Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

Neurosyphilis is a group of clinical syndromes caused by treponema pallidum invading the central nervous system and causing varying degrees of damage to the brain parenchyma, brain (spinal) membrane or spinal cord. Cerebral syphilitic gumma is the rarest form of neurosyphilis, and its clinical manifestations lack specificity, which is easily confused with other intracranial space occupying lesions on imaging. In this article, a patient with cognitive dysfunction, intracranial hypertension, and imaging findings similar to multicentric glioma was diagnosed as cerebral syphilitic gumma by serology, cerebrospinal fluid test and brain histopathology. The symptoms basically disappeared after treatment with standard penicillin. This report aims to raise awareness of cerebral syphilitic gumma in order to reduce missed diagnosis and misdiagnosis.

OBJECTIVE: To explore the potential role of mRNA m7G modification in the pathogenesis of human adenocarcinoma of esophagogastric junction (AEG). METHODS: Pathological tissue specimens from four AEG patients who underwent surgical treatment at the People's Hospital Affiliated to Jiangsu University between 2018 and 2019 were selected. Tumor tissues and adjacent normal tissues were collected from these patients. RNA was extracted from both tissue types and subjected to m7G methylated RNA immunoprecipitation sequencing (m7G-MeRIP-seq) to analyze the patterns of m7G modification, the characteristics of differential m7G modification sites, the differentially expressed mRNA, and the correlation between m7G modification and mRNA expression levels. Differential m7G-modified genes (MSH6, BRCA1, and SOX9) were further validated using methylated RNA immunoprecipitation quantitative PCR (MeRIP-qPCR), while the expression of METTL1 and WDR4 genes was examined by real-time quantitative PCR (RT-qPCR). This study was approved by the Medical Ethics Committee of the People's Hospital Affiliated to Jiangsu University (Ethics No. 20150083). RESULTS: m7G-MeRIP-seq analysis revealed that m7G modifications in both AEG and adjacent normal tissues were predominantly located in the GC-rich region surrounding the internal start codon of mRNA. Differential m7G modification sites between the two groups were closely associated with cancer-related genes. mRNA library analysis showed that differentially expressed mRNA were predominantly upregulated in AEG tissues and downregulated in adjacent normal tissues. Cross-analysis indicated that genes with hypermethylation tended to exhibit upregulated expression, while genes with hypomethylation were typically downregulated in AEG tissues. MeRIP-qPCR validation confirmed that the mRNA expression of MSH6, BRCA1, and SOX9 were significantly upregulated in AEG tissues compared to adjacent normal tissues (AEG vs. normal, P < 0.05). RT-qPCR results demonstrated that the mRNA expression levels of METTL1 and WDR4 were also upregulated in AEG tissues (AEG vs. normal, P < 0.000 5). CONCLUSION These findings suggest that mRNA m7G modification plays a significant role in the development of AEG. Furthermore, proteins as METTL1 and WDR4 may facilitate AEG progression by regulating mRNA m7G modification. These results provide valuable insights into the molecular mechanisms underlying AEG and may inform future therapeutic strategies for this malignancy.
Humans ; RNA, Messenger/metabolism* ; Adenocarcinoma/pathology* ; Esophagogastric Junction/metabolism* ; Esophageal Neoplasms/metabolism* ; Gene Expression Regulation, Neoplastic ; Female ; Male ; Middle Aged ; DNA Methylation ; Methyltransferases/metabolism* ; Stomach Neoplasms/genetics*

Objective To explore the application effect of periodic feedback method in pelvic floor function exercise for patients with low anal preservation.Methods A total of 83 rectal cancer patients with low anal preservation admitted to Zhejiang Cancer Hospital from December 2023 to February 2024 were selected as subjects.They were divided into control group(n=42)and experimental group(n=41)by using a random number table method.The control group received routine health education,while experimental group received guidance on periodic feedback method-based pelvic floor exercises.The compliance with pelvic floor muscle exercises,symptom scores for low anterior resection,and quality of life improvement were compared between two groups.Results After intervention,compliance with pelvic floor exercises was higher,symptom scores for low anterior resection was reduced,overall quality of life was improved in experimental group compared to control group(P＜0.05).Conclusion Periodic feedback method can enhance compliance with pelvic floor exercises and improve overall quality of life for rectal cancer patients with low anal preservation.

