ObjectiveTo approach the regulatory mechanism of high mobility group box-1 (HMGB1) on the expression of E-selectin in human umbilical vein endothelial cell (HUVEC).Methods Homeobox A9 (HOXA9) siRNA was transfected to HUVEC at logarithmic phase, real-time fluorescence quantitative polymerase chain reaction (real-time qPCR) and Western Blot were used to determine the HOXA9 mRNA expression and protein expressions; a blank control group and a nonsilence negative control group were set. HUVEC stable transfected with pRNA-u6.1/Neo-HMGB1 shRNA plasmids (HUVEC with low-expression HMGB1) was obtained, and HOXA9 and E-selectin mRNA expressions were determined with real-time qPCR; a nonsilence transfection group served as the negative control. The HOXA9 siRNA was transfected to HUVEC with low-expression HMGB1 as co-transfection group, and the E-selectin expressions was determined with real-time qPCR; a HMGB1 shRNA group and a HOXA9 nonsilence group served as control.Results① HOXA9 mRNA (2-ΔΔCT) and protein expression (integralA value) in blank control group were 1.094±0.115 and 1.031±0.060. Compared with nonsilence transfection group, HOXA9 siRNA transfection group could significantly reduced mRNA and protein expression of HOXA9 [HOXA9 mRNA (2-ΔΔCT): 0.257±0.030 vs. 1.035±0.091,t = 14.010,P = 0.002; HOXA9 protein (integralA value): 0.278±0.042 vs. 0.975±0.014,t = 27.310, P = 0.002].② Compared with nonsilence transfection group, HMGB1 shRNA transfection could up-regulate HOXA9 mRNA expression in HUVEC (2-ΔΔCT: 2.519±0.278 vs. 0.856±0.063,t = 10.100,P = 0.001), also could down-regulate E-selectin mRNA expression (0.311±0.046 vs. 1.080±0.201,t = 7.415,P = 0.000).③ Compared with HOXA9 nonsilence group and HMGB1 shRNA group, HMGB1 shRNA and HOXA9 siRNA co-transfected HUVEC cells could significantly elevate E-selectin mRNA expression (2-ΔΔCT: 3.445±0.428 vs. 1.085±0.212, 1.004±0.104,t1 = 8.507, t2 = 9.603, bothP< 0.001).Conclusion HMGB1 may regulate E-selectin expression through the HOXA9 regulation in HUVEC.

Objective To evaluate family economic burden of children with autism, or with physical disability or with intellectual disability.Methods227 parents of children with autism, children with physical disability, children with intellectual disability and normal children were interviewed for their family economic burden.ResultsThe medical cost and caring cost of children with disability were significantly more than those of normal children, and the education cost, clothes cost and amusement cost of children with disability were significantly less than those of normal children. Family income was only affected by education level of parents. Families of children with disability received more economic assistance than families of normal children except families of autistic children. More children the family had, less economic assistance the family acquired. Compared with normal children, the family economic burden of children with disability were as following, children with autism (19582.4 RMB per year), children with physical disability (16410.1 RMB per year), children with intellectual disability (6391.0 RMB per year). ConclusionFamilies of children with autism, children with physical disability and children with intellectual disability had heavier economic burden than families of normal children.

The 12th International Gastric Cancer Congress (12th IGCC ) was successfully held in Beijing, China on 20th-23rd April, 2017, which gave Chinese surgeons a great opportunity to share clinical progress and experience in the surgical treatment of gastric cancer with colleagues from different countries. At the end of 2017, this article hereby reviews briefly the achievements of surgical work of gastric cancer, which was done by our Chinese surgeons in this year. Some aspects will be reviewed, aiming at summarizing experience, affirming achievement, finding out the gap and promoting improvement in the future. These aspects include the conversion therapy for stageIIII( gastric cancer; the minimally invasive surgery for gastric cancer; the alimentary tract reconstruction after gastrectomy; enhanced recovery after radical gastrectomy and surgery quality control and patient's quality of life after surgery. In 2017, the gastric cancer surgery in China has made some new progress in many fields, and some achievements have reached or are close to international advanced level. However, looking ahead to the coming year and the future, there are still some important works to be done in the field of clinical surgery for gastric cancer in China, which include (1) strengthening big clinical data in gastric cancer collection and analysis platform construction for the promotion of scientific decision in therapeutic strategy; (2) further participating in international academic exchange and cooperation with taking advantages of our big number of gastric cancer cases, great amount of bio-tissue samples and big number of professional surgeons to actively join the international clinical research and expand our academic influence in the world;(3)developing more multicentre prospective randomized controlled trials in order to further improve the scientific significance in Chinese clinical guideline, norms and expert consensus in surgical treatment for gastric cancer; (4) further improving effectiveness of the multidisciplinary team (MDT) model in order to truly play the role of each subject in resolving some difficult cases; (5) in terms of surgical treatment for patients, it should be continue to keep going on minimally invasive operation, rational perioperative treatment, refinement technique, radical cure resection, and to further improve operation quality control system, aiming at realizing both goals simultaneously in prolonging survival time and improving quality of life for the patients with gastric cancer.

