ObjectiveTo investigate the mechanism of Yangxin Tongmai Formula （养心通脉方， YTF） in trea-ting coronary heart disease with blood stasis syndrome based on DNA methylation. MethodsSeventy-two SD rats were randomly divided into a control group （n=12） and a modeling group （n=60）. The modeling group was subjected to a high-fat diet， intragastric administration of vitamin D3， and subcutaneous injection of isoprenaline to establish the rat model of coronary heart disease with blood stasis syndrome. Forty-one successfully modeled rats were then randomly allocated into model group， YTF low-， medium-， and high-dose groups， and the atorvastatin calcium group， with 8 rats in each group and 1 rat reserved. The YTF low-， medium-， and high-dose groups received YTF at 6， 12， and 18 g/（kg·d） by gavage， respectively. The atorvastatin calcium group received atorvastatin calcium tablets at 1.8 mg/（kg·d） by gavage. The control group and the model group received 0.9% sodium chloride injection at 4 ml/（kg·d） by gavage. All administrations were performed once daily for 3 weeks. Twenty-four hours after the last administration， serum lipid levels including total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C）， myocardial enzymes including cardiac troponin T （cTnT）， creatine kinase MB （CK-MB）， and lactate dehydrogenase （LDH）， and inflammatory factors including interleukin-1β （IL-1β） and interleukin-10 （IL-10） were detected by ELISA. Pathological changes in myocardial tissue were observed via HE staining. Whole blood DNA methylation sequencing was used to analyze differential methylation gene expression among the control group， model group， and YTF high-dose group. Western Blotting was used to verify the protein levels of the key genes and downstream signaling pathways. ResultsCompared to the control group， the model group showed increased levels of TC， TG， LDL-C， cTnT， CK-MB， LDH， and IL-1β， along with decreased levels of HDL-C and IL-10 （P＜0.05 or P＜0.01）. Compared to the model group， all treatment groups exhibited decreased levels of TC， LDL-C， CK-MB， and LDH， along with increased IL-10 levels. Among these， the high-dose YTF group demonstrated superior efficacy in reducing cTnT levels compared to the other TCM groups （P＜0.05 or P＜0.01）. HE staining indicated that the YTF high-dose group ameliorated myocardial cell swelling， disordered arrangement， pyknosis， and disappearance of nuclei， thereby reducing myocardial cell damage. Whole blood DNA methylation sequencing identified 240 differentially methylated genes shared by the control group， model group， and YTF high-dose group， including 109 hypermethylated and 131 hypomethylated genes； eif2ak3 was identified as a key differentially methylated gene. Compared to the control group， the model group exhibited increased protein levels of eukaryotic translation initiation factor 2 alpha kinase 3 （eIf2ak3）， phosphorylated protein kinase RNA-like endoplasmic reticulum kinase （p-PERK）， activating transcription factor 4 （ATF4）， C/EBP homologous protein （CHOP）， and Bax， along with a decreased level of B-cell lymphoma-2 （Bcl-2） protein （P＜0.05 or P＜0.01）. Compared to the model group， the YTF high-dose group showed decreased protein levels of eIf2ak3， p-PERK， ATF4， CHOP， and Bax， and an increased level of Bcl-2 protein （P＜0.05 or P＜0.01）. ConclusionYTF may regulate key differentially methylated genes such as eIf2ak3 and the PERK/ATF4/CHOP signaling pathway， thereby inhibiting endoplasmic reticulum stress， reducing myocardial cell apoptosis， and exerting therapeutic effects in coronary heart disease blood stasis syndrome.

This article provides a systematic interpretation and review of the Society of Critical Care Medicine 2024 Guidelines on Adult ICU Design. Developed based on the Grading of Recommendations Assessment, Development and Evaluation methodology, the guideline address five core themes: ICU layout, room design, infection control, infrastructure, and staff spaces, and put forward 17 evidence-based recommendations, including 5 good practice statements. This article briefly introduces the guideline development methods and evidence characteristics, and focuses on summarizing key recommendations, including high-visibility layouts, single-bed ward settings, natural lighting and noise reduction strategies, integrated infection prevention and control design, remote monitoring, and flexible capacity expansion capabilities. Furthermore, it delves into the applicability and localized implementation pathways within China's healthcare environment, analyzing limitations in terms of evidence quality, specialty applicability, and cost-effectiveness. Furthermore, by integrating the Chinese Guidelines for the Construction and Development of Critical Care Medicine (2025 Edition) and current domestic practices, the article proposes tiered and phased implementation recommendations. This article aims to provide domestic healthcare institutions with a scientific reference that balances international cutting-edge concepts with China's real-world conditions for the construction and renovation of ICUs, thereby promoting the development of intensive care environments centered on patient safety, healthcare worker well-being, and infection control.

