Objective To preliminarily explore the potential efficacy of Xuesaitong Soft Capsule(XST)against post-stroke depression(PSD),and to investigate the material basis of XST's anti-PSD effect based on the metabolomics results to analyze its related pharmacokinetic(PK)characteristics and further analyze the pharmacodynamic(PD)equation of representative ingredients.Methods The initial evaluation of drug effica-cy was conducted by detecting the depressive-like behavior and neurotransmitter levels in rats.The Pearson correlation analysis was employed to analyze the correlation between the main metabolites regulated by XST and the saponin components entering the bloodstream.At various time points after drug administration,the blood concentration of ginsenoside Re and the concentration of norepinephrine(NE)in the serum of PSD rats were measured,and the compartment model was fitted accordingly.Furthermore,the liquid chromatography-mass spectrometry was utilized to determine the content of ginsenoside Re in the liver,spleen,kidney,prefron-tal cortex,hippocampus and striatum of PSD rats.Results Ginsenoside Re showed the optimal correlation by the Pearson correlation analysis.Based on its pharmacokinetic parameters,the pharmacodynamic equation with NE was E=160.462 × Ce/(38.663+Ce).The contents of ginsenoside Re in the liver,spleen,kidney,prefron-tal cortex,hippocampus and striatum of rats were(17.23+11.90),(19.05+5.67),(1.95+0.79),(70.13+6.75),(57.03+3.11),and(72.45+5.45)ng/g,respectively.Conclusion XST could improve the depressive-like behaviors in PSD rats by regulating the expression levels of neurotransmitter NE and 5-HT.Ginsenoside Re may be the pharmacodynamical material foundation for XST's preventative treatment of PSD.

Objective:To analyze and summarize clinical phenotypic characteristics and genetic variations in patients with intellectual disability and pathogenic variations of the DYNC1H1 gene across 4 generations within a single family. Methods:Retrospective case analysis.Clinical data of a child with epilepsy and intellectual disability and her family members were collected from the Children′s Medical Center, Peking University First Hospital on December 2019.The child was followed up regularly.DNA was extracted from the peripheral blood of the child′s family members.Then whole-exome sequencing and Sanger sequencing were performed to identify the genetic variation type in the proband and her family members.The relationship between genotype and phenotype was further analyzed.Results:A total of 13 patients across 4 generations in the family had intellectual disability, and the proband also had drug-resistant epilepsy.The variation c. 13556C> A (p.A4519E) of the DYNC1H1 gene was confirmed by gene testing in 8 patients (no blood samples were obtained from the remaining patients). Conclusions:DYNC1H1 gene-related intellectual disability in most previously reported cases are caused by novel variations of this gene.In this study, a large family of 13 intellectual disability patients across 4 generations caused by a pathogenic mutation in the DYNC1H1 gene was summarized.The findings make precise genetic counseling possible for this family and provide a basis for further studies on the relationship between the genotype and phenotype of the DYNC1H1 gene.

