Objective To explore the relationship between dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)and clinical pathological features of invasive breast cancer and lymphovascular invasion(LVI).Methods Imaging and clinical pathological data were retrospectively collected from 508 patients with invasive breast cancer who underwent breast DCE-MRI at the First Medical Center of Chinese PLA General Hospital from January 2019 to August 2021.Patients were divided into the LVI-positive(LVI+)group(n=79)and LVI-negative(LVI-)group(n=429)based on postoperative pathological results.Univariate and multivariate logistic regression analyses were used to identify risk factors for LVI.Results Compared with LVI-group,LVI+group had a higher proportion of patients aged<45 years(44.3%vs.27.0%,P=0.002),non-mass-like enhancement(NME)(31.7%vs.17.7%,P=0.004),Ki-67 expression rate(40.0%vs.30.0%,P<0.001),high Ki-67 expression(94.9%vs.78.1%,P=0.001),Luminal B subtype(76.0%vs.60.1%,P=0.008),and positive axillary lymph nodes rate(72.2%vs.31.5%,P<0.001),while the proportion of Luminal A subtype was lower(2.5%vs.21.5%,P<0.001).Univariate and multivariate logistic regression analyses showed that age≥45 years(OR=0.468,95%CI 0.280-0.783,P=0.004)was an independent protective factor for LVI,while NME(OR=1.987,95%CI 1.126-3.444,P=0.016)was an independent risk factor.Compared with Luminal A subtype,patients with Luminal B subtype(OR=10.482,95%CI 3.164-64.923,P=0.001),HER-2 overexpression subtype(OR=11.571,95%CI 2.755-79.341,P=0.003)and triple-negative subtypes(OR=8.433,95%CI 1.985-57.908,P=0.009)had a higher risk of LVI.Conclusions Age≥45 years is an independent protective factor for LVI,while NME is an independent risk factor.Among molecular subtypes,patients with Luminal B,HER-2 overexpression and triple-negative subtypes have a higher risk of LVI compared with the Luminal A subtype.

Objective To construct machine learning(ML)model for predicting early neurologi-cal deterioration(END)after intravenous thrombolysis(IVT)in patients with acute ischemic stroke(AIS),and to analyze risk factors of END using Shapley additive explanations(SHAP).Methods A total of 97 AIS patients who received IVT were enrolled.Patients were divided into END group(18 cases)and non-END group(79 cases)based on whether they experienced END within 24 hours post-IVT.All patients were randomly divided into training set(n=68)and validation set(n=29)at ra-tio of 7 to 3.Univariate and least absolute shrinkage and selection operator(LASSO)analyses were performed to screen important feature variables associated with END from clinical data.Six ML algo-rithms,including random forest,light gradient boosting machine,decision tree,support vector ma-chine,k-nearest neighbors and extreme gradient boosting,were employed to construct predictive mod-els.Receiver operating characteristic(ROC)curves,calibration curves and clinical decision curve analysis(DC A)were used to evaluate the performance of each ML model.The SHAP method was introduced to interpret the optimal ML model.Results Among the six ML algorithm models,the random forest model was identified as best predictive model.In the training set,it achieved area un-der the curve(AUC)of 0.909,with specificity,precision,recall and F1 score being 0.873,0.856,0.910 and 0.825,respectively.In the validation set,its AUC was 0.915,with correspond-ing values of 0.824,0.800,0.945 and 0.834.Calibration curves and DC A demonstrated that the random forest model had higher prediction accuracy and clinical net benefit.SHAP variable impor-tance plots revealed that the top six contributing imaging factors to END were large-area cerebral in-farction,pre-thrombolysis National Institutes of Health Stroke Scale(NIHSS)score,door-to-needle time(DNT),history of atrial fibrillation,white blood cell(WBC)levels and history of diabetes.Conclusion ML models can effectively predict the risk of END in IVT patients,with the random forest model demonstrating the best predictive performance.Combining SHAP for model visualization interpretation aids clinicians in understanding the contribution of each feature variable to the predic-tion results,thereby facilitating targeted preventive treatment strategies.

