[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.

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.

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.

[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.

[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.

[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.

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.

Revealing ß-relaxation mechanism based on energy distribution of flow units in metallic glass.

The ß-relaxation, which is the source of the dynamics in glass state and has practical significance to relaxation and mechanical properties of glasses, has been an open question for decades. Here, we propose a flow unit perspective to explain the structural origin and evolution of ß-relaxation based on experimentally obtained energy distribution of flow units using stress relaxation method under isothermal and linear heating modes. Through the molecular dynamics simulations, we creatively design various artificial metallic glass systems and build a direct relation between ß-relaxation behavior and features of flow units. Our results demonstrate that the ß-relaxation in metallic glasses originates from flow units and is modulated by the energy distribution of flow units, and the density and distribution of flow units can effectively regulate the ß-relaxation behavior. The results provide a better understanding of the structural origin of ß-relaxation and also afford a method for designing metallic glasses with obvious ß-relaxation and better mechanical properties.

Lack of association between the hOGG1 gene Ser326Cys polymorphism and gastric cancer risk: evidence from a case-control study and a meta-analysis.

The association between the human 8-oxoguanine glycosylase 1 (hOGG1) gene Ser326Cys polymorphism (rs1052133) and gastric cancer has been widely evaluated, yet a definitive answer to whether this association exists is lacking. We first conducted a case-control study to assess this association in a large Han Chinese population, and then performed a meta-analysis to further address this issue. This case-control study involved 448 patients clinically diagnosed with gastric cancer and 372 cancer-free control individuals from China. Genotyping was conducted using the polymerase chain reaction-ligase detection reaction method. Meta-analysis was performed by the STATA software. Data and study quality were assessed in duplicate. Our case-control association study indicated that there were no significant differences in the genotype and allele distributions of the Ser326Cys polymorphism between gastric cancer patients and controls (P = 0.8026 for genotype, and P = 0.5857 for allele), consistent with the results of the subsequent meta-analysis involving 2745 patients and 4588 controls under both allelic [odds ratio (OR) = 1.02; 95% confidence interval (CI) = 0.91-1.14; P = 0.739] and dominant (OR = 0.97; 95%CI = 0.78-1.21; P = 0.803) models. Further subgroup analyses by ethnicity, source of controls, and sample size also did not detect any positive associations in this meta-analysis. Overall, our study in the Han Chinese population, along with the meta-analysis, failed to confirm the association of the hOGG1 gene Ser326Cys polymorphism with gastric cancer risk, even across different ethnic populations.

Compositional origin of unusual ß-relaxation properties in La-Ni-Al metallic glasses.

The ß-relaxation of metallic glasses (MGs) bears nontrivial connections to their microscopic and macroscopic properties. In an effort to elucidate the mechanism of the ß-relaxation, we studied by dynamical mechanical measurements the change of its properties on varying the composition of La60Ni15Al25 in various ways. The properties of the ß-relaxation turn out to be very sensitive to the composition. It is found that the isochronal loss peak temperature of ß-relaxation, Tß,peak, is effectively determined by the total (La + Ni) content. When Cu is added into the alloy to replace either La, Ni, or Al, the Tß,peak increases with decrease of the (La + Ni) content. The trend is in accordance with data of binary and ternary MGs formed from La, Ni, Al, and Cu. Binary La-Ni MGs have pronounced ß-relaxation loss peaks, well separated from the α-relaxation. In contrast, the ß-relaxation is not resolved in La-Al and La-Cu MGs, showing up as an excess wing. For the ternary La-Ni-Al MGs, increase of La or Ni content is crucial to lower the Tß,peak. Keeping the Al content fixed, increase of La content lowers the Tß,peak further, indicating the more important role La plays in lowering Tß,peak than Ni. The observed effects on changing the composition of La60Ni15Al25 lead to the conclusion that the properties of the ß-relaxation are mainly determined by the interaction between the largest solvent element, La, and the smallest element, Ni. From our data, it is further deduced that La and Ni have high mobility in the MGs, and this explains why the ß-relaxation in this La-based MGs is prominent and well resolved from the α-relaxation as opposed to Pd- and Zr-based MGs where the solvent and largest atoms, Pd and Zr, are the least mobile.

[Clinical significance of combined therapy with immune checkpoint inhibitor in perioperative treatment for locally advanced gastric cancer or adenocarcinoma of gastroesophageal junction].

