The impact of LDL-C/HDL-C ratio on severity of coronary artery disease and 2-year outcome in patients with premature coronary heart disease: results of a prospective, multicenter, observational cohort study / 中华心血管病杂志

Objective: To explore the relationship between low density lipoprotein cholesterol (LDL-C)/high density lipoprotein cholesterol (HDL-C) ratio with the severity of coronary artery disease and 2-yeat outcome in patients with premature coronary heart disease. Methods: This prospective, multicenter, observational cohort study is originated from the PROMISE study. Eighteen thousand seven hundred and one patients with coronary heart disease (CHD) were screened from January 2015 to May 2019. Three thousand eight hundred and sixty-one patients with premature CHD were enrolled in the current study. According to the median LDL-C/HDL-C ratio (2.4), the patients were divided into two groups: low LDL-C/HDL-C group (LDL-C/HDL-C≤2.4, n=1 867) and high LDL-C/HDL-C group (LDL-C/HDL-C>2.4, n=1 994). Baseline data and 2-year major adverse cardiovascular and cerebrovascular events (MACCE) were collected and analyzed in order to find the differences between premature CHD patients at different LDL-C/HDL-C levels, and explore the correlation between LDL-C/HDL-C ratio with the severity of coronary artery disease and MACCE. Results: The average age of the low LDL-C/HDL-C ratio group was (48.5±6.5) years, 1 154 patients were males (61.8%); the average age of high LDL-C/HDL-C ratio group was (46.5±6.8) years, 1 523 were males (76.4%). The number of target lesions, the number of coronary artery lesions, the preoperative SNYTAX score and the proportion of three-vessel coronary artery disease in the high LDL-C/HDL-C group were significantly higher than those in the low LDL-C/HDL-C group (1.04±0.74 vs. 0.97±0.80, P=0.002; 2.04±0.84 vs. 1.85±0.84, P<0.001; 13.81±8.87 vs. 11.70±8.05, P<0.001; 36.2% vs. 27.4%, respectively, P<0.001). Correlation analysis showed that there was a significant positive correlation between LDL-C/HDL-C ratio and preoperative SYNTAX score, the number of coronary artery lesions, the number of target lesions and whether it was a three-vessel coronary artery disease (all P<0.05). The 2-year follow-up results showed that the incidence of MACCE was significantly higher in the high LDL-C/HDL-C group than that in the low LDL-C/HDL-C group (6.9% vs. 9.1%, P=0.011). There was no significant difference in the incidence of all-cause death, cardiac death, myocardial infarction, stroke, revascularization and bleeding between the two groups. Cox multivariate regression analysis showed that the LDL-C/HDL-C ratio has no correlation with 2-year MACCE, death, myocardial infarction, revascularization, stroke and bleeding events above BARC2 in patients with premature CHD. Conclusion: High LDL-C/HDL-C ratio is positively correlated with the severity of coronary artery disease in patients with premature CHD. The incidence of MACCE of patients with high LDL-C/HDL-C ratio is significantly higher during 2 years follow-up; LDL-C/HDL-C ratio may be an indicator for evaluating the severity of coronary artery disease and long-term prognosis in patients with premature CHD.

Digital design and 3D-printed customized flanged cups in hip revision with severe acetabular bone defects / 中华骨科杂志

Objective:To investigate the effect of 3D-printed customized flanged cup in hip revision with severe acetabular bone defects.Methods:Since February 2017, 10 cases of 3D-printed customized flanged cups were used in hip revision with severe acetabular bone defects, including 2 cases of Paprosky type IIIA and 8 cases of Paprosky type IIIB. There were 5 males and 5 females, mean age 73.6±8.1 yrs (range, 62-87 yrs), 5 left and 5 right cases. The preoperative thin-layer CT scan was preformed to reverse reconstruct digital pelvis. Five cases of one-piece flanged cups and 5 cases of decomposed flanged cups, including 3 cases of composite one-piece cups were designed by computer. The surgery was performed strictly according to the plan.Postoperative follow-up was performed to evaluate the Harris score. Operation time,intraoperative bleeding and other complications such as vascular and nerve injury, postoperative infection, and dislocation were counted. Pelvic X-ray was used to assess the height and horizontal position of the center of rotation and the stability of the prosthesis.Results:The surgical procedure was successful, with an average operative time of 147.9±48.3 min (range, 96-212 min) and an average intraoperative bleeding of 730.4±262.6 ml (range, 500-1 300 ml). The mean time of final follow-up was 40.8±18.7 months (range, 16-70 months) after surgery. At the last follow-up, the average Harris score was 83.80±6.73, with 4 cases excellent, 5 cases good, and 1 case fair. The excellent and good rate was 90%. The last Harris score was significantly higher than that before operation 28.60±8.40 ( t=16.84, P<0.001). The height of affected hip joint rotation center decreased from 46.24±7.74 mm before operation to 15.54±2.54 mm after operation with significant difference ( t=14.61, P<0.001). It was slightly higher than the opposite side (13.81±1.48 mm), which had no significant difference ( t=1.83, P=0.100). The horizontal distance of affected hip joint rotation center increased from 33.79±5.27 mm before operation to 40.53±4.50 mm after operation with significant difference ( t=3.62, P=0.006). It had no significant difference ( t=1.28, P=0.232) compared with the opposite side (38.54±3.46 mm). All incisions were healed in one stage without infection, vascular or nerve injury. During the following-up, all prostheses were in satisfied position without loosening, dislocation or screw breaks. Conclusion:Digitally assisted 3D-printed flanged cups can be used in hip revision with severe acetabular bone defect. It can not only improve hip joint function, but also restore the acetabular rotation center and the prosthesis stability, which can achieve good early and mid-term effect.

