Twelve compounds were isolated from the ethyl acetate fraction of the 80% aqueous ethanol extract of the roots and stems of Dalbergia rimosa Roxb. by silica gel, MCI, Sephadex LH-20 column chromatography, and semi-preparative HPLC. Their structures were identified by spectral analysis such as UV, IR, MS, 1D/2D NMR and by comparison with literature information as dalbergiquinol A (1), dalbergiquinol B (2), R-(-)-3′-hydroxy-2,4,5-trimethoxydalbergiquinol (3), neokhriol A (4), mucronulatol (5), (3R)-7,2′,3′-trihydroxy-4′-methoxy-isoflavane (6), isomucronulatol (7), (3S)-violanone (8), 3′-O-methylviolanone (9), eryvarin M (10), (±)-α,3,4,2′,4′-pentahydroxydihydrochalcone (11) and (-)-butin (12). Compound 1 and 2 are new compounds, and compounds 3-12 were isolated from this plant for the first time. Compounds 1, 2, 4, 6, 8, 11, 12 showed good scavenging effect on DPPH free radical.

Objective To summarize the epidemiological and clinical features of infectious diseases of the central nervous system(CNS)by a single-center analysis.Methods A retrospective analysis was conducted on the data of 1247 cases of CNS infectious diseases diagnosed and treated in the First Medical Center of PLA General Hospital from 2001 to 2020.Results The data for this group of CNS infectious diseases by disease type in descending order of number of cases were viruses 743(59.6％),Mycobacterium tuberculosis 249(20.0％),other bacteria 150(12.0％),fungi 68(5.5％),parasites 18(1.4％),Treponema pallidum 18(1.4％)and rickettsia 1(0.1％).The number of cases increased by 177 cases(33.1％)in the latter 10 years compared to the previous 10 years(P<0.05).No significant difference in seasonal distribution pattern of data between disease types(P>0.05).Male to female ratio is 1.87︰1,mostly under 60 years of age.Viruses are more likely to infect students,most often at university/college level and above,farmers are overrepresented among bacteria and Mycobacterium tuberculosis,and more infections of Treponema pallidum in workers.CNS infectious diseases are characterized by fever,headache and signs of meningeal irritation,with the adductor nerve being the more commonly involved cranial nerve.Matagenomic next-generation sequencing improves clinical diagnostic capabilities.The median hospital days for CNS infectious diseases are 18.00(11.00,27.00)and median hospital costs are ￥29,500(￥16,000,￥59,200).The mortality rate from CNS infectious diseases is 1.6％.Conclusions The incidence of CNS infectious diseases is increasing last ten years,with complex clinical presentation,severe symptoms and poor prognosis.Early and accurate diagnosis and standardized clinical treatment can significantly reduce the morbidity and mortality rate and ease the burden of disease.

ObjectiveHuman Ku70 protein mainly involves the non-homologous end joining (NHEJ) repair of double-stranded DNA breaks (DSB) through its DNA-binding properties, and it is recently reported having an RNA-binding ability. This paper is to explore whether Ku70 has RNA helicase activity and affects miRNA maturation. MethodsRNAs bound to Ku protein were analyzed by RNA immunoprecipitation sequencing (RIP-seq) and bioinfomatic anaylsis. The expression relationship between Ku protein and miRNAs was verified by Western blot (WB) and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assays. Binding ability of Ku protein to the RNAs was tested by biolayer interferometry (BLI) assay. RNA helicase activity of Ku protein was identified with EMSA assay. The effect of Ku70 regulated miR-124 on neuronal differentiation was performed by morphology analysis, WB and immunofluorescence assays with or without Zika virus (ZIKV) infection. ResultsWe revealed that the Ku70 protein had RNA helicase activity and affected miRNA maturation. Deficiency of Ku70 led to the up-regulation of a large number of mature miRNAs, especially neuronal specific miRNAs like miR-124. The knockdown of Ku70 promoted neuronal differentiation in human neural progenitor cells (hNPCs) and SH-SY5Y cells by boosting miR-124 maturation. Importantly, ZIKV infection reduced the expression of Ku70 whereas increased expression of miR-124 in hNPCs, and led to morphologically neuronal differentiation. ConclusionOur study revealed a novel function of Ku70 as an RNA helicase and regulating miRNA maturation. The reduced expression of Ku70 with ZIKV infection increased the expression of miR-124 and led to the premature differentiation of embryonic neural progenitor cells, which might be one of the causes of microcephaly.

