[Clinical significance of immune checkpoint inhibitors in neoadjuvant therapy for gastric cancer].

Multiple prospective clinical studies have demonstrated that chemotherapy combined with immune checkpoint inhibitors (ICIs) can prolong the survival of patients with far-advanced gastric cancer. For patients with locally advanced gastric cancer (LAGC), preoperative neoadjuvant chemotherapy combined with immunotherapy has also achieved some encouraging results which benefit some patients, achieve clinical downstage, attenuate hidden metastases, increase R0 resection rate and reduce postoperative recurrence rate, etc. How to apply ICIs or combine immunotherapy with other therapies correctly in the course of neoadjuvant comprehensive treatment for patients with LAGC is still a very challenging and difficult problem. There are three basic principles in immunotherapy to be grasped: (1) Based on high-level clinical practice guidelines; (2) Based on the results of high-quality evidence-based medical research; and (3) Based on molecular pathology and tumor biomarkers. Perioperative immunotherapy for gastric cancer can be correctly applied if these three principles are organically integrated. Referring to the results of domestic and international clinical research in recent years, the three basic principles are demonstrated in this article for readers.

[Interpretation of the National Regulation for the Rabies Exposure Prophylaxis (2023 Edition)].

Rabies is one of the important zoonotic infectious diseases, with a mortality rate of almost 100%. Rabies is a vaccine preventable disease, and proper rabies exposure prophylaxis can effectively prevent the occurrence of human rabies. In recent years, there has been significant progress in clinical research on the rabies exposure prophylaxis both domestically and internationally. World Health Organization (WHO) released the Rabies Vaccine: WHO Position Paper-April 2018. In order to guide medical institutions of all levels in rabies exposure prophylaxis, the National Administration of Disease Prevention and Control, in conjunction with the National Health Commission of the People's Republic of China, organized the Rabies Vaccine Working Group of the National Immunization Program Technical Working Group and invited experts to revise and issue the National Regulation for the Rabies Exposure Prophylaxis (2023 Edition). This article compares the National Regulation for the Rabies Exposure Prophylaxis (2009 Edition) and interprets the updated key points and supporting basis of the new version of the guidelines to guide clinical application and implementation.

[A multi-center retrospective study of perioperative chemotherapy for gastric cancer based on real-world data].

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.

[Current status and prospect of perioperative therapy for locally advanced gastric cancer].

Local advanced gastric cancer (LAGC) accounts for a large proportion of annual newly diagnosed gastric cancer patients in China. There is a general consensus for D2 radical gastrectomy followed by postoperative adjuvant chemotherapy for LAGC patients, and this therapeutic strategy has been confirmed by a series of clinical trials to obviously improve the patients' prognosis; however, the recurrence rate is still high (about 50%-80% in advanced stage), which makes it difficult to further improve the long-term survival. Perioperative therapy, especially whether preoperative neoadjuvant therapy (NAT) can improve the efficacy of patients with LAGC, has been paid more and more attention. NAT is mainly defined as a preoperative chemotherapy or chemoradiotherapy, aiming at increasing curative resection rate by downstaging tumor, eliminating micrometastases, and autologously testing of anti-cancer drug sensitivity etc. However, there are still some controversy whether LAGC patients could gain survival benefit from NAT and also lack of general consensus for this issue. In this paper, the author reviews and analyzes the current situation of perioperative therapies for LAGC patients, especially emphasize the results of neoadjuvant chemotherapy or chemoradiotherapy reported by various high-level clinical studies. The preliminary effect of perioperative chemotherapy combined with molecular targeted or immunotherapy has also aroused great interest and attention. While we continue to carry out NAT and look forward to more new high-level evidence trials on NAT, we must emphasize again that R0 gastrectomy remains the most important therapeutic modality for the patients with LAGC.

[Laparoscopic diagnosis of postoperative recurrence of peritoneal metastasis in gastric cancer patients and the clinical efficacy of bidirectional intraperitoneal and systemic chemotherapy].