Treatment strategy for pediatric supracondylar humeral fractures with callus formation and displacement neglected for over 1 week / 中华创伤骨科杂志

Objective:To investigate the treatment strategy for pediatric humeral supracondylar fractures with callus formation and displacement neglected for over 1 week.Methods:A retrospective analysis was made of the clinical data of 36 children who had been treated at Department of Pediatric Orthopaedics, Medical Center, The Second Affiliated Hospital, Inner Mongolia Medical University from January 2011 to January 2021 for humeral supracondylar fractures with callus formation and displacement neglected for over 1 week. There were 22 boys and 14 girls, with an age of (6.7±2.7) years (from 2.3 to 12.8 years). All fractures were Gartland type Ⅲ. The patients were divided into 2 groups according to their treatment methods: a closed reduction and percutaneous pinning (CRPP) group of 15 patients subjected to the CRPP treatment only, and a leverage group of 21 patients subjected to CRPP assisted by the "lever technique" with posterior elbow Kirschner wire prying and pulling. The 2 groups were compared in terms of operation time, fluoroscopy frequency, quality of reduction, and recovery time for elbow range of motion; the elbow range of motion, visual analogue scale (VAS), Mayo elbow performance score (MEPS) and complications were assessed at the last follow-up.Results:The 2 groups were comparable because there was no significant difference between them in the general information before operation ( P>0.05). All patients were followed up for (26.2±16.3) months (from 6 to 96 months). All the fractures obtained acceptable reduction and clinical union 4 to 6 weeks after operation. The operation time [(28.2±6.8) min] and fluoroscopy frequency [(27.0±6.0) times] in the leverage group were significantly less than those in the CRPP group [(40.8±10.8) min and (43.3±11.4) times] ( P<0.05). The CRPP group was significantly better than the leverage group in the intraoperative Baumann angle (78.1°±1.6° versus 73.7°±4.1°), lateral capitellohumeral angle (58.3°±2.6° versus 49.6°±5.2°) and horizontal rotation rate (109.5%±3.0% versus 103.2%±4.9%) ( P<0.05). The intraoperative reduction in the CRPP group was significantly closer to the normal mean value than that in the leverage group ( P<0.05). There was no significant difference in the recovery time for elbow range of motion between the CRPP and the leverage groups ( P>0.05). At the last follow-up, the Baumann angle (75.4°±2.8°) and the lateral capitellohumeral angle (53.2°±3.6°) in the leverage group were still significantly better than those in the CRPP group (78.3°±1.5° and 57.5°±2.3°) ( P<0.05). However, there was no significant difference in the elbow range of motion, VAS, MEPS or incidence of complications between the 2 groups ( P>0.05). Conclusion:To treat humeral supracondylar fractures with callus formation and displacement neglected for over 1 week in children, CRPP assisted by the "lever technique" with posterior elbow Kirschner wire prying and pulling is an efficient and accurate method, because it can lead to more satisfactory reduction than CRPP only.

