Lymphoid structure in repair of spinal cord acupuncture injury / 中国实验动物学报

Objective To observe the distribution and characteristics of lymphatic vessels in normal and injured mouse spinal cord,and to determine if lymphatic vessels participate in the repair of spinal cord injury.Methods Thirty-nine adult male KM mice were divided randomly into a normal group(n=6)and an injured group(n=33).Mice in the injured group were further divided randomly into mice examined on postoperative days 1,3,5,7,and 14.Three mice in the injury group died after acupuncture injury,and the sample was subsequently supplemented randomly.Spinal cord damage was induced in the injured group by acupuncture,while mice in the normal group had no spinal cord damage.The distribution of lymphatic endothelial cells(LECs)in the spinal cord was detected by immunohistochemistry,and expression levels of the lymphatic endothelial cell markers prospero-related homobox-1(prox-1),lymphatic vessel endothelial cell hyaluronic acid receptor-1(lyve-1),and flat foot protein(podoplanin),and the vascular endothelial cell marker CD34 were observed in the spinal cords in normal and acupuncture-injured mice.Spinal cord samples were examined by immunofluorescence staining,and the source of new LECs was explored by observing the co-expression of lyve-1/prox-1,lyve-1/podoplanin,and CD34/prox-1.Results Lymphangioid structures were present in the spinal cord in normal mice and were distributed in segments,laterally between the white matter and gray matter.Nascent lymphangioid-like structures appeared in the spinal cord at the site of acupuncture injury,and prox-1,podoplanin,lyve-1,and CD34 were expressed simultaneously;however,these nascent lymphangioid-like structures disappeared after scarring during spinal cord injury.Conclusions Segmental,transversely distributed lymphangioid-like structures are present in the spinal cord in normal adult mice,and neonatal lymphangioid-like structures are involved in the reconstruction of spinal cord injury.These nascent LECs may originate from the surrounding existing lymphatic vessels or from vascular endothelial cells.

Clinical research of first-line chemotherapy and immunotherapy combined with chest radiotherapy for extensive-stage small cell lung cancer / 中华放射肿瘤学杂志

Objective:To evaluate the safety and efficacy of sequential consolidation thoracic radiotherapy after first-line chemotherapy combined with immunotherapy for extensive-stage small cell lung cancer (SCLC).Methods:A retrospective analysis of patients with extensive-stage SCLC admitted to Jiangsu Cancer Hospital from January 2019 to September 2022 was conducted. Patients who achieved effective chemotherapy combined with immunotherapy received sequential consolidation thoracic radiotherapy. The safety was evaluated according to the common terminology criteria for adverse events (CTCAE) 5.0 standard, and the overall survival (OS) and progression-free survival (PFS) were analyzed by Kaplan-Meier method.Results:A total of 33 patients were enrolled, with a median age of 66 years (range, 50-79 years). The median follow-up time was 20 months (range, 3-33 months). Fifteen patients (46%) had disease progression, and 12 patients (36%) died. The toxicities mainly included leukopenia, thrombocytopenia, radiation esophagitis, anorexia, and fatigue, etc. Six patients (18%) had grade 4 hematological toxicity, mainly leukopenia. One patient (3%) had grade 3 radiation pneumonitis, and 3 patients (9%) had grade 1-2 radiation pneumonitis. No grade 5 toxicity was observed in all patient groups. The median PFS was 12 months (95% CI=3.9-20.1). The 6-month, 1-year, and 2-year PFS rates were 78%, 49.6%, and 35.6%, respectively. The median OS was 23 months (95% CI=15.98-30.01). The 6-month, 1-year, and 2-year OS rates were 86.2%, 74.5%, and 47.2%, respectively. Conclusions:Sequential consolidation thoracic radiotherapy after first-line chemotherapy combined with immunotherapy is a safe protocol for extensive-stage SCLC. It brings survival benefits to patients by increasing PFS and OS rates.

