In recent years, the rapid development of digital intelligence has provided a new path for rare disease data sharing and injected new power into the progress of research of rare diseases. This research is aimed at summarizing and consolidating relevant literatures on data sharing driven by digital intelligence (DI) in China and abroad, and constructing a local theoretical framework of DI-driven data sharing for rare diseases based on the status of rare diseases in China. Searching PubMed, EMbase, Cochrane, CNKI, Wanfang, and VIP database, we obtain a total of 214 representative literatures. Through literature review, we find that DI technologies have played important roles in different aspects of rare disease data sharing. China, the United States, and Europe have formed their own DI-driven data sharing systems for rare disease. From the theory of " Information Commons", we analyze the gap between China′s current situation and the goal of a " Rare Disease Data Commons". Based on the analysis, we put forward the idea of framework of " DI-STARS". China should develop the Data Sharing system making DI as the core of the system. Meanwhile, China should strengthen the data standardization system, create an innovation-encouraging environment, and build a bridge between different platforms. Using the DI-STARS theory, China will be able to build the " Rare Disease Data Commons" so that the diagnosis and treatment of rare diseases will be enhanced in China to meet the patients′ needs.

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

Extended circulation of anticancer nanodrugs in blood stream is essential for their clinical applications. However, administered nanoparticles are rapidly sequestered and cleared by cells of the mononuclear phagocyte system (MPS). In this study, we developed a biomimetic nanosystem that is able to efficiently escape MPS and target tumor tissues. The fabricated nanoparticles (TM-CQ/NPs) were coated with fibroblast cell membrane expressing tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL). Coating with this functionalized membrane reduced the endocytosis of nanoparticles by macrophages, but increased the nanoparticle uptake in tumor cells. Importantly, this membrane coating specifically induced tumor cell apoptosis via the interaction of TRAIL and its cognate death receptors. Meanwhile, the encapsulated chloroquine (CQ) further suppressed the uptake of nanoparticles by macrophages, and synergized with TRAIL to induce tumor cell apoptosis. The vigorous antitumor efficacy in two mice tumor models confirmed our nanosystem was an effective approach to address the MPS challenge for cancer therapy. Together, our TM-CQ/NPs nanosystem provides a feasible approach to precisely target tumor tissues and improve anticancer efficacy.

Humans ; Blast Crisis/genetics* ; Leukemia, Promyelocytic, Acute/genetics* ; Oncogene Proteins, Fusion/genetics* ; Tretinoin

The finite element method is a new method to study the mechanism of brain injury caused by blunt instruments. But it is not easy to be applied because of its technology barrier of time-consuming and strong professionalism. In this study, a rapid and quantitative evaluation method was investigated to analyze the craniocerebral injury induced by blunt sticks based on convolutional neural network and finite element method. The velocity curve of stick struck and the maximum principal strain of brain tissue (cerebrum, corpus callosum, cerebellum and brainstem) from the finite element simulation were used as the input and output parameters of the convolutional neural network The convolutional neural network was trained and optimized by using the 10-fold cross-validation method. The Mean Absolute Error (MAE), Mean Square Error (MSE), and Goodness of Fit ( R ²) of the finally selected convolutional neural network model for the prediction of the maximum principal strain of the cerebrum were 0.084, 0.014, and 0.92, respectively. The predicted results of the maximum principal strain of the corpus callosum were 0.062, 0.007, 0.90, respectively. The predicted results of the maximum principal strain of the cerebellum and brainstem were 0.075, 0.011, and 0.94, respectively. These results show that the research and development of the deep convolutional neural network can quickly and accurately assess the local brain injury caused by the sticks blow, and have important application value for understanding the quantitative evaluation and the brain injury caused by the sticks struck. At the same time, this technology improves the computational efficiency and can provide a basis reference for transforming the current acceleration-based brain injury research into a focus on local brain injury research.
Brain ; Brain Injuries ; Computer Simulation ; Finite Element Analysis ; Humans ; Neural Networks, Computer

