ObjectiveTo observe the inhibitory effect of sinomenine on human glioblastoma and its pharmacokinetic characteristics in glioblastoma. MethodA human glioblastoma U87 cell line stably expressing luciferase was constructed， and a mouse glioma model was established for use in both pharmacodynamic and pharmacokinetic studies. Pharmacodynamics： Model mice were randomly divided into model group and sinomenine low-， medium-， and high-dose groups （50， 100， 150 mg·kg^-1）. Sinomenine was administered intraperitoneally for 14 days. The fluorescence value of brain tumors was observed to analyze its inhibitory effect on glioblastoma proliferation. Brain tumors and the surrounding brain tissue were collected， and the expression levels of vascular endothelial growth factor A （VEGFA）， P-glycoprotein （P-gp）， breast cancer resistance protein （BCRP）， and Occludin were detected by Western blot. Pharmacokinetics： Mice were divided into a normal group （50 mg·kg^-1） and model groups （50， 100， 150 mg·kg^-1）. After a single intraperitoneal injection of sinomenine， extracellular fluid from brain tumors was collected in vivo by microdialysis every 15 min for 6 h. Sinomenine concentrations in the dialysate were detected by HPLC-MS/MS， and pharmacokinetic parameters were calculated to analyze pharmacokinetic characteristics of sinomenine in the brain and glioblastoma. ResultCompared with model group， after 14 days of sinomenine administration， the fluorescence value of brain tumors significantly decreased （P<0.05） in a dose-dependent manner. Sinomenine inhibited the increase in VEGF and the degradation of Occludin in the tissue surrounding the tumor and inhibited the expression of VEGF， P-gp， and BCRP in glioblastoma. After a single administration， sinomenine was detected in brain and tumor tissues within 7.5 min. Compared with normal group， the C_max and AUC in the tumor significantly increased， T_max shortened （from 1.63 h to 0.71 h）， and CLz/F decreased. In the dose range of 50-150 mg·kg^-1， sinomenine exhibited a linear pharmacokinetic process in glioblastoma. ConclusionSinomenine has a significant inhibitory effect on glioblastoma， which can inhibit VEGF elevation and drug transporter efflux， reduce tumor invasion， and maintain the integrity of the blood-brain barrier. Sinomenine can rapidly cross the blood-tumor barrier， reach peak concentration， and exhibit linear pharmacokinetic characteristics in the tumor.

Objective To compare the effects of visual rigid laryngoscope and visual laryngoscope in nasotracheal intubation(NTI)for patients with cervical spine immobilization simulated difficult airway.Methods Ninety patients scheduled for selective surgery under general anesthesia requiring NTI,52 males and 38 females,aged 18-64 years,BMI 18.5-25.0 kg/m2,ASA physical status Ⅰ or Ⅱ,were scheduled for selective surgery under general anesthesia requiring NTI.Before anesthesia induction,the spinal surgeon selected an appropriate cervical collar and adjusted it to fix patient's neck to establishing difficult airway sim-ulation model.All patients were randomly assigned into two groups:visual rigid laryngoscope(group R)and common visual laryngoscope(group C),45 patients in each group.NTI was performed using either visual rigid laryngoscope or visual laryngoscope in groups R and C,respectively.The nasal passage time,glottic exposure time,intubation time,number of successful first intubation attempts,and intubation attempts were recorded.Glottic exposure was assessed using the Cormack-Lehane(C-L)grading system,and the intuba-tion condition was quantitatively evaluated using the modified nasal intubation difficulty scale(NIDS).The blood pressure and heart rate were measured at baseline(T1),immediately after intubation(T2),and at 1 minute(T3)and 3 minutes(T4)after intubation.The occurrence of intubation-related complications(nasal bleeding,sore throat,hoarseness)was recorded.Results Compared with group C,the nasal passage time and proportion of successful intubations without difficulty were significantly increased in group R,and the glottic exposure time and intubation time were significantly decreased in group R(P<0.05).Compared with group C,the HR and MAP at T2 and T3 were significantly decreased in group R(P<0.05).Com-pared with group C,group R had significantly lower incidence rates of nasal bleeding,sore throat,and hoarseness(P<0.05).There were no statistically significant differences in the first intubation success rate,number of intubation attempts,or C-L grade between the two groups.Conclusion Patients with cer-vical spine immobilization simulated difficult airway,both visual rigid laryngoscope and visual laryngoscope can be performed safely and effectively in NTI.Compared with visual laryngoscope,visual rigid laryngoscope can provide faster glottic exposure,shorter intubation time,lower intubation difficulty,less hemodynamic impact,and lower incidence of complications.

