Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

[摘 要] 目的：探讨肝内胆管癌（intrahepatic cholangiocarcinoma，ICCA）围手术期外周血中性粒细胞与淋巴细胞比率（neutrophil-to-lymphocyte ratio，NLR）和血小板与淋巴细胞比率（platelet-to-lymphocyte ratio，PLR）对患者预后的预测价值。方法：收集2015年1月至2018年1月在上海市松江区中心医院接受肝切除术治疗的ICCA患者97例作为ICCA组，选择同期在本院做健康体检的志愿者100例作为正常对照组。检测两组受试者术前1 d、术后3 d和7 d外周血的NLR、PLR，采用单因素、多因素分析ICCA患者术后随访期死亡的危险因素，采用Kaplan-Meier生存曲线分析术后3 d的NLR和PLR对ICCA患者术后生存时间的影响，采用受试者工作特征曲线（receiver operating characteristic curve，ROC）分析术后3 d的NLR和PLR水平对患者术后随访期死亡的预测价值。结果：ICCA组患者术前1 d、术后3和7 d外周血的NLR、PLR均高于正常对照组（均P<0.05），术前1 d和7 d外周血NLR、PLR差异无统计学意义（P>0.05），术后3 d外周血NLR、PLR水平最高（P<0.05）。多发肿瘤、合并淋巴结转移、TNM分期Ⅲ~Ⅳ、CA199水平增高、术后3 d的NLR和PLR较高分别是ICCA患者随访期死亡的独立危险因素（均P<0.05）。ROC曲线显示，术后3 d的NLR和PLR高低对ICCA患者术后生存时间具有预测价值。Kaplan-Meier生存曲线显示，低NLR[（50.32±3.69） vs （30.12±2.36）个月]和低PLR[（53.6±3.75） vs （37.6±2.96）个月]患者生存时间均长于高NLR和PLR的ICCA患者（均P<0.05）。结论：ICCA术后3 d的NLR和PLR异常增高是患者肝切除术后死亡的独立危险因素，其对患者生存时间具有早期预测价值。

Wilms′ tumor is a common malignant tumor in children.Most patients have a good prognosis, but its pathogenesis is not yet clear.In recent years, some non-coding RNAs have been found to have a close relationship with the development of this tumor.Some non-coding RNAs may serve as biomarkers for the diagnosis, predictors indicators, or targets for gene therapy.This paper studied the relationship between some non-coding RNAs associated with nephroblastoma is now available.

Objective: To explore the safety and feasibility of transumbilical single channel laparoscopic cryptorchidopexy with conventional instruments in treatment of cryptorchidism in children. Methods: Thirty-five children with cryptorchidism were treated by transumbilical single channel laparoscopic cryptorchidopexy with conventional instruments from November 2017 to March 2018 at Department of Pediatric Surgery, the First Affiliated Hospital of Guangxi Medical University.Clinical data were recorded including the general information, operation time, intraoperative blood loss, postoperative testicular position and postoperative complications, etc. Results: All 35 patients completed the cryptorchidopexy in one operation.Among those 35 patients, 28 patients had unilateral lesions and 7 patients had bilateral lesions, with a total of 42 sides.Twenty-six patients were of groin type(33 sides), 9 patients abdominal type(9 sides). The average operation time was (40.4±8.2) min for unilateral lesion, and (62.5±15.3) min for bilateral lesions; the average intraoperative blood loss was (3.0±1.8) mL; and the average postoperative hospital stay was (6.4±2.1) h. Testis of 32 patients (40 sides) were fixed in the middle and bottoms of the scrotum, and testis of 2 patients (2 sides) were fixed on the top of the scrotum.One case had poor healing of naval incision, which was recovered in 1 week after dressing change.There were no postoperative complications such as scrotum hematoma, infection of incision, testicular epididymitis, testicular necrosis, testicular retraction or testicular atrophy, etc.No obvious visible scar was found in the abdomen review 2 weeks postoperatively, with the incidence of complications was 2.9%(1/35 cases). Conclusions Transumbilical single channel laparoscopic cryptorchidopexy with conventional instruments in treatment of cryptorchidism is characterized by small trauma, quick recovery, low complication rate and visible scar free result, which is worthy of clinical promotion, but the operation is relatively complex and the correct procedures are required.

