Structure-based development of potent and selective type-II kinase inhibitors of RIPK1

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Accuracy of a smartphone-assisted novel labeling method for marking target axial position in cataract surgery / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the convenience and accuracy of a novel smartphone-assisted “any-point two-step method” for finding the target axial position in cataract phacoemulsification combined with intraocular lens(IOL)implantation.METHODS: Prospective observational study. A total of 62 cases(62 eyes)of patients with age-related cataracts who underwent cataract phacoemulsification combined with IOL implantation in our hospital from October 2021 to April 2022 were selected. They were randomly divided into two groups: 31 cases(31 eyes)in the control group were applied with the “traditional two-step method” using slit lamp to mark the target axial position of the IOL, and 31 cases(31 eyes)in the experimental group were applied with the smartphone-assisted “two-step method” to mark the target axial position of the IOL. The Callisto eye navigation system was used as a standard reference, and the deviation of the reference marking point(deviation-1), the deviation of the target axial marking point(deviation-total), and the deviation of the angle from the reference marking point to the target axial marking point(deviation-2)were calculated and recorded as the preoperative axial marking time.RESULTS:Both deviation-1 and deviation-total values were lower in the experimental group than those in the control group(1.06°±1.39° vs 2.48°±2.23°, 1.77°±1.54° vs 2.81°±1.58°, all P<0.01), but there was no significant difference in the deviation-2 values between the two groups(1.35°±1.40° vs 1.48°±1.79°, P>0.05). The preoperative axial marking took shorter time in the experimental group than in the control group(1.77±1.70 min vs 2.88±3.20 min, P<0.01).CONCLUSION: The smartphone-assisted “any-point two-step method” for finding the target axial position in cataract phacoemulsification combined with IOL implantation is simple, time-saving, and accurate compared with the “traditional two-step method”.

Effects of different concentrations of brusatol on silicosis fibrosis in mice / 环境与职业医学

Background Silicosis is a diffuse fibrosis of the lungs caused by long-term inhalation of free silicon dioxide (SiO2). It has a complex pathogenesis and lacks effective treatment. Brusatol (Bru) has a variety of biological activities, and its role in silicosis fibrosis is unclear yet. Objective To investigate the effects of different concentrations of Bru on SiO2-induced silicosis fibrosis in mice. Methods Thirty male C57BL/6J mice were randomly divided into five groups: a control group, a silica group, and three Bru intervention groups with low, medium, and high doses (1, 2, and 4 mg·kg−1), with 6 mice in each group. Except the control group, the remaining groups were established as SiO2-induced silicosis mouse models by using a single tracheal infusion of 50 μL 60 mg·mL−1 SiO2 suspension. The control group was dosed with equal amount of saline. The Bru intervention groups were injected intraperitoneally with Bru for 5 consecutive days and then injected every other day. After 28 d of exposure, the mice were executed and lung tissues were collected. The lung coefficient of the mice was measured, and the pathological changes of the lung tissues were observed after hematoxylin-eosin (HE) and Masson staining. The levels of apoptotic protein Cleaved-caspase 3, fibrosis-related protein α-smooth muscle actin (α-SMA), type I collagen (Col-I), autophagy-associated protein Beclin1, microtubule-associated protein 1 light chain 3 (LC3), Sequestosome 1 (p62/SQSTM1), Kelch like ECH-associated protein-1 (Keap1), and nuclear factor erythroid 2 related factor 2 (Nrf2) were detected by Western blot. The mRNA levels of Caspase 3, α-SMA, and Col-I were measured by realtime fluorescence-based quantitative PCR. Results Compared with the control group, the lung coefficient of mice in the silica group was significantly increased (P < 0.01); the lung tissues of the silicosis mice showed damaged alveolar walls, along with infiltration of inflammatory cells, fibrous nodules, and collagen deposition; furthermore, the protein and mRNA levels of Cleaved-caspase 3, α-SMA, and Col-I were significantly increased (P < 0.01); the expression levels of Beclin1, LC3-II/I, p62, and Nrf2 were increased, while that of Keap1 was decreased (P < 0.05). The interventions with low and medium doses of Bru reduced lung coefficient (P < 0.05) and protected against pathological damage and collagen deposition in the lung tissues of the silicosis mice; the protein and mRNA expression levels of Cleaved-caspase 3, α-SMA, and Col-I were significantly decreased in the low and medium dose groups (P < 0.05, P < 0.01), the expression levels of Beclin1, LC3-II/I, p62, and Nrf2 were also decreased (P < 0.05, P < 0.01), and the expression level of Keap1 was increased in the medium dose group (P < 0.05). However, compared with the silica group, the differences in lung coefficient, pathological damage, and protein and mRNA expression levels of Cleaved-caspase 3, α-SMA, and Col-I in the Bru high dose group were not statistically significant (P > 0.05). In addition, the high dose of Bru decreased Beclin1, LC3-II/I, and Nrf2 expression levels (P < 0.01), did not change p62 protein expression level (P > 0.05), while increased Keap1 protein level (P < 0.01). Conclusion Low and medium doses of Bru might regulate autophagy through the Keap1-Nrf2 pathway, ameliorate autophagic degradation impairment, reduce pulmonary coefficient, attenuate apoptosis, and delay the progression of fibrosis in SiO2-induced silicosis mice.

