NESCA, a newly discovered signaling adapter protein in the NGF-pathway, contains a RUN domain at its N-terminus. Here we report the crystal structure of the NESCA RUN domain determined at 2.0-Å resolution. The overall fold of the NESCA RUN domain comprises nine helices, resembling the RUN domain of RPIPx and the RUN1 domain of Rab6IP1. However, compared to the other RUN domains, the RUN domain of NESCA has significantly different surface electrostatic distributions at the putative GTPase-interacting interface. We demonstrate that the RUN domain of NESCA can bind H-Ras, a downstream signaling molecule of TrkA, with high affinity. Moreover, NESCA RUN can directly interact with TrkA. These results provide new insights into how NESCA participates in the NGF-TrkA signaling pathway.
Adaptor Proteins, Signal Transducing ; chemistry ; genetics ; metabolism ; Amino Acid Sequence ; Binding Sites ; Crystallography, X-Ray ; Gene Expression ; Humans ; Models, Molecular ; Molecular Sequence Data ; Nerve Growth Factor ; chemistry ; genetics ; metabolism ; Oncogene Protein p21(ras) ; chemistry ; genetics ; metabolism ; Protein Binding ; Protein Structure, Tertiary ; Receptor, trkA ; chemistry ; genetics ; metabolism ; Recombinant Proteins ; chemistry ; genetics ; metabolism ; Sequence Homology, Amino Acid ; Signal Transduction ; rab GTP-Binding Proteins ; chemistry

Objective:To develop an diagnostic equipment with artificial intelligence (AI) real-time assistance under endoscopy (endoscopic AI equipment) for the detection of gastrointestinal protruding lesions, and to evaluate its performance and safety.Methods:From January to December 2017, at Endoscopy Center of West China Hospital, Sichuan University, the endoscopic images of individuals who underwent routine gastroscopy and colonoscopy were collected. The model was established based on convolutional neural network and the endoscopic AI equipment was developed. From June to December 2019, a prospective, single center, blinded and parallel controlled study was conducted to compare the differences in evaluation of protruding lesions of the same patient under gastroscopy or colonoscopy between endoscopist and the endoscopic AI equipment and to evaluated the impact of lesion size (lesions <5 mm and ≥5 mm) on the detection of endoscopic AI equipment. The main outcome measure was the detection time difference in reporting the protruding lesion between endoscopic AI equipment and endoscopist; and the secondary indicator was the accuracy of endoscopic AI equipment in detecting the protruding lesion. Wilcoxon rank sum test and chi-square test were used for statistical analysis.Results:A total of 71 582 white light endoscopy images were used for endoscopic AI equipment training, which included 41 376 images of protruding lesions. The endoscopic AI equipment was successfully developed and obtained the registration certificate of medical devices of the People′s Republic of China (Sichuan Instrument Standard, 20202060049). The accuracy, sensitivity, and specificity of endoscopic AI equipment in detecting protruding lesions were 96.4%, 95.1% and 92.8%, respectively. The detection time of each protruding lesions under gastroscopy of endoscopic AI equipment was 1.524 seconds faster than that of endoscopist; but the detection time of each protruding lesions under colonoscopy was 0.070 seconds slower than that of endoscopist, and the differences were statistically significant ( Z=-5.505 and -4.394, both P<0.01). The detection time of each protruding lesions under gastroscopy or colonoscopy of endoscopic AI equipment was not inferior to that of endoscopist. The detection rate of protruding lesions under colonoscopy by endoscopic AI equipment was 89.9% (249/277) and the sensitivity was 89.9%; the detection rate of protruding lesions under colonoscopy was 87.0% (450/517) and the sensitivity was 86.9%. There were no statistically significant differences in the detection time difference, sensitivity and missed diagnostic rate between the lesions <5 mm and ≥5 mm detected by endoscopic AI equipment under gastroscopy (all P>0.05). The sensitivity of endoscopic AI equipment in detecting the lesions ≥5 mm under colonoscopy was higher than that of lesions <5 mm (96.8% vs. 84.9%), and the missed diagnostic rate was lower than that of lesions <5 mm (3.2%, 3/94 vs. 15.1%, 61/405), and the differences were statistically significant ( χ2=9.615 and 9.612, both P=0.002). No adverse events on patients and medical staffs occurred, and there were no cases of equipment electricity leakage, and abnormal work reported during the use of endoscopic AI equipment. Conclusions:The endoscopic AI equipment can report the protruding lesions simultaneously with endoscopists, and the accuracy is close to 90%, which is expected to be a practical assistant for endoscopists to avoid missed detection of protruding lesions.