With the development of population aging in our country, the incidence of gastrointestinal cancer is increasing. The risk of developing gastrointestinal cancer in elderly over 75 years was 5-6 times and the risk of death of gastrointestinal cancer was 7-8 times of the general population. As compared to non-elderly, the incidence of gastric cancer was not decreased obviously but the total incidence of colorectal cancer was increased more quickly. Therefore, screening of gastrointestinal cancer should be performed in the elderly for early discovery, diagnosis and treatment. Because of the insidious onset of the illness in elderly patients, gastrointestinal cancers are mostly diagnosed at advanced or late stage (stage III or IV). Well differentiated cancer is more common, such as papillary or tubular adenocarcinoma. Lauren type, Borrmann II or III are more common in gastric cancer, which are relatively favorable. Compared with non-elderly patients, many elderly patients also suffer from comorbid diseases with higher operation risk and postoperative complication rates. Therefore, we must pay great attention to the perioperative management and the surgical operation for the elderly patients. In this paper, several key issues involved the development trend of incidence and mortality of gastrointestinal cancer, the clinicopathological characteristics, the comorbidity and surgical treatment in the elderly patients with gastrointestinal cancer will be elaborated, aiming at promoting further attention to the clinical therapeutic strategies, management measures and prognostic factors for the elderly patients with gastrointestinal cancer.
Adenocarcinoma ; epidemiology ; surgery ; Aged ; China ; epidemiology ; Colorectal Neoplasms ; epidemiology ; surgery ; Comorbidity ; Humans ; Postoperative Complications ; Stomach Neoplasms ; epidemiology ; surgery

Perioperative whole-process management (WPM) for patients with advanced gastric cancer (AGC) mainly focuses on some clinical issues which are easily neglected or underappreciated. WPM is helpful in making a scientific and rational therapeutic plan, and avoiding inadequate communication in multi-disciplinary participation, so that the diagnosis, treatment and rehabilitation for AGC patients can be integrated organically. Based on the current clinical practice for AGC patients, eight key issues in WPM should be emphasized.(1) Preoperative clinical staging. An accurate preoperative staging by endoscopy and imaging technique is helpful in setting up a rational therapeutic plan, and is also a prerequisite to start WPM. (2) Indications and value of diagnostic laparoscopy. Laparoscopic exploration is beneficial to find intraperitoneal micro-metastases so as to avoid unnecessary laparotomy. For cases of AGC infiltrating serosal layer or suspected of peritoneal metastasis, preoperative laparoscopic exploration should be routinely performed. (3) Neoadjuvant therapy. Multiple RCT studies have shown that neoadjuvant chemotherapy can benefit a majority of patients with AGC, improving prognosis and prolonging their overall survival. Therefore, neoadjuvant therapy should be considered first for stage III and IVA AGC patients. (4) Prediction of efficacy in neoadjuvant chemotherapy. Endoscopy, MDCT scan, PET-CT and liquid biopsy have certain predictive value individually, which can be used together or separately to improve the accuracy of prediction. (5) Effective prevention of postoperative peritoneal metastasis. Extensive intraoperative peritoneal lavage (EIPL), neoadjuvant intraperitoneal and systemic chemotherapy (NIPS), hyperthermic intraperitoneal chemotherapy (HIPEC), early postoperative intraperitoneal chemotherapy (EPIC), and normothermic intraperitoneal chemotherapy (NIPEC) have been shown to be of various efficacy in preventing peritoneal metastases. (6) Prediction of postoperative prognosis of AGC patients. The key pathological indicators are tumor regression grade (TRG) and ypTNM staging, especially if there is lymph node metastasis. Usually for AGC patients who received neoajuvant chemotherapy with TRG 0 or ypN0, their prognosis was comparable to that of patients with cTNM stage I.(7) Postoperative adjuvant chemotherapy. Postoperative adjuvant therapy is always an important part of the WPM management of AGC patients. Several recent RCT studies have shown that duplet chemotherapy can significantly reduce the risk of death after D2 radical gastrectomy compared to singlet chemotherapy, especially for stage III patients. (8) Perioperative nutritional support. Due to different degrees of malnutrition in AGC patients, enhanced nutritional treatment in the perioperative period can not only reduce surgical complications, but also enable patients to complete necessary course of chemotherapy, and ultimately further improve their survival rate.