Comparison of clinical effect and postopertaive incisions between No-touch technique and traditional retractor in treating calcaneal fracture / 中国骨伤

OBJECTIVE@#To compare clinical efficacy of No-touch technique and traditional retractor in treating calcaneal fracture.@*METHODS@#Clinical data of 74 calcaneal fracture patients with closed Sanders typeⅡ to Ⅳ were retrospectively analyzed from July 2019 to June 2021. According to different treatment methods, the patients were divided into No-touch group and conventional group, 37 patinets in each group. In No-touch group, there were 25 males and 12 females, aged from 19 to 70 years old with an average of (42.64±14.16) years old;17 patients were typeⅡ, 14 patinets with type Ⅲ, 6 patients with type Ⅳ according to Sanders fracture classification;three 2.0 mm Kirschner wires were implanted into the talus body, talus neck, and cuboid bone, and the flap was turned upward to expose the operation area. In conventional group, there were 30 males and 7 females, aged from 19 to 67 years old with an average of (41.56±11.38) years old;17 patients with typeⅡ, 12 patients with type Ⅲ, 8 patients with type Ⅳ according to Sanders fracture classification;the operation was completed by exposing the operation area with traditional retractor. Operation time, postoperative incision complications, postoperaive American Orthopedic Foot and Ankle Society (AOFAS) ankle hind foot score at 6 months between two groups were compared.@*RESULTS@#Seventy-four patients were followed up, and follow-up time in No-touch group ranged from 6 to 17 months with an average of(9.57±2.72) months, while in conventional group ranged from 6 to 16 months with an averge of(9.14±2.71) months, and no difference in follow-up between two groups (P>0.05). Operation time in No-touch group (55.67±7.94) min was shorter than that in conventional group (70.16±9.41) min (P<0.05);four patients in No-touch group occurred incision complications, while 8 patients in normal group, and had statistically difference(P<0.05). Daily activities and support, maximum walking distance (block), ground walking, limited degree of flexion, extension and valgus, foot alignment and total score of AOFAS scores in No-touch group was significantly higher than that of conventional group (P<0.05). There were no significant difference in pain degree, abnormal gait and ankle hind foot stability between two groups(P>0.05). According to AOFAS score, 19 patients got excellent result, 16 good and 2 poor in No-touch group;while 9 excellent, 24 good, and 4 poor in conventional group, and no difference between two groups (P>0.05).@*CONCLUSION@#Compared with traditional retractor in treating calcaneal fracture, No-touch technology could significantly shorten operation time, reduce incidence of postopertive complications, while two methods could improve excellent and good rate of ankle joint function recovery after operation.

Prevalence of chronic kidney disease and its association with lifestyle factors in adults from 10 regions of China / 中华流行病学杂志

Objective: To investigate the distribution of chronic kidney disease (CKD) in participants from the China Kadoorie Biobank (CKB) study and evaluate the association between lifestyle risk factors and CKD. Methods: Based on the baseline survey data and follow-up data (as of December 31, 2018) of the CKB study, the differences in CKD cases' area and population distributions were described. Cox proportional hazards regression model was used to estimate the association between lifestyle risk factors and the risk of CKD. Results: A total of 505 147 participants, 4 920 cases of CKD were recorded in 11.26 year follow up with a incidence rate of 83.43/100 000 person-years. Glomerulonephropathy was the most common type. The incidence of CKD was higher in the urban area, men, and the elderly aged 60 years and above (87.83/100 000 person-years, 86.37/100 000 person-years, and 132.06/100 000 person-years). Current male smokers had an increased risk for CKD compared with non-smokers or occasional smokers (HR=1.18, 95%CI: 1.05-1.31). The non-obese population was used as a control group, both general obesity determined by BMI (HR=1.19, 95%CI: 1.10-1.29) and central obesity determined by waist circumference (HR=1.27, 95%CI: 1.19-1.35) were associated with higher risk for CKD. Conclusion: The risks for CKD varied with area and population in the CKB cohort study, and the risk was influenced by multiple lifestyle factors.

