Objective To investigate the value of minimum apparent diffusion coefficient(ADCmin)and delta apparent diffusion coefficient(dADC)of quantitative parameters of MR diffusion weighted imaging(DWI)in differentiating benign from stage Ⅰ malignant ovarian epithelial tumors.Methods A total of 112 patients with primary ovarian epithelial tumors confirmed by operation and pathology(43 benign tumors and 69 stage Ⅰ malignant tumors)were retrospectively selected.All patients underwent routine MRI and DWI before operation.The ADCmin and dADC of solid portion were measured and compared between the two groups.Logistic regression anal-ysis and receiver operating characteristic(ROC)curve were used to evaluate diagnostic performance of each parameter alone and in combination in differentiating ovarian epithelial benign and stage Ⅰ malignant tumors.Results The ADCmin was greater in benign tumors than that in stage Ⅰ malignant tumors,while dADC was smaller in benign tumors than that in stage Ⅰ malignant tumors(P＜0.05).Logis-tic regression analysis showed that ADCmin and dADC were independent risk factors for stage Ⅰ malignant tumors.With threshold of 1.183 × 10-3 mm2/s for ADCmin and 0.579 × 10-3 mm2/s for dADC,the area under the curve(AUC)was 0.802 and 0.857,sensitivity and specificity of 0.885,0.808,0.714,0.857,respectively.According to regression equation logit(P)=7.154+0.267 × dADC-1.016 X ADCmin,the AUC(0.951)was greater than that of single parameter,the sensitivity was 0.890,the specificity was 0.995.Conclusion ADCmin and dADC are useful for differentiating ovarian epithelial benign from stage Ⅰ malignant tumors,and ADCmin combined with dADC can improve the diagnose accuracy before operation.

Objective:To investigate the effects of fluoride exposure on kidney injury in rats and the sirtuin 3 (SIRT3)-fork head protein O3a (FOXO3a)-tensin homolog induced putative kinase 1 (PINK1)/E3 ubiquitin ligase (PARKIN) pathway.Methods:Twenty-four 4-week-old SD rats (clean grade, body mass 100 - 150 g) were selected and divided into three groups according to the randomized numeric table: control group, low fluoride group, and high fluoride group, with eight rats in each group (half male and half female). The control group was given free access to tap water (fluoride ion concentration < 0.5 mg/L), while the low fluoride and high fluoride groups were given free access to tap water and sodium fluoride solutions with fluoride ion concentrations of 5.0 and 50.0 mg/L, respectively, for a period of 180 days. The formation of dental fluorosis in rats was observed and recorded, and the femur, urine and blood samples of rats were collected to measure bone fluoride, urinary fluoride, and blood fluoride levels, and to detect kidney function related indicators (serum uric acid, creatinine, and urea nitrogen contents). Morphological changes of renal tissues stained with hematoxylin-eosin (HE) were observed under a light microscope. Real-time fluorescence quantitative PCR (qRT-PCR) and Western blotting were used to detect the mRNA and protein expression levels of renal SIRT3, FOXO3a, PINK1, PARKIN, microtubule associated protein 1 light chain 3 (LC3), autophagy receptor protein (P62), respectively.Results:Seven and one rats in the low and high fluoride groups were found to haveⅠdegree dental fluorosis, while zero and seven rats were found to haveⅡdegree dental fluorosis. Compared with the control group, rats in the low and high fluoride groups had higher levels of bone fluoride (μg/g: 1.18 ± 0.06, 2.16 ± 0.07 vs 0.52 ± 0.05), urinary fluoride (mg/L: 4.43 ± 0.11, 7.46 ± 0.09 vs 2.58 ± 0.14), blood fluoride (μg/ml: 0.77 ± 0.06, 1.68 ± 0.10 vs 0.52 ± 0.08), serum uric acid (μg/ml: 61.01 ± 4.17, 103.92 ± 5.43 vs 28.68 ± 2.91), creatinine (μg/ml: 74.82 ± 9.61, 132.05 ± 5.35 vs 22.38 ± 4.11), and urea nitrogen (μg/ml: 13.36 ± 1.27, 14.55 ± 0.34 vs 0.29 ± 0.07, P < 0.05). Under the light microscope, the kidneys of the control group showed tight and orderly arrangement of renal tubules and glomerular cells, with complete and clear cell contours. The low fluoride group was similar to the control group and no significant abnormalities were observed. The high fluoride group showed abnormal glomerular structure and atrophy, with some areas of renal tubules showing epithelial cell edema and unclear intercellular boundaries. The results of qRT-PCR assay showed that compared with the control group, the low and high fluoride groups had lower mRNA expression levels of SIRT3 (0.82 ± 0.03, 0.58 ± 0.02 vs 1.00 ± 0.08), P62 (0.75 ± 0.07, 0.28 ± 0.09 vs 1.00 ± 0.07, P < 0.05), and higher mRNA expression levels of FOXO3a (1.35 ± 0.04, 3.01 ± 0.23 vs 1.00 ± 0.08), PINK1 (1.58 ± 0.09, 3.28 ± 0.09 vs 1.00 ± 0.07), PARKIN (1.51 ± 0.04, 1.67 ± 0.10 vs 1.00 ± 0.05), LC3 (1.74 ± 0.07, 2.38 ± 0.18 vs 1.00 ± 0.08, P < 0.05). The results of Western blotting showed that compared with the control group, the low and high fluoride groups had lower protein expression levels of SIRT3 (0.91 ± 0.01, 0.55 ± 0.03 vs 1.00 ± 0.01), P62 (0.94 ± 0.27, 0.66 ± 0.38 vs 1.00 ± 0.19, P < 0.05), and higher protein expression levels of FOXO3a (1.14 ± 0.03, 1.22 ± 0.05 vs 1.00 ± 0.02), PINK1 (1.46 ± 0.03, 1.56 ± 0.03 vs 1.00 ± 0.05), PARKIN (1.98 ± 0.02, 2.33 ± 0.11 vs 1.00 ± 0.06), LC3 (4.10 ± 0.58, 4.93 ± 0.33 vs 1.00 ± 0.13, P < 0.05). Conclusion:Exposure to fluoride can cause renal tissue injury in rats, with downregulation of SIRT3 and P62 expression levels, and upregulation of FOXO3a, PINK1, PARKIN, and LC3 expression levels.

