Objective To investigate the effect of sodium-glucose cotransporter 2 inhibitor (empagliflozin, EMPA) on myocardial remodeling in a mouse uremic cardiomyopathy (UCM) model induced by 5/6 nephrectomy, through the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (PKB/AKT)/p65 signaling pathway. Methods The animals were divided into three groups: Sham group (n=6), UCM group (n=8), and UCM＋EMPA group (n=8). A UCM model was established in C57BL/6N mice using the 5/6 nephrectomy. Starting from 5 weeks post-surgery, EMPA or a placebo was administered. After 16 weeks, blood pressure, serum creatinine, blood urea nitrogen, 24-hour urine glucose and urine sodium were measured. Cardiac structure and function were assessed by echocardiography. Hematoxylin-eosin (HE) staining and Masson trichrome staining were used to observe pathological changes in the heart and kidneys. Wheat germ agglutinin (WGA) staining was used to evaluate myocardial hypertrophy. The real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of myocardial hypertrophy- and fibrosis-related mRNAs. Western blotting was used to detect the expression levels of PI3K, AKT and p65 in myocardial tissues. Results After 16 weeks, UCM group exhibited significantly higher blood pressure, serum creatinine, blood urea nitrogen than sham group (P＜0.01); UCM＋EMPA group exhibited lower blood pressure, serum creatinine, blood urea nitrogen, and higher 24 h urine sodium and glucose than UCM group (P＜0.05). Echocardiographic results showed ventricular remodeling in the UCM group, evidenced by left ventricular wall thickening, left ventricular enlargement, increased left ventricular mass, and decreased systolic function (P＜0.05); ventricular remodeling was alleviated (P＜0.05), though there was no significant improvement in systolic function in UCM＋EMPA group. HE and Masson stainings revealed myocardial degeneration, necrosis, and interstitial fibrosis in UCM group (P＜0.01); the myocardial pathology improved with reduced collagen deposition in UCM＋EMPA group (P＜0.01). WGA staining confirmed myocardial hypertrophy in UCM group (P＜0.01), while myocardial hypertrophy was alleviated in UCM＋EMPA group (P＜0.01). RT-qPCR results showed myocardial hypertrophy- and fibrosis-related genes (NPPA, NPPB, MYH7, COL1A1, COL3A1, TGF-β1) were upregulated in UCM group (P＜0.05), but downregulated in UCM＋EMPA group. Western blotting showed PI3K, p-AKT/AKT ratio, and p-p65/p65 ratio were increased in UCM group, but decreased in UCM＋EMPA group (P＜0.05). Conclusion EMPA can improve myocardial hypertrophy and fibrosis in the UCM mouse model, and it may play the role through inhibiting the PI3K/AKT/p65 signaling pathway.

The 2025 European Lung Cancer Congress (ELCC) convened in Paris, France, centering on the optimization and innovation of immunotherapy for non-small cell lung cancer (NSCLC). Key topics at the congress included the application strategies for perioperative immunotherapy, breakthroughs in combination therapy models for advanced NSCLC, and the emerging roles of biomarkers in predicting diverse treatment outcomes. This paper integrates data from several key pivotal studies to systematically analyze the clinical value of neoadjuvant therapy within the perioperative setting, the potential of targeted combination regimens, and the challenges of managing drug resistance, thus offering new directions for clinical practice.

Objective To evaluate the safety and efficacy of total arterial off-pump coronary artery bypass grafting (OPCABG) using a left internal thoracic artery (LITA) combined with bilateral radial arteries (RAs). Methods We retrospectively analyzed the clinical data of patients with severe multi-vessel coronary artery disease who underwent total arterial OPCABG with a LITA and bilateral RAs at Sichuan Provincial People’s Hospital from November 2020 to April 2023. Results A total of 24 patients were included, comprising 23 males and 1 female, with a mean age of (53.63±4.33) years. The New York Heart Association (NYHA) functional class was Ⅱ to Ⅲ. The mean number of distal anastomoses was 3.17±0.38. A Y-graft was constructed in 12 patients and sequential grafting was performed in 4 patients. Concomitant procedures included coronary endarterectomy in 1 patient, intra-aortic balloon pump (IABP) implantation in 10 patients, and thymoma resection in 1 patient. The mean operative time was (308.13±30.39) min, mechanical ventilation time was (15.42±7.42) h, ICU stay was (46.08±27.32) h, and postoperative hospital stay was (11.71±1.90) d. There were no in-hospital deaths. Postoperative complications included one patient of acute renal failure and one patient of cerebral infarction. Pre-discharge color Doppler echocardiography revealed that the left ventricular end-diastolic diameter was significantly smaller than before surgery (P<0.05), while the left ventricular ejection fraction and fractional shortening were significantly higher (P<0.05). Coronary computed tomography angiography (CTA) showed that all arterial grafts were patent. During a mean follow-up of (14.58±8.75) months, no patients experienced angina recurrence or mortality. Repeat coronary CTA or angiography in 16 patients one year postoperatively confirmed that all arterial grafts remained patent. Conclusion Total arterial OPCABG using a LITA and bilateral RAs is a safe and effective treatment for patients with severe multi-vessel coronary artery disease. For high-risk patients, intraoperative IABP support is recommended.

