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.

OBJECTIVE: To investigate the mechanism of human embryonic stem cell-derived mesenchymal stem cells (hESC-MSC) in alleviating brain injury after resuscitation in swine with cardiac arrest (CA). METHODS: Twenty-nine healthy male large white swine were randomly divided into Sham group (n = 9), cardiopulmonary resuscitation (CPR) group (n = 10) and hESC-MSC group (n = 10). The Sham group only completed animal preparation. In CPR group and hESC-MSC group, the swine model of CA-CPR was established by inducing ventricular fibrillation for 10 minutes with electrical stimulation and CPR for 6 minutes. At 5 minutes after successful resuscitation, hESC-MSC 2.5×10⁶/kg was injected via intravenous micropump within 1 hour in hESC-MSC group. Venous blood samples were collected before resuscitation and at 4, 8, 24, 48 and 72 hours of resuscitation. The levels of neuron specific enolase (NSE) and S100B protein (S100B) were detected by enzyme linked immunosorbent assay (ELISA). At 24, 48 and 72 hours of resuscitation, neurological deficit score (NDS) and cerebral performance category (CPC) were used to evaluate the neurological function of the animals. Three animals from each group were randomly selected and euthanized at 24, 48, and 72 hours of resuscitation, and the hippocampus tissues were quickly obtained. Immunofluorescence staining was used to detect the distribution of hESC-MSC in hippocampus. Immunohistochemical staining was used to detect the activation of astrocytes and microglia and the survival of neurons in the hippocampus. The degree of apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL). RESULTS: The serum NSE and S100B levels of brain injury markers in CPR group and hESC-MSC group were significantly higher than those in Sham group at 24 hours of resuscitation, and then gradually increased. The levels of NSE and S100B in serum at each time of resuscitation in hESC-MSC group were significantly lower than those in CPR group [NSE (μg/L): 20.69±3.62 vs. 28.95±3.48 at 4 hours, 27.04±5.56 vs. 48.59±9.22 at 72 hours; S100B (μg/L): 2.29±0.39 vs. 3.60±0.73 at 4 hours, 2.38±0.15 vs. 3.92±0.50 at 72 hours, all P < 0.05]. In terms of neurological function, compared with the Sham group, the NDS score and CPC score in the CPR group and hESC-MSC group increased significantly at 24 hours of resuscitation, and then gradually decreased. The NDS and CPC scores of hESC-MSC group were significantly lower than those of CPR group at 24 hours of resuscitation (NDS: 111.67±20.21 vs. 170.00±21.79, CPC: 2.33±0.29 vs. 3.00±0.00, both P < 0.05). The expression of hESC-MSC positive markers CD73, CD90 and CD105 in the hippocampus of hESC-MSC group at 24, 48 and 72 hours of resuscitation was observed under fluorescence microscope, indicating that hESC-MSC could homing to the damaged hippocampus. In addition, compared with Sham group, the proportion of astrocytes, microglia and apoptotic index in hippocampus of CPR group were significantly increased, and the proportion of neurons was significantly decreased at 24, 48 and 72 hours of resuscitation. Compared with CPR group, the proportion of astrocytes, microglia and apoptotic index in hippocampus of hESC-MSC group decreased and the proportion of neurons increased significantly at 24 hours of resuscitation [proportion of astrocytes: (14.33±1.00)% vs. (30.78±2.69)%, proportion of microglia: (12.00±0.88)% vs. (27.89±5.68)%, apoptotic index: (12.89±3.86)% vs. (52.33±7.77)%, proportion of neurons: (39.44±3.72)% vs. (28.33±1.53)%, all P < 0.05]. CONCLUSIONS Application of hESC-MSC at the early stage of resuscitation can reduce the brain injury and neurological dysfunction after resuscitation in swine with CA. The mechanism may be related to the inhibition of immune cell activation, reduction of cell apoptosis and promotion of neuronal survival.
Animals ; Heart Arrest/therapy* ; Cardiopulmonary Resuscitation ; Swine ; Humans ; Male ; Human Embryonic Stem Cells/cytology* ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/cytology* ; Phosphopyruvate Hydratase/blood* ; Brain Injuries/therapy* ; S100 Calcium Binding Protein beta Subunit ; Apoptosis ; Disease Models, Animal

