Objective To explore the effects of combined exposure to bisphenol A (BPA) and high-fat diet on liver lipid metabolism and hepatocyte senescence in mice, and to elucidate the potential mechanisms of the onset and development of non-alcoholic fatty liver disease (NAFLD). Methods Specific pathogen free C57BL/6J mice were randomly divided into six groups, with 10 mice with equal numbers of each sex in each group. The mice in the control group and the simple BPA group were fed with regular diet, while others four groups of mice were fed with high-fat diet. At the same time, the mice in the simple BPA group were intragastric administered with BPA at a dose of 50 μg/kg body weight, while the mice in the low-, medium- and high-dose BPA+high-fat groups were intragastric administered with BPA at doses of 5, 50 and 500 μg/kg body weight respectively. The mice in the control group and the high-fat group were intragastric administered with the same volume of corn oil once per day for 90 consecutive days. Liver tissues were subjected to hematoxylin-eosin (HE) and Oil Red O staining. Liver coefficients and lipid-stained area ratios were calculated. Serum level of total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, and the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined using an automatic biochemical analyzer. The hepatic tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-10 levels were quantified by enzyme-linked immunosorbent assay. The relative expression of cholesterol regulatory element binding protein 1 (SREBP1), CCAAT enhancer binding protein α, P16, and phosphorylated histone H2AX (γ-H2AX) in liver tissues was detected using Western blotting. The interaction effect of the combined exposure to BPA and high-fat diet was observed based on the result of mice in the control group, the simple high-fat group, the simple BPA group, and the medium-dose BPA group+high-fat group (the combined exposure group) using a 2×2 factorial design. The results of mice in the simple high-fat group and the low-, medium-, and high-dose BPA+high-fat groups were used to observe the effect of BPA exposure dose under high-fat diet conditions. Results i) The interactive effect of combined exposure to BPA and high fat. The HE and Oil Red O staining results indicated that the combined exposure to BPA and high-fat diet successfully established NAFLD in mice. The interactive effect of combined exposure to BPA and high-fat diet on serum ALT activity and the relative expression of P16 in the liver tissue of female mice, as well as the serum ALT and AST activities and the relative expression of SREBP1 in the liver tissue of male mice was significant (all P<0.05). Specifically, the serum ALT activity of male mice in the combined exposure group was higher than that in the simple high-fat group (P<0.05), while the ALT activity in the serum of female mice in the combined exposure group was lower than that in the simple BPA group (P<0.05). The relative expression of SREBP1 protein in the liver tissue of male mice in the combined exposure group was higher than that in the control group, the simple high-fat group, and the simple BPA group (all P<0.05). For the other indicators, there were no significant differences in the interactive effect of combined exposure to BPA and high-fat diet (all P>0.05). ii) Dose effects of BPA exposure. The HE and Oil Red O staining result showed that the degree of vacuolar steatosis in the liver of female and male mice of medium- and high-dose BPA + high-fat groups was aggravated, and the range of inflammatory cell infiltration was expanded when compared with same-sex mice in the simple high-fat group. The serum ALT activity and the fat stained area ratio, as well as the relative expression of P16 in liver tissue of female mice in high-dose BPA + high-fat group increased (all P<0.05), while the level of IL-10 in liver tissue decreased (P<0.05), compared with the female mice in simple high-fat group. The serum ALT activity, the TNF-α level in liver tissue, and the relative expression of SREBP1, P16 and γ-H2AX proteins in liver tissue of male mice in high-dose BPA + high-fat group increased (all P<0.05), while the IL-6 level in liver tissue decreased (P<0.05), compared with the male mice in simple high-fat group. For the female or male mice in the low- and medium-dose BPA + high-fat groups, only some of the above indicators showed significant changes (all P<0.05). Conclusion The combined exposure to BPA and high-fat diet has a synergistic effect on the onset and development of NAFLD. The mechanism may be related to inducing cellular senescence and modulation of lipid synthesis pathways, thereby affecting liver steatosis. The exposure dose of BPA may affect the synergistic effect.

Objective The prediction of RR intervals in hypertensive patients can help clinicians to analyze and warn patients'heart condition.Methods Using 8 patients'data as samples,the RR intervals of patients were predicted by long short-term memory network(LSTM)and gradient lift tree(XGBoost),and the prediction results of the two models were combined by the inverse variance method to overcome the disadvantage of single model prediction.Results Compared with the single model,the proposed combined model had a different degree of improvement in the prediction of RR intervals in 8 patients.Conclusion LSTM-XGBoost model provides a method for predicting RR intervals in hypertensive patients,which has potential clinical feasibility.

