Association of Glial Activation and α-Synuclein Pathology in Parkinson's Disease / 神经科学通报·英文版

The accumulation of pathological α-synuclein (α-syn) in the central nervous system and the progressive loss of dopaminergic neurons in the substantia nigra pars compacta are the neuropathological features of Parkinson's disease (PD). Recently, the findings of prion-like transmission of α-syn pathology have expanded our understanding of the region-specific distribution of α-syn in PD patients. Accumulating evidence suggests that α-syn aggregates are released from neurons and endocytosed by glial cells, which contributes to the clearance of α-syn. However, the activation of glial cells by α-syn species produces pro-inflammatory factors that decrease the uptake of α-syn aggregates by glial cells and promote the transmission of α-syn between neurons, which promotes the spread of α-syn pathology. In this article, we provide an overview of current knowledge on the role of glia and α-syn pathology in PD pathogenesis, highlighting the relationships between glial responses and the spread of α-syn pathology.

Control rate of ambulatory blood pressure and influencing factors among hypertensive patients in Shanghai Fengpu community / 中华全科医师杂志

Objective:To analyze the control status of ambulatory blood (BP) pressure and influencing factors among hypertensive patients in Shanghai Fengpu community.Methods:From April 2020 to February 2022, 318 hypertensive patients in Shanghai Fengpu community were enrolled in the study. The basic information and thropometric indicators of patients, course of hypertension, the medication, complications, life habits, and biochemical indicators as well as the ambulatory BP monitoring (ABPM) data were collected. Multivariate analysis was used to evaluate the risk factors for lack of 24-hour BP control.Results:Among 318 patients, 63 cases (19.8%) had an average 24-hour BP controlled; the control rate of daytime BP and nighttime BP was 23.3% (74 cases) and 15.7% (50 cases), respectively. The proportion of combined medication in the control group and non-control group was 46.0% (29/63) and 51.8% (132/255), respectively (χ 2=0.66, P=0.415). There were significant differences in gender, proportion of patients with hypertension>10 years, the office blood pressure control rate, the abnormal diastolic circadian rhythm, abdominal obesity, the level of fasting blood glucose, diabetes, physical activity levels, and smoking and drinking (all P<0.05) between the control group and non-control group. Multivariate analyses showed that male gender ( OR=2.00, 95 %CI:1.07-3.76) and abdominal obesity ( OR=2.04, 95 %CI:1.10-3.76) were risk factors for uncontrolled ambulatory BP. Conclusions:The control rate of ambulatory BP in patients with hypertension is relatively low in Shanghai Fengpu community. The ABPM should be enhanced and the management for hypertensive patients with abdominal obesity and lack of physical activity should be strengthened in the community.

Efficacy of wrist arthroscopic transosseous footprint repair technique for the treatment of triangular fibrocartilage complex injury / 中华创伤杂志

Objective:To investigate the clinical efficacy of wrist arthroscopic transosseous footprint repair technique for treating triangular fibrocartilage complex (TFCC) injury.Methods:A retrospective case series study was conducted to analyze the clinical data of 56 patients with TFCC injury admitted to Shenzhen Second People′s Hospital from July 2017 to September 2020, including 38 males and 18 females, aged 17-45 years [(33.5±3.6)years]. All patients had unilateral injury. Physical examination showed instability of the distal radioulnar joint, and MRI and arthroscopy confirmed deep ligament injury of TFCC. All patients underwent repair of deep insertion of the TFCC by using wrist arthroscopic transosseous footprint. The operation time, intraoperative blood loss, wound healing and postoperative complications were recorded. The flexion and extension range of motion of the wrist, radial and ulnal deviation of the wrist, rotation range of motion of the forearm, patient related wrist evaluation (PRWE) score, modified Mayo wrist score, visual analogue scale (VAS), and percentage of grip strength between the affected side and unaffected side were compared preoperatively, at 3 months postoperatively and at 1 year postoperatively.Results:All patients were followed up for 12-18 months [(13.4±5.2)months]. The operation time was (61.3±8.9)minutes, with the intraoperative blood loss of (2.4±1.2)ml. All wounds were healed by first intension. There was no wound infection or ulnar nerve irritation symptom after operation. Four patients experienced clicking on the ulnar side of the wrist in a short period of time post-operation, with spontaneous disappearance of the symptom. At 3 months postoperatively, the radial and ulnar deviation of the wrist was decreased from (52.5±5.9)° preoperatively to (42.6±5.9)°, and rotation range of motion of the forearm was decreased from (94.9±8.4)°preoperatively to (84.6±5.9)° (all P<0.01). The flexion and extension range of motion of the wrist was (93.1±17.4)° preoperatively, with insignificant difference compared with (89.4±5.8)° at 3 months postoperatively ( P>0.05). At 1 year postoperatively, the flexion and extension range of motion of the wrist, radial and ulnar deviation range of motion of the wrist, and rotation range of motion of the forearm were significantly increased to (101.3±13.6)°, (52.4±6.6)°, and (116.4±16.4)° when compared with those at 3 months postoperatively (all P<0.01). At 3 months postoperatively, the PRWE score was increased to (17.1±3.8)points from (10.6±3.2)points preoperatively ( P<0.01), modified Mayo wrist score was decreased to (70.3±6.7) points from (78.1±12.7)points preoperatively ( P<0.01), VAS was decreased to (4.4±1.7)points from (6.2±1.5)points preoperatively ( P>0.05), and percentage of grip strength between the affected side and unaffected side was decreased to (55.7±8.7)% from (74.4±15.2)% preoperatively ( P<0.01). At 1 year postoperatively, the PRWE score was increased to (2.0±0.9)points, modified Mayo wrist score was increased to (94.8±3.3)points, VAS was decreased to (2.1±1.1)points, and percentage of grip strength between the affected side and unaffected side was increased to (93.2±8.7)% when compared with those at 3 months postoperatively (all P<0.01). Conclusion:Wrist arthroscopic transosseous footprint repair technique can effectively treat deep ligament injury of TFCC, with advantages of significantly improving postoperative joint range of motion and functional score, relieving the pain on the ulnar side of the wrist and enhancing grip strength.

