Objective To analyze the changes in myocardial injury markers and cardiac function in patients with hypertrophic obstructive cardiomyopathy (HOCM) after Liwen surgery. Methods A retrospective analysis was conducted on the clinical data of HOCM patients who underwent Liwen surgery at the Department of Cardiac Surgery, Wuhan Asia Heart Hospital from December 2019 to April 2023, mainly including preoperative and postoperative dynamic follow-up laboratory test results and echocardiograms. Results A total of 42 patients were included, with 25 males and 17 females, aged (44.76±17.72) years, and a postoperative follow-up time of (15.02±6.97) months. The myocardial troponin level of the patients decreased from preoperative 0.03 (0.02, 0.06) ng/mL to postoperative 0.02 (0.01, 0.05) ng/mL (P=0.006), and the N-terminal pro-brain natriuretic peptide level decreased from preoperative 748.95 (337.40, 1600.75) ng/L to postoperative 367.15 (126.93, 1030.25) ng/L (P<0.001). After surgery, the left atrial diameter of the patients decreased from preoperative (4.18±0.57) cm to postoperative (3.93±0.55) cm (P=0.004), the end-diastolic interventricular septum thickness decreased from preoperative 2.25 (1.90, 2.75) cm to postoperative 1.70 (1.50, 1.90) cm (P<0.001), the left ventricular mass index decreased from preoperative 211.73 (172.28, 261.54) g/m2 to postoperative 156.78 (132.34, 191.36) g/m2 (P<0.001), the left ventricular weight decreased from preoperative 368.89 (292.34, 477.72) g to postoperative 266.62 (224.57, 326.04) g (P<0.001), the end-diastolic posterior wall thickness of the left ventricle decreased from preoperative 1.30 (1.20, 1.60) cm to postoperative 1.20 (1.18, 1.40) cm (P<0.001), the relative wall thickness decreased from preoperative 0.78 (0.78, 1.02) to postoperative 0.63 (0.56, 0.72) (P<0.001), the end-systolic inner diameter of the left ventricle increased from preoperative (2.91±0.50) cm to postoperative (3.19±0.53) cm (P=0.001), and the end-diastolic inner diameter of the left ventricle increased from preoperative (4.41±0.48) cm to postoperative (4.66±0.52) cm (P=0.005). The left ventricular outflow diameter increased from preoperative (1.28±0.46) cm to postoperative (1.57±0.32) cm (P=0.001), the left ventricular outflow pressure gradient decreased from preoperative 58.50 (40.75, 92.50) mm Hg to postoperative 11.50 (7.75, 20.50) mm Hg (P<0.001), the left ventricular ejection fraction increased from preoperative 60.00% (56.75%, 65.00%) to postoperative 63.00% (62.00%, 66.00%) (P=0.024), and the degree of systolic anterior motion of the mitral valve leaflets decreased (P＜0.001). Conclusion The cardiac function of patients with HOCM is improved after Liwen surgery, myocardial injury marker levels are decreased, cardiac reverse remodeling occurres, and the surgical outcome is good.

Objective To evaluate tolerability,safety and pharmacokinetics of JS026 and JS026-JS016 single dose intravenous infusion in healthy adults.Methods This phase 1,randomized,double-blind,placebo-controlled,dose-escalation study totally included 48 participants:32 healthy subjects were enrolled in JS026 single intravenous infusion groups and 16 healthy subjects were enrolled in JS026-JS016 groups.JS026 was sequentially administered from low dose to high dose(30-1 000 mg),with intravenous infusion of JS026 or placebo in JS026 single-dose groups,and intravenous infusion of JS026-JS016 or placebo in the combination drug groups.Blood was collected according to the time point designed for trial.Serum concentrations of JS026 and JS016 were determined by enzyme linked immunosorbnent assay(ELISA),and pharmacokinetics parameters were calculated by WinNonlin 8.2.The power model method was used to evaluate the linear analysis of dose and drug exposure.Results 47 subjects completed trial and 1 subject lost to follow-up.After a single intravenous injection of JS026 of 30 mg,100 mg,300 mg,600 mg,and 1 000 mg,mean Cmax were(9.47±1.53),(33.20±4.95),(96.10±13.70),(177.00±22.20)and(353.00±56.70)μg·mL-1,respectively;mean AUC0-∞ were(4 225.00±607.00),(1.78 × 104±3 268.00),(5.83 × 104±1 038.00),(1.07 × 105±152.00),(1.66 × 105±327.00)μg·h·mL-1,respectively;mean t1/2 of JS026 were 563-709 h.The Cmax and AUC0-∞ of JS026 were basically similar alone or in combination with JS016.The results of Power model showed that Cmax and AUC0-∞ increased approximately linearly with the increasing dose of JS026.Treatment emergent adverse event was not increasing when dose increased and most of adverse event associated with drugs were abnormal on laboratory tests and haematuria,thus JS026 and JS016 was well tolerated in all groups.Conclusion The single intravenous infusion of JS026 can almost be thought to be a linear relationship between the doses and drug serum exposure.JS016 had no significant effect on serum concentration of JS026 and JS026 was well tolerated and safe in healthy subjects within 30-1 000 mg.