BACKGROUND: Maturity-onset diabetes of the young (MODY) is the most common monogenic diabetes. The aim of this study was to assess the prevalence of MODY in phenotypic type 2 diabetes (T2DM) among Chinese young adults. METHODS: From April 2015 to October 2017, this cross-sectional study involved 2429 consecutive patients from 46 hospitals in China, newly diagnosed between 15 years and 45 years, with T2DM phenotype and negative for standardized glutamic acid decarboxylase antibody at the core laboratory. Sequencing using a custom monogenic diabetes gene panel was performed, and variants of 14 MODY genes were interpreted as per current guidelines. RESULTS: The survey determined 18 patients having genetic variants causing MODY (6 HNF1A , 5 GCK , 3 HNF4A , 2 INS , 1 PDX1 , and 1 PAX4 ). The prevalence of MODY was 0.74% (95% confidence interval [CI]: 0.40-1.08%). The clinical characteristics of MODY patients were not specific, 72.2% (13/18) of them were diagnosed after 35 years, 47.1% (8/17) had metabolic syndrome, and only 38.9% (7/18) had a family history of diabetes. No significant difference in manifestations except for hemoglobin A1c levels was found between MODY and non-MODY patients. CONCLUSION The prevalence of MODY in young adults with phenotypic T2DM was 0.74%, among which HNF1A -, GCK -, and HNF4A -MODY were the most common subtypes. Clinical features played a limited role in the recognition of MODY.
Humans ; Diabetes Mellitus, Type 2/diagnosis* ; Cross-Sectional Studies ; Mutation ; Prevalence ; Phenotype

Objective:To investigate the influencing factors of anastomotic leakage after laparoscopic intersphincter resection (ISR) for extremely low rectal cancer and construction of nomogram prediction model.Methods:The retrospective case-control study was conducted. The clinicopathological data of 812 patients who underwent laparoscopic ISR for extremely low rectal cancer in the Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital) from February 2012 to February 2022 were collected. There were 459 males and 353 females, aged (51±11)years. Observation indicators: (1) surgical situations; (2) follow-up; (3) influencing factors of postoperative anastomotic leakage; (4) construction and evaluation of nomogram prediction model for postoperative anastomotic leakage. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. The COX proportional hazard model was used for univariate and multivariate analyses. The R software(3.5.1 version) was used to construct nomogram prediction model. The receiver operating characteristic (ROC) curve was drawn and the area under curve (AUC) was used to evaluate the efficacy of the nomogram prediction model. The Bootstrap method was used for internal verification and to calculate the average consistency index (C-index). Results:(1) Surgical situations. All 812 patients underwent laparoscopic ISR for extremely low rectal cancer, including 388 cases undergoing partial ISR, 218 cases undergoing subtotal ISR and 206 cases undergoing complete ISR. All 812 patients underwent ileal protective ostomy, and there were 306 cases with double anastomosis and 203 cases with left colic artery preserved, respectively. The operation time and volume of intraoperative blood loss of 812 patients was (179±33)minutes and (33±13)mL, respectively. (2) Follow-up. All 812 patients were followed up for (13.5±0.9)months. Of the 812 patients, there were 62 cases with postoperative anastomotic leakage and the healing time of these cases was (33±6)days. (3) Influencing factors of postoperative anastomotic leakage. Results of multivariate analysis showed that male, neoadjuvant chemoradiotherapy, failure of reser-ving left colic artery were independent risk factors of anastomotic leakage after laparoscopic ISR for extremely low rectal cancer ( hazard ratio=5.98, 4.00, 16.26, 95% confidence interval as 1.66-24.12, 1.30-12.42, 3.00-90.89, P<0.05). (4) Construction and evaluation of nomogram prediction model for postoperative anastomotic leakage. According to the results of multivariate analysis, male, neoadju-vant chemoradiotherapy and failure of reserving left colic artery were used to construct the nomogram prediction model for anastomotic leakage after laparoscopic ISR for extremely low rectal cancer, and the score of these indexes in the nomogram prediction model was 50, 49, 93, respectively. The total score of these index corresponded to the incidence rate of anastomotic leakage. Results of ROC curve showed that the AUC of nomogram prediction model of anastomotic leakage after laparoscopic ISR for extremely low rectal cancer was 0.87 (95% confidence interval as 0.80-0.93, P<0.05), with sensi-tivity and specificity 0.96 and 0.60, respectively. Results of internal verification showed that the C-index of nomogram prediction model was 0.87. Conclusion:Male, neoadjuvant chemoradiotherapy, failure of reserving left colic artery are independent risk factors of anastomotic leakage after laparo-scopic ISR for extremely low rectal cancer, and the nomogram prediction model based on these indexes can predict the incidence rate of postoperative anastomotic leakage.