OBJECTIVE: To identify pathogenic variants in two patients with suspected for Mowat-Wilson syndrome (MWS). METHODS: Genomic DNA was extracted from peripheral blood samples of the patients and his family members, and gene variants were analysis by Trio-whole exome sequences and copy number variation sequencing. RESULTS: Patient 1 was found to carried a de novo heterozygous c.2769C>A (p.Y923*) nonsense variant of ZEB2 gene. The variant was not found in his healthy parents and sister. Patient 2 carried a de novo heterozygous frameshift variant of the ZEB2 gene, namely c.315delC (p.A105Afs*3), which has not been previously reported. Both variants were predicted to be pathogenic and can lead to premature occurrence of stop codons. CONCLUSION The heterozygous c.2769C>A (p.Y923*) and c.315delC (p.A105Afs*3) variants of the ZEB2 gene probably underlay the pathogenesis in the two patients. Gene testing has facilitated confirmation of the diagnosis and genetic counselling.
DNA Copy Number Variations ; Facies ; Hirschsprung Disease ; Humans ; Intellectual Disability/genetics* ; Microcephaly/genetics* ; Zinc Finger E-box Binding Homeobox 2/genetics*

Arthroplasty, Replacement, Hip ; Female ; Femoral Neck Fractures/surgery* ; Humans ; Osteoporosis/surgery* ; Pregnancy

Objective To investigate the expression level and potential clinical value of serum HBV RNA in HBeAg-positive chronic hepatitis B (CHB) patients at different periods. Methods A total of 61 CHB patients who attended the outpatient and inpatient services of Department of Hepatology, Hangzhou Xixi Hospital, from August 2019 to December 2020 were enrolled, and according to the antiviral therapy for HBeAg-positive CHB patients, they can be divided into group A with untreated HBeAg-positive CHB (HBeAg+ and HBV DNA+) patients, group B with treatment-experienced patients before HBeAg seroconversion (HBeAg+ and HBV DNA-), and group C with treatment-experienced patients after HBeAg seroconversion (HBeAg- and HBV DNA-). Peripheral blood HBV RNA load was measured at different periods, and its correlation with HBsAg and HBV DNA was analyzed. The t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between groups; a Pearson or Spearman correlation analysis was used to describe the correlation between two variables. Results The positive rates of HBV RNA in these three groups were 100% (22/22), 88.2% (15/17), and 22.7% (6/22), respectively. In group A, HBV RNA was positively correlated with HBsAg and HBV DNA ( r =0.612 and 0.922, both P < 0.01), while in groups B and C, there was no correlation between HBV RNA and HBsAg. Group B had significantly higher levels of HBV RNA and HBsAg than group C ( Z =-4.44 and -2.41, both P < 0.05). The HBV DNA-positive group had a significantly higher level of HBV RNA than the HBV DNA-negative group ( Z =-6.16, P < 0.01). Conclusion After HBV DNA clearance achieved by antiviral therapy with nucleos(t)ide analogues in CHB patients, serum HBV RNA can still be detected in some of these patients. Since HBV RNA only comes from cccDNA in the liver, it can better reflect viral replication activity in the liver than HBV DNA and thus has a certain clinical value in the management of CHB patients.