Experimental study and clinical significance of intravascular angiography in vivo / 中华骨科杂志

Objective:To study the method of intravascular angiography in vivo, analyze the clinical significance, and supply the basis of diagnosis and treatment of related orthopaedic diseases.Methods:The development was realized by improving the developer to increase the local concentration. Based on the study of Lijianmin-Chengkun Complexes and using the theory of magnetic microspheres, Fe 3O 4 magnetic microspheres with amino (negatively charged) shell are used to adsorb the aggregated ionic developer meglumine diatrizoate (positively charged diatrizoate). That is, by improving the method of developer, the magnetic microspheres can carry the developer to make new nanoparticles magnetic imaging composite particles. Under the action of external magnetic field, the magnetic imaging composite particles brought by blood circulation continue to stay and gather in the blood vessels in the magnetic field area, and the developer carried by the magnetic microspheres in the blood vessels in the magnetic field area is concentrated to reach the imaging concentration, so as to realize in vivo intravascular vascular imaging. By adjusting the ratio of the two reagents, the charge can be neutralized and condensed into small groups to improve the development efficiency. Thus, the electron microscope experiment, CT in vivo experiment, rabbit imaging experiment, experimental rabbit tissue picture confirmation, CT in vivo human body (the author is a volunteer) imaging experiment were carried out step by step. Results:Electron microscope experiment: meglumine diatrizoate, scanning electron microscope, the particle diameter is about 20 nm. Scanning electron microscope showed that the diameter of the magnetic microspheres was about 100 nm and the distribution was uniform. After the two reagents are mixed in a certain proportion, the neutralizing charge condenses into small groups, but it still has magnetohydrodynamic properties and strong paramagnetism. In vivo rabbit imaging experiment: the ideal intraosseous vascular imaging of the proximal tibia was captured. The tissue pictures of experimental rabbits confirmed that the distribution of Fe 3O 4 was obviously visible in the blood vessels in the proximal tibia on the side with magnetic field, but not on the side without magnetic field. In vivo human imaging experiment: the ideal intraosseous vascular imaging of the proximal fibula was captured. Conclusion:Through the preparation of new reagent of magnetic imaging composite particles (magnetic microspheres + meglumine diatrizoate), the concentration of in vivo bone developer can be achieved under the action of external magnetic field, and the in vivo external diameter ≥ 0.5mm can be achieved under CT thin-layer scanning.

Role of the C9ORF72 Gene in the Pathogenesis of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia / 神经科学通报·英文版

Since the discovery of the C9ORF72 gene in 2011, great advances have been achieved in its genetics and in identifying its role in disease models and pathological mechanisms; it is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). ALS patients with C9ORF72 expansion show heterogeneous symptoms. Those who are C9ORF72 expansion carriers have shorter survival after disease onset than non-C9ORF72 expansion patients. Pathological and clinical features of C9ORF72 patients have been well mimicked via several models, including induced pluripotent stem cell-derived neurons and transgenic mice that were embedded with bacterial artificial chromosome construct and that overexpressing dipeptide repeat proteins. The mechanisms implicated in C9ORF72 pathology include DNA damage, changes of RNA metabolism, alteration of phase separation, and impairment of nucleocytoplasmic transport, which may underlie C9ORF72 expansion-related ALS/FTD and provide insight into non-C9ORF72 expansion-related ALS, FTD, and other neurodegenerative diseases.

Role of the C9ORF72 Gene in the Pathogenesis of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia / 神经科学通报·英文版

Since the discovery of the C9ORF72 gene in 2011, great advances have been achieved in its genetics and in identifying its role in disease models and pathological mechanisms; it is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). ALS patients with C9ORF72 expansion show heterogeneous symptoms. Those who are C9ORF72 expansion carriers have shorter survival after disease onset than non-C9ORF72 expansion patients. Pathological and clinical features of C9ORF72 patients have been well mimicked via several models, including induced pluripotent stem cell-derived neurons and transgenic mice that were embedded with bacterial artificial chromosome construct and that overexpressing dipeptide repeat proteins. The mechanisms implicated in C9ORF72 pathology include DNA damage, changes of RNA metabolism, alteration of phase separation, and impairment of nucleocytoplasmic transport, which may underlie C9ORF72 expansion-related ALS/FTD and provide insight into non-C9ORF72 expansion-related ALS, FTD, and other neurodegenerative diseases.