Objective To investigate the risk factors of perioperative complications of laparoscopic radical distal gastrectomy and influence of body shape on the short-term therapeutic effects.Methods The retrospective case-control study was conducted.The clinicopathological data of 506 patients (328 males and 178 females,average age 60 years with the range of 24-85 years) who underwent laparoscopic radical distal gastrectomy+D2 lymph nodes dissection in the 8 clinical centers between March 2016 and November 2018 were collected,including 143 in the First Affiliated Hospital of Xiamen University,66 in the Affiliated Hospital of Qinghai University,66 in the Second Affiliated Hospital of Wenzhou Medical University,64 in the Zhongshan Hospital of Xiamen University,54 in the Affiliated Hangzhou First people's Hospital of Zhejiang University School of Medicine,48 in the Zhangzhou Affiliated Hospital of Fujian Medical University,35 in the Affiliated Quanzhou First Hospital of Fujian Medical University,30 in the Second Affiliated Hospital of Xiamen Medical College.The maximum thickness of subcutaneous fat at the level of umbilicus (USCF),the maximum vertical distance between the anterior abdominal skin and the back skin at the level of the umbilicus (UAPD),the maximum horizontal distance between the anterior abdominal skin and the back skin at the level of the umbilicus (UTD),the maximum verticaldistance between the anterior abdominal skin and the back skin at the level of the xiphoid bone (XAPD),the maximum horizontal distance between the.anterior abdominal skin and the back skin at the level of the xiphoid bone (XTD),the distance between the anterior abdominal skin and the root of celiac artery (CAD) and the maximum horizontal distance at a right angle to CAD (CATD) were measured using preoperative imaging examinations.Observation indicators:(1) intraoperative and postoperative situations;(2) follow-up situations;(3) risk factors analysis of perioperative complications;(4) influence of body shape related indexes on intraoperative situations and postoperative recovery:① Pearson univariate correlation analysis,② liner regression model analysis.Followup using outpatient examination and telephone interview was performed to detect the postoperative survival and tumor recurrence or metastasis up to December 2018.Measurement data with normal distribution were represented as Mean±SD.Measurement data with skewed distribution were described as M (range).Comparisons of count data were analyzed using the chi-square test.Comparisons of ordinal data were analyzed by Mann-Whitney U nonparametric test.Risk factors of perioperative complications of laparoscopic distal gastrectomy were analyzed by Logistic regression model.Influence of body shape related indexes on intraoperative situations and postoperative recovery was analyzed by Pearson univariate correlation analysis and liner regression model.Results (1) Intraoperative and postoperative situations:all the 506 patients underwent successful laparoscopic distal gastrectomy,including 103 with Billroth Ⅰ anastomosis,140 with Billroth Ⅱ anastomosis,201 with Billroth Ⅱ + Braun anastomosis,62 with Roux-en-Y anastomosis.The operation time,volume of intraoperative blood loss,number of lymph nodes dissected,time to postoperative anal exsufflation,time for initial fluid diet intake,time for initial semi-fluid diet