In the treatment of persistent atrial fibrillation with radiofrequency ablation,it is often necessary to add the ablation of external trigger foci of pulmonary vein on the basis of annular pulmonary vein isolation,including linear ablation,BOX ablation and fragmentation potential ablation.The isthmus of mitral valve is the most important component of linear ablation,but it is difficult to reach the isthmus of mitral valve for complete blockade by conventional radiofrequency ablation.The guide catheter was transported through the inferior vena cava to the coronary sinus,and the injection of Marshall vein anhydrous ethanol for ablation could achieve epicardial and myocardial block in the mitral isthmus,and the ablation combined with the endocardial patch ablation in the mitral isthmus could significantly improve the ablation effect,but there were disadvantages such as Marshall vein and coronary vein injury,high surgical cost and long time.This paper reports a case of persistent atrial fibrillation treated by self-made perforated balloon with Marshall intravenous anhydrous ethanol combined with individualized ablation strategy.No major adverse cardiovascular events or recurrence of atrial fibrillation occurred during 6 months of follow-up after discharge.

Serine/arginine-rich splicing factor 6 (SRSF6) is a member of the serine and arginine-rich (SR) protein family,and it plays a crucial regulatory role in RNA splicing.Dysregulation of SRSF6 ex-pression or function can lead to aberrant alternative splicing of certain genes,and contribute to the devel-opment and progression of inflammatory diseases,including tumors,diabetes,and pleural fibrosis.How-ever,the role of SRSF6 in inflammation remains unclear.In this study,we found that the expression of inflammatory factors,including tumor necrosis factor-α(TNF-α) and cyclooxygenase-2 (COX-2),was induced by lipopolysaccharides (LPS) .Concurrently,both the levels of SRSF6 mRNA and protein ex-pression significantly increased with prolonged LPS stimulation (P<0.05) .Furthermore,we investigated the change of SRSF6 expression on the expression of inflammatory factors.The results showed that upreg-ulation of SRSF6 enhanced the expression of LPS-induced inflammatory factors (P<0.05),while down-regulation of SRSF6 inhibited their expression (P<0.05) .Additionally,the activation of the nuclear fac-tor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways was suppressed by SRSF6 knockdown (P<0.05),indicating that SRSF6 is involved in regulating inflammatory responses in macrophages.Myeloid differentiation factor 88 (MyD88) is a key adaptor protein in the TLR4 signaling pathway,with its splicing isoforms MyD88-L and MyD88-S exerting pro-inflammatory and anti-inflamma-tory effects,respectively.Analysis of RNA-binding protein database and RNA immunoprecipitation showed that SRSF6 binds to MyD88 mRNA.Splicing analysis indicated that downregulation of SRSF6 promoted the expression of the anti-inflammatory MyD88-S mRNA isoform (P<0.01) .Moreover,knock-down of MyD88-S could rescue the expression of inflammatory factors suppressed by SRSF6 downregula-tion.These findings suggest that SRSF6 regulates MyD88 alternative splicing in macrophages,thereby af-fecting the activation of inflammatory signaling pathways and the expression of inflammatory factors.This study provides a foundation for further elucidating the role of SRSF6 in inflammatory diseases.

Objective:To investigate the clinical characteristics of adult eosinophilic esophagitis (EoE) and the diagnostic value of endoscopic ultrasonography (EUS).Methods:Data from 12 adult patients with EoE diagnosed at the First Affiliated Hospital of Zhejiang University School of Medicine from 2011 to 2022 were retrospectively analyzed for the clinical manifestations, imaging and endoscopic findings, EUS characteristics, treatment and prognosis.Results:Among the 12 EoE patients, 9 were male and 3 were female, with a mean age at diagnosis of 48.5 years (17-73 years). Two patients had a history of asthma, 1 had urticaria, and 5 had a history of food and/or drug allergy. The time from symptom onset to diagnosis ranged from 2 weeks to 30 years. The most common clinical symptoms were acid regurgitation (8 cases), abdominal pain (8 cases), and obstruction dysphagia (5 cases). Four (4/11) patients had increased peripheral blood eosinophils and 4 (4/10) patients had increased peripheral blood immunoglobulin E. Contrast-enhanced CT of the esophagus showed esophageal wall thickening and enhancement in 7 patients (7/8). One (1/8) patient showed multiple mediastinal lymph nodes enlargement. Under endoscopy, edema (12 cases), linear furrows (5 cases), rings (4 cases), exudates (1 case), and luminal narrowing (1 case) were observed in the mucosa. Eight patients underwent EUS, and all of them showed esophageal wall thickening, and the muscularis propria thickening being the most common (5.0-12.5 mm), with various hierarchical structures and unclear boundaries. Topical corticosteroid therapy led to significant symptom improvement and mucosal healing in 6 patients. Biopsy showed that the infiltration of eosinophils in the esophageal mucosa was significantly reduced or completely relieved. The clinical symptoms recurred in 5 patients after receiving acid suppression therapy, and 2 of them still had eosinophil infiltration in esophageal mucosal.Conclusion:The clinical presentation of EoE in adults can mimic gastroesophageal reflux disease, highlighting the importance of accurate diagnosis. The typical endoscopic findings of EoE are edema, linear furrows, rings, exudates and luminal narrowing. EUS can be used for the diagnosis, differential diagnosis, and objective evaluation of esophageal wall remodeling in patients with EoE. Adult patients with EoE have poor response to antacid therapy alone, while topical corticosteroid therapy can achieve good clinical efficacy and pathological remission.