OBJECTIVE To explore the mechanism of steam-processed Polygonatum sibiricum polysaccharides(SPSP) in prophylaxis and treatment of mice with blood deficiency syndrome(BDS) by RNA sequencing(RNA-seq) technology. METHODS The mice were randomly divided into five groups(10 mice in each group), namely normal group, model group, SPSP groups(0.1, 0.4 g·kg−1), Danggui Buxue oral liquid(DOL) group. BDS model was induced in mice by acetylphenyl-hydrazine and cyclophosphamide. Blood routine, body weight and body temperature were tested after a consecutive administration for 14 d. The differential expressed genes(DEGs) related to anti-BDS by SPSP were screened through the transcriptome sequencing of the hepatic tissue in BDS mice. Functional annotation and enrichment analysis were performed to screen out the gene expression signaling pathways related to the treatment of SPSP on BDS mice. Quantitative polymerase chain reaction(qPCR) was used to verify the experiment. RESULTS Compared with the model group, SPSP(0.4 g·kg−1) could elevate the blood routine indexes such as red blood cell, white blood cell, hemoglobin, platelet, mean corpuscular hemoglobin concen-tration(P<0.01), and reverse the body weight and body temperature to normal(P<0.01 or P<0.05). The result of transcriptomic analysis showed that the underlying mechanism was mainly related to hematopoietic cell line, retinol metabolism, steroid hormone biosynthesis, platelet activation, B cell receptor signaling pathway, and leukocyte transendothelial migration, etc. The result of qPCR showed that SPSP(0.4 g·kg−1) could elevate the expression of JAK1, STAT1 and GATA1 mRNA (P<0.01 or P<0.05). CONCLUSION SPSP has therapeutic effects on BDS. The key DEGs in the treatment of BDS by SPSP are mainly related to the restoration of hematopoietic function, regulation of hormone and immune function. The mechanism of SPSP on treatment of BDS might be the regulation of JAK1/STAT1 signaling pathway.

ObjectiveTo analyze the failure of antiretroviral therapy (ART) and drug resistance characteristics among the newly reported HIV-infected patients in Taizhou City from 2020 to 2022. MethodsBlood samples, sociodemographic characteristics and ART information of the newly reported HIV-infected patients who received ART for ≥6 months in Taizhou City from 2020 to 2022 were collected for the detection of recent infections and HIV-1 genotypic drug resistance. Multivariate logistic regression analysis was used to analyze the influencing factors of treatment failure. The gene sequences of cases with failed ART were submitted to the HIV drug resistance database of Stanford University to determine the drug resistance mutation sites and drug resistance characteristics. ResultsAmong the 1 023 newly reported HIV-infected patients receiving ART, the median age （P₂₅，P₇₅） was 47 (33, 58) years, 81.4% were male, 66.4% (679/1 023) were infected through heterosexual transmission, 74.7% had a WHO clinical stage Ⅰ/Ⅱ, 62.2% had a baseline CD4 count of >200 cell·μL^-1, 94.4% (966/1 023) received an immediate ART, and 78.7% were long-term infected. Among the 66 patients with treatment failure (6.5%), the likelihood of treatment failure was lower in those with homosexual transmission (OR=0.39, 95%CI: 0.17‒0.84) and without history of sexually transmitted disease (STD) (OR=0.45, 95%CI: 0.24‒0.92), but higher in those with a baseline CD4 count of ≤200 cell·μL^-1, delayed ART (OR=3.19, 95%CI: 1.24‒7.52), and primary drug resistance (OR=4.69, 95%CI: 1.68‒11.89). Among the 36 HIV-infected patients with virological failure, 27 sequences were successfully amplified, with a successful amplification rate of 75.0% (27/36). The total drug resistance rate was 55.6% (15/27), of which the drug resistance rates of nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were 37.0% (10/27), 51.9% (14/27) and 3.7% (1/27), respectively. Among the NNRTIs, the degree of resistance to efavirenz and nevirapine was consistent, with a majority (51.9%) of highly drug-resistant. K103N and M184V were the most common mutation sites, but PIs mutations occured less frequently. A total of 8 genotypes of HIV-1 were detected, in which subtype CRF01_AE accounted for 37.0% (10/27), followed by CRF07_BC [14.8% (4/27)], CRF08_BC [14.8% (4/27)] and subtype C [14.8% (4/27)]. ConclusionDuring the period from 2020 to 2022, the newly reported HIV-infected individuals in Taizhou City were predominated by long-term infections. Immediate initiation of ART can reduce the risk of treatment failure in HIV-infected individuals. Virological treatment failures are primarily associated with resistance to NRTIs and NNRTIs. It is recommended to strengthen active detection and promptly initiate ART to minimize the occurrence of ART failure. Simultaneously, there is a need to intensify drug resistance detection targeted for those with treatment failure, so as to provide a scientific guidance for drug replacement.