Objective: To explore the diagnostic value of laparoscopy in the postoperative recurrence of peritoneal metastasis in gastric cancer, and to investigate the efficacy of bidirectional intraperitoneal and systemic (BIPS) chemotherapy for the recurrence. Methods: The descriptive case series study was conducted. Case inclusion criteria: (1) gastric cancer patients without synchronous distant metastasis received D2 radical gastrectomy; (2) postoperative adjuvant chemotherapy was administered; (3) no other distant metastasis except recurrence of peritoneal metastasis; (4) age of 18-75 years; (5) Eastern Cooperative Oncology Group (ECOG) performance-status score≤2; (6) pretreatment evaluation suggested that surgery and chemotherapy could be tolerated. Eight consecutive gastric cancer patients with postoperative recurrence of peritoneal metastasis who met the above criteria at Department of Gastrointestinal Surgery of Ruijin Hospital from September 2015 to September 2016 were enrolled into the study. There were 6 males and 2 females with the median age of 52 (38-68) years. They received laparoscopy or laparotomy first, and then were evaluated with reference to the Sugarbaker peritoneal cancer index (PCI) and the peritoneal metastasis classification of gastric cancer developed by the Japanese Gastric Cancer Research Association. A peritoneal access port was implanted in the subcutaneous space of the lower abdomen and the patients received chemotherapy for 21 days as a course of treatment. All the patients received intraperitoneal 20 mg/m(2) of paclitaxel (PTX) via implanted subcutaneous peritoneal access ports and intravenous 50 mg/m(2) of PTX at day 1 and day 8, meanwhile 80 mg/m(2) of Tigio was orally administered per day for 14 consecutive days, followed by 7 days of interval. Follow-up ended on December 15, 2019. Results: Of these 8 patients with recurrence of peritoneal metastasis after gastric cancer surgery, 1 case underwent laparotomy and loop stoma of terminal ileum because of complete colonic obstruction, and the remaining 7 cases underwent laparoscopy successfully and the recurrence of peritoneal metastasis was clearly diagnosed. Two patients with ovarian metastasis underwent laparoscopic bilateral adnexectomy. The median follow-up time was 17.5 (1.5 to 39.0) months, the median number of BIPS chemotherapy course was 11 (1 to 30), and the median survival time (MST) after BIPS chemotherapy was 17.0 months. The major adverse reaction in BIPS treatment was mainly myelosuppression, of which grade 3/4 leukopenia and neutropenia developed in 1 and 2 cases respectively. No BIPS-related death occurred. The MST of gastric cancer after radical gastrectomy was 40.0 months. Conclusions: Laparoscopy is a safe and feasible method for diagnosing the recurrence of peritoneal metastasis of gastric cancer. BIPS chemotherapy is effective and safe for its treatment and deserves further study.

Adjuvant chemotherapy for patients with gastric neuroendocrine carcinomas or mixed adenoneuroendocrine carcinomas.

BACKGROUND: The aim of this study was to evaluate whether adjuvant chemotherapy is associated with improved survival in patients with resectable gastric neuroendocrine carcinomas (G-NECs) or mixed adenoneuroendocrine carcinomas (G-MANECs). METHODS: The study included patients with G-NECs or G-MANECs who underwent surgery in one of 21 centres in China between 2004 and 2016. Propensity score matching analysis was used to reduce selection bias, and overall survival (OS) in different treatment groups was estimated by the Kaplan-Meier method. RESULTS: In total, 804 patients with resectable G-NECs or G-MANECs were included, of whom 490 (60·9 per cent) received adjuvant chemotherapy. After propensity score matching, OS in the chemotherapy group was similar to that in the no-chemotherapy group. Among patients with G-NECs, survival in the fluorouracil (5-FU)-based chemotherapy group and the non-5-FU-based chemotherapy group was similar to that in the no-chemotherapy group. Similarly, etoposide plus cisplatin or irinotecan plus cisplatin was not associated with better OS in patients with G-NECs. Among patients with G-MANECs, OS in the non-5-FU-based chemotherapy group was worse than that in the no-chemotherapy group. Patients with G-MANECs did not have better OS when platinum-based chemotherapy was used. CONCLUSION: There was no survival benefit in patients who received adjuvant chemotherapy for G-NECs or G-MANECs.

