Objective:To evaluate the efficacy and safety of immunotherapy combined with chemotherapy as conversion therapy for initially unresectable locally advanced esophageal squamous cell carcinoma.Methods:This retrospective case series study analyzed clinical and pathological data of 32 patients with initially unresectable locally advanced esophageal squamous cell carcinoma who received immunotherapy combined with chemotherapy at the Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University, from June 2020 to December 2024. The cohort included 27 males and 5 females, with an age ( M(IQR)) of 61(9)years (range:46 to 73 years). Five patients were diagnosed with stage Ⅲ, 27 with stage ⅣA. All patients received PD-1 inhibitor sintilimab combined with nedaplatin and albumin-bound paclitaxel. Radiological evaluations were performed every two cycles, the multidisciplinary team evaluation was conducted to determine conversion to resectable status, and patients with successful conversion underwent radical esophagectomy. Follow-up was conducted via telephone or outpatient visits every 3 to 6 months after the last treatment. The primary endpoint was R0 resection rate, secondary endpoints included objective response rate (ORR), pathological complete response (pCR) rate, major pathological response (MPR) rate, event-free survival (EFS), disease-free survival (DFS) in patients with R0 resection, overall survival (OS) and safety. Kaplan-Meier method was used to plot survival curves and estimate median EFS, DFS, OS rates and their 95% CI. The 95% CI for ORR, pCR rate, MPR rate, and downstaging rate were calculated using the Clopper-Pearson method. Results:The median treatment cycle of 2(1) (range:2 to 8). As of June 2025, the median follow-up was 32.5(13.5)months (range:6.4 to 59.1 months). Among the 32 patients, 9 experienced progression or recurrence, including 2 with liver and lymph node metastases, 2 with lung metastases, 2 with thoracic vertebral metastases, and 3 with mediastinal lymph node metastases. After conversion therapy, 29 patients underwent surgery, achieving an R0 resection rate of 84.4% (95% CI:67.2% to 94.7%), a pCR rate of 27.6% (95% CI:12.7% to 47.2%), and an MPR rate of 55.2% (95% CI:35.7% to 73.6%). Grade 3 or higher surgical complications occurred in 6.9%(2/29) of patients, and grade 3 or higher treatment-related adverse events were observed in 15.6%(5/29). Among the 32 patients, the ORR was 56.3% (95% CI:37.7% to 73.6%),the 3-year EFS rate and OS rate was 59.4% (95% CI:40.8% to 86.4%) and 59.7% (95% CI:40.0% to 89.0%) respectively. Conclusion:Immunotherapy combined with chemotherapy demonstrates high conversion rates and favorable safety in the conversion therapy of initially unresectable locally advanced esophageal squamous cell carcinoma, representing a promising treatment strategy.

Objective To analyze the current research status,hotspots,and trends in the field of mechanical ventilation weaning.Methods Literatures in the field of mechanical ventilation wea-ning were retrieved from the Web of Science Core Collection,PubMed,China National Knowledge In-frastructure(CNKI),and Wanfang Data Knowledge Platform from January 1,2010 to November 27,2024.CiteSpace software was used to analyze the research status and future trends.Results A total of 705 English and 494 Chinese eligible articles were included in this study.The author with the most publications was Laurent Brochard(14 articles).Research hotspots focused on mechanical ventila-tion,weaning,non-invasive ventilation,respiratory failure,etc.New research hotspots have shifted towards mechanical ventilation weaning failure,weaning complications,and prolonged weaning.Con-clusion Further research is needed on weaning failure,complications,and prolonged weaning,par-ticularly in the direction of invasive-high-flow oxygen therapy sequential therapy,which will help opti-mize clinical treatment plans and reduce patients' suffering and economic burdens.

