ObjectiveTo observe the effects of modified Shaofu Zhuyutang on key proteins of the epidermal growth factor receptor （EGFR）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway in SD rats with endometriosis. MethodsAfter successful establishment of an endometriosis model in 60 female SD rats of SPF grade via the auto-transplantation method， the rats were randomly divided into a model group， modified Shaofu Zhuyutang high-， medium-， and low-dose groups， and a gestrinone group， with another 12 rats serving as a blank group. The blank and model groups were administered 10 mL·kg^-1 normal saline， while the high-， medium-， and low-dose groups received 30， 15， and 7.5 g·kg^-1 modified Shaofu Zhuyutang， respectively. The gestrinone group was administered 0.25 mg·kg^-1 gestrinone suspension. After four weeks of treatment， uterine contractions were induced with 2 U of oxytocin， and the writhing response of rats was observed. After 24 h， the rats were euthanized， and the weight and volume of ectopic endometrial tissue were recorded. Hematoxylin-eosin （HE） staining was used to observe pathological changes in endometrial tissues， while the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL） assay was used to evaluate the apoptosis rate of endometrial tissues. Immunofluorescence was used to detect the relative expression areas of the B-cell lymphoma-2 gene-associated promoter （Bad） and B-cell lymphoma-2 （Bcl-2） proteins in endometrial tissues. Serum levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， epidermal growth factor （EGF）， and EGFR were measured by enzyme-linked immunosorbent assay （ELISA）. The relative protein expression levels of EGFR， PI3K， phosphorylated PI3K （p-PI3K）， Akt， and phosphorylated Akt （p-Akt） in endometrial tissues were analyzed by Western blot. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of EGFR， PI3K， and Akt. ResultsCompared with the blank group， the model group showed endometrial thickening， glandular and mesenchymal hyperplasia， a significant decrease in the relative expression area of Bad in ectopic endometrial tissues， a significant increase in the relative expression area of Bcl-2， and a significant reduction in the apoptosis rate as indicated by TUNEL staining. Serum levels of IL-1β， IL-6， TNF-α， EGF， and EGFR were significantly elevated （P<0.01）. The relative protein expression levels of EGFR， PI3K， p-PI3K， Akt， and p-Akt， as well as the mRNA expression levels of EGFR， PI3K， and Akt， were also significantly increased （P<0.01）. Compared with the model group， the high- and medium-dose groups of modified Shaofu Zhuyutang and the gestrinone group exhibited reduced glandular and mesenchymal hyperplasia to varying degrees， with dilated glandular lumens. The number of writhing responses was significantly reduced， the latency to writhing response was significantly prolonged， and the weight and volume of ectopic endometrial tissue were significantly decreased. The relative expression area of Bad in ectopic endometrial tissue was significantly increased， the relative expression area of Bcl-2 was significantly decreased， and the apoptosis rate was significantly elevated as shown by TUNEL staining. Serum levels of IL-1β， IL-6， TNF-α， EGF， and EGFR were significantly reduced， and the relative protein expression levels of EGFR， PI3K， p-PI3K， Akt， and p-Akt， as well as the mRNA expression levels of EGFR， PI3K， and Akt， were significantly decreased （P<0.05，P<0.01）. ConclusionModified Shaofu Zhuyutang may exert therapeutic effects on endometriosis by interfering with key proteins of the EGFR/PI3K/Akt signaling pathway and inducing apoptosis in ectopic endometrial tissue.

