Image 1.

Lipophagy, the selective engulfment of lipid droplets (LDs) by autophagosomes for lysosomal degradation, is critical to lipid and energy homeostasis. Here we show that the lipid transfer protein ORP8 is located on LDs and mediates the encapsulation of LDs by autophagosomal membranes. This function of ORP8 is independent of its lipid transporter activity and is achieved through direct interaction with phagophore-anchored LC3/GABARAPs. Upon lipophagy induction, ORP8 has increased localization on LDs and is phosphorylated by AMPK, thereby enhancing its affinity for LC3/GABARAPs. Deletion of ORP8 or interruption of ORP8-LC3/GABARAP interaction results in accumulation of LDs and increased intracellular triglyceride. Overexpression of ORP8 alleviates LD and triglyceride deposition in the liver of ob/ob mice, and Osbpl8-/- mice exhibit liver lipid clearance defects. Our results suggest that ORP8 is a lipophagy receptor that plays a key role in cellular lipid metabolism.
Animals ; Mice ; Lipid Droplets ; Autophagy ; Autophagosomes ; Homeostasis ; Triglycerides

AIM: To evaluate the clinical efficacy and safety of He-wei-zhi-xie (HWZX) capsules in diarrhea patients. METHODS: The clinical study was conducted in 35 clinical trials centers from October 2015 to December 2017 by multicenter, prospective, open and uncontrolled design methods. The primary efficacy endpoint is the effective rate of diarrhea, the secondary endpoints include recovery rate of diarrhea, recovery time of diarrhea, number of irregular stools and Leeds dyspepsia questionnaire. The pharmacodynamics model of time course was established by nonlinear mixed effect model, and the effect of covariates on pharmacodynamic parameters was investigated. The safety measures were the incidence of adverse events, adverse reactions and the laboratory test indicators. RESULTS: A total of 2 285 cases were included in full analysis set. The effective rate of diarrhea was 90.8%, and the diarrhea recovery rate was 77.3%. The median time of recovery was 3 days, and the Leeds score was reduced by 3.6 points. It is found that baseline has a significant effect on model parameter E

The Genome Warehouse (GWH) is a public repository housing genome assembly data for a wide range of species and delivering a series of web services for genome data submission, storage, release, and sharing. As one of the core resources in the National Genomics Data Center (NGDC), part of the China National Center for Bioinformation (CNCB;https://ngdc.cncb.ac.cn), GWH accepts both full and partial (chloroplast, mitochondrion, and plasmid) genome sequences with different assembly levels, as well as an update of existing genome assemblies. For each assembly, GWH collects detailed genome-related metadata of biological project, biological sample, and genome assembly, in addition to genome sequence and annotation. To archive high-quality genome sequences and annotations, GWH is equipped with a uniform and standardized procedure for quality control. Besides basic browse and search functionalities, all released genome sequences and annotations can be visualized with JBrowse. By May 21, 2021, GWH has received 19,124 direct submissions covering a diversity of 1108 species and has released 8772 of them. Collectively, GWH serves as an important resource for genome-scale data management and provides free and publicly accessible data to support research activities throughout the world. GWH is publicly accessible at https://ngdc.cncb.ac.cn/gwh.

Objective To explore the feasibility of extracorporeal membrane oxygenation (ECMO) in protecting the donor liver in donation after citizen's death. Methods Clinical data of 16 donors and recipients undergoing liver transplantation using ECMO to protect the donor liver were retrospectively analyzed. The effect of ECMO on different indicators of the donors was evaluated. The liver function and clinical prognosis of the recipients after liver transplantation were observed. Results Compared with the time before ECMO, the heart rate, total bilirubin (TB), alanine transaminase (ALT) and aspartate transaminase (AST) of the donors after ECMO were significantly reduced, whereas the systolic blood pressure, diastolic blood pressure and partial pressure of arterial oxygen (PaO₂) were remarkably increased (all P < 0.05). The liver function of the recipients was properly recovered after liver transplantation, and gradually restored normal at postoperative 7 to 28 d. Postoperative complications occurred in 3 recipients, including delayed liver function recovery in 1 case, biliary tract stenosis in 1 case and portal vein thrombosis in 1 case. Among them, the patient with portal vein thrombosis died after secondary operation, and the other 2 patients were recovered and discharged after symptomatic treatment. Conclusions The hemodynamics, liver function and other indicators of donors from donation after citizen's death are significantly improved after ECMO, and the liver function of the recipients also recover well.

Objective To explore the clinical application of renal replacement therapy in renal transplan-tation from donation after citizen's death(DCD).Methods A total of 41 cases of the patients with renal replace-ment therapy after renal transplantation from DCD from January 2013 to December 2016 were involved,of which 14 cases received peritoneal dialysis,21 intermittent hemodialysis(IHD)and 6 continuous renal replacement ther-apy(CRRT).The therapeutic effect and complications of three renal replacement therapies were retrospectively ana-lyzed. Results After dialysis treatment,the concentration of blood BUN,Crea,and potassium was significantly lower than that before the treatment(P<0.05);the difference of Crea and BUN before and after the treatment in IHD and CRRT group was higher than that in peritoneal dialysis group(P<0.05)but there was no statistically sig-nificant difference between IHD and CRRT group(P > 0. 05). Conclusion The renal replacement after kidney transplantation from DCD should be based on the patient's condition,which is the key to protect their kidneys even to save patients'lives.

