Precancerous lesions of gastric cancer （PLGC） are a group of pathological changes caused by abnormalities in the structure， morphology， and differentiation of gastric mucosal epithelial cells. Since the early symptoms are hidden and non-specific， PLGC is not easy to be diagnosed and it has often developed into intermediate or advanced gastric cancer once being diagnosed and missed the best time for treatment. Accordingly， the incidence of this disease is increasing year by year， which lifts a heavy burden on the patients. The pathogenesis of PLGC is complex， involving inflammatory microenvironment， bile reflux， glycolysis， autophagy， and apoptosis. Currently， PLGC is mainly treated with anti-inflammatory and endoscopic therapies， which are difficult to curb the development of PLGC. Therefore， seeking a safe and effective therapy is an important topic of modern research. Traditional Chinese medicine （TCM）， characterized by treatment based on syndrome differentiation and a holistic view， exerts effects via multiple pathways， mechanisms， and targets. Recent studies have confirmed that TCM can regulate the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR）， Wnt/β-catenin， Sonic Hedgehog， nuclear factor-κB （NF-κB）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， hypoxia-inducible factor-1α （HIF-1α）， neurogenic locus notch homolog protein （Notch）， nuclear factor E₂-related factor 2 （Nrf2） and other signaling pathways. By targeting these pathways， TCM can inhibit aerobic glycolysis， reduce oxidative stress， repair the inflammatory microenvironment， regulate cellular autophagy， and promote vascular normalization， thereby delaying or reversing PLGC. However， few researchers have systematically summarized the TCM regulation of PLGC-associated pathways. By reviewing the relevant articles at home and abroad， this paper summarized the roles of the above signaling pathways in the development of PLGC and the research progress in the regulation of signaling pathways by TCM in the treatment of PLGC， with a view to providing a new theoretical basis for the clinical research on PLGC and the drug development for this disease.

Objective To propose a whole-life cycle management model for valvular heart disease (VHD), systematically elucidate its underlying logic and implementation pathways, and concurrently review and analyze its preliminary application outcomes. Methods Since 2020, West China Hospital of Sichuan University has established a management system encompassing "assessment-decision-intervention-follow-up", including: (1) a risk-stratified, tiered management pathway; (2) six core functions ("promotion, screening, prevention, diagnosis, treatment, and rehabilitation") coordinated by disease-specific managers; (3) an intelligent decision support information platform; and (4) a collaborative network of multidisciplinary teams and regional academic alliances. To evaluate the effectiveness of this management model, we retrospectively included three cohorts: (1) the population screened by echocardiography from 2020 to 2024, analyzing the detection rate of aortic valve disease and risk stratification; (2) patients enrolled in the whole-life cycle management from April 2021 to December 2024, assessing follow-up outcomes, hospital satisfaction, and changes in quality of life; (3) patients who underwent transcatheter aortic valve replacement (TAVR) from January 2022 to January 2024, evaluating the one-year all-cause mortality rate, perioperative complications, and improvements in New York Heart Association (NYHA) classification. Results Between 2020 and 2024, a total of 583 874 individuals underwent echocardiographic screening. A total of 48 089 patients with aortic valve disease were identified, including 3 401 (7.1%) high-risk patients, 18 657 (38.8%) moderate-risk patients, and 26 031 (54.1%) low-risk patients. Among them, 2 417 patients were enrolled in whole-life cycle management. Patient satisfaction scores showed a yearly increase, rising from 73.89 points before 2020 to 93.74 points in 2024. The 1-year mortality rate in the TAVR cohort decreased to 5.3%, significantly lower than the 8.2% observed under early standard management between 2014 and 2019 (P<0.01). Conclusion Through process optimization and resource integration, the VHD whole-life cycle management model has demonstrated significant effectiveness in standardizing diagnostic and follow-up procedures, enhancing patient satisfaction and quality of life, and reducing mortality. These outcomes highlight its practical value for broader implementation in China.

Objective To investigate the effects of dexmedetomidine(Dex)on osteoporosis(OP)rats and possible mechanisms.Methods The rats were divided into sham operation group,osteoporosis model group(OP,replica-ting the OP rat model with bilateral ovariectomies),Dex-L,M,and H(Dex low,medium,and high dose treat-ments)groups and Dex-H+XAV-939 group(Wnt/β-catenin pathway inhibitor).Micro-CT was applied to meas-ure bone mineral density(BMD)and bone microstructure of rat femurs.The three-point bending experiment was applied to analyze the biomechanics of the femur(maximum load,fracture deflection,elastic modulus).HE stai-ning was applied to observe pathological changes in the femur of rats.ELISA method was applied to evaluate bone metabolism indicators such as alkaline phosphatase(ALP),typeⅠ procollagen amino-terminal peptide(PINP)and typeⅠcollagen cross-linked C-telopeptide(CTX-Ⅰ).The expression of Runx2 and Wnt3a was examined by Immunohistochemistry.Western blot was applied to detect the protein expression of Runx2 and Wnt3a/β-catenin pathway in femoral tissue.Results Compared to the Sham group,the bone volume and number of trabeculae in OP group were obviously reduced,the maximum load,fracture deflection,elastic modulus,BMD,Tb.Th,Tb.N,BV/TV,ALP,PINP,Runx2,Wnt3a,β-catenin expression decreased,CTX-Ⅰ increased(P＜0.05).Compared to the OP group,the bone trabecular structure in the Dex-L,M,and H groups was restored,the maxi-mum load,fracture deflection,elastic modulus,BMD,Tb.Th,Tb.N,BV/TV,ALP,PINP,Runx2,Wnt3a,β-catenin expression all increased but CTX-Ⅰ decreased(P＜0.05).Compared to the Dex-H group,the bone trabecular injury in the Dex-H+XAV-939 group showed a more severe damage.The maximum load,fracture de-flection,elastic modulus,BMD,Tb.Th,Tb.N,BV/TV,ALP,PINP,Runx2,Wnt3a,β-catenin expression decreased while CTX-Ⅰ increased(P＜0.05).Conclusions Dex may antagonize OP effects by improving bone density,biomechanical properties and microstructure.The underlying mechanism might be related to the activation of the Wnt/β-catenin signaling pathway.

