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

Based on latent structure model and association rule analysis, this study investigates the prescription patterns used by professor YANG Zhong-qi in treating hypertension with traditional Chinese medicine(TCM) and infers the associated TCM syndromes, providing a reference for clinical syndrome differentiation and treatment. The observation window spanned from January 8, 2013, to June 26, 2024, during which qualified herbal decoction prescriptions meeting efficacy criteria were extracted from the outpatient medical record system of the First Affiliated Hospital of Guangzhou University of Chinese Medicine and compiled into a standardized database. Statistical analysis of high-frequency herbs included frequency counts and herbal property-channel tropism analysis. Latent structure modeling and association rule analysis were performed using R 4.3.2 and Lantern 5.0 software to identify core herbal combinations and infer TCM syndrome patterns. A total of 2 436 TCM prescriptions were included in the study, involving 263 drugs with a cumulative frequency of 29 783. High-frequency herbs comprised Uncariae Ramulus cum Uncis, Poria, Glycyrrhizae Radix et Rhizoma, Puerariae Lobatae Radix, and Alismatis Rhizoma, predominantly categorized as deficiency-tonifying, heat-clearing, and blood-activating and stasis-resolving herbs. Latent structure analysis identified 18 latent variables, 74 latent classes, 5 comprehensive clustering models, and 15 core herbal combinations, suggesting that the core syndrome clusters include liver Yang hyperactivity pattern, Yin deficiency with Yang hyperactivity pattern, phlegm-stasis intermingling pattern, and liver-kidney insufficiency pattern. Association rule analysis revealed 22 robust association rules. RESULTS:: indicate that hypertension manifests as a deficiency-rooted excess manifestation, significantly associated with functional dysregulation of the liver, lung, spleen-stomach, heart, and kidney. Key pathogenic mechanisms involve liver Yang hyperactivity, phlegm-stasis interaction, and liver-kidney insufficiency. Therapeutic strategies should prioritize liver-calming, spleen-fortifying, and deficiency-tonifying principles, supplemented by dynamic regulation of Qi-blood and Yin-Yang balance according to syndrome evolution, alongside pathogen-eliminating methods such as phlegm-resolving and stasis-dispelling. Synergistic interventions like mind-tranquilizing therapies should be tailored to individual conditions.
Hypertension/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Drug Prescriptions ; Latent Class Analysis

OBJECTIVE: This study aimed to evaluate the association between susceptibility genes and non-alcoholic fatty liver disease (NAFLD) in children with obesity. METHODS: We conducted a two-step case-control study. Ninety-three participants were subjected to whole-exome sequencing (exploratory set). Differential genes identified in the small sample were validated in 1,022 participants using multiplex polymerase chain reaction and high-throughput sequencing (validation set). RESULTS: In the exploratory set, 14 genes from the NAFLD-associated pathways were identified. In the validation set, after adjusting for sex, age, and body mass index, ECI2 rs2326408 (dominant model: OR = 1.33, 95% CI: 1.02-1.72; additive model: OR = 1.22, 95% CI: 1.01-1.47), C6orf201 rs659305 (dominant model: OR = 1.30, 95% CI: 1.01-1.69; additive model: OR = 1.21, 95% CI: 1.00-1.45), CALML5 rs10904516 (pre-ad dominant model: OR = 1.36, 95% CI: 1.01-1.83; adjusted dominant model: OR = 1.40, 95% CI: 1.03-1.91; and pre-ad additive model: OR = 1.26, 95% CI: 1.04-1.66) polymorphisms were significantly associated with NAFLD in children with obesity ( P < 0.05). Interaction analysis revealed that the gene-gene interaction model of CALML5 rs10904516, COX11 rs17209882, and SCD5 rs3733228 was optional ( P < 0.05), demonstrating a negative interaction between the three genes. CONCLUSION In the Chinese population, the CALML5 rs10904516, C6orf201 rs659305, and ECI2 rs2326408 variants could be genetic markers for NAFLD susceptibility.
Humans ; Non-alcoholic Fatty Liver Disease/genetics* ; Child ; Male ; Female ; Genetic Predisposition to Disease ; Case-Control Studies ; Exome Sequencing ; Adolescent ; Polymorphism, Single Nucleotide ; Obesity/complications* ; Pediatric Obesity/complications* ; China

