P=0.020) and β blocker use (OR=1.74,95%CI 1.13-2.68,P=0.012)were influence factors of OAC treatment. However, the influence factors of no-OAC use were female(OR=0.54,95%CI 0.34-0.86,P=0.001), HAS-BLED≥3 (OR=0.33,95%CI 0.19-0.57,P<0.001), and antiplatelet drug(OR=0.04,95%CI 0.03-0.07,P<0.001). Conclusion: The rate of OAC treatment in NVAF patients with CAD is still low and needs to be further improved. The training and assessment of medical personnel should be strengthened to improve the utilization rate of OAC in these patients.

Research progress in microevolutionary process of excellent traits and quality of Dao-di herbs / 中国中药杂志

Dao-di herbs are the treasure of Chinese materia medica and one of the characteristic research objects of traditional Chinese medicine(TCM). Probing into the microevolution of Dao-di herbs can help to reveal their biological essence and quality formation mechanisms. The progress in molecular biology and omics provides the possibility to elucidate the phylogenetic and quality forming characteristics of Dao-di herbs at the molecular level. In particular, genomics serves as a powerful tool to decipher the genetic origins of Dao-di herbs, and molecular markers have been widely used in the research on the genetic diversity and population structure of Dao-di herbs. Focusing on the excellent traits and quality of Dao-di herbs, this paper reviews the studies about the microevolution process of quality formation mechanisms of Dao-di herbs with the application of molecular markers and omics, aiming to underpin the protection and utilization of TCM resources.

Research on applying genetic and environmental risk score in risk-adapted colorectal cancer screening / 中华流行病学杂志

Objective: To evaluate the effectiveness of a risk-adapted colorectal cancer screening strategy constructed utilizing genetic and environmental risk score (ERS). Methods: A polygenic risk score (PRS) was constructed based on 20 previously published single nucleotide polymorphisms for colorectal cancer in East Asian populations, using 2 160 samples with MassARRAY test results from a multicenter randomized controlled trial of colorectal cancer screening in China. The ERS was calculated using the Asia-Pacific Colorectal Screening Score system. Logistic regression was used to analyze the association between PRS alone and PRS combined with ERS and colorectal neoplasms risk, respectively. We also designed a risk-adapted screening strategy based on PRS and ERS (high-risk participants undergo a single colonoscopy, low-risk participants undergo an annual fecal immunochemical test, and those with positive results undergo further diagnostic colonoscopy) and compared its effectiveness with the all-acceptance colonoscopy strategy. Results: The high PRS group had a 26% increased risk of colorectal neoplasms compared with the low PRS group (OR=1.26, 95%CI: 1.03-1.54, P=0.026). Participants with the highest PRS and ERS were 3.03 times more likely to develop advanced colorectal neoplasms than those with the lowest score (95%CI: 1.87-4.90, P<0.001). As the risk-adapted screening simulation reached the third round, the detection rate of the PRS combined with ERS strategy was not statistically different from the all-acceptance colonoscopy strategy (8.79% vs. 10.46%, P=0.075) and had a higher positive predictive value (14.11% vs. 10.46%, P<0.001) and lower number of colonoscopies per advanced neoplasms detected (7.1 vs. 9.6, P<0.001). Conclusion: The risk-adapted screening strategy combining PRS and ERS helps achieve population risk stratification and better effectiveness than the traditional colonoscopy-based screening strategy.

Recent advances of small molecule inhibitors directly targeting HBV / 药学学报

Hepatitis B virus infection is a serious threat to human life and health. The approved anti-HBV drugs including interferons and nucleos(t)ide analogues have serious adverse effect, rebound phenomena after drug withdrawal, and drug resistance. And the cccDNA cannot be completely eliminated by both of them, which is the reason why a complete cure for hepatitis B cannot be achieved. Therefore, developing anti-HBV drugs directly targeting protein or nucleic acid of HBV remains a current public health priority. Based on the analysis of representative literature from the last decade, this article reviews recent developments in small molecule inhibitors directly targeting HBV from a medicinal chemistry perspective.

Development and Validation of a Predictive Risk Model for Vision-threatening Diabetic Retinopathy in Patients with Type 2 Diabetes / 中山大学学报(医学科学版)

ObjectiveTo develop and validate a predictive risk model for vision-threatening diabetic retinopathy in patients with type 2 diabetes using readily accessible clinical data， which may provide a convenient and effective prediction tool for early identification and referral of at-risk populations. MethodsA nomogram model was developed using a dataset obtained from patients with T2DM who participated in the Guangzhou Diabetic Eye Study from November 2017 to December 2020. Logistic regression was used to construct the model， and model performance was evaluated using receiver operating characteristic curve， Hosmer-Lemeshow test， calibration curve and decision curve analysis. The model underwent internal validation through the mean AUC of k-fold cross-validation method， and further external validation was conducted in the Dongguan Eye Study. ResultsA total of 2 161 individuals were included in the model development dataset， of whom 135 （6.25%） people were diagnosed with VTDR. Age （P＜0.001，OR=0.927，95%CI：0.898~0.957） and body mass index （P＜0.001，OR =0.845，95%CI：0.821~0.932） were found to be negatively correlated with VTDR， whereas diabetes duration （P＜0.001，OR=1.064，95%CI：1.035~1.094）， insulin use （P =0.045，OR =1.534，95%CI：1.010~2.332）， systolic blood pressure （P＜0.001，OR =1.019，95%CI：1.008~1.029）， glycated hemoglobin （P＜0.001，OR =1.484，95%CI：1.341~1.643）， and serum creatinine （P＜0.001，OR =1.017，95%CI：1.010~1.023） were positively correlated with VTDR. All these variables were included in the model as predictors. The model showed strong discrimination in the development dataset with an area under the receiver operating characteristic curve （AUC） of 0.797 and in the external validation dataset （AUC 0.762）. The Hosmer-Lemeshow test（P＞0.05）and the calibration curve displayed good agreement. Decision curve analysis showed that the nomogram produced net benefit in the two datasets. ConclusionsIndependent factors influencing VTDR include age， duration of diabetes mellitus， insulin use， body mass index， systolic blood pressure， glycosylated hemoglobin， and serum creatinine. The nomogram constructed using these variables demonstrates a high degree of predictive validity. The model can serve as a valuable tool for early detection and referral of VTDR in primary care clinics. Therefore， its application and promotion are highly recommended.

Design, synthesis and antidiabetic activity studies of purine derivatives / 药学学报

Based our previous work, twelve purine derivatives were designed and synthesized as dual modulators of GPR119 and DPP-4by conjugating the GPR119 activating and DPP-4 inhibiting fragments with the position 6 and 9 of purine core via an approach of merged pharmacophores. Compound 11, bearing 2-fluoro-4-methylsulphonyl anilide and cyanopyrrolidine moieties, exhibited the most potent GPR119 agonistic activities (EC50 = 0.33 μmol·L-1, IA = 71.1%) and DPP-4 inhibitory (58.4% inhibition at 10 μmol·L-1, 21.2% inhibition at 1 μmol·L-1) activities in the in vitro antidiabetic study. Subsequently, we performed studies on structure activity relationships and molecular docking to guide the further drug design.