AIM: To establish individualized drug therapy strategy for patients with rejection and hyperglycemia after liver transplantation. METHODS: Clinical pharmacist collaborated with the surgeons and participated in the diagnosis and treatment of rejection and hyperglycemia after liver transplantation. Taking together liver function, therapeutic drug monitoring, drug-drug interactions between tacrolimus and wuzhi capsule, individualized drug therapy was adapted to improve the prognosis. RESULTS: The patient recovered well and survived in good health till now. CONCLUSION: It is highly suggested that clinical pharmacists actively involved in treatment of more severe and difficult-to-treat disease and design the individualized dosing regimens. This will largely contribute in reduced adverse drug reaction, improved safety and effectiveness in drug use as well as the quality of life in the "post-transplantation era".

Objective:To investigate the correlation between pulmonary arteriovenous fistula (PAVF) and ischemic stroke, and to improve the diagnosis and treatment of embolic strokes of undetermined source.Methods:Five patients with ischemic stroke caused by PAVF admitted to Xiangya Hospital of Central South University from January 2017 to December 2020 were collected. The diagnosis, treatment and prognosis of stroke caused by PAVF were summarized based on literature review.Results:Among the 5 patients, 1 is male and 4 are females, with age of (34.4±9.3) years. Weakness of unilateral limb, slurred speech, vision changes, drooping eyelids, etc., were the first manifestations of stroke. The location of cerebral infarction was indefinite. In this study, 5 patients were all isolated PAVF, including 3 cases of left lower lung, 1 case of left upper lung and 1 case of right lower lung. All 5 patients underwent interventional therapy, were followed-up for 6 months and 12 months after surgery, and none of them had a new stroke attack, and only 1 case had recanalization of PAVF.Conclusions:PAVF is a rare vascular lesion, stroke caused by which is even rarer, with a lack of specificity in clinical manifestations. For young patients with unexplained embolic stroke, if the stroke has a sudden onset, the anterior and posterior circulation can be involved, and multiple vascular distribution regions are often involved, and it is difficult to find a clear emboli basis, with manifestations such as hypoxemia, PAVF should be considered. Percutaneous catheter intervention for PAVF is safe and effective, and is the preferred method for the treatment of PAVF.