The study was conducted to investigate the mechanism of Xinyang Tablets( XYP) in modulating the fat mass and obesity-associated protein(FTO)/N6-methyladenosine(m6A) signaling pathway to ameliorate ventricular remodeling in heart failure(HF). A mouse model of HF was established by transverse aortic constriction(TAC). Mice were randomized into sham, model, XYP(low, medium, and high doses), and positive control( perindopril) groups(n= 10). From day 3 post-surgery, mice were administrated with corresponding drugs by gavage for 6 consecutive weeks. Following the treatment, echocardiography was employed to evaluate the cardiac function, and RT-qPCR was employed to determine the relative m RNA levels of key markers, including atrial natriuretic peptide( ANP), B-type natriuretic peptide( BNP), β-myosin heavy chain(β-MHC), collagen type I alpha chain(Col1α), collagen type Ⅲ alpha chain(Col3α), alpha smooth muscle actin(α-SMA), and FTO. The cardiac tissue was stained with Masson's trichrome and wheat germ agglutinin(WGA) to reveal the pathological changes. Immunohistochemistry was employed to detect the expression levels of Col1α, Col3α, α-SMA, and FTO in the myocardial tissue. The m6A modification level in the myocardial tissue was measured by the m6A assay kit. An H9c2 cell model of cardiomyocyte injury was induced by angiotensin Ⅱ(AngⅡ), and small interfering RNA(siRNA) was employed to knock down FTO expression. RT-qPCR was conducted to assess the relative m RNA levels of FTO and other genes associated with cardiac remodeling. The m6A modification level was measured by the m6A assay kit, and Western blot was employed to determine the phosphorylated phosphatidylinositol 3-kinase(p-PI3K)/phosphatidylinositol 3-kinase(PI3K) and phosphorylated serine/threonine kinase(p-Akt)/serine/threonine kinase(Akt) ratios in cardiomyocytes. The results of animal experiments showed that the XYP treatment significantly improved the cardiac function, reduced fibrosis, up-regulated the m RNA and protein levels of FTO, and lowered the m6A modification level compared with the model group. The results of cell experiments showed that the XYP-containing serum markedly up-regulated the m RNA level of FTO while decreasing the m6A modification level and the p-PI3K/PI3K and p-Akt/Akt ratios in cardiomyocytes. Furthermore, FTO knockdown reversed the protective effects of XYP-containing serum on Ang Ⅱ-induced cardiomyocyte hypertrophy. In conclusion, XYP may ameliorate ventricular remodeling by regulating the FTO/m6A axis, thereby inhibiting the activation of the PI3K/Akt signaling pathway.
Animals ; Ventricular Remodeling/drug effects* ; Heart Failure/physiopathology* ; Signal Transduction/drug effects* ; Mice ; Male ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred C57BL ; Humans ; Adenosine/analogs & derivatives* ; Myocytes, Cardiac/metabolism* ; Disease Models, Animal

This study investigates the effect and underlying mechanism of Guizhi Tongluo Tablets(GZTL) in treating atherosclerosis(AS) in a mouse model. Apolipoprotein E-knockout(ApoE~(-/-)) mice were randomly assigned to the following groups: model, high-, medium-, and low-dose GZTL, and atorvastatin(ATV), and age-matched C57BL/6J mice were selected as the control group. ApoE~(-/-) mice in other groups except the control group were fed with a high-fat diet for the modeling of AS and administrated with corresponding drugs via gavage for 8 weeks. General conditions, signs of blood stasis, and body mass of mice were monitored. Aortic plaques and their stability were assessed by hematoxylin-eosin, Masson, and oil red O staining. Serum levels of total cholesterol(TC), triglycerides(TG), and low-density lipoprotein cholesterol(LDL-C) were measured by biochemical assays, and those of interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) were determined via enzyme-linked immunosorbent assay. Apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL). Single-cell RNA sequencing(scRNA-seq) was employed to analyze the differential expression of CD72hi macrophages(CD72hi-Mφ) in the aortas of AS patients and mice. The immunofluorescence assay was employed to visualize CD72hi-Mφ expression in mouse aortic plaques, and real-time fluorescence quantitative PCR was utilized to determine the mRNA levels of IL-1β, TNF-α, and IL-6 in the aorta. The results demonstrated that compared with the control group, the model group exhibited significant increases in body mass, aortic plaque area proportion, necrotic core area proportion, and lipid deposition, a notable decrease in collagen fiber content, and an increase in apoptosis. Additionally, the model group showcased elevated serum levels of TC, TG, LDL-C, IL-1β, TNF-α, and IL-6, alongside marked upregulations in the mRNA levels of IL-1β, TNF-α, and IL-6 in the aorta. In comparison with the model group, the GZTL groups and the ATV group showed a reduction in body mass, and the medium-and high-dose GZTL groups and the ATV group demonstrated reductions in aortic plaque area proportion, necrotic core area proportion, and lipid deposition, an increase in collagen fiber content, and a decrease in apoptosis. Furthermore, the treatment goups showcased lowered serum levels of TC, TG, LDL-C, IL-1β, TNF-α, and IL-6. The data of scRNA-seq revealed significantly elevated CD72hi-Mφ signaling in carotid plaques of AS patients compared with that in the normal arterial tissue. Animal experiments confirmed that CD72hi-Mφ expression, along with several pro-inflammatory cytokines, was significantly upregulated in the aortas of AS mice, which were downregulated by GZTL treatment. In conclusion, GZTL may alleviate AS by inhibiting CD72hi-Mφ activity.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Atherosclerosis/immunology* ; Mice ; Mice, Inbred C57BL ; Macrophages/immunology* ; Male ; Humans ; Apolipoproteins E/genetics* ; Tablets ; Tumor Necrosis Factor-alpha/genetics* ; Apoptosis/drug effects* ; Interleukin-1beta/genetics* ; Interleukin-6/genetics* ; Disease Models, Animal ; Mice, Knockout