Evidence mapping was performed to review the clinical trials and systematic reviews about the treatment of hyperlipidemia with Chinese patent medicines in recent ten years. A total of 387 clinical studies and 18 systematic reviews/Meta-analysis involving 45 Chinese patent medicines commonly used in the treatment of hyperlipidemia in recent ten years were retrieved from Chinese and English academic publication databases. The article information was extracted by reading the abstract and full text, and the evidence of publication trend, combined medication, intervention course, complications, and outcome indicators was sorted out. The Cochrane risk-of-bias assessment tool was used to evaluate the quality of some randomized controlled trial(RCT), and the research results were presented by figures combined with tables. The Chinese patent medicines mostly mentioned included Xuezhikang Capsules, Yindan Xinnaotong Capsules, Hedan Tablets, Pushen Capsules, and Compound Danshen Dropping Pills. The outcome indicators included blood lipid levels(total cholesterol, low-density lipoprotein, etc.), clinical efficacy(markedly effective, effective, and ineffective), adverse reactions(mainly including gastrointestinal reactions), hemorheological indicators, and liver and kidney functions. The available studies generally had small sample sizes, short period, and insufficient attention to traditional Chinese medicine(TCM) syndromes. The RCT and systematic reviews/Meta-analysis generally had low quality, and thus the results had low reliability. Nevertheless, the studies demonstrated a heightened focus on adverse reactions, diverse combined intervention measures, and varied options for addressing different complications. It is recommended that the clinical research on Chinese patent medicines for hyperlipidemia should strive to improve research quality, standardize research protocols, and devote greater attention to TCM syndromes, thereby enhancing the influence and effectiveness of these medicines.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Hyperlipidemias/drug therapy* ; Nonprescription Drugs/therapeutic use* ; Randomized Controlled Trials as Topic

The cerebellum is heavily connected with other brain regions, sub-serving not only motor but also nonmotor functions. Genetic mutations leading to cerebellar dysfunction are associated with mental diseases, but cerebellar outputs have not been systematically studied in this context. Here, we present three dimensional distributions of 50,168 target neurons of cerebellar nuclei (CN) from wild-type mice and Nlgn3R451C mutant mice, a mouse model for autism. Our results derived from 36 target nuclei show that the projections from CN to thalamus, midbrain and brainstem are differentially affected by Nlgn3R451C mutation. Importantly, Nlgn3R451C mutation altered the innervation power of CN→zona incerta (ZI) pathway, and chemogenetic inhibition of a neuronal subpopulation in the ZI that receives inputs from the CN rescues social defects in Nlgn3R451C mice. Our study highlights potential role of cerebellar outputs in the pathogenesis of autism and provides potential new therapeutic strategy for this disease.
Animals ; Mice ; Disease Models, Animal ; Cerebellar Nuclei ; Autistic Disorder/pathology* ; Neurons/metabolism* ; Mutation ; Nerve Tissue Proteins/metabolism* ; Male ; Membrane Proteins ; Cell Adhesion Molecules, Neuronal