Polyphyllin Ⅰ(PPⅠ)and polyphyllin Ⅱ(PⅡ)are the main active substances in the Paris polyphylla.However,liver toxicity of these compounds has impeded their clinical application and the potential hepatotoxicity mechanisms remain to be elucidated.In this work,we found that PPⅠ and PⅡ exposure could induce significant hepatotoxicity in human liver cell line L-02 and zebrafish in a dose-dependent manner.The results of the proteomic analysis in L-02 cells and transcriptome in zebrafish indicated that the hepa-totoxicity of PPⅡ and PⅡwas associated with the cholesterol biosynthetic pathway disorders,which were alleviated by the cholesterol biosynthesis inhibitor lovastatin.Additionally,3-hydroxy-3-methy-lglutaryl CoA reductase(HMGCR)and squalene epoxidase(SQLE),the two rate-limiting enzymes in the choles-terol synthesis,selected as the potential targets,were confirmed by the molecular docking,the over-expression,and knockdown of HMGCR or SQLE with siRNA.Finally,the pull-down and surface plasmon resonance technology revealed that PPⅠ could directly bind with SQLE but not with HMGCR.Collectively,these data demonstrated that PPⅠ-induced hepatotoxicity resulted from the direct binding with SQLE protein and impaired the sterol-regulatory element binding protein 2/HMGCR/SQLE/lanosterol synthase pathways,thus disturbing the cholesterol biosynthesis pathway.The findings of this research can contribute to a better understanding of the key role of SQLE as a potential target in drug-induced hepatotoxicity and provide a therapeutic strategy for the prevention of drug toxic effects with similar structures in the future.