Arthroscopic bone grafting with percutaneous fixation in treating scaphoid nonunion / 中华骨科杂志

Objective@#To analyze the clinical effects of arthroscopic autologous bone grafting and percutaneous fixation in treating scaphoid nonunion.@*Methods@#From May 2013 to August 2017, a total of 25 cases of patients including 20 males and 5 females with unilateral scaphoid fractures and nonunion were reviewed, with mean age of 35.80±2.41 years (18-65 years). The duration from injury to treatment was averaged 11.70±1.90 months (5-18 months). All of the cases sustained waist and proximal end fractures. X-ray and CT scan showed sclerosis and bone resorption without any callus at the fracture sites. However, there were no serious deformities and wrist arthritis. The patients suffered pain and weakness at the radial side of the wrist. The type of the fractures were Slade-Geissler's III-VI, including grade III 4 cases, grade IV 13 cases, grade V 7 cases and grade VI 1 case. The patients were treated with arthroscopic debridement of the sclerotic bone, autologous bone grafting, percutaneous screw (9 cases) or K-wires fixation (16 cases) and immobilization by plaster for 3 weeks after operation, followed by functional rehabilitation training. Bone union was assessed by serial plain radiographs and CT scan regularly. The functional effects were evaluated by comparing the modified Mayo wrist score with the visual analogue scale (VAS) for pain, range of motion (ROM) and the grip strength, which were measured before operation and at 18 months after operation.@*Results@#All cases were followed up. Bone union was achieved in all of 25 nonunion. The average radiological union duration was 10.24±2.10 weeks (6-20 weeks). The average VAS score decreased from 6.75±1.10 preoperatively to 1.33±0.21. The mean ROM of wrist was improved to 168.48°±12.41° (92.90% of that of the normal side), compared to that of 135.24°±17.47° preoperatively (79.80% of that of the normal side). The mean grip strength showed improvement from an average of 35.68±3.81 kg (80.46% of that of normal side) preoperatively to 48.75±4.42 kg (90.65% of that of normal side). The average modified Mayo wrist score improved from 61.52±6.32 preoperatively to 85.88±8.37.@*Conclusion@#Arthroscopic autologous bone grafting with percutaneous cannulated screw and K-wires fixation is an effective and minimally invasive treatment for scaphoid nonunion, which could protect the blood supply of the fracture sites, decrease the surgical complications, promote bone healing and lead to a faster recovery.

Robotic and endoscopic cooperative surgery in the third space for the resection of gastric submucosal tumors / 中华普通外科杂志

Objective@#To evaluate combined robotic and endoscopic surgery in the third space for gastric submucosal tumors(SMTs).@*Methods@#Combined surgery in 4 patients were compared with 19 patients who underwent laparoscopic wedge resection between Aug 2017 and Feb 2018.@*Results@#R0 resection was achieved in all combined surgery patients. The operation time was longer (112±29 )min vs. (93±11 ) min (t=2.338, P<0.05), but less blood loss, (11±6)ml vs.(59±6)ml (t=15.102, P<0.01). In combined surgery group, there was a larger tumor over resected tissue percentage, 65.4%±28.2% vs.22.8%±19.6% ( t=3.680, P<0.05). Combined surgery group patients were with earlier first breaking wind (3±1.4) d vs.(4.1±0.9) d (t=2.026, P>0.05), and shorter hospital stay (6.5±1.3) d vs.( 8.5±0.6) d (t=4.902, P<0.01), but a little higher hospitalization costs(57 651±10 097)rmb vs.(42 620±5 086)rmb (t=4.508, P<0.01). There were no major postoperative complications occurred in neither groups, nor tumor recurrences after 3-month follow-up.@*Conclusion@#Combined robotic and endoscopic surgery in the third space for submucosal gastric tumors is a novel operation with short operation time, less blood loss and good result.

Robotic and endoscopic cooperative surgery in the third space for the resection of gastric submucosal tumors / 中华普通外科杂志

Objective To evaluate combined robotic and endoscopic surgery in the third space for gastric submucosal tumors (SMTs).Methods Combined surgery in 4 patients were compared with 19 patients who underwent laparoscopic wedge resection between Aug 2017 and Feb 2018.Results R0 resection was achieved in all combined surgery patients.The operation time was longer (112 ±29)min vs.(93 ±11) min (t =2.338,P＜0.05),but less blood loss,(11 ±6)ml vs.(59 ±6)ml (t =15.102,P＜ 0.01).In combined surgery group,there was a larger tumor over resected tissue percentage,65.4％ ± 28.2％ vs.22.8％ ± 19.6％ (t =3.680,P ＜ 0.05).Combined surgery group patients were with earlier first breaking wind (3 ± 1.4) d vs.(4.1 ± 0.9) d (t =2.026,P ＞ 0.05),and shorter hospital stay (6.5 ± 1.3) d vs.(8.5 ±0.6) d (t =4.902,P＜0.01),but a little higher hospitalization costs(57 651 ± 10 097) rmb vs.(42 620 ± 5 086) rmb (t =4.508,P ＜ 0.01).There were no major postoperative complications occurred in neither groups,nor tumor recurrences after 3-month follow-up.Conclusion Combined robotic and endoscopic surgery in the third space for submucosal gastric tumors is a novel operation with short operation time,less blood loss and good result.

