[摘 要] 目的：探讨环状RNA CEMIP（circCEMIP）对膀胱癌UMUC-3细胞增殖、迁移和侵袭的影响及其分子机制。方法：通过TCGA数据库分析circCEMIP在膀胱癌组织中的表达水平，分析其表达与膀胱癌患者临床分期及生存期的关系。采用qPCR法检测circCEMIP在膀胱癌细胞5637、UMUC-3、MGH-U3、J82和T24中的表达。利用RNA干扰技术，分别将si-circCEMIP及其阴性对照（si-NC）、anti-miR-335及其阴性对照（anti-miR-NC）转染UMUC-3细胞，记为si-circCEMIP组、si-NC组、si-circCEMIP + anti-miR-335组和si-circCEMIP + anti-miR-NC组。采用克隆形成实验、划痕愈合实验和Transwell实验分别检测circCEMIP和miR-335表达对UMUC-3细胞增殖、迁移和侵袭能力的影响，双萤光素酶报告基因实验验证circCEMIP与miR-335的靶向关系，WB法检测细胞中VEGF-C信号通路相关蛋白的表达。构建UMUC-3细胞裸鼠皮下移植瘤模型，观察敲低circCEMIP对移植瘤生长的影响。结果：膀胱癌组织中circCEMIP呈高表达（P < 0.01），其表达水平与膀胱癌的临床分期正相关（P < 0.01），circCEMIP高表达患者生存率较低（P < 0.01）。circCEMIP在膀胱癌5637、UMUC-3、MGH-U3、J82和T24细胞中呈高表达（均P < 0.01）。敲低circCEMIP显著降低UMUC-3细胞的增殖、迁移和侵袭能力（均P < 0.01）。circCEMIP可靶向结合miR-335（P < 0.01），敲低circCEMIP能显著上调miR-335表达（P < 0.01）。抑制miR-335表达能逆转敲低circCEMIP对UMUC-3细胞增殖、迁移和侵袭的抑制作用（均P < 0.01）。敲低circCEMIP能明显下调VEGF-C信号通路相关蛋白VEGF-C、MMP-2、MMP-9和β-catenin表达（均P < 0.01），抑制miR-335表达能部分逆转敲低circCEMIP对该通路相关蛋白表达的抑制作用（均P < 0.01）。体内实验证实，敲低circCEMIP能够抑制裸鼠膀胱癌移植瘤的生长（P < 0.01）。结论：敲低circCEMIP通过上调miR-335表达抑制膀胱癌UMUC-3细胞的增殖、迁移和侵袭。

ObjectiveTo investigate the clinical effect of Ershen Zhenwu Decoction on chronic heart failure （CHF） due to heart-kidney Yang deficiency and blood stasis and its regulatory effects on miR-423-5p/Smad7/transforming growth factor-β₁ （TGF-β₁）/Smads axis and myocardial fibrosis indicators. MethodsOne hundred and fourteen patients with heart failure with reduced ejection fraction （HFrEF） and heart failure with mildly reduced ejection fraction （HFmrEF） were randomly allocated into a control group and an observation group. The control group was treated with dapagliflozin tablets， sacubitril-valsartan sodium tablets， metoprolol succinate， and spironolactone， and the observation group was treated with Ershen Zhenwu Decoction on the basis of the therapy in the control group. The course of treatment was 8 weeks in both groups. The 6-min walking distance， New York Heart Association （NYHA） heart function grade， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， angiotensin Ⅱ （Ang Ⅱ）， left ventricular ejection fraction （LVEF）， left ventricular end-diastolic diameter （LVIDd）， left ventricular end-systolic diameter （LVIDs）， interventricular septum thickness at diastole （IVSd）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left ventricular shortening fraction （FS）， miR-423-5p， Smad7， Smad2， Smad3， Smad4， TGF-β₁， Ang Ⅱ， type Ⅰ collagen （Col Ⅰ）， type Ⅲ collagen （Col Ⅲ）， mRNA levels of fibronectin （Fn） and α-smooth muscle actin （α-SMA） in the myocardial tissue were observed before and after treatment in both groups to evaluate the efficacy of cardiac function and drug safety. ResultsAfter treatment， both groups showed declined levels of NT-proBNP， Ang Ⅱ， miR-423-5p， Smad2， Smad3， Smad4， TGF-β₁， Col Ⅰ， Col Ⅲ， and mRNA levels of Fn and α-SMA （P0.05）， and the levels of the indicators above were lower in the observation group than in the control group （P0.05）. After treatment， the Smad7 level increased obviously in both groups （P0.05） and was higher in the observation group than in the control group （P0.05）. After treatment， both groups showed decreased MLHFQ scores and increased 6-min walking distance （P0.05）， and the observation group had lower MLHFQ score and longer 6-min walking distance than the control group （P0.05）. After treatment， the control group showed increased LVEF and FS （P0.05） and the observation group showcased decreased LVIDd and LVIDs and increased LVEF and FS （P0.05）. Moreover， the observation group had lower LVIDd and LVIDs （P0.05） and higher LVEF and FS （P0.05） than the control group. The total response rate of cardiac function in the observation group was 90.38% （47/52）， which was higher than that （70.59%， 36/51） in the control group （P0.05）. No adverse reactions associated with Ershen Zhenwu Decoction were observed during the study period. ConclusionErshen Zhenwu Decoction can improve the cardiac function， exercise tolerance， and quality of life， regulate neuroendocrine factors， and slow down/reverse myocardial remodeling in the patients with HFrEF and HFmrEF （syndrome of heart-kidney Yang deficiency and blood stasis by regulating the miR-423-5p/Smad7/TGF-β₁/Smads axis， inhibiting α-SMA and Fn expression， and alleviating myocardial fibrosis. It is worthy of further study.

