1.Research on the Improvement of Ferroptosis and Cognitive Function Impairment in APP/PS1 Alzheimer's Mice by Bingchan-gsan via the Nrf2/HO-1 Signaling Pathway
Shaobo GUO ; Wenhui ZHU ; Yu BAI ; Biao ZHANG
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(6):598-607
OBJECTIVE To explore whether inhaling Bingchangsan(BCS can modulate the Nrf2/HO-1 signaling pathway to improve ferroptosis and cognitive dysfunction in Alzheimer's Disease(AD mouse models.METHODS 30 APP/PS1 mice were ran-domly divided into three groups:a model group(APP/PS1 group,a low-dose Bingchangsan group(BCS-L group,and a high-dose Bingchangsan group(BCS-H group.10 age-matched wild-type(WT mice were used as a control group.The WT group and the APP/PS1 group were treated with nebulized pure water,while the BCS-L group received 0.5μL of Bingchangsan inhalation solution per day,and the BCS-H group received 1μL,both administered via nebulization for 10 min daily for 2 weeks.2 weeks post-treat-ment,spatial cognitive abilities of the mice were assessed using the Morris water maze test.Following the water maze experiment,the mice were euthanized,and their brain tissues were collected for Aβ1-42 immunofluorescence,P-tau immunohistochemistry,and Nissl staining.Hippocampal tissues were extracted for Western blot and qPCR analysis to measure the protein and mRNA expression levels of Keap1,Nrf2,HO-1,GPX4,SCL7A11,TFRC,DMT1,FTL,and FTH1.Additionally,brain tissues were used for glutathione(GSH content measurement using a GSH assay kit.RESULTS In the BCS groups,the latency period for escape shortened,and the time spent in the quadrant with the platform,as well as the number of times crossing the platform,increased.Compared to the APP/PS1 group,the expression levels of Aβ1-42 and P-tau in the hippocampal CA1 region and cortex of mice in the BCS groups were signifi-cantly reduced(P<0.05,P<0.01.Nissl staining revealed a denser arrangement of neurons with more Nissl bodies in the BCS groups.In the hippocampal tissue,compared to untreated APP/PS1 mice,significant increases in the protein and mRNA levels of Nrf2,HO-1,SLC7A11,GPX4,and FTL were observed in all BCS groups(P<0.05,P<0.01.While the BCS-L group showed in-creased levels of FTH1 protein and mRNA,these changes were not statistically significant.Furthermore,the expression levels of TFRC,DMT1,and Keap1 were significantly downregulated in the BCS groups(P<0.05,P<0.01.Additionally,treatment with BCS effectively restored the glutathione(GSH content in the brain(P<0.01.CONCLUSION Inhalation of BCS can improve cognitive dysfunction in APP/PS1 mice.BCS activates the Nrf2/HO-1 pathway,increases the expression of GPX4,and enhances Nrf2 tran-scriptional activity by inhibiting Keap1.This leads to an upregulation of SLC7A11 and restoration of GSH levels,effectively countering ferroptosis.Additionally,BCS effectively inhibits TFRC and DMT1,while upregulating FTL and FTH1 expression,thereby maintaining intracellular iron homeostasis.This contributes to mitigating the impact of ferroptosis on APP/PS1 mice,subsequently enhancing their cognitive functions.