Differentiated embryonic chondrocyte gene 2 (DEC2) inhibits transdifferentiation of mouse glomerular endothelial cells and renal fibrosis by blocking TGF-β/ROCK1 signaling pathway / 细胞与分子免疫学杂志

Objective To explore the protective mechanism of transdifferentiation of glomerular endothelial cells based on the differentiated embryonic chondrocyte gene 2 (DEC2) via the TGF-β/ROCK1 signaling pathway. Methods The 24 mice were randomly divided into sham group, UUO group, UUO combined with vector group and UUO combined with DEC2 group, with 6 mice in each group. A unilateral ureteral obstruction (UUO) model was established in each group, except for the sham group. In the UUO combined with vector group and UUO combined with DEC2 group, 10 μL (108 PFU) of vector or DEC2 was injected into each kidney on day 0 (immediately after UUO) under the guidance of the ultrasound system. The mice were sacrificed 14 days after the operation, and the kidneys were collected for histological examination and Western blot analysis: HE staining was used to observe the histological changes of kidneys, Masson staining to observe the renal fibrosis, and Western blot analysis to detect the protein expression. In vitro, normal human glomerular endothelial cells (GEnCs) was selected as the research objects. GEnCs stimulated with TGF-β were treated with ROCK1 inhibitor Y-27632 or DEC2 transfection. Western blot analysis was used to detect the expression of ROCK1, α-SMA, DEC2 and E-cadherin in GEnC exposed to transforming growth factor β (TGF-β). The localization of ROCK1 and DEC2 in GEnCs cells was detected by immunofluorescence cytochemistry. The relationship between the ROCK1 and DEC2 was confirmed by co-immunoprecipitation. Results Compared with the sham group, the UUO groups showed significant renal fibrosis and collagen accumulation on the 14th day. In the UUO groups, the expression of DEC2 and E-cadherin in the kidney tissue of the mice was significantly reduced, and the expression of α-SMA significantly increased. Compared with the UUO combined with vector group, the kidney fibrosis and collagen accumulation in the UUO combined with DEC2 group decreased, and the expression of ROCK1 and α-SMA decreased and the expression of DEC2 and E-cadherin increased in the kidney tissue. TGF-β enhanced the expression of ROCK1 and α-SMA in GEnCs cells in a time-dependent manner, and the levels of DEC2 and E-cadherin decreased. Treatment with the ROCK1 inhibitor Y-27632 partially abrogated the TGF-β-induced increase in the expression of ROCK1 and α-SMA and decrease in the expression of DEC2 and E-cadherin. In addition, transfection of GEnCs cells with DEC2 before TGF-β stimulation reduced the expression of ROCK1 and α-SMA, and increased the expression of DEC2 and E-cadherin. Immunofluorescence cytochemical staining showed that DEC2 co-localized with ROCK1 in GEnCs, and the co-immunoprecipitation showed that DEC2 and ROCK1 pulled down each other. Conclusions DEC2 is down-regulated in fibrotic renal tissue, while up-regulated DEC2 inhibits epithelial myofibroblast transdifferentiation and renal fibrosis of GEnC by blocking TGF-β/ROCK1 signaling pathway.

Construction of a clinical mortality risk prediction model for extracorporeal membrane oxygenation based on nomogram / 中华急诊医学杂志

Objective:To explore the risk factors of death in patients receiving ECMO treatment and to construct a nomogram prediction model.Methods:The clinical data of 412 consecutive patients with acute heart and (or) pulmonary failure who received ECMO treatment between April 2018 and June 2022 were retrospectively included.According to the patients' in-hospital survival, univariate correlation analysis was used to select risk factor variables, and then Lasso regression was used to screen all variables, combined with common variables, combined with clinical practice, plotted a nomogram to predict the probability of early mortality, using the area under the ROC curve (AUC), Harrell C index and calibration curve were used to evaluate and internally validate the performance of the model.Decision curve analysis was applied to assess its clinical utility.Results:Cerebral infarction, diabetes, history of cardiopulmonary resuscitation, neurological complications, acute kidney injury, lactate, hemoglobin, albumin, and platelet count were risk factors for death in patients receiving ECMO ( P<0.05).At the same time, according to the actual situation and difference variables, we constructed a nomogram with high reliability to predict the probability of death. Conclusions:The study identified the risk factors of death in patients receiving ECMO, successfully constructed and validated a nomogram prediction model, and provided a simple and reliable tool for ECMO death prediction, which is of great significance for individualized treatment of patients.