Arthroscopic bone grafting with percutaneous fixation in treating scaphoid nonunion / 中华骨科杂志

Objective To analyze the clinical effects of arthroscopic autologous bone grafting and percutaneous fixation in treating scaphoid nonunion.Methods From May 2013 to August 2017,a total of 25 cases of patients including 20 males and 5 females with unilateral scaphoid fractures and nonunion were reviewed,with mean age of 35.80±2.41 years (18-65 years).The duration from injury to treatment was averaged 11.70± 1.90 months (5-18 months).All of the cases sustained waist and proximal end fractures.X-ray and CT scan showed sclerosis and bone resorption without any callus at the fracture sites.However,there were no serious deformities and wrist arthritis.The patients suffered pain and weakness at the radial side of the wrist.The type of the fractures were Slade-Geissler's Ⅲ-Ⅵ,including grade Ⅲ 4 cases,grade Ⅳ 13 cases,grade Ⅴ 7 cases and grade Ⅵ 1 case.The patients were treated with arthroscopic debridement of the sclerotic bone,autologous bone grafting,percutaneous screw (9 cases) or K-wires fixation (16 cases) and immobilization by plaster for 3 weeks after operation,followed by functional rehabilitation training.Bone union was assessed by serial plain radiographs and CT scan regularly.The functional effects were evaluated by comparing the modified Mayo wrist score with the visual analogue scale (VAS) for pain,range of motion (ROM) and the grip strength,which were measured before operation and at 18 months after operation.Results All cases were followed up.Bone union was achieved in all of 25 nonunion.The average radiological union duration was 10.24±2.10 weeks (6-20 weeks).The average VAS score decreased from 6.75± 1.10 preoperatively to 1.33±0.21.The mean ROM of wrist was improved to 168.48°± 12.41 ° (92.90％ of that of the normal side),compared to that of 135.24°± 17.47° preoperatively (79.80％ of that of the normal side).The mean grip strength showed improvement from an average of 35.68±3.81 kg (80.46％ of that of normal side) preoperatively to 48.75±4.42 kg (90.65％ of that of normal side).The average modified Mayo wrist score improved from 61.52±6.32 preoperatively to 85.88±8.37.Conclusion Arthroscopic autologous bone grafting with percutaneous cannulated screw and K-wires fixation is an effective and minimally invasive treatment for seaphoid nonunion,which could protect the blood supply of the fracture sites,decrease the surgical complications,promote bone healing and lead to a faster recovery.

Effects of timosaponin B-II on differentiation of rat neural stem cells into tyrosine hydroxylase posi-tive neurons in vitro / 中华行为医学与脑科学杂志

Objective To explore the effect of timosaponin B-II ( TB-II) on the differentiation of neural stem cells (NSCs) into tyrosine hydroxylase (TH) positive neurons in neonatal rats. Methods The biological functions of self-proliferation and multi-differentiation of NSCs were identified by primary culture, cell proliferation counting,morphological observation and immunology. NSCs of SD rats were cultured in vitro and treated with different concentrations of TB-II (10 μg/ml,30 μg/ml ,100 μg/ml) for 7 days. Immuno-histochemistry was used to detect the effect of TB-II on the differentiation of NSCs into TH-positive neurons, and Western blot was used to detect the expression of TH protein in neurons. Results ( 1) The cultured cells had the ability to self-proliferation,expressed nestin protein and differentiated into neurons and glial cells. So the cultured cells were conformed to the biological function of neural stem cells. (2)Compared with the control group,the TH positive cell ratio of TB-II 30 μg/ml group and TB-II 100 μg/ml group increased ((10. 03± 1. 36)%),( 20. 01± 3. 37)%),(31. 32± 3. 98)%) ,the difference was significant ( t=6. 15, 16. 54,both P<0. 05). There was no significant difference between TB-II 10 μg/ml group and control group (P>0. 05). (3)Western results showed that the relative expression of TH protein in TB-II 30 g/ml group and TB-II 100 μg/ml group was higher than that in control group,the difference was statistically significant (con-trol group: (1. 02±0. 24),TB-II 30μg/ml group: (3. 64±1. 78),TB-II 100 μg/ml group: (5. 88±2. 34);t=12. 58,9. 15,both P<0. 05). There was no significant difference between TB-II 10 μg/ml group and con-trol group (P>0. 05). Conclusion TB-II can promote the differentiation of NSCs into TH-positive neurons.

