Objective:To analyze the relationship between 24-hour urinary calcium (24 h UCa) level and the risk of end-stage kidney disease (ESKD), cardiovascular disease (CVD), and all-cause mortality.Methods:In the Chinese Cohort Study of Chronic Kidney Disease, we examined 3 375 patients aged 18-74 years with CKD stages 1-4. Kaplan-Meier survival and Cox proportional hazard regression models were used to test a time-to-event association between levels of 24 h UCa and incidence of ESKD, CVD, and all-cause mortality.Results:During a follow-up of 4.17 (3.37, 5.20) years, 179, 145, 104 and 38 ESKD events occurred in <0.60, 0.60-, 1.20-, ≥2.32 mmol 24 h UCa groups. Higher levels of 24 h UCa (1.20-,≥2.32 mmol) were independently associated with a lower incidence of ESKD events in patients with CKD, with HR (95% CI) of 0.71 (0.54-0.93) and 0.43 (0.29-0.64), respectively. No significant associations with CVD and all-cause mortality endpoints were detected. Conclusion:Among patients with CKD, levels of 24 h UCa displayed an association with the risk of ESKD among patients with CKD stages 1-4.

Objective To apply a random forest model combined with logistic regression in the understudied area of pneumoconiosis complications,and to investigate the incidence and risk factors of pneumoconiosis complicated by bacterial pneumonia,and the effect of concomitant bacterial pneumonia on the survival and prognosis of patients with pneumoconiosis.Methods Pneumoconiosis patients admitted to the West China Fourth Hospital,Sichuan University,between January 2018 and April 2022 were enrolled and divided into a group of those with only pneumoconiosis and another group of those with pneumoconiosis complicated by bacterial pneumonia.Univariate analyses,including chi-squared test,t-test,or rank sum test,were conducted to examine the differences between the groups.A random forest model was used to screen the variables,and the risk factors of pneumoconiosis complicated by bacterial pneumonia were identified by stepwise forward logistic regression method.Cox regression was applied to the survival data to assess the effect of concomitant bacterial pneumonia on the survival and prognosis of pneumoconiosis patients.Results Among the 742 pneumoconiosis patients,536 cases(72.24%)had concomitant bacterial pneumonia.Among the 55 deaths,36 cases(65.45%)had concomitant bacterial pneumonia.Univariate analysis showed statistically significant differences in age,duration of disease,lung function,duration of exposure,lung lavage,pulmonary tuberculosis,and emphysema between the two groups(P<0.05).The variables were screened using the random forest model,and the risk factors were ranked in a descending order of their importance—the types of dust,duration of exposure,lung function,lung lavage,and pulmonary tuberculosis.After screening,multivariate logistic regression analysis showed that the types of dust(compared with silica dust,silicate dust:odd ratio[OR]=8.100,95%CI,1.386-47.331;carbon dust:OR=1.728,95%CI,1.034-2.887;artificial inorganic dust:OR=2.138,95%CI,1.146-3.988),impaired lung function(compared with undamaged lung function group,the group of patients with mild,moderate,and moderately severe damage:OR=2.292,95%CI,1.482-3.544),and pulmonary tuberculosis(OR=1.559,95%CI,1.071-2.271)were risk factors for pneumoconiosis complicated by bacterial pneumonia.The median follow-up was 30.0 months,ranging from 1.0 month to 64.0 months.Cox regression analysis showed that the mortality risk for pneumoconiosis patients with concomitant bacterial pneumonia was 2.369 times higher than that for patients without bacterial pneumonia(95%CI,1.286-4.367).Conclusion Pneumoconiosis patients are susceptible to bacterial pneumonia and are influenced by multiple risk factors.Concomitant bacterial pneumonia markedly affects the patient prognosis.