Single lung transplantation assisted by extracorporeal membrane oxygenation technique duringperioperative period:a report of 6 cases / 中华器官移植杂志

Objective To summarize the application experiences and curative efficacies of single lung transplantation assisted by extracorporeal circulation with coated lung ,centrifugal pump and coated pipe .Methods Retrospective analysis was conducted for clinical data of 6 adult patients with respiratory insufficiency undergoing single lung transplantation .The changes of hemodynamics and oxygenation before and after adjuvant treatment were observed ,the effects of adjuvant evaluated and the experiences of application summarized .Results The hemodynamic parameters post-assistance significantly improved as compared with that pre-assistance and pulmonary arterial pressure dropped from (56 ± 15 ) to (45 ± 13 ) mmHg with statistically significant differences . Arterial blood gas parameters significantly improved .PO2 spiked from (47 ± 12) to (68 ± 9) mmHg and PCO2 declined from (65 ± 14) to (55 ± 12)mmHg .And there were statistically significant differences .All patients were discharged successfully .Conclusions The simple extracorporeal membrane oxygenation system of coated lung , centrifugal pump and coated pipe during routine extracorporeal circulation may guarantee the operative safety of single lung transplantation and provide a new therapeutic option .

Promoter methylation and protein expression of tumor suppressor candidate 1 gene in adolescent papillary thy-roid carcinoma / 中华实用儿科临床杂志

Objective To study the relationship between status of methylation of tumor suppressor candidate 1 gene(TUSC1) promoter and expression of its protein in adolescent papillary thyroid carcinoma(PTC). Methods Forty cases of adolescent PTC were chosen and the corresponding para carcinoma tissues were taken from July 2010 to Decem-ber 2013 in the First Affiliated Hospital of Zhengzhou University surgical specimens of the thyroid gland and were con-firmed by pathology. Male 12 cases,female 28 cases,median age 14 (10-18) years old. Tumor node metastasis (TNM) stageⅠ-Ⅱ13 cases,Ⅲ-Ⅳstage 27 cases;gradeⅠin 15 cases,gradeⅡin 25 cases;lymph node metastasis in 22 cases,18 cases were negative. Methylation-specific polymerase chain reaction (MSP) and Western blot were applied respectively to examine the methyaltion of TUSC1 gene promoter and its protein expression of 40 samples of adolescent PTC and their matched adjacent non-cancerous epithelium. Results The results of MSP revealed that there was no methylation of TUSC1 gene promoter in adjacent non-cancerous epithelium,while in the adolescent PTC,the hyper-methylation rate was 60%(24/60 cases,χ2=34. 28,P<0. 05). In additional,it was related to the TNM stage,pathological grade and lymph node metastasis (χ2=4. 862,7. 111,5. 625,all P<0. 05). The result of Western blot revealed that the positive expression rate of TUSC1 protein was 100% in adjacent non-cancerous epithelium and 30%(12/40 cases) in adolescent PTC (χ2=14. 118,P<0. 05),which was related to the TNM stage,pathological grade and lymph node metastasis (χ2=5. 215,6. 222, 5. 079,all P<0. 05). There was distinct correlation between methylation of TUSC1 gene promoter and the protein expres-sion (r=-0. 84,P<0. 05). Conclusions Methylation of promoter might be one of the important mechanisms of inactiva-tion of TUSC1 gene,and might play an important role in carcinogenesis and progression of adolescent PTC.