[ ABSTRACT] AIM:To investigate the protective effect of 1, 3-dicyclopentyl-1, 2, 3, 6-tetrahydropyrimidine-4, 5-dicarboxylic acid diethyl ester (ZL-5015) on lethal endotoxin-challenged mice and to explore the underlying mechanism. METHODS:Mouse model of lethal endotoxin challenge and endotoxemia were established by intraperitoneal administration of lipopolysaccharide (LPS) at a dose of 70 mg/kg to the C57BL/6J mice.Mouse peritoneal macrophages stimulated with LPS (10 mg/L) were used as an in vitro inflammatory model.The levels of interleukin-1β( IL-1β) , interleukin-10 ( IL-10) and tumor necrosis factor-α(TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA).Real-time PCR was used to evaluate the mRNA expression of the cytokines.RESULTS:Prophylactic treatment of the mice with ZL-5015 (100 and 200 mg/kg, ig) slightly increased the survival rate, extended the survival time, decreased the serum levels of IL-1βand TNF-α, and increased the serum level of IL-10 in the early stage of endotoxemia as compared with model group.The results of in vitro study demonstrated that treatment of the endotoxin-stimulated mouse peritoneal macrophages with ZL-5015 (10, 20 and 40μmol/L) inhibited the expression of IL-1βand TNF-αat both mRNA and protein levels but promoted the expression of IL-10 at both mRNA and protein levels.CONCLUSION: The tetrahydropyrimidine derivative ZL-5015 shows a moderate anti-endotoxin effect by increasing the survival rate and extending the survival time of the mice challenged by endotoxin, which may result from inhibition of the expression of pro-inflammatory cytokines such as IL-1βand TNF-α, and promotion of the expression of anti-inflammatory cytokine IL-10.

Objective To discuss the correlation between procrastination and the mentalities of anxiety and depression among medical postgraduates,so as to carry out mental health work effectively.Methods 423 medical postgraduates in Central South University were assessed randomly, using General Procrastination Scale (GPS),Self-rating Anxiety Scale(SAS),Self-rating Depression Scale (SDS).Results Procrastination score and incidence in medical postgraduates was 54.92±8.40 and 60.99%respectively,the differences of procrastination scores(53.3l±8.21,55.90±8.30,55.75±8.49,P=0.013)and incidences(52.60%,66.09%,65.58%.P =0.028)among three grades were statistically significant.Both total coarse score of anxiety and that of depressionwere higher than that of the whole country(31.24±7.40,29.78±10.07,P=0.000;34.8±8.11,33.46±8.55,P=0.000),the differences were statistically significant.Procrastination had a positive correlation with anxiety and depression significantly(r=0.304,P=0.000;r=0.369,P=0.000),the higher the grade was,the weaker the intensity of correlation was.Hish-delay group,low-delay group and normal-behavior group had different deglees of anxiety(46.63±10.55,44.01±10.12,38.32±7.57,P=0.000)and depression(51.45±10.12,47.81±10.78,40.69±8.23,P=0.000),which was statistically significant.Conclusion Anxiety and depression among medical postgraduates were outstanding and had a close relationship with procrastination behavior,which should be taken seriously and handled by strengthening mental health education.

Based on the survey on Anhui indigenous medicine and the protection for the traditional Chinese medicine knowledge, we made an analysis and summary for the survey result of Anhui indigenous and special acupuncture techniques in terms of area distribution, types, diseases of treatment, etc. The result shows that though acupuncture and moxibustion are widely applied for all kinds of diseases in most areas of Anhui grassroots regions, they mainly concentrat in major cities like Hefei, Wuhu, Anqing, etc. The techniques are mainly used in orthopedics department and neurology department. They have weighted too much on needling skills, but moxibustion and other special techniques are not paid attention to. We propose that special acupuncture-moxibustion techniques should be promoted, and the relevant training for grassroots medical workers should be developed so as to further enhance their ability to serve grassroots people as well as inherit and innovate the techniques.