OBJECTIVE To construct a preoperative medication reconciliation model assisted by a localized large language model （LLM） for gastric cancer and evaluate its clinical efficacy. METHODS A total of 249 gastric cancer patients with a history of continuous medication before admission in the Gastric Surgery Department of Jiangsu Cancer Hospital were retrospectively enrolled. Patients were divided into training set （154 cases） and validation set （95 cases） based on the order of time. Based on guidelines， drug package inserts， and other evidence， a standardized medication reconcili ation process and a structured knowledge base were constructed. DeepSeek-V3 LLM was deployed privately in the hospital， combined with retrieval-augmented generation technology， to achieve automated integration of medication information， risk screening， and generation of personalized recommendations. The quality of LLM-generated recommendations was evaluated using automatic metrics （BERT Score and ROUGE-1， 2， L） and manual scoring [seven-dimensional index （7DI） ] . Spearman correlation analysis was performed to explore the correlation between automatic scores and manual scores. Cronbach’s α coefficient was used to test the internal consistency of manual scoring results. The time consumed by manual and LLM-assisted medication reconciliation was compared across tasks of different difficulty levels （simple， moderate， and high）. RESULTS A structured knowledge base covering 8 major drug categories was finally established， covering common and high-risk preoperative medication scenarios and providing structured retrieval support for the LLM. For automatic evaluation， the precision， recall， and F1-score of BERT Score were 0.783±0.033， 0.811±0.038， and 0.796±0.028， respectively. The F1-scores of ROUGE-1， ROUGE-2 and ROUGE-L were 0.566±0.067， 0.338±0.076 and 0.468±0.082， respectively. The 7DI scores from three manual raters ranged from 32.06 to 33.45. The F1-score of automatic scoring was significantly positively correlated with the 7DI score of manual scoring （maximum coefficient of determination＝0.611， P ＜0.001）， and the internal consistency of manual scoring was good （Cronbach’s α ＝ 0.876）. In terms of efficiency， LLM-assisted medication reconciliation reduced time consumption by more than 90% compared with manual reconciliation in the simple， moderate， and high-difficulty groups （ P ＜0.001）. CONCLUSIONS The medication reconciliation model constructed based on a localized LLM and structured knowledge base shows high accuracy， consistency， and clinical applicability in complex preoperative medication scenarios for gastric cancer. It can improve the efficiency of medication reconciliation and reduce potential medication risks.

OBJECTIVE To evaluate the cost-effectiveness of fluzoparib monotherapy versus combination with apatinib as second-line or later-line treatment for patients with germline BRCA1 / 2 -mutated human epidermal growth factor receptor 2-negative （HER2－） metastatic breast cancer， from the perspective of the Chinese healthcare system. METHODS Based on the FABULOUS trial， a partitioned survival model was developed to simulate disease progression， with a cycle length of 21 days and a time horizon of 10 years. A discount rate of 4.5% per annum was applied. Model outputs included total costs and quality-adjusted life years （QALYs）. Cost-utility analysis was conducted by comparing the incremental cost-effectiveness ratio （ICER） between the two regimens against a willingness-to-pay （WTP） threshold set at twice China’s per capita gross domestic product in 2025 （199 330 yuan/QALY）. Robustness of the base-case results was tested through one-way sensitivity analysis， probabilistic sensitivity analysis， and scenario analyses. RESULTS For patients with germline BRCA1/2 -mutated HER2－ metastatic breast cancer， fluzoparib combination with apatinib provided greater health benefits （1.91 QALYs vs. 1.69 QALYs） and incurred lower total costs （1 634 119.3 yuan vs. 1 855 264.2 yuan） compared with fluzoparib monotherapy， thus representing a dominant strategy. One-way sensitivity and probabilistic sensitivity analyses confirmed the robustness of the base-case findings. Scenario analyses showed that the conclusion remained robust when the time horizon was shortened to 5 years or when the discount rate was changed to 3%； however， the results reversed when the extrapolation distribution model was altered. CONCLUSIONS Under the current WTP threshold， compared with fluzoparib monotherapy， the combination of fluzoparib and apatinib is more cost-effective as a second-line or later-line treatment for Chinese patients with germline BRCA1 / 2 -mutated HER2－ metastatic breast cancer.