2.A community-based serological cohort study on incidence of seasonal influenza virus infection in Macheng city from winter 2019 to spring 2020
Jinsong FAN ; Jianbo ZHAN ; Yue CHEN ; Shaobo DONG ; Jian LU ; Junfeng GUO ; Xiaojing LIN ; Yu LAN ; Kun QIN ; Jianfang ZHOU ; Bing HU ; Cuiling XU
Chinese Journal of Experimental and Clinical Virology 2024;38(3):311-318
Objective:To determine incidence of seasonal influenza virus infection in the community and to analyze the factors influencing seasonal influenza virus infection.Methods:This study recruited residents aged 6-59 years to build a cohort in 15 villages/streets in Macheng city in November 2019. Meanwhile, a cross-sectional baseline survey was conducted immediately to collect sera, information on demographics and child protection knowledge, behaviors, as well as attitudes using a questionnaire from the participants enrolled in the cohort (i.e., before the influenza epidemic season). In July 2020, a cross-sectional follow-up survey was conducted to collect sera once again (i.e., after the influenza season). Paired sera from the two cross-sectional surveys were tested for influenza virus-specific antibodies by hemagglutination inhibition (HI) test or micro-neutralization (MN) test using a circulating representative strain of each subtype/lineage of influenza virus as the test antigen. The infections with influenza virus subtype/lineage was confirmed if there was a four-fold or more increase in titers of antibodies against circulating representative strain of the subtype/lineage of influenza virus. Factors influencing infection with influenza A (H3N2) and B/Victoria viruses were analyzed using univariable and multivariable logistic regression.Results:In November 2019, 800 study participants were enrolled in the cohort, including 340 children aged 6-17 years and 460 adults aged 18-59 years; 605 study participants (including 224 children and 381 adults) were followed up in July 2020 and their paired sera were obtained before and after the influenza season. 25.3% (153/605) of the participants were confirmed to be infected with at least one subtype/lineage of seasonal influenza virus by HI and MN tests. The overall incidence of influenza viruses of all subtypes/lineages in children was 44.2% (95% CI: 37.6%-50.8%) which was significantly higher than the incidence of 14.1% in adults (95% CI: 10.7%-17.7%). Children had the highest incidence of influenza A (H3N2) virus infection, followed by B/Victoria. MN or HI antibody titers in A (H3N2)[ OR=0.88 (95% CI: 0.84-0.93)] and B/Victoria[ OR=0.97 (95% CI: 0.95-0.99)] before the influenza season were significantly associated with whether children were infected with that subtype/lineage of influenza virus. Conclusions:The residents aged 6-59 years in Macheng city had a substantial incidence of seasonal influenza virus infection during the influenza season from winter 2019 to spring 2020. Notably, almost half of children aged 6-17 years have been infected with seasonal influenza virus. Higher titers of HI/MN antibodies against seasonal influenza virus before the influenza season would be likely to reduce the risk of infection with influenza A (H3N2) and B/Victoria.
3.Therapeutic effects of adjuvant chemotherapy and adjuvant immunotherapy combined chemotherapy after radical cystectomy for MIBC with high risk of recurrence
Zhi LI ; Shaobo YANG ; Zejin WANG ; Chong SHEN ; Yinglang ZHANG ; Yu ZHANG ; Runxue JIANG ; Zhe ZHANG ; Yong XU ; Hailong HU
Chinese Journal of Urology 2024;45(3):187-194
Objective:To explore the efficacy of adjuvant chemotherapy and adjuvant immunotherapy combined chemotherapy after radical cystectomy for muscle-invasive bladder cancer (MIBC) with high recurrence risk (pT 2 with positive lymph nodes, and pT 3-4a with or without positive lymph nodes). Methods:A retrospective analysis was conducted on clinical data of 217 patients with bladder cancer admitted to Tianjin Medical University Second Hospital from August 2016 to January 2022. Among them, 183 were male (84.3%) and 34 were female (15.7%), with an average age of (67.3±8.6) years old. All 217 patients underwent radical cystectomy with pelvic lymph node dissection. Based on postoperative adjuvant treatment, the patients were divided into an observation group (147 cases, 67.7%) and a treatment group (70 cases, 32.3%). The observation group and treatment group had similar demographic and pathological characteristics. The age of the observation group and treatment group was (67.4±9.0) years and (66.3±7.6) years, respectively ( P=0.14). The postoperative pathological stages T 2 with lymph node positivity were observed in 8 cases (5.4%) in the observation group and 6 cases (8.6%) in the treatment group. For stages T 3-4awith lymph node positivity, there were 34 cases (23.1%) in the observation group and 18 cases (25.7%) in the treatment group. And there were 105 cases (71.5%) in the observation group and 46 cases (65.7%) in the treatment group of stages T 3-4a without lymph node positivity, respectively( P>0.05). Tumor diameter ≥3 cm was found in 118 cases (80.3%) in the observation group and 54 cases (77.1%) in the treatment group ( P>0.05), while tumor diameter <3 cm was observed in 29 cases (19.7%) in the observation group and 16 cases (22.9%) in the treatment group ( P>0.05).In the treatment group, 36 patients (16.6%) received postoperative chemotherapy with gemcitabine (1 000 mg/m 2, days 1 and 8) and cisplatin (75 mg/m 2, days 2 to 4) (chemotherapy group), while 34 patients (15.7%) received postoperative immunotherapy with checkpoint inhibitors (intravenous infusion of sintilimab 200 mg, terlizumab 200 mg, or toripalimab 240 mg on day 1) in combination with albumin-bound paclitaxel (200 mg on day 2)(immunotherapy combined chemotherapy group). The age of the chemotherapy group and immunotherapy combined chemotherapy group was (66.8±8.4) years and (65.8±6.8) years, respectively ( P>0.05). Postoperative pathological stages T 2 with lymph node positivity were observed in 3 cases (8.3%) in the chemotherapy group and 3 cases (8.8%) in the immunotherapy combined chemotherapy group ( P>0.05). For stages T 3-4awith lymph node positivity, there were 6 cases (16.7%) in the chemotherapy group and 12 cases (35.3%) in the immunotherapy combined chemotherapy group. And there were 27 cases (75.0%) in the observation group and 19 cases (55.9%) in the treatment group of stages T 3-4a without lymph node positivity, respectively( P>0.05). Lymph node involvement was seen in 9 cases (25.0%) in the chemotherapy group and 15 cases (44.1%) in the immunotherapy combined chemotherapy group ( P>0.05). Tumor diameter ≥3 cm was found in 30 cases (83.3%) in the chemotherapy group and 10 cases (29.4%) in the immunotherapy combined chemotherapy group ( P>0.05), while tumor diameter <3 cm was observed in 6 cases (16.7%) in the chemotherapy group and 24 cases (70.6%) in the immunotherapy combined chemotherapy group ( P>0.05). Kaplan-Meier method and multivariate Cox regression test were used to analyze the overall survival (OS) at 1 and 3 years in the observation group and treatment group, as well as the disease-free survival (DFS) at 1 and 3 years in the chemotherapy group and immunotherapy combined chemotherapy group. Additionally, common adverse events were evaluated and compared between the chemotherapy group and immunotherapy combined chemotherapy group based on the criteria published by the U. S. Department of Health and Human Services. Results:The median follow-up time in this study was 18.4 (8.2, 34.7) months. The median follow-up time in the observation group and treatment group was 19.0 (8.3, 35.2) months and 17.5 (7.9, 33.2) months, respectively. The 1-year survival rate was significantly higher in the treatment group compared to the observation group (90.0% vs. 76.2%, χ2=6.92, P=0.009). Similarly, the 3-year survival rate was significantly higher in the treatment group compared to the observation group (82.9% vs. 57.8%, χ2=13.22, P<0.01). The median OS was 35.9 months in the observation group and was not reached in the treatment group, with a statistically significant difference ( HR=2.51, 95% CI 1.36-4.65, P=0.003).In the chemotherapy group and immunotherapy combined chemotherapy group, the median follow-up time was 10.7 (7.4, 22.1) months and 14.4 (6.3, 40.7) months, respectively. The 1-year disease-free survival rate was significantly higher in the immunotherapy combined chemotherapy group compared to the chemotherapy group (91.2% vs. 67.6%, χ2=4.60, P=0.032). The 3-year disease-free survival rate was significantly higher in the chemotherapy group compared to the immunotherapy combined chemotherapy group (88.2% vs. 55.6%, χ2=8.37, P=0.004). The median DFS was 27.7 months in the chemotherapy group and was not reached in the immunotherapy combined chemotherapy group, with a statistically significant difference ( HR=3.39, 95% CI 1.46-7.89, P=0.016).The treatment group had complications classified as follows: 140 cases of grade 1, 39 cases of grade 2, 8 cases of grade 3, 2 cases of grade 4, and 0 case of grade 5 adverse reactions. In the chemotherapy group and the immunotherapy combined chemotherapy group, there were both 5 cases with adverse reactions of grade 3 or higher. Specifically, in the chemotherapy group, there were 2 cases of anemia, 2 cases of decreased platelet count, and 1 case of decreased neutrophil count. In the immunotherapy combined chemotherapy group, there was 1 case of anemia, 1 case of decreased platelet count, and 2 cases of decreased neutrophil count. Additionally, there was 1 case with elevated gamma-glutamyltransferase (γ-GT) in the immunotherapy combined chemotherapy group. The incidence of adverse events of grade 3 or higher in the chemotherapy group and immunotherapy combined chemotherapy group was 13.9% and 14.7%, respectively, with no statistically significant difference( χ2=0.01, P=0.922). Conclusions:Adjuvant therapy significantly prolongs the overall survival in high risk of recurrence for MIBC patients after radical cystectomy. For patients intolerant to platinum-based chemotherapy or refusing platinum-based adjuvant chemotherapy, immunotherapy with checkpoint inhibitors combined with albumin-bound paclitaxel can be considered as an effective and well-tolerated adjuvant treatment after radical cystectomy.