Learning curve of Da Vinci robot-assisted radical gastrectomy for gastric cancer / 中华消化外科杂志

Objective To investigate the learning curve of Da Vinci robot-assisted laparoscopic radical gastrectomy for gastric cancer.Methods The retrospective cohort study was conducted.The clinicopathological data of 42 patients who underwent Da Vinci robot-assisted radical gastrectomy for gastric cancer in the First Affiliated Hospital of Xi'an Jiaotong University from October 2017 to August 2018 were collected.There were 30 males and 12 females,aged from 36 to 84 years,with an average age of 59 years.The learning curve was evaluated using the cumulative sum (CUSUM) analysis and the best fitting curve method.According to the minimum number of surgeries required to cross the learning curve,the patients were divided into learning stage group and mastery stage group.Then general data and surgical efficacy of the two groups were compared.Observation indicators:(1) surgical situations;(2) results of CUSUM analysis;(3) comparison of general data between the two groups;(4) comparison of surgical efficacy between the two groups;(5) follow-up.Patients were followed up by outpatient examination or telephone interview to detect the postoperative complications,tumor recurrence and metastasis up to February 2019.Measurement data with normal distribution were presented as Mean±SD,and comparison between groups was done using the independent sample t test.Count data were represented as absolute number,and comparison between groups was analyzed using the chi-square test or Fisher exact propability.Comparison of ordinal data between groups was analyzed using the Mann-Whitney U test.Results (1) Surgical situations:all the 42 patients underwent Da Vinci robot-assisted radical gastrectomy for gastric cancer successfully,without conversion to open surgery or perioperative death.Fourteen out of 42 patients underwent Da Vinci robot-assisted total radical gastrectomy and 28 underwent Da Vinci robot-assisted distal radical gastrectomy.The operation time and docking time were (213±31)minutes and (26± 11)minutes.The operation time and docking time had a tendency to decreasing as the surgical cases increasing.(2) Results of CUSUM analysis.The CUSUM learning curve were best modeled as a polynomial with equation:CUSUM (operation time)=0.016 9X3-1.913 3X2+ 50.985X-16.595,CUSUM (docking time) =0.012 8X3-1.070 7X2 + 22.189X-23.097 respectively (X means the surgical case).The P value of fitting test of models was ＜ 0.05,with goodness-of-fit (R2) as 0.960 and 0.985.The CUSUM learning curve of operation time reached its peak when the number of surgical cases accumulated to the 19th case.Nineteen cases were the minimum number of surgeries required to cross the learning curve.Similarly,The CUSUM learning curve of docking time reached its peak when the number of surgical cases accumulated to the 14th case,and 14 cases were the minimum number of surgeries required to skillfully master robot installation across the learning curve.(3) Comparison of general data between the two groups:patients were divided into learning stage group and mastery stage group with 19 cases as the cut-off point.Males,females,age,body mass index (BMI),cases in grade 1,2,3 of American society of anesthesiologists (ASA),cases with previous abdominal surgery history,cases with basic diseases,cases in T1,T2,T3,T4 stages of preoperative ultrasonic gastroscopic tumor T staging,maximum tumor diameter,cases in Ⅰ,Ⅱ,Ⅲ stages of postoperative clinical staging,cases with total gastrectomy and distal gastrectomy (surgical method) were 14,5,(60± 13)years,(23.7±2.9)kg/m2,1,16,2,3,8,5,3,3,8,(4.1±3.5)cm,6,7,6,10,9 in the learning stage group,and 16,7,(58±10)years,(23.7±1.3)kg/m2,1,17,5,2,14,3,6,9,5,(4.7±2.7)cm,8,9,6,18,5 in the mastery stage group,respectively.There was no significant difference in the sex,age,BMI,ASA score,basic diseases,preoperative ultrasonic gastroscopic tumor T staging,maximum tumor diameter,postoperative clinical staging,and surgical method between the two groups (x2 =0.086,t =0.475,-0.007,Z =-0.884,x2 =1.469,Z =-0.301,t =-0.651,Z =-0.079,-0.236,x2 =3.076,P ＞ 0.05).There was no significant difference in the previous abdominal surgery history between the two groups (P ＞ 0.05).(4) Comparison of surgical efficacy between the two groups:operation time,volume of intraoperative blood loss,number of lymph nodes harvested,time to first liquid food intake,cases with postoperative complications and duration of postoperative hospital stay were (230±25) minutes,(176± 103) mL,21±7,(5.1 ± 2.0) days,2,(9.3± 2.5)days in the learning stage group,and (191±18) minutes,(95±41)mL,21±6,(4.7±1.7)days,3,(8.4± 2.1)days in the mastery stage group,respectively.There were statistically significant differences in the operation time and volume of intraoperative blood loss between the two groups (t =5.951,-3.359,P＜0.05).There was no statistically significant difference in number of lymph nodes harvested,time to first liquid food intake,and duration of postoperative hospital stay between the two groups (t =-0.120,0.538,1.303,P＞0.05).There was no significant difference in the cases with postoperative complications between the two groups (P＞0.05).(5) Follow-up:all the 42 patients were followed up for 6-16 months,with a median time of 11 months.No serious long-term complications,tumor recurrence and metastasis or death occurred during the follow-up.Conclusions The CUSUM learning curve of Da Vinci robot-assisted radical gastrectomy for gastric cancer can be divided into the learning stage and the mastery stage.It is suggested that the surgeons need to finish 19 cases or more to master Da Vinci robot-assisted radical gastrectomy for gastric cancer.