ObjectiveTo investigate the clinical effect of Ershen Zhenwu Decoction on chronic heart failure （CHF） due to heart-kidney Yang deficiency and blood stasis and its regulatory effects on miR-423-5p/Smad7/transforming growth factor-β₁ （TGF-β₁）/Smads axis and myocardial fibrosis indicators. MethodsOne hundred and fourteen patients with heart failure with reduced ejection fraction （HFrEF） and heart failure with mildly reduced ejection fraction （HFmrEF） were randomly allocated into a control group and an observation group. The control group was treated with dapagliflozin tablets， sacubitril-valsartan sodium tablets， metoprolol succinate， and spironolactone， and the observation group was treated with Ershen Zhenwu Decoction on the basis of the therapy in the control group. The course of treatment was 8 weeks in both groups. The 6-min walking distance， New York Heart Association （NYHA） heart function grade， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， angiotensin Ⅱ （Ang Ⅱ）， left ventricular ejection fraction （LVEF）， left ventricular end-diastolic diameter （LVIDd）， left ventricular end-systolic diameter （LVIDs）， interventricular septum thickness at diastole （IVSd）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left ventricular shortening fraction （FS）， miR-423-5p， Smad7， Smad2， Smad3， Smad4， TGF-β₁， Ang Ⅱ， type Ⅰ collagen （Col Ⅰ）， type Ⅲ collagen （Col Ⅲ）， mRNA levels of fibronectin （Fn） and α-smooth muscle actin （α-SMA） in the myocardial tissue were observed before and after treatment in both groups to evaluate the efficacy of cardiac function and drug safety. ResultsAfter treatment， both groups showed declined levels of NT-proBNP， Ang Ⅱ， miR-423-5p， Smad2， Smad3， Smad4， TGF-β₁， Col Ⅰ， Col Ⅲ， and mRNA levels of Fn and α-SMA （P0.05）， and the levels of the indicators above were lower in the observation group than in the control group （P0.05）. After treatment， the Smad7 level increased obviously in both groups （P0.05） and was higher in the observation group than in the control group （P0.05）. After treatment， both groups showed decreased MLHFQ scores and increased 6-min walking distance （P0.05）， and the observation group had lower MLHFQ score and longer 6-min walking distance than the control group （P0.05）. After treatment， the control group showed increased LVEF and FS （P0.05） and the observation group showcased decreased LVIDd and LVIDs and increased LVEF and FS （P0.05）. Moreover， the observation group had lower LVIDd and LVIDs （P0.05） and higher LVEF and FS （P0.05） than the control group. The total response rate of cardiac function in the observation group was 90.38% （47/52）， which was higher than that （70.59%， 36/51） in the control group （P0.05）. No adverse reactions associated with Ershen Zhenwu Decoction were observed during the study period. ConclusionErshen Zhenwu Decoction can improve the cardiac function， exercise tolerance， and quality of life， regulate neuroendocrine factors， and slow down/reverse myocardial remodeling in the patients with HFrEF and HFmrEF （syndrome of heart-kidney Yang deficiency and blood stasis by regulating the miR-423-5p/Smad7/TGF-β₁/Smads axis， inhibiting α-SMA and Fn expression， and alleviating myocardial fibrosis. It is worthy of further study.