Heart failure refers to a group of clinical syndromes caused by structural or functional abnormalities of the heart that lead to impaired ejection or filling of the ventricles. The traditional Chinese medicine （TCM） theory of cardiac and renal coordination holds that the kidney governs water and plays a key role in maintaining the balance of fluid metabolism. Therefore， the treatment of water retention in heart failure can start from the heart and kidney. The basic pathogenesis of heart failure is kidney deficiency， blood stasis， and water stagnation， and the therapies including dredging the heart and kidneys， warming yang and excreting water， tonifying kidneys and activating blood， and dredging meridians and collaterals. Aquaporins （AQPs）， the key molecular basis of water metabolism， are involved in the pathogenesis of water retention in heart failure together with the arginine vasopressin system （AVP）， renin-angiotensin-aldosterone system （RAAS）， and diuretic resistance. Studies have shown that herbal medicines that regulate the heart and kidney can alleviate water retention in heart failure by targeting AQPs， thereby delaying or even reversing the progression of heart failure. This paper expounds the TCM name and pathogenesis of heart failure from the theory of cardiac and renal coordination， the role of AQPs in the pathogenesis of water retention in heart failure， and the modern connotation of the therapy of tonifying heart and kidney for heart failure， aiming to provide ideas for the prevention and treatment of water retention in heart failure by TCM.

Objective To observe the clinical efficacy of Shuxuening injection combined with compound coenzyme in the treatment of chronic allograft nephropathy (CAN). Methods A retrospective analysis of 108 patients with chronic allograft nephropathy (CAN) admitted to our hospital from June 2014 to May 2018 were divided into two groups according to different treatments. The 43 cases in the experimental group were given Shuxuening injection combined with compound coenzyme, and the 65 cases in control group were given non-Shu Xuening + compound coenzyme. The original immunization protocol was maintained in both groups. After 4 weeks of treatment, the changes of hemodynamic parameters, clinical efficacy, biochemical parameters, coagulation function and adverse reactions were observed before and after treatment. Results There was no significant difference in baseline data between the two groups before treatment (P> 0.05). After treatment, the peak systolic velocity of the intersegmental artery and cortical arteriole in the experimental group were significantly higher than that the control group (P < 0.05) , and the resistance index was lower than that in the control group (P < 0.05). After treatment, serum creatinine, 24 h urine protein quantitation, urinary microalbumin, total cholesterol and triglycerides were lower than that before treatment (P < 0.05) , and estimated glomerular filtration rate (eGFR) and serum. Albumin increased significantly (P < 0.05) , but the 24 h urine protein quantitation and urinary albumin decreased significantly in the experimental group compared with the control group (P < 0.05). After treatment, the total amount of cholesterol, triglycerides showed no significant difference (P> 0.05). After treatment, the platelet count, fibrinogen and D-dimer of the experimental group were significantly lower than those before treatment (P < 0.05) , and the activated partial thrombin time (APT) was significantly higher than that before treatment (P < 0.05). Significant difference in platelet count, fibrinogen, D-dimer and APTT was found after treatment (P < 0.05). After 4 weeks of treatment, the values of urea nitrogen and serum creatinine were significantly lower than those of the control group (P < 0.05). The recovery of transplanted kidney function in the experimental group was higher than that in the control group (P < 0.05). The experimental group reported 2 cases of fatigue complain and 1 case of dizziness, but no special treatment was given to them and their condition improved after symptomatic treatment; 1 case of mild phlebitis which was cured after given slowed drip rate and local hot compress therapy. The incidence of adverse events was 9.3％ (4/43). The control group reported 2 cases of fatigue complain, 1 case of nausea, 1 case of facial flushing, and all cured with no special treatment was given; 1 case of mild phlebitis, and cured after slowed the i.v. drip rate and ocal hot compress; The adverse events rate was 7.7％ (5/65). No serious adverse reactions occurred during the entire clinical trial. There was no significant difference in the incidence of adverse events between the experimental group and the control group (χ2=0.054, P=0.732). Conclusion Combined with Shuxuening injection and compound coenzyme can improve blood flow of transplanted kidney, reduce proteinuria, reduce blood urea nitrogen and creatinine in patients with CAN after renal transplantation and effectively improve patient's hemodynamic parameters and safety.

Circulating tumor DNA (ctDNA) detection is one of "liquid biopsy"analysis. It has shown promising clinical application in cancer precise medicine due to its noninvasive sampling and real-time observation. Nowadays, ctDNA analysis has been clinically validated and successfully applied in advanced cancer, including selecting personalized treatment, monitoring treatment responses, minimal residual disease and recurrence. Although there has been rapidly increasing interests in ctDNA, its clinical application in cancer precise medicine is still facing few challenges, especially in screening and diagnosing cancer at early stages. Here, the latest progress in the applications and challenges of ctDNA in advancedstage tumor therapy were reviewed to provide references for future studies on ctDNA.

