Research progress of non-coding RNA in methamphetamine-induced addiction and neurotoxicity / 中国比较医学杂志

Methamphetamine(METH)is highly addictive and neurotoxic,which causes cognitive and memory dysfunction in abusers.The harm of METH lies not only in its own toxicity,but also in the high physical and mental dependence of drug addicts,often causing mental disorders and violent behavior,bringing great safety risks to society.Non-coding RNA(ncRNA)does not encode proteins and is an important factor in regulating gene expression at the post-transcriptional level.Studies have shown that ncRNA plays an important regulatory role in methamphetamine-induced addiction and neurotoxicity,but the specific mechanism is unclear.This article reviews the current research progress of ncRNA in regulating METH-induced addiction and neurotoxicity to provide a reference for ncRNA as a forensic identification index and potential therapeutic target for METH abusers.

Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines,anti-PD-1 and poly I:C / 药物分析学报

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Effects of Weichang'an Pill on contraction of isolated ileum smooth muscles in rats / 中国药理学通报

Aim To investigate the impact and mechanism of Weichang'an Pill(WCA),its ethanol extract(EE),water extract(WE),and active ingredients on the contraction of isolated rat ileum smooth muscles induced by acetylcholine(ACh). Methods In vitro tissue bath experiment,WCA,EE,WE,or their active ingredients were added under the action of ACh,and then the contraction tension of isolated ileum smooth muscle from rats was recorded. The binding affinity ofthe active ingredients to the muscarinic acetylcholine M3 receptor was explored by molecular docking. Results WCA,EE,and WE were able to considerably inhibit the excitatory contraction of the ileal smooth muscles induced by ACh. Costunolide,dehydrocostus lactone,santalol,muscone,emodin,chrysophanol,physcion,crotonoside,magnolol,and honokiol were also significantly effective against ACh-induced ileal smooth muscle contraction. Conclusions WCA,EE,WE,and their active ingredients may help to promote intestinal smooth muscle relaxation by blocking the binding of the M3 receptor on the membrane of ileal smooth muscle with ACh.

Research progress on mechanisms of neuroinflammation induced by methamphetamine and HIV-1 Tat protein / 中国药理学通报

Methamphetamine abuse and HIV infection are extremely serious public health and social problems facing the world today. Methamphetamine and HIV-1 Tat protein can induce neurotoxicity in an individual and synergistic way, and neuroinflammation is one of the most important mechanisms for ca-using neurotoxicity. Neuroinflammation can be mediated by glial cells, cytokines, NLRP3 inflammasomes, etc. This paper reviews the research progress of neuroinflammation induced by methamphetamine and HIV-1 Tat protein in recent years, with the aim of providing reference and basis for further exploration of the mechanisms of neuroinflammation caused by them and effective drug intervention targets in the future.

Production of carboxylic acids by metabolically engineered Yarrowia lipolytica: a review / 生物工程学报

Yarrowia lipolytica is a non-conventional yeast with unique physiological and metabolic characteristics. It is suitable for production of various products due to its natural ability to utilize a variety of inexpensive carbon sources, excellent tolerance to low pH, and strong ability to secrete metabolites. Currently, Y. lipolytica has been demonstrated to produce a wide range of carboxylic acids with high efficiency. This article summarized the progress in engineering Y. lipolytica to produce various carboxylic acids by using metabolic engineering and synthetic biology approaches. The current bottlenecks and solutions for high-level production of carboxylic acids by engineered Y. lipolytica were also discussed, with the aim to provide useful information for relevant studies in this field.

Value of SpyGlass single-operator choledochoscopy system in the diagnosis and treatment of patients with biliary tract diseases / 临床肝胆病杂志

