Diabetic retinopathy(DR)is one of the most common and serious microvascular complications of diabetes, posing a significant threat to patients' visual health. In recent years, epigenetic mechanisms have garnered increasing attention in the scientific community for their pivotal role in the onset and progression of DR. This paper systematically examines the regulatory roles of epigenetic mechanisms in DR, covering key pathways such as DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs. Under hyperglycemic conditions in diabetes, these epigenetic mechanisms modulate gene expression, thereby influencing critical pathological processes such as oxidative stress, inflammatory responses, mitochondrial dysfunction, and metabolic memory. This article reviews recent advances in epigenetic regulation in DR, providing an in-depth analysis of its underlying molecular mechanisms and complex regulatory networks, and explores the potential of epigenetic markers as diagnostic biomarkers and therapeutic targets. Additionally, this article highlights emerging therapeutic strategies targeting epigenetic modifications, aiming to provide a theoretical foundation and research direction for the early diagnosis and precision treatment of this disease.

Uveal melanoma(UM)is the most common primary intraocular malignancy in adults, characterized by high invasiveness and unique metastatic biological features. Although local treatments(such as proton beam therapy and brachytherapy)can effectively control the primary lesion, approximately 50% of patients eventually develop distant metastasis, with the liver being the primary target organ(occurring in 90% of cases). This highlights a paradigm shift in treatment focus from mere local control to systemic prevention and management. For metastatic UM(mUM), current treatment strategies encompass biomarker-guided molecular targeted therapy, immunotherapy(including Tebentafusp, vaccines, and oncolytic virus therapy), and liver-directed therapy. Focusing on the synergy between local and systemic prevention and control, this article systematically elaborates on the precision local treatment for primary UM, the decision-making pathway for systemic treatment of metastatic UM based on molecular subtyping, the integration of local and systemic therapies for liver metastases, and the translational value of nanomedicine in addressing therapeutic bottlenecks. It provides insights for optimizing clinical management of mUM and developing novel therapeutic strategies.

From the perspective of narrative medicine， focusing on the “three focal points，” integrating the “three elements，” and grounding in the “four relationships，” this study employed a close reading framework of “metaphor， time， space， and voice” to conduct a detailed interpretation on the approach and methodology of the medical narrative in the classic traditional Chinese medical case record Yi’s Medical Case. The close reading revealed that the author of the case record， Yi Dagen， demonstrated exceptional sensitivity to time and space. He excelled in tracing the complete process of disease occurrence and development within the natural rhythms of life， and in discerning the full truth of disease within the unified “body-society-nature” heaven-human field. When facing different subjects in diagnosis and treatment， Yi Dagen consistently rejected one-way knowledge inculcation and instead chose egalitarian dialogue. He was particularly adept at using metaphorical tools to embed obscure medical theories into patients’ disease stories through the form of life experience， thereby building shared medical understanding among different subjects and achieving the “co-creation of meaning” of disease stories. Through a reflective representation of the findings from the close reading， it was argued that Yi Dagen’s diagnostic and therapeutic narrative logic of “pulse-pattern-symptom-treatment” and the metaphorical narrative possessing dual functions of ontological cognition and an interpretive tool were an important means for fostering empathy and facilitating healing， as well as a concentrated manifestation of Yi Dagen’s “patient-centered” medical attitude. Analyzing Yi Dagen’s sophisticated narrative strategies and techniques provides wisdom references for cultivating medical staff’s narrative competence and offers historical insights for the localized development of narrative medicine.

Abnormal amino acid metabolism promotes tumor progression by inducing malignant behaviors in tumor cells and altering the immune landscape within the tumor microenvironment. However, the underlying mechanisms remain unclear. In this study, we constructed colorectal cancer (CRC) organoids and patient-derived tumor xenograft (PDX) models, performing multifaceted validation to confirm that T-complex protein 1 subunit epsilon (CCT5), mediates the biosynthesis of aspartate and enhances sensitivity to anti-PD-L1 immunotherapy. Mechanistically, CCT5 directly binds to asparagine synthetase (ASNS) and promotes the synthesis of aspartate (Asn). The Asn-mTORC1 axis facilitates tumor cell proliferation while upregulating PD-L1 expression, which leads to a reduction in the number of effector CD8⁺ T cells. Treatment with l-asparaginase (ASNase) combined with anti-PD-L1 therapy effectively reverses the growth of CRC characterized by high CCT5 expression. In summary, we identify CCT5 as a potential biomarker to guide the combined use of ASNase and anti-PD-L1 antibodies in CRC treatment.

