ObjectiveTo investigate the effects of Shenxiong Huanglian Jiedu decoction on the clearance of amyloid β-protein （Aβ） and neuronal damage in the mouse model of Alzheimer's disease （AD）. MethodsA total of 36 SPF-grade 2-month-old C57BL/6J mice were used in this study， and the modeling was performed by bilateral hippocampal injection of Aβ oligomers in C57BL/6J mice. The experiment was conducted with a blank group， a sham operation group， a model group， low- and high-dose （3.27，6.54 g·kg^-1， respectively） Shenxiong Huanglian Jiedu decoction groups， and a positive control （donepezil hydrochloride， 0.65 mg·kg^-1） group. At the end of the drug intervention， the learning and memory abilities and the activities of mice were evaluated by the Morris water maze and open field tests. Brain histopathology was examined by hematoxylin-eosin and Nissl staining. Additionally， in vivo imaging was employed to measure the metabolism of fluorescent Aβ in the cerebrospinal fluid， and staining of ionized calcium-binding adapter molecule-1 （Iba-1） was employed to assess microglial activation in the hippocampal tissue. Additionally， neurotrophin-3 （NT-3） and brain-derived neurotrophic factor （BDNF） levels in the brain tissue and serum were determined by the immunofluorescence assay and enzyme-linked immunosorbent assay. Western blot was conducted to determine the expression of inflammation and pathway-related proteins in the hippocampal tissue. ResultsCompared with the blank group and the sham operation group， the escape latency of the mice in the model group was prolonged， the platform residence time was shortened， the hippocampal tissue showed pathological manifestations such as neuronal pyknosis， Nissl body dissolution， and microglia activation. The metabolic rate of fluorescent Aβ through cerebrospinal fluid was slowed down， and the expression levels of BDNF， NT-3， and interleukin-10 （IL-10） in the hippocampus were significantly decreased （P<0.01）. The expression levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， Toll-like receptor 4 （TLR4）， myeloid differentiation factor 88 （MyD88） and phosphorylated nuclear transcription factor-κB （p-NF-κB p65） in hippocampus were significantly increased （P<0.05， P<0.01）. Compared with the model group， the escape latency of mice in the low and high dose groups of Chinese medicine and donepezil group was shortened， and the platform residence time was prolonged. Neuronal karyopyknosis， Nissl body dissolution and microglia activation in hippocampus were improved. Fluorescence Aβ was metabolized faster by cerebrospinal fluid. The expression of BDNF and NT-3 in hippocampus was increased （P<0.01）， and the expression of TLR4， MyD88 and p-NF-κB p65 was significantly decreased （P<0.05， P<0.01）. The expression of TNF-α in the hippocampus of the high-dose group was significantly decreased （P<0.05）， and the expression of IL-10 was significantly increased （P<0.05）. The expression of TNF-α， IL-6 and IL-1β in the hippocampus of the donepezil group was significantly decreased （P<0.05， P<0.01）. ConclusionShenxiong Huanglian Jiedu decoction may mitigate neuronal damage and enhance cerebrospinal fluid flow in the mouse model of AD， thereby promoting the clearance of Aβ and improving the learning and memory abilities. These beneficial effects are likely mediated through the inhibition of microglial activation， reduction of inflammation， and modulation of the TLR4/MyD88/NF-κB signaling pathway.