4.Mechanism of mechanical stress in knee osteoarthritis synovial fibrosis mediated via the Piezo1/ERK1/2 axis
Likai YU ; Di TIAN ; Zishan SU ; Lishi JIE ; Shaobo GUO ; Peimin WANG ; Nongshan ZHANG
Chinese Journal of Comparative Medicine 2024;34(10):47-56
Objective To investigate the effect of Piezo1 activated by mechanical stress on knee osteoarthritis synovial fibrosis via the extracellular signal-regulated kinase(ERK)1/2 signaling pathway.Methods Twenty-five Sprague Dawley rats were divided into blank,exercise,exercise+GsMTx4,exercise+PD98059,and exercise+GsMTx4+PD98059 groups(n=5 per group).After modeling,serum and synovial tissue were extracted and collagen deposition was evaluated by Sirius red and Masson staining.Expression levels of Piezo1,ERK1/2,phospho(p)-ERK1/2,α-smooth muscle actin(SMA),transforming growth factor(TGF)-β,Collagen Ⅰ,and tissue inhibitor of metalloproteinase(TIMP)-1 were detected by Western blot and reverse transcription-quantitative polymerase chain reaction(RT-qPCR),and the interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)-α contents were detected by enzyme-linked immunosorbent assay.For cell experiments,synovial cells were divided into blank,pull,pull+GsMTx4,pull+PD98059,and pull+GsMTx4+PD98059 groups and the above indices were detected in the model cells by Western blot,RT-qPCR,and other techniques.Results Mechanical stress increased collagen deposition in synovial tissues in the rats,and increased the protein and mRNA expression levels of the pathway-related and fibrosis-specific indicators Piezo1,p-ERK/ERK,α-SMA,TGF-β,Collagen I,and TIMP-1(P<0.05).Piezo1 expression was significantly down-regulated by both inhibitors(P<0.05),but the ERK inhibitor(PD98059)had no significant effect on Piezo1 gene expression.Levels of serum inflammatory factors were significantly higher in the exercise group compared with the blank group(P<0.05),and levels were significantly reduced by the inhibitors(P<0.05).The in vitro experiments showed the same trends as the animal experiments.Conclusions The Piezo1 ion channel can sense mechanical stress and activate the ERK 1/2 pathway to mediate knee synovial fibrosis.
5.The application of kissing-stent in treating chronic iliac-vena cava occlusion
Shaobo ZHAI ; Zhixiang LV ; Zhihua ZHANG ; Jifeng SUN ; Yangyang YU ; Cheng GAO
Journal of Interventional Radiology 2024;33(7):763-766
Objective To evaluate the clinical efficacy of kissing-stent implantation in the treatment of chronic iliac-vena cava occlusion.Methods The clinical data of 22 patients with chronic iliac-vena cava occlusion,who received kissing-stent implantation,were retrospectively analyzed.The surgical success rate and the procedure-related complications were recorded,the postoperative 3-,6-and 12-month stent patency rates were calculated,and the postoperative 6-month Villalta score was compared with its preoperative value.Results The technical success rate of kissing-stent implantation was 100%.No procedure-related surgical complications occurred.The postoperative 3-,6-and 12-month stent patency rates were 95.5%,90.9%and 86.1%respectively.The postoperative 6-month Villalta score was(12.14±2.80)points,which was remarkably lower than preoperative(20.91±3.16)points,the difference was statistically significant(P<0.05).Conclusion The implantation of kissing-stent can successfully reconstruct iliac-vena cava with satisfactory short-term efficacy for chronic iliac-vena cava occlusion.