OBJECTIVE T o explore the prevention and control measures for the hospital-acquired pulmonary mu-cormycosis caused by Cunninghamella bertholletiae.METHODS One case of patient with pulmonary mucormyco-sis caused by Cunninghamella bertholletiae who was treated in pediatric intensive care unit(PICU)of a three-A general hospital was enrolled in the study,the process of clinical diagnosis and treatment was summarized.A ret-rospective survey regarding four aspects including people,machine,materials and environment was conducted.The related factors leading to the hospital-acquired infections in the patient were analyzed.RESULTS The child was diagnosed with severe aplastic anemia and underwent hematopoietic stem cell transplantation,the child was treated with various invasive procedures during the treatment period and was infected with pulmona-ry mucormycosis caused by the rare Cunninghamella bertholletiae.The occurrence of the pulmonary mucormyco-sis was associated with the poor management of medical textile,insufficient environmental cleaning and disinfec-tion and nonstandard invasive procedures.CONCLUSIONS The Cunninghamella bertholletiae infection is less com-mon,but the risk of death is high.It is necessary for the medical institutions to complete the prevention and con-trol measures and intensify the health care workers'capabilities in identification of the pathogenic fungus so as to reduce the incidence of pulmonary mucormycosis caused by the pathogen.

Objective:To analyze the relationship between 24-hour urinary calcium (24 h UCa) level and the risk of end-stage kidney disease (ESKD), cardiovascular disease (CVD), and all-cause mortality.Methods:In the Chinese Cohort Study of Chronic Kidney Disease, we examined 3 375 patients aged 18-74 years with CKD stages 1-4. Kaplan-Meier survival and Cox proportional hazard regression models were used to test a time-to-event association between levels of 24 h UCa and incidence of ESKD, CVD, and all-cause mortality.Results:During a follow-up of 4.17 (3.37, 5.20) years, 179, 145, 104 and 38 ESKD events occurred in <0.60, 0.60-, 1.20-, ≥2.32 mmol 24 h UCa groups. Higher levels of 24 h UCa (1.20-,≥2.32 mmol) were independently associated with a lower incidence of ESKD events in patients with CKD, with HR (95% CI) of 0.71 (0.54-0.93) and 0.43 (0.29-0.64), respectively. No significant associations with CVD and all-cause mortality endpoints were detected. Conclusion:Among patients with CKD, levels of 24 h UCa displayed an association with the risk of ESKD among patients with CKD stages 1-4.

OBJECTIVE T o explore the prevention and control measures for the hospital-acquired pulmonary mu-cormycosis caused by Cunninghamella bertholletiae.METHODS One case of patient with pulmonary mucormyco-sis caused by Cunninghamella bertholletiae who was treated in pediatric intensive care unit(PICU)of a three-A general hospital was enrolled in the study,the process of clinical diagnosis and treatment was summarized.A ret-rospective survey regarding four aspects including people,machine,materials and environment was conducted.The related factors leading to the hospital-acquired infections in the patient were analyzed.RESULTS The child was diagnosed with severe aplastic anemia and underwent hematopoietic stem cell transplantation,the child was treated with various invasive procedures during the treatment period and was infected with pulmona-ry mucormycosis caused by the rare Cunninghamella bertholletiae.The occurrence of the pulmonary mucormyco-sis was associated with the poor management of medical textile,insufficient environmental cleaning and disinfec-tion and nonstandard invasive procedures.CONCLUSIONS The Cunninghamella bertholletiae infection is less com-mon,but the risk of death is high.It is necessary for the medical institutions to complete the prevention and con-trol measures and intensify the health care workers'capabilities in identification of the pathogenic fungus so as to reduce the incidence of pulmonary mucormycosis caused by the pathogen.