ObjectiveTo investigate the effects of Shenxiong Huanglian Jiedu decoction on the clearance of amyloid β-protein （Aβ） and neuronal damage in the mouse model of Alzheimer's disease （AD）. MethodsA total of 36 SPF-grade 2-month-old C57BL/6J mice were used in this study， and the modeling was performed by bilateral hippocampal injection of Aβ oligomers in C57BL/6J mice. The experiment was conducted with a blank group， a sham operation group， a model group， low- and high-dose （3.27，6.54 g·kg^-1， respectively） Shenxiong Huanglian Jiedu decoction groups， and a positive control （donepezil hydrochloride， 0.65 mg·kg^-1） group. At the end of the drug intervention， the learning and memory abilities and the activities of mice were evaluated by the Morris water maze and open field tests. Brain histopathology was examined by hematoxylin-eosin and Nissl staining. Additionally， in vivo imaging was employed to measure the metabolism of fluorescent Aβ in the cerebrospinal fluid， and staining of ionized calcium-binding adapter molecule-1 （Iba-1） was employed to assess microglial activation in the hippocampal tissue. Additionally， neurotrophin-3 （NT-3） and brain-derived neurotrophic factor （BDNF） levels in the brain tissue and serum were determined by the immunofluorescence assay and enzyme-linked immunosorbent assay. Western blot was conducted to determine the expression of inflammation and pathway-related proteins in the hippocampal tissue. ResultsCompared with the blank group and the sham operation group， the escape latency of the mice in the model group was prolonged， the platform residence time was shortened， the hippocampal tissue showed pathological manifestations such as neuronal pyknosis， Nissl body dissolution， and microglia activation. The metabolic rate of fluorescent Aβ through cerebrospinal fluid was slowed down， and the expression levels of BDNF， NT-3， and interleukin-10 （IL-10） in the hippocampus were significantly decreased （P<0.01）. The expression levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， Toll-like receptor 4 （TLR4）， myeloid differentiation factor 88 （MyD88） and phosphorylated nuclear transcription factor-κB （p-NF-κB p65） in hippocampus were significantly increased （P<0.05， P<0.01）. Compared with the model group， the escape latency of mice in the low and high dose groups of Chinese medicine and donepezil group was shortened， and the platform residence time was prolonged. Neuronal karyopyknosis， Nissl body dissolution and microglia activation in hippocampus were improved. Fluorescence Aβ was metabolized faster by cerebrospinal fluid. The expression of BDNF and NT-3 in hippocampus was increased （P<0.01）， and the expression of TLR4， MyD88 and p-NF-κB p65 was significantly decreased （P<0.05， P<0.01）. The expression of TNF-α in the hippocampus of the high-dose group was significantly decreased （P<0.05）， and the expression of IL-10 was significantly increased （P<0.05）. The expression of TNF-α， IL-6 and IL-1β in the hippocampus of the donepezil group was significantly decreased （P<0.05， P<0.01）. ConclusionShenxiong Huanglian Jiedu decoction may mitigate neuronal damage and enhance cerebrospinal fluid flow in the mouse model of AD， thereby promoting the clearance of Aβ and improving the learning and memory abilities. These beneficial effects are likely mediated through the inhibition of microglial activation， reduction of inflammation， and modulation of the TLR4/MyD88/NF-κB signaling pathway.

Objective:To explore the safety and therapeutic effect of programmed death 1 (PD-1) antibody combined with chemotherapy as a neoadjuvant therapy for patients with stage Ⅱ to Ⅲ non-small cell lung cancer (NSCLC).Methods:Thirteen patients, who had been diagnosed as stage Ⅱ-Ⅲ NSCLC and received PD-1 inhibitor plus chemotherapy as a neoadjuvant treatment in National Cancer Center/Cancer Hospital were recruited. The patients received consecutive neoadjuvant chemotherapy for 21 days as a cycle and the therapeutic efficacy was evaluated after two cycles.Results:At the last time of follow-up on December 2, 2019, the objective response rate (ORR) and disease control rate (DCR) of these patients were 61.5% (95% CI 30.9%-92.1%) and 100%, respectively. The downregulation rate of disease stage was 61.5% (8/13). The resectable rate was 38.5% (5/13), among them, the major pathologic response (MPR) was 60.0% (3/5) and the complete pathologic response (CPR) was 20.0% (1/5). The neoadjuvant chemotherapy displayed a low incidence of adverse reaction. The main grade 3 to 4 toxicities were neutropenia (38.5%) and leukopenia (23.1%). There was no significant immune-related toxicity. The safety and tolerability of perioperative period of patients underwent resection were promising. Conclusions:Immunotherapy combined with chemotherapy as a neoadjuvant treatment is an effective, low-toxicity treatment manner, which has perioperative safety and high rate of MPR for patients with resectable NSCLC. It is a promising treatment option for patients with stage Ⅱ to Ⅲ NSCLC.