Developmental toxicity and programming alterations of multiple organs in offspring induced by medication during pregnancy

Medication during pregnancy is widespread, but there are few reports on its fetal safety. Recent studies suggest that medication during pregnancy can affect fetal morphological and functional development through multiple pathways, multiple organs, and multiple targets. Its mechanisms involve direct ways such as oxidative stress, epigenetic modification, and metabolic activation, and it may also be indirectly caused by placental dysfunction. Further studies have found that medication during pregnancy may also indirectly lead to multi-organ developmental programming, functional homeostasis changes, and susceptibility to related diseases in offspring by inducing fetal intrauterine exposure to too high or too low levels of maternal-derived glucocorticoids. The organ developmental toxicity and programming alterations caused by medication during pregnancy may also have gender differences and multi-generational genetic effects mediated by abnormal epigenetic modification. Combined with the latest research results of our laboratory, this paper reviews the latest research progress on the developmental toxicity and functional programming alterations of multiple organs in offspring induced by medication during pregnancy, which can provide a theoretical and experimental basis for rational medication during pregnancy and effective prevention and treatment of drug-related multiple fetal-originated diseases.

Directed differentiation of human induced pluripotent stem cells into midbrain / 南方医科大学学报

OBJECTIVE@#To establish an efficient protocol for directed differentiation of human induced pluripotent stem cells (hiPSCs) into functional midbrain dopaminergic progenitor cells (DAPs) in vitro.@*METHODS@#hiPSCs were induced to differentiate into DAPs in two developmental stages. In the first stage (the first 13 days), hiPSCs were induced into intermediate cells morphologically similar to primitive neuroepithelial cells (NECs) in neural induction medium containing a combination of small molecule compounds. In the second stage, the intermediate cells were further induced in neural differentiation medium until day 28 to obtain DAPs. After CM-DiI staining, the induced DAPs were stereotactically transplanted into the right medial forebrain bundle (MFB) of rat models of Parkinson's disease (PD). Eight weeks after transplantation, the motor behaviors of PD rats was evaluated. Immunofluorescence assay of brain sections of the rats was performed at 2 weeks after transplantation to observe the survival, migration and differentiation of the transplanted cells in the host brain microenvironment.@*RESULTS@#hiPSCs passaged stably on Matrigel showed a normal diploid karyotype, expressed the pluripotency markers OCT4, SOX2, and Nanog, and were positive for alkaline phosphatase. The primitive neuroepithelial cells obtained on day 13 formed dense cell colonies in the form of neural rosettes and expressed the neuroepithelial markers (SOX2, Nestin, and PAX6, 91.3%-92.8%). The DAPs on day 28 highly expressed the specific markers (TH, FOXA2, LMX1A and NURR1, 93.3-96.7%). In rat models of PD, the hiPSCs-DAPs survived and differentiated into TH+, FOXA2+ and Tuj1+ neurons at 2 weeks after transplantation. Eight weeks after transplantation, the motor function of PD rats was significantly improved as shown by water maze test (P < 0.0001) and apomorphine-induced rotation test (P < 0.0001) compared with rats receiving vehicle injection.@*CONCLUSION@#HiPSCs can be effectively induced to differentiate into DAPs capable of differentiating into functional neurons both in vivo and in vitro. In rat models of PD, the transplanted hiPSCs-DAPs can survive for more than 8 weeks in the MFB and differentiate into multiple functional neurocytes to ameliorate neurological deficits of the rats, suggesting the potential value of hiPSCs-DAPs transplantation for treatment of neurological diseases.

Secular trends of age at menarche and age at menopause in women born since 1951 from a county of Shandong Province, China / 北京大学学报(医学版)

OBJECTIVE@#To describe the secular trends of age at menarche and age at natural menopause of women from a county of Shandong Province.@*METHODS@#Based on the data of the Premarital Medical Examination and the Cervical Cancer and Breast Cancer Screening of the county, the secular trends of age at menarche in women born in 1951 to 1998 and age at menopause in women born in 1951 to 1975 were studied. Joinpoint regression was used to identify potential inflection points regarding the trend of age at menarche. Average hazard ratios (AHR) of early menopause among women born in different generations were estimated by performing multivariate weighted Cox regression.@*RESULTS@#The average age at menarche was (16.43±1.89) years for women born in 1951 and (13.99±1.22) years for women born in 1998. The average age at menarche was lower for urban women than that for rural women, and the higher the education level, the lower the average age at menarche. Joinpoint regression analysis identified three inflection points: 1959, 1973 and 1993. The average age at menarche decreased annually by 0.03 (P < 0.001), 0.08 (P < 0.001), and 0.03 (P < 0.001) years respectively for women born during 1951-1959, 1960-1973, and 1974-1993, while it remained stable for those born during 1994-1998 (P=0.968). As for age at menopause, compared with women born during 1951-1960, those born during 1961-1965, 1966-1970 and 1971-1975 showed a gradual decrease in the risk of early menopause and a tendency to delay the age at menopause. The stratified analysis presented that the risk of early menopause gradually decreased and the age of menopause showed a significant delay among those with education level of junior high school and below, but this trend was not obvious among those with education level of senior high school and above, where the risk of early menopause decreased and then increased among those with education level of college and above, and the corresponding AHRs were 0.90 (0.66-1.22), 1.07 (0.79-1.44) and 1.14 (0.79-1.66).@*CONCLUSION@#The age at menarche for women born since 1951 gradually declined until 1994 and leveled off, with a decrease of nearly 2.5 years in these years. The age at menopause for women born between 1951 and 1975 was generally delayed over time, but the trend of first increase and then decrease was observed among those with relatively higher education levels. In the context of the increasing delay in age at marriage and childbearing and the decline of fertility, this study highlights the necessity of the assessment and monitoring of women' s basic reproductive health status, especially the risk of early menopause.