Objective To investigate the value of SpyGlass single-operator choledochoscopy system in the diagnosis and treatment of patients with unexplained biliary stricture, complex bile duct stones, or other biliary tract diseases. Methods A retrospective analysis was performed for the clinical data of the patients with biliary tract diseases who were diagnosed and treated with SpyGlass in The Second Affiliated Hospital of Nanjing Medical University from December 2017 to June 2020. For the patients with biliary stricture, the biliary lesions were fully visualized under the guidance of SpyGlass, and SpyBite biopsy was performed if necessary; the patients with bile duct stones were treated with SpyGlass-guided direct-view laser lithotripsy; for the patients with gallbladder disease, the cystic duct was superselected with the assistance of SpyGlass. The SpyGlass system was analyzed in terms of its sensitivity, specificity, and accuracy rate in diagnosis and treatment, lithotripsy success rate, stone clearance rate, procedure success rate, and incidence rate of complications. Results A total of 58 patients underwent SpyGlass procedure. SpyGlass was used to evaluate biliary stricture of unknown nature in 44 (76%) patients; SpyGlass visual impression had a diagnostic sensitivity of 92% (24/26), a specificity of 94% (17/18), and an accuracy of 93% (41/44), and SpyBite biopsy had a diagnostic sensitivity of 71% (15/21), a specificity of 92% (11/12), and an accuracy of 79% (26/33). SpyGlass was used for the treatment of bile duct stones in 8 patients (14%), with a lithotripsy success rate of 83% (5/6) and a stone clearance rate of 88% (7/8). A guide wire under the SpyGlass system was to superselect the cystic duct in 5 patients (9%), with a procedure success rate of 80% (4/5). In one patient (1%), SpyGlass was used to assist the removal of common bile duct stones after liver transplantation and the treatment of bile duct anastomotic stricture. A total of 5 patients (9%) experienced complications after surgery. Conclusion The SpyGlass choledochoscopy system is accurate, safe, and effective in the diagnosis and treatment of unexplained biliary stricture, complex bile duct stones, and other biliary tract diseases.

Value of SpyGlass single-operator choledochoscopy system in the diagnosis and treatment of patients with biliary tract diseases / 临床肝胆病杂志

Objective To investigate the value of SpyGlass single-operator choledochoscopy system in the diagnosis and treatment of patients with unexplained biliary stricture, complex bile duct stones, or other biliary tract diseases. Methods A retrospective analysis was performed for the clinical data of the patients with biliary tract diseases who were diagnosed and treated with SpyGlass in The Second Affiliated Hospital of Nanjing Medical University from December 2017 to June 2020. For the patients with biliary stricture, the biliary lesions were fully visualized under the guidance of SpyGlass, and SpyBite biopsy was performed if necessary; the patients with bile duct stones were treated with SpyGlass-guided direct-view laser lithotripsy; for the patients with gallbladder disease, the cystic duct was superselected with the assistance of SpyGlass. The SpyGlass system was analyzed in terms of its sensitivity, specificity, and accuracy rate in diagnosis and treatment, lithotripsy success rate, stone clearance rate, procedure success rate, and incidence rate of complications. Results A total of 58 patients underwent SpyGlass procedure. SpyGlass was used to evaluate biliary stricture of unknown nature in 44 (76%) patients; SpyGlass visual impression had a diagnostic sensitivity of 92% (24/26), a specificity of 94% (17/18), and an accuracy of 93% (41/44), and SpyBite biopsy had a diagnostic sensitivity of 71% (15/21), a specificity of 92% (11/12), and an accuracy of 79% (26/33). SpyGlass was used for the treatment of bile duct stones in 8 patients (14%), with a lithotripsy success rate of 83% (5/6) and a stone clearance rate of 88% (7/8). A guide wire under the SpyGlass system was to superselect the cystic duct in 5 patients (9%), with a procedure success rate of 80% (4/5). In one patient (1%), SpyGlass was used to assist the removal of common bile duct stones after liver transplantation and the treatment of bile duct anastomotic stricture. A total of 5 patients (9%) experienced complications after surgery. Conclusion The SpyGlass choledochoscopy system is accurate, safe, and effective in the diagnosis and treatment of unexplained biliary stricture, complex bile duct stones, and other biliary tract diseases.