Objective:To explore the potential role of mRNA m7G modification in the pathogenesis of human adenocarcinoma of esophagogastric junction (AEG).Methods:Pathological tissue specimens from four AEG patients who underwent surgical treatment at the People′s Hospital Affiliated to Jiangsu University between 2018 and 2019 were selected. Tumor tissues and adjacent normal tissues were collected from these patients. RNA was extracted from both tissue types and subjected to m7G methylated RNA immunoprecipitation sequencing (m7G-MeRIP-seq) to analyze the patterns of m7G modification, the characteristics of differential m7G modification sites, the differentially expressed mRNA, and the correlation between m7G modification and mRNA expression levels. Differential m7G-modified genes ( MSH6, BRCA1, and SOX9) were further validated using methylated RNA immunoprecipitation quantitative PCR (MeRIP-qPCR), while the expression of METTL1 and WDR4 genes was examined by real-time quantitative PCR (RT-qPCR). This study was approved by the Medical Ethics Committee of the People′s Hospital Affiliated to Jiangsu University (Ethics No. 20150083). Results:① m7G-MeRIP-seq analysis revealed that m7G modifications in both AEG and adjacent normal tissues were predominantly located in the GC-rich region surrounding the internal start codon of mRNA. Differential m7G modification sites between the two groups were closely associated with cancer-related genes. ② mRNA library analysis showed that differentially expressed mRNA were predominantly upregulated in AEG tissues and downregulated in adjacent normal tissues. ③ Cross-analysis indicated that genes with hypermethylation tended to exhibit upregulated expression, while genes with hypomethylation were typically downregulated in AEG tissues. ④ MeRIP-qPCR validation confirmed that the mRNA expression of MSH6, BRCA1, and SOX9 were significantly upregulated in AEG tissues compared to adjacent normal tissues (AEG vs. normal, P<0.05). ⑤ RT-qPCR results demonstrated that the mRNA expression levels of METTL1 and WDR4 were also upregulated in AEG tissues (AEG vs. normal, P<0.000 5). Conclusion:These findings suggest that mRNA m7G modification plays a significant role in the development of AEG. Furthermore, proteins as METTL1 and WDR4 may facilitate AEG progression by regulating mRNA m7G modification. These results provide valuable insights into the molecular mechanisms underlying AEG and may inform future therapeutic strategies for this malignancy.

Objective:To construct and evaluate the nomogram prediction model of spontaneous rupture of primary liver cancer (STRPLC), and make the web-based dynamic online nomogram.Methods:Clinical data of 346 patients with PLC treated in the Second Affiliated Hospital of Kunming Medical University were retrospectively analyzed, including 87 males and 15 females, aged 58.15±10.32 years. Single factor and multiple factor logistic regression analysis were used to screen the influencing factors of STRPLC, and the prediction model was constructed based on the nomogram. Receiver operating characteristic (ROC) curve, calibration curve and clinical decision analysis were used to evaluate the model. The web-based dynamic online nomogram was developed using the DynNom package in R4.3.1 software.Results:Multivariate logistic regression analysis showed that the independent risk factors for spontaneous rupture and hemorrhage of tumor were no history of systematic anti-tumor therapy, alpha-fetoprotein (AFP) level, tumor protrusion on liver surface, tumor length, invasion of major blood vessels, and moderate to large amount of ascites (all P<0.05). The area under the receiver operating characteristic curve (AUC) of the prediction model constructed by this nomogram is 0.913 (95% CI: 0.884-0.943), the best cutoff value is 0.254, with a sensitivity of 0.892, and a specificity of 0.803. The calibration curve shows a good agreement between the predicted probability and the actual probability. The decision curve of the model is above the two invalid lines of " none" and " all" in the horizontal range of 0.07-0.98, and the clinical net benefit of the model is >0. Then user-friendly web-based dynamic online nomogram is constructed. Conclusion:Large tumor size, superficial location, no history of systematic anti-tumor therapy, high AFP level, invasion of major blood vessels, and moderate to large amount of ascites are independent risk factors for STRPLC. The prediction model and dynamic online nanogram constructed by this method can effectively assess the risk of STRPLC.

Objective To study the safety of amlodipine post-marketing and to mine the potential adverse drug event(ADE)signals,and to construct an intelligent query platform for ADE signals that can be popularized and applied to a variety of drugs.Methods The data from the first quarter of 2004 to the fourth quarter of 2024 were retrieved from the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database.A variety of disproportionality methods were used,including the reporting odds ratio(ROR)method,the United Kingdom Medicines and Healthcare products Regulatory Agency(MHRA)comprehensive standard method,Bayesian confidence propagation neural network(BCPNN)method,and the multi-item Gamma-Poisson shrinker(MGPS)method,to mine the signals of ADEs related to amlodipine.At the same time,a general query platform for mining ADE signals was developed based on the DeepSeek AI model to achieve the monitoring and analysis of the safety of various drugs.Results A total of 51,166 ADE reports were obtained,in which amlodipine was the primary suspected drug.Through the combined screening of the four algorithms,multiple potential ADE signals which had not been mentioned in the existing package inserts were found,including diseases of the ear and labyrinth(such as sensorineural hearing loss),diseases of the respiratory system,thorax and mediastinum(such as non-cardiogenic pulmonary edema),mental disorders(such as completed suicide),etc.The constructed digital intelligent platform had achieved the automated processing and monitoring of ADE data,providing a rapid access for clinicians and regulatory authorities to obtain drug safety information.Conclusion This study reveals potential safety risks associated with the use of amlodipine through real-world data mining.A risk assessment of patients' medication should be carried out before clinical use.In addition to paying attention to known ADEs,newly discovered potential risk signals should also be closely monitored.The construction of the digital intelligent platform provides an efficient tool for pharmacovigilance work.It can be popularized and applied to the safety monitoring of a variety of drugs,which is of great significance for improving the level of pharmacovigilance and the safety of medication.