Evaluation of right ventricular function using two-dimensional speckle tracking echocardiography and analysis of the risk factors for right ventricular dysfunction in patients with silicosis / 中华劳动卫生职业病杂志

Objective: To evaluate the right ventricular function using two-dimensional speckle tracking echocardiography (2-D STE) and analyze the associated risk factors of right ventricular dysfunction in patients with silicosis. Methods: All 104 patients with silicosis treated in the Department of Occupational Medicine and Toxicology in Beijing Chao-Yang Hospital, Capital Medical University from May 2021 to September 2022 were enrolled in this study in October 2022. The clinical information of patients such as general data, arterial blood gas analysis and pulmonary function test were collected. The right ventricular function of patients was evaluated by 2-D STE-derived right ventricular free wall longitudinal strain (RVFWLS) and conventional echocardiographic-derived parameters, including right ventricular fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE) and doppler tissue imaging-derived tricuspid lateral annular systolic velocity (S'), respectively. Based on their RVFWLS, the patients were divided into right ventricular dysfunction group and normal right ventricular function group. Risk factors for right ventricular dysfunction in patients with silicosis were analyzed using binary logistic regression analysis. Results: A total of 104 silicosis patients were enrolled, with aneverage age (65.52±11.18) years old, among whom including 57 cases diagnosed with stage Ⅰ/Ⅱ silicosis and 47 cases diagnosed with stage Ⅲ silicosis. 26 (25.00%) patients concurrent right ventricular dysfunction. The abnormal rates of RVFAC, TAPSE and S' in patients were 16.35% (17 cases), 21.15% (22 cases) and 6.73% (7 cases), respectively. The RVFAC and TAPSE in right ventricular dysfunction group were lower than those in normal right ventricular function group, and the incidence of pulmonary arterial systolic pressure ≥36 mmHg was higher than that in normal right ventricular function group (P<0.05). Logistic regression analysis showed that arterial partial pressure of oxygen (OR=0.932, 95%CI: 0.885-0.981, P=0.007) was the protective factor, and the forced expiratory volume in 1 second (FEV(1)) /forced vital capacity (FVC) ratio<70% (OR=5.484, 95%CI: 1.049-28.662, P=0.044) and stage Ⅲ silicosis (OR=6.343, 95%CI: 1.698-23.697, P=0.007) were the risk factors for silicosis patients concurrent right ventricular dysfunction. Conclusion: The incidence of right ventricular dysfunction is higher in patients with stage Ⅲ silicosis than that in patients with stage Ⅰ/Ⅱ silicosis. Using 2-D STE can help the early detection of silicosis with right ventricular dysfunction. Hypoxemia, airflow limitation and the stage Ⅲ silicosis are the risk factors for silicosis patients concurrent right ventricular dysfunction.

Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF) / 中华内科杂志

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.

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.

Constructions and advances of animal models of Pseudomonas aeruginosa infection / 中华预防医学杂志

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogenic bacterium with complex pathogenesis and drug resistance mechanisms. It has high morbidity and mortality and can cause acute and chronic infections in immunocompromised individuals, with lung infections, wound infections, and bloodstream infections being the most common. The animal infection model of P. aeruginosa is of great value for in-depth research on the pathogenicity, drug resistance, and therapeutic measures of P. aeruginosa by simulating the pathways of human bacterial infections. This article firstly summarizes the selection, anesthesia, and disposal of experimental animals in the construction of animal models of P. aeruginosa infection, and then reviews the methods of construction, model evaluation, and applications of animal models of P. aeruginosa pulmonary infection, wound infection, and bloodstream infection, in order to provide a reference for scientific research related to P. aeruginosa infectious diseases.