Objective To investigate the impact of whole body vibration training combined with intermittent blood flow restriction on the motor function and community activity in elderly stroke patients with hemiplegia.Methods A total of 80 convalescent hemiplegic patients after stroke who were hospitalized in the Rehabilitation Medicine Department of Yichang Central People's Hospital(Xiling Campus)from October 2021 to December 2023 were included and randomly divided into control group(n=25),vibration group(n=28)and combination group(n=27)using the random number table method.All patients received conventional rehabilitation training,on the basis;the vabration group received whole body vibration training,while the combination group received whole body vibration training combined with intermittent blood flow restriction.Before and after 6 weeks of training,the balance function was evaluated with Berg balance scale(BBS),while the gait function was tested with 6-minute walking test(6MWT)and the Community Balance and Mobility scale(CB&M)was used to assess the community activity ability.The community balance and mobility(CB&M)were evaluated in the first and third month after discharge.Results There was no significant difference in BBS,CB&M scores and 6MWT walking distance between the three groups before training(P>0.05).After 6 weeks of training,the three groups showed significant increases in the BBS,CB&Mscores and the walk distance of 6MWT(P<0.001).Furthermore,compared with the control group,the combination group and the vibration group were significantly beter(P<0.05),and there was no signifi-cant difference between the combination group and the vibration group(P>0.05).At the first and third month of follw-up after discharge,the CB&M scores of the three groups were significantly higher than those of the control group(P<0.05),while there was no significant difference between the CB&M scores of the combination group and the vibration group at the first month of follow-up(P>0.05).But the CB&M scores of the combination group was higher than those of the vibration group at the third month of follow-up,and the difference was statistically signifi-cant(P<0.05).Conclusion On the basis of conventional rehabilitation,whole body vibration training combined with intermittent blood flow restriction can significantly enhance balance function,balance confidence,walking ability and mobility in early stage of community life for elderly stroke patients with hemiplegia,potentially facilitat-ing their return to community life.

Off-label use means that the intended use of the drug is not included in the instructions approved by the National Medical Products Administration,including unapproved indication,dosage,the course of treatment,route of administration,or population.The formulation of Pharmaceutical Supply Services-Key Medications Management-Off-label Uses is based on relevant laws,regulations,normative documents,guidelines,literatures,and expert opinions,and follows the principles of scientificity,versatility,instructiveness,and operability.This standard regulates and standardizes the institutional and organizational construction,process management,and the whole process of quality management and evaluation improvement of off-label uses,which is the basis for medical institutions to carry out off-label uses management.This article introduced the formulation process of the off-label uses standard and analyzed the key contents of the standard,which would help medical institutions to better comply with and meet the requirements of this standard in the practice of off-label use management.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective:To analyze the diagnostic value of positron emission tomography/computed tomography (PET/CT) for mediastinal lymph node metastasis in non-small cell lung cancer (NSCLC) patients.Methods:A retrospective analysis was conducted on the clinical data of 120 NSCLC patients admitted to the Suqian Hospital Affiliated to Xuzhou Medical University from July 2017 to June 2021. All patients underwent preoperative chest CT and PET/CT examination ( 18F-FDG imaging agent), and underwent total thoracoscopic lobectomy+ mediastinal lymph node dissection. Using the pathological results obtained from surgery as the gold standard, the diagnostic efficacy of chest CT and PET/CT examination for mediastinal lymph node metastasis in NSCLC patients was analyzed. Results:The surgical pathological results showed that 53 out of 120 patients had lymph node metastasis (33 cases of adenocarcinoma, 17 cases of squamous cell carcinoma, and 3 cases of adenocarcinoma), with 15, 32, and 6 cases of pN1, pN2, and pN3 staging, respectively; Preoperative chest CT examination identified 28 cases of true positive, 52 cases of true negative, 15 cases of false positive, and 25 cases of false negative with mediastinal lymph node metastasis, while PET/CT examination identified 44 cases, 61 cases, 6 cases, and 9 cases, respectively. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT in diagnosing mediastinal lymph node metastasis were higher than those of chest CT (all P<0.05); The consistency rate between PET/CT examination of lymph node metastasis N stage and surgical N stage [79.25% (42/53)] was higher than that of chest CT examination [45.28% (24/53)] ( P<0.05); The maximum standard uptake value (SUV) of lung cancer primary lesion in patients with mediastinal lymph node metastasis was higher than that in patients without lymph node metastasis ( P<0.05). Conclusions:PET/CT examination has high diagnostic value for mediastinal lymph node metastasis in NSCLC patients, and those who have objections to the results need further thoracoscopic examination to clarify the diagnosis.