6.Clinical effects of total laparoscopic technique in the treatment of pelvic and acetabular fractures
Siyuan QING ; Shaobo ZHANG ; Ruizhe ZHAO ; Jie LI ; Guqi HONG ; Yu ZHANG ; Jun HU ; Xiaodong QIN
Chinese Journal of Orthopaedics 2024;44(7):463-469
Objective:To investigate the clinical efficacy of total laparoscopic technique in the treatment of pelvic and acetabular fractures.Methods:A total of 7 patients with pelvic and acetabular fractures admitted to the First Affiliated Hospital of Nanjing Medical University from April 2017 to August 2023 were retrospectively analyzed. There were 5 males and 2 females, aged 43.9±9.9 years (range, 27-56 years). There was 1 pelvic fracture (Tile B3) and 6 acetabular fractures, Letournel typing transverse in 2 cases, double column in 1 case, transverse combined anterior column in 1 case, anterior column in 1 case, and "T" shape in 1 case. The causes of injury included traffic accident in 4 cases, falling from height in 1 case, falling in 1 case, and heavy object injury in 1 case. The operation time, intraoperative blood loss, iatrogenic injuries of blood vessels, nerves, bladder and rectum, and incidence of postoperative complications were recorded. Matta imaging criteria was used to evaluate the quality of fracture reduction, and the hip function was evaluated by modified Merle d'Aubigné-Postel score.Results:All 7 patients were successfully operated and followed up for 12.0 (7.0, 72.0) months (range, 7-77 months). The operation time was 251.1±80.2 min (range, 150.0-370.0 min), and the intraoperative blood loss was 100.0 (50.0, 300.0) ml (range, 50-350 ml). There was no nerve, blood vessel, bladder or rectum injury during operation. Postoperative pelvic X-ray and CT showed no internal fixation into the joint. Anatomic reduction was achieved in 5 cases and satisfactory reduction in 2 cases. One patient with a transverse acetabular fracture had a slight separation and displacement of the posterior column, but the acetabular articular surface was flat as a whole without obvious steps and was not fixed. One patient with pelvic fracture had a comminuted anterior pelvic ring with severe displacement and did not achieve anatomical repositioning intraoperatively, but the anterior pelvic ring was a non-intra-articular fracture, and the fracture ends were immobilized with bilateral plates, and the morphology and stability of the anterior pelvic ring recovered well after the operation. The Merle d'Aubigné - Postel score at the final follow-up was 18.0 (17.0, 18.0) points (range, 17.0-18.0 points), with 4 excellent and 3 good cases. All 7 patients achieved clinical healing with a healing time of 2.5 (2.5, 3.0) months (range, 1.0-3.0 months). No delayed union or nonunion occurred. At the last follow-up, there were no complications such as internal fixation fracture, incision and internal fixation infection, and deep vein thrombosis.Conclusion:Total laparoscopic technique for the treatment of pelvic and acetabular fractures has less intraoperative blood loss, less surgical trauma, and satisfactory clinical efficacy. It can be used as a new choice of minimally invasive treatment of pelvic and acetabular fractures.
7.Targeting a cryptic allosteric site of SIRT6 with small-molecule inhibitors that inhibit the migration of pancreatic cancer cells.
Qiufen ZHANG ; Yingyi CHEN ; Duan NI ; Zhimin HUANG ; Jiacheng WEI ; Li FENG ; Jun-Cheng SU ; Yingqing WEI ; Shaobo NING ; Xiuyan YANG ; Mingzhu ZHAO ; Yuran QIU ; Kun SONG ; Zhengtian YU ; Jianrong XU ; Xinyi LI ; Houwen LIN ; Shaoyong LU ; Jian ZHANG
Acta Pharmaceutica Sinica B 2022;12(2):876-889
SIRT6 belongs to the conserved NAD+-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD+. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC50 of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.