A 12-year-old boy was admitted with symptoms of cough and fever lasting over a month, accompanied by weight loss 2 kg. Prior anti-infective treatments proved ineffective in alleviating the symptoms. Chest imaging revealed diffuse interstitial pulmonary edema in the right lung with obstructed lymphatic drainage. Combined with histopathological examinations, the diagnosis was confirmed as lung cancer with pulmonary lymphangitic carcinomatosis. The patient underwent chemotherapy with docetaxel and carboplatin, yet the disease progressively worsened, resulting in death three months after diagnosis. This case highlights lung cancer should not be overlooked in patients with persistent respiratory symptoms of unknown etiology. Early imaging examinations, along with necessary pathological evaluations, are crucial for timely detection and diagnosis. The presence of pulmonary lymphangitic carcinomatosis often indicates an advanced-stage of cancer, associated with a poor prognosis.
Humans ; Male ; Lung Neoplasms/complications* ; Child ; Carcinoma/drug therapy*

Cyclin-dependent kinase 9 (CDK9) is a member of the transcription CDK subfamily and plays a role in transcriptional regulation. Selective CDK9 degraders possess potent clinical advantages over reversible CDK9 inhibitors. Herein, we report the first ATG101-recruiting selective CDK9 degrader, AZ-9, based on the hydrophobic tag kinesin degradation technology. AZ-9 showed significant degradation effects and selectivity toward other homologous cell cycle CDKs in vitro and in vivo, which could also affect downstream related phenotypes. Mechanism research revealed that AZ-9 recruits ATG101 to initiate the autophagy-lysosome pathway, and forms autophagosomes through the recruitment of LC3, which then fuses with lysosomes to degrade CDK9 and the partner protein Cyclin T1. These dates validated the existence of non-proteasomal degradation pathway of hydrophobic driven protein degradation strategy for the first time, which might provide research ideas for chemical induction intervention on other types of pathogenic proteins.

Acute symptomatic osteoporotic thoracolumbar compression fracture (ASOTLF) can lead to chronic low back pain, kyphosis deformity, pulmonary dysfunction, loss of mobility, and even life-threatening complications. Vertebral augmentation is currently the mainstream treatment method for this condition. In 2019, the Editorial Board of Chinese Journal of Trauma and the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association collaboratively led the development of Clinical guideline for vertebral augmentation for acute symptomatic osteoporotic thoracolumbar compression fractures. Six years later, with advances in clinical diagnosis and treatment techniques as well as accumulating evidence in related fields, the 2019 guideline requires updating. To this end, the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association, the Spinal Health Professional Committee of China Human Health Science and Technology Promotion Association, and the Minimally Invasive Orthopedics Professional Committee of Shaanxi Medical Doctor Association have organized experts in the field to develop the Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures ( version 2025) , based on the latest evidence-based medical researches. This guideline incorporates 3 recommendations retained from the 2019 version with updated strength of evidence, along with 12 new recommendations. It provides recommendations from six aspects of diagnosis, pain management, treatment option selection, prevention of postoperative complications, anti-osteoporosis therapy, and postoperative rehabilitation, aiming to provide a reference for standard treatment of vertebral augmentation for ASOTLF in hospitals at all levels.