ANTECEDENTES: El objetivo de este estudio fue evaluar si la quimioterapia adyuvante mejoraba la supervivencia en pacientes con carcinomas gástricos resecables neuroendocrinos (gastric neuroendocrine carcinomas, G-NECs) y carcinomas adenoneuroendocrinos mixtos (mixed adenoneuroendocrine carcinomas, G-MANECs). MÉTODOS: Se incluyeron pacientes con G-NECs y G-MANECs tratados quirúrgicamente en 21 centros en China entre 2004 y 2016. Se utilizó un análisis de emparejamiento por puntaje de propensión para reducir el sesgo de selección y el método de Kaplan-Meier para estimar la supervivencia global (overall survival, OS) de los pacientes en los diferentes grupos de tratamiento. RESULTADOS: En total, se incluyeron en el estudio 804 pacientes con G-NECs y G-MANECs resecables y 490 pacientes (60,9%) recibieron quimioterapia adyuvante. Después del emparejamiento por puntaje de propensión, la OS del grupo con quimioterapia fue similar a la del grupo sin quimioterapia. En los pacientes con G-NECs, la supervivencia en los grupos con quimioterapia basada en 5-FU (fluorouracilo) y de quimioterapia sin 5-FU fue similar a la del grupo sin quimioterapia. Asimismo, la combinación de etopósido y cisplatino o de irinotecán y cisplatino no se asoció con una mejor OS en pacientes con G-NECs. En pacientes con G-MANECs, la OS del grupo con quimioterapia sin 5-FU fue peor que la del grupo sin quimioterapia. Los pacientes con G-MANECs no presentaron una mejor OS cuando se administró quimioterapia basada en platinos. CONCLUSIÓN: La administración de quimioterapia adyuvante en pacientes con G-NECs y G-MANECs no mejoró la supervivencia.

[Specifications for diagnosis and treatment of non-neonatal tetanus].

Tetanus consists of neonatal tetanus and non-neonatal tetanus. Non-neonatal tetanus remains a serious public health problem, although neonatal tetanus has been eliminated in China since 2012. Non-neonatal tetanus is a potential fatal disease. In the absence of medical intervention, the mortality rate of severe cases is almost 100%. Even with vigorous treatment, the mortality rate is still 30%-50% globally. These specifications aim to regulate non-neonatal tetanus diagnosis and treatment in China, in order to improve medical quality and safety. These specifications introduce the etiology, epidemiology, pathogenesis, clinical manifestations and laboratory tests, diagnosis, differential diagnosis, grading and treatment of non-neonatal tetanus.

[Key points of perioperative whole-process management for patients with advanced gastric cancer].

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 research on gastric cancer: Ruijin experience].

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.

Anastomosis for distal gastrectomy in Chinese patients: uncut roux-Y or roux-Y?