Objective:To investigate the construction and application value of a nomogram predictive model for the prognosis of rectal cancer liver metastases based on Surveillance, Epidemio-logy, and End Results (SEER) database.Methods:The retrospective cohort study was conducted. The clinicopathological data of 6 192 patients with rectal cancer liver metastases in the SEER database ( http://seer.cancer.gov/) and 312 patients who were admitted to The Second Affiliated Hospital of Naval Medical University January 2010 to December 2016 were collected. Of 6 192 patients, there were 3 592 males and 2 600 cases. There were 1 076 cases with age lower than 50 years, 2 862 cases with age as 50-69 years, 2 254 cases with age equal to or more than 70 years, respectively. Of 312 pati-ents, there were 177 males and 135 cases. There were 51 cases with age lower than 50 years, 155 cases with age as 50-69 years, 109 cases with age equal to or more than 70 years, respectively. Patients of the SEER database were set as the training set, and patients in The Second Affiliated Hospital of Naval Medical University were set as the validation set. Univariate and multivariate COX proportional hazards regression models were used to analyze risk factors associated with prognosis, and construct and verify the accuracy of nomogram predictive model for the prognosis of rectal cancer liver metas-tasis. The training set were used to construct the nomogram prediction model, and the validation set were used to verify its performance. Observation indicators: (1) prognostic factors analysis in patients with rectal cancer liver metastases; (2) construction and verificative of the predictive model for the prognosis of rectal cancer liver metastasis. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was analyzed using the rank sum test. The COX regression model was used for univariate and multivariate analyses. Kaplan-Meier method was used to calculate survival rates, and Log-Rank test was used for survival analysis. Results:(1) Prognostic factors analysis in patients with rectal cancer liver metastases. Results of multivariate analysis showed that age >50 years, TNM Ⅱ-Ⅳ stage, stage T3-T4, stage N1-N2, the number of lymph nodes dissected <12, tumor diameter >5.1 cm, positive carcinoembryonic antigen, peripheral nerve infiltration, radiotherapy and adjuvant chemotherapy, poorly differentiated or undifferented tumor were independent prognostic factors of patients ( P<0.05). (2) Construction and verification of the predictive model for the prognosis of rectal cancer liver metastasis. A nomogram predictive model for the prognosis of rectal cancer liver metastasis was constructed based in the multivariate analysis. The C-index of the nomogram predictive model was 0.91, with area under the curve as 0.726, indicating a good discriminant ability. Results of the calibration curve in validation dataset showed that the colorectal cancer survival rate predicted by the nomogram predictive model was consistent with the actual survival rate. Conclusion:The nomogram predictive model can accurately predict the survival probability of patients with rectal cancer liver metastases.