Ideal cardiovascular health and mortality: pooled results of three prospective cohorts in Chinese adults / 中华医学杂志(英文版)

BACKGROUND@#Evidence on the relations of the American Heart Association's ideal cardiovascular health (ICH) with mortality in Asians is sparse, and the interaction between behavioral and medical metrics remained unclear. We aimed to fill the gaps.@*METHODS@#A total of 198,164 participants without cancer and cardiovascular disease (CVD) were included from the China Kadoorie Biobank study (2004-2018), Dongfeng-Tongji cohort (2008-2018), and Kailuan study (2006-2019). Four behaviors (i.e., smoking, physical activity, diet, body mass index) and three medical factors (i.e., blood pressure, blood glucose, and blood lipid) were classified into poor, intermediate, and ideal levels (0, 1, and 2 points), which constituted 8-point behavioral, 6-point medical, and 14-point ICH scores. Results of Cox regression from three cohorts were pooled using random-effects models of meta-analysis.@*RESULTS@#During about 2 million person-years, 20,176 deaths were recorded. After controlling for demographic characteristics and alcohol drinking, hazard ratios (95% confidence intervals) comparing ICH scores of 10-14 vs. 0-6 were 0.52 (0.41-0.67), 0.44 (0.37-0.53), 0.54 (0.45-0.66), and 0.86 (0.64-1.14) for all-cause, CVD, respiratory, and cancer mortality. A higher behavioral or medical score was independently associated with lower all-cause and CVD mortality among the total population and populations with different levels of behavioral or medical health equally, and no interaction was observed.@*CONCLUSIONS@#ICH was associated with lower all-cause, CVD, and respiratory mortality among Chinese adults. Both behavioral and medical health should be improved to prevent premature deaths.

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.

Research progress of influenza vaccination, pneumococcal vaccination and COVID-19 vaccination among cancer patients / 中华预防医学杂志

This article reviews the relevant studies on the efficacy and safety of influenza, pneumococcal and COVID-19 vaccination among tumor patients worldwide in recent years. By combing and analyzing the retrieved literature, the results show that influenza and pneumococcal vaccination can significantly reduce the morbidity and hospitalization rate of infectious diseases in tumor patients, reduce the risk of cardiovascular events and death, and significantly improve survival prognosis. COVID-19 vaccination can also protect tumor patients, especially those who have completed full dose vaccination. Authoritative guidelines and consensuses worldwide all recommend that tumor patients receive influenza, pneumococcal and COVID-19 vaccines. We should carry out relevant researches, as well as take effective measures to strengthen patient education, so that tumor patients can fully experience the health protection brought by the vaccine to this specific group.

Electro-acupuncture promotes gut motility and alleviates functional constipation by regulating gut microbiota and increasing butyric acid generation in mice / 中西医结合学报

OBJECTIVE@#Abnormalities in the gut microbiota and intestinal short-chain fatty acid (SCFA) levels are implicated in the pathogenesis of functional constipation (FC). Electro-acupuncture (EA) has been shown to improve constipation-related symptoms and rebalance the gut microbiota. However, it is currently unknown whether the gut microbiota is a key mechanistic target for EA or how EA promotes gut motility by regulating the gut microbiota and SCFAs. Therefore, we assessed the effects of EA in FC mice and pseudo-germfree (PGF) mice to address these questions.@*METHODS@#Forty female Kunming mice were randomly separated into a normal control group (n = 8), an FC group (n = 8), an FC + EA group (n = 8), a PGF group (n = 8) and a PGF + EA group (n = 8). The FC group and FC + EA group were treated with diphenoxylate to establish the FC model; the PGF group and PGF + EA group were given an antibiotic cocktail to initiate the PGF model. After maintaining the model for 14 d, mice in the FC + EA and PGF + EA groups received EA stimulation at the ST25 and ST37 acupoints, once a day, 5 times per week, for 2 weeks. Fecal parameters and intestinal transit rate were calculated to assess the efficacy of EA on constipation and gastrointestinal motility. Colonic contents were used to quantify gut microbial diversity using 16S rRNA sequencing, and measure SCFA concentrations using gas chromatography-mass spectrometry.@*RESULTS@#EA significantly shortened the first black stool defecation time (P < 0.05) and increased the intestinal transit rate (P < 0.01), and fecal pellet number (P < 0.05), wet weight (P < 0.05) and water content (P < 0.01) over 8 h, compared with the FC group, showing that EA promoted gut motility and alleviated constipation. However, EA treatment did not reverse slow-transit colonic motility in PGF mice (P > 0.05), demonstrating that the gut microbiota may play a mechanistic role in the EA treatment of constipation. In addition, EA treatment restored the Firmicutes to Bacteroidetes ratio and significantly increased butyric acid generation in FC mice (P < 0.05), most likely due to the upregulation of Staphylococcaceae microorganisms (P < 0.01).@*CONCLUSION@#EA-mediated resolution of constipation occurs through rebalancing the gut microbiota and promoting butyric acid generation. Please cite this article as: Xu MM, Guo Y, Chen Y, Zhang W, Wang L, Li Y. Electro-acupuncture promotes gut motility and alleviates functional constipation by regulating gut microbiota and increasing butyric acid generation in mice. J Integr Med. 2023; Epub ahead of print.