To evaluate the efficacy and safety of dye-free submucosal injection solution for gastric endoscopic submucosal dissection (ESD), a retrospective cohort study was performed on data of inpatients with early gastric cancer and precancerous lesions who underwent ESD at the Digestive Endoscopy Center of Jiangsu Province Hospital of Traditional Chinese Medicine from January to December 2020. Cases were divided into dye-free submucosal injection solution group (the observation group) and dye-containing solution group (the control group). A total of 108 cases met the eligibility criteria for analysis (39 VS 69). Baseline characteristics were comparable between the two groups ( P>0.05). Compared with the control group, the observation group showed similar median procedure time (30.5 min VS 35.0 min), median dissection speed (0.3 cm2/min VS 0.4 cm2/min), mean volume of injection solution used (39.2 mL VS 38.8 mL), en bloc resection rate [100.0% (39/39) VS 98.6% (68/69)], and curative resection rate [97.4% (38/39) VS 97.1% (67/69)] (all P>0.05). Postoperative stay was 3.0±0.8 days in the observation group and 3.2±0.8 days in the control group ( t=-0.908, P=0.378). Delayed bleeding occurred in 3 (7.7%) patients VS 2 (2.9%) patients ( P=0.349), and postoperative infection occurred in 3 (7.7%) patients VS 8 (11.6%) patients ( P=0.743), respectively. In gastric ESD, dye-free submucosal injection solution demonstrates efficacy comparable with dye-containing solution and does not appreciably increase the incidence of intraoperative or postoperative complications.

Objective:To investigate the role and mechanism of IL-17 in hypertensive heart failure in rats.Methods:The spon-taneously hypertensive(SHR)model of hypertensive heart failure was established by abdominal aortic ligation.IL-17+IgG and IL-17 protein were injected intraperitoneally into the rats with hypertensive heart failure.After 4 weeks,cardiac structure and function were monitored,and peripheral blood and myocardial tissue were collected.The role and mechanism of IL-17 in hypertensive heart failure were studied by HE staining,immunohistochemistry,Western blot,qRT-PCR and ELISA.Results:After intraperitoneal injection of exogenous IL-17,the levels of IL-17,NT-proBNP,P38 and MK2 protein expressions were increased,and the levels of VEGF and Cav1.2 protein expression were decreased.Exogenous intraperitoneal injection of IL-17+IgG blocked IL-17,increased VEGF level and Cav1.2 protein expression,and decreased NT-proBNP level,P38 and MK2 protein expressions.Conclusion:IL-17 can be activated P38 lightning/MK2-Cav1.2 signaling pathways involved in high blood pressure,heart failure and cardiac function in rats damage;inhi-bition of IL-17 can effectively improve the cardiac function damage caused by hypertensive heart failure.

Objective:To investigate the role and mechanism of IL-17 in hypertensive heart failure in rats.Methods:The spon-taneously hypertensive(SHR)model of hypertensive heart failure was established by abdominal aortic ligation.IL-17+IgG and IL-17 protein were injected intraperitoneally into the rats with hypertensive heart failure.After 4 weeks,cardiac structure and function were monitored,and peripheral blood and myocardial tissue were collected.The role and mechanism of IL-17 in hypertensive heart failure were studied by HE staining,immunohistochemistry,Western blot,qRT-PCR and ELISA.Results:After intraperitoneal injection of exogenous IL-17,the levels of IL-17,NT-proBNP,P38 and MK2 protein expressions were increased,and the levels of VEGF and Cav1.2 protein expression were decreased.Exogenous intraperitoneal injection of IL-17+IgG blocked IL-17,increased VEGF level and Cav1.2 protein expression,and decreased NT-proBNP level,P38 and MK2 protein expressions.Conclusion:IL-17 can be activated P38 lightning/MK2-Cav1.2 signaling pathways involved in high blood pressure,heart failure and cardiac function in rats damage;inhi-bition of IL-17 can effectively improve the cardiac function damage caused by hypertensive heart failure.

To evaluate the efficacy and safety of dye-free submucosal injection solution for gastric endoscopic submucosal dissection (ESD), a retrospective cohort study was performed on data of inpatients with early gastric cancer and precancerous lesions who underwent ESD at the Digestive Endoscopy Center of Jiangsu Province Hospital of Traditional Chinese Medicine from January to December 2020. Cases were divided into dye-free submucosal injection solution group (the observation group) and dye-containing solution group (the control group). A total of 108 cases met the eligibility criteria for analysis (39 VS 69). Baseline characteristics were comparable between the two groups ( P>0.05). Compared with the control group, the observation group showed similar median procedure time (30.5 min VS 35.0 min), median dissection speed (0.3 cm2/min VS 0.4 cm2/min), mean volume of injection solution used (39.2 mL VS 38.8 mL), en bloc resection rate [100.0% (39/39) VS 98.6% (68/69)], and curative resection rate [97.4% (38/39) VS 97.1% (67/69)] (all P>0.05). Postoperative stay was 3.0±0.8 days in the observation group and 3.2±0.8 days in the control group ( t=-0.908, P=0.378). Delayed bleeding occurred in 3 (7.7%) patients VS 2 (2.9%) patients ( P=0.349), and postoperative infection occurred in 3 (7.7%) patients VS 8 (11.6%) patients ( P=0.743), respectively. In gastric ESD, dye-free submucosal injection solution demonstrates efficacy comparable with dye-containing solution and does not appreciably increase the incidence of intraoperative or postoperative complications.