Objective:To explore the safety and therapeutic effect of programmed death 1 (PD-1) antibody combined with chemotherapy as a neoadjuvant therapy for patients with stage Ⅱ to Ⅲ non-small cell lung cancer (NSCLC).Methods:Thirteen patients, who had been diagnosed as stage Ⅱ-Ⅲ NSCLC and received PD-1 inhibitor plus chemotherapy as a neoadjuvant treatment in National Cancer Center/Cancer Hospital were recruited. The patients received consecutive neoadjuvant chemotherapy for 21 days as a cycle and the therapeutic efficacy was evaluated after two cycles.Results:At the last time of follow-up on December 2, 2019, the objective response rate (ORR) and disease control rate (DCR) of these patients were 61.5% (95% CI 30.9%-92.1%) and 100%, respectively. The downregulation rate of disease stage was 61.5% (8/13). The resectable rate was 38.5% (5/13), among them, the major pathologic response (MPR) was 60.0% (3/5) and the complete pathologic response (CPR) was 20.0% (1/5). The neoadjuvant chemotherapy displayed a low incidence of adverse reaction. The main grade 3 to 4 toxicities were neutropenia (38.5%) and leukopenia (23.1%). There was no significant immune-related toxicity. The safety and tolerability of perioperative period of patients underwent resection were promising. Conclusions:Immunotherapy combined with chemotherapy as a neoadjuvant treatment is an effective, low-toxicity treatment manner, which has perioperative safety and high rate of MPR for patients with resectable NSCLC. It is a promising treatment option for patients with stage Ⅱ to Ⅲ NSCLC.

Objective: To investigate the changes of surgical invitations on necrotizing pancreatitis in recent 14 years by reviewing single center data. Methods: One thousand and eighty patients with necrotizing pancreatitis who received surgical invitation were involved in the study.All the patients were treated at Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2005 to December 2018. Six hundred and seventy-eight were males and 402 were females. The median (range) age of the study patients was 45 (20-76) years.The etiology of the disease was related to cholelithiasis in 335 cases(31.02%), hyperlipemia in 302 cases(27.96%), alcohol in 226 cases(20.93%), endoscopic retrograde cholangiopancreatography in 28 cases(2.59%), pregnancy in 50 cases(4.63%), idiopathic factors in 72 cases(6.67%) and other causes in 67 cases(6.20%). The patients were divided into two groups according to the time of admission. Group 1 included 1 475 patients that admitted from January 2005 to December 2010, and group 2 included 1 539 patients that admitted from January 2011 to December 2018. The surgical interventions, morbidity and mortality of the two group were compared, and χ² test was used for the statistical test. Results: Two hundred and sixty-six among the 1 080 cases were treated with drainage procedures because of the pseudocyst.One hundred and seventy-five drainage procedures were performed between January 2005 and December 2018, which account for 11.87%(175/1 475) of all patients of necrotizing pancreatitis; 91 drainage procedures were performed between January 2011 and December 2018, which account for 5.91%(91/1 539) of all patients of necrotizing pancreatitis. Eight hundred and fourteen cases received surgical intervention for infection of necrotizing tissues. Of these cases, 410 cases received percutaneous catheter drainage(PCD) of retroperitoneal fluid or residual infection. Debridement of necrotic tissues was performed on 756 cases. Of these cases, 32 cases received minimal invasive retroperitoneal debridement with/without denotes video assistant, 4 cases received transluminal endoscopic debridement, 21 cases received laparoscopic debridement, and 709 cases received open laparotic debridement.Three hundred and sixty-five cases were admitted to our institute during January 2005 to December 2010, and the other 391 cases were admitted to our institute from January 2011 to December 2018. Of the first period, all debridement were performed with open laparotic procedures. Of the second period, debridement were performed with open laparotic procedures and minimal invasive procedures. The average times of surgical invasion, morbidity of principal local complications and mortality of the two periods were 1.27 and 1.34,28.22%(103/365) and 29.92%(117/346), and 6.03%(23/365) and 6.91%(27/346), respectively. Conclusions Minimal invasive procedures can be considered for debridement in patients with necrotizing pancreatitis in some selected conditions.The involvements of minimal invasive procedures in treatment of necrotizing pancreatitis don′t decrease the morbidity of principal local complications and mortality in recent years. Rational surgical procedures and appropriate surgical timing are the keys to improve the efficacy of necrotizing pancreatitis.