Progress in gastric cancer with positive peritoneal cytology / 中华胃肠外科杂志

Gastric cancer with positive peritoneal cytology is a hotspot in the study of gastric cancer, and its prognosis is poor. Intraperitoneal free cancer cells may be associated with cancer cells migration, invasion and metastasis. Tumor T stage, peritoneal metastasis, lymph node metastasis, low histological differentiation, linitis plastica, adenocarcinoma of esophagogastric junction, and operation are the clinicopathological risk factors of gastric cancer with positive peritoneal cytology. Currently, the acquisition of free cancer cells is mainly through diagnostic laparoscopy combined with peritoneal lavage, and cytopathological examination is gold standard for diagnosis. Its treatment strategies are not in consensus, including preoperative chemotherapy combined with radical resection, postoperative chemotherapy and peritoneal local treatment, which can prolong the survival of patients. At present, postoperative chemotherapy is often used in China, and the best treatment strategies remain to be further studied.

Research progress on the precancerous lesions of cholangiocarcinoma / 中华肝胆外科杂志

Cholangiocarcinoma is a malignant tumor originating from bile duct epithelium, with insidious onset and high degree of malignancy. Most of the patients were diagnosed at the middle and late stages and the survival rate is very poor. The etiology of cholangiocarcinoma is still unknown. Billary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, biliary mucinous cystic neoplasm and intraductal tubular/tubulopapillary neoplasm of the bile duct are considered as precancerous lesions of cholangiocarcinoma. Improving the understanding of precancerous lesions of cholangiocarcinoma, and early treatment of these lesions are important for enhancingthe patients’ quality of life. However, the current understanding of precancerous lesions of cholangiocarcinoma is limited. Development of molecular diagnostic technology is deeply needed. And sensitive and specific biomarkers are urgently needed for the early diagnosis of the high-risk persons accurately, so as to achieve " early detection, early diagnosis and early treatment" . This article reviews how to recognize and deal with precancerous lesions of cholangiocarcinoma.

High expression of ENA-78 in lymphatic epithelial cells associated with cholangiocarcinoma promotes lymphangiogenesis / 医学研究生学报

ObjectiveLymphatic epithelial cells (LECs) are important links involved in lymphatic metastasis in the microenvironment of cholangiocarcinoma. This study aims to detect the modulation of inflammatory factors and chemokines secreted by LECs after stimulation of cholangiocarcinoma cells, and observe the effects of highly expressed factors on lymphangiogenesis.MethodsThe culture medium of cholangiocarcinoma (RBE, HCCC9810), LECs stimulated by cholangiocarcinoma cell culture medium (CCM), and normal LECs were prepared. Inflammatory factors and chemokines in the culture medium were detected using protein chip. The experiments are divided into the following groups, including a blank control group, CCM group, CCM coupled with Anti-ENA-78 group, Anti-ENA-78 group, ENA-78 group, ENA-78 coupled with SB2252002, and SB225002 group. The relationship between the content of factor and time was investigated using ELISA, while the relation between target factors and lymphangiogenesis obtained by cell proliferation and tubule formation assay.ResultsWe found ENA-78, IP-10, GCP-2, MCP-2, MCP-3, MIP-3a, HCC-1, and Lymphotactin expression increased in LECs supernatant after CCM stimulation. However, I-TAC, MIP-1d, IL-10, MIG, PDGF-BB, and CXCL16 factors showed down-regulation. The secretion of ENA-78 in CCM was relatively low. By ELISA, we found that the ENA-78 protein in RBE-LECs and HCCC9810-LECs gradually increased over time, and reached the plateau phase at the point of 48h. The lymphatic tube forming ability of LECs cultured in CCM was significantly increased compared with that of the control group, and this ability could be partially weakened by ENA-78 neutralizing antibodies. In the exogenous ENA-78 protein group, the lymphatic tube formation ability was as well significantly increased compared with that in the control group, and this ability could be effectively blocked by the IL-8B inhibitor.ConclusionThe increased secretion ENA-78 of lymphatic epithelial cells induced by cholangiocarcinoma may play a role in promoting lymphangiogenesis through the IL-8B receptor.