BACKGROUND: An appropriate method of anastomosis is crucial for gastric cancer patients who require gastrojejunal anastomosis. Surgeons have proposed different types of modified gastrojejunostomies in the last two decades. We focused on two types of standard anastomosis, i.e., Uncut Roux-Y and Roux-Y gastrojejunostomies, and compared the differences in immediate postoperative complications between the two types. METHODS: This is a retrospective study on 236 gastric cancer patients who underwent curative distal gastrectomy with gastrojejunal Roux-Y or Uncut Roux-Y anastomosis for six consecutive years. Immediate postoperative complications were compared between the two groups. The authors discussed the causes of the significant complications and their management. RESULTS: There was no difference in demographics between the two groups (92 Roux-y Versus 144 Uncut Roux-y). The overall complication rate was 20.8% with 1.4% anastomotic leakage in the Uncut Roux-Y group versus 33.7% with 7.6% anastomotic failures in the Roux-Y group (p < 0.05). More abdominal infections occurred in the Roux-Y anastomosis group compared with the Uncut Roux-Y anastomosis group (p < 0.05). Duration of postoperative stay was significantly longer in patients with Roux-y anastomosis group (p < 0.05). CONCLUSIONS: Considering the surgical simplicity and postoperative complications, the Uncut Roux-Y is a better choice for anastomosis in patients with gastric cancer undergoing gastrojejunostomy. A well-designed large cohort in a multi-centre randomized controlled trial is necessary to support these findings and compare other aspects.

[Specifications for diagnosis and treatment of non-neonatal tetanus].

Tetanus consists of neonatal tetanus and non-neonatal tetanus. Although neonatal tetanus in China has been eliminated since 2012, non-neonatal tetanus remains a serious public health problem. Non-neonatal tetanus is a potential fatal disease, and the mortality rate of severe cases is almost 100% in the absence of medical intervention. Even with vigorous treatment, the mortality rate is still 30~50% globally. In order to standardize the diagnosis and treatment of non-neonatal tetanus in China, this specification is hereby formulated. This standard includes etiology, epidemiology, pathogenesis, clinical manifestations, laboratory tests, diagnosis, differential diagnosis, classification, grading and treatment of non-neonatal tetanus.

[Analysis and comparison of the clinical features and prognosis between extra - gastrointestinal stromal tumors and duodenal gastrointestinal stromal tumors].

Objective: To investigate the differences of clinicopathological features, diagnosis, treatment and prognosis between patients with extra-gastrointestinal stromal tumors (EGIST) and duodenal gastrointestinal stromal tumors (DGIST). Methods: A retrospective case - control study was performed. Case inclusion criteria: (1) tumor confirmed by histology and pathology; (2) primary tumor locating in the extra - gastrointestinal tract or duodenum; (3) without other synchronous tumors; (4) complete clinical and pathological data. Clinical data of 20 EGIST patients and 32 DGIST patients from March 2011 to September 2016 at Department of Gastrointestinal Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine were retrospectively collected and analyzed. The observational parameters included clinicopathological characteristics, treatment and prognosis conditions. Continuous data of abnormal distribution were expressed as median (range) and compared using the Mann-Whitney U-test. Survival curves were drawn by the Kaplan-Meier method and compared with the Log-rank test. Results: Of the 20 EGIST patients, 8 were males and 12 were females with age of 61.0 (30.0 to 86.0) years and of the 32 DGIST patients, 12 were males and 20 were females with age of 55.5 (27.0 to 70.0) years. Compared with DGIST patients, EGIST patients were older (U=188.000, P=0.012], had larger tumor size [10.0 (3.0 to 29.0) cm vs. 4.0 (1.5 to 10.0) cm, U=98.500, P<0.001] and higher ratio of high risk classification [85.0% (17/20) vs. 12.5% (4/32), χ(2)=26.870, P<0.001]. Among the 20 EGIST patients, 5 were diagnosed with distal metastasis and received imatinib (400 mg/d), and the other 15 patients underwent radical resection who were included in survival analysis. All the 32 DGIST patients underwent radical resection. The median follow-up of whole group was 43 (14 to 76) months. The 3-year recurrence/metastasis-free survival rate of 15 cases undergoing radical resection in the EGIST group was 85.6%, which was lower than that of the DGIST group (88.6%), and the difference was not statistically significant (P=0.745). There was no significant difference in the 3-year overall survival rate between the EGIST group (92.9%) and the DGIST group (100%) (P=0.271). Conclusions: As compared to DGIST, EGIST mostly occurs in those with older age, larger tumor size and higher risk grade. The prognosis of EGIST patients after radical resection is similar to that of DGIST patients.