Effect of Liangfang Wenjing Decoction on expression of key glycolytic enzymes in uterus and ovaries of rats with coagulating cold and blood stasis syndrome / 中国中药杂志

This study aimed to investigate the relationship between coagulating cold and blood stasis syndrome and glycolysis, and observe the intervention effect of Liangfang Wenjing Decoction(LFWJD) on the expression of key glycolytic enzymes in the uterus and ovaries of rats with coagulating cold and blood stasis. The rat model of coagulating cold and blood stasis syndrome was established by ice-water bath. After modeling, the quantitative scoring of symptoms were performed, and according to the scoring results, the rats were randomly divided into a model group and LFWJD low-, medium-and high-dose groups(4.7, 9.4, 18.8 g·kg~(-1)·d~(-1)), with 10 in each group. Another 10 rats were selected as the blank group. After 4 weeks of continuous administration by gavage, the quantitative scoring of symptoms was repeated. Laser speckle flowgraphy was used to detect the changes of microcirculation in the ears and uterus of rats in each group. Hematoxylin-eosin(HE) staining was used to observe the pathological morphology of uterus and ovaries of rats in each group. The mRNA and protein expressions of pyruvate dehydrogenase kinase 1(PDK1), hexokinase 2(HK2) and lactate dehydrogenase A(LDHA) in the uterus and ovaries of rats were examined by real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. The rats in the model group showed signs of coagulating cold and blood stasis syndrome, such as curl-up, less movement, thickened veins under the tongue, and reduced blood perfusion in the microcirculation of the ears and uterus, and HE staining revealed a thinning of the endometrium with disorganized arrangement of epithelial cells and a decrease in the number of ovarian follicles. Compared with the model group, the treatment groups had alleviated coagulating cold and blood stasis, which was manifested as red tongue, reduced nail swelling, no blood stasis at the tail end as well as increased blood perfusion of the microcirculation in the ears and uterus(P<0.05 or P<0.01). Among the groups, the LFWJD medium-and high-dose groups had the most significant improvement in coagulating cold and blood stasis, with neatly arranged columnar epithelial cells in uterus, and the number of ovarian follicles was higher than that in the model group, especially mature follicles. The mRNA and protein expressions of PDK1, HK2, LDHA in uterus and ovaries were up-regulated in the model group(P<0.05 or P<0.01), while down-regulated in LFWJD medium-and high-dose groups(P<0.05 or P<0.01). The LFWJD low-dose group presented a decrease in the mRNA expressions of PDK1, HK2 and LDHA in uterus and ovaries as well as in the protein expressions of HK2 and LDHA in uterus and HK2 and PDK1 in ovaries(P<0.05 or P<0.01). The therapeutic mechanism of LFWJD against coagulating cold and blood stasis syndrome is related to the down-regulation of key glycolytic enzymes PDK1, HK2 and LDHA, and the inhibition of glycolytic activities in uterus and ovaries.

Molecular mechanism of ginsenoside Rg_1 against radiation enteritis: based on network pharmacology and in vitro experiment / 中国中药杂志

