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

Postzygotic mutations are acquired in normal tissues throughout an individual's lifetime and hold clues for identifying mutagenic factors.Here,we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals.In blood,sperm,and muscle cells,we resolved three common types of mutational signatures.Signatures A and B represent clock-like mutational processes,and the polymorphisms of epigenetic regulation genes influence the pro-portion of signature B in mutation profiles.Notably,signature C,characterized by C＞T transitions at GpCpN sites,tends to be a feature of diverse normal tissues.Mutations of this type are likely to occur early during embryonic development,supported by their relatively high allelic frequencies,presence in multiple tissues,and decrease in occurrence with age.Almost none of the public datasets for tumors feature this signature,except for 19.6％of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1(HIF-1)signaling pathway.Moreover,the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α.Thus,embryonic hypoxia may explain this novel signature across multiple normal tissues.Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C＞T transitions at GpCpN sites;and indi-viduals'genetic background may also influence their postzygotic mutation profiles.

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 investigate the expression of serum pentraxin3（PTX3） and microRNA-199a（miR-199a） in patients with acute stroke，and to further analyze the relationship between PTX3 and miR-199a and the neurological function of the patients and their value in the diagnosis of the disease.Methods 83 patients with acute stroke who were treated in our hospital from January 2018 to December 2019 were selected as the study group. According to National Institute of Health stroke scale（NIHSS） score，the patients were divided into mild group（26 cases），moderate group（30 cases） and severe group（27 cases）.Another 40 volunteers who had physical examination in our hospital at the same time were selected as the control group. Serum levels of PTX3，miR-199a，soluble protein 100β（S100-β），and neuron specific enolase（NSE） in all subjects were detected.Results The levels of PTX3，S100-β and NSE in the study group were higher than those in the control group，and the levels of miR-199a in the study group were lower than those in the control group（P<0.05）；The levels of PTX3，S100 -β，NSE，NIHSS and miR-199a in severe group were higher than those in moderate group and mild group（P<0.05），and the levels of PTX3，S100-β，NSE and NIHSS in the moderate group were higher than those in the mild group，and the level of miR-199a was lower than that in the mild group（P<0.05）；Pearson analysis showed that PTX3 was positively correlated with S100-β，NSE and NIHSS scores in patients with acute stroke（P<0.05），and miR-199a was negatively correlated with S100-β，NSE and NIHSS scores（P<0.05）；ROC analysis showed that serum PTX3 and miR-199a had certain diagnostic value for acute stroke.The area under the curve was 0.864（95%CI 0.799～0.928）and 0.807（95%CI：0.704～0.910），respectively. The combination of the two could further improve the diagnostic value for acute stroke.Conclusion Serum PTX3 is highly expressed and miR-199a is lowly expressed in patients with acute stroke，and the expression of both is closely related to the patient’s nerve function.Both of them have a certain value of diagnosis.

Objective:To explore the methods, complications and follow-up results of limb salvage for primary malignant tumors of the femoral shaft.Methods:From October 2006 to October 2019, 41 cases of primary malignant tumors of femoral shaft were analyzed retrospectively, 37 cases were followed up, including 22 males and 15 females, aged 8-46 years with an average age of 20.56±4.72 years old. All the lesions were located in the femoral shaft, and The Enneking stage was IIB. Tumor lesion ranged in the femur from 10 cm to 24 cm, and there was no pathological fracture. Pre-operative puncture biopsy was performed in all cases.22 cases were confirmed as osteosarcoma, 8 as chondrosarcoma, 5 as Ewing sarcoma, 2 as malignant fibrous histiocytoma. Neoadjuvant chemotherapy has been used to treat both osteosarcoma and Ewing sarcoma. Among the 37 patients, 8 cases of patients received total femoral prosthesis replacement, 14 cases of intramedullary nail fixation with allogenic bone graft, 8 cases of allograft-prosthetic composite (APC), and 7 cases of 3D printed prosthesis. The limb function was graded according to MSTS 93 system.Results:37 out of 41 patients were followed up, and the average follow-up time was 23.15±16.74 months (6-62 months). There were 9 patients with pulmonary metastases (26.47%), among which 6 patients passed away due to multiple metastases. 28 patients survived without tumor at last follow-up. The MSTS score was18-28 (average of 22.55±2.57). The average score of 3D printing prosthesis group was 27±1.74, allogeneic bone transplantation group was 22.85±2.59, total femoral prosthesis replacement group was 20.25±2.25, and the APC prosthesis group was 20.5±2.07. There was statistical difference between 3D printing group and other groups. The overall excellent and good rate of lower limb function was 79.41%, in which the 3D group was 100%, allogeneic bone group was 78.5%, APC prosthesis group was 87.5%, total femoral prosthesis replacement group was 62.5%. There was no statistical difference in the excellent and good rate of limb function among the groups. There weren't any cases of hip joint dislocation after total femoral prosthesis replacement. Delayed union of bone healing was seen in 3 cases of allogeneic bone transplantation and 2 cases APC patients. One patient suffered from the postoperative hemorrhage-related diseases-sciatic nerve compression, and the nerve recovered after emergency debridement. One patient suffered from poor wound healing. The overall complication rate was 24.32% (9/37).Conclusion:The patients with primary malignant tumors of the femoral shaft can effectively recover the lower extremity function by choosing the appropriate surgical scheme, in order to achieve the purpose of limb preservation and improve the quality of life of the patients. 3D printing prosthesis provides a new choice in the treatment of femoral shaft tumors.