Objective To explore the value of the application of albumen powder during the early standardized nutritional support in ICU. Methods Totally 80 patients treated in ICU were enrolled. Randomized digital tables were used to divide patients into experimental and control groups. Nutritive medium was used for enteral nutrition in the control group, and intermixture of nutritive medium and albumen powder was used in experimental group. Results After the intervention, the value of index was significantly better than the control group. The sebum thickness, muscle thickness and plasma total protein and serum album in experimental group before intervention were (0.99±0.72) cm, (2.19±1.14) cm, (62.14±6.87) g/L,(35.32±2.98) g/L, and were (1.01±0.72) cm, ( 2.18±1.13) cm,(64.31±6.97) g/L, ( 36.13± 3.02)g/L in control group, the difference between the two groups was not statistically significant .After intervention, the value were (1.06±0.53)cm,(2.25±0.69) cm,(69.87±7.16)g/L,(40.32±3.17) g/L in control group, (1.39±0.63)cm,(2.62±0.81)cm,(44.21±3.22)g/L,(75.24±7.32)g/L in experimental group, there were significant difference between two groups (t=2.182- 5.445, P<0.01 or 0.05). The incidence of gastrointestinal reaction in experimental group was 20％ (8/40) which was lower than 35％(14/40) of control group significantly(χ2=19.57,P=0.000). Conclusion Application of albumen powder could improve the index including sebum thickness, muscle thickness, plasma total protein and serum album and reduce the incidence of gastrointestinal reaction of patients in ICU.

Golgi protein 73(GP73) was closely correlated with primary hepatic carcinoma(PHC). GP73 had a higher sensitivity and specificity than alpha fetal protein(AFP), so GP73 had a great diagnostic value for early PHC. Although there were many related research reports in the domestic and foreign, their conclusions were inconsistent. This article reviewed these studies results.

Objective To explore the role of CD4+CD25+CD127low/-regulatory T cells (Tregs) in the pathogenesis of psoriasis vulgaris(PV). Methods Flow cytometry analysis was used to detect the amount of Tregs in peripheral blood and ELISA to test the levels of IL-10 and TGF-β1 in blood serum; the suppressive function of Tregs on autologous CD4+CD25-T cells was determined by MTT method. Results No significant difference was found in the proportion of Tregs in PV patients and healthy controls(P>0.05). There was a diminished suppression of Tregs from patients on autologous CD4+CD25- responder T cell proliferation in PV patients when compared with that in controls (P < 0.01). The serum level of IL-10 in patients was lower than that in controls (P < 0.01) while that of TGF-β1 in PV patients was significantly higher than that in controls(P < 0.01). Conclusion Abnormal function of Tregs and low secretion of IL-10 in PV patients might be related to the pathogenesis of psoriasis.

Objective To explore the levels of serum hepatitis B surface antigen (HBsAg) in different clinical stages of hepatitis B virus(HBV) infection and their correlation with serum HBV DNA. Methods Five hundred and seventy-five patients with HBsAg-positive and without antiviral therapy were enrolled in this study. The patients were classified into six group:IT group (immune tolerant phase, 120 patients), EPH group (hepatitis B e antigen positive hepatitis, 110 patients), LR group (low replicative phase, 90 patients), ENH group (hepatitis B e antigen negative hepatitis, 110 patients), LC group (liver cirrhosis stage, 85 patients) and HCC group (hepatocellular carcinoma, 60 patients). Serum HBsAg and HBV DNA levels were quantified and analyzed through statistics. Results The levels of serum HBsAg in IT group, EPH group, LR group, ENH group, LC group and HCC group were (4.58 ± 0.40), (4.12 ± 0.50), (2.60 ± 0.68), (3.31 ± 0.27), (2.82 ± 0.57) and (3.03 ± 0.39) lg U/ml respectively, and there was significantly different among the different phase (P<0.01). The levels of serum HBsAg in IT group, EPH group, LR group, ENH group, LC group and HCC group had positive correlation with serum HBV DNA level, and the correlation coefficients were 0.627, 0.579, 0.134, 0.317, 0.159 and 0.224 respectively. Conclusions The levels of serum HBsAg is significantly different in the different clinical phase of HBV infection, and the tendency of the correlation between serum HBsAg and serum HBV DNA gradually weakens in general.