Objective:To investigate the association between relative mitochondrial DNA copy number (mtDNA-CN) and coal-burning-borne endemic fluorosis (abbreviated as coal-burning-borne fluorosis).Methods:From June 2018 to March 2019, using cross-sectional study, 482 patients with coal-burning-borne fluorosis were selected as the case group in Bijie City, a typical coal-burning-borne fluorosis area of Guizhou Province; meanwhile, 212 healthy individuals from Changshun County, a non-coal-burning-borne fluorosis area in Guizhou Province, were selected as the control group. Questionnaire survey and physical examination were used to collect general condition such as basic information and living habits of the two groups, peripheral venous blood samples were collected, and real-time fluorescence quantitative PCR was used to detect the relative mtDNA-CN in peripheral blood. The correlation between relative mtDNA-CN and coal-burning-borne fluorosis was analyzed by binary and unordered multi-class logistic regression.Results:There were significant differences in the body mass index (BMI), and the distribution of gender rario, marital status and education level between the control group and the case group ( t = 7.91, χ 2 = 5.11, 13.33, 34.32, P < 0.05). The relative mtDNA-CN in the control group was higher than that in the case group [median (quartile): 202 (138, 292) vs 131 (96, 217), Z = - 7.80, P < 0.001]. The results of binary logistic regression analysis [odds ratio (95% confidence interval)] showed that educational level [primary school: 0.572 (0.377 - 0.868), junior high school and above: 0.292 (0.174 - 0.493)], relative mtDNA-CN [131 - < 217: 0.265 (0.144 - 0.488), ≥217: 0.183 (0.100 - 0.335)] and BMI [1.222 (1.142 - 1.307)] were the influencing factors for the risk of coal-burning-borne fluorosis( P < 0.05). In subgroups with different BMI and educational levels, the relative mtDNA-CN was significantly negatively correlated with the risk of coal-burning-borne fluorosis( Ptrend < 0.05), and there was no interaction between mtDNA-CN and BMI and educational levels ( Pinteraction > 0.05). The results of unordered multi-class logistic regression analysis showed that the relative mtDNA-CN were significantly negatively correlated with the risk of dental fluorosis and skeletal fluorosis ( Ptrend < 0.05). Conclusion:The higher the relative mtDNA-CN, the lower the risk of coal-burning-borne fluorosis, suggesting that mtDNA-CN may be a potential biomarker of coal-burning fluorosis.

Gliomas are the most common and malignant intracranial tumors in adults. Recent studies have revealed the significance of functional genomics for glioma pathophysiological studies and treatments. However, access to comprehensive genomic data and analytical platforms is often limited. Here, we developed the Chinese Glioma Genome Atlas (CGGA), a user-friendly data portal for the storage and interactive exploration of cross-omics data, including nearly 2000 primary and recurrent glioma samples from Chinese cohort. Currently, open access is provided to whole-exome sequencing data (286 samples), mRNA sequencing (1018 samples) and microarray data (301 samples), DNA methylation microarray data (159 samples), and microRNA microarray data (198 samples), and to detailed clinical information (age, gender, chemoradiotherapy status, WHO grade, histological type, critical molecular pathological information, and survival data). In addition, we have developed several tools for users to analyze the mutation profiles, mRNA/microRNA expression, and DNA methylation profiles, and to perform survival and gene correlation analyses of specific glioma subtypes. This database removes the barriers for researchers, providing rapid and convenient access to high-quality functional genomic data resources for biological studies and clinical applications. CGGA is available at http://www.cgga.org.cn.

Objective To investigate the the preventive and management methods of pure-NOTES transanal total mesorectal excision (pure-NOTES TaTME) with postoperative anastomotic complications.Methods Retrospectively analyzed the clinical data of 59 cases with low and middle rectal cancer who were underment pure-NOTES TaTME in Linzi District People's Hospital,and discussed the situction of the complications.Results Postoperative anastomotic complications were occurred in 3 cases,anastomotic leakage in 1 case,anastomotic stenosis in 1 case,anastomotic stenosis and leakage in 1 case,accounting for 5.1％.Conclusions For suitable rectal neoplasms patients,pure-NOTES TaTME operation doesn't increase the incidence of anastomotic complication,and it's is safe and feasible.Preoperative preparation,good blood supply,tension-free anastomosis,and correct choice and using of stapler and anastomotic drainage tube are the key to reduce anastomotic complications.