[Laparoscopic peritoneal dialysis catheter implantation in peritoneal chemotherapy for gastric cancer with peritoneal metastasis].

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/m(2)) was administered through peritoneal dialysis catheter, and paclitaxel (50 mg/m(2)) 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.

[Expert consensus on rabies exposure prophylaxis].

Rabies is a zoonotic infectious disease caused by lyssavirus and characterized by central nervous system symptoms. The fatality rate of rabies is almost 100%. About 59 000 cases die of rabies worldwide every year, mainly in Asia and Africa. China is an epidemic country of rabies. Grade II and III exposures are the main types of rabies exposures in China. Standardized post-exposure prophylaxis (PEP) can prevent rabies almost 100%. Human Rabies Vaccine Technical Working Group, National Immunization Advisory Committee and invited experts reached an expert consensus on PEP by referring to the World Health Organization's position paper on rabies vaccine in 2018 and related research progress in recent.

[The clinical significance of Th17 cells in patients with myelodysplastic syndrome and iron overload].

Objective: To study the significance of Th17 cells in patients with myelodysplastic syndrome (MDS) and iron overload. Methods: A total of 77 patients with MDS admitted to Guangzhou First People's Hospital were enrolled from January 2017 to December 2018,who were divided into iron overload group (37 cases) with serum ferritin (SF) over 1000 µg/L and non-ferrous overload group(40 cases). CD(4)(+)T cells in peripheral blood (PB) and bone marrow (BM) were sorted by flow cytometry. The ratio of Th17 cells and cells with abnormal karyotype were compared. IL-17 and IL-6 protein and RNA expression were detected by ELISA and quantitative real-time PCR(qRT-PCR). Results: The proportions of Th17 cells in PB and BM in iron overload group were significantly higher than those in non-iron overload group [(41.06±0.96)% vs. (26.80±1.21)%; (47.39±1.60)% vs. (34.29±1.03)%; P<0.01]. The Th17 positive cells with abnormal karyotype in iron overload group were more than those in non-iron overload group[(4.96±0.53)% vs. (3.67±0.12)% in PB; (10.06±1.67)% vs. (4.36±0.43)% in BM; P<0.01]. Similarly,the protein levels as well as mRNA expression of IL-6 and IL-17 in patients with iron overload were significantly higher than those in non-iron overload group (P<0.01 both in PB and BM). Conclusions: As hematopoietic regulators secreted by Th17 cells, the expression of IL-6 and IL-17 in MDS patients with iron overload are elevated. This may predict the influence of these factors to the differentiation of Th17 cells.

[Predictive factors for lymph node metastasis in patients with poorly differentiated early gastric cancer].