Translational medicine refers to translating basic research achievements into the clinical application for diagnosis and treatment. There are still many issues of gastric cancer to be solved in clinical diagnosis and treatment. We need to focus on clinical questions, by means of basic research and multidisciplinary intersection approach, to further improve the overall efficacy of gastric cancer. Based on Ruijin Hospital′s translational research experiences, in this paper, the authors describe the future direction in the field of translational research, such as the etiology and pathogenesis of gastric cancer, tumor markers for early diagnosis, prediction of recurrence and metastasis, classification criteria, evaluation of chemotherapy, tumor heterogeneity, targeted therapy, immunotherapy and research platform establishment. In addition, here we share our perspective of the research on serum biomarkers, specific antibodies and improvement of drug delivery for gastric cancer.

OBJECTIVERNA interference was used to silence geranylgeranyltransferase Ⅰ(GGTase-Ⅰ) in vitro and to study the effect of GGTase-Ⅰ on the migration and invasion of tongue squamous cancer cells.

METHODSThree small interfering RNAs (siRNA) were designed according to the GGTase-Ⅰ sequence by Genebank and were transfected into tongue squamous cancer cells Cal-27 to knock down GGTase-Ⅰ expression. The tested cells were divided into three groups, as follows: the RNA-interfered groups (GGTase-Ⅰ siRNA1, GGTase-Ⅰ siRNA 2, GGTase-Ⅰ siRNA 3), a negative control group (disrupted by random sequence NC-siRNA), and a blank control group. GGTase-Ⅰ and RhoA gene expressions were examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. The optimum interference group was screened by qRT-PCR and Western blot and was assigned as the experimental group. Matrix metalloproteinase (MMP)-2 and MMP-9 protein expressions were examined by Western blot. GTP-RhoA expression of protein was examined by GST-pull down. The migration and invasion abilities were analyzed by wound healing assay and Transwell motility assay.

RESULTSGGTase-Ⅰ mRNA and protein expression in Cal-27 decreased significantly after transfection of GGTase-I siRNA (P<0.05). No significant difference of RhoA gene expression was detected. MMP-2, MMP-9, and GTP-RhoA protein expressions decreased significantly (P<0.05). The migration and invasion abilities were inhibited (P<0.05).

CONCLUSIONSTo inhibit GGTase-Ⅰ expression, the migration and invasion abilities of tongue squamous cancer cells should also be inhibited. Further studies on GGTase-Ⅰ may provide novel effective molecular targets for tongue squamous cancer cells.