Objective To explore the value of magnetic resonance relaxation time quantitative imaging in predicting molecular subtypes of invasive ductal carcinoma(IDC)of breast.Methods A total of 79 IDC patients underwent routine magnetic resonance imaging(MRI)scanning and relaxation time quantitative imaging.According to immunohistochemical results of lesions,patients were divided into different immunohistochemical index groups and molecular subtype groups.The differences in MRI signs,T1 values and T2 values of lesions were statistically compared between each group.Patient operating characteristic(ROC)curve was used to evaluate values of T1 and T2 alone and the combination of them in differential diagnosis of IDC molecular subtypes.Results There were 82 samples of lesion in 79 patients,in which,Luminal A type 16(19.51%),Luminal B1 type 11(13.41%),Luminal B2 type 27(32.93%),tyrosine kinase receptor-2 overexpression type(Erb-B2)14(17.07%)and TNBC 14(17.07%).There were no significant differences in patient age,lesion distribution,maximum diameter,morphology,margin and enhancement performance between patients with various molecular subtypes(P>0.05).Among the immunohistochemical indexes,only the Ki-67 positive group had higher T1 value than the negative group(P<0.05).In ROC analysis,the critical T1 value of Ki-67 positive lesions was 2 145 ms,Yoden index was 0.368,the sensitivity was 53.47%,the specificity was 83.33%and the area under the curve(AUC)was 0.640(95%CI:0.527-0.744).There were no significant differences in T1 and T2 values between Luminal A,Luminal B1,Luminal B2,Erb-B2 enriched and TNBC subtypes(P<0.05).T1 and T2 values were lower in Luminal type lesion than those of TNBC type lesion(P＜0.05).ROC curve analysis showed that the combined T1 and T2 values were more effective in differentiating Luminal/TNBC type than those of T1 and T2 values alone.Conclusion T1 mapping can be used as one of the methods to predict the high or low expression levels of Ki-67 in IDC tumors.The combination of T1 and T2 values can improve the ability to predict Luminal/TNBC subtypes.

Objective:To evaluate the efficiency of the four domestic language models,ERNIE Bot,ChatGLM2,Spark Desk and Qwen-14B-Chat,all with a massive user base and significant social attention,in response to consultations about PCa-related perio-perative nursing and health education.Methods:We designed a questionnaire that includes 15 questions commonly concerned by patients undergoing radical prostatectomy and 2 common nursing cases,and inputted the questions into each of the four language models for simulation consultation.Three nursing experts assessed the model responses based on a pre-designed Likert 5-point scale in terms of accuracy,comprehensiveness,understandability,humanistic care,and case analysis.We evaluated and compared the performance of the four models using visualization tools and statistical analyses.Results:All the models generated high-quality texts with no mis-leading information and exhibited satisfactory performance.Qwen-14B-Chat scored the highest in all aspects and showed relatively sta-ble outputs in multiple tests compared with ChatGLM2.Spark Desk performed well in terms of understandability but lacked comprehen-siveness and humanistic care.Both Qwen-14B-Chat and ChatGLM2 demonstrated excellent performance in case analysis.The overall performance of ERNIE Bot was slightly inferior.All things considered,Qwen-14B-Chat was superior to the other three models in con-sultations about PCa-related perioperative nursing and health education.Conclusion:In PCa-related perioperative nursing,large language models represented by Qwen-14B-Chat are expected to become powerful auxiliary tools to provide patients with more medical expertise and information support,so as to improve the patient compliance and the quality of clinical treatment and nursing.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Microglial surveillance plays an essential role in clearing misfolded proteins such as amyloid-beta, tau, and α-synuclein aggregates in neurodegenerative diseases. However, due to the complex structure and ambiguous pathogenic species of the misfolded proteins, a universal approach to remove the misfolded proteins remains unavailable. Here, we found that a polyphenol, α-mangostin, reprogrammed metabolism in the disease-associated microglia through shifting glycolysis to oxidative phosphorylation, which holistically rejuvenated microglial surveillance capacity to enhance microglial phagocytosis and autophagy-mediated degradation of multiple misfolded proteins. Nanoformulation of α-mangostin efficiently delivered α-mangostin to microglia, relieved the reactive status and rejuvenated the misfolded-proteins clearance capacity of microglia, which thus impressively relieved the neuropathological changes in both Alzheimer's disease and Parkinson's disease model mice. These findings provide direct evidences for the concept of rejuvenating microglial surveillance of multiple misfolded proteins through metabolic reprogramming, and demonstrate nanoformulated α-mangostin as a potential and universal therapy against neurodegenerative diseases.