Objective:To evaluate the efficacy and safety of immunotherapy combined with chemotherapy as conversion therapy for initially unresectable locally advanced esophageal squamous cell carcinoma.Methods:This retrospective case series study analyzed clinical and pathological data of 32 patients with initially unresectable locally advanced esophageal squamous cell carcinoma who received immunotherapy combined with chemotherapy at the Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University, from June 2020 to December 2024. The cohort included 27 males and 5 females, with an age ( M(IQR)) of 61(9)years (range:46 to 73 years). Five patients were diagnosed with stage Ⅲ, 27 with stage ⅣA. All patients received PD-1 inhibitor sintilimab combined with nedaplatin and albumin-bound paclitaxel. Radiological evaluations were performed every two cycles, the multidisciplinary team evaluation was conducted to determine conversion to resectable status, and patients with successful conversion underwent radical esophagectomy. Follow-up was conducted via telephone or outpatient visits every 3 to 6 months after the last treatment. The primary endpoint was R0 resection rate, secondary endpoints included objective response rate (ORR), pathological complete response (pCR) rate, major pathological response (MPR) rate, event-free survival (EFS), disease-free survival (DFS) in patients with R0 resection, overall survival (OS) and safety. Kaplan-Meier method was used to plot survival curves and estimate median EFS, DFS, OS rates and their 95% CI. The 95% CI for ORR, pCR rate, MPR rate, and downstaging rate were calculated using the Clopper-Pearson method. Results:The median treatment cycle of 2(1) (range:2 to 8). As of June 2025, the median follow-up was 32.5(13.5)months (range:6.4 to 59.1 months). Among the 32 patients, 9 experienced progression or recurrence, including 2 with liver and lymph node metastases, 2 with lung metastases, 2 with thoracic vertebral metastases, and 3 with mediastinal lymph node metastases. After conversion therapy, 29 patients underwent surgery, achieving an R0 resection rate of 84.4% (95% CI:67.2% to 94.7%), a pCR rate of 27.6% (95% CI:12.7% to 47.2%), and an MPR rate of 55.2% (95% CI:35.7% to 73.6%). Grade 3 or higher surgical complications occurred in 6.9%(2/29) of patients, and grade 3 or higher treatment-related adverse events were observed in 15.6%(5/29). Among the 32 patients, the ORR was 56.3% (95% CI:37.7% to 73.6%),the 3-year EFS rate and OS rate was 59.4% (95% CI:40.8% to 86.4%) and 59.7% (95% CI:40.0% to 89.0%) respectively. Conclusion:Immunotherapy combined with chemotherapy demonstrates high conversion rates and favorable safety in the conversion therapy of initially unresectable locally advanced esophageal squamous cell carcinoma, representing a promising treatment strategy.