Objective To develop a risk assessment scale for immune checkpoint inhibitor (ICI)-associated myocarditis based on multidisciplinary collaboration, and to evaluate its diagnostic performance. Methods Based on multidisciplinary cooperation, integrating clinical experience from oncology and cardiology, literature data, and patient conditions, a risk assessment scale for ICI-associated myocarditis was developed. A total of 101 patients with malignancies who received immunotherapy at Zhongshan Hospital, Fudan University, from October 2020 to October 2024 were included as the validation cohort. Patients were stratified into low-risk (0-1 point), medium-risk (2-4 points), and high-risk (≥5 points) groups based on their scale scores. The association between pretictive risk stratifications and actual assessment results was assessed using the Cox proportional hazards regression model. The predictive value of the scale for ICI-associated myocarditis was evaluated using receiver operating characteristic (ROC) curve. Agreement between the scale scores and actual assessment results was assessed using Cohen’s Kappa coefficient. Results Based on the scale pretictive results, 28(27.7%), 8(7.9%), 65(64.4%) patients were at low risk, medium risk, and high risk for ICI-related myocarditis, respectively; however, 46(45.5%), 8(7.9%), 47(46.5%) were at low risk, medium risk, and high risk actually. Kaplan-Meier survival analysis showed that the cumulative incidence of ICI-related myocarditis in the high-risk group was significantly higher than that in the medium- and low-risk groups (P＜0.05). In the multivariable-adjusted Cox proportional hazards model, the ICI-related myocarditis risk in high-risk group was about 4 times that in the low-risk group. ROC curve analysis demonstrated that the average area under the curve (AUC) for predicting ICI-related myocarditis was 0.81, with an accuracy of 0.74. The Cohen’s Kappa coefficient was 0.55, indicating moderate agreement. In the actual high-risk group, no patient was predicted to be at low risk; in the actual low-risk group, 16 patients were predicted to be at high risk. Conclusions This risk assessment scale for ICI-associated myocarditis shows high predictive performance. It provides oncologists with a simple yet effective multidisciplinary diagnostic reference tool, potentially enhancing early identification of ICI-associated myocarditis.

Circadian rhythm is a biological endogenous process regulated by the suprachiasmatic nucleus of the hypothalamus, which transmits light signals to peripheral clocks and synchronizes the body with the external environment through balanced expression of circadian rhythm genes. Working the night shift, sleep disorders, and exposure to artificial light can lead to disturbances in circadian rhythm and genetic imbalances. A substantial body of research has demonstrated that circadian rhythm plays a significant role in the treatment of autoimmune diseases and neurodegenerative disorders, with increasing attention being directed toward their impact on oral health. Disturbances in circadian rhythm primarily affect psycho-neuro-immune mechanisms, oxidative stress responses, and oral microflora through pathways such as the hypothalamic-pituitary-adrenal axis (HPA axis), brain and muscle ARNT-like 1 (BMAL1)-brain-derived neurotrophic factor (BDNF) signaling, and BMAL1-nuclear factor kappa-B (NF-κB) interactions. These disruptions may influence the progression of oral diseases. Certain pharmacological agents (e.g., melatonin, vitamin D, nobiletin, and propofol) have been shown to regulate mood disorders, immune function, and sleep-wake cycles by upregulating BMAL1 expression, thus alleviating disturbances in circadian rhythm. In addition, non-pharmacological interventions, such as sleep management strategies, psychotherapy approaches, and light therapy, also modulate these processes through HPA axis regulation. Currently, the specific mechanisms by which circadian rhythm regulates BDNF levels, T cell subsets, and inflammatory signals—thereby influencing both pathogenesis and treatment outcomes for oral diseases—remain unclear. Future research should focus on elucidating these molecular mechanisms as well as identifying therapeutic targets related to circadian rhythm within the oral health context. Further, multidisciplinary collaboration encompassing pharmacy, sleep behavior studies, and psychology will be instrumental in advancing prevention strategies and treatments for oral diseases.