High expression of ENA-78 in lymphatic epithelial cells associated with cholangiocarcinoma promotes lymphangiogenesis / 医学研究生学报

ObjectiveLymphatic epithelial cells (LECs) are important links involved in lymphatic metastasis in the microenvironment of cholangiocarcinoma. This study aims to detect the modulation of inflammatory factors and chemokines secreted by LECs after stimulation of cholangiocarcinoma cells, and observe the effects of highly expressed factors on lymphangiogenesis.MethodsThe culture medium of cholangiocarcinoma (RBE, HCCC9810), LECs stimulated by cholangiocarcinoma cell culture medium (CCM), and normal LECs were prepared. Inflammatory factors and chemokines in the culture medium were detected using protein chip. The experiments are divided into the following groups, including a blank control group, CCM group, CCM coupled with Anti-ENA-78 group, Anti-ENA-78 group, ENA-78 group, ENA-78 coupled with SB2252002, and SB225002 group. The relationship between the content of factor and time was investigated using ELISA, while the relation between target factors and lymphangiogenesis obtained by cell proliferation and tubule formation assay.ResultsWe found ENA-78, IP-10, GCP-2, MCP-2, MCP-3, MIP-3a, HCC-1, and Lymphotactin expression increased in LECs supernatant after CCM stimulation. However, I-TAC, MIP-1d, IL-10, MIG, PDGF-BB, and CXCL16 factors showed down-regulation. The secretion of ENA-78 in CCM was relatively low. By ELISA, we found that the ENA-78 protein in RBE-LECs and HCCC9810-LECs gradually increased over time, and reached the plateau phase at the point of 48h. The lymphatic tube forming ability of LECs cultured in CCM was significantly increased compared with that of the control group, and this ability could be partially weakened by ENA-78 neutralizing antibodies. In the exogenous ENA-78 protein group, the lymphatic tube formation ability was as well significantly increased compared with that in the control group, and this ability could be effectively blocked by the IL-8B inhibitor.ConclusionThe increased secretion ENA-78 of lymphatic epithelial cells induced by cholangiocarcinoma may play a role in promoting lymphangiogenesis through the IL-8B receptor.

Computed Tomography Arteriography for Detecting the Origin of the Inferior Pyloric Artery in Patients with Gastric Cancer

OBJECTIVE: To analyze the detection rate of the inferior pyloric artery (IPA) in patients with gastric cancer by computed tomography arteriography (CTA). MATERIALS AND METHODS: Fifty-four patients (48 males and 6 females; mean age, 59.0 ± 1.5 years) who had undergone radical gastrectomy for gastric cancer from September 2016 to July 2017 at our institution were recruited prospectively. Patients underwent abdominal contrast-enhanced CT scans and CTA imaging reconstruction before the operation. The origin of the IPA in all cases was determined by a radiologist based on CTA images and verified by the surgeon. The accuracy of CTA in diagnosing the origin of the IPA was calculated. Dominant vessels of the origin were analyzed. RESULTS: IPAs were detected by CTA in 51 patients (94.4%). Among these, IPAs originated from the right gastroepiploic artery (RGEA) (24 cases), the gastroduodenal artery (GDA) (4 cases), and the anterior superior pancreaticoduodenal artery (ASPDA) (20 cases). In the remaining 3 cases, the IPAs contained two branches originating from the RGEA and ASPDA, respectively. During surgery, in 2 (3.7%) of the 54 cases of gastric cancer, IPAs could not be detected; the IPAs originated from the RGEA (22 cases), GDA (5 cases), and ASPDA (24 cases). One case had an IPA originating from both the RGEA and the GDA. Finally, the accuracy of CTA in diagnosing the origin artery of the IPA was 85.2% (46/54). CONCLUSION: CTA can detect the origin of the IPA accurately, which can aid surgeons while performing pylorus-preserving operations.

Therapeutic value of endoscopic ultrasonography-guided hepaticogastrostomy for high malignant biliary obstructive jaundice / 中华消化内镜杂志