Objective To evaluate the clinical value of 6 androgens in the serum of Sj?gren's syndrome (SS) measured by liquid chromatography tandem mass spectrometry (LC-MS).Methods 32 SS patients (SS group) and 25 healthy people (healthy group) were included in this study.6 androgens in the serum were analyzed by LC-MS after prepared.PCA,PLS-DA models and t-test were used to class differentiation of androgens between two groups.Results The results of PLS-DA showed that SS group and healthy group could be well classed by 6 androgens.The levels of testerone (T),dihydrotestosterone (DHT),dehydroepiandrosterone (DHEA),androsterone and DHEAS in SS group were significantly lower than those in healthy group (t=8.536,2.438,3.172,4.158,4.489,all P<0.05).The samples before or after menopause could be distinguished between the two groups by PLS-DA.Conclusion The significant difference of androgens was discovered between SS patients and healthy people via the measurement of 6 androgens in serum.It may arise a new idea for diagnosis and treatment of SS.

Objective To summarize the preliminary experience of donor liver protection and function evaluation for organ donation after citizen's death. Methods Clinical data of 35 donors from organ donation after citizen's death and 33 recipients were retrospectively analyzed. Donor liver procurement and clinical prognosis of the recipients were summarized. According to serum level of sodium ion (serum sodium) before organ procurement, all recipients were divided into the serum sodium <155 mmol/L, 155-160 mmol/L and 161-180 mmol/L groups. The incidence of liver graft dysfunction early after liver transplantation was statistically compared among three groups. Results In 35 donors,27 cases were Chinese type Ⅱ and 8 cases were Chinese type Ⅲ. Thirty-three donor livers were used for liver transplantation, and the remaining 2 cases of donor livers were excluded due to congestive cirrhosis. In 33 liver transplantation recipients, 30 cases were successfully recovered. The liver function was gradually restored at postoperative 7-14 d, and normal liver function was obtained during long-term follow-up. Postoperatively, 3 recipients died including 2 cases dying from portal vein thrombosis and 1 case from pulmonary infection complicated with multiple organ failure. The incidence of early liver graft dysfunction of the recipients after liver transplantation was 18%, 23% and 4/5 in the serum sodium <155 mmol/L, 155-160 mmol/L and 161-180 mmol/L groups, respectively. Statistical significance was observed between the 161-180 mmol/L and <155 mmol/L groups (P<0.05). Conclusions Timely protection of donor liver, accurate evaluation and maintenance of liver function play a pivotal role in enhancing the utilization rate of donor liver, maintaining liver function and yielding good efficacy for transplantation.

Objective To investigate the growth inhibition of human osteosareoma cell line(MG-63) intervened by Hydralazine and 5'-aza-2'-deoxycytidine (5-Aza-CdR),and the effect on the mRNA expression of gene WW domain-containing oxidoreductase (WWOX).Methods Certain volume of 5 × 104/ml of human osteosarcoma cell line MG-63 in logarithmic growth phase were added into 96-well plate.There were Hydralazine group (drug concentration,0.1,1.0,10 μmol/L),5-Aza-CdR group (drug concentration,5,10,20 μmol/L),Hydralazine combined with 5-Aza-CdR group (drug concentration,0.1 μmo/L + 5 μmol/L,1.0 μmol/L + 10 μmol/L,10 μmol/L + 20 μmol/L) and control group (culture medium).Methyl thiazol tetrazolium(MTT) colorimetric methods were used to test the growth inhibition of MG-63 cells intervened by different concentrations of Hydralazine and 5'-aza -2'-deoxycytidine (5-Aza-CdR).Flow cytometry AnnexinV-FITC/PI methods were used to assay the effects of Hydralazine and 5-Aza-CdR inducing apoptosis in osteosarcoma cells in vitro.Real-time polymerase chain reaction (Real-Time PCR)methods were used to detect amplification of WWOX mRNA induced by Hydralazine combined with 5-Aza-CdR or alone.Western-blotting methods were used to examine the expression of WWOX in MG-63 cells.Results Hydralazine and 5-Aza-CdR effectively inhibited the growth of MG-63 cells in a concentration and time-dependent manner.Combined effect was more obvious.Further more the expression levels of WWOX mRNA and protein were increased significantly in combined groups as compared with other groups.Conclusion Hydralazine and 5-Aza-CdR could effectively inhibit the proliferation of MG-63 cells and induce apoptosis which is concurrent with the promotion of the expression of WWOX.The mechanism may be that Hydralazine/5-Aza-CdR effectively cause the demethylated of WWOX gene CpG-rich promoter regions,leading to the high expression of WWOX and inhibit the growth of MG-63 cells.The use of hydralazine in the treatment of osteosarcoma is worthy of further investigation.

Objective To explore clinical feasibility of liver transplant from child of brain death to adult, to summarize the clinical experiences that a child of brain death transplants liver to an adult. Methods The recipient was a 39-year-old woman patient with primary hepatic carcinoma and posthepatitis cirrhosis (decompensation stage); while the donor was a 8-old-year child of brain death because of brain neoplasms. Donated liver was gained by the method of en bloc multivisceral procurement in a short time; the operative method was classic orthotopic liver transplantation. The postoperative managements included immunosuppression, prevention of infection, hepatic protection, and other relevant supports etc. Results The transplantation operative duration was 6 hours, after which not only did the recipient survive but also her body functioned well including the liver part, with no severe postoperative complications. Conclusions The technology of transplanting livers from children to adults is feasible. The key to ensure the success of transplant operation is systematic preoperative evaluation, excellent operative technique, and perfect postoperative treatment.