New discoveries in the field of metabolism by applying single-cell and spatial omics / 药物分析学报

Single-cell multi-Omics(SCM-Omics)and spatial multi-Omics(SM-Omics)technologies provide state-of-the-art methods for exploring the composition and function of cell types in tissues/organs.Since its emergence in 2009,single-cell RNA sequencing(scRNA-seq)has yielded many groundbreaking new discoveries.The combination of this method with the emergence and development of SM-Omics tech-niques has been a pioneering strategy in neuroscience,developmental biology,and cancer research,especially for assessing tumor heterogeneity and T-cell infiltration.In recent years,the application of these methods in the study of metabolic diseases has also increased.The emerging SCM-Omics and SM-Omics approaches allow the molecular and spatial analysis of cells to explore regulatory states and determine cell fate,and thus provide promising tools for unraveling heterogeneous metabolic processes and making them amenable to intervention.Here,we review the evolution of SCM-Omics and SM-Omics technologies,and describe the progress in the application of SCM-Omics and SM-Omics in metabolism-related diseases,including obesity,diabetes,nonalcoholic fatty liver disease(NAFLD)and cardiovascular disease(CVD).We also conclude that the application of SCM-Omics and SM-Omics approaches can help resolve the molecular mechanisms underlying the pathogenesis of metabolic diseases in the body and facilitate therapeutic measures for metabolism-related diseases.This review concludes with an overview of the current status of this emerging field and the outlook for its future.

The concept and development direction of elderly oriented food / 中华预防医学杂志

Active response to the challenges posed by aging has been established as a national strategy, accompanied by continuous refinement of policies concerning aging work. Decreased digestive system function is commonly present in the natural aging process of older people, which directly affects their food intake, digestion, and absorption, leading to decreased appetite and various forms of malnutrition. It is also a risk factor for age-related diseases such as sarcopenia, osteoporosis, cognitive impairment, and frailty. Nutrition is the foundation for achieving healthy aging. In order to meet the nutritional needs of the elderly population, the Nutrition and Healthy Aging Working Group at the Shanghai Junshi Institute of Life Sciences introduced the concept of "elderly-oriented food" in 2022. In the future, there is an urgent need for comprehensive collaborative efforts to conduct a series of investigations focused on the dietary habits and nutritional requirements of older individuals, in order to evaluate the level of awareness, genuine demands, dietary preferences, and capabilities of selection regarding to the elderly-oriented food. Simultaneously, it is recommended to introduce "Guidelines for the production and application of elderly-oriented food" at the national level to promote the sustainable and orderly development in food industry.

Risk factors of in-hospital death in severe pneumonia patients receiving enteral nutrition support / 中华临床营养杂志

Objective:The decline in nutritional status in patients with severe pneumonia may contribute to an increase in in-hospital mortality. Enteral nutrition support can improve the nutritional status of patients, and is relatively easy to manage, with low cost and fewer serious complications. On the other hand, adverse reactions such as gastric retention and gastric microbiota translocation may increase the incidence of nosocomial pneumonia and increase the uncertainty of patient prognosis. There is no predictive model for in-hospital death in severe pneumonia patients receiving enteral nutrition support. The objective of this study was to investigate the risk factors of in-hospital death in patients with severe pneumonia receiving enteral nutrition support and to establish a prognostic model for such patients.Methods:This was a single-center retrospective study. Patients with severe pneumonia who were hospitalized in Peking Union Medical College Hospital and received enteral nutrition support were included from January 1, 2015 to December 31, 2020. The primary endpoints were in-hospital mortality rate and unordered discharge rate. The independent risk factors were determined using univariate and multifactorial logistic regression analysis, the nomogram scoring model was constructed, and the decision curve analysis (DCA) was performed.Results:A total of 632 severe pneumonia patients who received enteral nutrition support were included. Patients were divided into death and survival groups according to the presence or absence of in-hospital death, and 24 parameters were found with significant differences between groups. Nine parameters were independent predictors of mortality, namely the duration of ventilator use, the presence of malignant hyperplasia diseases, the maximal levels of platelet and prothrombin during hospitalization, and the nadir levels of alanine aminotransferase, serum albumin, sodium, potassium, and blood glucose. Based on these variables, a risk prediction scoring model was established (ROC = 0.782; 95% CI: 0.744 to 0.819, concordance index: 0.772). Calibration curves, DCA, and clinical impact curve were plotted to evaluate the goodness of function, accuracy, and applicability of the predictive nomogram, using the training and test sets. Conclusion:This study summarized the clinical characteristics of patients with severe pneumonia receiving enteral nutrition support and developed a scoring model to identify risk factors and establish prognostic models.