Poly-PR in C9ORF72-Related Amyotrophic Lateral Sclerosis/Frontotemporal Dementia Causes Neurotoxicity by Clathrin-Dependent Endocytosis / 神经科学通报·英文版

GGGGCC repeat expansions in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). It has been reported that hexanucleotide repeat expansions in C9ORF72 produce five dipeptide repeat (DPR) proteins by an unconventional repeat-associated non-ATG (RAN) translation. Within the five DPR proteins, poly-PR and poly-GR that contain arginine are more toxic than the other DPRs (poly-GA, poly-GP, and poly-PA). Here, we demonstrated that poly-PR peptides transferred into cells by endocytosis in a clathrin-dependent manner, leading to endoplasmic reticulum stress and cell death. In SH-SY5Y cells and primary cortical neurons, poly-PR activated JUN amino-terminal kinase (JNK) and increased the levels of p53 and Bax. The uptake of poly-PR peptides by cells was significantly inhibited by knockdown of clathrin or by chlorpromazine, an inhibitor that blocks clathrin-mediated endocytosis. Inhibition of clathrin-dependent endocytosis by chlorpromazine significantly blocked the transfer of poly-PR peptides into cells, and attenuated poly-PR-induced JNK activation and cell death. Our data revealed that the uptake of poly-PR undergoes clathrin-dependent endocytosis and blockade of this process prevents the toxic effects of synthetic poly-PR peptides.

Effects of artemisinin on learning and memory, inflammatory cytokines and monoamine neurotransmitters in aged mice / 中华行为医学与脑科学杂志

Objective@#To investigate whether the artermisinin has beneficial efficacy to improve the learning and memory in aged mice, as well as the possible mechanisms regarding the inflammatory cytokines and monoamlne neurotransmitters.@*Methods@#30 aged mice(22 month old) were randomly divided into the aged mouse model control group(n=10), the artemisinin low dose group(artemisinin 0.1% in feed, n=10)and the artemisinin high dose group(artemisinin 0.3% in feed, n=10). Another 10 mice(2 month old) served as young mouse model control group. The artemisinin low dose group and the artemisinin high dose group fed artemisinin feed for 10 weeks. The aged mouse model control group and the young mouse model control group were fed standard feed.Morris water maze test was performed to assess learning and memory capacities for evaluation of the cognitive degree. Serum TNF-α and IL-6 were also detected by ELISA and dopamine, norepinephrine, serotonin in the brain were analyzed by HPLC.@*Results@#(1) Morris water maze test showed, the retention time of the aged mouse model control group was significantly longer than that of the young mouse model control group (P<0.05). The retention time of the artemisinin low dose group and the artemisinin high dose group was significantly shorter than that of the aged mouse model control group (P<0.05). In the ninth days of the reverse recessive platform experiment, the retention time of the artemisinin low dose group ((50.1±19.9) s) and the artemisinin high dose group ((43.2±17.6) s) was significantly shorter than that of the aged mouse model control group ((66.1±29.1)s, P<0.05). (2) Serum inflammatory factors test showed, the level of IL-6 and TNF-αin the artemisinin low dose group (IL-6 : (28.4±4.3) pg/ml, TNF-α: (51.8±8.2) pg/ml) and the artemisinin high dose group(IL-6 : (17.6±2.3) pg/ml, TNF-α: (38.6±12.5) pg/ml) were significantly lower than those in aged mouse model control group(IL-6 : (36.12±7.98)pg/ml), TNF-α : (67.32±10.27) pg/ml, P<0.05). (3) Neurotransmitter content test in the brain showed, the content of DA((19.96±3.89) mmol/ml) and 5-HT((5.73±0.93)mmol/ml) in low dose artemisinin group was higher than that in aged mouth model control group. The content of DA((26.13±5.66) mmol/ml), NE((16.31±2.69) mmol/ml) and 5-HT((8.03±1.93) mmol/ml) in high dose artemisinin group was higher than that in aged mouth model group(DA(13.96±3.89) mmol/ml, NE(8.73±2.16) mmol/ml, 5-HT (3.82±1.09)mmol/ml, all P<0.05).@*Conclusion@#Artemisinin can improve the ability of learning and memory in aged mice. The mechanism may be related to inhibiting the inflammation and promoting the level of neurotransmitters in the brain of aged mice.

Found of tibial intercondylar eminence hole and its relationship between tumor intrusion behavior / 中华骨科杂志