Aim To explore the regulatory effect of Cangfudaotan Decoction on the ovarian Toll receptor 4 (TLR4)/nuclear transcription factor kBp65 (NF-κB p65) signaling pathway in obese PCOS-IR rats. Methods Forty-eight female rats were randomly divided into normal group (n = 8) and model group (n = 40). The obese PCOS-IR rats were established by letrozole (1 mg · kg

Methamphetamine abuse and HIV infection are extremely serious public health and social problems facing the world today. Methamphetamine and HIV-1 Tat protein can induce neurotoxicity in an individual and synergistic way, and neuroinflammation is one of the most important mechanisms for ca-using neurotoxicity. Neuroinflammation can be mediated by glial cells, cytokines, NLRP3 inflammasomes, etc. This paper reviews the research progress of neuroinflammation induced by methamphetamine and HIV-1 Tat protein in recent years, with the aim of providing reference and basis for further exploration of the mechanisms of neuroinflammation caused by them and effective drug intervention targets in the future.

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*

OBJECTIVE: To investigate the expression of CSF3R mutation in acute myeloid leukemia (AML) and analyze its clinical characteristics and prognosis. METHODS: A retrospective study was conducted in 212 patients with AML who were newly diagnosed in the Second Hospital of Shanxi Medical University from January 1th 2018 to June 30th 2021, including 22 patients with CSF3R mutations as mutation group and 190 patients with CSF3R wild type ［66 cases of them were screened by propensity score matching (PSM), as control group］. The early efficacy and survival between the two groups were compared. RESULTS: The median age of patients in the mutation group was 50(17-73) years old, and the ratio of male to female was 1.2:1 The main types were AML with maturation (11 cases) and acute myelomonocytic leukemia (9 cases). Prognostic stratification was carried out according to the risk stratification system of the European leukemia network in 2017, with 16 cases (72.73%) in the middle and high-risk group. At the initial diagnosis, the median count of white blood cell (WBC) was 44.75(1.30-368.71)×10⁹/L, among which 15 cases (68.18%) were >10×10⁹/L, and the median count of platelet (PLT) was 24(4-55)×10⁹/L. CSF3R T618I (68.18%) was a common mutation site, which had concomitant gene mutations, in which CEBPA mutation was the most common (10 cases, 45.45%), but only existed in CSF3R T618I mutation. The CR/CRi rate was 68.18% and 71.21% in the mutant group and the control group (P >0.05), the median over all survival time was 15 months and 9 months (P >0.05), and the median disease-free survival time was 8 months and 4 months (P >0.05), respectively. CONCLUSION Most AML patients with CSF3R mutation are middle-aged patients, the main types are AML with maturation and acute myelomonocytic leukemia, and most of them have middle and high-risk prognosis. CSF3R mutation may not be an independent prognostic marker for newly diagnosed AML patients.
Middle Aged ; Humans ; Male ; Female ; Aged ; Leukemia, Myelomonocytic, Acute ; Retrospective Studies ; Leukemia, Myeloid, Acute/diagnosis* ; Prognosis ; Mutation ; Receptors, Colony-Stimulating Factor/genetics*