The clinical application of immune checkpoint inhibitor (ICI) offers novel treatment modality for locally advanced gastric cancer (LAGC) and adenocarcinoma of the gastroesophageal junction (AGEJ), with the crucial benefit of providing higher cure rates. These agents have become part of standard treatments in the perioperative setting for selected cases, such as tumor with MSI-H/dMMR, high expression of CPS (≥5) or EBV (+), MSI-H and MSS/TP53+ according to tumor immunohistochemical, genetic testing or molecular characterization. An in-depth understanding of the immune response mechanisms in "cold" and "hot" tumors enables us to better identify ICI beneficiary and further provide a rationale for converting nonresponsive "cold" tumors into responsive "hot" tumors, subsequently allowing nonresponders to benefit from ICI immunotherapy. Several recent clinical trials clearly demonstrated a synergistic and complementary effect of combining ICI with chemotherapy or chemoradiotherapy, as well as combining ICI with anti-HER2 or anti-VEGF/VEGFR and chemotherapy. Compared with chemotherapy alone, the combination treatment can significantly improve pCR, MRR or ypT0N0, and is expected to improve the prognosis. This article reviews the results of a series of clinical trials in recent years in the field of perioperative application of ICI with other modalities in LAGC/AGEJ, aiming at expanding upon the discussion of current standard neoadjuvant and adjuvant therapies for LAGC/AGEJ and exploring the feasibility of new perioperative combined immunotherapy in the future.

[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.

Effects of alfalfa meal on growth performance and gastrointestinal tract development of growing ducks.

A study was conducted to evaluate effects of alfalfa meal on growth performance and gastrointestinal tract development of growing layer ducks to provide evidence for application of alfalfa meal in the duck industry. Two hundred and fifty-six healthy Shaoxing 7-wk old growing layer ducks were selected and randomly allocated to 1 of 4 dietary treatments based on corn and soybean meal and containing 0, 3, 6, and 9% of alfalfa meal for 8 wks. Each treatment consisted of 4 replicates of 16 ducks each. Briefly, birds were raised in separate compartments, and each compartment consisted of three parts: indoor floor house, adjacent open area and a connecting water area. The results showed: i) Growing ducks fed alfalfa meal diet were not significantly different in average daily gain, feed intake and gain-to-feed ratio from those fed no alfalfa diet (p>0.05). ii) Alfalfa meal increased the ratio crop, gizzard to live weight, caecum to live weight, the caecum index of growing ducks (p<0.05). iii) Villus height in duodenum and jejunum of growing ducks increased significantly with the increase of alfalfa meal levels (p<0.05). Crypt depth in duodenum and jejunum of growing ducks decreased significantly with the increase of alfalfa meal levels (p<0.05). This experiment showed that feeding of alfalfa meal to growing layer ducks could improve gastrointestinal tract growth and small intestinal morphology without effect on performance. This experiment provides evidence that alfalfa meal is a very valuable feedstuff for growing layer ducks.

CC chemokine ligand 21 enhances the immunogenicity of the breast cancer cell line MCF-7 upon assistance of TLR2.

CC chemokine ligand 21 (CCL21) is a known attractant for CCR7-positive (CCR7+) cells, but its additional role in the immunogenicity of CCR7+ cells remains poorly understood. This study explored the effects of CCL21-CCR7 ligation on cancer immunogenicity and related antitumor immune response, in the presence and absence of mitomycin C (MMC) treatment. CCL21-CCR7 binding upregulated human leukocyte antigen class I-restricted tumor antigen presentation with increased expression of human leukocyte antigen class I and transporter associated with antigen processing-1. In addition, CCL21 restrained the tumor-derived immunosuppressive factors FasL and transforming growth factor-ß. Consequently, CCL21 facilitated cancer-educated lymphocytes reaction in vitro. In the tumor-bearing mouse, CCL21 inhibited tumor growth and prolonged mouse survival via lymphocytes, especially in CCR7+ cancer cells. Furthermore, Toll-like receptor 2 activation of lymphocytes assisted the tumor-suppression functions of CCL21, in vitro and in vivo. This study implies that CCL21 improved the immunogenicity of the CCR7+ breast cancer cell line even with MMC treatment and triggered antitumor response by lymphocytes. These findings provide a new insight into the research and application of CCL21-associated antitumor response.

[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.

[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.

Size of the largest lymph node visualized on multi-detector-row computed tomography (MDCT) is useful in predicting metastatic lymph node status of gastric cancer.

This study was designed to investigate whether the size of the largest lymph node (long-axis diameter [LAD] and short-axis diameter [SAD]) visualized using multi-detector-row computed tomography (MDCT) was useful for predicting the metastatic lymph node (MLN) status of gastric cancer. A retrospective analysis of 305 gastric cancer patients who underwent pre-operative MDCT was performed, followed by a prospective study in 61 gastric cancer patients to determine the diagnostic effectiveness of LAD and SAD. In the retrospective study, the accuracy of LAD and SAD for predicting the MLN status of gastric cancer was 51.1% and 45.9%, respectively. In the prospective study, the accuracy of LAD and SAD measurement and the traditional MDCT method of counting MLNs was 52.5%, 49.2% and 57.4%, respectively; the differences were not significant. In conclusion, the size of the largest lymph node in terms of LAD and SAD visualized on MDCT was useful for predicting the MLN status of gastric cancer, with accuracy comparable to the traditional MDCT method of counting the total number of MLNs detected.

[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.

[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.