Objective To examine the operation efficiency of hospital clinical departments and explore ways to improve inefficient units from an input-output perspective.Methods We used the data envelopment analysis(DEA) to analyze the panel data in 2013-2017 from 30 clinical departments of a hospital,applying the CCR model and the BCC model.Results The overall operation efficiency of the hospital was as high as 26.32％ of its clinical departments showed the increasing returns to scale.The scale efficiency was found to be high when the bed size in clinical departments ranged from 1 to 20,from 41 to 80,or from 91 to 100.There was an irrationality in fixed assets and staff deployment.Conclusions Size and input of clinical departments should be carefully planned to increase resource utilization efficiency.

T cells are an important adaptive immune response arm that mediates cell-mediated immunity. T cell metabolism plays a central role in T cell activation, proliferation, differentiation, and effector function. Specific metabolic programs are tightly controlled to mediate T cell immune responses, and alterations in T cell metabolism may result in many immunological disorders. In this review, we will summarize the main T cell metabolic pathways and the important factors participating in T cell metabolic programming during T cell homeostasis, differentiation, and function.
Animals ; Cell Physiological Phenomena ; Humans ; Immunity, Cellular ; physiology ; Metabolic Networks and Pathways ; immunology ; T-Lymphocytes ; immunology ; metabolism

Objective:To obtain recombinant Profilin of silkworm,identify its immunogenicity,predict its B cell epitopes and construct the evolutionary trees. Methods: The nucleotide sequence of Profilin was acquired from NCBI,synthesized it and cloned it into pET-28 vector. Then,the recombinant plasimids were transformed to E. coli BL21. After induced by IPTG,recombinant protein was purified by Affinity chromatography. Furtherly,its allergenicity was identified by Western blot,the potential B cell epitopes was analyzed through DNAStar and build the evolutionary trees by MEGA5. 05. Results: The recombinant protein of Profilin was successfully expressed and purified by affinity chromatography. Besides,the protein contains a high IgE-binding activity with IgE existing in serum of patients allergic to silkworm. Conclusion: The recombinant proflilin has IgE-binding activity, and it is meaningful for fundamental research and specific diagnosis studies of allergic diseases caused by silkworm.

Objective To evaluate the effect of conversion from mycophenolic acid (MPA) to mizoribine (MZR) in renal transplant recipients with gastrointestinal tract (GI) symptoms.Methods A total of 355 renal transplant recipients with GI symptoms caused by MPA administration were enrolled from April 2015 to March 2017 in 25 different renal transplant centers in China.The symptomatic improvement of GI before (baseline) and after conversion to MZR (1,2,4 weeks) was assessed by each item of GI symptoms indication.In addition,the efficacy and safety of the conversion therapy during 12 months were determined.Results Patients showed improvement in GI symptoms including diarrhea,abdominal pain,abdominal distention and stomachache after conversion to MZR 1,2,4 weeks (P＜0.05).In patients with different severity of diarrhea,conversion to MZR therapy significantly improved diarrhea (P＜0.05).During 12 months,no patient experienced clinical immune rejection.We did not observe any infections,leucopenia and other serious side effects.Conclusion MZR could markedly improve GI symptoms caused by MPA administration in renal transplant recipients.

Objective To explore the application of allergen detection in children with recurrent asthma and its clinical signifi‐cance .Methods The clinical data of 524 cases of children with recurrent asthma in this hospital ,from February 2013 to February 2015 ,were retrospectively analysed .According to age ,these children with recurrent asthma were divided into three groups:250 ca‐ses were enrolled into infants group(0- <1 years old) ,150 cases enrolled into cheepers group(1- <3 years old) ,124 cases were enrolled in children group (≥3 years old) .Children in the three groups were treated with allergen detection ,and positive rates and distribution of allergens were compared among three groups .Results The total positive rate of allergen detection was 39 .69%(208/524) .The positive rate of allergen detection was the highest in children group(66 .13% ) ,and the lowest in infants group (24 .00% ) ,and there were statistically significant differences in the positive rates among the three groups(P<0 .05) .The top 3 common allergens were milk ,household dust mite and cat dander .The positive rates of household dust mite and house dust were the highest in children group ,but lowest in infants group ,there were statistically significant differences in the positive rate among the three groups(P<0 .05) .Conclusion Allergen detection is particularly important for children with recurrent asthma ,which not only could quickly find the etiology of asthma and identify children who are susceptible to asthma ,but also provide references for early intervention in childhood asthma .