Objective To study the therapeutic value of endoscopic ultrasonography-guided hepaticogastrostomy( EUS-HG) for patients with high malignant biliary obstructive jaundice. Methods A total of 56 patients with high malignant obstructive jaundice hospitalized at the Second Affiliated Hospital of Nanjing Medical University and the Second Affiliated Hospital of Xuzhou Medical University from January 2014 to December 2017 were included in the study. There were 29 males and 27 females with median age of 72 (60-82) years. Patients were randomized into two groups according to the random number table, the EUS-HG group ( n=20) treated with EUS-HG and the percuteneous transhepatic cholangiodrainge( PTCD) group (n=36) treated with PTCD. The operative success rate, curative effect, complications and operation cost were compared between the two groups, and the median unblock period of plastic double pig tail stent was observed. Results (1) The success rates were 100％ in both groups. (2) Preoperative and one-month postoperative levels of the following were tested and compared. Levels of total bilirubin were 362. 15 ± 138. 27 μmol/L, 56. 85 ± 28. 57 μmol/L in the EUS-HG group and 356. 47 ± 130. 69 μmol/L, 60. 93 ± 25. 79 μmol/L in the PTCD group, respectively. Levels of alkaline phosphatase were 896. 57±357. 29 U/L, 146. 59±48. 63 U/L in the EUS-HG group and 883. 65 ± 364. 32 U/L, 151. 57 ± 49. 73 U/L in the PTCD group, respectively. Levels of alanine aminotransferase were 252. 36±38. 77 U/L, 60. 29±31. 57 U/L in the EUS-HG group and 246. 26 ± 32. 57 U/L, 62. 56 ± 32. 87 U/L in the PTCD group. Levels of aspartate aminotransferase were 259. 37 ± 30. 64 U/L, 62. 28 ± 26. 58 U/L in the EUS-HG group and 242. 37 ± 29. 52 U/L, 60. 28±29. 57 U/L in the PTCD group, and there was no significant difference between the two groups (P>0. 05). CRP levels were 52. 57±31. 95 mg/L, 16. 95±8. 77 mg/L in the EUS-HG group and 53. 42± 35. 79 mg/L, 25. 13 ± 14. 77 mg/L in the PTCD group ( P<0. 05) . ( 3 ) There was significant difference in remission rate of anorexia and abdominal distension between the two groups [ 80. 0％( 16/20) VS 52. 8％( 19/36) , P<0. 05] . There was no significant difference in symptom relief of jaundice, pruritus or abdominal pain between the two groups [ 90. 0％( 18 /20) VS 91. 7％( 33/36) ,P>0. 05] . ( 4) The incidence of total complications in the EUS-HG group ( 20. 0％,4/20) was significantly lower than that in the PTCD group (47. 2％,17/36, P<0. 05). (5)The cost of operation in the EUS-HG group (22685. 26±2356. 16 yuan) was slightly higher than that in the PTCD group (20529. 57±4135. 63 yuan, P>0. 05). (6) The median unblock period of double pig tail plastic stents in EUS-HG group patients was 102 days. Conclusion EUS-HG is a safe and effective method for the treatment of high malignant biliary obstructive jaundice. It can be used as the first choice for treatment after failure of conventional ERCP.

Therapeutic value of endoscopic ultrasonography-guided hepaticogastrostomy for high malignant biliary obstructive jaundice / 中华消化内镜杂志