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

Objective:To investigate the effects of surgical timing on incidence of perioperative complications and postoperative 30-day mortality in elderly patients with hip fracture.Methods:The data were retrospectively analyzed of the 450 elderly patients with hip fracture who had been admitted to Department of Joint Surgery, Beijing Shijitan Hospital, Capital Medical University from January 2016 to December 2021. The patients were divided into 2 groups according to the time from admission to surgery. In the early surgery group of 143 cases [41 males and 102 females with an age of 82(75, 86) years], the time from admission to surgery was ≤ 48 hours. In the delayed surgery group of 307 cases [88 males and 219 females with an age of 83(77, 87) years], the time from admission to surgery was over 48 hours. The 2 groups were compared in terms of comorbidities, perioperative complications, death events within postoperative 30 days, ICU transfer rate and total length of hospital stay.Results:There was no significant difference in the preoperative general data like age and gender between the 2 groups, indicating comparability ( P>0.05). The proportions of patients with coronary atherosclerotic heart disease [30.0%(92/307)], a stroke history [19.9%(61/307)], abnormal heart function [55.4%(170/307)] and abnormal kidney function [24.4%(75/307)] in the delayed surgery group were significantly higher than those in the early surgery group [18.2%(26/143), 10.5% (15/143), 39.2%(56/143), and 12.6%(18/143)] ( P<0.05). The proportions of perioperative pulmonary infection [22.5% (69/307)] and urinary infection [21.2%(65/307)] in the delayed operation group were significantly higher than those in the early operation group [11.9%(17/143) and 11.2%(16/143)] ( P<0.05). The total hospital stay in the delayed operation group [18(14, 22) d] was significantly longer than that in the early operation group [14(10, 17) d] ( P<0.05). There was no significant difference in ICU transfer rate or postoperative 30-day mortality between the 2 groups ( P>0.05). Conclusion:For elderly patients with hip fracture, delayed surgery may increase the incidence of pulmonary infection and urinary infection, and extend their total hospital stay, but have no effect on the postoperative 30-day mortality.