intake and duration of postoperative hospital stay were (233±44)minutes,(102±86)mL,34±13,(3.6±1.5)days,(5.8±3.3)days,(8.3±3.8)days,(12.2±5.7)days respectively in the 506 patients.Of 506 patients,196 were defined as pathological stage Ⅰ,122 were defined as pathological stage Ⅱ and 188 were defined as pathological stage Ⅲ postoperatively.Of 506 patients,93 had 106 times of perioperative complications,including 33 times of pulmonary and upper respiratory infection,12 times of incisional infection,11 times of anastomotic leakage,11 times of abdominal infection,8 times of intestinal obstruction,8 times of gastroplegia,6 times of abdominal hemorrhage,5 times of bacteremia,3 times of anastomotic hemorrhage,3 times of lymph fluid leakage,2 times of pancreatic leakage,1 time of urinary infection,1 time of anatomotic stenosis,1 time of deep venous thrombosis and 1 time of pulmonary embolism;the same patient can merge multiple complications.Eleven patients were in the Clavien-Dindo classification ≥ Ⅲ.(2) Follow-up situations:465 of 506 patients were followed up for 1-32 months with a median time of 12 months.During the follow-up,451 had postoperative survival and 38 had tumor recurrence or metastasis.(3) Risk factors analysis of perioperative complications.① Results of univariate analysis showed that age,body mass index (BMI),preoperative hemoglobin,preoperative serum albumin and XAPD were related factors affecting perioperative complications of laparoscopic distal gastrectomy (x2 =10.289,7.427,5.269,5.481,4.285,P＜ 0.05).② Results of multivariate analysis showed that age,BMI,preoperative serum albumin were independent related factors affecting perioperative complications of laparoscopic distal gastrectomy (odds ratio =1.033,1.118,0.937,95％ interval confidence:1.011-1.057,1.025-1.219,0.887-0.990,P＜0.05).(4) Influence of body shape related indexes on intraoperative situations and postoperative recovery.① Results of Pearson univariate correlation analysis showed correlations between UAPD,XAPD,CAD,CATD and volume of intraoperative blood loss (r=0.107,0.169,0.179,0.106,P＜0.05),between UAPD,XAPD,CAD and the number of lymph nodes dissected (r=-0.137,-0.143,-0.173,P＜0.05),between USCF,XAPD and time to postoperative anal exsufflation (r =0.122,0.109,P＜0.05),between USCF,XAPD,CAD and time for initial fluid diet intake (r=0.132,0.108,0.132,P＜0.05),between USCF,XAPD and duration of postoperative hospital stay (r=0.116,0.100,P＜0.05).② Results of liner regression model analysis showed a positive correlation between CAD and volume of intraoperative blood loss (r =6.776),a negative correlation between CAD and the number of lymph nodes dissected (r =-0.841),with statistically significant differences (t =2.410,-1.992,P＜ 0.05);a positive correlation between USCF and time to postoperative anal exsufflation (r=0.170),between USCF and time for initial fluid diet intake (r=0.365),between USCF and duration of postoperative hospital stay (r=0.636) respectively,with statisticallysignificant differences (t =2.188,1.981,2.107,P＜ 0.05).Conclusions Abdominal shape can influence intraoperative situations and postoperative recovery of laparoscopic distal gastrectomy,but cannot increase risks ofperioperative complications.Age,BMI and preoperative serum albumin are independent related factors affecting perioperative complications of laparoscopic distal gastrectomy.