Objective To develop and compare the predictive performance of five machine learning models for adverse postoperative outcomes in cardiac surgery patients, and to identify key decision factors through SHapley Additive exPlanations (SHAP) interpretability analysis. Methods A retrospective collection of perioperative data (including demographic information, preoperative, intraoperative, and postoperative indicators) with 88 variables was conducted from adult cardiac surgery patients at the First Affiliated Hospital of Xinjiang Medical University in 2023. Adverse postoperative outcomes were defined as the occurrence of acute kidney injury and/or in-hospital mortality during the postoperative hospitalization period following cardiac surgery. Patients were divided into an adverse outcome group and a favorable outcome group based on the presence of adverse postoperative outcomes. After screening feature variables using the least absolute shrinkage and selection operator (LASSO) regression method, five machine learning models were constructed: eXtreme gradient boosting (XGBoost), random forest (RF), gradient boosting machine (GBM), light gradient boosting machine (LightGBM), and generalized linear model (GLM). The dataset was randomly divided into a training set and a test set at a 7 : 3 ratio using stratified sampling, with postoperative outcome as the stratification factor. Model performance was evaluated using receiver operating characteristic curves, decision curve analysis, and F1 Score. The SHAP method was applied to analyze feature contribution. Results A total of 639 patients were included, comprising 395 males and 244 females, with a median age of 62 (55, 69) years. The adverse outcome group consisted of 191 patients, while the favorable outcome group included 448 patients, resulting in an adverse postoperative outcome incidence of 29.9%. Univariate analysis showed no significant differences between the two groups for any variables (P>0.05). Using LASSO regression, 16 feature variables were selected (including cardiopulmonary bypass support time, blood glucose on postoperative day 3, creatine kinase-MB isoenzyme, systemic inflammatory response index, etc.), and five machine learning models (GLM, RF, GBM, LightGBM, XGBoost) were constructed. Evaluation results demonstrated that the XGBoost model exhibited the best predictive performance on both the training set (n=447) and test set (n=192), with area under the curve values of 0.761 [95%CI (0.719, 0.800) ] and 0.759 [95%CI (0.692, 0.818) ], respectively. It also significantly outperformed other models in positive predictive value, and balanced accuracy in the test set. Decision curve analysis further confirmed its clinical utility across various risk thresholds. SHAP analysis indicated that variables such as cardiopulmonary bypass support time, blood glucose on postoperative day 3, creatine kinase-MB isoenzyme, and inflammatory markers (SIRI, NLR, CAR) had high contributions to the prediction. Conclusion The XGBoost model effectively predicts adverse postoperative outcomes in cardiac surgery patients. Clinically, attention should be focused on cardiopulmonary bypass support time, postoperative blood glucose control, and monitoring of inflammatory levels to improve patient prognosis.

Objective:To analyze and summarize clinical phenotypic characteristics and genetic variations in patients with intellectual disability and pathogenic variations of the DYNC1H1 gene across 4 generations within a single family. Methods:Retrospective case analysis.Clinical data of a child with epilepsy and intellectual disability and her family members were collected from the Children′s Medical Center, Peking University First Hospital on December 2019.The child was followed up regularly.DNA was extracted from the peripheral blood of the child′s family members.Then whole-exome sequencing and Sanger sequencing were performed to identify the genetic variation type in the proband and her family members.The relationship between genotype and phenotype was further analyzed.Results:A total of 13 patients across 4 generations in the family had intellectual disability, and the proband also had drug-resistant epilepsy.The variation c. 13556C> A (p.A4519E) of the DYNC1H1 gene was confirmed by gene testing in 8 patients (no blood samples were obtained from the remaining patients). Conclusions:DYNC1H1 gene-related intellectual disability in most previously reported cases are caused by novel variations of this gene.In this study, a large family of 13 intellectual disability patients across 4 generations caused by a pathogenic mutation in the DYNC1H1 gene was summarized.The findings make precise genetic counseling possible for this family and provide a basis for further studies on the relationship between the genotype and phenotype of the DYNC1H1 gene.

Objective:To compare the effect of self-radiopaque markers guiding physician-modified fenestration, chimney technique and hybrid Ⅳb technique on reconstruction of left subclavian artery (LSA) in endovascular treatment of aortic dissection (TEVAR).Methods:The clinical and follow-up data of 312 TEVAR patients treated with LSA blood supply reconstruction technology from Jan 2016 to Dec 2019 at Fuwai hospital were retrospectively analyzed.Results:There were 35 patients in the hybrid Ⅳb technique group, 93 in the chimney technique group, and 184 in the in vitro fenestration group. The follow-up period ranged from 12 to 24 months. No artificial blood vessel and stent occlusion occurred in all patients during follow-up, and the LSA blood flow was unobstructed. A total of 19 patients had endoleak by the last follow-up, and there was no statistical difference between the three groups. Eleven patients underwent reintervention surgery, all were from chimney technique group and in vitro fenestration group, with no statistical difference ( P>0.05). Severe complications occurred in 28 patients during hospitalization, and the incidence of complications was the highest in the hybrid Ⅳb technique group ( P<0.01). During follow-up, 4 patients died in the bypass group, 6 died in the external window group, and 8 died in the chimney group, with no significant difference ( P>0.05). Conclusions:The safety and efficacy of the left subclavian artery flow reconstruction by in vitro fenestration and chimney technique were similar. The occurrences of early complications were lower than that of the hybrid Ⅳb technique, but the reintervention rate of endoleak was higher.