Formulation and meaning of evidence-based and differentiated exercise prescription / 中华行为医学与脑科学杂志

Exercise is a crucial method for preventing and controlling chronic diseases, as well as promoting the health of Chinese residents.As guidelines for residents' exercise, traditional exercise prescriptions have limitations such as copying foreign experiences, uneven quality control, and general classification of population characteristics, which affect the applicability and practicality of their application in the Chinese population.A new model of exercise prescription is put forward and named evidence-based and differentiated exercise prescription.In terms of evidence selection, only studies based on Asian populations are selected.In terms of evidence quality control, standardized quality assessment processes are required.In terms of evidence application, accurate classification of candidate populations and personalized application of evidence are achieved.Evidence-based and differentiated exercise prescription provides scientific and accurate exercise prescription guidance for Chinese residents, realizes the integration of sports and medicine, which is conducive for the prevention and control of chronic diseases and the improvement of residents' health level.

Effect of exercise on prehypertension and hypertension in middle-aged and elderly people in Asian populations: a meta-analysis / 中华行为医学与脑科学杂志

Objective:To systematically evaluate the effect of exercise on blood pressure of middle-aged and elderly Asian populations with prehypertension and hypertension, and to provide theoretical basis for formulating accurate exercise prescriptions.Methods:Randomized controlled trials on the effect of exercise on blood pressure in middle-aged and elderly patients with prehypertension and hypertension were collected by PubMed, EMBASE, the Cochrane Library, Web of Science, CNKI and Wanfang Database.The quality of the included studies was evaluated by the Cochrane risk bias assessment tool, and the meta-analysis was performed with Stata 15.0 software.Results:A total of 23 articles and 2 095 subjects were included.Meta analysis showed that compared with the control group, aerobic exercise(WMD=-9.94, 95% CI=-12.59--7.29, P<0.001), resistance exercise(WMD=-11.15, 95% CI=-18.36--3.95, P=0.002) and aerobic combined resistance exercise(WMD=-6.09, 95% CI=-8.87--3.31, P=0.005) could reduce the systolic blood pressure level.Aerobic exercise(WMD=-6.46, 95% CI=-8.20--4.72, P<0.001) and resistance exercise(WMD=-4.38, 95% CI=-8.07--0.69, P=0.02) could reduce the level of diastolic blood pressure, while aerobic combined resistance exercise(WMD=-4.88, 95% CI=-12.87-3.11, P=0.232)had no significant effect on diastolic blood pressure.The results of subgroup analysis indicated that the differences of age, baseline blood pressure, exercise intensity, exercise time, exercise frequency, and motion cycle were the main sources of heterogeneity.The funnel plot and Egger's test indicated that there was no publication bias in this Meta-analysis. Conclusion:Aerobic exercise and resistance exercise both have positive effects on reducing blood pressure of middle-aged and elderly Asian populations with prehypertension and hypertension.

Establishment and validation of a risk prediction model for portal vein thrombosis in liver cirrhosis by nomogram / 中华消化内镜杂志

Objective:To explore the independent risk factors of portal vein thrombosis (PVT) in liver cirrhosis, and to establish and evaluate a risk prediction model for PVT in patients with cirrhosis.Methods:A total of 295 cases of cirrhosis hospitalized in Renmin Hospital of Wuhan University from December 2019 to October 2021 were divided into a modeling set ( n=207) and an internal validation set ( n=88) by the random number table. In addition, patients with cirrhosis hospitalized in Yichang Central People's Hospital, Wuhan Puren Hospital, No.2 People's Hospital of Fuyang City and People's Hospital of China Three Gorges University during the same period were collected as an external validation set ( n=92). The modeling set was divided into PVT group ( n=56) and non-PVT group ( n=151). Univariate analysis was used to preliminarily screen the related indicators of PVT, and then multivariate logistic regression analysis with forward stepwise regression was used to determine independent risk factors for PVT. A nomogram prediction model was constructed based on the independent risk factors obtained. The internal and external validation set were used to verify the predictive ability of the model. Distinction degree was used to evaluate the ability of the model to distinguish patients with or without PVT. Hosmer-Lemeshow goodness-of-fit test was used to evaluate the consistency between predicted risk and the actual risk of the model. Results:Univariate analysis showed that smoking, history of splenectomy, trans-jugular intrahepatic portosystemic shunt (TIPS), gastrointestinal bleeding and endoscopic variceal treatment, and levels of hemoglobin, alanine aminotransferase, aspartate aminotransferase and D-dimer were significantly different between the PVT group and the non-PVT group ( P<0.05). Multivariate logistic regression analysis found that smoking ( P=0.020, OR=31.21, 95% CI: 1.71-569.40), levels of D-dimer ( P=0.003, OR=1.12, 95% CI: 1.04-1.20) and hemoglobin ( P=0.039, OR=0.99, 95% CI: 0.97-1.00), history of TIPS ( P=0.011, OR=18.04, 95% CI: 1.92-169.90) and endoscopic variceal treatment ( P=0.001, OR=3.21, 95% CI: 1.59-6.50) were independent risk factors for PVT in patients with liver cirrhosis. Receiver operator characteristic (ROC) curve analysis showed that the area under the ROC curve (AUC) for the internal validation set was 0.802 (95% CI: 0.709-0.895) ( P<0.001), and the AUC for the external validation set was 0.811 (95% CI: 0.722-0.900) ( P<0.001). Both AUC were larger than 0.75. The calibration curve of Hosmer-Lemeshow goodness-of-fit test showed that the P values of both internal validation set ( χ2=3.602, P=0.891) and the external validation set ( χ2=11.025, P=0.200) were larger than 0.05. Conclusion:Smoking, history of TIPS or endoscopic variceal treatment, levels of D-dimer and hemoglobin are independent risk factors for PVT in patients with liver cirrhosis. The prediction nomogram model based on the above factors has strong predictive ability.

