Objective:To explore the prognostic significance of preoperative carcinoembryonic antigen (CEA) in patients with stage Ⅳ colon cancer with simultaneous liver and/or lung metastasis, and establish a predictive model.Methods:Using the SEER database, 5 149 patients diagnosed with colon cancer from 2010 to 2015 were collected based on inclusion and exclusion criteria. They were divided into a CEA positive group and a CEA negative group based on their preoperative CEA status. Based on the different CEA status and metastatic sites, we plotted different survival curves and analyzed the differences using the Log rank method. We used the Cox proportional risk model to analyze the risk factors affecting the prognosis of patients with simultaneous liver and/or lung metastasis in colon cancer, and constructed a column chart based on the results. The area under the receiver operating characteristic (ROC) curve of different variable models was calculated and the model discrimination wasevaluated. By using x-tile software, the optimal cutoff value for individual total scores was selected and risk levels were classified to predict patient prognosis.Results:CEA positive colon cancer patients with liver and/or lung metastasis had a poor prognosis, with a 5-year survival rate of 13.4%. Cox proportional risk analysis showed that CEA positive patients had an increased risk of death compared to negative patients after adjusting for other factors ( HR=1.64). After incorporating the CEA+ X, X (independent risk factors other than CEA), and AJCC T+ N models, the areas under the ROC curve were 0.712, 0.706, and 0.59, respectively. According to the prediction score given in the column chart, the x-tilie selected for the best cutoff score was 262.5, which can be divided into high-risk and low-risk populations. The Log rank test was P<0.05. Conclusions:The preoperative CEA level has important predictive value for the prognosis of stage IV colon cancer patients with simultaneous liver and/or lung metastasis. The survival prediction model and column chart for colorectal cancer patients with liver and/or lung metastasis established based on the Cox proportional risk model are of great significance for patient prognosis evaluation and are conducive to the selection of personalized treatment plans.

Microglial surveillance plays an essential role in clearing misfolded proteins such as amyloid-beta, tau, and α-synuclein aggregates in neurodegenerative diseases. However, due to the complex structure and ambiguous pathogenic species of the misfolded proteins, a universal approach to remove the misfolded proteins remains unavailable. Here, we found that a polyphenol, α-mangostin, reprogrammed metabolism in the disease-associated microglia through shifting glycolysis to oxidative phosphorylation, which holistically rejuvenated microglial surveillance capacity to enhance microglial phagocytosis and autophagy-mediated degradation of multiple misfolded proteins. Nanoformulation of α-mangostin efficiently delivered α-mangostin to microglia, relieved the reactive status and rejuvenated the misfolded-proteins clearance capacity of microglia, which thus impressively relieved the neuropathological changes in both Alzheimer's disease and Parkinson's disease model mice. These findings provide direct evidences for the concept of rejuvenating microglial surveillance of multiple misfolded proteins through metabolic reprogramming, and demonstrate nanoformulated α-mangostin as a potential and universal therapy against neurodegenerative diseases.

Medicine, Chinese Traditional ; Drugs, Chinese Herbal ; China

Objective:To investigate the expression of long non-coding RNA MALAT1, interleukin 6(IL-6) and apoptosis induced factor(AIF) in peripheral venous blood of premature infants with bronchopulmonary dysplasia (BPD) and its clinical significance.Methods:Preterm infants admitted to the Department of Neonatology, Shanghai Children′s Hospital from January 2015 to December 2016 were enrolled.The selection criteria included gestational age (GA) ≥28 weeks and ≤32 weeks, and birth weight (BW) < 1 500 g. According to the diagnosis, they were divided into BPD group (20 cases) and control group (20 cases). The clinical data of the two groups of premature infants were collected and analyzed, and the levels of MALAT1, IL-6 and AIF in the blood of 40 premature infants were detected by real-time polymerase chain reaction (RT-PCR). T test was used to compare gestational age, birth weight, MALAT1, IL-6 and AIF between the two groups. Results:(1)There was no significant differences in sex ( χ2=1.76), gestational age ( t= 0.17) and birth weight ( t=1.25) of premature infants in BPD group, compared with the control group (all P >0.05). (2)Compared with the control group, the expression of MALAT1 in the peripheral blood of premature infants in BPD group were significantly increased (0.273 4±0.067 3 vs. 0.375 5±0.081 9, P<0.05). (3)Compared with the control group, the expression of IL-6 in the peripheral blood of premature infants in BPD group were obviously decreased (1.448 8±0.191 8 vs.4.444 6±0.165 7, P<0.05). (4)Compared with the control group, the expression of AIF in the peripheral blood of premature infants in BPD group were remarkably decreased(0.006 8±0.002 0 vs.0.004 5±0.001 9, P<0.05). Conclusions:MALAT1 and IL-6 levels of long non-coding RNA in BPD and non-BPD preterm infants are different, which may be related to the incidence of BPD.IL-6 may be a predictor of BPD, and MALAT1 may protect premature infants with BPD.