OBJECTIVE: Meta-analysis of the clinical efficacy of plate and external fixator fixation in the treatment of AO-C type distal radius fractures. METHODS: PubMed, Embase, Cochrane Medical Library, Web of Science, CNKI, Wanfang, VIP and SinoMed databases were searched for all literature on randomized controlled clinical trials of AO-C distal radius fractures. The search time limits were from each database. The database will be established until June 30, 2023. The included studies were extracted according to the Cochrane Handbook (Version 6.3, 2022) for information extraction and literature quality evaluation. RevMan 5.4 was used to evaluate the risk of Publication bias, test heterogeneity and Perform Meta-analysis. The outcome indicators were:imaging anatomy indicators (volar inclination angle, ulnar deviation angle, radial height), wrist joint mobility (flexion, extension, rotation, ulnar deviation), complication rate, and comparison of surgical treatments (operative blood loss, operation time, hospitalization time, fracture healing time) and wrist joint function scores and related scales. RESULTS: (1) A total of 28 studies were included, with a total of 2 192 patients, including 1 096 cases in the plate internal fixation group and 1 096 cases in the external fixation group.(2) Meta analysis results showed:the surgical treatment situation of the external fixation group:surgical blood loss MD=-37.93, 95%CI(-48.54, -27.31), P<0.000 01;operation time MD=-31.58, 95%CI(-48.96, -14.20), P<0.000 4;hospitalization time MD=-4.58, 95%CI(-5.44, -3.71), P<0.000 01;the fracture healing time MD=-0.88, 95%CI(-1.35, -0.41), P<0.000 2, which were significantly better than that of the plate internal fixation group(P<0.05).(3) The two groups:palmar inclination angle MD=-0.17, 95%CI(-0.95, 0.61), P=0.68;ulnar declination MD=0.22, 95%CI(-0.73, 1.17), P=0.65, radial height MD=-0.24, 95%CI(-1.15, 0.67), P=0.60;flexion and extension MD=-5.63, 95%CI(-11.85, 0.58), P=0.08;rotation MD=-5.80, 95%CI(-12.77, 1.17), P=0.10, radioulnar deviation MD=-2.86, 95%CI(-10.87, 5.15), P=0.48;complication rate RR=0.96, 95%CI(0.63, 1.46), P=0.83;Gartland-Werley clinical wrist score MD=0.13, 95%CI(-0.80, 1.06), P=0.78;excellent and good rate of Gartland-Werley wrist clinical score RR=0.93, 95%CI(0.87, 1.01), P=0.08;excellent and good rate of Cooney wrist score RR=0.99, 95%CI(0.62, 1.59), P=0.98;wrist DASH score MD=-4.67, 95%CI(-14.96, 5.62), P=0.37;the differences were not significant (P>0.05). CONCLUSION Compared with internal fixation with plate, external fixation can significantly reduce the amount of surgical bleeding, shorten the operation time, hospitalization time and fracture healing time, and its imaging anatomical indicators, wrist mobility, and complications can be significantly reduced in treating AO-C distal radius fractures. Rates and wrist function scores were equivalent.
Humans ; External Fixators ; Bone Plates ; Radius Fractures/surgery* ; Fracture Fixation/methods* ; Fracture Fixation, Internal ; Wrist Fractures

Aim To investigate the effect of p-AMPK activity on autophagy in different subtypes of MDA-MB-231(triple-negative breast cancer cells)and MCF-7(estrogen receptor-positive cells)and its regulatory mechanism.Methods MDA-MB-231 cells were trea-ted with EBSS,Baf-A1,and EBSS+Baf-A1 for four hours,and MCF-7 cells for eight hours.The effects of autophagy on cell proliferation and apoptosis were ob-served,mitochondrial morphology was examined,and the expression of autophagy markers LC3B,P62,LAMP1,TOM20,AMPK,p-AMPK,ULK1,and Bec-lin1/VPS34 proteins was detected.The autophagy pathway was validated by inhibiting AMPK activity.Results Breast cancer cells underwent autophagy af-ter starvation induction(EBSS),with inconsistent au-tophagy processes observed in different subtypes of breast cancer cells.Autophagy inhibited cell prolifera-tion.In MDA-MB-231 cells,autophagy led to an in-crease in p-AMPK levels and a decrease in ULK1 lev-els,initiating autophagy through p-AMPK activation of ULK1.In MCF-7 cells,both p-AMPK and ULK1 levels decreased after autophagy,suggesting that autophagy might not be mediated by p-AMPK activation.Conclu-sions MDA-MB-231 cells primarily initiate autophagy by directly activating ULK1 by p-AMPK,independent of the MTOR pathway.In MCF-7 cells autophagy might be triggered by inhibiting MTOR through AMPK activity or directly activating MTOR through other up-stream factors.Regulating p-AMPK activity based on the autophagy pathways in different cell subtypes could enable more precise targeting and treatment of different types of breast cancer.