Objective: This study aimed to identify clinicopathological factors predictive of lymph node metastasis in patients with the poorly differentiated early gastric cancer (EGC) to assess the feasibility of using endoscopic submucosal dissection (ESD). Methods: The records of patients with poorly differentiated early gastric cancer undergoing gastric radical resection between January 2012 and December 2016 were reviewed in Ruijin hospital. Those with distant metastasis, two or more malignant tumors, remnant gastric cancer, neo adjuvant therapy, previous history of gastric surgery or clear history of perigastric lymphadenectomy, and mixed tumors were excluded. Age, sex, presence of ulcerous lesion, tumor size, tumor location, depth of invasion, type of differentiation, lymphatic vessel invasion, vascular invasion, nerve invasion and HER2 expression were collected. Univariate and multivariate stepwise logistic regression analyses were used to identify the independent risk factors of perigastric lymph node metastasis.According to the Guidelines for the Treatment of Gastric Cancer (2018 edition) of the Chinese Society of Clinical Oncology (CSCO), the expanded indications of ESD for EGC are as follows: (1)no ulcerative lesions, the maximum diameter of lesions >2 cm of differentiated intramucosal cancer; (2)ulcerative lesions, the maximum diameter of lesions ≤3 cm of differentiated intramucosal cancer; (3)no ulcerative lesions, undifferentiated intramucosal carcinoma with diameter ≤2 cm. The relationship between clinicopathological factors and lymph node metastasis was analyzed. Results: A total of 517 patients, aged 21-83 (57.1±11.7), including 307 males and 210 females, were enrolled in the study. Among them, 114 (22.0%) patients had lymph node metastasis. Univariate analysis showed that ulcerative lesion (P=0.042), tumor diameter (P=0.048), depth of invasion (P<0.001), location of tumors (P<0.001), lymphatic vessel invasion (P=0.009), vascular invasion (P<0.001) and nerve invasion (P=0.028) were related to lymph node metastasis after radical resection of poorly differentiated early adenocarcinoma. Age, sex, type of differentiation and HER2 expression were not significantly correlated to lymph node metastasis (P>0.05). Multivariate analysis showed that tumor size (OR=1.61, 95% CI: 1.03-2.52, P=0.037), depth of invasion (OR=2.77, 95% CI:1.66-4.63, P<0.001), lymphatic duct invasion (OR=14.74, 95% CI:1.58-137.36, P=0.018) were independent risk factors for lymph node metastasis in poorly differentiated EGC, and ulcerative lesion was not a risk factor for lymph node metastasis (OR=0.82, 95% CI:0.56-1.18,P=0.285). A total of 119 patients with poorly differentiated EGC fully complied with the relative indications of ESD recommended by the Japanese Statute and the criteria for radical resection after ESD. Among them, 14 (11.8%) still had perigastric lymph node metastasis, while the gender, tumor diameter, location, differentiation and HER2 expression were not associated with lymph node metastasis (P>0.05). Conclusion: For patients with poorly differentiated EGC, the application of ESD should be carefully weighed with precise assessment of tumor diameter, depth of invasion, and lymphatic duct invasion.

[Infiltration of tumor associated macrophages in multiple myeloma and its clinical significance].

Objective: To investigate the clinical significance of tumor associated macrophages (TAM) in multiple myeloma (MM) and the relationship with angiogenesis and immunosuppression. Methods: Seventy cases of MM patients diagnosed from August 2015 to June 2017 were enrolled in the study as experimental group, 20 cases of benign hematological diseases (13 with iron deficiency anemia and 7 with megaloblastic anemia) patients as control group. Immunohistochemical method was used to detect the expression of CD163, CD34 and VEGF in bone marrow samples, and flow cytometry was used to detect the proportion of regulatory T cell (Treg cells), ELISA was used to detect the level of IL-10, and the clinical features were analyzed. Results: ①Among the 70 patients, there were 31 males and 39 females with a median age of 65 (50~78) years old. TAM infiltration density, microvascular density (MVD), VEGF expression level, Treg ratio and IL-10 level in bone marrow samples of 70 MM patients were significantly higher than those of benign hematological diseases (P<0.05). ②In the MM group, the above indexes of the patients with disease stabilized (15 cases) were lower than those of the newly diagnosed group (35 cases) and the relapse refractory group (20 cases) (P<0.05), those of relapse refractory group were higher than those of newly diagnosed group (P>0.05). ③Of the 35 newly diagnosed MM patients, 27 completed 4 courses of treatment. In the effective group (15 cases), the TAM infiltration density after treatment was significantly lower than that before treatment, the difference was statistically significant[(20.20±7.66) vs (28.87±11.97), t=2.362, P=0.025]; while in the ineffective group of 12 cases, the difference of the TAM infiltration density before and after treatment was not statistically significant[(42.00±13.76) vs (48.25±13.59), t=1.119, P=0.275]. ④TAM infiltration density in the effective group after bortezomib treatment (21 cases) were lower than those in the non-bortezomib treatment group (18 cases)[(16.52 ±4.26) vs (19.27 ±5.82), t=1.662, P=0.170]. ⑤The TAM infiltration density in MM patients was positively correlated with MVD, VEGF expression level, Treg cell ratio and IL-10 level (P<0.001). Conclusion: The infiltration of TAM in the microenvironment of MM, which may promoting angiogenesis and inhibiting immune response, is related to the occurrence, development, therapeutic effect and drug resistance of MM.