Objective:To investigate the value of surgical classification and pelvic floor reconstruction in pelvic exenteration for locally recurrent or locally advanced rectal cancer. Methods:A retrospective descriptive study method was used.Perioperative data were collected from 67 consecutive patients with locally advanced or locally recurrent rectal cancer who underwent pelvic exenteration at the Department of Anorectal Surgery,the Second Affiliated Hospital of Navy Military Medical University between November 2021 and November 2022 through the Chinese Combined Pelvic Exenteration Case Database for rectal cancer.The surgical range was divided into two categories:mainly localized in the pelvic cavity(48 cases)and combined with resection of the main tissue of the pelvic wall(1 9 cases).Outcome indexes included:(1)preoperative general data of patients;(2)intraoperative conditions;(3)postoperative recovery and complications(postoperative complications were evaluated by international Clavien-Dindo classification);(4)follow-up(outpatient and telephone follow-up were used to understand the postoperative survival,tumor recurrence and metastasis of patients,and the follow-up time was up to February 28,2023 or the case died).Measurement data are expressed by median(range),and enumeration data are expressed by example(％). Results:In the pelvic resection group,the median age of 48 patients was 57.5 years(range:31-82 years);29 were males and 19 were females;26 of them had locally advanced rectal cancer and 22 had locally recurrent rectal cancer;39 had a history of chemotherapy,immunotherapy or targeted therapy,and 26 had a history of radiotherapy;the median operation time was 425 min(range:240-1 020 min);the median intraoperative blood loss was 500 mL(range:200-4 000 mL);the median time to recovery of intestinal function was 3 d(range:1-9 d);the median recovery time of empty pelvis syndrome was 25.3 d(range:5-105 d);43 patients had postoperative complications＜grade Ⅲ,and of the 5 patients with ≥ grade Ⅲcomplications,2 died of multiple organ failure 7 d after operation,2 patients had surgical hemostasis for massive hemorrhage of pelvic floor wounds after operation,and 1 patient recovered from postoperative respiratory failure after rescue.In the combined pelvic wall resection group,the median age of 1 9 patients was 54.5 years(range:43-76 years);9 were males and 10 were females;4 patients had locally advanced rectal cancer and 15 patients had locally recurrent rectal cancer,all of whom had a history of chemotherapy,immunotherapy or targeted therapy,and 1 5 patients had a history of radiotherapy;the median operation time was 580 min(range:360-960 min);the median intraoperative blood loss was 1 600 mL(range:400-4 000 mL);the median intestinal function recovery time was 3 d(range:2-7 d);the median empty pelvis syndrome recovery time was 62.3 d(range:7-120 d);15 patients had postoperative complications＜grade Ⅲ,and of the 4 patients with grade ≥ Ⅲ,3 patients had surgical hemostatis for postoperative pelvic floor wound bleeding and 1 patient recovered after the second operation for intestinal obstruction.As of February 28,2023 or death,67 patients were followed up for a median of 7.5 months(range:3-1 5 months),and 3 patients died 3-8 months after operation due to rapid tumor progression,severe urinary tract infection,and sudden heart disease during the follow-up period.The remaining 62 cases survived. Conclusion:The surgical classification has guiding significance for preoperative surgical planning in patients with locally advanced or locally recurrent rectal cancer who undergo combined pelvic exenteration,and the method of pelvic floor reconstruction based on biological mesh is safe and feasible in combined pelvic exenteration for locally advanced or locally recurrent rectal cancer.