ObjectiveTo investigate the effect and mechanism of Sishenwan in restoring the intestinal barrier function in the rat model of diarrhea-predominant irritable bowel syndrome （IBS-D） due to spleen-kidney Yang deficiency based on intestinal flora and short-chain fatty acids. MethodsAfter the delivery of 10 SPF-grade pregnant rats， 4 male suckling rats were kept in each litter for the experiment. The male suckling rats were randomly allocated into blank， model， low-dose （3.51 g·kg^-1） Sishenwan， high-dose （7.02 g·kg^-1） Sishenwan， and Peifeikang （0.54 g·kg^-1） groups， with 8 rats in each group. The blank group was fed conventionally， and the other groups were subjected to mother-child separation and Sennae Folium gavage （1 g·mL^-1， 10 mL·kg^-1） for the modeling of IBS-D due to spleen-kidney Yang deficiency. After the modeling was completed， the rats in Sishenwan groups were administrated with the corresponding dose of Sishenwan decoction by gavage， and the Peifeikang group with bifidobacterium triple live powder+normal saline suspension. The blank and model groups were treated with an equal volume of normal saline by gavage. The general conditions and fecal characteristics of rats were observed. After 2 weeks of administration， the rats were anesthetized for sample collection. The pathological changes of the colon tissue in rats were observed by hematoxylin-eosin staining. Enzyme-linked immunosorbent assay was employed to measure the levels of transforming growth factor-beta （TGF-β）， interleukin-10 （IL-10）， and interleukin-22 （IL-22）. Immumohistochemical staining （IHC） was performed to detect the positive expression of zonula occludens-1 （ZO-1） and occludin in the colon tissue. Western blot was employed to determine the protein levels of ZO-1 and occludin in the colon tissue of rats， and 16S rRNA gene sequencing was performed for intestinal flora. Gas chromatography-mass spectrometry was employed to determine the content of short-chain fatty acids （SCFAs） in the cecum contents of rats. ResultsThe colon tissue in the blank group presented a clear structure， neat glands， and no inflammatory cell infiltration. In the model group， the colon tissue showcased a disorganized structure， irregular arrangement of glands， and inflammatory cell infiltration. Compared with the model group， the low-dose and high-dose Sishenwan groups and the Peifeikang group exhibited an intact colon tissue structure， regular arrangement of glands， and reduced inflammatory cell infiltration. Compared with the blank group， the modeling lowered the levels of TGF-β， IL-10， and IL-22 in the serum （P<0.01）， down-regulated the protein levels of ZO-1 and occludin in the colon tissue （P<0.01）， and decreased the content of acetic acid and propionic acid and increased the content of butyric acid in cecum contents （P<0.05）. Compared with the model group， low-dose and high-dose Sishenwan raised the levels of TGF-β， IL-10， and IL-22 in the serum （P<0.05， P<0.01）， and Peifeikang elevated the levels of TGF-β and IL-10 in the serum （P<0.01）. High-dose Sishenwan and Peifeikang up-regulated the protein levels of ZO-1 and occludin （P<0.05， P<0.01）， increased the content of acetic acid and propionic acid in cecum contents （P<0.05）， and decreased the content of butyric acid （P<0.05）. The 16S rRNA gene sequencing results showed that the intestinal flora structure of the model group changed compared with that of the blank group. Compared with the model group， Sishenwan and Peifeikang increased the relative abundance of Lachnospiraceae， Muribaculaceae， Akkermansiaceae， Ligilactobacillus， UBA3282， Akkermansia， and Corynebacterium while reducing the relative abundance of Oscillospiraceae， Desulfovibrionaceae， Lactobacillus， Romboutsia， and Desulfovibrio. They can restore the intestinal flora structure similar to that in the blank group. ConclusionSishenwan can alleviate diarrhea symptoms and colonic mucosal inflammation， increase the expression of tight junction proteins in the colonic mucosa， and strengthen the intestinal barrier in IBS-D rats with the syndrome of spleen-kidney Yang deficiency. The mechanism of action may be related to optimizing the structure and balance of intestinal flora and regulating the SCFAs， and the effect of high-dose Sishenwan is obvious.