Via network pharmacology, molecular docking, and cellular experiment, this study explored and validated the potential molecular mechanism of ginsenoside Rg_1(Rg_1) against radiation enteritis. Targets of Rg_1 and radiation enteritis were retrieved from BATMAN-TCM, SwissTargetPrediction, and GeneCards. Cytoscape 3.7.2 and STRING were employed for the construction of protein-protein interaction(PPI) network for the common targets, and screening of core targets. DAVID was used for Gene Ontology(GO) term and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment to predict the possible mechanism, followed by molecular docking of Rg_1 with core targets and cellular experiment. For the cellular experiment, ~(60)Co-γ irradiation was performed for mo-deling of IEC-6 cells, which were then treated with Rg_1, protein kinase B(AKT) inhibitor LY294002, and other drugs to verify the effect and mechanism of Rg_1. The results showed that 29 potential targets of Rg_1, 4 941 disease targets, and 25 common targets were screened out. According to the PPI network, the core targets were AKT1, vascular endothelial growth factor A(VEGFA), heat shock protein 90 alpha family class A member 1(HSP90AA1), Bcl-2-like protein 1(BCL2L1), estrogen receptor 1(ESR1), etc. The common targets were mainly involved in the GO terms such as positive regulation of RNA polymerase Ⅱ promoter transcription, signal transduction, positive regulation of cell proliferation, and other biological processes. The top 10 KEGG pathways included phosphoinositide 3-kinase(PI3K)/AKT pathway, RAS pathway, mitogen-activated protein kinase(MAPK) pathway, Ras-proximate-1(RAP1) pathway, and calcium pathway, etc. Molecular docking showed that Rg_1 had high binding affinity to AKT1, VEGFA, HSP90AA1, and other core targets. Cellular experiment indicated that Rg_1 can effectively improve cell viability and survival, decrease apoptosis after irradiation, promote the expression of AKT1 and B-cell lymphoma-extra large(BCL-XL), and inhibit the expression of the pro-apoptotic protein Bcl-2-associated X protein(BAX). In conclusion, through network pharmacology, molecular docking, and cellular experiment, this study verified the ability of Rg_1 to reduce radiation enteritis injury. The mechanism was that it regulated PI3K/AKT pathway, thereby suppressing apoptosis.

Establishment and characterization of bone marrow mesenchymal stem cell lines stably synthesizing high-level dopamine / 生物工程学报

A triple-transgenic (tyrosine hydroxylase/dopamine decarboxylase/GTP cyclohydrolase 1, TH/DDC/GCH1) bone marrow mesenchymal stem cell line (BMSCs) capable of stably synthesizing dopamine (DA) transmitters were established to provide experimental evidence for the clinical treatment of Parkinson's disease (PD) by using this cell line. The DA-BMSCs cell line that could stably synthesize and secrete DA transmitters was established by using the triple transgenic recombinant lentivirus. The triple transgenes (TH/DDC/GCH1) expression in DA-BMSCs was detected using reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and immunofluorescence. Moreover, the secretion of DA was tested by enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC). Chromosome G-banding analysis was used to detect the genetic stability of DA-BMSCs. Subsequently, the DA-BMSCs were stereotactically transplanted into the right medial forebrain bundle (MFB) of Parkinson's rat models to detect their survival and differentiation in the intracerebral microenvironment of PD rats. Apomorphine (APO)-induced rotation test was used to detect the improvement of motor dysfunction in PD rat models with cell transplantation. The TH, DDC and GCH1 were expressed stably and efficiently in the DA-BMSCs cell line, but not expressed in the normal rat BMSCs. The concentration of DA in the cell culture supernatant of the triple transgenic group (DA-BMSCs) and the LV-TH group was extremely significantly higher than that of the standard BMSCs control group (P < 0.000 1). After passage, DA-BMSCs stably produced DA. Karyotype G-banding analysis showed that the vast majority of DA-BMSCs maintained normal diploid karyotypes (94.5%). Moreover, after 4 weeks of transplantation into the brain of PD rats, DA-BMSCs significantly improved the movement disorder of PD rat models, survived in a large amount in the brain microenvironment, differentiated into TH-positive and GFAP-positive cells, and upregulated the DA level in the injured area of the brain. The triple-transgenic DA-BMSCs cell line that stably produced DA, survived in large numbers, and differentiated in the rat brain was successfully established, laying a foundation for the treatment of PD using engineered culture and transplantation of DA-BMSCs.

Epidemiological characteristics and influencing factors of Blastocystis hominis infection among children with diarrhea under five years of age in Guangzhou City / 中国血吸虫病防治杂志

Objective To investigate the prevalence and influencing factors of Blastocystis hominis infection among children with diarrhea under five years of age in Guangzhou City. Methods Children with diarrhea under 5 years of age admitted to Guangzhou Children’s hospital, Guangzhou Maternity and Child Healthcare Hospital and Guangzhou Women and Children’s Medical Center during the period between January 1 and December 31, 2020, were enrolled. Participants’ demographics, living environments and health status were collected using questionnaire surveys. Stool samples were collected from participants and nucleic acid was extracted. B. hominis infection was identified using PCR assay and sequence alignment, and the factors affecting B. hominis infection among children with diarrhea under 5 years of age were identified using univariate analysis and multivariate logistic regression analysis. Results A total of 684 children with diarrhea under 5 years of age were enrolled, including 468 male children and 216 female children, with a mean age of (1.79 ± 1.12) years. The overall prevalence of B. hominis infection was 4.97% [34/684, 95% confidential interval (CI): (3.59%, 6.86%)] among participants, and there was no significant difference in the prevalence of B. hominis infection between children with chronic [7.52% (20/266), 95% CI: (4.92%, 11.33%)] and acute diarrhea [3.35% (14/418), 95% CI: (2.01%, 5.54%)] (χ2 = 5.983, P = 0.014). Multivariate logistic regression analysis identified keeping pet [odds ratio (OR) = 6.298, 95% CI: (2.711, 14.633)], drinking non-tap water [OR = 4.522, 95% CI: (1.769, 11.561)], lactose intolerance [OR = 4.221, 95% CI: (1.043, 17.087)], antibiotic use [OR = 0.125, 95% CI: (0.017, 0.944)] and chronic diarrhea [OR = 2.172, 95% CI: (1.018, 4.637)] as factors affecting B. hominis infection among children with diarrhea under 5 years of age in Guangzhou City. Conclusions B. hominis infections is detected in children with diarrhea under five years of age in Guangzhou City. Improving home environments and pet-keeping hygiene is recommended to reduce the likelihood of B. hominis infection among children.