Gallbladder carcinoma,a relatively rare malignancy within the biliary tract,presents a grave prognosis primarily due to asymptomatic early stages leading to advanced stage diagnosis and the absence of efficacious treatment options.Research has identified chronic inflammation,predom-inantly caused by gallstones,as a critical etiological factor.While surgical intervention offers potential curative outcomes in early stages,the majority of cases are identified too late for optimal surgical outcomes.Chemotherapy and targeted therapy,despite offering new therapeutic avenues,have not significantly improved overall survival rates.Thus,understanding the pathogenesis of gallbladder cancer,especially its association with key genetic and molecular pathways,is imperative for devising novel therapeutic strategies.This review delineates the epidemiology,pathogenesis,current treat-ment modalities,and research advancements in gallbladder cancer,aiming to provide innovative in-sights for clinical management and guide future research endeavors.

Objective To investigate the predictive value of morphology-voltage-P wave duration(MVP)electrocardiogram(ECG)score for major adverse cardiovascular events(MACE)in elder-ly patients with coronary heart disease(CHD)and atrial fibrillation(AF)within 1 year after treatment.Methods A total of 122 elderly CHD patients with concomitant AF admitted to our department from August 2020 to June 2023 were enrolled,and divided into MACE group(n=31)and non-MACE group(n=91)according to whether MACE occurred within 1 year after treat-ment.Their clinical data,treatment,laboratory indicators and ECG data were collected and ana-lyzed.Multivariate logistic regression analysis was used to identify the risk factors of MACE,and ROC curve was drawn to calculate the AUC value of MVP ECG score in the prediction of MACE occurrence.Results The MACE group had significantly higher Gensini score,C-reactive protein(CRP)level and MVP ECG score,and lower LVEF value than the non-MACE group(P＜0.01).Multivariate logistic regression analysis showed that Gensini score,CRP,LVEF and MVP ECG score were the influencing factors for MACE in elderly CHD patients complicated with AF within 1 year after treatment(OR=4.562,95％CI:1.881-11.064,P=0.001;OR=5.127,95％CI:1.865-14.096,P=0.001;OR=0.998,95％CI:0.687-0.959,P=0.012;OR=4.829,95％CI:2.343-9.953,P=0.001).ROC curve analysis indicated that the AUC value of MVP ECG score in predic-ting MACE within 1 year after treatment in these patients was 0.820,and the optimal cut-off val-ue was 3,the sensitivity was 77.78％and the specificity was 61.00％.Conclusion MVP ECG score has a good predictive value for MACE in elderly CHD patients with concomitant AF within 1 year after treatment.

Objective To compare the early outcomes of domestic third-generation magnetically levitated left ventricular assist device (LVAD) with or without concomitant mitral valvuloplasty (MVP). Methods The clinical data of 17 end-stage heart failure patients who underwent LVAD implantation combined with preoperative moderate to severe mitral regurgitation in Fuwai Central China Cardiovascular Hospital from May 2018 to March 2023 were retrospectively analyzed. The patients were divided into a LVAD group and a LVAD+MVP group based on whether MVP was performed simultaneously, and early outcomes were compared between the two groups. Results There were 4 patients in the LVAD group, all males, aged (43.5±5.9) years, and 13 patients in the LVAD+MVP group, including 10 males and 3 females, aged (46.8±16.7) years. All the patients were successful in concomitant MVP without mitral reguragitation occurrence. Compared with the LVAD group, the LVAD+MVP group had a lower pulmonary artery systolic pressure and pulmonary artery mean pressure 72 h after operation, but the difference was not statistically different (P>0.05). Pulmonary artery systolic pressure was significantly lower 1 week after operation, as well as pulmonary artery systolic blood pressure and pulmonary artery mean pressure at 1 month after operation (P<0.01). There was no statistically significant difference in blood loss, operation time, cardiopulmonary bypass time, aortic cross-clamping time, mechanical ventilation time, or ICU stay time between the two groups (P>0.05). The differences in 1-month postoperative mortality, acute kidney injury, reoperation, gastrointestinal bleeding, and thrombosis and other complications between the two groups were not statistically significant (P>0.05). Conclusion Concomitant MVP with implantation of domestic third-generation magnetically levitated LVAD is safe and feasible, and concomitant MVP may improve postoperative hemodynamics without significantly increasing perioperative mortality and complication rates.