Objective: The role of planned neoadjuvant radiotherapy or chemoradiotherapy in the non-radical resection of esophageal squamous cell carcinoma was unclear. The study aimed to evaluate their therapeutic effect and analyze the prognostic factors. Methods: We retrospectively analyzed the clinical data of locally advanced esophageal squamous cell carcinoma who received neoadjuvant radio therapy (33 patients) and concurrent chemoradiotherapy (119 patients) from January 2004 to December 2016 in our single-institution database.The survival rates were calculated by Kaplan-Meier method. The prognostic factors were analyzed by using Log rank test and Cox proportional hazards model. Results: The median follow-up was 29.8 months. One hundred and one patients survived more than 3 years. The rates of overall survival (OS) and disease-free survival (DFS) at 3 years were 63.9% and 55.6%, respectively.The rates of complete, partial and minimal pathological response of the primary tumor were 50.3%, 38.4%, 11.3%, the corresponding 3-year OS were 75.5%, 57.4%, 27.3% (P<0.001) and 3-year DFS were 72.0%, 44.7%, 17.6% (P<0.001), respectively.The postoperative lymph node metastasis rate was 27.0%. The 3-year OS and DFS of the lymph node positive group was 45.6% and 32.8%, significantly lower than 70.8% and 63.7% of the negative group (both P<0.001). The 3-year OS and DFS of pathologic stage Ⅰ, Ⅱ, ⅢA, ⅢB and Ⅵ A were 76.2%, 57.4%, 64.7%, 35.0%, 33.3% (P<0.001) and 70.1%, 49.3%, 41.2%, 22.1%, 33.3% (P<0.001), respectively.The operation-related mortality was 3.3%. Multivariate analysis showed that chest pain, postoperative respiratory failure, pathological differentiation, more than 15 lymph node dissection and ypTNM stage were the independent prognostic factors of OS (P<0.05 for all). Conclusions The planned neoadjuvant radiotherapy or chemoradiotherapy for the non-radical resection of advanced esophageal squamous cell carcinoma could result in favorable survival. The chest pain, postoperative respiratory failure, pathological differentiation, the number of lymph node resection and ypTNM stage are the independent prognostic factors of the prognosis of these patients.

Objective The role of planned neoadjuvant radiotherapy or chemoradiotherapy in the non?radical resection of esophageal squamous cell carcinoma was unclear. The study aimed to evaluate their therapeutic effect and analyze the prognostic factors. Methods We retrospectively analyzed the clinical data of locally advanced esophageal squamous cell carcinoma who received neoadjuvant radio therapy ( 33 patients) and concurrent chemoradiotherapy (119 patients) from January 2004 to December 2016 in our single?institution database.The survival rates were calculated by Kaplan?Meier method. The prognostic factors were analyzed by using Log rank test and Cox proportional hazards model. Results The median follow?up was 29.8 months. One hundred and one patients survived more than 3 years. The rates of overall survival (OS) and disease?free survival ( DFS) at 3 years were 63.9% and 55.6%, respectively.The rates of complete, partial and minimal pathological response of the primary tumor were 50.3%, 38.4%, 11.3%, the corresponding 3?year OS were 75.5%, 57.4%, 27.3%( P＜0.001) and 3?year DFS were 72.0%, 44.7%, 17.6%(P＜0.001), respectively.The postoperative lymph node metastasis rate was 27.0%. The 3?year OS and DFS of the lymph node positive group was 45.6% and 32.8%, significantly lower than 70.8% and 63.7%of the negative group (both P＜0.001).The 3?year OS and DFS of pathologic stage Ⅰ,Ⅱ,ⅢA,ⅢB andⅥ A were 76.2%, 57.4%, 64.7%, 35.0%, 33.3%( P＜0.001) and 70.1%, 49.3%, 41.2%, 22.1%, 33.3%(P＜0.001), respectively.The operation?related mortality was 3.3%. Multivariate analysis showed that chest pain, postoperative respiratory failure, pathological differentiation, more than 15 lymph node dissection and ypTNM stage were the independent prognostic factors of OS ( P＜0.05 for all). Conclusions The planned neoadjuvant radiotherapy or chemoradiotherapy for the non?radical resection of advanced esophageal squamous cell carcinoma could result in favorable survival. The chest pain, postoperative respiratory failure, pathological differentiation, the number of lymph node resection and ypTNM stage are the independent prognostic factors of the prognosis of these patients.