Objective:To study the early predictive value of urine neutrophil gelatinase-associated lipoprotein (NGAL) and kidney injury molecule-1 (KIM-1) for acute kidney injury (AKI) in neonates with severe asphyxia.Method:From January 2019 to June 2020, neonates with severe asphyxia admitted to our hospital within 6 hours after birth were enrolled in the study. The dynamic changes of urine NGAL and KIM-1 at admission, 24 h, 48 h and 1 w after birth were examined. Neonates were assigned into AKI group and non-AKI group according to the clinical practice guidelines for AKI issued by KDIGO (Kidney Disease: Improving Global Outcome). The sensitivity and specificity of NGAL and KIM-1 predicting AKI at different time points were evaluated using ROC curve and area under curve (AUC).Result:According to the diagnostic criteria of neonatal AKI, 9 cases were in the AKI group and 42 cases in the non-AKI group, and the incidence of AKI was 17.6%. Urine NGAL was significantly increased in AKI group at admission and 24 h after birth compared with the non-AKI group [(115.6±75.5) ng/ml vs. (49.8±29.0) ng/ml, (90.7±35.6) ng/ml vs. (55.6±30.7) ng/ml] ( P<0.05). No significant differences existed at 48 h and 1 w after birth between the two groups. At 24 h after birth, urine KIM-1 in the AKI group was significantly higher than the non-AKI group [(808.3±555.3) pg/ml vs. (318.4±234.0) pg/ml, P<0.05] and no significant differences existed between the two groups at admission, 48 h and 1 w after birth. The AUC of NGAL predicting AKI at admission, 24 h, 48 h and 1w after birth were 0.804 (95% CI 0.573~1.000), 0.792 (95% CI 0.580~1.000), 0.732 (95% CI 0.517~0.947) and 0.551(95% CI 0.371~0.730), respectively. The AUC of KIM-1 predicted AKI at admission, 24 h, 48 h and 1 w after birth was 0.860 (95% CI 0.676~1.000), 0.824 (95% CI 0.655~0.993), 0.768 (95% CI 0.622~0.914), 0.622 (95% CI 0.392~0.852), respectively. Conclusion:At admission, 24 h and 48 h after birth, urine NGAL and KIM-1, as kidney injury markers, may predict the occurrence of AKI after severe neonatal asphyxia.

As an important branch of artificial intelligence, machine learning is widely used in various fields. Machine learning has similarity to classical statistical methods, but can solve many problems which are difficult for traditional statistics, so it is one of the important tools in epidemiological research. This paper introduced 9 common algorithms of machine learning and summarized their characteristics and applications in epidemiological research. Readers could choose appropriate machine learning method according to the research purpose for the better application of machine learning in epidemiological research.

At present, traditional methods on statistics have limitations in controlling time- varying confounding. This paper introduces an analysis method, parametric g-formula, which would adjust time-varying confounding, and also exemplifies the steps of its implementation for purpose to provide a new reference for researchers to deal with long-term observational data.

Objective To analyze the prevalence of schistosomiasis in Hunan province,and provide scientific evidence for the control and elimination of schistosomiasis.Methods The changes of infection rates ofSchistosoma (S.)japonicum among residents and cattle in Hunan from 1984 to 2015 were analyzed by using dynamic trend diagram;and the time regression model was used to fit the infection rates of S.japonicum,and predict the recent infection rate.Results The overall infection rates of S.japonicum in Hunan from 1984 to 2015 showed downward trend (95.29％ in residents and 95.16％ in cattle).By using the linear regression model,the actual values of infection rates in residents and cattle were all in the 95％ confidence intervals of the value predicted;and the prediction showed that the infection rates in the residents and cattle would continue to decrease from 2016 to 2020.Conclusion The prevalence of schistosomiasis was in decline in Hunan.The regression model has a good effect in the short-term prediction of schistosomiasis prevalence.