Objective To investigate the effect and mechanism of IL-17 on heart failure(HF)in hy-pertensive rats based on NF-κB/sarco-endoplasmic reticulum calcium ATPase 2(SERCA2)signa-ling pathway.Methods Thirty SPF male spontaneously hypertensive rats(SHR)aged 6-8 weeks were divided into control group,model group,phosphate buffer salt(PBS)solution injec-tion group(PBS group),IL-17 protein injection group(IL-17 group)and IL-17 and antibody injec-tion group(IL-17+IgG group),with 6 animals in each group.Hypertensive HF model was estab-lished,and corresponding agents were applied to the PBS group,IL-17 group and IL-17+IgG group intraperitoneally,respectively.The role of IL-17,NF-κB and SERCA2 in hypertensive HF was studied with HE staining,immunohistochemical assay,Western blotting,RT-qPCR and ELISA.Results Significantly higher serum levels of NT-proBNP and IL-17,enhanced myocardial expression of IL-17 mRNA and NF-κB protein,lower serum VEGF level,and down-regulated pro-tein level of SERCA2 in heart tissue were observed in the model group and the PBS group when compared with the control group(P＜0.01).The IL-17 group had obviously higher serum NT-proBNP and IL-17 levels and myocardial expression of IL-17 mRNA and NF-κB protein,and reduced serum VEGF level and SERCA2 protein level in heart tissue than the model group(P＜0.01).IL-17+IgG treatment resulted in notably lower serum IL-17 level and myocardial NF-κB protein level when compared with those of model group(8.98±1.20 vs 11.19±1.22,0.88±0.03 vs 0.93±0.03,P＜0.01),and also resulted in remarkably reduced serum levels of NT-proBNP and IL-17 and myocardial expression of IL-17 mRNA and NF-κB protein but increased serum VEGF level and SERCA2 protein level in heart tissue when compared with the IL-17 group(P＜0.01).The heart rate,SBP,IVSd,LVPWd,LVEDD and LVESD were significantly lower,while LVFS was notably higher in the IL-17+IgG group than the model group and IL-17 group(P＜0.01).The IL-17+IgG group had obviously higher LVEF than the IL-17 group[(70.81±6.50)％vs(62.77±5.43)％,P＜0.01].Conclusion IL-17/NF-κB/SERCA2 signaling pathway is involved in the regulation of inflammatory response after hypertensive HF,and inhibiting IL-17 can effective-ly improve the cardiac dysfunction caused by hypertensive HF.

Humans ; May-Thurner Syndrome ; Coronary Restenosis ; Constriction, Pathologic/surgery* ; Stents/adverse effects* ; Iliac Vein ; Treatment Outcome ; Retrospective Studies

ObjectiveTo explore the effects of Bushen Jianpi prescription on the autophagy and phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway in the patients with aplastic anemia （AA）. MethodA total of 30 AA patients admitted to Xiyuan Hospital and 6 healthy donors who were prepared to undergo peripheral blood hematopoietic stem cell transplantation in 304 Hospital from September 2020 to August 2021 were enrolled and assigned into an AA group and a control group. The AA group was treated with Bushen Jianpi prescription combined with cyclosporin A （CsA） and androgen for 3 months. The mononuclear cells from bone marrow in the AA group before and after treatment and the peripheral blood of the control group were collected. Transmission electron microscopy was then employed to detect autophagosomes. Western blotting was employed to determine the protein levels of microtuble-associated protein 1 light chain 3 （LC3）Ⅰ， LC3Ⅱ， mTOR， phosphorylated （p）-mTOR， Akt， p-Akt， PI3K， and p-PI3K， and real-time polymerase chain reaction （PCR） to determine the mRNA levels of LC3， mTOR， Akt， and PI3K. ResultIn the AA group， the treatment was completed in 29 patients， and the total response rate was 51.72% （15/29）. ① The AA group showed lower levels of white blood cell （WBC）， hemoglobin （HGB）， platelet （PLT）， and absolute neutrophil count （ANC） in the peripheral blood （P<0.01） and lower number of intracellular autophagosomes than the control group before treatment. Moreover， the AA group showed lower mRNA level of LC3 （P<0.01） and protein levels of LC3Ⅰ and LC3Ⅱ （P<0.01） and higher mRNA levels of mTOR， Akt， and PI3Kα （P<0.01） and protein levels of Akt， p-Akt， PI3K， p-PI3K， mTOR， and p-mTOR （P<0.01） than the control group. ② In AA group， the levels of HGB and PLT elevated （P<0.05） and the number of intracellular autophagosomes increased after treatment compared with those before treatment. Moreover， the mRNA level of LC3 and the protein levels of LC3Ⅰ and LC3Ⅱ were up-regulated （P<0.01）， the mRNA levels of mTOR， Akt， and PI3Kα （P<0.01） and the protein levels of Akt， p-PI3K （P<0.01）， p-Akt， PI3K， mTOR， p-mTOR （P<0.05） were down-regulated after treatment. ConclusionAA patients show lower autophagy levels， while Bushen Jianpi prescription can effectively improve the autophagy level and down-regulated the expression of PI3K/Akt/mTOR signaling pathway in AA patients.