Objective To investigate the changes of surgical invitations on necrotizing pancreatitis in recent 14 years by reviewing single center data.Methods One thousand and eighty patients with necrotizing pancreatitis who received surgical invitation were involved in the study.All the patients were treated at Department of Pancreatic Surgery,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology from January 2005 to December 2018. Six hundred and seventy?eight were males and 402 were females. The median (range) age of the study patients was 45 (20-76) years.The etiology of the disease was related to cholelithiasis in 335 cases(31.02%), hyperlipemia in 302 cases(27.96%), alcohol in 226 cases(20.93%), endoscopic retrograde cholangiopancreatography in 28 cases(2.59%), pregnancy in 50 cases(4.63%), idiopathic factors in 72 cases(6.67%) and other causes in 67 cases(6.20%). The patients were divided into two groups according to the time of admission. Group 1 included 1 475 patients that admitted from January 2005 to December 2010, and group 2 included 1 539 patients that admitted from January 2011 to December 2018. The surgical interventions, morbidity and mortality of the two group were compared, and χ2 test was used for the statistical test. Results Two hundred and sixty?six among the 1 080 cases were treated with drainage procedures because of the pseudocyst.One hundred and seventy?five drainage procedures were performed between January 2005 and December 2018, which account for 11.87%(175/1 475) of all patients of necrotizing pancreatitis; 91 drainage procedures were performed between January 2011 and December 2018,which account for 5.91%(91/1 539) of all patients of necrotizing pancreatitis. Eight hundred and fourteen cases received surgical intervention for infection of necrotizing tissues. Of these cases, 410 cases received percutaneous catheter drainage(PCD) of retroperitoneal fluid or residual infection. Debridement of necrotic tissues was performed on 756 cases. Of these cases, 32 cases received minimal invasive retroperitoneal debridement with/without denotes video assistant,4 cases received transluminal endoscopic debridement, 21 cases received laparoscopic debridement, and 709 cases received open laparotic debridement.Three hundred and sixty?five cases were admitted to our institute during January 2005 to December 2010, and the other 391 cases were admitted to our institute from January 2011 to December 2018. Of the first period, all debridement were performed with open laparotic procedures. Of the second period,debridement were performed with open laparotic procedures and minimal invasive procedures. The average times of surgical invasion, morbidity of principal local complications and mortality of the two periods were 1.27 and 1.34,28.22%(103/365) and 29.92%(117/346),and 6.03%(23/365) and 6.91%(27/346), respectively. Conclusions Minimal invasive procedures can be considered for debridement in patients with necrotizing pancreatitis in some selected conditions.The involvements of minimal invasive procedures in treatment of necrotizing pancreatitis don′t decrease the morbidity of principal local complications and mortality in recent years. Rational surgical procedures and appropriate surgical timing are the keys to improve the efficacy of necrotizing pancreatitis.