Objective:To understand the perceptions, attitudes and treatment selection of Chinese surgeons for proximal gastrectomy (PG) and digestive tract reconstruction.Methods:A cross-sectional survey was used in this study. Selection of subjects: (1) Domestic public grade IIIA (provincial and prefecture-level) tumor hospitals or general hospitals possessing the diagnosis and treatment qualifications for gastric cancer.(2) Surgeons with senior attending physician, associate chief physician and chief physician. The "Questionnaire Star" platform was used to design a questionnaire about cognition, attitude and treatment choice of "proximal gastrectomy and digestive tract reconstruction". The questionnaire contained 32 questions, such as the basic information of surgeons, the current status of gastric cancer surgery, the selection and management of surgical methods and related details for proximal gastric cancer, the choice of proximal gastrectomy and reconstruction of digestive tract, the related complications and nutritional status monitoring after proximal gastrectomy. A total of 76 questionnaires were linked to the respondents via WeChat between July 29 and August 25, 2019. Statistical analysis was performed using Chi-square test or Kruskal-Wallis test for categorical variables.Results:A total of 47 grade IIIA hospitals were included, and 76 questionnaires were sent out. The proportions of recovered and valid questionnaires were both 100%. For early and middle stage adenocarcinoma of esophagogastric junction (AEG), especially those smaller than 4 cm, 72.37% (55/76) of surgeons preferred proximal gastrectomy, while 22.37% (17/76) of surgeons chose total gastrectomy. For early AEG, 90.79% (69/76) of surgeons thought that endoscopic submucosal dissection (ESD) or proximal gastrectomy could be considered. For AEG below T3 stage and shorter than 4 cm, 60.53% (46/76) of surgeons gave priority to proximal gastrectomy, and 60.53% (46/76) of the surgeons believed that the advanced AEG with a higher radical cure should be treated with proximal gastrectomy, and the residual stomach should not be less than half stomach. Considering anti-reflux effect, postoperative weight recovery, clinical efficacy, wide application and easy popularization, surgeons preferred double-tract reconstruction. The surgeons in tumor hospitals had a higher approval rate for the application of proximal gastrectomy and the fact that the Kamikawa anastomosis was the most difficult to promote than the surgeons in provincial/municipal general hospitals. The surgeons with an annual surgical volume of more than 200 were more likely to choose proximal gastrectomy for early and middle stage AEG patients and the proportion was as high as 8/9. From the perspective of good clinical results, wide range of application, and easy popularization, the surgeons with a higher ratio (60.00%, 15/25) of double-tract reconstruction were those surgeons with 50-100 operations per year.Conclusions:The general level of cognition and acceptability of Chinese surgeons for proximal gastrectomy and reconstruction of digestive tract is suboptimal. In the future, it is urgent to promote the "Chinese consensus on digestive tract reconstruction after proximal gastrectomy" so as to guide and optimize treatment in proximal gastric cancer.

Objective:To understand the perceptions, attitudes and treatment selection of Chinese surgeons for proximal gastrectomy (PG) and digestive tract reconstruction.Methods:A cross-sectional survey was used in this study. Selection of subjects: (1) Domestic public grade IIIA (provincial and prefecture-level) tumor hospitals or general hospitals possessing the diagnosis and treatment qualifications for gastric cancer.(2) Surgeons with senior attending physician, associate chief physician and chief physician. The "Questionnaire Star" platform was used to design a questionnaire about cognition, attitude and treatment choice of "proximal gastrectomy and digestive tract reconstruction". The questionnaire contained 32 questions, such as the basic information of surgeons, the current status of gastric cancer surgery, the selection and management of surgical methods and related details for proximal gastric cancer, the choice of proximal gastrectomy and reconstruction of digestive tract, the related complications and nutritional status monitoring after proximal gastrectomy. A total of 76 questionnaires were linked to the respondents via WeChat between July 29 and August 25, 2019. Statistical analysis was performed using Chi-square test or Kruskal-Wallis test for categorical variables.Results:A total of 47 grade IIIA hospitals were included, and 76 questionnaires were sent out. The proportions of recovered and valid questionnaires were both 100%. For early and middle stage adenocarcinoma of esophagogastric junction (AEG), especially those smaller than 4 cm, 72.37% (55/76) of surgeons preferred proximal gastrectomy, while 22.37% (17/76) of surgeons chose total gastrectomy. For early AEG, 90.79% (69/76) of surgeons thought that endoscopic submucosal dissection (ESD) or proximal gastrectomy could be considered. For AEG below T3 stage and shorter than 4 cm, 60.53% (46/76) of surgeons gave priority to proximal gastrectomy, and 60.53% (46/76) of the surgeons believed that the advanced AEG with a higher radical cure should be treated with proximal gastrectomy, and the residual stomach should not be less than half stomach. Considering anti-reflux effect, postoperative weight recovery, clinical efficacy, wide application and easy popularization, surgeons preferred double-tract reconstruction. The surgeons in tumor hospitals had a higher approval rate for the application of proximal gastrectomy and the fact that the Kamikawa anastomosis was the most difficult to promote than the surgeons in provincial/municipal general hospitals. The surgeons with an annual surgical volume of more than 200 were more likely to choose proximal gastrectomy for early and middle stage AEG patients and the proportion was as high as 8/9. From the perspective of good clinical results, wide range of application, and easy popularization, the surgeons with a higher ratio (60.00%, 15/25) of double-tract reconstruction were those surgeons with 50-100 operations per year.Conclusions:The general level of cognition and acceptability of Chinese surgeons for proximal gastrectomy and reconstruction of digestive tract is suboptimal. In the future, it is urgent to promote the "Chinese consensus on digestive tract reconstruction after proximal gastrectomy" so as to guide and optimize treatment in proximal gastric cancer.