Objective Examine and analyze the current situation of the construction of national regional medical centers for children in China,in order to provide reference for promoting the high-quality development of national regional medical centers for children and other categories.Methods Refer to literature and official websites of relevant national departments and hospitals to obtain the required data and establish an analysis database for children's national regional medical centers.Using PEST analysis method,conduct research from four perspectives:politics,economy,society,and technology.Results The development trend of national regional medical centers for children is good,with a favorable policy environment,increasing demand for children's medical and health services,and high social expectations.However,there are issues such as targeted support policies that need to be improved,varying levels of economic security,regional cultural conflicts,and differences in technological resource levels.Conclusion It is suggested to improve the targeted policy support system,establish a sound compensation mechanism,actively integrate into the overall development of regional society,and integrate the advantages of various technological resources.

The drug therapy pathway is an important part of the clinical pathway,aiming to enhance the efficiency and quality of healthcare services,optimize the allocation of healthcare resources,enhance patients' adherence to treatment,reduce the rate of medical errors,and ultimately improve patients' treatment outcomes through clear steps of drug therapy.The drug therapy pathway in the United States emphasizes multidisciplinary teamwork,and pharmacists play a key role in the formulation and implementation of the pathway;the drug therapy pathway in the United Kingdom is jointly formulated by the National Health Service of the United Kingdom and the National Institute for Health and Clinical Excellence of the United Kingdom,and pharmacists provide professional advice in the formulation and implementation of the pathway;and the management of the drug therapy pathway in Japan is the responsibility of the Japan Clinical Pathway Society,and pharmacists play an important role in the promotion and implementation of the pathway.Pharmacists play an important role in the promotion and implementation of pathways.This article analyzes the experiences and models of the United States,the United Kingdom,and Japan in the development of drug therapy pathways,to provide a reference for the development of drug therapy pathways in China.

Objective To construct an evaluation index system for rational drug use management of key monitoring drugs,and to provide references for medical institutions.Methods The preliminary index framework was formed by researching the policies and regulations,management norms,and guiding principles related to key monitoring drugs.Two rounds of Delphi questionnaire survey were conducted with 26 experts to improve and optimize the index system.The weights of the indicators were obtained by constructing the judgment matrix by analytic hierarchy process(AHP).Results The recovery rates of the two rounds of questionnaire were both 100％,and the authority coefficient was 0.87.The key monitoring drug rational use management evaluation index system was finally constructed to include three primary indicators[ex-ante management(0.253 6),in-process management(0.503 1),and ex-post management(0.243 2)],15 secondary indicators[including prescription review(0.302 6),formulate rational drug use norms(0.133 1),supernormal early warning management(0.103 2)],and 62 tertiary indicators[inclu-ding formulate strict prescription review rules(0.152 5),pharmacists prescription intervention strength(0.085 7)and effective-ness management(0.052 5)].and the index judgment matrix passed the consistency test.Conclusion The evaluation index system for the rational drug use management of key monitoring drugs constructed can satisfy the closed loop of the supervision and management process,achieve the prior reminder,monitoring,and post-supervision,and provide references for medical institutions to ensure the refinement and standardization of the management process.

In January 2023, a patient with soft tissue degloving defect of right index, middle, ring and little fingers was treated in the Department of Hand Surgery, Suzhou Ruihua Orthopaedic Hospital. Seven free flaps from a leg were harvested to reconstruct the defected wound of fingers in primary surgery. Flap thinning and plastic surgery were performed in stage-II surgery. Over the 22 months of postoperative follow-up, the flaps in right index, middle, ring and little fingers survived well with the colour and texture close to proximal skin. There was no obvious swelling of the flaps and sensation of the flaps recovered to S 3. The donor sites healed well and the donor leg walked normally.

Objective:To quantitatively evaluate the policy texts on mutual recognition of examination and inspection results at the national and local levels in China from 2006 to 2025 based on the PMC index model,and provide reference for policy formulation and improvement.Methods:The ROSTCM6 software was used to sort out and conduct text mining on 27 policy documents issued at the national and local levels,establishing the PMC index model for the mutual recognition of examination and inspection results in China.Quantitative analysis was conducted through a PMC evaluation system consisting of 9 first-level variables and 39 second-level variables.Results:The average PMC index was 6.06(excellent level).Among the 27 policies,4 were rated as perfect,18 as excellent,and 5 as acceptable.Conclusions:Current policies need to strengthen the formulation of scientific and feasible goals,improve legal guarantees and medical insurance coordination mechanisms,and build a complete data security maintenance system to provide policy support and guarantees for the continuous advancement of the mutual recognition of examination and inspection results.