OBJECTIVE To further standardize the technical operations and management processes throughout therapeutic drug monitoring （TDM）， clarify the clinical value of TDM implementation， improve the scientific validity and reliability of monitoring results， and provide a solid reference basis for the formulation and optimization of clinical individualized precision dosing regimens. METHODS The Guidelines for the Management of Therapeutic Drug Monitoring were formulated in accordance with the latest definition of guidelines by the Institute of Medicine of the National Academies and the standard guideline development methodology of the World Health Organization， and in compliance with the requirements of the appraisal of guidelines for research and evaluation. A modified Delphi method was adopted to establish the research question system； evidence-based medicine research methods were applied to systematically search multiple databases to screen the latest and most comprehensive evidence. Evidence was graded and evaluated based on the evidence grading system of the Chinese Evidence-Based Medicine Center， and the grading criteria for recommendation strength from the Oxford Centre for Evidence-Based Medicine were used to determine the recommendation strength. The recommendation opinions were formed through multidisciplinary expert consensus. RESULTS The Guidelines for the Management of Therapeutic Drug Monitoring cover four core modules， including TDM application indications， technical procedures， result interpretation and clinical application， and quality control， involving 18 primary research questions， 34 secondary research questions， and yield 82 recommendations. CONCLUSIONS The guidelines systematically standardize the key technical links and management requirements of the whole TDM process， provide scientific and operable standardized tools， help improve the standardization level of TDM work， promote the translation of monitoring results into clinical decision-making， and provide strong support for precision personalized medicine and ensuring the safety and rationality of medication use.

Objective:The SARS-CoV-2 has a high natural mutation rate, and dynamic monitoring of virus variants remains a key focus in current COVID-19 prevention and control efforts.Methods:In this study, a sensitive and rapid method for detecting SARS-CoV-2 omicron variant nucleic acid was established based on the BMD-PCR technology.Results:This method showed good specificity, and had no cross-reactivity with 11 common viruses transmitted via the respiratory and gastrointestinal tracts, and the limit of detection is 555 copies/ml. Compared with SARS-CoV-2 whole-genome sequencing result, among 50 samples with original Ct values ≤32 tested for the Omicron variant, 49 samples tested positive for the N679K mutation site using BMD-PCR Omicron variant detection, achieving a concordance rate of 98.00%. For 30 samples JN.1 lineage, 29 samples tested positive for the K356T mutation site using BMD-PCR JN.1 lineage detection, with a concordance rate of 96.67%. For 10 samples with original SARS-CoV-2 detection Ct values between 35 and 32, 7 samples tested positive for the N679K mutation site using BMD-PCR Omicron variant detection, Resultsing in a detection rate of 70.00%. For samples with SARS-CoV-2 nucleic acid detection Ct values>35, the detection rate for the N679K mutation site in the BMD-PCR Omicron variant was 20.00%.Conclusions:This method can serve as a high-throughput supplementary approach for the preliminary identification of SARS-CoV-2 variant genotypes.