Objective:To investigate the effect of microRNA-27b-3p (miR-27b-3p)/nuclear factor-E2-related factor 2 (Nrf2) on metabolic memory impairment of human retinal pigment epithelial (RPE) cells and to explore its regulatory mechanism.Methods:ARPE-19 cells were divided into normal control group, metabolic memory group, miR-27b-3p control group, miR-27b-3p inhibitor group, and liraglutide group.Cells in normal control group were cultured in 5.5 mmol/L normal glucose medium for 6 days.Cells in metabolic memory group were cultured in 30 mmol/L glucose for 3 days and changed to 5.5 mmol/L for 3 days.Cells in miR-27b-3p inhibitor group were added with puromycin after lentiviral transfection to select the successfully transfected cells, and were cultured in 30 mmol/L glucose for 3 days then 5.5 mmol/L glucose for 3 days.Cells in liraglutide group were cultured in 30 mmol/L glucose with liraglutide for 3 days then 5.5 mmol/L glucose for 3 days.The regulatory relationship between miR-27b-3p and Nrf2 was verified by lentiviral transfection.Expressions of miR-27b-3p, Nrf2, NAD(P)H dehydrogenase[quinone]1 (NQO1), heme oxygenase-1 (HO-1) mRNA and protein levels were analyzed by real-time quantitative PCR.Total and nuclear Nrf2 protein expressions were detected by Western blot.The cell proliferation rates of various groups were determined by cell counting kit-8 (CCK-8).The reactive oxygen species (ROS) level was detected by the DHE kit.Results:The miR-27b-3p mRNA relative expression of normal control group, metabolic memory group, miR-27b-3p control group, miR-27b-3p inhibitor group was 1.000±0.000, 1.881±0.034, 1.683±0.088 and 0.111±0.008, respectively, with a statistically significant difference ( F=850.815, P<0.001).The miR-27b-3p mRNA relative expression level was lower in normal control group than in metabolic memory group, lower in miR-27b-3p inhibitor group than in normal control group, and the differences were statistically significant (both at P<0.01).The expression levels of Nrf2 mRNA, total protein, and nuclear protein were decreased in metabolic memory group in comparison with normal control group and were significantly increased in miR-27b-3p inhibitor group in comparison with miR-27b-3p control group, showing statistically significant differences (all at P<0.01).The NQO1 and HO-1 mRNA expressions were decreased in metabolic memory group in comparison with normal control group, and were significantly higher in miR-27b-3p inhibitor group compared with miR-27b-3p control group, showing statistically significant differences (all at P<0.01).The fluorescence intensity of Nrf2, NQO1, and HO-1 was lower in metabolic memory group than in normal control group, and was higher in miR-27b-3p inhibitor group than in miR-27b-3p control group, showing statistically significant differences (all at P<0.01).Compared with metabolic memory group, the relative expression of miR-27b-3p mRNA declined in liraglutide group, with a statistically significant difference ( P<0.05).The relative expression levels of Nrf2 mRNA, NQO1 mRNA, HO-1 mRNA, total and nuclear Nrf2 protein of liraglutide group were enhanced in comparison with metabolic memory group, with statistically significant differences (all at P<0.05).The fluorescence intensity of Nrf2, NQO1, and HO-1 was enhanced in liraglutide group in comparison with metabolic memory group, and the differences were statistically significant (all at P<0.05).Compared with normal control group and liraglutide group, the cell proliferation viability was decreased in metabolic memory group, and the differences were statistically significant (both at P<0.01).The relative content of ROS was higher in metabolic memory group than in normal control group and liraglutide group, and the difference was significant (all at P<0.01). Conclusions:Liraglutide reverses the inhibition of metabolic memory on Nrf2, NQO1, and HO-1 by downregulating miR-27b-3p.

Objective To investigate the influencing factors for the prognosis of adult patients with chronic drug-induced liver injury (DILI). Methods A total of 255 patients who were diagnosed with chronic DILI by liver biopsy in The Fifth Medical Center of Chinese PLA General Hospital from January 2014 to December 2018 were enrolled, and according to the liver function after 2 years, they were divided into non-recovery group and recovery group. The two groups were analyzed in terms of the clinical data including age, sex, body mass index, types of drugs used, type of DILI injury, severity of DILI injury, underlying diseases, laboratory markers, liver histology, and 2-year prognosis. The t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate logistic regression analyses were used to investigate the independent risk factors for the prognosis of chronic DILI. Results After 2 years of follow-up, 195 patients (76.5%) achieved the recovery of liver function, while 60 patients (23.5%) did not achieve such recovery. There were significant differences between the two groups in the type of DILI injury ( P =0.028), the proportion of patients with diabetes ( P =0.048), and the degree of liver fibrosis ( P < 0.001), and compared with the recovery group, the non-recovery group had significantly higher levels of baseline white blood cell count, platelet count (PLT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase, and total bile acid and a significantly lower level of cholinesterase (ChE) (all P < 0.05). The baseline characteristics were included in the univariate logistic regression analysis, and the results showed that PLT, ALT, AST, ChE, and fibrosis degree were significantly associated with the prognosis of chronic DILI (all P < 0.05). The multivariate logistic regression analysis of the above variables showed that PLT < 100×10 9 /L (odds ratio [ OR ]=3.592, 95% confidence interval [ CI ]: 1.128-11.438, P =0.003) and ALT > 2×upper limit of normal (ULN) ( OR =3.080, 95% CI : 1.331-7.127, P =0.009) were independent risk factors for the prognosis of chronic DILI. Conclusion When patients meet the diagnostic criteria for chronic DILI, the independent risk factors PLT < 100×10 9 /L and ALT > 2×ULN may be used to screen out the patients who are more likely to have poor prognosis.