Relationship between plasma exosomal miR-346 and treatment outcomes in patients with multidrug resistant pulmonary tuberculosis / 中国热带医学

@#Abstract： Objective　To investigate the relationship between plasma exosomal microRNA (miRNA)-346 and treatment outcomes in patients with multidrug-resistant tuberculosis (MDR-TB), to provide more reference basis for the treatment of MDR-TB patients. Methods　A total of 406 patients with MDR-TB admitted to Tuberculosis Control and Prevention Institute of Shaanxi Provincial between January 2018 and May 2021 were selected as the study subjects. General clinical data of the patients were collected and analyzed. The expression level of plasma exosomal miR-346 was detected by real-time fluorescence quantitative polymerase chain reaction. The predictive value of plasma exosomal miR-346 for treatment outcome was analyzed using receiver operating characteristic (ROC) curve analysis. Furthermore, the relationship between the expression of plasma exosomal miR-346 and treatment outcome was analyzed using a multivariable logistic regression model. After standard treatment, patients were divided into good treatment outcome group (n=226) and poor treatment outcome group (n=180) according to the treatment outcome. Results　Typical exosomes were identified by transmission electron microscopy, particle size analysis and Western blot, that is, plasma exosomes were successfully extracted. In the poor treatment outcome group, more patients were complicated with diabetes or HIV infection, and the proportion of patients with pulmonary cavity, acid-fast bacilli smear positive rate >1+, previous treatment history and fluoroquinolone resistance was also significantly increased, and the levels of white blood cells, neutrophils, and monocytes were significantly increased, while the level of albumin was significantly decreased, with statistical significance (P>0.05). Compared with the good treatment outcome group [0.61 (0.46, 0.74)], the expression level of plasma exosomal miR-346 in the poor treatment outcome group [1.23 (0.60, 2.02)] was significantly higher (Z=-13.185, P<0.001). ROC curve analysis showed that the area under the curve of plasma exosomal miR-346 to predict adverse outcomes of MDR-TB treatment was 0.881 (95%CI: 0.846-0.915), with a sensitivity of 78.3% and specificity of 86.7%. The corresponding cut-off value was 0.81. Multivariate logistic regression analysis showed that diabetes, AIDS virus infection, pulmonary cavity, AFB smear positive degree>1+, previous treatment history, fluoroquinolones resistance and high expression of plasma exosomal miR-346 were independent influencing factors for poor treatment results of MDR-TB (P<0.05). Conclusions　High expression of plasma exosomal miR-346 is associated with the high risk of adverse outcome of MDR-TB treatment, and it is promising to be a useful marker for predicting the outcome of MDR-TB treatment.