Humans ; Hemangiosarcoma/pathology* ; Colonic Neoplasms ; Molecular Biology

Objective: To explore the predictive factors of concurrent bile duct injury following transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). Methods: A retrospective study was conducted on 483 HCC patients in relation to TACE postoperative complications. A total of 21 cases of bile duct injury were observed following the TACE procedure. Laboratory data, imaging data, and clinically relevant medical histories were recorded before and after one week following the TACE procedure and follow-up. The χ (2) test, or Fisher's exact probability method, was used for categorical variables. The mean of the two samples was compared using a paired t-test or Wilcoxon rank sum test. The comparison of multiple mean values was conducted using an analysis of variance. Results: Twenty-one cases with bile duct injury had intrahepatic bile duct dilatation, bile tumors, hilar biliary duct stenoses, and other manifestations. 14.3% (3/21) of patients showed linear high-density shadows along the bile duct on a plain CT scan, while 76.2% (16/21) of patients had ALP > 200 U/L one week following TACE procedure, and bile duct injury occurred in later follow-up. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and γ-glutamyl transferase (GGT) were significantly increased in all patients following TACE procedure (t = -2.721, P = 0.014; t = -2.674, P = 0.015; t = -3.079, P = 0.006; t = -3.377, P = 0.003, respectively). Conclusion: The deposition of iodized oil around the bile duct on plain CT scan presentation or the continuous increase of ALP (> 200 U/L) one week following TACE procedure has a certain predictive value for the later bile duct injury.
Humans ; Liver Neoplasms/therapy* ; Carcinoma, Hepatocellular/therapy* ; Retrospective Studies ; Chemoembolization, Therapeutic/methods* ; Bile Ducts

Objective To explore hemodynamics of the aortic arch and supraarch vessels after thoracic endovascular aortic repair with fenestration and parallel grafts techniques, and compare the differences of these techniques. Methods Four patients with aortic arch lesions whose supraarch vessels were reconstructed by different surgical techniques (fenestration, chimney and periscope) were studied, and three-dimensional (3D) geometric models were established based on postoperative image data. The physiological flow obtained from two dimensional (2D) phase contrast magnetic resonance imaging were imposed on the ascending aorta inlet and the supraarch vessels outlets. The pressure waveform of 3-element Windkessel model was imposed on the descending aorta outlet. Through computational fluid dynamics ( CFD ) simulations, the hemodynamic parameters were obtained, including the pressure of supraarch vessels, the velocity vector of the stent inlet, and the relative residence time. Results The pressure change of the periscope stent was the largest, followed by the fenestration stent, and the pressure change of the chimney stent was the smallest. The velocity of the fenestration and periscope stent inlet was uneven, which might form vortex. The velocity of the chimney stent inlet was even. The high relative residence time concentrated in distal end of the fenestration stent outer wall, the ‘gutter’ part, and the place where the chimney and periscope stent adhered to the vessel wall. Conclusions The pressure difference between the inner and outer walls of the fenestration and periscope stent was high, so it was recommended to use the balloon-expandable stent. The pressure difference between the inner and outer walls of the chimney stent was low, so it was recommended to use the self-expanding stent. The predicted location of thrombosis was consistent with the clinical follow-up data, so it may be used for surgical planning and risk assessment of interventional treatment of aortic arch lesions.

Objective To study the process of single stent and double-stent thrombectomy at the Y-shaped bifurcation of the ideal internal carotid artery by finite element simulation, analyze the stent-thrombus-vessel interaction during the thrombectomy process based on the simulation results, and provide guidance for improving the effect of stent thrombectomy at the bifurcation. Methods The CAD software was used to build the model and the finite element analysis software was used to simulate the process of single stent and double-stent thrombectomy. Results Thrombectomy was unsuccessful in single stent model and successful in double-stent model, and the maximum stress of thrombus during embolus retrieval was twice that of single stent, the maximum strain was 1.12 times that of single stent, and the maximum contact pressure on the surface of vessel was approximately twice that of single stent. Conclusions Double Solitaire stents can effectively prevent thrombus displacement at the bifurcation and successfully retrieve the thrombus, but there is a risk of fracture due to the high stress level in the middle section of the thrombus. The contact pressure of the vessel on the anterior artery side is higher during thrombectomy, and the risk of vessel damage is greater. Therefore, it is necessary to optimize the design of the stent-retriever to improve its flexibility.