New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.
Angiotensin-Converting Enzyme 2 ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Epitopes ; Humans ; SARS-CoV-2/genetics* ; Spike Glycoprotein, Coronavirus/genetics*

Objective:To design a replaceable corneal scaler and explore its effect on improving the positive detection rate of corneal bacteria and the cure rate of patients with infectious keratitis.Methods:Totally 100 patients with infectious keratitis treated in the Eye&Ent Hospital of Fudan University in Shanghai from June 2020 to October 2021 were conveniently selected as the application object, 50 patients from June 2020 to January 2021 were selected as the control group, and 50 patients from February 2021 to October 2021 were selected as the experimental group. The control group used the traditional corneal scalpel for corneal scraping, and the experimental group used the replaceable corneal scalpel for corneal scraping. The positive detection rate of bacteria, the cure rate of patients as of the date of data collection, the comfort status of patients and the operation difficulty score of medical staff were compared between the two groups.Results:The 28 cases (56%) were positive in the experimental group, and 30 cases (60%) were cured as of the date of data collection; 16 cases (32%) were positive in the control group and 18 cases (36%) were cured as of the date of data collection. The difference between the two groups was statistically significant ( χ2=-2.47, -2.20, all P<0.05). The score of comfort in the experimental group was (83.92 ± 6.40) and that in the control group was (54.04 ± 10.69). The difference between the two groups was statistically significant ( t=17.14, P<0.01). The operation difficulty score of medical staff in the experimental group was (1.46 ± 0.54) and that of medical staff in the control group was (3.24 ± 0.72). The difference between the two groups was statistically significant ( t=-13.50, P<0.01). Conclusions:The use of replaceable corneal scalpel can not only improve the positive detection rate of patients, improve the treatment effect of patients, improve the comfort and satisfaction of patients, but also improve the work efficiency of medical staff and reduce the operational risk of medical staff, so as to improve the real professional value of medical staff.

Objective: To screen and analysis of antihepatic steatosis active components and cell metabolism withinrhubarb anthraquinones in vitro. Methods: Lipid-lowering activity of liver cell affinity components in rhubarbanthraquinones was evaluated by hepatic steatosis in vitro model. Hepatocyte-specific affinity compositions werescreened by hepatocyte affinity chromatography. Hep G2 cells were incubated with rhubarb anthraquinones in vitro andwere detected by HPLC and HPLC-Q-TOF-MS method. Results: Compared with normal group, the intracellular TGcontent of model group were significantly increased (P＜0.05) . Respectively treated with different concentrations ofrhubarb anthraquinones, the intracellular TG content were significantly decreased in a dose dependent manner (P＜0.05) in comparison with model group. Compared with rhubarb solution, there are mainly four hepatocyte-specific affinitycompositions of aloe-emodin, emodin, chrysophanol and physcion, except for rhein. Conclusion: The lipid-lowering experiment in vitro verified that five rhubarb anthraquinones have significant lipid-lowering activity. This research established a biochromatography method to screen out four hepatocyte-specific affinity compositions of aloe-emodin, emodin, chrysophanol and physcion from rhubarb anthraquinones, while the conjugation sites of rhein were ambiguous.Combined hepatocyte affinity chromatography with hepatic steatosis in vitro model, it could evaluate and screen lipidlowering active ingredient in vitro and cell metabolism of Chinese traditional medicine for the drug development of lipidlowering rhubarb anthraquinones.

Objective · To improve the surgical procedure of correcting upper eyelid retraction.Methods · Patients suffering upper eyelid retraction of 2-5 mm caused by thyroid-associated ophthalmopathy were treated with modified levator lengthening technique in Shanghai Ninth People's Hospital (Shanghai Jiao Tong University School of Medicine,China) from July 2013 to December 2014.Results· Of the 34 patients underwent the modified levator lengthening surgery for upper eyelid retraction correction,there were 7 males and 27 females.After 6 months,upper eyelid retraction got fully resolved in 25 cases and partly improved in 9 cases.The palpebral fissure height demonstrated an average decrease of 3.7 mm (P=0.000).Patient's ocular discomfort such as photophobia and tearing were either cured or improved.Conclusion · Modified levator lengthening surgery can effectively correct upper eyelid retraction,improve the patient's appearance and cure their ocular discomfort.