OBJECTIVE：To optim ize the ultrafiltration technology of enzymatic hydrolysate from Eucommia ulmoides peel. METHODS：The single factor test was adopted to investigate the effects of molecular weight of ultrafiltration membrane ，liquid temperature，operating pressure ，operating frequency ，membrane filtration time ，liquid concentration and pH on transfer rates of aucubin，geniposide and chlorogenic acid as well as solid removal rate in enzymatic hydrolysate from E. ulmoides peel. Setting the molecular cut off of fixed ultrafiltration membrane of 100 000，liquid concentration of 7 g/L，and pH value of 7，the ultrafiltration technology was optimized by Box-Behnken design response-surface methodology and validated with liquid temperature ，operating pressure，operating frequency and membrane passing time as factors ，using comprehensive scores calculated from transfer rates of aucubin，geniposide and chlorogenic acid as well as solid removal rate as indexes. RESULTS ：The optimal ultrafiltration technology of enzymatic hydrolysate from E. ulmoides peel was as follows as liquid temperature of 35 ℃，operating pressure of 0.5 MPa，operating frequency of 35 Hz and membrane passing time of 42 min. Results of validation tests showed that the comprehensive scores of the transfer rates of aucubin ，geniposide and chlorogenic acid as well as solid removal rate in enzymatic hydrolysate from E. ulmoides peel was 78.06％（RSD＝1.43％，n＝3），and its relative error with the predicted value （77.18％） was 1.14％. CONCLUSIONS ：The optimized ultrafiltration technology is stable and reliable ，and can be used for the ultrafiltration purification of enzymatic hydrolysate from E. ulmoides peel.

Clinical and laboratory data of 5 cases of fulmiant type 1 diabetes mellitus (FTlDM) hospitalized in our department of endocrinology and metabolism from February 2014 to December 2016 were collected analyzed.All these patients characterized by acute onset and severe ketoacidosis,with course of 1-3 d.At admission,the blood glucose level was 31.8 ～ 58.9 mmol/L,HbA1c 6.0％ ～ 7.5％,F-CP 0.01～0.05 nmol/L and 2 hC-P 0.02～0.05 nmol/L The pancreatic βcell function had no significant improvement after 1year.FTlDM patients have clinical features of abrupt onset,often with severe metabolic disorders,poor prognosis and seriously damaged islet β cell function.

Objective To investigate the relationship between leptin level of IGR patients and intima-media thickness (IMT) of carotid arterial. Methods One hundred and eighteen IGR patents were enrolled into the following three groups according to the result of oral glucose tolerance test (OGTT): 38 cases of the purely impaired fasting glucose (IFG) group, 42 cases of the purely impaired glucose tolerance (IGT) group and 42 cases of the IFG combining with IGT (IFG + IGT) group. Thirty-eight cases with normol glucose tolerance (NGR) were enrolled in the NGR group. The blood fat, fasting blood-glucose (FBG), fasting insulin (insulin), fasting C peptide , 2 h-postprandial blood glucose , 2 h-insulin , 2 h-C peptide , glycosylated hemoglobin (HbA1C), C-reactive protein (CRP), body mass index (BMI), leptin and IMT were determined in patients of the three groups and the healthy controls. The multiple linear regression was used to analyze the relationship between leptin level and IMT , and person correlation was further used to analyze the affinity degree between leptin level and IMT. Results Compared with the NGT group, the inter-group comparison showed that leptin level was significantly increased in the IFG, IGT and (IFG + IGT) groups (P < 0.05, respectively). Compared with the IFG and IGT groups, IMT and the leptin level were increased in the (IFG + IGT) group (P < 0.05, respectively). The multiple linear regression analysis showed that leptin level was correlated with the increase of IMT in the (IFG + IGT) group (P < 0.05), but not in the IFT group and the IGT group. Conclusion The leptin level in the IGR group and the IMT in the IFG + IGT ) group were significantly increased , the leptin level was closely associated with IMT.