ObjectiveTo investigate the effect and mechanism of Sishenwan in restoring the intestinal barrier function in the rat model of diarrhea-predominant irritable bowel syndrome （IBS-D） due to spleen-kidney Yang deficiency based on intestinal flora and short-chain fatty acids. MethodsAfter the delivery of 10 SPF-grade pregnant rats， 4 male suckling rats were kept in each litter for the experiment. The male suckling rats were randomly allocated into blank， model， low-dose （3.51 g·kg^-1） Sishenwan， high-dose （7.02 g·kg^-1） Sishenwan， and Peifeikang （0.54 g·kg^-1） groups， with 8 rats in each group. The blank group was fed conventionally， and the other groups were subjected to mother-child separation and Sennae Folium gavage （1 g·mL^-1， 10 mL·kg^-1） for the modeling of IBS-D due to spleen-kidney Yang deficiency. After the modeling was completed， the rats in Sishenwan groups were administrated with the corresponding dose of Sishenwan decoction by gavage， and the Peifeikang group with bifidobacterium triple live powder+normal saline suspension. The blank and model groups were treated with an equal volume of normal saline by gavage. The general conditions and fecal characteristics of rats were observed. After 2 weeks of administration， the rats were anesthetized for sample collection. The pathological changes of the colon tissue in rats were observed by hematoxylin-eosin staining. Enzyme-linked immunosorbent assay was employed to measure the levels of transforming growth factor-beta （TGF-β）， interleukin-10 （IL-10）， and interleukin-22 （IL-22）. Immumohistochemical staining （IHC） was performed to detect the positive expression of zonula occludens-1 （ZO-1） and occludin in the colon tissue. Western blot was employed to determine the protein levels of ZO-1 and occludin in the colon tissue of rats， and 16S rRNA gene sequencing was performed for intestinal flora. Gas chromatography-mass spectrometry was employed to determine the content of short-chain fatty acids （SCFAs） in the cecum contents of rats. ResultsThe colon tissue in the blank group presented a clear structure， neat glands， and no inflammatory cell infiltration. In the model group， the colon tissue showcased a disorganized structure， irregular arrangement of glands， and inflammatory cell infiltration. Compared with the model group， the low-dose and high-dose Sishenwan groups and the Peifeikang group exhibited an intact colon tissue structure， regular arrangement of glands， and reduced inflammatory cell infiltration. Compared with the blank group， the modeling lowered the levels of TGF-β， IL-10， and IL-22 in the serum （P<0.01）， down-regulated the protein levels of ZO-1 and occludin in the colon tissue （P<0.01）， and decreased the content of acetic acid and propionic acid and increased the content of butyric acid in cecum contents （P<0.05）. Compared with the model group， low-dose and high-dose Sishenwan raised the levels of TGF-β， IL-10， and IL-22 in the serum （P<0.05， P<0.01）， and Peifeikang elevated the levels of TGF-β and IL-10 in the serum （P<0.01）. High-dose Sishenwan and Peifeikang up-regulated the protein levels of ZO-1 and occludin （P<0.05， P<0.01）， increased the content of acetic acid and propionic acid in cecum contents （P<0.05）， and decreased the content of butyric acid （P<0.05）. The 16S rRNA gene sequencing results showed that the intestinal flora structure of the model group changed compared with that of the blank group. Compared with the model group， Sishenwan and Peifeikang increased the relative abundance of Lachnospiraceae， Muribaculaceae， Akkermansiaceae， Ligilactobacillus， UBA3282， Akkermansia， and Corynebacterium while reducing the relative abundance of Oscillospiraceae， Desulfovibrionaceae， Lactobacillus， Romboutsia， and Desulfovibrio. They can restore the intestinal flora structure similar to that in the blank group. ConclusionSishenwan can alleviate diarrhea symptoms and colonic mucosal inflammation， increase the expression of tight junction proteins in the colonic mucosa， and strengthen the intestinal barrier in IBS-D rats with the syndrome of spleen-kidney Yang deficiency. The mechanism of action may be related to optimizing the structure and balance of intestinal flora and regulating the SCFAs， and the effect of high-dose Sishenwan is obvious.

Objective:To investigate the clinicopathological features, treatment-effect assessment and prognosis of SMARCA4-deletion non-small cell lung cancer (NSCLC) that was treated with neoadjuvant therapy.Methods:Eleven consecutive cases of SMARCA4-deletion NSCLC treated with neoadjuvant therapy in Guangdong Provincial People′s Hospital, Guangzhou, China from January 2007 to October 2024 were collected. Their clinicopathological features, pathological assessment of treatment effect, and prognosis were retrospectively analyzed.Results:All the 11 patients were male. Their median age at diagnosis was 56 (49,64) years. Nine patients were smokers (9/11). Ten patients received neoadjuvant chemoimmunotherapy, and one received neoadjuvant targeted therapy. Eleven biopsy samples showed SMARCA4 complete loss, including 7 cases of invasive non-mucinous adenocarcinoma, 1 case of invasive mucinous adenocarcinoma, 1 case of non-keratinizing squamous cell carcinoma, and 2 cases of NSCLC, not otherwise specified. The histological response to neoadjuvant therapy in resected specimens varied, including tumor necrosis, foam cell aggregation, cholesterol clefts, immune cell infiltrates, reactive granulomas, and stromal fibrosis. Three cases of the primary lesion achieved major pathological response (MPR), and 2 cases achieved complete pathological response (CPR). The MPR rate of neoadjuvant chemoimmunotherapy was 3/10 while its CPR ratio was 2/10. Of the 9 resected specimens that did not achieve CPR, 5 showed a post-treatment histological type different from the pre-treatment one. Eight tumors showed complete SMARCA4 loss, while 1 showed heterogeneous expression. Of the 11 biopsy specimens examined using next generation sequencing, 9 cases showed class 1 SMARCA4 mutations (including 7 nonsense mutations and 2 acquired nonsense mutations), and 2 cases showed wild-type SMARCA4. Taking immunohistochemistry as the gold standard, the sensitivity of next generation sequencing for the detection of SMARCA4-deletion NSCLC was 9/11. After follow-up of 6.9 to 46.6 months, five patients experienced postoperative recurrence, and 6 patients were disease free. The disease-free survival ranged from 0.7 to 27.5 months (median, 7.6 months).Conclusions:The surgical specimens of SMARCA4-deletion NSCLC with neoadjuvant therapy show varying degrees of treatment response. The tumor components sensitive to chemoimmunotherapy and targeted therapy are mostly adenocarcinoma and squamous cell carcinoma, while large cell carcinoma, spindle cell carcinoma and giant cell carcinoma are relatively less sensitive to treatment. Assessment of MPR and CPR suggests that some NSCLC patients with SMARCA4-deletion can benefit from neoadjuvant therapy.