Objective To investigate the short-term clinical effects of selecting duodenal transection timing on laparoscopic-assisted distal gastrectomy (LADG).Methods The retrospective cohort study was conducted.The clinicopathological data of 239 gastric cancer (GC) patients undergoing LADG in the 5 medical centers between March 2016 and March 2018 were collected,including 104 in the First Affiliated Hospital of Xiamen University,45 in Zhangzhou Affiliated Hospital of Fujian Medical University,35 in Quanzhou Affiliated Hospital of Fujian Medical University,30 in the Second Affiliated Hospital of Xiamen Medical College,25 in Zhongshan Hospital of Xiamen University.Of 239 patients undergoing LADG + D2 lymph node dissection,107 receiving duodenal transection and then lymph node dissection in the upper region of pancreas after lymph node dissection in the lower region of pylorus and 132 receiving lymph node dissection in the upper region of pancreas and then duodenal transection were respectively divided into anterior approach group and posterior approach group.Sixty-four,8,16,14 and 5 patients in the anterior approach group and 40,37,19,16 and 20 patients in the posterior group respectively came from the First Affiliated Hospital of Xiamen University,Zhangzhou Affiliated Hospital of Fujian Medical University,Quanzhou Affiliated Hospital of Fujian Medical University,Second Affiliated Hospital of Xiamen Medical College and Zhongshan Hospital of Xiamen University.Observation indicators:(1) surgical and postoperative situations;(2) postoperative complications;(3) stratified analyses of surgical and postoperative situations in patients with different TNM staging,body mass index (BMI) and maximum tumor dimension;(4) follow-up and survival.Follow-up using outpatient examination and telephone interview was performed to detect postoperative overall survival and tumor recurrence or metastasis up to April 2018.Measurement data with normal distribution were represented as (-x)±s,and comparison between groups was analyzed using the independent-samples t test.Measurement data with skewed distribution were described as M (Q),and comparison between groups was analyzed using the nonparametric test.Comparisons of count data were analyzed using chi-square test or Fisher exact probability.Comparison of ordinal data was done by the rank-sum test.Results (1) Surgical and postoperative situations:all the patients underwent successful operation,without perioperative death.Number of lymph node dissection in the upper region of pylorus in the anterior and posterior approach groups were respectively 3.9±2.6 and 3.0±2.5,with a statistically significant difference between groups (t=2.778,P＜0.05).Cases with Billroth Ⅰ,Billroth Ⅱ,Billroth Ⅱ +Bruan and Roux-en-Y of digestive tract reconstruction,operation time,dissected times of lymph nodes in greater curvature of stomach,lower region of pylorus,upper region of pancreas and lesser curvature of stomach,cases with visible port vein,volume of intraoperative blood loss,number of overall lymph node dissection,numbers of lymph node dissection in greater curvature of stomach,lower region of pylorus,upper region of pancreas and lesser curvature of stomach,time to postoperative anal exsufflation,time for postoperative fluid diet intake,time for postoperative semi-fluid diet intake,intraperitoneal drainage-tube removal time and duration of postoperative hospital stay were respectively 16,32,47,12,(233.0±41.0)minutes,(14.6±5.4)tninutes,(21.9±6.3)nminutes,(32.7±6.8) minutes,(7.4±2.9)minutes,74,(87±73)mL,35.0±10.0,8.5±4.1,4.8±4.2,13.3±5.2,4.3± 3.3,(4.1±2.6)days,(5.4±2.8) days,(7.9± 3.5) days,(8.9± 2.9) days,(11.7± 4.5) days in the anterior approach group and 17,47,61,7,(243.0±44.0) minutes,(15.7±5.2) minutes,(23.1±8.0) minutes,(34.2±7.1) minutes,(7.9±2.8)minutes,79,(93±57)mL,33.0±10.0,8.1±4.8,5.3±4.9,12.5±5.6,3.8±2.4,(3.8±3.3)days,(5.0±3.6)days,(7.5±4.0) days,(8.5±3.8)days,(11.3±5.7) days in the posterior approach group,with no statistically significant difference between groups (x2 =3.431,t =-1.836,-1.546,-1.324,-1.634,-1.228,x2=2.552,t=-0.684,1.630,0.797,-0.871,1.148,1.314,0.954,0.951,0.884,1.065,0.694,P＞0.05).