Objective:To summarize the clinical characteristics and treatment experience of patients with botulism after cosmetic botulinum toxin injection.Methods:A retrospective study was conducted on patients admitted to the Department of Medical Aesthetic and Plastic Surgery of the Fifth Affiliated Hospital of Zhengzhou University for botulism after cosmetic botulinum toxin injection between January 1, 2023, and October 31, 2024. Clinical data and treatment regimens were collected. Patients received botulinum antitoxin injection, neurotrophic therapy, nutrition supplementation, modulation and enhancement of cellular immune function, and systemic supportive care based on their condition. Prior to antitoxin administration, a skin test was performed. Patients with a negative test received intramuscular injections of 10 000 U of antitoxin serum every 12 hours, while those with a positive result underwent a desensitization protocol. The cessation criterion was significant improvement of toxic symptoms. Data collected included age, gender, region, time of presentation, injection location, brand and type of toxin, injection time, sites and dose of injection, time to onset of initial symptoms, main symptoms, skin test result for antitoxin, dosage of antitoxin administered, length of hospital stay, adverse reactions and prognosis. Data analysis was performed using GraphPad Prism Version 10.2.0.Results:A total of 179 patients were included, with 8 cases in 2023 and 171 cases in 2024. The majority were female (97.2%, 174 cases). The age range was 18-62 years, with a median age of 35 years; the highest proportion was in the 20-40 age group (71.5%, 128 cases). Patients were from 23 different provinces, autonomous regions, and municipalities directly under the central government in China. The injected product was mostly an unspecified brand of botulinum toxin (57.5%, 103 cases). Injections were primarily administered in non-medical institutions, with beauty salons or private studios accounting for 88.8% (159 cases). Injection sites included the platysma (92 cases), masseter muscle (82 cases), orbicularis oculi muscle (82 cases), frontalis muscle (67 cases), among others, with some patients receiving injections at multiple sites. 69 cases (38.5%) of patients were unaware of the injected dose; for the remaining cases, based on information provided, the injected doses were all within the safe range. The incubation period was mostly 1-7 days. The main symptoms included fatigue (171 cases), dysphagia (137 cases), dizziness (101 cases), blurred vision (76 cases), and difficulty opening eyes (66 cases). 176 patients received botulinum antitoxin treatment; 82 cases (46.6%) had a positive skin test and received desensitization injections, while 94 cases (53.4%) had a negative test. The total dosage of antitoxin used ranged from 10 000 U to 240 000 U. Three patients received only adjuvant therapy such as neurotrophic support. Adverse reactions during treatment primarily included induration at the injection site and serum sickness, all of which resolved after symptomatic treatment with antihistamines, steroids, etc. The hospital stay ranged from 1 to 24 d, with an average of 4.6 d. Upon discharge, symptoms in all patients had alleviated or resolved. At the 6-month follow-up after discharge, 14 patients were lost to follow-up; the remaining patients recovered well with no other complications.Conclusion:Poisoning incidents due to the illegal or improper use of botulinum toxin are increasing. Administration of botulinum antitoxin is an effective means to ameliorate intoxicating symptoms. Patients should seek timely medical intervention and receive antitoxin treatment as early as possible. Desensitization administration does not affect the efficacy of the antitoxin.

Objective To explore the predictive value of troponin Ⅰ(TnⅠ)peak value upon admission for predicting left ventricular ejection fraction(LVEF)＜50％in patients with acute myocardial infarction(AMI)during the recovery period.Methods A retrospec-tive analysis was carried out on 220 AMI patients admitted to Beijing Friendship Hospital from 2018 to the present.The patients were di-vided into three groups based on the peak value of TnⅠ during their stay in hospital,and the baseline data were compared.Subsequently,three progressively complex regression models were constructed to evaluate the relationship between TnⅠ and LVEF＜50％.The optimal cutoff value was determined through restricted cubic spline and smooth curve analysis.Additionally,subgroup analysis was carried out to explore differences in the predictive value of TnⅠ in different populations.Results TnⅠ peak value was significantly associated(P＜0.05)with the ratio of emergency percutaneous coronary intervention(PCI),neutrophil-to-lymphocyte ratio,white blood cell count,neutro-phils,intra-aortic balloon pump usage,N-terminal pro-brain natriuretic peptide peak value,and so on.All three models showed a sig-nificant increase in the risk of LVEF＜50％with higher TnⅠ peak value(P＜0.05).Restricted cubic spline and smooth curve analysis re-vealed a linear relationship between TnⅠ peak value and LVEF values,with the optimal cutoff value for TnⅠ peak value consistently at 29.80ng/ml across the three models.Subgroup analysis showed that the predictive value of peak TnⅠ for LVEF＜50％demonstrated statisti-cally significant differences across the following subgroups:male patients,those with high BMI,hypertension,acute interventional treat-ment,as well as different age groups,and whether patients had diabetes,smoked,or consumed alcohol.Conclusion An admission TnⅠpeak value exceeding 29.80ng/ml is an independent risk factor for predicting LVEF＜50％during the recovery period in AMI patients.It can be used to identify high-risk individuals and provide a basis for early aggressive intervention.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Gastric cancer is a high-incidence malignancy that poses a serious threat to public health in China, ranking among the top three cancers in both incidence and mortality. The majority of patients are diagnosed at an advanced stage, resulting in limited treatment options and poor prognosis. To address key challenges in gastric cancer diagnosis and treatment, a research team led by Professor Jiafu Ji at Peking University Cancer Hospital has focused on the project "Development and Dissemination of Precision Medicine Approaches in Gastric Cancer Management". Through a series of high-quality multicenter clinical studies, the team established a set of new international standards in perioperative treatment, individua-lized drug selection, intelligent noninvasive diagnostics, and novel immunotherapy strategies. These advances have significantly improved treatment efficacy and reduced surgical trauma, achieving key technological breakthroughs in diagnosis, therapy, and mechanistic understanding, and systematically enhancing outcomes for gastric cancer patients. The project ' s findings had a broad international impact, including hosting China ' s first International Gastric Cancer Congress. Through nationwide dissemination, they have promoted the development of precision diagnosis and treatment of gastric cancer as a discipline, and led the formulation of the National Health Commission's guidelines for gastric cancer diagnosis and treatment. In recognition of its achievements, the project was awarded the First Prize of the 2024 Chinese Medical Science and Technology Award.
Stomach Neoplasms/genetics* ; Humans ; Precision Medicine/methods* ; China ; Immunotherapy/methods*