Prospective association between physical activity and mortality in patients with chronic kidney disease / 中华流行病学杂志

Objective: To investigate the prospective association of physical activity with all-cause, cardiovascular disease (CVD), and chronic kidney disease (CKD) mortality in CKD patients in China. Methods: Cox proportional hazard models were used to evaluate the association of total, domain-specific, and intensity-specific physical activity with the risk of all-cause, CVD, and CKD mortality based on data from the baseline survey of China Kadoorie Biobank. Results: During a median follow-up of 11.99 (11.13, 13.03) years, there were 698 deaths in 6 676 CKD patients. Compared with the bottom tertile of total physical activity, participants in the top tertile had a lower risk of all-cause, CVD, and CKD mortality, with hazard ratios (HRs) (95%CIs) of 0.61 (0.47-0.80), 0.40 (0.25-0.65), and 0.25 (0.07-0.85), respectively. Occupational, commuting, and household physical activity were negatively associated with the risk of all-cause and CVD mortality to varying degrees. Participants in the top tertile of occupational physical activity had a lower risk of all-cause (HR=0.56, 95%CI: 0.38-0.82) and CVD (HR=0.39, 95%CI: 0.20-0.74) mortality, those in the top tertile of commuting physical activity had a lower risk of CVD mortality (HR=0.43, 95%CI: 0.22-0.84), and those in the top tertile of household physical activity had a lower risk of all-cause (HR=0.61, 95%CI: 0.45-0.82), CVD (HR=0.44, 95%CI: 0.26-0.76) and CKD (HR=0.03, 95%CI: 0.01-0.17) mortality, compared with the bottom tertile of corresponding physical activity. No association of leisure-time physical activity with mortality was observed. Both low and moderate-vigorous intensity physical activity were negatively associated with the risk of all-cause, CVD and CKD mortality. The corresponding HRs (95%CIs) were 0.64 (0.50-0.82), 0.42 (0.26-0.66) and 0.29 (0.10-0.83) in the top tertile of low intensity physical activity, and the corresponding HRs (95%CIs) were 0.63 (0.48-0.82), 0.39 (0.24-0.64) and 0.23 (0.07-0.73) in the top tertile of moderate-vigorous intensity physical activity. Conclusion: Physical activity can reduce the risk of all-cause, CVD, and CKD mortality in CKD patients.

Epidemiological distribution characteristics of peripheral blood mosaic chromosomal alteration in adults from 10 regions of China / 中华流行病学杂志

Objective: To describe the epidemiological distribution characteristics of peripheral blood mosaic chromosomal alteration (mCA) in community adults aged 30-79 years in 10 regions of China. Methods: A total of 100 297 participants with complete baseline information (demographic characteristics, lifestyle, physical examination, etc.) and genotyping data of blood-derived DNA in ten regions of the China Kadoorie Biobank study were included. The mCAs were detected with the Mosaic Chromosomal Alterations pipeline, and logistic regression models were used to compare the differences in the detection rate of mCAs in different regions and populations. Results: A total of 5 810 mCA carriers were detected, with the detection rate of 5.8%. The standardized detection rate was 5.1%. The baseline detection rate of mCA increased with age, which were 3.4%, 5.0%, and 9.4% in those aged 30-, 51-, and >60 years, respectively (trend test P<0.001). A more significant proportion of mCAs were found in men (8.0%) than women (4.0%), as well as in urban areas (6.4%) than in rural areas (5.3%), the difference was significant (P<0.001). After adjusting for age and gender, the detection rate of mCA was higher in current smokers or people quitting smoking due to illness and people with low physical activity level, and the mCA detection rate was lower in obesy people (5.3%) than that in people with normal body weight (5.9%) (P=0.006). Conclusions: The detection rate of mCAs varied with region and population in community adults aged 30-79 years in 10 regions of China. The study results might contribute to the molecular identification of aging populations and guide precision prevention of age-related diseases such as cancers.

Tea consumption and cancer: a Mendelian randomization study / 中华流行病学杂志

Objective: A Mendelian randomization (MR) analysis was performed to assess the relationship between tea consumption and cancer. Methods: There were 100 639 participants with the information of gene sequencing of whole genome in the China Kadoorie Biobank. After excluding those with cancer at baseline survey, a total of 100 218 participants were included in this study. The baseline information about tea consumption were analyzed, including daily tea consumption or not, cups of daily tea consumption, and grams of daily tea consumption. We used the two-stage least square method to evaluate the associations between three tea consumption variables and incidence of cancer and some subtypes, including stomach cancer, liver and intrahepatic bile ducts cancer, colorectal cancer, tracheobronchial and lung cancer, and female breast cancer. Multivariable MR and analysis only among nondrinkers were used to control the impact of alcohol consumption. Sensitivity analyses were also performed, including inverse variance weighting, weighted median, and MR-Egger. Results: We used 54, 42, and 28 SNPs to construct non-weighted genetic risk scores as instrumental variables for daily tea consumption or not, cups of daily tea consumption, and grams of daily tea consumption, respectively. During an average of (11.4±3.0) years of follow-up, 6 886 cases of cancer were recorded. After adjusting for age, age2, sex, region, array type, and the first 12 genetic principal components, there were no significant associations of three tea consumption variables with the incidence of cancer and cancer subtypes. Compared with non-daily tea drinkers, the HR (95%CI) of daily tea drinkers for cancer and some subtypes, including stomach cancer, liver and intrahepatic bile ducts cancer, colorectal cancer, tracheobronchial and lung cancer, and female breast cancer, are respectively 0.99 (0.78-1.26), 1.17 (0.58-2.36), 0.86 (0.40-1.84), 0.85 (0.42-1.73), 1.39 (0.85-2.26) and 0.63 (0.28-1.38). After controlling the impact of alcohol consumption and performing multiple sensitivity analyses, the results were similar. Conclusion: There is no causal relationship between tea consumption and risk of cancer in population in China.