Objective: To investigate the clinical value of laparoscopic peritoneal dialysis catheter implantation in peritoneal chemotherapy for gastric cancer with peritoneal metastasis. Methods: From January 2019 to June 2019, the clinical data of 6 patients diagnosed as gastric cancer with peritoneal metastasis were retrospectively analyzed in the Gastrointestinal Surgery Department of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine. Five were male and 1 was female. The median age was 69.5 (28-77) years. The median body mass index (BMI) was 22.8 (19.6-23.5). All procedures were performed under general anesthesia with endotracheal intubation. The patient′s body position and facility layout in the operating room were consistent with those of laparoscopic gastrectomy. The operator′s position: the main surgeon was located on the right side of the patient, the first assistant stood on the left side of the patient, and the scopist stood between the patient′s legs. Surgical procedure: (1) trocar location: three abdominal trocars was adopted, with one 12 mm umbilical port for the 30° laparoscope (point A). Location of the other two trocars was dependent on the procedure of exploration or biopsy as well as the two polyester cuff position of the peritoneal dialysis catheter: Usually one 5 mm port in the anterior midline 5 cm inferior to the umbilicus point was selected as point B to ensure that the distal end of the catheter could reach the Douglas pouch. The other 5 mm port was located in the right lower quadrant lateral to the umbilicus to establish the subcutaneous tunnel tract, and the proximal cuff was situated 2 cm away from the desired exit site (point C).(2) exploration of the abdominal cavity: a 30° laparoscope was inserted from 12 mm trocar below the umbilicus to explore the entire peritoneal cavity. The uterus and adnexa should be explored additionally for women. Once peritoneal metastasis was investigated and identified, primary laparoscopic peritoneal dialysis catheter implantation was performed so as to facilitate subsequent peritoneal chemotherapy. Ascites were collected for cytology in patients with ascites. (3) peritoneal dialysis catheter placement: the peritoneal dialysis catheter was introduced into the abdominal cavity from point A. Under the direct vision of laparoscopy, 2-0 absorbable ligature was reserved at the expected fixation point of the proximal cuff (point B) for the final knot closure. Non-traumatic graspers were used to pull the distal cuff of peritoneal dialysis catheter out of the abdominal cavity through point B. The 5-mm trocar was removed simultaneously, and the distal cuff was fixed between bilateral rectus sheaths at the anterior midline port site preperitoneally. To prevent subsequent ascites and chemotherapy fluid extravasation, the reserved crocheted wire was knotted. From point C the subcutaneous tunnel tract was created before the peritoneal steath towards the port site lateral to the umbilicus. Satisfactory catheter irrigation and outflow were then confirmed. Chemotherapy regimen after peritoneal dialysis catheterization: all patients began intraperitoneal chemotherapy on the second day after surgery. On the 1st and 8th day of each 3-weeks cycle, paclitaxel (20 mg/m²) was administered through peritoneal dialysis catheter, and paclitaxel (50 mg/m²) was injected intravenously. Meanwhile, S-1 was orally administered twice daily at a dose of 80 mg·m^-2·d^-1 for 14 consecutive days followed by 7-days rest. To observe the patients′ intraoperative and postoperative conditions. Results: All the procedures were performed successfully without intraoperative complications or conversion to laparotomy. No 30 day postoperative complications were observed. The median operative time was 33.5 (23-38) min. The median time to first flatus was 1(1-2) days, and the median postoperative hospital stay was 3 (3-4) days, without short-term complications within 30 days postoperatively. The last follow-up was up to July 10, 2019, and the patients were followed for 4(1-6) months. No ascites extravasation was observed and no death occurred in the 6 patients. There was no catheter obstruction or peritoneal fluid extravasation during and after chemotherapy. Conclusion Laparoscopic peritoneal dialysis catheter implantation was safe and feasible for patients with peritoneal metastasis of gastric cancer. The abdominal exploration, tumor staging and the abdominal chemotherapy device implantation can be completed simultaneously, which could simplify the surgical approach, improve the quality of life for patients and further propose a new direction for the development of abdominal chemotherapy.

OBJECTIVETo investigate the clinicopathological features and postoperative short-term complications in the elderly gastric cancer patients.

METHODSClinical data of 270 elderly patients with gastric cancer who underwent gastrectomy in Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine between July 2012 and June 2014 were analyzed retrospectively. Among 270 patients, 220 were 70 to 79 years old( old group) and 50 were ≥80 years old(oldest group). The clinicopathological features were compared between the two groups. Perioperative factors were analyzed to determine if they are associated with postoperative complications. Multivariate logistic regression model was performed.

RESULTSBefore operation, most elderly patients (n=161, 59.6%) had 2 or more than 2 comorbidities, including hypertension (n=154, 57.0%), anaemia (n=126, 46.7%), diabetes (n=53, 19.6%), arhythmia (n=52, 19.3%), cardiovascular disease(n=33, 12.2%), and chronic pulmonary disease(n=28, 10.4%). Elderly gastric cancers were more likely to locate at the lower third of the stomach (n=116, 43.0%). The pathological type was mainly the poorly differentiated carcinoma (n=152, 56.3%), and stage III was more common in TNM staging(n=138, 51.1%). As compared to the old group, the oldest group had more preoperative comorbid diseases(P=0.048), more previous surgery(P=0.029), more preoperative transfusion (P=0.019), more combined cholecystectomy (P=0.007) and feeding jejunostomy (P=0.037), but less tumor invasion of nerves(P=0.045). No significant differences in other clinicopathological parameters were found between the two groups (all P>0.05). A total of 121 (44.8%) patients presented postoperative complications, including severe complication in 30 cases(11.1%) and death in 4 cases(1.5%). Forty-seven patients(17.4%) presented operation-associated complications, including infection in 28 cases(10.4%) and leakage in 21 cases(7.8%). One hundred and seven(39.6%) patients presented non-operation-associated complications, including pneumonia in 48 cases(17.8%), hypertension in 23 cases(8.5%), and arhythmia in 17 cases(6.3%). Postoperative morbidities of Clavien-Dindo class II complication and non-operation-associated complication were higher in the oldest group compared with old group(P<0.05), while other postoperative complications were compared between the two groups, only urinary tract infection was significantly different(P<0.05). Univariate analysis showed that postoperative complications were significantly associated with age(χ(2)=7.308, P=0.007), number of comorbid diseases (χ(2)=10.872, P=0.001), cardiovascular disease (χ(2)=9.412, P=0.002), hypertension (χ(2)=4.934, P=0.026) and preoperative transfusion (χ(2)=3.911, P=0.048). Multivariate analysis showed that only the number of comorbid diseases was an independent risk factor for postoperative complications(OR=2.810, 95% CI: 1.710 to 4.616, P=0.000).