Objective: To investigate the role of epidemiological history in the screening of Corona Virus Disease 2019 (COVID-19) in fever clinic, to improve the efficiency in fever clinic and reduce the incidence of cross infection. Methods: This is a retrospective study. Patients who were admitted to the fever clinic in West China Hospital of Sichuan University from January 23^th, 2020 to February 11^th, 2020 included the study. According to epidemiological history, the patients were divided into epidemiological history group (the experimental group) and no epidemiological history group (the control group). The two groups of patients were admitted and treated separately. The clinical data, NEWS score, etiology results, viral pneumonia showed on CT, time of visit, COVID-19 patient ratio, and admission composition ratio were compared between the two groups. The measurement data were presented as the mean ± standard deviation (SD), and the numeration data were expressed as ratio or constituent ratio. The measurement data of normal distribution between the two groups were compared by independent sample t test. The measurement data of skewed distribution are expressed by the median (interquartile range), and the comparison between the two groups is tested by non-parameter. The differences between enumeration data were assessed by chi-square test. A P<0.05 was considered statistically significant. Results: A total of 2423 patients were included, including 927 patients in the experimental group and 1296 patients in the control group. There were no significant differences in gender, NEWS score and clinical symptoms between the two groups (P> 0.05). The age (35.00 ± 12.80 vs 38.13 ± 15.57 years) , the proportion of fever patients (28.80% vs 32.75%) and waiting time (31.72 vs 58.08 min) of the experimental group were lower than the control group, the difference was statistically significant (P <0.05). The CT examination ratio (37.54% vs 20.39%), viral pneumonia ratio showed on CT (9.77% vs 2.95%), ratio of examined COVID-19 nucleic acid test (85.44% vs 56.75%), and the admission ratio (16.72% vs 9.63%) of the experimental group were higher than the control group, and the differences were statistically significant (P <0.05); There was no significant difference in the positive rates of influenza virus and rhinovirus between the two groups (P> 0.05). Conclusion It is necessary to adjust the management mode of fever clinic during the Corona Virus Disease 2019, and to manage the patients according to the epidemiological history which can improve the screening efficiency and reduce the risk of cross infection.

Objective:To study the effect of laparoscopic transabdominal preperitoneal (TAPP) and mesh plug repair on the sexual function of patients with indirect inguinal hernia.Methods:One hundred and four patients with indirect inguinal hernia who were treated in the No.922 Hospital of PLA Joint Logistics Support Force from January 2018 to October 2019 were selected and divided into two groups according to the method of random number table: routine group and TAPP group, with 52 cases in each group. The routine group was treated with mesh plug repair, and the TAPP group was treated with TAPP. The international erectile function index-5 (IIEF-5) was used to evaluate the sexual function of the patients after operation for 6 months, the visual analog pain scale (VAS) was used to evaluate the pain after operation for 1 month, and the relevant indexes of the operation and the incidence of complications were compared.Results:The IIEF-5 scores at 6 months after operation in two groups was higher than that before operation, the testicular volume and the maximum blood flow velocity of testicular artery in two groups were lower than those before operation, and the differences were statistically significant ( P<0.05); the IIEF-5 scores at 6 months after operation in the TAPP group was higher than that in the routine group [(23.86 ± 1.5) scores vs. (21.45 ± 3.85) scores], and the testicular volume and the maximum blood flow velocity of testicular artery were higher than those in the routine group [(9.65 ± 0.08) cm 3 vs. (9.39 ± 0.09) cm 3, (3.83 ± 1.05) cm/s vs. (2.88 ± 0.36) cm/s], and the differences were statistically significant ( P<0.05). One month after operation, the pain scores of two group were lower than that before operation, and the pain scores of TAPP group was lower than that of routine group [(1.65 ± 0.35) scores vs. (2.78 ± 0.39) scores], and the differences were statistically significant ( P<0.05). The operation time of TAPP group was higher than that of routine group [(44.35 ± 6.26) min vs. (41.80 ± 5.95) min], the bleeding volume, the time of getting out of bed, the time of hospitalization of TAPP group were lower than those of routine group [(54.66 ± 8.98) ml vs. (73.25 ± 15.25) ml, [(12.75 ± 2.42) h vs. (23.55 ± 3.66) h], (3.25 ± 1.01) d vs. (7.85 ± 1.44) d], and the differences were statistically significant ( P<0.05). The incidence of operation complications of TAPP group was lower than that of routine group [3.85%(2/52) vs. 21.15%(11/52)], and the difference was statistically significant ( χ2=7.121, P<0.05). Conclusions:Compared with conventional hernia repair, laparoscopic hernia repair can improve the sexual function, relieve the pain, improve the therapeutic effect and reduce the complications.