Objective@#To study the therapeutic value of endoscopic ultrasonography-guided hepaticogastrostomy(EUS-HG) for patients with high malignant biliary obstructive jaundice.@*Methods@#A total of 56 patients with high malignant obstructive jaundice hospitalized at the Second Affiliated Hospital of Nanjing Medical University and the Second Affiliated Hospital of Xuzhou Medical University from January 2014 to December 2017 were included in the study. There were 29 males and 27 females with median age of 72 (60-82) years. Patients were randomized into two groups according to the random number table, the EUS-HG group (n=20) treated with EUS-HG and the percuteneous transhepatic cholangiodrainge(PTCD) group (n=36) treated with PTCD. The operative success rate, curative effect, complications and operation cost were compared between the two groups, and the median unblock period of plastic double pig tail stent was observed.@*Results@#(1)The success rates were 100% in both groups. (2) Preoperative and one-month postoperative levels of the following were tested and compared. Levels of total bilirubin were 362.15±138.27 μmol/L, 56.85±28.57 μmol/L in the EUS-HG group and 356.47±130.69 μmol/L, 60.93±25.79 μmol/L in the PTCD group, respectively. Levels of alkaline phosphatase were 896.57±357.29 U/L, 146.59±48.63 U/L in the EUS-HG group and 883.65±364.32 U/L, 151.57±49.73 U/L in the PTCD group, respectively. Levels of alanine aminotransferase were 252.36±38.77 U/L, 60.29±31.57 U/L in the EUS-HG group and 246.26±32.57 U/L, 62.56±32.87 U/L in the PTCD group. Levels of aspartate aminotransferase were 259.37±30.64 U/L, 62.28±26.58 U/L in the EUS-HG group and 242.37±29.52 U/L, 60.28±29.57 U/L in the PTCD group, and there was no significant difference between the two groups (P>0. 05). CRP levels were 52.57±31.95 mg/L, 16.95±8.77 mg/L in the EUS-HG group and 53.42±35.79 mg/L, 25.13±14.77 mg/L in the PTCD group (P<0.05). (3)There was significant difference in remission rate of anorexia and abdominal distension between the two groups [80.0%(16/20) VS 52.8%(19/36), P<0.05]. There was no significant difference in symptom relief of jaundice, pruritus or abdominal pain between the two groups [90.0%(18 /20)VS 91.7%(33/36), P>0.05]. (4) The incidence of total complications in the EUS-HG group (20.0%, 4/20) was significantly lower than that in the PTCD group (47.2%, 17/36, P<0.05). (5)The cost of operation in the EUS-HG group (22 685.26±2 356.16 yuan) was slightly higher than that in the PTCD group (20 529.57±4 135.63 yuan, P>0.05). (6) The median unblock period of double pig tail plastic stents in EUS-HG group patients was 102 days.@*Conclusion@#EUS-HG is a safe and effective method for the treatment of high malignant biliary obstructive jaundice. It can be used as the first choice for treatment after failure of conventional ERCP.

Current treatment status and trends of early gastric cancer in China: analyzed based on the data of China Gastrointestinal Cancer Surgery Union / 中国实用外科杂志

Gastric cancer is one of the most common cancersin China. The proportion of early gastric cancer(EGC) is stillrelatively low in China. The data of China Gastrointestinal Can-cer Surgery Union from 2014 to 2017 can reflect the currentstatus and trends of diagnose and treatment of EGC in China.The union collected data of 134,111 cases of gastric cancer in95 centers in China. The trend analysis was performed with da-ta from centers with at least 3 years data collected. Within allthe patients, the proportion of EGC was 19.7%. The propor-tions of EGC were higher in Zhejiang, Beijing, Jiangsu, Tian-jin, and Shanghai, and were lower in Qinghai, Hainan, InnerMongolia, Yunnan, and Guangxi. The proportion of EGC in-creased from 19.7% in 2014 to 20.9% in 2017. In terms oftreatment, the proportions of endoscopic treatment, laparoscop-ic surgery, and open surgery were 24.3%, 37.7%, and 38.0%.From 2014 to 2017, the proportions of endoscopic treatmentand laparoscopic surgery increased while the proportion ofopen surgery decreased. Among patients received surgery,5.9% of pT1 a patients and 19.6% of pT1 b patients were withlymph node metastasis. In conclusion, the proportion of EGCincreased slightly in China but was still lower than that of Ja-pan and South Korea. Minimally invasive treatment graduallybecome the main treatment method of EGC.

Esophageal stent placement versus endoscopic incision for the treatment of refractory esophageal anastomotic stricture / 医学研究生学报

Objective Few reports are seen comparing esophageal stent placement (ESP) and the endoscopic incision method (EIM) in the treatment refractory esophageal anastomotic strictures (EAS) following esophageal carcinoma resection (ECR). This study was to evaluate the effect ESP versus that of EIM in the treatment of refractory EAS after ECR. Methods We retrospectively analyzed the clinical data on 50 cases of post-ECR refractory EAS treated by ESP (n = 32) or EIM (n = 18) in our Center of Digestive Medicine between January 2012 and December 2018. We recorded and compared the pre- and post-operative dysphagia scores, post-operative complications and follow-up results between the two groups of patients. Results Compared with the EIM group, the patients of the ESP group had a remarkably lower dysphagia score post-operatively (1.4±0.5 vs 1.0±0.0, P<0.01), a smaller diameter of the dilated esophagus ([19.9±1.8] vs [11.0±1.9] mm, P<0.01), higher incidence rates mild and severe chest pain (P=0.022), and a higher rate of relief of esophageal stricture at 12 months after surgery (P<0.05). Conclusion EIM can rapidly relieve the symptoms of esophageal anastomotic stricture, while ESP may achieve a longer duration of relief. Both of the procedures are safe for patients with refractory esophageal anastomotic stricture.

