Albendazole-glucan particles(ABZ-GPS)and abendazole(ABZ)were used to treat secondary alveolar echinococ-cosis in mice.The therapeutic effects of ABZ-GPS on alveolar echinococcosis in vivo were evaluated,and the feasibility of using glucan particles as anti-hydatid drug carriers was further verified.Mice with echinococcosis were randomly divided into an ABZ group,glucan nanoparticle(GP)group,ABZ-GPS group,and control group.After four courses of administration with a final concentration of 50 mg/mL,the therapeutic effects of ABZ-GPS were evaluated on the basis of imaging,histopathological changes,ultrastructure,and immunology.After ABZ-GPS and ABZ administration,clear liver lesion tissue necrosis and large numbers of infiltrating lymphocytes were observed.Significant differences in the average cyst wet weight(t=7.83,P＜0.05),were observed between the ABZ-GPS group and ABZ group.Imaging revealed that ABZ-GPs were targeted to liver tissue.Pa-thology and ultrastructure analyses demonstrated that the alveolar hydatid cells in the liver in the control group and GP group grew well,and the vesicles were large,filled with cystic fluid,and translucent or transparent;the cyst wall tension was high;no calcification was observed;the stratum corneum and germinal layer were clear;and more fertile capsules and different num-bers of protocephalospora were present in the liver.In the ABZ group,the capsular cavity collapsed,and showed partial necro-sis and lymphocyte infiltration.In the ABZ-GP group,the corneum and germinal layer of echinococcus vesicles were difficult to identify,and we observed bulbous necrosis,central calcification,fibrous tissue hyperplasia,inflammatory cell infiltration,coarser,shorter or absent microvilli of the germinal layer,nuclear shrinkage,dissolution or disappearance,clear expansion of cytoplasmic microtubules,and myelin-like or vacuole-like changes.Therefore,ABZ-GPs showed good targeting and killing ac-tivity in vivo in mice with secondary alveolar coccosis.

Albendazole-glucan particles(ABZ-GPS)and abendazole(ABZ)were used to treat secondary alveolar echinococ-cosis in mice.The therapeutic effects of ABZ-GPS on alveolar echinococcosis in vivo were evaluated,and the feasibility of using glucan particles as anti-hydatid drug carriers was further verified.Mice with echinococcosis were randomly divided into an ABZ group,glucan nanoparticle(GP)group,ABZ-GPS group,and control group.After four courses of administration with a final concentration of 50 mg/mL,the therapeutic effects of ABZ-GPS were evaluated on the basis of imaging,histopathological changes,ultrastructure,and immunology.After ABZ-GPS and ABZ administration,clear liver lesion tissue necrosis and large numbers of infiltrating lymphocytes were observed.Significant differences in the average cyst wet weight(t=7.83,P＜0.05),were observed between the ABZ-GPS group and ABZ group.Imaging revealed that ABZ-GPs were targeted to liver tissue.Pa-thology and ultrastructure analyses demonstrated that the alveolar hydatid cells in the liver in the control group and GP group grew well,and the vesicles were large,filled with cystic fluid,and translucent or transparent;the cyst wall tension was high;no calcification was observed;the stratum corneum and germinal layer were clear;and more fertile capsules and different num-bers of protocephalospora were present in the liver.In the ABZ group,the capsular cavity collapsed,and showed partial necro-sis and lymphocyte infiltration.In the ABZ-GP group,the corneum and germinal layer of echinococcus vesicles were difficult to identify,and we observed bulbous necrosis,central calcification,fibrous tissue hyperplasia,inflammatory cell infiltration,coarser,shorter or absent microvilli of the germinal layer,nuclear shrinkage,dissolution or disappearance,clear expansion of cytoplasmic microtubules,and myelin-like or vacuole-like changes.Therefore,ABZ-GPs showed good targeting and killing ac-tivity in vivo in mice with secondary alveolar coccosis.

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

Objective To describe the current state of research and future research hotspots through a metrological analysis of the literature in the field of forensic anthropological remains identification re-search.Methods The data retrieved and extracted from the Web of Science Core Collection (WoSCC),the core database of the Web of Science information service platform (hereinafter referred to as "WoS"),was used to analyze the trends and topic changes in research on forensic identification of human re-mains from 1991 to 2022.Network visualisation of publication trends,countries (regions),institutions,authors and topics related to the identification of remains in forensic anthropology was analysed using python 3.9.2 and Gephi 0.10.Results A total of 873 papers written in English in the field of forensic anthropological remains identification research were obtained.The journal with the largest number of publications was Forensic Science International (164 articles).The country (region) with the largest number of published papers was China (90 articles).Katholieke Univ Leuven (Netherlands,21 articles) was the institution with the largest number of publications.Topic analysis revealed that the focus of forensic anthropological remains identification research was sex estimation and age estimation,and the most commonly studied remains were teeth.Conclusion The volume of publications in the field of forensic anthropological remains identification research has a distinct phasing.However,the scope of both international and domestic collaborations remains limited.Traditionally,human remains identifica-tion has primarily relied on key areas such as the pelvis,skull,and teeth.Looking ahead,future re-search will likely focus on the more accurate and efficient identification of multiple skeletal remains through the use of machine learning and deep learning techniques.