8.Postnatal outcomes and prognosis of fetal intra-abdominal solid masses diagnosed by prenatal ultrasound
Shaobo YANG ; Yanbing HUANG ; Kuiran DONG ; Luming SUN ; Yu XIONG ; Chun SHEN
Chinese Journal of Perinatal Medicine 2022;25(5):355-359
Objective:To investigate the clinical outcomes and prognosis of children who were prenatally diagnosed with solid space-occupying abdominal lesions by ultrasound.Methods:This study retrospectively enrolled 30 children with solid space-occupying abdominal lesions that were indicated by prenatal ultrasound at Children's Hospital of Fudan University from March 2015 to March 2021. Prenatal ultrasound findings, postnatal treatment, clinical outcomes, and prognosis were analyzed.Results:These subjects included 18 male and 12 female infants, with the median gestational age at the first sonographic diagnosis of 36 weeks (28 to 39 weeks). The intra-abdominal solid masses were postnatally confirmed to be located in liver, retroperitoneum, and gastrointestinal tract, which were hepatic hemangioma ( n=14), hepatoblastoma ( n=2), neuroblastoma ( n=6), abdominal teratoma ( n=4), adrenal hematoma ( n=1), adrenocortical adenoma ( n=1), hyperplasia of renal capillary ( n=1), and gastrointestinal teratoma ( n=1). The accuracy of prenatal ultrasound in detecting the location of masses was 73% (22/30) and which was 13/16 in detecting masses from liver and 9/14 in that outside the liver. Among the 30 cases, 73% (22/30) were benign tumors, and 27% (8/30) were malignant tumors (hepatoblastoma in two cases and neuroblastoma in six cases). Among 15 patients with benign tumors (hepatic hemangioma and adrenal hematoma) who received close follow-up or drug therapy, tumor/lesion regression occurred in 13 cases and the other two were observed with stable hepatic hemangiomas. Fourteen patients, including six with neuroblastoma, two with hepatoblastoma, five with teratoma, one with adrenocortical adenoma, and one with hyperplasia of renal capillary, had good prognosis after primary tumor resection or combined with postoperative chemotherapy. One hepatoblastoma case died after withdrawing treatment. The overall survival rate was 97% (29/30) with a median follow-up time of 24 months (4 to 60 months). Conclusions:Prenatal ultrasound has high accuracy in identifying the anatomic region of fetal solid space-occupying abdominal lesions. With close postnatal follow-up and proper treatment, most of the affected fetuses will have a good outcome and prognosis.
9.Study on the high expression of angiopoietin 1 in plasma of hyperhomocysteinemia rats and its protective effect on endothelial cells
Tongtong Shen ; Limin Zhou ; Shuangshuang Dong ; Xinxin Wang ; Xiaohong Xu ; Yu Liu ; Fan Zheng ; Shaobo Ma ; Bing Shen
Acta Universitatis Medicinalis Anhui 2022;57(5):679-683
Objective:
To investigate the changes of plasma protein expression profile in hyperhomocysteinemia rats and the protective effect of highly expressed angiopoietin 1 in plasma on endothelial cells.
Methods:
The hyperhomocysteinemia animal model was established. The difference in plasma protein content was analyzed by label-free protein spectroscopy. The effects of homocysteine and angiopoietin 1 on endothelial cell migration and proliferation were detected by wound healing and CCK-8 proliferation assay.
Results:
The results of protein profiling showed that 5 proteins were significantly up-regulated and 17 proteins were significantly down-regulated in the plasma of hyperhomocysteinemia rats, among which angiopoietin 1 was significantly up-regulated. In endothelial cells in the superior mesenteric artery of rats, treatment with 30 or 50 μmol/L homocysteine for 24 h significantly inhibited the migration and proliferation. Angiopoietin 1(600 ng/ml) significantly reduced the migration and proliferation of endothelial cells inhibited by 30 μmol/L homocysteine, but had no significant effect on the migration and proliferation of endothelial cells inhibited by 50 μmol/L homocysteine.
Conclusion
Hyperhomocysteinemia can significantly affect the protein expression profile in plasma. Angiopoietin 1 in plasma can compensate for the damage of vascular endothelial migration and proliferation function caused by homocysteine in a certain concentration range.
10.Risk factors for anastomotic leakage after laparoscopic lower anterior resection of rectal cancer and application value of risk assessment scoring model: a multicenter retrospective study
Yang LUO ; Minhao YU ; Ran JING ; Hong ZHOU ; Danping YUAN ; Rong CUI ; Yong LI ; Xueli ZHANG ; Shichun FENG ; Shaobo LU ; Rongguo WANG ; Chunlei LU ; Shaojun TANG ; Liming TANG ; Yinxin ZHANG ; Ming ZHONG
Chinese Journal of Digestive Surgery 2021;20(12):1342-1350