Inductive effect of solamargine on the apoptosis of human esophageal cancer KYSE150 cells and its action mechanism / 医学研究生学报

Objective Solamargine (SM), with its anti-inflammatory and anti-tumor effects, inhibits the proliferation and promotes the apoptosis of various tumor cells. This study was to investigate the effects of SM on the proliferation and apoptosis of human esophageal cancer KYSE150 cells and its action mechanism. Methods We treated KYSE150 cells with SM at the concentrations of 0 (the blank control group), 2, 4, 6 and 8 μmol/L for 24 hours. Then, we observed the morphological changes of the cells under the inverted microscope, detected their proliferation and apoptosis by MTT assay and flow cytometry respectively, and determined the expressions of the classical NF-κB signaling pathway-related proteins NF-κB, p-NF-κB, IKKα, IKKβ, IkBα and p-IkBα) and apoptosis-related proteins Bax, caspase-3, cleaved caspase-3 and Bcl-2 in different groups of the cells by Western blot. Results Compared with the blank control, the inhibition rate of the proliferation of the KYSE150 cells in the 2, 4, 6 and 8 μmol/L SM groups was increased significantly in a concentration-dependent manner (0 vs [15.03 ± 0.15]%, [47.94 ± 1.74]%, [68.72 ± 0.47]% and [77.51 ± 1.70]%, P<0.05), and so was the apoptosis rate ([8.17 ± 0.51]% vs [14.50 ± 0.73]%, [18.57 ± 2.08]%, [65.10 ± 10.88]% and [81.55 ± 5.48]%, P<0.05). The expression of the apoptosis-related protein Bax in the SM treated cells was up-regulated, those of Bcl-2, IKKα, IKKβ and p-IkBα down-regulated, and the activity of caspase-3 and cleaved caspase-3 promoted, all in a concentration-dependent manner, with statistically significant differences between the blank control and the 4, 6 and 8 μmol/L SM groups (P<0.05). Statistically significant differences were also found in the expressions of NF-κB, p-NF-κB and IkBα between the blank control and the 6 and 8 μmol/L SM groups (P<0.05). Conclusion Solamargine can significantly inhibit the proliferation and promote the apoptosis of KYSE150 cells, probably by suppressing the classical NF-κB signaling pathway.

MiR-217 regulates colorectal cancer cell proliferation partly through ERK1/2 signal pathway / 医学研究生学报