(2) Postoperative complications:cases with overall complications,anastomotic leakage,anastomotic stenosis,anastomotic bleeding,pancreatic fistula,postoperative gastroparesis,intra-abdominal hemorrhage,incision infection,pneumonia,intra-abdominal infection,bacteremia,intestinal obstruction,endolymphatic leakage,Clavien-Dindo grade Ⅰ,Ⅱ,Ⅲa,Ⅲb and Ⅳa of postoperative complications were respectively 15,1,1,1,0,3,1,2,3,0,1,3,0,3,9,1,2,0 in the anterior approach group and 25,3,0,1,2,2,2,5,7,3,2,3,1,6,14,1,2,2 in the posterior approach group,with no statistically significant difference between groups (x2=1.027,0.643,0.022,0.479,0.161,0.765,0.921,0.161,0.063,Z=-1.055,P＞0.05).Patients in 2 groups with complications were cured by symptomatic treatment.(3) Stratified analyses of surgical and postoperative situations in patients with different TNM staging,BMI and maximum tumor dimension:operation time,dissected times of lymph nodes in upper region of pancreas,cases with visible port vein,number of overall lymph node dissection,numbers of lymph node dissection in upper region of pylorus and upper region of pancreas were respectively (236.0±41.0)minutes,(33.9±6.2) minutes,32,36.0±12.0,3.8±3.0,13.4±5.5 in patients of the anterior approach group with Ⅲ stage of TNM staging and (253.0± 45.0) minutes,(36.5 ±7.0) minutes,29,31.0±t9.0,2.5±2.0,11.4±4.6 in patients of the posterior approach group with Ⅲ stage of TNM staging,with statistically significant differences between groups (t =-1.988,-2.066,x2 =4.686,t =2.472,2.757,2.016,P＜0.05).Numbers of overall lymph node dissection and number of lymph node dissection in upper region of pylorus were respectively 37.0± 12.0,3.6±3.1 in patients of the anterior approach group with BMI ≥ 25 kg/m2 and 30.0±7.0,2.0± 1.3 in patients of the posterior approach group with BMI ≥ 25 kg/m2,with statistically significant differences between groups (t =2.211,2.205,P＜0.05).Volume of intraoperative blood loss and number of lymph node dissection in upper region of pylorus were respectively (80±45) mL,4.0±2.6 in patients of the anterior approach group with maximum tumor dimension ≥ 3.3 cm and (110±67)mL,2.8± 1.8 in patients of the posterior approach group with maximum tumor dimension ≥ 3.3 cm,with statistically significant differences between groups (t =-2.320,2.589,P ＜ 0.05).(4) Follow-up and survival:of 239 patients,202 were followed up for 2-24 months,with a median time of 12 months,including 89 in the anterior approach group and 113 in the posterior approach group.During the follow-up,cases with overall survival,tumor recurrence and metastasis were respectively 85,3,8 in the anterior approach group and 109,3,11 in the posterior approach group,with no statistically significant difference between groups (x2=0.032,0.089,0.119,P＞0.05).Conclusions Both of anterior approach and posterior approach are safe and feasible in LADG,with equivalent short-term efficacies.The anterior approach in LADG has an advantage of the lymph node dissection in the upper region of pylorus compared with posterior approach,and it also is better for patients with later tumor staging,higher BMI and bigger tumor.

OBJECTIVETo explore the value of serum neuron-specific enolase (NSE) before treatment in predicting brain metastases and prognosis of advanced non-small cell lung cancer (NSCLC).

METHODSA total of 128 hospitalized patients with advanced NSCLC from Jan 2012 to Mar 2012 were followed up, and their clinicopathological data, serum NSE, carcinoembryonic antigen, cytokeratin 21-1 (cyfra21-1) levels, albumin (ALB), white blood cell (WBC) before treatment were analyzed retrospectively to determine the factors affecting brain metastasis and prognosis of advanced NSCLC.

RESULTSAmong the 128 NSCLC patients, 90 cases were of adenocarcinoma, 30 cases were of squamous cell carcinoma, and 8 cases were of large cell carcinoma. The median levels of pre-treatment NSE, CEA and cyfra21-1 were 13.6 ng/ml, 7.8 ng/ml and 6.1 ng/ml, respectively. The average levels of ALB and WBC were (35.41 ± 5.60) g/L and (8.16 ± 2.53) × 10⁹/ml, respectively. Multi-variate logistic regression analysis showed that serum NSE before treatment was associated with brain metastasis of advanced NSCLC (P = 0.030). Pre-treatment NSE levels were (34.18 ± 28.48) ng/ml in 28 patients with brain metastasis and (13.87 ± 4.49) ng/ml in 98 patients without brain metastasis (P < 0.05). The median survival time were 3.5 months in patients with normal levels of NSE, and 10.7 months in patients with elevated levels of NSE pre-treatment (P < 0.05).