Objective Less surveys on the economic burden of hepatitis B (HB)-related diseases have been conducted in China,so the socioeconomic harm caused by the diseases is not clear and the key parameters for economic evaluation of hepatitis B prevention and treatment are lacking.This study aimed to analyze the direct,indirect and intangible expenditures of hospitalized patients with HB-related diseases during hospitalization and during a year in different areas of China.Methods The hospitals for infectious diseases and the large general hospitals in 12 areas in China were selected in the study.All the inpatients with HB-related diseases were surveyed by cluster sampling of consecutive cases.The direct expenditure included direct medical cost and direct non-medical cost.The indirect expenditure,including work loss of patients and caregivers,were calculated by using human capital method for urban and rural populations in 12 areas.The intangible expenditure were reflected by willing to pay and stochastic tournament.The influencing factors of direct and indirect costs were identified by stepwise linear multi-variation regression analysis.Results A total of 27 hospitals in 12 areas were included in the survey.A total of 4 718 cases were surveyed,the overall response rate was 77.7％.The average hospital stay was 29.2 days (27-34) and the hospitalization expenditure was averagely 16 832.80 yuan (RMB) per case,in which the highest proportion (61.2％)was medicine fees [10 365.10 yuan (RMB)].The average direct expenditure and indirect expenditure were consistent with the severity of illness,which were 18 336.10 yuan (RMB) and 4 759.60 yuan (RMB) respectively,with the ratio of 3.85:1.The direct medical expenditure [17 434.70 yuan (RMB)] were substantially higher than the direct non-medical expenditure [901.40 yuan (RMB)].It was found that the hospitalization expenses was highest in direct medical expenditure and the transportation expenses was highest in direct non-medical expenditures.Among the average indirect expenditure,the loss of income for the patients [3 832.50 yuan (RMB)] was higher than that for the caregivers [927.20 yuan (RMB)],The total direct and indirect expenditure was highest for liver transplantation,followed by severe hepatitis,hepatocellular carcinoma and decompensated cirrhosis,acute hepatitis B,compensated cirrhosis and chronic hepatitis B.The influencing factors for both direct and indirect expenditure were high hospital level,severity of hepatitis B,living in urban area,antiviral therapy,long hospitalization and monthly income of family.For average 3.74 outpatient visits and 1.51 hospitalization,the average annual direct,indirect and intangible expenditure for HB-related diseases were 30 135.30,6 253.80 and 44 729.90 yuan (RMB) [totally 81 119.00 yuan (RMB)],accounting for 37.3％,7.7％ and 55.0％,respectively.Of the annual direct medical expenditure [28 402.80 yuan (RMB)],which were much higher than non-medical expenditure [1 732.50 yuan (RMB)],hospitalization expenditure [26 074.20 yuan (RMB)] was higher than outpatient visit expenditure [4 061.10 yuan (RMB)].The annual indirect expenditures for outpatient visit and hospitalization were 763.60 and 5 490.10 yuan (RMB),respectively.Of the annual intangible expenditure,the highest was that for/primary hepatocellular carcinoma,followed by cirrhosis,chronic hepatitis B,severe hepatitis B,liver transplantation and acute hepatitis B.Conclusions A heavy economic burden has been caused by HB-related diseases in China,and patients are more likely to rely on medical service rather than non-medical service.It is necessary to take effective treatment measures to prevent the adverse outcome of HB related diseases and achieve significant economic benefits.The influence of HB related diseases on mental health of the people can be reflected by an economics term,intangible expenditure.

Objective To understand the current distribution and characteristics of advanced schistosomiasis patients who accepted medical assistance in Hunan Province in 2015,so as to provide the evidence for perfecting the policy and measures of the medical assistance to advanced schistosomiasis patients. Methods The patients who had been diagnosed as advanced schis-tosomiasis were verified and confirmed according to the standard of the medical assistance to advanced schistosomiasis patients in Hunan Province in 2015. The epidemiological survey was conducted to investigate the demographic characteristics,history of diagnosis and treatment,and medical assistance to these persons. Results There were 3850 advanced schistosomiasis patients who accepted the medical assistance in Hunan Province in 2015,and among them,2664 patients were male(69.19%),and 1186 were female(30.81%). Most of them(92.82%)came from the main schistosomiasis endemic areas,such as Yueyang, Changde and Yiyang. There were 2369 cases of ascites(61.53%),1466 cases of splenomegaly(38.08%),15 cases of colon proliferation and dwarf(0.39%). The mean age of advanced schistosomiasis patients who accepted the medical assistance was (62.94 ± 11.67)years old,with 64.31% of them being more than 60 years old. The age of initial diagnosis of advanced schistoso-miasis was(53.85 ± 21.32)years old,and it was concentrated in 40-60 years old(68.57%). The mean duration of advanced schistosomiasis was(9.58 ± 10.06)years,and it was mainly distributed in 10 years(75.95%). The mean duration from initial diagnosis of schistosomiasis to advanced schistosomiasis was(22.33 ± 14.20)years. The priority of the medical assistance to ad-vanced schistosomiasis patients was given to the county hospitals(76.57%);and the effective rate of assistance was 94.46%. To-tally 86.57% of the patients with advanced schistosomiasis got the medical insurance(rural cooperative medical care,urban medical care,etc.). Conclusions The burden of the medical assistance to advanced schistosomiasis patients is still heavy be-cause of many patients and low cure rate in Hunan Province. The ascites patients and high age patients should be the important objects of the medical assistance.