The investigation of vaccination in patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective:To investigate the prevalence of influenza, pneumococcal, hepatitis B virus (HBV), human papillomavirus (HPV), and varicella zoster virus (VZV) vaccination in patients with systemic lupus erythematosus (SLE), and to analyze the factors related to vaccination.Methods:Data were obtained from 1 203 patients with SLE, via a multi-center web-based survey using an online questionnaire. Data about their social conditions, clinical presentations, willingness for being vaccinated, vaccination within 5 years were collected. Demographic data were shown by descriptive analysis. Chi-square and logistic regression analysis were used to assess the power of related indexes as predictors of vaccination.Results:The vaccination rates of influenza, pneumococcal, HBV, HPV, and VZV were 5.49% (66/1 203), 0.66% (8/1 203), 2.08% (25/1 203), 3.82% (46/1 203), and 0.17% (2/1 203), respectively. Data analysis showed that higher education ( χ2=30.94, P<0.001) and higher income ( χ2=10.70, P=0.001) had greater effects on influenza vaccination. There was a relationship between HPV vaccination and higher education ( χ2=20.96, P<0.001), higher income ( χ2=20.56, P<0.001), younger age ( χ2=8.54, P=0.001), and single ( χ2=5.63, P=0.018). Male ( χ2=10.27, P=0.001) and higher education ( χ2=4.52, P=0.034) were associated with HBV vaccination. The multivariate logistic regression analysis revealed that higher education [ OR (95% CI)=2.14 (1.10, 4.18), P=0.026], having children under 18 years-old [ OR(95% CI)=1.802(1.02, 3.18), P=0.042], and hydroxychloroquine usage [ OR(95% CI)=2.55(1.06, 6.15), P=0.037], had a positive correlation with influenza vaccination. Male [ OR(95% CI)=4.24(1.37, 13.08), P=0.012], had an impact on HBV vaccination. The factors related to HPV vaccination included age <45 [ OR (95% CI)=0.93(0.89, 0.97), P=0.001], higher education [ OR(95% CI)=2.28(1.11, 4.65), P=0.024], higher income [ OR(95% CI)=2.68(1.32, 3.41), P=0.006] and the usage of immunosuppressive agents [ OR(95% CI)=1.92(1.03, 3.59), P=0.041]. Conclusion:The prevalence of vaccination in patients with SLE is low. Patients with higher education and income are more likely to being vaccinated.

Impact of geriatric syndrome on the quality of life of elderly diabetic patients in community / 中华全科医师杂志

Objective:To investigate the impact of geriatric syndromes (GS) on the quality of life in community-dwelling elderly patients with diabetes.Methods:A questionnaire survey was conducted among 326 diabetes patients aged ≥60 years in Shanghai Caohejing Community Health Service Center of Fengxian District from September to December 2020. The questionnaire contained 8 items of GS (polypharmacy, falls, chronic pain, incontinence, depression, malnutrition, daily life ability defects, cognitive dysfunction) and quality of life of patients. Multiple linear regression and hierarchical regression analysis were used to identify the influencing factors of quality of life and the impact of GS explained on the quality of life.Results:A total of 326 questionnaires were distributed, 304 valid questionnaires were retrieved with a valid recovery rate of 93.3%. The prevalence of GS in the participants was 78.6% (239/304). The most common three types of GS were chronic pain 43.4% (132/304), polypharmacy (128/304) and depression 37.2% (113/304). The overall health score was the lowest and their mental health score was the highest (32.5±19.9 and 71.6±19.0, respectively). The cumulative effect of GS attributed to 23.8% of the variance in the Physical Component Summary (PCS) and 34.0% of the variance in the Mental Component Summary (MCS), respectively. The number of GS was negatively correlated with PCS ( r=-0.584, P<0.001) and MCS ( r=-0.340, P<0.001). Multiple linear regression analysis showed that age, chronic pain score and activities of daily living score were the influencing factors for PCS ( P<0.05). The course of diabetes, PHQ-9 score, activities of daily living score and malnutrition score were the influencing factors of MCS ( P<0.05). Conclusions:The survey shows that the prevalence of GS in community-dwelling elderly diabetic patients is high, and the cumulative effect of GS on the quality of life is relatively large. Chronic pain and daily life ability defects can affect PCS, while depression, daily life ability defects and malnutrition can affect MCS in diabetic patients.