CONCLUSIONSA higher pre-treatment level of NSE is closely correlated with brain metastasis of advanced NSCLC, and can be used as a predictor of brain metastases in advanced NSCLC. High pre-treatment levels of NSE indicate a poor prognosis in advanced NSCLC patients.

Adenocarcinoma ; blood ; enzymology ; secondary ; Antigens, Neoplasm ; blood ; Brain Neoplasms ; secondary ; Carcinoembryonic Antigen ; blood ; Carcinoma, Large Cell ; blood ; enzymology ; secondary ; Carcinoma, Non-Small-Cell Lung ; blood ; enzymology ; secondary ; Carcinoma, Squamous Cell ; blood ; enzymology ; secondary ; Humans ; Keratin-19 ; blood ; Leukocyte Count ; Lung Neoplasms ; blood ; enzymology ; pathology ; Phosphopyruvate Hydratase ; blood ; Prognosis ; Retrospective Studies ; Serum Albumin ; analysis

ObjectiveTo evaluate the clinical efficacy and safety of Tripterygium wilfordii polyglycoside tablets （TWP） in the treatment of rheumatoid arthritis （RA） in the real world. MethodDiagnosis and treatment data of patients with RA in Chinese medicine rheumatology registration research information platform information database （CERTAIN） from January 1，2019 to January， 2024 were collected. According to the inclusion and exclusion criteria， data were screened. The included data were divided into an exposure group and a control group according to the use of TWP or not. Propensity score matching （PSM） was used in both groups to keep the baseline balanced and comparable. The disease activity score （DAS28-ESR） of 28 joints based on the erythrocyte sedimentation rate （ESR）before and after treatment was compared between the two groups， as well as health assessment questionnaire （HAQ），visual analogue scale （VAS），tender joint count （TJC），swollen joint count （SJC）， patient's global assessment （PGA），evaluator's global assessment （EGA），laboratory indexes， clinical curative effect， and adverse reactions. ResultA total of 3 978 patients were included，including 929 in the exposure group and 3 049 in the control group. Before PSM，there were significant differences in demographic information，DAS28-ESR score，PGA，EGA，HAQ，VAS scores，SJC， and TJC between the two groups （P<0.05）. After successful PSM matching，922 patients in the exposure group and 922 patients in the control group were included. There was no significant difference in demographic information and DAS28-ESR between the two groups before treatment，and the differences in other indexes between the two groups decreased to varying degrees. After treatment，the DAS28-ESR，PGA，EGA，HAQ，SJC，TJC，VAS scores， ESR，and IgG immune index of the two groups were significantly lower （P<0.01）. Compared with those in the control group after treatment，the DAS28-ESR，PGA，EGA，HAQ，VAS scores， and ESR in the exposure group after treatment decreased more significantly （P<0.05，P<0.01）. There was no significant difference in TJC in the exposure group after treatment. However， TJC in the exposure group was significantly higher than that in the control group before treatment （P<0.05）. In terms of TJC reduction，the exposure group performed better than the control group. There was no significant difference in SJC and IgG between the exposure group and the control group after treatment. After treatment，the clinical symptoms of poor appetite，insomnia and many dreams，upset，fatigue，and fear of wind and cold in the two groups were improved. Except that the proportion of women in the exposure group was higher than that in the control group （P<0.01），there was no significant difference in the incidence of other adverse reactions between the two groups after treatment. ConclusionTWP to treat RA can effectively reduce DAS28-ESR，PGA，EGA，HAQ，TJC，and VAS scores and improve the general symptoms. Except for the women at childbearing age with fertility requirements that TWP is not applicable，it shows good security.