Objective To analyze the clinical characteristics of the recipients infected with cryptococcus neoformans after renal transplantation. Methods Clinical data of 9 patients infected with cryptococcus neoformans after renal transplantation were retrospectively analyzed, including the infection site, clinical manifestations, mycological, histopathological, imaging examination results, treatment process and clinical prognosis. Results Nine recipients were treated with routine triple immunosuppressive therapy of tacrolimus (FK506) + mycophenolate mofetil (MMF)+prednisone. The median time of onset was 6 years (1-13 years) after operation. Among them, 1 case was diagnosed with cryptococcal meningitis, 5 cases of cryptococcal meningitis complicated with cryptococcal pneumonia, 2 cases of cryptococcal pneumonia and 1 case of cutaneous cryptococcal infection. Cryptococcal pneumonia was clinically manifested as fever, cough, expectoration, shortness of breath and chest pain, etc. Chest CT demonstrated the signs of nodules and pleural effusion, etc. The diagnosis was mainly confirmed by lung biopsy and negative ink staining of the alveolar lavage fluid. Clinical manifestations of cryptococcal meningitis primarily included fever and paroxysmal headache accompanied by vomiting, which was mainly confirmed by blood culture and negative ink staining of the cerebrospinal fluid. Cutaneous cryptococcal infection was characterized by a mass in the right shoulder, which was confirmed by skin biopsy. All patients were given with standard antifungal therapy including amphotericin B and fluconazole, and immunosuppressive therapy at a reduced dosage. Among 9 recipients, 1 recipient died, and the other recipients obtained excellent clinical prognosis. Conclusions Cryptococcus neoformans infection dominantly occurs in the middle and late stage after renal transplantation presenting with non-specific clinical symptoms. Blood culture, lung biopsy and cerebrospinal fluid examination should be timely performed to validate the diagnosis of this disease. Standard anti-fungal therapy can reduce the mortality rate.

Objective To investigate the safety and efficacy of hepatitis B surface antigen (HBsAg) positivity of the donors on graft survival and liver complications in HBsAg (+) renal transplant recipients.Methods We retrospectively evaluated 96 HBsAg (+) patients who received HBsAg(+) donor kidney transplant fellow-up during 20～ 139 months,in order to observe the renal allograft dysfunction,liver dysfunction and others complications.Results All 96 patients underwent renal transplantation successfully in our hospital.during the follow-up period,18 cases accepted entecavir-treated,one case lost graft function,two cases died,one of them developed drug resistance and liver function failure,the other because of cancer of the liver.Twenty-three of the 78 lamivudinetreated patients (29.5％) developed drug resistance in 7～96 months,and 3 cases developed liver function failure,2 cases died and one cured,15 of the 19 cases who been salvage treated with entecavir was successful and well tolerated after 1 year,2 cases who been salvage treated with adefovir and lamivudine with HBV DNA-negative after 12 months and 23 months.The 5-year patient/graft rates of patients who been treated with lamivudine and entecavir were 88.5％/84.6％ and 88.9％/83.3％ respectively.Conclusion It is safe and feasible for renal transplantation from HBsAg(+) donors to HBsAg(+) recipients with antiviral treatment,patients would require lifelong anti-viral suppression and strictly follow-up,which is important for patient and graft survival,anti-viral drugs resistance and the liver complications should be closely monitored and treated.

Osteoporosis (OP) is one of the bone metabolic diseases which seriously harms the health and lives of people. The main cause of OP is that the balance between bone formation and bone absorption, i.e. the balance of the bone remodeling process,is no longer exist. When the bone absorption dominates the process, it will lead to osteopenia, destruction of bone microstructure and increased rate of fracture. Previous studies have shown that casein kinase 2-interacting protein-1 (CKIP-1) plays an important role in the process of bone tissue proliferation and differentiation. It mainly interacts with Smad ubiquitination regulatory factor 1 (Smurf 1) to affect bone metabolism. This review analyzes and summarizes the impact of CKIP-1 on bone tissue osteogenic differentiation direction and its mechanism, which may provide new idea and research orientation for future clinical treatment of osteoporosis.

Objective To explore the clinical efficacy and complications of the surgical treatment of sternal tumor resection and titanium mesh reconstruction.Methods From 2008 January to 2012 June,there were 8 cases of sternal tumor patients in our hospital,including 5 male and 3 female,with an average age of 50.4 (37-66) years old.The histological morphology included 2 cases of chondrosarcoma,1 case of osteosarcoma,2 cases of malignant fibrous histiocytoma,eosinophilic granuloma in 1 case,and 2 cases of sternal metastasis of breast cancer.Tumor invasion sites included the sternal manubrium in 3 cases,the body in 2 cases,and both in 3 cases.All patients had undergone preoperative puncture or incision biopsy.8 cases of sternal tumor patients were treated with sternal tumor resection and reconstruction of the thorax using titanium mesh.The clinical effect and complications were retrospectively analyzed.Results All patients were followed up for 9 months to 4 years.The operations went well in all cases,with no intraoperative crisis or operative death.Deep wound hematoma occurred in 1 patient 1 week postoperatively,who healed 2 weeks after drainage and debridement.There was no abnormal breathing,subcutaneous emphysema,pneumothorax,infection or other complications in other cases.1 case of malignant fibrous histiocytoma died of lung metastasis at 9 months follow-up,and 1 died of liver metastasis at 14 months,while other patients got no tumor recurrence,with good thoracic shape,free breathing,no titanium mesh loosening,dyspnea,chest tightness,pain,or abnormal respiratory discomfort during follow-up period.The chest radiograph showed no chest deformity,no loosening or fracture of the fixation device.Conclusion Sternal tumor resection and reconstruction with titanium mesh has the advantages of good shaping effect,fewer complications,and simple operation,showing that titanium mesh is an ideal material for the reconstruction of sternum.