Xin'an doctor discussed acupuncture and moxibustion on ' and , calling it "orthodox needling method". 's academic thoughts on moxibustion were mainly reflected in () and (). made an incisive exposition of moxibustion treatment of heat syndrome, ulcer and other issues, and there is a corresponding test case for mutual reference. He believed that the moxibustion method only adapts to sick patients and holds opposition to moth moxibustion care for those who were disease-free; he also advocated that detailed verification of different syndrome should be conducted before acupuncture. This paper expounds 's academic thoughts on moxibustion can be used for heat syndrome, moxibustion does not stay phlegm, moxibustion need syndrome and moxibustion treatment of ulcer. It is believed that can present his own unique insights on the basis of his successors. He had played a guiding and promoting role in the development of academic theory of moxibustion.

Objective To evaluate the accuracy of different noninvasive methods for the diagnosis of nonalcoholic steatohepatitis(NASH) and hepatic fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) combined with type 2 diabetes mellitus(T2DM). Method A prospective comparative study was performed for 91 patients with T2DM and NAFLD, which were diagnosed by glucose tolerance test and liver biopsy. The height and body mass of the patient were measured, and the body mass index(BMI) was calculated. The fasting venous blood of the patient was collected, and then the blood routine, liver function and ferritin were measured. NPS, neutrophil lymphocyte ratio(NLR), BARD score, FIB-4 index, APRI, and NAFLD fibrosis score(NFS) were calculated. All patients underwent transient elastography (Fibrotouch) to evaluate the degree of liver stiffness measurement (LSM) and controlled attenuation parameter. All the liver biopsy specimens were categorized by SAF as the gold standard for evaluating NASH and liver fibrosis NASH. Correlation analysis was applied to compare the correlation between the noninvasive methods and SAF. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to assess the diagnostic value of the noninvasive methods for NASH and liver fibrosis NASH. Results In T2DM combine with NAFLD patients, NPS, LSM, NFS, APRI, FIB4 and BMI scores were positively correlated with SAF (r value was 0.509, 0.508, 0.252, 0.396, 0.313 and 0.213, respectively; P value was <0.001, <0.001, 0.016,<0.001, 0.003 and 0.043, respectively). LSM, NPS, NFS and FIB4 scores were positively correlated with liver fibrosis (r value was 0.535, 0.337, 0.315 and 0.315, respectively; P value was <0.001, 0.001, 0.002, 0.002, respectively). The ROC curve shows that the area under the curve of NPS, LSM, APRI, FIB4 and BMI for diagnosing NASH was 0.838, 0.760, 0.734, 0.623 and 0.682, respectively, and P value was 0.000, 0.000, 0.000, 0.044 and 0.003, respectively. For the diagnosis of fibrotic NASH, that value of LSM, NFS, FIB4 and NPS was 0.795, 0.765, 0.686 and 0.623, respectively, and P value was 0.000, 0.001, 0.020 and 0.123, respectively. Conclusions NPS, LSM and APRI have good clinical diagnostic value for NASH. LSM and NFS have good diagnostic value for fibrotic NASH.

Objective To explore the gender heterogeneity of depression and thyroid hormone and homocysteine levels in infertile patients.Methods Totally 250 patients with infertility were selected in Tangshan Maternal and Child Health Care Hospital affiliated to North China University of Science and Technology from December 2015 to April 2017.The Self-Rating Depression Scale(SDS) was used to evaluated the patients's depression.The patients with infertility and depression were divided into infertility and depression group,and the patients with infertility but without depression were infertile and non-depressed group,patients with infertility and depression were divided into male infertility and depression group and female infertility group with depression,and the levels of thyroid hormone and homocysteine were measured respectively.Results ①The thyroid stimulating hormone and homocysteine levels in infertility patients with depression were significantly higher than those without depression ((2.045± 1.253) uIU/ml,(2.412± 1.236) uIU/ml,t=-2.287,P=0.023;(15.411 ±9.143) mmol/L,(19.129± 13.087) mmol/L,t=-2.467,P=0.014).②There was no statistically significant difference in the degree of depression between male and female infertility patients (x2=0.483,P=0.785).③ The levels of triodothyronine,thyroxine and homocysteine in male infertility patients with depression were significantly higher than those in female patients ((1.926±0.648)nmol/L,(1.712 ±0.416) nmol/L,t=2.457,P=0.015;(117.86± 19.311) nmol/L,(110.185± 18.999) nmol/L,t=2.434,P=0.016;(15.575±4.139) mmol/L,(12.277±3.921) mmol/L,t=4.982,P＜0.01),and the TSH was lower than that in the female group((2.496± 1.329) uIU/ml,(3.057± 1.583) uIU/ml,t=-2.303,P=0.023).④The TSH and Hcy levels of male and female infertility patients were significantly positively correlated with SDS indexes,and had a significant positive predictive power to SDS score.Conclusion The levels of thyroid hormone and homocysteine are different in gender in infertile patients with depression,and the thyroid hormone and homocysteine are related to the depression.so we should pay attention to the depression symptoms of infertility patients and the changes of their biological levels,especially the gender heterogeneity.