Objective To investigate the changes of surgical invitations on necrotizing pancreatitis in recent 14 years by reviewing single center data.Methods One thousand and eighty patients with necrotizing pancreatitis who received surgical invitation were involved in the study.All the patients were treated at Department of Pancreatic Surgery,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology from January 2005 to December 2018. Six hundred and seventy?eight were males and 402 were females. The median (range) age of the study patients was 45 (20-76) years.The etiology of the disease was related to cholelithiasis in 335 cases(31.02%), hyperlipemia in 302 cases(27.96%), alcohol in 226 cases(20.93%), endoscopic retrograde cholangiopancreatography in 28 cases(2.59%), pregnancy in 50 cases(4.63%), idiopathic factors in 72 cases(6.67%) and other causes in 67 cases(6.20%). The patients were divided into two groups according to the time of admission. Group 1 included 1 475 patients that admitted from January 2005 to December 2010, and group 2 included 1 539 patients that admitted from January 2011 to December 2018. The surgical interventions, morbidity and mortality of the two group were compared, and χ2 test was used for the statistical test. Results Two hundred and sixty?six among the 1 080 cases were treated with drainage procedures because of the pseudocyst.One hundred and seventy?five drainage procedures were performed between January 2005 and December 2018, which account for 11.87%(175/1 475) of all patients of necrotizing pancreatitis; 91 drainage procedures were performed between January 2011 and December 2018,which account for 5.91%(91/1 539) of all patients of necrotizing pancreatitis. Eight hundred and fourteen cases received surgical intervention for infection of necrotizing tissues. Of these cases, 410 cases received percutaneous catheter drainage(PCD) of retroperitoneal fluid or residual infection. Debridement of necrotic tissues was performed on 756 cases. Of these cases, 32 cases received minimal invasive retroperitoneal debridement with/without denotes video assistant,4 cases received transluminal endoscopic debridement, 21 cases received laparoscopic debridement, and 709 cases received open laparotic debridement.Three hundred and sixty?five cases were admitted to our institute during January 2005 to December 2010, and the other 391 cases were admitted to our institute from January 2011 to December 2018. Of the first period, all debridement were performed with open laparotic procedures. Of the second period,debridement were performed with open laparotic procedures and minimal invasive procedures. The average times of surgical invasion, morbidity of principal local complications and mortality of the two periods were 1.27 and 1.34,28.22%(103/365) and 29.92%(117/346),and 6.03%(23/365) and 6.91%(27/346), respectively. Conclusions Minimal invasive procedures can be considered for debridement in patients with necrotizing pancreatitis in some selected conditions.The involvements of minimal invasive procedures in treatment of necrotizing pancreatitis don′t decrease the morbidity of principal local complications and mortality in recent years. Rational surgical procedures and appropriate surgical timing are the keys to improve the efficacy of necrotizing pancreatitis.

Objective The role of planned neoadjuvant radiotherapy or chemoradiotherapy in the non?radical resection of esophageal squamous cell carcinoma was unclear. The study aimed to evaluate their therapeutic effect and analyze the prognostic factors. Methods We retrospectively analyzed the clinical data of locally advanced esophageal squamous cell carcinoma who received neoadjuvant radio therapy ( 33 patients) and concurrent chemoradiotherapy (119 patients) from January 2004 to December 2016 in our single?institution database.The survival rates were calculated by Kaplan?Meier method. The prognostic factors were analyzed by using Log rank test and Cox proportional hazards model. Results The median follow?up was 29.8 months. One hundred and one patients survived more than 3 years. The rates of overall survival (OS) and disease?free survival ( DFS) at 3 years were 63.9% and 55.6%, respectively.The rates of complete, partial and minimal pathological response of the primary tumor were 50.3%, 38.4%, 11.3%, the corresponding 3?year OS were 75.5%, 57.4%, 27.3%( P＜0.001) and 3?year DFS were 72.0%, 44.7%, 17.6%(P＜0.001), respectively.The postoperative lymph node metastasis rate was 27.0%. The 3?year OS and DFS of the lymph node positive group was 45.6% and 32.8%, significantly lower than 70.8% and 63.7%of the negative group (both P＜0.001).The 3?year OS and DFS of pathologic stage Ⅰ,Ⅱ,ⅢA,ⅢB andⅥ A were 76.2%, 57.4%, 64.7%, 35.0%, 33.3%( P＜0.001) and 70.1%, 49.3%, 41.2%, 22.1%, 33.3%(P＜0.001), respectively.The operation?related mortality was 3.3%. Multivariate analysis showed that chest pain, postoperative respiratory failure, pathological differentiation, more than 15 lymph node dissection and ypTNM stage were the independent prognostic factors of OS ( P＜0.05 for all). Conclusions The planned neoadjuvant radiotherapy or chemoradiotherapy for the non?radical resection of advanced esophageal squamous cell carcinoma could result in favorable survival. The chest pain, postoperative respiratory failure, pathological differentiation, the number of lymph node resection and ypTNM stage are the independent prognostic factors of the prognosis of these patients.