Objective:To explore the clinical effect of thin superficial circumflex iliac artery perforator flap with venous superdrainage in treatment of wound in extremities.Methods:Clinical data of 20 patients who were treated from January 2018 to January 2024 in the Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University were retrospectively analysed. The soft tissue defects in extremity were reconstructed with thin perforator flaps of superficial iliac circumflex artery with venous superdrainage. There were 13 patients with upper limb defects and 7 with ankle defects. Of the defects, 12 were of trauma, 2 of tumour resection, 3 of scar release surgery and 3 of donor flat harvesting. The defects ranged from 5.0 cm×4.0 cm to 18.0 cm×7.0 cm in size. During the surgery, portable Doppler was used to detect the perforating branches of the superficial rotational iliac artery and design flaps. The flaps were 5.0 cm×5.0 cm to 20.0 cm×7.0 cm in size, including 16 single-lobed flaps, 3 double-lobed flaps and 1 triple-lobed flaps. The flaps were 2-7 mm in thickness, with an average of 4 mm. Based on the distribution of perforators, the flaps carried the superficial helioiliac artery and the accompanying vein, as well as the superficial helioiliac vein. The superficial helioiliac artery and the accompanying vein were anastomosed during the surgery, and the superficial helioiliac vein was anastomosed to the superficial or deep vein of the recipient site for superreflux. The donor sites were all directly sutured and closed. Postoperative follow-up was conducted by visits of outpatient clinic, and via telephone and WeChat interviews. The survival and appearance of the flaps and complications were observed.Results:A total of 22 arteries and 42 veins of the 20 flaps were anastomosed in surgery. All flaps survived. The donor sites were closed in the first stage. No vascular compromise occurred. One patient had early exudate under the flap on the exposed wound of interphalangeal joint, which healed after routine dressing change and drainage. All patients were included in the postoperative follow-up, with a peroid over 5 to 40 months, at 10.8 months in average. The flaps were thin and soft, with good wear resistance and without pigmentation. The healing of donor sites was good except 1 donore site that had early lymphatic leakage, which was cured after compression and drainage. A linear scar left at the donor sites and it was acceptable to the patients.Conclusion:The treatment of defective soft tissue wounds in extremities using thin perforator flap with venous superdrainage of the superficial circumflex iliac artery is safe and feasible. No further flap thinning surgery is required, and there is a reliable clinical effect.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Objective To explore the occurrence and influencing factors of MODS in elderly pa-tients with SAH.Methods A retrospective analysis was conducted on 187 elderly SAH patients admitted in the Second Affiliated Hospital of Guizhou Medical University from January 2021 to June 2024.According to the presence or absence of MODS,they were divided into MODS group(81 cases)and non-MODS group(106 cases).Their general clinical data were compared between the two groups.Multivariate logistic regression analysis was used to identify the risk factors for MODS in elderly SHA patients.ROC curve analysis was applied to evaluate the predictive value of the major risk factors for MODS in the patients.Results The MODS group had significantly ad-vanced age,larger proportion of modified Fisher grades Ⅲ—Ⅳ,higher APACHE Ⅱ score,and in-creased FPG level than the non-MODS group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that APACHE Ⅱ score(OR=1.108,95％CI:1.070-1.148,P=0.000)and mo-dified Fisher grade(OR=1.143,95％CI:1.095-1.194,P=0.000)were independent risk factors for MODS in elderly SAH patients.ROC curve analysis suggested that the AUC value of APACHE Ⅱ score,modified Fisher grade and their combination in predicting the occurrence of MODS in elderly SAH patients was 0.809,0.737 and 0.880,respectively,with a sensitivity of 59.35％,88.93％and 84.02％,and a specificity of 88.73％,58.52％and 81.15％,respectively.The combined detection showed better predictive performance than the indicator alone(P＜0.01).Con-clusion The incidence of MODS is quite high in elderly patients with SAH.APACHE Ⅱ score and modified Fisher grade are the main risk factors affecting the occurrence of MODS.

Objective To analyze the main epidemiological characteristics of fungal infection in this hospital in the past 7 years,and to provide reference for clinical treatment and prevention and control strategies of fun-gal infection.Methods The fungal data and clinical data of related patients isolated from clinical samples in Peking Union Medical College Hospital from early January 2018 to the end of May 2024 were selected,and the main epidemiological characteristics of fungal infection in this hospital were identified and described through multi-angle statistical analysis.Results A total of 4 479 patients with filamentous fungal infection were en-rolled.The proportion of male patients[57.5％(2 576/4 479)]was higher than that of female patients[42.5％(1 903/4 143)],mainly distributed in internal medicine,Intensive Care Unit(ICU)and emergency de-partment,among which internal medicine accounted for the highest proportion[50.0％(2 241/4 479)].About 90.0％of the specimens were from the lower respiratory tract,in addition to specimens from skin and soft tis-sue,tissue,ear and blood culture.In terms of seasonal distribution,there are more patients in winter.The fun-gi were mainly composed of Aspergillus,Mucor,Cerdosporium,Fusarium and Penicillium,among which As-pergillus was the most abundant,accounting for 74.6％of the total.Aspergillus fumigatus was the most a-bundant Aspergillus,accounting for 42.5％of the total Aspergillus(1 418/3 340).Among the related infec-tions caused by mold,Aspergillus was the most common in the lower respiratory tract,accounting for 76.8％.Among them,Aspergillus fumigatus accounted for the highest proportion(33.6％).98.6％of the molds infected the ear were Aspergillus,of which Aspergillus niger and Aspergillus terreus were the most common.Skin infections are mainly caused by Sporothrix schenckii,Trichophyton rubrum,Microsporum ca-nis.The results of in vitro drug sensitivity test showed that the four common Aspergillus isolated in this hos-pital were sensitive to voriconazole,and amphotericin B had better antifungal activity against Mucorales in vitro.Conclusion Based on the main epidemiological characteristics of fungal infections in this hospital,it is recommended that special attention be paid to the admission of patients in the respiratory department during the peak infection period in autumn and winter.In the treatment of fungal infections in different regions and on different body parts,attention should be paid to the differences in the distribution of bacterial species.