CONCLUSIONNon-operation-associated postoperative complications are more likely to occur in the elderly patients due to more comorbid diseases. Perioperative intensive care should be carried out for the elderly gastric cancer patients with comorbid diseases in order to improve surgical safety and efficacy.

Aged ; Aged, 80 and over ; China ; Comorbidity ; Gastrectomy ; adverse effects ; Humans ; Hypertension ; complications ; Logistic Models ; Multivariate Analysis ; Neoplasm Staging ; Postoperative Complications ; Retrospective Studies ; Risk Factors ; Stomach Neoplasms ; complications ; surgery

OBJECTIVE: To investigate the clinical characteristics and prognostic factors of reoperation patients with postoperative recurrence or metastasis of gastrointestinal stromal tumor (GIST). METHODS: A retrospective case-control study was performed on the clinical data of 31 patients with GIST who had recurrence or metastasis after the first surgery and underwent one or more operations again from February 2003 to January 2016 at Ruijin Hospital, Shanghai Jiaotong University School of Medicine. The clinical characteristics of these patients were analyzed. Kaplan-Meier survival curve was used to calculate the survival rate, Cox univariate and multivariate regression model was applied to prognosis analysis. RESULTS: Age of these 31 patients at the first operation was 35-78 (median 49) years, including 17 males (54.8%) and 14 females (45.2%). The tumors of 21 cases located in small intestines (67.7%), 2 cases in stomach (6.5%), 4 cases (12.9%) in colorectum and of 4 cases (12.9%) in other sites. According to NIH criteria, risk assessment indicated 26 cases were(83.8%) with high risk, 3 cases (9.7%) with moderate risk, and 2 cases (6.5%) with low risk. After the first operation, 15 cases received the IM (imatinib) therapy regularly based on NCCN guideline,10 cases received the therapy irregularly, and the other 6 cases did not receive the therapy. R0 resection was performed in 29 cases (93.5%) and R1/R2 resection was performed in 2 cases (6.5%). The median interval between the first operation to the recurrence was 32.3 (5.2-117.6) months and the median age of recurrence was 56 years old. Refer to the recurrent location, 28 cases (90.3%) were found in the same location or liver, 1 case in greater omentum, and 2 cases in pelvic cavity. The median diameter of the tumor in reoperation was 6.5 cm. Twenty-three cases(74.2%) received R0 excision and the other 8 cases(25.8%) received R1/R2 excision. At diagnosis of tumor recurrence, 20 cases (64.5%) received the second surgery immediately and the other 11 cases received surgery after imatinib or sunitinib treatment. Twenty-nine (93.5%) patients were followed up for 7.3 to 160.3 (median 49.5) months. After the second surgery, the relapse-free survival (RFS) of the whole group was 3.2 to 148.6(median: 29.7) months. Till the end of follow-up, 9 cases died of recurrence. Among 20 alive cases, 8 cases were living with the tumor, 1 case received the third surgery. The median overall survival (OS) time was 38.4(6.2-160.3) months. The 5-year RFS and the 5-year OS of 15 cases who received regular targeted therapy after the first operation were 73.4% and 81.7% respectively, significantly higher than those of the other 16 cases who received irregular or no targeted therapy(37.6%, P=0.015 and 38.9%,P=0.023,respectively). The 5-year RFS rate and the 5-year OS rate of the 11 patients who were diagnosed or complicated with liver metastasis were 29.8% and 32.2% respectively, which were significantly lower than those of the 20 patients without liver metastasis (79.1% and 88.1% respectively, both P<0.001). Cox model for OS, the results showed that regular targeted therapy after first surgery(HR=0.362, 95%CI:0.210-1.074, P=0.089) and the liver metastasis (HR=5.342, 95%CI: 0.902-12.580, P=0.057) were not the independent risk factors. CONCLUSIONS Regular targeted therapy according to the guideline after the first operation for GIST patients with recurrence or metastasis may improve the prognosis. Prognosis of GIST patients with postoperative liver metastasis is poor.
Case-Control Studies ; China ; Female ; Gastrointestinal Stromal Tumors ; diagnosis ; surgery ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Prognosis ; Reoperation ; Retrospective Studies