Objective: To investigate the optimal duration of pegylated-alpha interferon (Peg-INFα) combined with ribavirin (RBV) in treating chronic hepatitis C infection in human immunodeficiency virus (HIV)-infected patients. Methods: A multicenter prospective study was conducted. The study subjects were divided into two groups; HIV/HCV co-infections (Group A, n = 158) and control with HCV-monoinfections (Group B, n = 60). All recruited patients received standard Peg-INFα plus RBV therapy. Group A was divided into 3 subgroups according to CD4⁺ cell counts: A1 subgroup, 79 cases, CD4⁺ counts > 350 cells /μl, who received anti-HCV before combination antiretroviral therapy(cART); A2 subgroup, 45 cases, CD4⁺ counts between 200 and 350 cells/μl, who did not start anti-HCV until they could tolerate cART well; A3 subgroup, 34 cases, CD4⁺ counts < 200 cells /μl, cART was administered first, and anti-HCV therapy was started when CD4⁺ counts > 200 cells/μl. The anti-HCV efficacy of two groups and 3 subgroups were compared. Statistical analysis for normal distribution and homogeneity of variance data was calculated by t-test and the counting data was analyzed by χ ² test. The Mann-Whitney U test was used for non-normal data. A one-way analysis of variance (ANOVA) was used for the comparison of multiple groups, followed by SNK method. Multiple independent samples were used for non-parametric tests. Results: There was no significant difference in age and baseline HCV RNA levels between groups and subgroups (P > 0.05). By an intent-to-treat (ITT) analysis, in Group A, the ratio of complete early virological response (cEVR) rate was 75.3% (119/158), the ratio of end of treatment virological response (eTVR) rate was 68.4% (108/158), and the ratio of sustained virological response (SVR) rate was 48.7% (77/158); in Group B, the ratio of cEVR rate was 93.3% (56/60), the ratio of eTVR rate was 90.0% (54/60), and the ratio of SVR rate was 71.7% (43/60); The therapeutic index of Group A were lower than those of Group B (P≤0.05). By per-protocol (PP) analysis, the ratio of cEVR rate in Group A [75.2% (88/112)] was still lower than that in Group B [93.3% (56/60)], but no significant differences were found in the ratio of eTVR rate and SVR rate between 2 groups (P > 0.05). Comparing the efficacy of subgroups (A1, A2 and A3) by ITT analysis, the ratios of cEVR rate were respectively 78.5% (62/79), 75.6% (34/45) and 67.6% (23/34); the ratios of eTVR rate were respectively 68.4%(54/79), 80.0%(36/45)and 52.9%(18/34); and the ratios of SVR rate were respectively 41.8%(33/79), 64.4%(29/45)and 44.1%(15/34). The ratio of eTVR in subgroup A2 was obviously higher than that in subgroup A3 and the ratio of SVR in subgroup A2 was statistically higher than that of subgroup A1(P≤0.05). However, by PP analysis, no significant differences of the therapeutic indexes were found among the respective subgroups (P > 0.05). Conclusion HIV-HCV co-infected patients would have better anti-HCV efficacy with Peg-INFα-2a plus RBV than HCV- monoinfected patients. The best time for initiating anti-HCV therapy in HIV-HCV co-infected patients is when CD4⁺ counts 200 cells/ μl.

Objective To explore the skills and summarize the experience in the establishment of orthotopic liver transplantation rat models from donation after cardiac death (DCD). Methods According to the time of warm ischemia, 120 rats were divided into 3 groups: group A (warm ischemia for 0 min, n=40 pairs), group B (warm ischemia for 10 min, n=40 pairs) and group C (warm ischemia for 20 min, n=40 pairs). Orthotopic liver transplantation was performed by the modified two-cuff technique in 3 groups. The time of each stage of surgery was recorded in 3 groups. The survival rate at the end of surgery, 24 h, 72 h and 7 d after surgery was recorded in 3 groups. The dead rats were immediately subject to anatomical examination to identify the cause of death. Results The cold ischemia time of donor liver, anhepatic phase and operation time of the recipients did not significantly differ among three groups (all P>0.05). In groups A, B and C, the survival rate at the end of surgery was 97%, 97%, and 100% respectively. The survival rate at postoperative 24 h was 92%, 90% and 92% respectively. The survival rate at postoperative 72 h was 90%, 80% and 77% respectively. The survival rate at postoperative 7 d was 85%, 70% and 57% respectively. The survival rate at the end of surgery, postoperative 24 h and 72 h did not significantly differ among 3 groups (all P>0.05). At postoperative 7 d, the survival rate in group C was significantly lower than that in group A (P<0.05). Surgical operation was the major cause of intraoperative and postoperative 24 h death. Bile leakage and ischemic hepatic failure were the causes of death at postoperative 72 h. Biliary duct complications were the main causes of death at postoperative 7 d. The quantity of rats developing with biliary duct complications was increased along with the prolongation of warm ischemic time. Conclusions The success of stable establishment of rat models with orthotopic liver transplantation from DCD depends upon the protection of the liver and biliary function. The difficulty lies in the anastomosis of the suprahepatic inferior vena cava and the shortening of anhepatic phase.