Objective A variety of miRNAs have been found to be involved in the occurrence and development of colorectal cancer. This paper aim to investigate the clinical and biological relevance of miR-217 and the pathway by which miR-217 may be involved in progression in colorectal cancer. Methods According to the diameter of tumor, the tumor was divided into tumors>5 cm(n=22) and tumors≤5 cm(n=28); 18 cases of colorectal cancer I-II specimens and 32 of III-IV patients; according to median expression of miR-217, the specimens were divided into high expression group and low expression group. The expression of miR-217 in 50 colon cancer patients’ carcinoma and adjacent tissues was determined by qRT-PCR. Cells were grouped: overexpression control Group (transfected control mimic) and miR-217 overexpression group(transfected miR-217 mimic), low expression control group((transfected control inhibitor) and miR-217 low expression group(transfected miR-217 inhibitor), miR-217&ERK1/2 low expression group(transfected miR-217 inhibitor+U0126). MiR-217 and HCT116 cells were over expressed in SW480 cells,and miR-217 was knocked down. A series of biological function assays were performed to assess cell viability (cck-8 assay), clony formation ability (clony formation assay), proliferation (edu assay), Changes in ERK1/2 expression were measured at protein level, and the relationship between miR-217 and ERK1/2 in colorectal cancer cells was explored by relevant rescue experiments. Results Compared with colorectal adjacent noncancerous tissues, the expression of miR-217 was significantly decreased in carcinoma tissues(-1.360±0.645 vs 2.244±0.168, P<0.01); the expression of miR-217 in tumors with a diameter >5cm was significantly lower than that of tumors with a diameter ≤5cm(-1.718±0.272 vs -0.587±0.288, P<0.01); the expression of miR-217 in stage I-II colorectal cancer tissues was significantly higher than that stage III-IV(-0.413±0.330 vs -01.463±0.230, P<0.05); the expression of miR-217 in the miR-217 overexpression group was significantly higher than miR-217 overexpression control group(15.120±0.522 vs 1.004±0.003, P<0.01), and the number of clone formation was significantly less than that of the overexpression control group(199.30±15.62 vs 439.70±18.91, P<0.01) . In HCT116 cells, the expression of miR-217 in the miR-217low expression group was significantly lower than miR-217 low expression control group(0.2070±0.021 vs 1.006±0.003, P<0.01), and the number of clone formation was significantly higher than that control group(237.30±12.14 vs 117.00±7.00, P<0.01) . When miR-217 overexpressed in SW480, the protein expression of ERK1/2 decreased; when miR-217 was inhibited in HCT116, the protein expression of ERK1/2 increased. The number of colons in ERK1/2 low expression group was significantly lower than that miR-217&ERK1/2 low expression group(221.70±12.73 vs 108.00±5.51) , the difference was statistically significant(P<0.01). Conclusion Low expression of miR-217 is observed in both colorectal cancer tissues and cells, and miR-217 can affect tumor cell proliferation in the progression of colorectal cancer partly by inhibiting the expression of ERK1/2.

Molecular Mechanism of Erzhiwan in Inhibiting Benign Prostatic Hyperplasia Base on Network Pharmacology / 中国实验方剂学杂志

Objective: To explain the "multi-components, multi-targets, multi-pathways" mechanism of Erzhiwan in treating benign prostatic hyperplasia(BPH) based the network pharmacology. Method: Ingenuity pathway analysis(IPA) was used to construct components-targets-diseases network and PPI network, then the classified enrichment analysis of gene ontology (GO) and pathway enrichment analysis (KEGG) were carried out on the main function of its gene sets, so as to discuss the mechanism of Erzhiwan in the treatment of BPH. Result: Erzhiwan has 19 components in IPA; and apigenin,luteolin,oleanolic acid and quercitrin were common components of Ligustri Lucidi Fructus and Echiptae Herba and the main component of Erzhiwan. Muscarinic acetylcholine receptor M3 (CHRM3), muscarinic acetylcholine receptor M2 (CHRM2), urokinase plasminogen activator receptor (PLAUR), kinin releasing enzyme 3 (KLK3), cadherin 1 (CDH1), chemokines 3 (CCL3) and metalloproteinase-1 (MMP-1) were important targets for Erzhiwan to treat BPH. The target proteins in PPI network were enriched with 20 GO functions and 5 main KEGG pathways, and Docking was verified for relevant targets. Conclusion: Erzhiwan may play a role in treating BPH by activating MMP-1 and inhibiting KLK3 and CCL3 protein expressions, inducing apoptosis, inhibiting cell proliferation and intervening relevant pathways of mitogen-activated protein kinase/extracellular signal-regulated kinase(MAPK/ERK) and nuclear factor(NF)-κB(NF-κB).

Risk factors and drug resistance in early-onset neonatal group B streptococcal disease / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

In recent years, group B streptococcus (GBS) has become an important pathogen that causes infections in many neonatal organs, including the brain, lung, and eye (Ballard et al., 2016). A series of studies performed on GBS infections in western countries have revealed that GBS is one of the primary pathogens implicated in perinatal infection, and GBS infections are a major cause of neonatal morbidity and mortality in the United States (Decheva et al., 2013). In China, GBS is mainly found by screens for adult urogenital tract and perinatal infections, and neonatal GBS infections have been rarely reported. The incidence rate of early-onset neonatal GBS disease is thought to be lower in China than in western countries; however, this data is controversial since it also reflects the clinical interest in GBS (Dabrowska-Szponar and Galinski, 2001).