Objective To establish drug use evaluation(DUE)standard of etamsylate and to evaluate the use of etamsylate by weighted superior and inferior solution distance(TOPSIS)method,so as to provide a basis for promoting its clinical rational use.Methods Based on the instructions of etamsylate for injection,the DUE criteria of etamsylate were established according to the relevant guidelines of hemostasis at home and abroad,evidence-based literature and expert consultation.The weighted TOPSIS method based on the attribute hierarchy model was used to evaluate the utilization of etamsylate in Beijing Beiya Orthopaedic Hospital.Results Among the 119 cases,2 cases(1.68%)were with the relative closeness degree between each case and the optimal regimen(Ci)no less than 0.8,which was evaluated as reasonable;70 cases(58.82%)were with the Ci ranging between 0.8 and 0.6,which was evaluated as basically reasonable;47 cases(39.50%)were with the Ci less than 60%,which was evaluated as unreasonable.The top three unreasonable rates were dose and frequency(66.39%),configuration method(49.58%),and drug interaction(24.37%).Conclusion The method of DUE of etamsylate based on weighted TOPSIS method can synthesize several evaluation indexes,and the evaluation method is simple and flexible.The rational rate of use of etamsylate in this hospital is low,especially there are problems in configuration method,administration dose and frequency,drug interaction,treatment course and so on,and the management still needs to be strengthened.

Objective: To evaluate the long-term efficacy and safety of the implantable ventricular assist system EVAHEART I in clinical use. Methods: Fifteen consecutive patients with end-stage heart failure who received left ventricular assist device therapy in Fuwai Hospital from January 2018 to December 2021 were enrolled in this study, their clinical data were retrospectively analyzed. Cardiac function, liver and kidney function, New York Heart Association (NYHA) classification, 6-minute walk distance and quality of life were evaluated before implantation and at 1, 6, 12, 24 and 36 months after device implantation. Drive cable infection, hemolysis, cerebrovascular events, mechanical failure, abnormally high-power consumption and abnormal pump flow were recorded during follow up. Results: All 15 patients were male, mean average age was (43.0±7.5) years, including 11 cases of dilated cardiomyopathy, 2 cases of ischemic cardiomyopathy, and 2 cases of valvular heart disease. All patients were hemodynamically stable on more than one intravenous vasoactive drugs, and 3 patients were supported by preoperative intra aortic balloon pump (IABP). Compared with before device implantation, left ventricular end-diastolic dimension (LVEDD) was significantly decreased ((80.93±6.69) mm vs. (63.73±6.31) mm, P<0.05), brain natriuretic peptide (BNP), total bilirubin and creatinine were also significantly decreased ((3 544.85±1 723.77) ng/L vs. (770.80±406.39) ng/L; (21.28±10.51) μmol/L vs. (17.39±7.68) μmol/L; (95.82±34.88) μmol/L vs. (77.32±43.81) μmol/L; P<0.05) at 1 week after device implantation. All patients in this group were in NYHA class Ⅳ before implantation, and 9 patients could recover to NYHA class Ⅲ, 3 to class Ⅱ, and 3 to class Ⅰ at 1 month after operation. All patients recovered to class Ⅰ-Ⅱ at 6 months after operation. The 6-minute walk distance, total quality of life and visual analogue scale were significantly increased and improved at 1 month after implantation compared with those before operation (P<0.05). All patients were implanted with EVAHEART I at speeds between 1 700-1 950 rpm, flow rates between 3.2-4.5 L/min, power consumption of 3-9 W. The 1-year, 2-year, and 3-year survival rates were 100%, 87%, and 80%, respectively. Three patients died of multiple organ failure at 412, 610, and 872 d after surgery, respectively. During long-term device carrying, 3 patients developed drive cable infection on 170, 220, and 475 d after surgery, respectively, and were cured by dressing change. One patient underwent heart transplantation at 155 d after surgery due to bacteremia. Three patients developed transient ischemic attack and 1 patient developed hemorrhagic stroke events, all cured without sequelae. Conclusion: EVAHEART I implantable left heart assist system can effectively treat critically ill patients with end-stage heart failure, can be carried for long-term life and significantly improve the survival rate, with clear clinical efficacy.
Humans ; Male ; Adult ; Middle Aged ; Female ; Heart Failure/complications* ; Follow-Up Studies ; Retrospective Studies ; Heart-Assist Devices ; Quality of Life