Objective To compare the clinical efficacy between Jian Huan Tong Tiao needling (acupuncture at both healthy and affected sides) and acupuncture at the affected side alone in treating peripheral facial paralysis (FP) in acute stage, and to provide evidences for the acupuncture treatment of peripheral FP in acute stage.Method Fifty patients were randomized into a Jian Huan Tong Tiao needling group (25 cases) and an affected side needling group (25 cases). By selecting the same acupoints, the Jian Huan Tong Tiao needling group received acupuncture at both sides, while the affected side needling group received acupuncture only at the affected side, once every other day, successively for 4 weeks. House-Brackmann (H-B) facial nerve grading system was used to score the facial nerve function before and after the treatment, and the therapeutic efficacies were compared between the two groups.Result The facial nerve function was improved in both groups, while the therapeutic efficacy was superior in the Jian Huan Tong Tiao needling group to that in the affected side needling group (P<0.05); after 2-week treatment, the H-B score was higher in the Jian Huan Tong Tiao needling group than in the affected side needling group (P<0.05); of the recovered cases, the relapse rate was lower in theJian Huan Tong Tiao needling group than in the affected side needling group (P<0.05). Conclusion Jian Huan Tong Tiao needling can boost the recovery of the facial nerve function in peripheral FP, reduce the relapse rate, and produce a higher therapeutic efficacy than needling the affected side alone.

OBJECTIVE: To explore the mechanisms for an increase in susceptibility of asthma induced by respiratory syncytial virus (RSV), to observe the expression of interleukin-8 (IL-8) in human bronchial epithelial cells (HBECs) after RSV infection and to invesigate the regulatory effect of IL-8 on Th17/Treg differentiation.
 METHODS: HBECs were divided into a control group and a RSV infected group. The RSVE-infected model of HBECs was established and examined. The expression of IL-8 mRNA was detected by real-time PCR, and the levels of IL-8 were measured by ELISA. Peripheral blood lymphocytes in healthy people were extracted and divided into a control group and an IL-8 treatment group. Based on concentration of IL-8 in RSV-infected HBECs, lymphocytes were treated by a matched concentration of human recombinant IL-8 for 24 h. The distribution of Th17 and Treg subsets in lymphocytes were examined by flow cytometry.
 RESULTS: The RSV-infected HBECs model was successfully established. The infected HBECs were still able to split and passage. The RSV could be detected in every passage in the infected cells. Virus particles indicated by bright yellow green fluorescence were seen under fluorescence microscope. Edema of mitochondrias, expansion of endoplasmic reticulum, fissure around nucleus and intracellular virus particles were all observed under electron microscope. The expression IL-8 mRNA were significantly enhanced in the RSV-infected group, and the level of IL-8 in the RSV-infected group was higher than that in the control group (P<0.05). After IL-8 treatment for 24 h, the ratio of Th17 subsets in lymphocytes were dramatically increased compared to the control group (P<0.05), but there was no difference in the ratio of Treg subsets between the 2 groups (P>0.05).
 CONCLUSION Over-secretion of IL-8 by the RSV-infected HBECs may promote the differentiation of Th17 subsets and maintain the Th17/Tred imbalance.
Cell Differentiation ; Cells, Cultured ; Epithelial Cells ; drug effects ; virology ; Flow Cytometry ; Humans ; Interleukin-8 ; immunology ; pharmacology ; Real-Time Polymerase Chain Reaction ; Recombinant Proteins ; pharmacology ; Respiratory Syncytial Virus Infections ; immunology ; Respiratory Syncytial Viruses ; T-Lymphocytes, Regulatory ; cytology ; Th17 Cells ; cytology