Objective: To evaluate the clinical efficacy of two different digestive tract reconstruction methods in the Siewert Ⅱ or Ⅲ adenocarcinoma of esophagogastric junction underwent proximal gastrectomy and piggyback jejunal interposition. Methods: A total of 84 patients with Siewert Ⅱ or Ⅲ AEG who underwent proximal gastrectomy and interposition jejunal anastomosis were enrolled prospectively according to the exclusion criteria, from October 2015 to August 2017 at Department of Digestive Minimally Invasive Surgery, Shanxi Cancer Hospital. There were 61 male and 23 female patients, aged 48-69 years with an average age of 59.7 years. They were divided into single-tract reconstruction group (n=41) and double-tract reconstruction group (n=43) according to random number table. Both groups underwent proximal gastrectomy and piggyback jejunal interposition. After side-to-side anastomosis of the remnant stomach and jejunum was performed in the single-tract group, jejunum 3 cm below the anastomosis was ligated or closed. The jejunum in the double-tract group was not treated during the operation. Relevant nutritional indicators were collected at 3 months and 6 months after operation. The data were analyzed by repeated measurement of variance analysis to determine the nutritional status. Results: There was no significant difference in preoperative general condition between single-tract reconstruction group and double-tract reconstruction group (P>0.05). There was no significant difference in perioperative related indicators (P>0.05). Nutritional indicators in single-channel reconstruction group were higher than those in double-channel reconstruction group (hemoglobin: F=23.374, P=0.000; albumin: F=6.149, P=0.003; total protein: F=18.362, P=0.000; weight: F=74.255, P=0.000). The quality of life was compared half year after operation, there was no significant difference in the incidence of subjective symptoms such as reflux, heart burning, nausea and vomiting, dysphagia and sternum discomfort in the two groups (P>0.05), as well as the results of QLQ-STO22 score (27.0±3.8 vs. 27.6±3.3, t=-0.688, P=0.494). The results of gastroscopy showed that the incidence and degree of the two groups were almost the same whether in the incidence of reflux esophagitis (2/41 vs. 2/43, P=1) or in the contrast of reflux degree (Z=-1.528, P=0.127). Conclusion For patients with type Siewert Ⅱ or Ⅲ esophagogastric junction adenocarcinoma who underwent proximal gastrectomy and piggyback jejunal operation, single tract reconstruction is ideal.

Objective To evaluate the survival and prognostic factors of esophageal cancer treated with definitive ( chemo ) radiotherapy by applying novel radiation techniques including three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT). Methods Clinical data of 2762 patients with non-operated esophageal squamous cell carcinoma who underwent definitive ( chemo ) radiotherapy from 2002 to 2016 in 10 hospitals were retrospectively analyzed.The prognostic factors were also identified and analyzed. Results The median follow-up time was 60. 8 months. The 1-, 2-, 3-and 5-year overall survival (OS) of all patients was 71. 4％,48. 9％,39. 3％,and 30. 9％,respectively.The 1-,2-,3-and 5-year progression-free survival (PFS) was 59.5％,41.5％,35.2％,and 30％,respectively.The median survival was 23 months.The median time to progression was 17. 2 months.Multivariate analysis demonstrated that age, primary tumor location, clinical stage, tumor target volume, EQD2 and treatment mode were the independent prognostic factors for OS.Primary tumor location,clinical stage,tumor target volume and EQD2 were the independent prognostic factors for PFS. Conclusions In this first large-scale multi-center retrospective analysis of definitive ( chemo) radiotherapy for esophageal squamous cell carcinoma in China, the 5-year OS of patients with esophageal squamous cell carcinoma is significantly improved by 3DCRT, IMRT combined with chemotherapy drugs. However, the findings remain to be validated by prospective clinical trials with high-level medical evidence.