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.
Humans ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Treatment Outcome

OBJECTIVE: To develop and validate a user-friendly risk score for older mitral regurgitation (MR) patients, referred to as the Elder-MR score. METHODS: The China Senile Valvular Heart Disease (China-DVD) Cohort Study functioned as the development cohort, while the China Valvular Heart Disease (China-VHD) Study was employed for external validation. We included patients aged 60 years and above receiving medical treatment for moderate or severe MR (2274 patients in the development cohort and 1929 patients in the validation cohort). Candidate predictors were chosen using Cox's proportional hazards model and stepwise selection with Akaike's information criterion. RESULTS: Eight predictors were identified: age ≥ 75 years, body mass index < 20 kg/m², NYHA class III/IV, secondary MR, anemia, estimated glomerular filtration rate < 60 mL/min per 1.73 m², albumin < 35 g/L, and left ventricular ejection fraction < 60%. The model displayed satisfactory performance in predicting one-year mortality in both the development cohort (C-statistic = 0.73, 95% CI: 0.69-0.77, Brier score = 0.06) and the validation cohort (C-statistic = 0.73, 95% CI: 0.68-0.78, Brier score = 0.06). The Elder-MR score ranges from 0 to 15 points. At a one-year follow-up, each point increase in the Elder-MR score represents a 1.27-fold risk of death (HR = 1.27, 95% CI: 1.21-1.34, P < 0.001) in the development cohort and a 1.24-fold risk of death (HR = 1.24, 95% CI: 1.17-1.30, P < 0.001) in the validation cohort. Compared to EuroSCORE II, the Elder-MR score demonstrated superior predictive accuracy for one-year mortality in the validation cohort (C-statistic = 0.71 vs. 0.70, net reclassification improvement = 0.320, P < 0.01; integrated discrimination improvement = 0.029, P < 0.01). CONCLUSIONS The Elder-MR score may serve as an effective risk stratification tool to assist clinical decision-making in older MR patients.

ObjectiveTo analyze the transcriptome characteristics of Xianlian Jiedu prescription （XLJDP） in the intervention of colorectal carcinoma by high-throughput cDNA-sequencing （RNA-seq）. MethodNinety male C57BL/6 mice were randomly divided into the control group， colorectal carcinoma due to dampness， heat， stasis， and toxin model group， and XLJDP group， with 30 mice in each group. Mice in the model group and XLJDP group were fed a high-fat diet and provided with azoxymethane and dextran sodium sulfate （AOM/DSS） for inducing colorectal carcinoma. Those in the XLJDP group were further treated with intragastric administration of 12.9 g·kg^-1 XLJDP since the day of modeling for 112 days. The colorectal tissues were collected from each group 4 h after the last drug treatment and stained with hematoxylin-eosin （HE） and methylene blue for observing the pathological changes. The total RNA was extracted from colorectal tissues for RNA-Seq-based transcriptome profiling， followed by gene oncology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment analysis and the screening and verification of differentially expressed genes. ResultCompared with the model group， XLJDP significantly relieved the colorectal congestion and edema and decreased tumor number and volume in mouse colorectal tissues. The methylene blue staining results indicated that XLJDP significantly suppressed the development of aberrant crypt foci （ACF，P<0.01）. As revealed by HE staining， XLJDP significantly alleviated the injury and dysplasia of colorectal tissues. Transcriptome analysis identified 615 differentially expressed genes （446 up-regulated and 169 down-regulated） between the model group and the blank group and 54 differentially expressed genes （29 up-regulated and 25 down-regulated） between the XLJDP group and model group. XLJDP mainly affected the expression of NIMA-related protein kinase 7 gene （Nek7， P<0.01）， Mucin 16 （Muc16， P<0.01）， SiahE3 ubiquitin protein ligase family member 3 （Siah3， P<0.01）， regenerating islet-derived protein 3-gamma （Reg3g， P<0.01）， RNA polymerase Ⅱ elongation factor-associated factor 2 （Eaf2， P<0.01）， transforming growth factor‐alfa gene （TGF-α， P<0.05）， secretoglobin family 1A member 1 （Scgb1a1， P<0.05）， family with sequence similarity 227 member B （Fam227B， P<0.05）， cytochrome P450 family 2 subfamily c polypeptide 40 （Cyp2c40， P<0.01）， and ankyrin repeat and EF-hand domain containing protein 1 （Ankef1， P<0.05）. Enrichment analysis showed that intestinal epithelial cell proliferation， metabolism of xenobiotics by cytochrome P450， and arachidonic acid metabolism signaling pathway were significantly enriched. ConclusionXLJDP is able to interfere with colorectal tumorigenesis and development due to dampness， heat， stasis， and toxin in mice， which has been proved by transcriptome analysis to be related to the regulation of metabolism-related pathways.

Child ; Consensus ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Respiratory System