Objective:To investigate the effects of surgical timing on incidence of perioperative complications and postoperative 30-day mortality in elderly patients with hip fracture.Methods:The data were retrospectively analyzed of the 450 elderly patients with hip fracture who had been admitted to Department of Joint Surgery, Beijing Shijitan Hospital, Capital Medical University from January 2016 to December 2021. The patients were divided into 2 groups according to the time from admission to surgery. In the early surgery group of 143 cases [41 males and 102 females with an age of 82(75, 86) years], the time from admission to surgery was ≤ 48 hours. In the delayed surgery group of 307 cases [88 males and 219 females with an age of 83(77, 87) years], the time from admission to surgery was over 48 hours. The 2 groups were compared in terms of comorbidities, perioperative complications, death events within postoperative 30 days, ICU transfer rate and total length of hospital stay.Results:There was no significant difference in the preoperative general data like age and gender between the 2 groups, indicating comparability ( P>0.05). The proportions of patients with coronary atherosclerotic heart disease [30.0%(92/307)], a stroke history [19.9%(61/307)], abnormal heart function [55.4%(170/307)] and abnormal kidney function [24.4%(75/307)] in the delayed surgery group were significantly higher than those in the early surgery group [18.2%(26/143), 10.5% (15/143), 39.2%(56/143), and 12.6%(18/143)] ( P<0.05). The proportions of perioperative pulmonary infection [22.5% (69/307)] and urinary infection [21.2%(65/307)] in the delayed operation group were significantly higher than those in the early operation group [11.9%(17/143) and 11.2%(16/143)] ( P<0.05). The total hospital stay in the delayed operation group [18(14, 22) d] was significantly longer than that in the early operation group [14(10, 17) d] ( P<0.05). There was no significant difference in ICU transfer rate or postoperative 30-day mortality between the 2 groups ( P>0.05). Conclusion:For elderly patients with hip fracture, delayed surgery may increase the incidence of pulmonary infection and urinary infection, and extend their total hospital stay, but have no effect on the postoperative 30-day mortality.

The lymphatic system, as well as pathological changes of the lymphatic system, underlies the progress of an array of diseases and conditions, including cancer, inflammation and autoimmune disorders, infectious diseases and metabolic syndrome. A variety of biological targets in the lymphatic system can be employed to modulate these high-burden diseases, and the pharmacokinetics and drug delivery strategies in the context of lymphatics are of critical importance to optimise drug exposure to lymphatic-related targets. As such, research and drug development in this field has gained increasing attention in recent years. This article aims to provide an overview of pharmaceutical research with a focus on the lymphatic system and therapeutic targets within the lymphatics, followed by lymphatic drug delivery approaches, which may be of interest for researchers in academia, pharmaceutical industry and regulatory sciences.

The aim of this study was to clarify the genetic diversity and population history of Ixodes persulcatus in some ar-eas of Inner Mongolia in order to provide accurate data for effective vector control programs and reveal the transmission mecha-nism.Samples were collected in 10 areas of Inner Mongolia during the active tick season(April 2021-July 2023)using the flag-dragging and manual sampling methods.The 16S rRNA and COI gene were sequenced to clarify genetic diversity of I.per-sulcatus.The positivity rates for the COI gene and 16S rRNA were 90.00％and 98.33％respectively.Overall,18 and 15 haplotypes were identified for the COI gene and 16S rRNA,respectively,with a total haplotype diversity＞0.762 and total nucleotide diversity＜0.005.The Tajima's values and Fu's Fs were negative for significance.A nucleotide mismatch map was shown as a single peak.The genetic differentiation index FST of the population indicates a small degree of genetic differ-entiation of the population,while analysis of molecular vari-ance indicates that the variation within populations was greater than between populations.Phylogenetic tree and haplotype network plots showed confounding distributions between hap-lotypes.I.persulcatus from the Hinggan League and Hulun-buir regions can adapt to environmental changes and possess abundant genetic diversity.Genetic differentiation is mainly concentrated within the population and no geographical isolation was observed.

This is the first reported case of a female with monkeypox infection in Kunming City,Yunnan Province.An epi-demiological investigation was conducted to provide a scientific basis for the prevention and control of monkeypox epidemics in China,especially for early detection in females in accordance with the"Monkeypox prevention and control program(2023 ver-sion)".Diagnosis was performed as described in the"Monkeypox Diagnosis and Treatment Guidelines(2022 version)".Speci-mens were collected for laboratory testing.The epidemiological investigation determined that the female patient had sexual in-tercourse with her newly married husband once before disease onset and the husband hid his history of male homosexual sex.The laboratory test results of the woman and her husband were positive for the nucleic acid of the monkeypox virus.Both had typical clinical symptoms,including rash.The epidemiological investigation,clinical symptoms,laboratory test results,and previous epidemic data of monkeypox in Yunnan province confirmed the woman as the first female infected with monkeypox in Yunnan Province and her husband was the presumed source of infection.