Genetic and healthy lifestyle factors in relation to the incidence and prognosis of severe liver disease in the Chinese population / 中华医学杂志(英文版)

BACKGROUND@#Severe liver disease (SLD), including cirrhosis and liver cancer, constitutes a major disease burden in China. We aimed to examine the association of genetic and healthy lifestyle factors with the incidence and prognosis of SLD.@*METHODS@#The study population included 504,009 participants from the prospective China Kadoorie Biobank aged 30-79 years. The individuals were from 10 diverse areas in China without a history of cancer or liver disease at baseline. Cox regression was used to estimate adjusted hazard ratios (HRs) for incident SLD and death after SLD diagnosis associated with healthy lifestyle factors (smoking, alcohol, physical activity, and central adiposity). Additionally, the contribution of genetic risk for hepatitis B virus (HBV, assessed by genetic variants in major histocompatibility complex, class II, DP/DQ [ HLA - DP / DQ ] genes) was also estimated.@*RESULTS@#Compared with those with 0-1 healthy lifestyle factor, participants with 2, 3, and 4 factors had 12% (HR 0.88 [95% confidence interval [CI] 0.85, 0.92]), 26% (HR 0.74 [95%CI: 0.69, 0.79]), and 44% (HR 0.56 [95%CI: 0.48, 0.65]) lower risks of SLD, respectively. Inverse associations were observed among participants with both low and high genetic risks (HR per 1-point increase 0.83 [95%CI: 0.74, 0.94] and 0.91 [95%CI: 0.82, 1.02], respectively; Pinteraction = 0.51), although with a non-significant trend among those with a high genetic risk. Inverse associations were also observed between healthy lifestyle factors and liver biomarkers regardless of the genetic risk. Despite the limited power, healthy lifestyle factors were associated with a lower risk of death after incident SLD among participants with a low genetic risk (HR 0.59 [95%CI: 0.37, 0.96]).@*CONCLUSIONS@#Lifestyle modification may be beneficial in terms of lowering the risk of SLD regardless of the genetic risk. Moreover, it is also important for improving the prognosis of SLD in individuals with a low genetic risk. Future studies are warranted to examine the impact of healthy lifestyles on SLD prognosis, particularly among individuals with a high genetic risk.

Characterization of potential bitterness critical quality attributes in Xiaoer Ganmao Oral Liquid based on UHPLC-LTQ-Orbitrap MSn / 药学学报

To identify the bitter compounds of real-world Xiaoer Ganmao Oral Liquid sugar-free intermediates, an integrated strategy has been developed by using ultra-high performance liquid chromatography with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MSn) method and BitterX database prediction. The chromatographic operating conditions were as follows, chromatographic column: Acquity UPLC BEH C18 (100 mm × 2.1 mm, 1.7 μm), mobile phase: 0.1% formic acid-water solution (A)-acetonitrile (B) with gradient elution. The data were collected in positive and negative ion modes, respectively. The accurate molecular mass and structural information of the target compounds were obtained based on quasi-molecular ions and fragmentation ions provided by high-resolution mass spectrometry. The compounds were identified by combining retention time, reference substances, reports, and other relevant data, and a total of 57 constituents including flavonoids, alkaloids, and phenylpropanoids were finally identified. Further, the BitterX database was used to predict binding probability of compounds to bitter receptors and identify potential bitter critical quality attributes, finally 33 potential bitter compounds, including kukoamine A and linarin, were predicted. This study comprehensively characterized the material basis of Xiaoer Ganmao Oral Liquid sugar-free intermediates, it provides an effective method for bitter compound screening and a reference for further improving the undesirable taste of Xiaoer Ganmao Oral Liquid.