Objective To evaluate drug-related problems(DRPs)and to analyze the influencing factors of patients un-dergoing video-assisted thoracoscopic surgery(VATS)before operation in thoracic surgery.Methods Clinical pharmacists used the Pharmaceutical Care Network Europe(PCNE)classification system(version 9.1)to analyze DRPs and influencing fac-tors of patients who received VATS from March 1 to May 31,2023,and had at least one comorbidity.Results Out of 300 pa-tients,174 were involved in a total of 200 DRPs.The most common category of DRPs is treatment safety(47.50％),followed by treatment effectiveness(46.00％)and others(6.50％).The most common cause of the problem is drug selection(33.83％),fol-lowed by other(33.33％)and patient cause(19.90％).367 interventions were conducted for DRPs,with the most interventions being at the drug level(55.86％),followed by the doctor level(39.24％)and the patient level(3.54％).In the end,96.00％of the intervention plan was accepted,and 86.50％of the problems were resolved.There were significant differences(P＜0.05)in the number of underlying diseases,medication varieties,body mass index(BMI),and length of hospital stay between the group with and without DRPs.The results of multivariate analysis showed that comorbidities,number of medication types,and BMI were independent risk factors for preoperative occurrence(or potential)of DRPs in VATS patients in thoracic surgery(OR＞1,P＜0.05).Conclusions Clinical pharmacists can effectively evaluate preoperative DRPs in patients undergoing VATS in thoracic surgery through the PCNE classification system.Comorbidities,number of medications,and BMI are influential factors for the oc-currence of preoperative DRPs.Future clinical practice should focus on these risk factors to optimize treatment strategies and re-duce the occurrence of DRPs.

Objective:To investigate the impact of para-tumoral micro-metastasis(PTMM) and other clinicopathological characteristics on the prognosis of patients with intrahepatic cholangiocarcinoma (ICC).Methods:This is a retrospective cohort study. Clinical data from 137 ICC patients who underwent radical resection at the Hepatobiliary Surgery Center, Department of General Surgery, Huashan Hospital, Fudan University, between January 2017 and December 2022 were analyzed retrospectively. The cohort included 91 males and 46 females, with age ( M(IQR)) of 63 (13) years (range: 32 to 82 years). Kaplan-Meier curves were used to estimate median survival times, while Log-rank tests assessed differences in overall survival (OS) and recurrence-free survival (RFS). Univariate and multivariate Cox regression models were employed to identify factors associated with OS and RFS. Results:The median OS for all 137 ICC patients was 34 months, with 1-, 2-, and 3-year OS rates of 90.7%, 69.4%, and 39.5%, respectively. The results of univariate and multivariate Cox analysis showed that Child-Pugh grade, CA19-9, carcinoembryonic antigen, and PTMM were independent prognostic factors for OS in ICC patients after radical resection (all P<0.05), Child-Pugh grade, maximum tumor diameter, whether lymph node metastasis, and PTMM were independent prognostic factors for RFS in radical resection in ICC patients (all P<0.05). PTMM-positive patients had a median OS of 21 months and median RFS of 12 months, whereas PTMM-negative patients exhibited a median OS exceeding 60 months and median RFS of 36 months. Log-rank tests demonstrated statistically significant differences in OS and RFS between PTMM-positive and PTMM-negative patients ( P<0.01 and P=0.001, respectively). Conclusion:Preliminary findings suggest that PTMM holds significant prognostic value in evaluating outcomes for ICC patients undergoing curative resection.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP