AIM:To explore the effect of miR-1246 on high glucose-induced retinal microvascular endothelial cells(RMECs)injury by regulating methyltransferase like 3(METTL3)mediated sirtuin 1(SIRT1)N6-methyladenosine(m6A)modification.METHODS:Dual luciferase assay was used to detect miR-1246 regulation of METTL3 expression; RMECs cells were divided into control group, high glucose(HG)group, high glucose+knocking down control(HG+anti-miR-NC)group, high glucose+knocking down miR-1246 expression(HG+anti-miR-1246)group, high glucose+overexpression control(HG+NC)group, high glucose+overexpression METTL3(HG+METTL3)group, high glucose+overexpression miR-1246+control(HG+miR-1246+NC)group, and high glucose+overexpression miR-1246+METTL3(HG+miR-1246+METTL3)group. After induction of high glucose for 48 h, CCK-8 method was used to detect cell survival; Annexin V-FITC/PI method was used to detect cell apoptosis; Transwell experiment was used to detect cell migration and invasion; ELISA method was used to detect cell oxidative stress and inflammation levels; Colorimetric method was used to detect m6A methylation level in total RNA; MeRIP-qPCR method was used to detect SIRT1 m6A methylation level; Real-time quantitative PCR was used to detect miR-1246, METTL3, SIRT1 mRNA expression in cells; Western blot was used to detect METTL3, SIRT1 and endothelial mesenchymal transition(EndMT)markers protein expression in cells.RESULTS: The MiR-1246 regulated METTL3 expression. Compared with the control group, cell survival rate was decreased in the HG group, apoptosis rate was increased, and the number of migrating and invading cells were increased, lactate dehydrogenase(LDH)activity, tumor necrosis factor-α(TNF-α), and interleukin(IL)-6 levels in cell culture supernatant were increased, IL-10 level was decreased, malondialdehyde(MDA)level was increased, superoxide dismutase(SOD)activity was decreased, miR-1246 expression was increased, total RNA m6A level and SIRT1 m6A level were decreased, METTL3, SIRT1, cluster of differentiation 31(CD31)and vascular endothelial cadherin(VE-cadherin)expression were decreased, while Vimentin and Snail1 expression were increased(all P<0.05); compared with the HG+anti-miR-NC group, cell survival rate was increased in the HG+anti-miR-1246 group, apoptosis rate was decreased, and the number of migrating and invading cells were decreased, LDH activity, TNF-α, and IL-6 levels in cell culture supernatant were decreased, IL-10 level was increased, MDA level was decreased, SOD activity was increased, miR-1246 expression was decreased, total RNA m6A level and SIRT1 m6A level were increased, METTL3, SIRT1, CD31 and VE-cadherin expression were increased, while Vimentin and Snail1 expression were decreased(all P<0.05); compared with the HG+NC group, cell survival rate was increased in the HG+METTL3 group, apoptosis rate was decreased, and the number of migrating and invading cells were decreased, LDH activity, TNF-α, and IL-6 levels in cell culture supernatant were decreased, IL-10 level was increased, MDA level was decreased, SOD activity was increased, miR-1246 expression was decreased, total RNA m6A level and SIRT1 m6A level were increased, METTL3, SIRT1, CD31 and VE-cadherin expression were increased, while Vimentin and Snail1 expression were decreased(all P<0.05); compared with the HG+miR-1246+NC group, cell survival rate was increased in the HG+miR-1246+METTL3 group, apoptosis rate was decreased, and the number of migrating and invading cells were decreased, LDH activity, TNF-α, and IL-6 levels in cell culture supernatant were decreased, IL-10 level was increased, MDA level was decreased, SOD activity was increased, miR-1246 expression was decreased, total RNA m6A level and SIRT1 m6A level were increased, METTL3, SIRT1, CD31 and VE-cadherin expression were increased, while Vimentin and Snail1 expression were decreased(all P<0.05).CONCLUSION:The miR-1246 promotes high glucose-induced apoptosis, invasion and metastasis, oxidative stress, inflammatory response, and EndMT process in RMECs cells by regulating METTL3 mediated SIRT1 m6A modification.

Objective To elucidate the molecular mechanism of sirtuin-3 (SIRT3) in regulating mitochondrial biogenesis in human renal tubular epithelial cells. Methods Cells were stimulated with different concentrations of H₂O₂ and divided into four groups: control (NC), 50 μmol/L H₂O₂, 110 μmol/L H₂O₂ and 150 μmol/L H₂O₂. SIRT3 protein expression was then measured. SIRT3 was knocked down with siRNA, and cells were further assigned to five groups: control (NC), negative-control siRNA (NCsi), SIRT3-siRNA (siSIRT3), NCsi+H₂O₂, and siSIRT3+H₂O₂. After 24 h, cellular adenosine triphosphate (ATP) and mitochondrial superoxide anion (O₂•⁻) levels were determined, together with mitochondrial expression of SIRT3, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), superoxide dismutase 2 (SOD2), acetylated-SOD2 and adenosine monophosphate activated protein kinase α1 (AMPKα1). Results The 110 and 150 μmol/L H₂O₂ decreased SIRT3 protein (both P<0.05). ATP and mitochondrial O₂•⁻ did not differ between NC and NCsi groups (both P>0.05). Compared to the NCsi group, the siSIRT3 group exhibited elevated O₂•⁻ level, decreased SIRT3 protein and increased expression levels of SOD2 and acetylated SOD2 protein (all P<0.05). Compared to the NCsi group, the NCsi+H₂O₂ group exhibited decreased cellular ATP levels, elevated mitochondrial O₂•⁻ levels, and reduced protein expression levels of SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 (all P<0.05). Compared with the siSIRT3 group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 protein expression levels and a decrease in acetylated SOD2 protein expression levels (all P<0.05). Compared with the NCsi+H₂O₂ group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, AMPKα1, PGC-1α and NRF1, TFAM protein expression levels, and an increase in SOD2 and acetylated SOD2 protein expression levels (all P<0.05). Conclusions SIRT3 promotes mitochondrial biogenesis in tubular epithelial cells via the AMPK/PGC-1α/NRF1/TFAM axis, representing a key mechanism through which SIRT3 ameliorates oxidative stress-induced mitochondrial dysfunction.

Antibody-drug conjugates （ADCs） are a novel class of anti-tumor agents composed of a targeted monoclonal antibody， a cytotoxic drug， and a linker connecting the two. They combine the high specificity of antibodies with the potent cytotoxicity of chemotherapeutic agents. Triple-negative breast cancer （TNBC） is characterized by high aggressiveness， elevated risks of recurrence and metastasis， and poor prognosis， largely due to the lack of effective therapeutic targets. This review summarizes the research progress of ADCs in the treatment of TNBC. It has been found that ADCs targeting human epidermal growth factor receptor 2 （such as trastuzumab deruxtecan）， trophoblast cell surface antigen 2 （such as sacituzumab govitecan and datopotamab deruxtecan）， zinc transporter LIV-1 （such as ladiratuzumab vedotin）， HER-3 （such as patritumab deruxtecan）， epidermal growth factor receptor （such as AVID100）， and glycoprotein non-metastatic melanoma protein B （such as glembatumumab vedotin） have all demonstrated promising therapeutic effects against TNBC. Despite challenges including acquired resistance and treatment-related toxicities， ADCs are undoubtedly reshaping the therapeutic landscape for TNBC and are expected to occupy a more central position in TNBC treatment in the future.

OBJECTIVE To analyze the distribution characteristics of mirtazapine steady-state trough concentration and concentration-to-dose ratio （ C / D ）， and to investigate the influence of clinical and genetic factors on C / D . METHODS A retrospective study was conducted on hospitalized patients with depression who received mirtazapine treatment and underwent therapeutic drug monitoring at the First Hospital of Hebei Medical University from May 2022 to May 2025. The collected data included patients’ gender， age， body mass index， daily dose， steady-state trough concentration， smoking status， history of liver disease， drug type， concomitant medications， and CYP2D6 metabolic phenotype. The C / D was calculated. Spearman rank correlation was used to analyze the relationship between mirtazapine steady-state trough concentration and daily dose. Univariate analysis and multiple linear regression model were employed to screen the factors potentially influencing the C / D of mirtazapine. RESULTS A total of 226 patients were included. The daily dose of mirtazapine was 25.00 （24.82， 30.00） mg/d， the steady-state trough concentration was 44.46 （20.00， 70.00） ng/mL， and the C / D was 1.83 （1.00， 2.00） （ng·d）/（mL·mg）. Steady-state trough concentrations were within the reference range （30-80 ng/mL） in 121 patients （53.54%）， below the lower limit in 80 patients （35.40%）， and above the upper limit in 25 patients （11.06%）. A positive correlation was observed between mirtazapine steady-state trough concentration and daily dose （coefficient of determination was 0.320 8， P ＜0.001）. Gender， smoking status， and CYP2D6 metabolic phenotype were significantly associated with the mirtazapine C / D （ P ＜0.05）. CONCLUSIONS Significant interindividual variability exists in mirtazapine steady-state trough concentrations. Gender， smoking status， and CYP2D6 metabolic phenotype are identified as independent influencing factors for the mirtazapine C / D ， with higher C / D ratios observed in females， non-smokers， and intermediate metabolizers.

The importance of consensus research in medical decision-making has become increasinglyprominent. However, this field has long lacked unified terminology definitions and reporting standards, leading to significant heterogeneity in study design, implementation, and result presentation that affects the credibility and reproducibility of outcomes. The ACCurate COnsensus Reporting Document (ACCORD) in the field of biomedical research provides a structured writing framework for various consensus methods such as the Delphi method and nominal group technique, aiming to enhance the completeness and transparency of study reports. Combined with specific cases, this article interprets the core items of ACCORD, offering references for the design, implementation, and reporting of high-quality consensus research in China.

ObjectiveTo investigate the clinical efficacy and mechanisms of Qigui Didang decoction in the treatment of kidney collateral stasis syndrome in patients with stage Ⅲ-Ⅳ diabetic kidney disease （DKD） in a real-world setting. MethodsPatients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome admitted to Beijing Aerospace General Hospital from January 2022 to December 2024 were selected for clinical study. According to treatment methods， patients were divided into the Qigui Didang decoction group （Qigui Didang decoction + conventional treatment） and the control group （conventional treatment alone）. A 1∶1 propensity score matching （PSM） method was used to reduce bias caused by confounding factors. Clinical efficacy， traditional Chinese medicine （TCM） symptom scores， renal function indicators， mRNA expression related to pathway mechanisms， glycolipid metabolism indices， and adverse reactions were compared between the two groups. ResultsA total of 120 patients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome were included， including 62 cases in the Qigui Didang Decoction group and 58 cases in the control group. Before matching， there were statistically significant differences between the two groups in DKD stage， baseline urinary albumin-to-creatinine ratio （UACR）， 24-hour urine total protein （24 h-UTP）， and estimated glomerular filtration rate （eGFR） （P<0.05）. After matching， 47 cases were included in each group， and there was no statistically significant difference in baseline data between the two groups. After matching， the total clinical effective rate of the Qigui Didang decoction group was significantly higher than that of the control group （χ²=4.681， P<0.05）. Compared with data before treatment， the scores of primary and secondary TCM symptoms in the Qigui Didang decoction group were significantly decreased （P<0.05）. Compared with data before treatment， serum creatinine （SCr）， 24 h-UTP， and UACR levels were significantly decreased， while eGFR was significantly increased in the Qigui Didang decoction group （P<0.05）. Compared with data before treatment， the mRNA expression of silent information regulator 1 （Sirt1） was significantly upregulated， while the mRNA expression of nuclear factor-kappa B （NF-κB） and tumor suppressor protein p53 （p53） was significantly downregulated in the Qigui Didang decoction group （P<0.05）. Compared with data before treatment， fasting plasma glucose （FPG）， 2-hour postprandial plasma glucose （2 hPG）， glycated hemoglobin A1c （HbA1c）， total cholesterol （TC）， triglycerides （TG）， and low-density lipoprotein cholesterol （LDL-C） levels were decreased， while high-density lipoprotein cholesterol （HDL-C） levels were increased （P<0.05）. There was no statistically significant difference in adverse reactions between the two groups. ConclusionQigui Didang decoction combined with conventional treatment can significantly improve renal function， glycolipid metabolism， and TCM syndromes in patients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome， with good safety. The mechanism may be related to the regulation of the Sirt1/NF-κB/p53 signaling pathway.

ObjectiveTo investigate the clinical efficacy and mechanisms of Qigui Didang decoction in the treatment of kidney collateral stasis syndrome in patients with stage Ⅲ-Ⅳ diabetic kidney disease （DKD） in a real-world setting. MethodsPatients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome admitted to Beijing Aerospace General Hospital from January 2022 to December 2024 were selected for clinical study. According to treatment methods， patients were divided into the Qigui Didang decoction group （Qigui Didang decoction + conventional treatment） and the control group （conventional treatment alone）. A 1∶1 propensity score matching （PSM） method was used to reduce bias caused by confounding factors. Clinical efficacy， traditional Chinese medicine （TCM） symptom scores， renal function indicators， mRNA expression related to pathway mechanisms， glycolipid metabolism indices， and adverse reactions were compared between the two groups. ResultsA total of 120 patients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome were included， including 62 cases in the Qigui Didang Decoction group and 58 cases in the control group. Before matching， there were statistically significant differences between the two groups in DKD stage， baseline urinary albumin-to-creatinine ratio （UACR）， 24-hour urine total protein （24 h-UTP）， and estimated glomerular filtration rate （eGFR） （P<0.05）. After matching， 47 cases were included in each group， and there was no statistically significant difference in baseline data between the two groups. After matching， the total clinical effective rate of the Qigui Didang decoction group was significantly higher than that of the control group （χ²=4.681， P<0.05）. Compared with data before treatment， the scores of primary and secondary TCM symptoms in the Qigui Didang decoction group were significantly decreased （P<0.05）. Compared with data before treatment， serum creatinine （SCr）， 24 h-UTP， and UACR levels were significantly decreased， while eGFR was significantly increased in the Qigui Didang decoction group （P<0.05）. Compared with data before treatment， the mRNA expression of silent information regulator 1 （Sirt1） was significantly upregulated， while the mRNA expression of nuclear factor-kappa B （NF-κB） and tumor suppressor protein p53 （p53） was significantly downregulated in the Qigui Didang decoction group （P<0.05）. Compared with data before treatment， fasting plasma glucose （FPG）， 2-hour postprandial plasma glucose （2 hPG）， glycated hemoglobin A1c （HbA1c）， total cholesterol （TC）， triglycerides （TG）， and low-density lipoprotein cholesterol （LDL-C） levels were decreased， while high-density lipoprotein cholesterol （HDL-C） levels were increased （P<0.05）. There was no statistically significant difference in adverse reactions between the two groups. ConclusionQigui Didang decoction combined with conventional treatment can significantly improve renal function， glycolipid metabolism， and TCM syndromes in patients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome， with good safety. The mechanism may be related to the regulation of the Sirt1/NF-κB/p53 signaling pathway.

ObjectiveIn the context of the digital transformation of education, this study aims to construct a triadic interactive teaching model for surgical animal surgery in clinical medicine using modern information technology. It explores the effectiveness of different teaching methods in improving students' practical skills, aseptic awareness, and teamwork abilities, providing a reference for the reform of clinical practice education. MethodsA quasi-experimental research design was adopted. A total of 80 students from the eight-year clinical medicine program at Nanjing University were selected, including the Class of 2020 (control group, n=40) and the Class of 2021 (experimental group, n=40). The control group received traditional teaching methods, while the experimental group implemented the "Teacher-Student-AI" triadic interactive teaching model. This model utilized a smart teaching platform for personalized pre-class preparation , as well as data-driven post-class review and feedback throughout the entire teaching process. The "assessment indicators and scoring criteria for the surgical animal surgery course" were used to evaluate teaching effectiveness, with independent samples t-tests used for statistical analysis. ResultsPre-course assessments revealed no statistically significant differences in baseline theoretical knowledge or practical skills between the two groups (P>0.05). Upon completion of the course, the experimental group achieved higher scores than the control group across three key dimensions: practical skills (47.98±1.34 vs 46.92±2.51, P=0.022), aseptic awareness (17.84±1.16 vs 16.94±2.29, P=0.029), and teamwork (16.82±1.44 vs 15.95±1.22, P=0.004). However, no statistically significant difference was observed in the scores for humane care awareness between the two groups (8.24±0.70 vs 8.16±0.53, P=0.589). ConclusionThe AI-based triadic interactive teaching model can, to some extent, address the limitations of traditional surgical animal surgery education. It plays a positive role in enhancing medical students' surgical skills, aseptic awareness, and collaborative abilities. This model facilitates the transition from traditional to personalized teaching and offers a practical framework for the digital reform of clinical practice education.

Parkinson's disease （PD） is a common neurodegenerative disorder characterized by motor impairments， with its pathological mechanisms involving multiple processes such as the degeneration of dopaminergic neurons and the abnormal aggregation of α-synuclein. Current Western medical treatments face challenges including diminished long-term efficacy and motor complications. In recent years， Traditional Chinese Medicine （TCM） has demonstrated advantages in the prevention and treatment of PD through its systematic regulatory capabilities， featuring multi-component， multi-target， and multi-pathway approaches.This article systematically reviews the roles of seven key signaling pathways-NF-κB， AMPK/mTOR， PI3K/Akt， MAPKs， Nrf2/ARE， Wnt/β-catenin， and BDNF/TrkB-in the pathological process of PD and the regulatory mechanisms of TCM. Research indicates that active ingredients of Chinese herbs and compound formulations can synergistically modulate these pathways， exerting comprehensive effects in inhibiting neuroinflammation， alleviating oxidative stress， promoting autophagy to clear abnormal proteins， and enhancing neurotrophic support. These signaling pathways form a complex regulatory network through crosstalk among key nodal molecules， constituting an intricate regulatory system in PD pathology. The multi-target intervention characteristics of TCM align well with this network-based regulatory requirement， achieving integrated anti-inflammatory， antioxidant， autophagy-regulating， and neurorestorative effects through synergistic multi-pathway modulation. This article systematically outlines the mechanisms of TCM in the coordinated regulation of multiple pathways， providing a theoretical basis for elucidating the pathological process of PD and the intervention mechanisms of TCM， while also offering new perspectives and directions for modern research on TCM in the prevention and treatment of PD.

ObjectiveTo evaluate the clinical efficacy and economic value of the Jiangsu Traditional Chinese Medicine （TCM） Diagnosis and Treatment Protocol for Dominant Diseases （abbreviated as the Diagnosis and Treatment Protocol） in adult patients with non-severe community-acquired pneumonia （CAP） based on real-world clinical data. MethodsA retrospective real-world cohort study was conducted using electronic medical records of adult patients hospitalized for non-severe CAP from September 1st， 2023 to December 31st， 2024 across 10 TCM hospitals in Jiangsu province. Patients were classified into an exposure group and a non-exposure group based on whether they received Chinese herbal medicine （CHM） according to the Diagnosis and Treatment Protocol. The non-exposure group received only conventional western medicine， while the exposure group additionally received differentiated CHM for at least five consecutive days. Outcomes were compared between two patient groups， including cough resolution rate， sputum resolution rate （assessed by volume， color， and consistency）， incidence of abnormal C-reactive protein （CRP）， incidence of abnormal white blood cell （WBC） count， and radiographic resolution rate of pulmonary infiltrates on chest imaging. Multivariable logistic regression was performed to identify factors influencing clinical efficacy. Subgroup analyses were conducted according to age， gender， smoking status， history of hypertension， and pneumonia severity score （CURB-65）， and the efficacy of treatment for cough and sputum was analyzed within each subgroup. Cost-effectiveness analysis was conducted using cough resolution rate as the outcome measure， evaluating the pharmacoeconomics of the two groups. ResultsA total of 1688 patients were included with 1293 in the exposure group and 395 in the non-exposure group. Compared to the non-exposure group， the exposure group demonstrated significantly higher resolution rates of cough， sputum volume， color， and consistency， as well as a significantly lower incidence of abnormal CRP （P＜0.05）. No statistically significant difference was observed between the groups in terms of abnormal WBC count and radiographic resolution rate of pulmonary infiltrates （P＞0.05）. Logistic regression analysis showed that the cough resolution rate in the exposure group was 1.83 times that of the non-exposure group， while the probabilities of resolution in sputum volume， color， and consistency were 1.37， 2.09， and 1.56 times those of the non-exposure group， respectively （P＜0.05）. Subgroup analyses showed that the exposure group achieved significantly higher cough resolution rates across most subgroups except for populations with a CURB-65 score ≥2 or those with a history of hypertension （P＜0.05）. Specifically， among females， patients aged ≥18 and ＜65 years， non-smokers， those without hypertension， and those with a CURB-65 score of 0， the exposure group showed a higher cough resolution rate than the non-exposure group （P＜0.05）. From an economic perspective， total hospitalization cost， length of stay， antibiotic cost， and CHM cost all differed significantly between groups （P＜0.05）. The cost-effectiveness ratio （CER） was 10,788.80 CNY/case in the exposure group， while 22,513.80 CNY/case in the non-exposure group. This implies that， compared with the exposure group， the non-exposure group incurred an additional 17,302.27 CNY to achieve one case of cough resolution. When the willingness-to-pay threshold ranged from 0 to 50,000 CNY， the probability of economic advantage was consistently higher in the exposure group than in the non-exposure group. ConclusionOn the basis of conventional western medicine， the addition of CHM in accordance with the Diagnosis and Treatment Protocol can effectively improve clinical symptoms， reduce inflammatory markers， promote clinical recovery， and is more cost-effective in treating adults with non-severe CAP.