Objective To explore the mechanism of melanoma differentiation associated gene-7(mda-7) in combination with adriamycin(ADM) killing the HCC HepG2 cells and reversing their multidrug resistance (MDR). Methods The experiment was conducted in three groups including the combined group, ADM group and mda-7 group. MTT assay and FCM were used to determine the differences among the 3 groups and clarify the reversing effect of combined treatment on multidrug resistance of the tumor cells. Expression levels of MDR-1, STAT-3, BCL-2, BAXmRNA were determined with real-time PCR. Western blotting was performed to observe the changes of proteins gp-l70, stat3,P-stat3, PKB, bcl-2,bax in all 3 groups. Result After transfection with 100VP/cell Ad. mda-7,the growth suppression rate of HepG2 treated by ADM (1.5 mg/L) rose from 17.46% to 79. 5%.According to the changes, killed HepG2 cells were increased by a factor of 4.55. times. MDR-1 mRNA was decreased from (16.49 ± 0. 11) to (5.48±0.05) and STAT-3 mRNA increased from (13.17±0. 08) to (21. 57±0. 11)(P＜0.05). Western blotting also showed that P-170 and PKB was decreased and the phosphorylation-stat-3 increased after the combined treatment. Conclusion Ad.mda-7 can reverse the multidrug resistance HepG2 cells. It inhibits the expression of MDR-1 mRNA,then arrests PKB protein and the signaling pathway of active stat-3 to induce apoptosis of HCC cells.

Objective To investigate the location,fine structure of melanocytes in human fetal scalp hair follicles.Methods The scalp with hair follicles was obtained from a dead fetus of 6 months of age,and divided into two parts.One part was embedded in paraffin,tissue sections were prepared with a width of 7 μm and stained with NKI/beteb,monoclonal antibodies to HMB-45,tyrosinase and tyrosinase-related protein 1(TRP1),respectively.The other part with hair follicles was treated with collagenase type Ⅱ 0.1 g/L and trypsin,then,cell suspension was collected and cultured.After 14-day culture,follicle melanocyte cells (FMC)were separated from keratinocytes by differential trypsinization,and fibroblasts were removed with geneticin.Following three times of pure passage,FMC were seeded and fixed on mica for scanning electron microscopy(SEM)and atomic force microscope(AFM)scanning.Results Histopathological examination showed that NKI/beteb positive cells located at the outer root sheath of human hair follicles,and these cells stained negatively for HMB-45,tyrosinase and TRP1 antibodies.However,in the hair bulb,lots of cells expressed HMB-45,tyrosinase and TRP1 antigens.After fibroblasts and keratinocytes were removed,two kinds of melanocytes remained in the culture:one was small in number and showed abundant melanin,which was lost after subsequent passage;the othgr was large in number and had no melanin initially,but proliferated very rapidly.After three passages,almost all the melanocytes were positive for NKI/beteb.As SEM and AFM showed,most cultured melanocytes appeared fusiform with two(rarely three)dendrites,and the cell body was round or oval with a few melanosomes scattered in but no clear secondary branches on the dendrites.Conclusions The melanocytes in outer root sheath of hair follicles from the fetal scalp are presumed as melanocyte stem cells or their progenies.In vitro,these cells proliferate very rapidly during early phases,but the morphology and function of them still remain immature,which is unfavorable for melanosome transport.