The concept and development direction of elderly oriented food / 中华预防医学杂志

Active response to the challenges posed by aging has been established as a national strategy, accompanied by continuous refinement of policies concerning aging work. Decreased digestive system function is commonly present in the natural aging process of older people, which directly affects their food intake, digestion, and absorption, leading to decreased appetite and various forms of malnutrition. It is also a risk factor for age-related diseases such as sarcopenia, osteoporosis, cognitive impairment, and frailty. Nutrition is the foundation for achieving healthy aging. In order to meet the nutritional needs of the elderly population, the Nutrition and Healthy Aging Working Group at the Shanghai Junshi Institute of Life Sciences introduced the concept of "elderly-oriented food" in 2022. In the future, there is an urgent need for comprehensive collaborative efforts to conduct a series of investigations focused on the dietary habits and nutritional requirements of older individuals, in order to evaluate the level of awareness, genuine demands, dietary preferences, and capabilities of selection regarding to the elderly-oriented food. Simultaneously, it is recommended to introduce "Guidelines for the production and application of elderly-oriented food" at the national level to promote the sustainable and orderly development in food industry.

Effects of sciatic nerve electrical stimulation on motor function and expression of BDNF⁃TrkB in rats with spinal cord inj ury / 安徽医科大学学报

Objectives @#To investigate the effect of sciatic nerve electrical stimulation ( SNES) on motor function recovery in rats with incomplete spinal cord injury (SCI) and its possible mechanism.@*Methods @#The incomplete SCI model was constructed by modified Allen ′s method. Forty⁃five Sprague⁃Dawley (SD) rats were randomly divided into three groups : Sham , SCI , and SNES. Electrical stimulation parameters were 1 ms pulse width and 100 Hz , with 20 mins each time , once a day for 21 days. The motor function was assessed by Basso⁃Beattie⁃Bresnahan (BBB) locomotor function scale , and the action potential conduction was detected by electrophysiology. Hematoxy⁃lin⁃eosin (HE) staining was used to observe the pathological changes in the spinal cord and the average cross⁃sectional area (CSA) of biceps femoris muscle fibers. The number of brain⁃derived neurotrophic factor (BDNF) and tropomyosin⁃related kinase B (TrkB) positive cells , relative mRNA and protein expression were analyzed by immunohistochemistry , reverse transcription polymerase chain reaction (RT PCR) and Western blot separately.@*Results@#On 21 d , the BBB score and average amplitude of action potential of SNES group were higher than those of SCI group , and the difference was statistically significant (P < 0. 05) . Compared with SCI group , the pathological injury of spinal cord tissue in SNES group was significantly improved , and the average CSA of biceps femoris muscles had a statistical difference (P < 0. 05) . The number of BDNF and TrkB positive cells in SNES group was higher than that in SCI group , and there were statistical differences (P < 0. 05) . The relative mRNA and protein expressions of BDNF and TrkB in SNES group were higher than those in SCI group , with statistical differences ( P <0. 05) . The relative mRNA and protein expressions of BDNF and TrkB in SNES group were higher than those in SCI group , with statistical differences ( P <0. 05) . @*Conclusion @#These results show that SNES contributes to alleviating spinal cord tissue injury , promoting the recovery of motor function and delaying the atrophy of muscles below the injury level. The possible mechanism is related to the increased expression of BDNF⁃TrkB proteins.

Diagnostic criteria and research progress on pancreas allograft pathology / 器官移植

Pancreas transplantation and pancreas-kidney transplantation are the optimal treatment for renal failure caused by type 1 diabetes mellitus, partial type 2 diabetes mellitus and their complications. Pancreas transplantation mainly includes simultaneous pancreas-kidney transplantation (SPK), pancreas transplantation after kidney transplantation (PAK) and pancreas transplantation alone (PTA). Among all types of pancreas transplantation, biopsy of pancreas allograft remains the best method for definitively diagnosing rejection and differentiate it from other complications. In this article, biopsy methods of pancreas allograft and related research progress, diagnostic criteria and research progress on rejection of pancreas allograft biopsy, and main complications and pathological manifestations of pancreas allograft were illustrated, aiming to provide reference for guiding the clinical diagnosis of the above mentioned complications and ensuring the long-term survival of pancreas allografts and recipients.