Objective:This study aimed to propose an innovative modular surgical technique and explore its safety and application value in laparoscopic total gastrectomy combined with spleen-preserving hilar lymphadenectomy for advanced proximal gastric cancer invading the greater curvature.Methods:A retrospective collection was conducted on 34 patients with proximal gastric cancer invading the greater curvature who underwent laparoscopic total gastrectomy combined with spleen-preserving hilar lymphadenectomy in the same center from October 2020 to December 2022. The technical key points, precautions and crucial steps of the modular surgical technique were summarized, and the Clinical indicators were analyzed.Results:All 34 patients successfully completed the operation under laparoscopy without conversion to open surgery. The average operation duration was 151.9±4.1 minutes, and the duration of splenic hilar lymphadenectomy was 12.9±1.5 minutes. The median intraoperative blood loss was 50(20, 50) ml, and the blood loss during splenic hilar lymphadenectomy was 5 (2, 5) ml. The median number of harvested lymph nodes was 32.0 (23.5,39.5), and the number of submitted No.10 lymph nodes was 3 (2, 4). The metastasis rate of No.10 lymph nodes was 20.6% (7/34). No patient had intraoperative complications. During the postoperative hospital stay, one patient had incision infection (Clavien-Dindo I), and one patient had pulmonary infection (Clavien-Dindo II). The time for the first postoperative feeding was 3 (2, 5) days, the time for the first postoperative flatus was 2 (2,3) days, the time for the first postoperative defecation was 3 (3, 4) days, the total postoperative drainage volume was 1047.5 (607.5,1397.5) mL, the time for postoperative drainage tube removal was 7 (6, 9) days, and the length of postoperative hospital stay was 7.0 (6.0, 9.5) days.Conclusions:The application of the innovative modular surgical technique in laparoscopic total gastrectomy combined with spleen-preserving hilar lymphadenectomy can simplify surgical process and enable safe, precise and comprehensive dissection of splenic hilar lymph nodes.

Objective To study the safety of amlodipine post-marketing and to mine the potential adverse drug event(ADE)signals,and to construct an intelligent query platform for ADE signals that can be popularized and applied to a variety of drugs.Methods The data from the first quarter of 2004 to the fourth quarter of 2024 were retrieved from the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database.A variety of disproportionality methods were used,including the reporting odds ratio(ROR)method,the United Kingdom Medicines and Healthcare products Regulatory Agency(MHRA)comprehensive standard method,Bayesian confidence propagation neural network(BCPNN)method,and the multi-item Gamma-Poisson shrinker(MGPS)method,to mine the signals of ADEs related to amlodipine.At the same time,a general query platform for mining ADE signals was developed based on the DeepSeek AI model to achieve the monitoring and analysis of the safety of various drugs.Results A total of 51,166 ADE reports were obtained,in which amlodipine was the primary suspected drug.Through the combined screening of the four algorithms,multiple potential ADE signals which had not been mentioned in the existing package inserts were found,including diseases of the ear and labyrinth(such as sensorineural hearing loss),diseases of the respiratory system,thorax and mediastinum(such as non-cardiogenic pulmonary edema),mental disorders(such as completed suicide),etc.The constructed digital intelligent platform had achieved the automated processing and monitoring of ADE data,providing a rapid access for clinicians and regulatory authorities to obtain drug safety information.Conclusion This study reveals potential safety risks associated with the use of amlodipine through real-world data mining.A risk assessment of patients' medication should be carried out before clinical use.In addition to paying attention to known ADEs,newly discovered potential risk signals should also be closely monitored.The construction of the digital intelligent platform provides an efficient tool for pharmacovigilance work.It can be popularized and applied to the safety monitoring of a variety of drugs,which is of great significance for improving the level of pharmacovigilance and the safety of medication.

Objective This article focuses on the investment promotion policies at the municipal and district levels(park management committee level)of biomedical industrial parks in China at different development stages.It aims to reveal the characteristics and patterns of these policies,providing a reference for the formulation of development policies for biomedical industrial parks in China.Methods A total of 166 policies issued by three biomedical industrial parks(LifeBay,Nanjing Biotech and Pharmaceutical Valley and BioBay)from January 2013 to June 2023 were coded and quantitatively analyzed using a three-dimensional analytical framework of policy tool-development stage-issuing body.Results At the municipal level,the use of policy tools by administrative development is supply-oriented and environmental-oriented.At the district level,the types of policy tools used are closely related to the stage of the park.Start-up parks have a high proportion of supply-based policy tools,growth parks have a high proportion of demand-based policy tools,and mature parks have a high proportion of environmental policy tools.Conclusion Policy insights such as the strategic use of policy tools according to the development stage of the park,the optimization of the internal structure of the tools and the enhancement of the complementarity and coordination among the tools,and the use of policy tools to promote industrial agglomeration in line with local realities are put forward.