To analyze statistically the situation of the National Natural Science Foundation of China (NSFC) from 2007 to 2016 in the field of acupuncture and moxibustion for supporting the national Universities colleges of traditional Chinese medicine on the General Program (GP) and the National Science Fund for Young Scholars (NSFYS). In view of five aspects, named fund, supporting units, key words, method, disorder and signal path, the differences were compared between GP and NSFYS, the following characteristics were summarized. ① The fund aid was increased from 2007 through 2013 and down-regulated from 2013 through 2016. In recent ten years, the funding condition was fluctuated, but increasing in tendency generally. ② The relevant projects of the same research direction had been approved continuously for over 3 years in a part of TCM universities, in which, the research continuity was the hot topic. ③ Regarding the therapeutic methods, acupuncture was the chief therapy; electroacupuncture, moxibustion and acupoints were involved as well. ④ The disorders involved in the research were cerebral ischemia, myocardial ischemia and reperfusion injury. It is suggested that the ischemic disorder is predominated in the research. ⑤ The signal path occupied the main research index system, including cell proliferation, metabolism, immune, apoptosis and autophagy. The researches on the other aspects were less.
Acupuncture Therapy ; trends ; China ; Humans ; Ischemia ; therapy ; Medicine, Chinese Traditional ; Moxibustion ; trends ; Universities

OBJECTIVETo investigate the regulation of α-Tocopherol on NFκB and Nrf2 signaling pathway at early stage of N-nitrosomethylbenzylamine (NMBzA)-induced human esophageal carcinogenesis.

METHODSHuman normal esophageal HET-1A cells were treated with NMBzA at 50 µmol/L, 100 µmol/L for 24 h to intimate the initiation of esophageal carcinogenesis. For intervention groups, HET-1A cells were pre-treated with α-T at 25, 50, 100 µmol/L for 3 h and then co-treated with NMBzA (100 µmol/L) for 24 h. In comparison with HET-1A cells, human esophageal cancer EC109 cells were treated with α-T at corresponding concentrations. Cells treated with 0.1% DMSO were used as negative control. Immunofluorence staining was used for the determination of distribution and activation of NFκB p65 and Nrf2 in the cell. Real time PCR and Western blot were used to determine the expression levels of target genes including cyclinD1, KI67, proliferating cell nuclear antigen (PCNA), cyclo-oxygen-ase 2 (COX2), 5LOX, HO-1, NQO1 and GCLC. Flow cytometry was utilized to analyze the reactive oxygen species contents in the cells.