Objective To introduce the tibial intercondylar eminence hole (TIEH) and study its structure.Explore the connection between TIEH and the pathway how proximal tibial aggressive tumor break into the bony structure from articular cavity.Methods This retrospective study included 200 patient's CT 3-dimensional reconstruction materials from May 2017 to November 2017 in Qilu hospital randomly.There were 115 males and 85 females,the average age was 49 years (ranged from 12 to 90 years).To observe the existence of TIEH and identify its location and measurement with imaging techniques.According to 50 tibial plateau specimen after TKA and 5 specimen after car accident or amputation due to tumor,physical proof the existence of TIEH.The specific location,peripheral structure,coverage,content of TIEH as well as its top,walls and bottom were researched and analysed.Pathological staining was used and 1 cases undertook preoperation contrast agent observation.1 cases of typical cases were reviewed.Results TIEH was ubiquity according to all of the 200 cases.TIEH was located on the depression of tibial plateau,between the attachments of ACL and PCL.The hole was round type,and the diameter was 1.6±0.3 mm,the depth was 9.1±2.1 mm.1-3 Paraforamen (semidiamete≤7 mm) were found around the main TIEH in 53％ patients (106/200),the diameter and depth was less than the main hole.The CT value showed the orifice (472.5±30.1 HU) ＞ the pore wall (312.3±22.5 HU) ＞ the pore bottom (202.4±17.3 HU) ＞ the pore (118.3±10.4 HU) ＞ the orifice covering (75.0±11.1 HU).The synovial tissue septum was only 1 mm between the top of hole and the articular cavity.The top of TIEH was surrounded by articular cartilage,the walls and bottom were spongy bone,the content was dense connective tissue that didn't attach to the walls tightly.The peripheral spongy bone was easy to infiltrate by methylene blue.Preoperation radiography showed that TIEH had poor barrier function.Conclusion Tibial intercondylar eminence hole is an intrinsic structure of the human body.The coverage is weak,and it is easy to cause the tumor to hide and recur.The tumor may pass through this hole and bidirectionally enter between the proximal humerus and the joint cavity.

Loss of VAPB Regulates Autophagy in a Beclin 1-Dependent Manner / 神经科学通报·英文版

Autophagy is an evolutionarily-conserved self-degradative process that maintains cellular homeostasis by eliminating protein aggregates and damaged organelles. Recently, vesicle-associated membrane protein-associated protein B (VAPB), which is associated with the familial form of amyotrophic lateral sclerosis, has been shown to regulate autophagy. In the present study, we demonstrated that knockdown of VAPB induced the up-regulation of beclin 1 expression, which promoted LC3 (microtubule-associated protein light chain 3) conversion and the formation of LC3 puncta, whereas overexpression of VAPB inhibited these processes. The regulation of beclin 1 by VAPB was at the transcriptional level. Moreover, knockdown of VAPB increased autophagic flux, which promoted the degradation of the autophagy substrate p62 and neurodegenerative disease proteins. Our study provides evidence that the regulation of autophagy by VAPB is associated with the autophagy-initiating factor beclin 1.

Expression of acetyl coenzyme A synthetase 2 in colorectal cancer and its biological role / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the expression of acetyl coenzyme A synthetase short-chain family member 2 (ACSS2) in patients with colorectal cancer (CRC) and its biological role.</p><p><b>METHODS</b>A total of 74 CRC tissue samples and 40 normal colorectal tissues were tested by immunohistochemical staining to detect the expression of ACSS2 (cell staining intensity score: 0 points: without staining, 1 points: weak staining, 2 points: intensity staining, 3 point: strong staining; the percentage of positive cells in tumor or negative score: 0 points: negative, 1 point: <25% positive cells, 2 points: 25%-50% positive cells, 3 points: 50%-75% positive cells, 4 points: >75% positive cells. The product of above two scores was the final score.). Association of ACSS2 expression with clinicopathological characteristics was analyzed. Small interfering RNA (siRNA, including A and B group) was used to knock down the expression of ACSS2 in colorectal cell lines (Lovo, HCT116) and their proliferation, migration and epithelial-mesenchymal transition (E-cadherin and Snail as markers) after knocking down were observed.</p><p><b>RESULTS</b>The expression of ACSS2 was significant higher in CRC tissue than that in normal colorectal tissue (tumor average score 6.284, normal tissue average score 3.625, P<0.01) and the percentage of positive cell was higher than that in normal tissue (tumor 69.9%, normal tissue 45.1%, P=0.000). The use of ACSS2 siRNA successfully knocked down the expression of ACSS2 in Lovo and HCT116 cells. A mild suppression of cell proliferation was observed 5 days after planked (A450 value: Lovo-NC 1.758±0.041, Lovo-ACSS2-siA 1.485±10.026, Lovo-ACSS2-siB 1.371±0.049; HCT116-NC 2.609±0.038, HCT116-ACSS2-siA 2.260±0.042, HCT116-ACSS2-siB 2.295±0.029). While a remarkable ability decline of cell migration was found (Lovo-NC 225±5/field, Lovo-ACSS2-siA 40±5/field, Lovo-ACSS2-siB 79±3/field; HCT116-NC 198±7/field, HCT116-ACSS2-siA 96±7/field, HCT116-ACSS2-siB 77±9/field, P<0.05). Real-time quantitative PCR detection showed that in Lovo cells, expression of E-cadherin up-regulated and expression of Snail down-regulated, while in HCT116 cells, E-cadherin up-regulated slightly [E-cadherin: Lovo NC 1.000±0.211, Lovo-siA 3.403±0.207, Lovo-siB 2.658±0.420 (P<0.05); HCT116 NC 1.000±0.121, HCT116-siA 1.349±0.197, HCT116-siB 1.528±0.147(P>0.05); Snail: Lovo NC 1.000±0.085, Lovo-siA 0.468±0.030, Lovo-siB 0.499±0.088 (P<0.05); HCT116 NC 1.000±0.118, HCT116-siA 0.265±0.020, HCT116-siB 0.194±0.017 (P<0.05)].</p><p><b>CONCLUSION</b>CRC tissues have high expression of ACSS2, which may be associated with cell migration and epithelial-mesenchymal transition.</p>