Analyzing polysorbate 20(PS20)composition and the impact of each component on stability and safety is crucial due to formulation variations and individual tolerance.The similar structures and polarities of PS20 components make accurate separation,identification,and quantification challenging.In this work,a high-resolution quantitative method was developed using single-dimensional high-performance liquid chromatography(HPLC)with charged aerosol detection(CAD)to separate 18 key components with multiple esters.The separated components were characterized by ultra-high-performance liquid chro-matography-quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS)with an identical gradient as the HPLC-CAD analysis.The polysorbate compound database and library were expanded over 7-time compared to the commercial database.The method investigated differences in PS20 samples from various origins and grades for different dosage forms to evaluate the composition-process relationship.UHPLC-Q-TOF-MS identified 1329 to 1511 compounds in 4 batches of PS20 from different sources.The method observed the impact of 4 degradation conditions on peak components,identifying stable components and their tendencies to change.HPLC-CAD and UHPLC-Q-TOF-MS results provided insights into fingerprint differences,distinguishing quasi products.

Objective:To explore the efficacy and safety of bortezomib or thalidomide combined with recombinant human erythropoietin(rhEPO)in the treatment of multiple myeloma(MM).Methods:A total of 80 patients with MM who were treated in the Second People's Hospital ofWuhu from January 2013 to December 2018 were selected as the research subjects,and they were divided into bortezomib group(n=40)and thalidomide group(n=40)by the simple randomization method.The bortezomib group received bortezomib regimen combined with rhEPO therapy,and the thalidomide group was given thalidomide regimen combined with rhEPO therapy,and all patients were treated for 3 courses with every 3 weeks as a course of treatment.The clinical efficacy after 3 courses of treatment,and tumor-related biochemical indicators[lactate dehydrogenase(LDH),β 2-microglobulin([3 2-MG),vascular endothelial growth factor(VEGF),apoptosis inhibitory protein Survivin],bone marrow-related indicators[serum M-protein,bone marrow plasma cells,hemoglobin(Hb)]and coagulation function indicators[activated partial thromboplastin time(APTT),prothrombin time(PT),plasminogen activator inhibitor(PAI),total circulating microparticles(TMPs)]before treatment and after 3 courses of treatment were compared between the two groups of patients.The occurrence of adverse reactions during the treatment in the two groups of patients was recorded.Results:After 3 courses of treatment,the ORR rate of 92.5％in bortezomib group was higher than 90.0％in thalidomide group,but the difference was not statistically significant(P＞0.05).The levels of LDH,[3 2-MG,VEGF,Survivin,serum M-protein,bone marrow plasma cells,APTT,PT,PAI and TMPs in the two groups after 3 courses of treatment were significantly lower or shorter than those before treatment,and the above indicators in bortezomib group were significantly lower or shorter than those in thalidomide group(P＜0.05).After 3 courses of treatment,the expression level of Hb in the two groups was significantly higher than that before treatment,and the Hb level in bortezomib group was significantly higher than that in thalidomide group(P＜0.05).During the treatment process,the incidence rates of adverse reactions in bortezomib group were significantly lower than those in thalidomide group(P＜0.05).Conclusion:Thalidomide regimen or bortezomib regimen combined with rhEPO has similar clinical efficacy on MM,but bortezomib regimen combined with rhEPO is more prominent and safer on improving tumor-related biochemical indicators,bone marrow-related indicators and coagulation status in patients with MM.