Comparison of outcomes between off-pump versus on-pump coronary artery bypass surgery in elderly patients: a meta-analysis.

The aim of this study was to analyze if off-pump coronary artery bypass surgery (CABG) is associated with better treatment outcomes in elderly patients (>70 years of age) than on-pump CABG, using meta-analysis. Medline, PubMed, Cochrane and Google Scholar databases were searched until September 13, 2016. Sensitivity and quality assessment were performed. Twenty-two studies, three randomized control trials (RCTs) and 20 non-RCTs were included with 24,127 patients. The risk of death associated with on-pump or off-pump CABG in the RCTs were similar (pooled OR=0.945, 95%CI=0.652 to 1.371, P=0.766). However, in the non-RCTs, mortality risk was lower in patients treated with off-pump CABG than on-pump CABG (pooled OR=0.631, 95%CI=0.587 to 0.944, P=0.003). No differences were observed between the two treatment groups in terms of the occurrence of 30-day post-operative stroke or myocardial infarction (P≥0.147). In the non-RCTs, off-pump CABG treatment was associated with a shorter length of hospital stay (pooled standardized difference in means=-0.401, 95%CI=-0.621 to -0.181, P≤0.001). The meta-analysis with pooled data from non-RCTs, but not RCTs, found that mortality was lower with off-pump compared with on-pump CABG, and suggested that there may be some benefit of off-pump CABG compared with on-pump CABG in the risk of mortality and length of hospital stay.

Association between the resistin gene-420 C>G polymorphism and obesity: an updated meta-analysis.

OBJECTIVE: The aim of this study was to assess the relationship of the resistin gene (RETN)-420 C>G polymorphism and obesity susceptibility by conducting an updated meta-analysis. MATERIALS AND METHODS: The electronic databases including PubMed, Medline, Embase, China National Knowledge Infrastructure, Chinese Wanfang Database, and Chinese VIP database were searched for relevant studies published before December 2013. The fixed effect model or random effects model was used based on the heterogeneity test results. The sensitivity analysis was performed in the allelic model and the dominant genetic model, respectively. Publication bias was assessed via funnel plot. The meta-analysis was performed using the software of RevMan 5.2. RESULTS: Data were obtained from 10 included studies, involving 5,069 cases and 6,673 controls. The overall odds ratios (ORs) with its 95% confidence interval (CI) showed no association between RETN-420 C>G polymorphism and obesity in the allelic model (p = 0.09; OR = 1.10; 95% CI = 0.991.24), the dominant model (p = 0.09; OR = 1.16; 95% CI = 0.98-1.36), and the recessive model (p = 0.71; OR = 1.02; 95% CI = 0.90-1.16). Sensitivity analysis showed statistical differences of association analysis within the allelic model (p = 0.04; OR = 1.14; 95% CI = 1.01-1.28) and the dominant genetic model (p = 0.04; OR = 1.21; 95% CI = 1.01-1.45), when 1 study was omitted. No publication bias was observed. CONCLUSIONS: The RETN-420 C>G polymorphism may be related to obesity with G allele as a risk factor.

A fast dynamic mode in rare earth based glasses.

Metallic glasses (MGs) usually exhibit only slow ß-relaxation peak, and the signature of the fast dynamic is challenging to be observed experimentally in MGs. We report a general and unusual fast dynamic mode in a series of rare earth based MGs manifested as a distinct fast ß'-relaxation peak in addition to slow ß-relaxation and α-relaxation peaks. We show that the activation energy of the fast ß'-relaxation is about 12RTg and is equivalent to the activation of localized flow event. The coupling of these dynamic processes as well as their relationship with glass transition and structural heterogeneity is discussed.