Objective:To investigate the risk factors for anastomotic leakage after laparo-scopic lower anterior resection (LAR) of rectal cancer, and the application value of its risk assess-ment scoring model.Methods:The retrospective case-control study was conducted. The clinico-pathological data of 539 patients who underwent laparoscopic LAR of rectal cancer in 13 medical centers, including 248 cases in Renji Hospital of Shanghai Jiaotong University School of Medicine, 35 cases in Ningbo First Hospital, 35 cases in Changzhou Second People's Hospital, 32 cases in the First People's Hospital of Nantong, 32 cases in Linyi People's Hospital, 31 cases in Changzhou Wujin People's Hospital, 28 cases in Jiading District Hospital of Traditional Chinese Medicine, 27 cases in the First Hospital of Taizhou, 26 cases in Shanghai Pudong Gongli Hospital, 21 cases in the People's Hospital of Rugao, 11 cases in Central Hospital of Fengxian District, 7 cases in Ningbo Hangzhou Bay Hospital and 6 cases in Jiangsu jianhu People's Hospital, from January 2016 to November 2020 were collected. There were 157 males and 382 females, aged (62.7±0.5)years. Observation indicators: (1) follow-up; (2) risk factors for anastomotic leakage after laparoscopic LAR; (3) establishment of risk assessment scoring model for anastomotic leakage after laparoscopic LAR. Follow-up was conducted by outpatient examination or telephone interview. Patients were followed up at 1 week after discharge or 1 month after the operation to detect the anastomotic leakage. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were represented as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Univariate analysis was conducted using the chi-square test and multivariate analysis was conducted usong the Logistic regression model. The area under curve of receiver operating characteristic curve was used to estimate the efficiency of detecton methods. The maximum value of the Youden index was defined as the best cut-off value. Results:(1) Follow-up: 539 patients were followed up at postoperative 1 week and 1 month. During the follow-up, 79 patient had anastomotic leakage, with an incidence of 14.66%(79/539). Of the 79 patients, 39 cases were cured after conservative treatment, 40 cases were cured after reoperation (ileostomy or colostomy). (2) Risk factors for anastomotic leakage after laparoscopic LAR. Results of univariate analysis showed that sex, age, body mass index, smoking and/or drinking, tumor diameter, diabetes mellitus, hemoglobin, albumin, grade of American Society of Anesthesio-logists (ASA), neoadjuvant chemoradiotherapy, distance from anastomotic level to dentate line, the number of pelvic stapler, reinforced anastomosis, volume of intraoperative blood loss, placement of decompression tube, preservation of left colic artery, operation time and professional doctors were related factors for anastomotic leakage after laparoscopic LAR ( χ2=14.060, 4.387, 5.039, 4.094, 17.488, 33.485, 25.066, 28.959, 34.973, 34.207, 22.076, 13.208, 16.440, 17.708, 17.260, 4.573, 5.919, 5.389, P<0.05). Results of multivariate analysis showed that male, tumor diameter ≥3.5 cm, diabetes mellitus, hemoglobin <90 g/L, albumin <30 g/L, grade of ASA ≥Ⅲ, neoadjuvant chemoradiotherapy, distance from anastomotic level to dentate line <1 cm, the number of pelvic stapler ≥3, non-reinforced anastomosis, volume of intraoperative blood loss ≥100 mL and no placement of decom-pression tube were independent risk factors for anastomotic leakage after laparoscopic LAR ( odds ratio=2.864,3.043,12.556,7.178,8.425,12.895,8.987,4.002,3.084,4.393,3.266,3.224,95% confidence interval as 1.279?6.411, 1.404?6.594, 4.469?35.274, 2.648?19.459, 2.471?28.733, 4.027?41.289, 3.702?21.777, 1.746?9.171, 1.365?6.966, 1.914?10.083, 1.434?7.441, 1.321?7.867, P<0.05). (3) Establishment of risk assessment scoring model for anastomotic leakage after laparoscopic LAR. based on the results of univariate analysis, clinicopathological factors with χ2>20, χ2>10 and ≤20 or χ2≤10 were defined as scoring of 3, 2, 1, respectively. The cumulative clinicopatho-logical factors scoring ≥6 was defined as an effective evaluating indicator for postoperative anastomotic leakage. The risk assessment scoring model (6-321) for anastomotic leakage after laparoscopic LAR was established. The cumulative value ≥6 indicated high incidence of anastomotic leakage, and the cumulative value <6 indicated low incidence of anastomotic leakage. Conclusions:Male, tumor diameter ≥3.5 cm, diabetes mellitus, hemoglobin <90 g/L, albumin <30 g/L, grade of ASA ≥Ⅲ, neo-adjuvant chemoradiotherapy, distance from anastomotic level to dentate line <1 cm, the number of pelvic stapler ≥3, non-reinforced anastomosis, volume of intraoperative blood loss ≥100 mL and no placement of decompression tube are independent risk factors for anastomotic leakage after laparoscopic LAR. The risk assessment scoring model (6-321) is established according to the above results.The cumulative value ≥6 indicates high incidence of anastomotic leakage and the cumulative value <6 indicates low incidence of anastomotic leakage.


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