OBJECTIVE: To investigate the effects of fecal microbiota transplantation (FMT) on intestinal microbiome and organism in patients with severe pneumonia during the convalescence period. METHODS: A prospective non-randomized controlled study was conducted. From December 2021 to May 2022, patients with severe pneumonia during the convalescence period who received FMT (FMT group) and patients with severe pneumonia during the convalescence period who did not receive FMT (non-FMT group) admitted to the First Affiliated Hospital of Guangzhou Medical University were enrolled. The differences of clinical indicators, gastrointestinal function and fecal traits between the two groups were compared 1 day before and 10 days after enrollment. The 16S rDNA gene sequencing technology was used to analyze the changes of intestinal flora diversity and different species in patients with FMT before and after enrollment, and metabolic pathways were analyzed and predicted by Kyoto Encyclopedia of Genes and Genomes database (KEGG). Pearson correlation method was used to analyze the correlation between intestinal flora and clinical indicators in FMT group. RESULTS: The level of triacylglycerol (TG) in FMT group was significantly decreased at 10 days after enrollment compared with before enrollment [mmol/L: 0.94 (0.71, 1.40) vs. 1.47 (0.78, 1.86), P < 0.05]. The level of high-density lipoprotein cholesterol (HDL-C) in non-FMT group was significantly decreased at 10 days after enrollment compared with before enrollment (mmol/L: 0.68±0.27 vs. 0.80±0.31, P < 0.05). There were no significant differences in other clinical indexes, gastrointestinal function or fecal character scores between the two groups. Diversity analysis showed that the α diversity indexes of intestinal flora in FMT group at 10 days after enrollment were significantly higher than those in non-FMT group, and β diversity was also significantly different from that in non-FMT group. Differential species analysis showed that the relative abundance of Proteobacteria at the level of intestinal flora in FMT group at 10 days after enrollment was significantly lower than that in non-FMT group [8.554% (5.977%, 12.159%) vs. 19.285% (8.054%, 33.207%), P < 0.05], while the relative abundance of Fusobacteria was significantly higher than that in non-FMT group [6.801% (1.373%, 20.586%) vs. 0.003% (0%, 9.324%), P < 0.05], and the relative abundance of Butyricimonas, Fusobacterium and Bifidobacterium at the genus level of the intestinal flora was significantly higher than that in non-FMT group [Butyricimonas: 1.634% (0.813%, 2.387%) vs. 0% (0%, 0.061%), Fusobacterium: 6.801% (1.373%, 20.586%) vs. 0.002% (0%, 9.324%), Bifidobacterium: 0.037% (0%, 0.153%) vs. 0% (0%, 0%), all P < 0.05]. KEGG metabolic pathway analysis showed that the intestinal flora of FMT group was changed in bisphenol degradation, mineral absorption, phosphonate and phosphinate metabolism, cardiac muscle contraction, Parkinson disease and other metabolic pathways and diseases. Correlation analysis showed that Actinobacteria and prealbumin (PA) in intestinal flora of FMT group were significantly positively correlated (r = 0.53, P = 0.043), Bacteroidetes was positively correlated with blood urea nitrogen (BUN; r = 0.56, P = 0.029) and complement C3 (r = 0.57, P = 0.027), Firmicutes was positively correlated with BUN (r = 0.56, P = 0.029) and complement C3 (r = 0.57, P = 0.027), Fusobacteria was significantly positively correlated with immunoglobulin M (IgM; r = 0.71, P = 0.003), Proteobacteria was significantly positively correlated with procalcitonin (PCT; r = 0.63, P = 0.012) and complement C4 (r = 0.56, P = 0.030). CONCLUSIONS FMT can reduce TG level, reconstruct intestinal microecological structure, change body metabolism and function, and alleviate inflammatory response by reducing the relative abundance of harmful bacteria in patients with severe pneumonia during the convalescence period.
Humans ; Fecal Microbiota Transplantation ; Complement C3 ; Convalescence ; Prospective Studies ; Feces

Peptides are increasingly important resources for biological and therapeutic development, however, their intrinsic susceptibility to proteolytic degradation represents a big hurdle. As a natural agonist for GLP-1R, glucagon-like peptide 1 (GLP-1) is of significant clinical interest for the treatment of type-2 diabetes mellitus, but its in vivo instability and short half-life have largely prevented its therapeutic application. Here, we describe the rational design of a series of α/sulfono-γ-AA peptide hybrid analogues of GLP-1 as the GLP-1R agonists. Certain GLP-1 hybrid analogues exhibited enhanced stability (t _1/2 > 14 days) compared to t _1/2 (<1 day) of GLP-1 in the blood plasma and in vivo. These newly developed peptide hybrids may be viable alternative of semaglutide for type-2 diabetes treatment. Additionally, our findings suggest that sulfono-γ-AA residues could be adopted to substitute canonical amino acids residues to improve the pharmacological activity of peptide-based drugs.

Evasion of apoptosis is a hallmark of cancer, attributed in part to overexpression of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2). In a variety of cancer types, including lymphoma, Bcl-2 is overexpressed. Therapeutic targeting of Bcl-2 has demonstrated efficacy in the clinic and is the subject of extensive clinical testing in combination with chemotherapy. Therefore, the development of co-delivery systems for Bcl-2 targeting agents, such as small interfering RNA (siRNA), and chemotherapeutics, such as doxorubicin (DOX), holds promise for enabling combination cancer therapies. Lipid nanoparticles (LNPs) are a clinically advanced nucleic acid delivery system with a compact structure suitable for siRNA encapsulation and delivery. Inspired by ongoing clinical trials of albumin-hitchhiking doxorubicin prodrugs, here we developed a DOX-siRNA co-delivery strategy via conjugation of doxorubicin to the surface of siRNA-loaded LNPs. Our optimized LNPs enabled potent knockdown of Bcl-2 and efficient delivery of DOX into the nucleus of Burkitts' lymphoma (Raji) cells, leading to effective inhibition of tumor growth in a mouse model of lymphoma. Based on these results, our LNPs may provide a platform for the co-delivery of various nucleic acids and DOX for the development of new combination cancer therapies.

Adventitia ; Atherosclerosis/genetics* ; Cell Communication ; Humans ; Hyperhomocysteinemia/genetics* ; Sequence Analysis, RNA

Clostridioides difficile infection (CDI) is an infectious disease with fever, abdominal pain and diarrhea as the main clinical manifestations. At present, CDI is mainly treated with antibiotics and faecal microbiota transplantation. As recurrent and refractory CDI continues to increase, it is important to seek a more effective alternative therapy. However, many of the studies on the prevention and control of CDI by probiotics are still in the early stage. This paper summarized the research on the types, mechanisms and technical means of probiotics in the treatment of CDI.