In recent years, along with the rapid progress of innovative drugs, novel devices, frontier technologies, and artificial intelligence, the therapeutic model for tumors has undergone tremendous changes, with a greater emphasis on precise diagnosis and treatment of clinical issues. Nevertheless, in clinical practice, numerous problems still impede the implementation of precise treatment. This article intends to be guided by the crucial clinical issues in the diagnosis, surgery, and drug treatment of gastric cancer, to explore the strategies of precise diagnosis and treatment for gastric cancer and the frontier research directions, thereby providing new concepts and potential research directions for further enhancing the precision, efficacy of gastric cancer diagnosis and treatment, and the quality of life of patients.

In the era of intelligence and individualization, gastric cancer surgery is under-going multidimensional advancements. The authors focus on the cutting-edge progress and future challenges of artificial intelligence (AI) in the diagnosis and decision-making, treatment and drug development, as well as postoperative rehabilitation in gastric cancer surgery. In terms of diagnosis, AI integrates imaging, liquid biopsy, pathology, and multimodal technologies to enhance diagnostic comprehensiveness and accuracy. Regarding decision-making, AI assists in formulating personalized treatment plans, conducting risk assessments, and predicting prognoses. In the treatment domain, AI facilitates the advancement of individualized surgical approaches, supports postoperative follow-up, and aids in physician education and training. In drug development, the introduction of virtual cell models and AlphaFold has improved the efficiency and accuracy of mechanistic and clinical research. For postoperative rehabilitation guidance, AI provides personalized recommendations to optimize treatment outcomes.AI holds great promise in gastric cancer surgery across diagnosis and decision-making, treatment and drug development, and postoperative rehabilitation. However, current AI technologies face challenges such as data sharing and privacy protection, multicenter research and model generalization, human-machine collaboration, interpretability, ethical considerations, sustaina-bility, and widespread adoption. Addressing these challenges will require collective efforts to fully leverage AI′s advantages in gastric cancer diagnosis and treatment.

Objective To explore the predictive value of troponin Ⅰ(TnⅠ)peak value upon admission for predicting left ventricular ejection fraction(LVEF)＜50％in patients with acute myocardial infarction(AMI)during the recovery period.Methods A retrospec-tive analysis was carried out on 220 AMI patients admitted to Beijing Friendship Hospital from 2018 to the present.The patients were di-vided into three groups based on the peak value of TnⅠ during their stay in hospital,and the baseline data were compared.Subsequently,three progressively complex regression models were constructed to evaluate the relationship between TnⅠ and LVEF＜50％.The optimal cutoff value was determined through restricted cubic spline and smooth curve analysis.Additionally,subgroup analysis was carried out to explore differences in the predictive value of TnⅠ in different populations.Results TnⅠ peak value was significantly associated(P＜0.05)with the ratio of emergency percutaneous coronary intervention(PCI),neutrophil-to-lymphocyte ratio,white blood cell count,neutro-phils,intra-aortic balloon pump usage,N-terminal pro-brain natriuretic peptide peak value,and so on.All three models showed a sig-nificant increase in the risk of LVEF＜50％with higher TnⅠ peak value(P＜0.05).Restricted cubic spline and smooth curve analysis re-vealed a linear relationship between TnⅠ peak value and LVEF values,with the optimal cutoff value for TnⅠ peak value consistently at 29.80ng/ml across the three models.Subgroup analysis showed that the predictive value of peak TnⅠ for LVEF＜50％demonstrated statisti-cally significant differences across the following subgroups:male patients,those with high BMI,hypertension,acute interventional treat-ment,as well as different age groups,and whether patients had diabetes,smoked,or consumed alcohol.Conclusion An admission TnⅠpeak value exceeding 29.80ng/ml is an independent risk factor for predicting LVEF＜50％during the recovery period in AMI patients.It can be used to identify high-risk individuals and provide a basis for early aggressive intervention.