Objective To analyze the molecular markers of various nuclei in the human basal ganglia and the differentially expressed genes(DEGs)among different nuclei,gender,and Parkinson's disease(PD),followed by the biological function annotations of the DEGs.Methods Forty-five specimens of basal ganglia from 10 human postmortem brains were divided into control and PD groups,and the control group was further categorized into female and male groups.RNA from each sample was extracted for high-throughput transcriptome sequencing.Bioinformatic analysis was conducted to identify molecular markers of each nuclei in the control group,nuclei-specific,gender-specific,and PD-specific DEGs,followed by gene enrichment analysis and functional annotation.Results Sequencing analysis revealed top DEGs such as DRD1,FOXG1,and FAM183A in the caudate;SLC6A3,EN1,SLC18A2,and TH in the substantia nigra;MEPE and FGF10 in the globus pallidus;and SLC17A6,PMCH,and SHOX2 in the subthalamic nucleus.In them,putamen showed some overlapping DEGs with caudate,such as DRD1 and FOXG1.A significant number of DEGs were identified among different nuclei in the control group,with the highest number between caudate and globus pallidus(9321),followed by putamen and globus pallidus(6341),caudate and substantia nigra(6054),and substantia nigra and subthalamic nucleus(44).Gene enrichment analysis showed that downregulated DEGs between caudate and globus pallidus were significantly enriched in processes like myelination of neurons and cell migration.Upregulated DEGs between putamen and globus pallidus were enriched processes like chemical synaptic transmission and regulation of membrane potential,while downregulated DEGs were enriched in myelination and cell adhesion.Upregulated DEGs between caudate and substantia nigra were enriched in processes like chemical synaptic transmission and axonal conduction,while downregulated DEGs were enriched in myelination of neurons.Totally 468,548,1402,333,and 341 gender-specific upregulated DEGs and 756,988,2532,444,and 1372 downregulated DEGs were identified in caudate,putamen,substantia nigra,globus pallidus,and subthalamus nucleus.Gene enrichment analysis revealed upregulated DEGs mostly enriched in pathways related to immune response and downregulated DEGs in chemical synaptic transmission.At last,709,852,276,507,and 416 PD-specific upregulated DEGs and 830,2014,1218,836,and 1730 downregulated DEGs were identified in caudate,putamen,substantia nigra,globus pallidus,and subthalamus nucleus.Gene enrichment analysis revealed upregulated DEGs mostly enriched in apoptotic regulation and downregulated DEGs in chemical synaptic transmission and action potential regulation.Conclusion We identified and analysed the molecular markers of different human basal ganglia nuclei,as well as DEGs among different nuclei,different gender,and between control and PD.

Objective:To explore the influencing factors for low back pain after decompression and fusion in patients with lumbar spinal stenosis and to construct a Nomogram prediction model.Methods:A retrospective study was conducted to analyze the 132 patients with lumbar spinal stenosis who had been treated at Department of Orthopedics, Nanyang Central Hospital from May 2021 to March 2022. The patients were divided into 2 groups according to their visual analog scale (VAS) pain score: a back pain-free group (104 cases with VAS ≤ 2) and a back pain group (28 cases with VAS > 2). Univariate and multiple logistic regression analyses were employed to identify the influencing factors for occurrence of lower back pain and a Nomogram prediction model for the risk of lower back pain was constructed in patients with lumbar spinal stenosis after decompression and fusion. The accuracy of the model was assessed using the receiver operating characteristic (ROC) curve. Furthermore, the model accuracy was pre-tested using an external validation model which included 66 illegible patients with lumbar spinal stenosis treated at Department of Orthopedics, Nanyang Central Hospital from May 2022 to March 2023. A comparison was made between the outcomes predicted by the model and the actual outcomes observed. The fit of the model was evaluated through the Hosmer-Lemeshow test.Results:The results of the multifactorial analysis indicated that interleukin (IL-1 β), postoperative aseptic inflammation in the vertebral canal, and intraoperative blood loss were independent influencing factors for the occurrence of lower back pain (all P < 0.05). A risk Nomogram prediction model was thus established based on these factors. The area under the curve (AUC) was 0.975, the sensitivity 92.90%, the specificity 91.30%, and the Youden index 0.842. External validation of the model showed an overall accuracy of 99.80%. The Hosmer-Lemeshow test demonstrated good model fit ( χ2=3.512, P=0.898). Conclusions:IL-1 β, postoperative aseptic inflammation in the vertebral canal, and intraoperative blood loss may be the primary influencing factors for the occurrence of lower back pain in patients with lumbar spinal stenosis after decompression fusion surgery. The Nomogram prediction model based on these influencing factors demonstrates excellent predictive efficacy for lower back pain.