Effect of docosapentenoic acid on the neurite outgrowth in PC12 cells / 中华行为医学与脑科学杂志

ObjectiveTo explore the inductive action of docosapentenoic acid(DPA) on neurite outgrowth in PC12 cells in vitro.MethodsNeurite outgrowth in PC12 cells was examined after the treatment with different concentration of DPA using Motic Zamges Plus software mapping cell image system.Western blot was performed to detect the expression of β Ⅲ-tubulin regulated protein kinase,a neuronal marker as well as ERK and protein kinase B (Akt) phosphorylation.ResultsPC12 cell neurite formation rate was increased in a concentration dependent manner in the induction of DPA,increased by 2.4% (DPA 10 μg/ml,P>0.05),18.6% (DPA 30 μg/ml,P<0.05) and 25.0% (DPA 50 μg/ml,P<0.05) compared with that in the control group.DPA promoted the expression of β Ⅲ-tubulin (P<0.05) and the phosphorylation level of ERK and Akt (P<0.05,P<0.01).ConclusionDPA promotes PC12 cell neurites growth and its mechanism may be related to the activation of ERK and Akt signaling pathways.

Clinical effects of damage control surgery in treatment of severe craniocerebral injury combined with multiple extremity fractures / 中华创伤杂志

Objective To investigate the effects of damage control surgery (DCS) in the treatment of severe craniocerebral injury patients combined with multiple extremity fractures.Methods The clinical data of 128 patients with severe craniocerebral injury[Glasgow coma scale (GCS) scored 3-8] combined with multiple extremity fractures admitted from May 2011 to August 2015 were retrospectively analyzed by case-control study.There were 81 males and 47 females,with an average age of 37.3 years (range,19-77 years).The patients were treated with intracranial pressure monitoring in addition to the common administration.The patients were subdivided into two groups:87 patients treated with DCS concept as damage control group and 41 patients treated with non-DCS routine concept as control group.The DCS group received craniotomy and fracture fixation operation in stage Ⅰ with selective operation of open reduction and internal fixation.The control group received craniotomy and open reduction and internal fixation in stage Ⅰ.The postoperative intracranial pressure,operation duration,intraoperative blood loss,hospital stay and prognosis [Glasgow outcome scale (GOS)] were analyzed statistically.Results No intracranial infection was found in all patients during the treatment process.In damage control group,the postoperative intracranial pressure was normal in 44 cases (51％),which was significantly better than that in control group [8 cases (20％)] (P ＜ 0.05).In damage control group,operation duration [(150.1 ± 12.4)minutes],intraoperative blood loss [(270.6 ± 15.3)ml],and hospital stay [(29.7 ± 9.3) days] were significantly shortened compared with control group,whose operation duration,intraoperative blood loss and hospital stay were (270.6 ± 9.8) minutes,(460.2 ± 17.5) ml,and (34.4 ± 6.2) days,respectively (P ＜ 0.05).The GOS rating of damage control group (70％) was notably higher than that in control group (42％) (P ＜ 0.05).Conclusion For severe craniocerebral injury patients combined with multiple extremity fractures,the application of DCS contributes to control of postoperative intracranial pressure,which can also shorten the duration of hospitalization and improve prognosis.

NSC-640358 acts as RXRα ligand to promote TNFα-mediated apoptosis of cancer cell

Retinoid X receptor α (RXRα) and its N-terminally truncated version tRXRα play important roles in tumorigenesis, while some RXRα ligands possess potent anti-cancer activities by targeting and modulating the tumorigenic effects of RXRα and tRXRα. Here we describe NSC-640358 (N-6), a thiazolyl-pyrazole derived compound, acts as a selective RXRα ligand to promote TNFα-mediated apoptosis of cancer cell. N-6 binds to RXRα and inhibits the transactivation of RXRα homodimer and RXRα/TR3 heterodimer. Using mutational analysis and computational study, we determine that Arg316 in RXRα, essential for 9-cis-retinoic acid binding and activating RXRα transactivation, is not required for antagonist effects of N-6, whereas Trp305 and Phe313 are crucial for N-6 binding to RXRα by forming extra π-π stacking interactions with N-6, indicating a distinct RXRα binding mode of N-6. N-6 inhibits TR3-stimulated transactivation of Gal4-DBD-RXRα-LBD by binding to the ligand binding pocket of RXRα-LBD, suggesting a strategy to regulate TR3 activity indirectly by using small molecules to target its interacting partner RXRα. For its physiological activities, we show that N-6 strongly inhibits tumor necrosis factor α (TNFα)-induced AKT activation and stimulates TNFα-mediated apoptosis in cancer cells in an RXRα/tRXRα dependent manner. The inhibition of TNFα-induced tRXRα/p85α complex formation by N-6 implies that N-6 targets tRXRα to inhibit TNFα-induced AKT activation and to induce cancer cell apoptosis. Together, our data illustrate a new RXRα ligand with a unique RXRα binding mode and the abilities to regulate TR3 activity indirectly and to induce TNFα-mediated cancer cell apoptosis by targeting RXRα/tRXRα.