RESULTSAs compared to the control group (1.00 ± 0.08), the expression of CyclinD1 (2.99 ± 0.15), KI67 (2.35 ± 0.38) and PCNA (2.46 ± 0.25) in HET-1A were all markedly increased by NMBzA treatment (F values were 97.23, 65.28, 34.62, P < 0.001). Also, the proportion of cells with nucleus translocation of NFκB p65 (71.0%, 98/138) or Nrf2 (36.3%, 49/135) were significantly increased (χ² values were 194.71, 133.72, P < 0.001), and the expression of COX2 (3.22 ± 0.17), 5LOX (2.87 ± 0.12) as well as HO-1 (1.87 ± 0.22), NQO1 (2.14 ± 0.08), GCLC (2.63 ± 0.41) at protein levels were elevated (F values were 72.35, 43.87, 69.23, 71.34, 85.79, P values were 0.013, 0.015, 0.010, 0.011, 0.002). Under the treatment with 50 µmol/L α-T, comparing with the control group(59.1%,65/110),the nuclear translocation of NFκB p65 (77.7%, 8/104) was clearly inhibited (χ² = 148.1, P < 0.001), and protein expression levels of COX2 (0.74 ± 0.19) and 5LOX (0.42 ± 0.13) were decreased (F values were 56.31, 73.25, P values were 0.003, 0.001). However, no changes on Nrf2 signaling pathway were observed; α-T showed little impact on NFκB or Nrf2 pathway in EC109 cells.

CONCLUSIONSAt the early stage of NMBz-induced esophageal cancer, α-T could block the initiation of carcinogenesis through suppressing the activation of NFκB signaling pathway. It might be the major mechanism by which α-T is potentially chemopreventive to esophageal cancer. During the progression of esophageal cancer, the cells may acquire the adaptive functions to accommodate oxidative stress via activating Nrf2 pathway.

Carcinogenesis ; Cyclooxygenase 2 ; Dimethylnitrosamine ; analogs & derivatives ; Esophageal Neoplasms ; Heme Oxygenase-1 ; Humans ; NAD(P)H Dehydrogenase (Quinone) ; NF-E2-Related Factor 2 ; NF-kappa B ; Oxidative Stress ; Reactive Oxygen Species ; Signal Transduction ; alpha-Tocopherol

Objective: To investigate the effect of dietary control combined with different exercise modes on plasma vaspin, irisin, and metabolic parameters in patients with non-alcoholic fatty liver disease (NAFLD) through a randomized open parallel-controlled study. Methods: The patients aged 30-65 years who visited Tianjin Third Central Hospital from January 2013 to December 2014 and were diagnosed with NAFLD by liver ultrasound and fat content determination were screening, and 474 patients were enrolled in this randomized controlled trial and divided into aerobic exercise group, resistance exercise group, and control group. All patients received dietary intervention. The three groups were compared in terms of biochemical parameters, fat content, NFS score, energy metabolic parameters, body composition index, and levels of vaspin and irisin at baseline and after 6 months of intervention. SPSS 19.0 was used for statistical analysis. The t-test, the Mann-Whitney U test, the chi-square test, and an analysis of variance were used for comparison between groups. The multiple imputation method was used for missing data, and the results were included in the intention-to-treat analysis. Results: There were no significant differences in age, sex, anthropometrical parameters, and biochemical parameters between the three groups at baseline. Compared with dietary control alone, aerobic exercise and resistance exercise helped to achieve significant reductions in waist circumference, diastolic pressure, percentage of body fat, volatile fatty acid, fasting blood glucose, homeostasis model assessment of insulin resistance, triglyceride, low-density lipoprotein cholesterol, free fatty acid, uric acid, alanine aminotransferase, and liver fat content after 6 months of intervention (P < 0.05). The aerobic exercise group had a significant increase in non-protein respiratory quotient and significant reductions in body mass index and aspartate aminotransferase after intervention, as well as a significant increase in resting energy expenditure and significant reductions in abdominal fat ratio and total cholesterol after 6 months of resistance exercise (P < 0.05). The aerobic exercise group and the resistance exercise group had a significant reduction in vaspin and a significant increase in irisin after intervention (P < 0.05), and the resistance exercise group had significantly greater changes in these two adipokines than the aerobic exercise group (P < 0.05). Conclusion Exercise therapy is an effective method for the treatment of metabolism-associated diseases, and a combination of resistance and aerobic exercises is more reasonable and effective in clinical practice. As a relatively safe exercise mode, resistance exercise can also effectively improve the metabolic state of NAFLD patients.