The efficacy of neoadjuvant chemotherapy is different for type 4 and large type 3 gastric cancer.

BACKGROUND: In the JCOG0501 study, neoadjuvant chemotherapy (NAC) failed to demonstrate survival benefits for type 4 and large type 3 gastric cancer (GC). The prognosis of these patients is still poor. We conducted this study to explore the value of NAC with non-SP regimens for type 4 and large type 3 â€‹GC in the Chinese population. METHODS: We retrospectively collected data from our electronic medical record system. Patients with large type 3 or type 4 â€‹GC who underwent D2 gastrectomy and AC were included. Patients were divided into two groups based on whether they received NAC: the CSC (NAC â€‹+ â€‹surgery â€‹+ â€‹AC) and SC (surgery â€‹+ â€‹AC) groups. The survival and perioperative outcomes for large type 3 or type 4 â€‹GC were analyzed between the CSC and SC groups, separately. RESULTS: Between May 2009 and December 2018, 189 patients were reviewed. Among large type 3 â€‹GC, the 5-year overall survival (OS) rates for patients in the CSC and SC groups were 54.4 â€‹% and 28.0 â€‹%, respectively (P â€‹= â€‹0.0008). Among type 4 â€‹GC, the 5-year OS rates for patients in the CSC and SC groups were 15.8 â€‹% and 24.8 â€‹%, respectively (P â€‹> â€‹0.05). CONCLUSIONS: This study showed NAC can improve the prognosis of large type 3 â€‹GC. However, NAC did not demonstrate significant survival advantages for type 4 â€‹GC.

Sintilimab combined neoadjuvant intraperitoneal and systemic chemotherapy in gastric cancer with peritoneal metastasis.

Intraperitoneal chemotherapy combined with systemic chemotherapy is one of the therapeutic modalities currently used for the treatment of gastric cancer patients with peritoneal metastasis. This study was designed to evaluate the efficacy and safety of sintilimab plus S-1 combined intraperitoneal and intravenous paclitaxel. This is an open-label, single-center, phase II study including 36 gastric adenocarcinoma patients with peritoneal metastases diagnosed by laparoscopy. All enrolled patients received sintilimab, intraperitoneal and intravenous paclitaxel plus oral S-1 every 3 weeks. Conversion operation should be considered when a patient responds to the regimen and the peritoneal metastasis disappears. After gastrectomy, the protocol treatment is repeated until disease progression, unacceptable toxicity, investigator decision or patient withdrawal. The primary end point is the 1-year survival rate. Clinical Trial Registration: NCT05204173 (ClinicalTrials.gov).

The association between GLIM criteria-defined malnutrition and 2-year unplanned hospital admission in outpatients with unintentional weight loss: A retrospective cohort study.

BACKGROUND: This study aimed to assess malnutrition using the Global Leadership Initiative on Malnutrition (GLIM) criteria and Subjective Global Assessment (SGA) at baseline and determine the GLIM criteria that best predicted unplanned hospitalization in outpatients with unintentional weight loss (UWL). METHODS: We performed a retrospective cohort study of 257 adult outpatients with UWL. The GLIM criteria and SGA agreement were reported using the Cohen kappa coefficient. Kaplan-Meier survival curves and adjusted Cox regression analyses were used for survival data. Logistic regression was used for the other correlation analysis. RESULTS: This study collected data from 257 patients for 2 years. Based on the GLIM criteria and SGA, malnutrition prevalence was 79.0% and 72.0%, respectively (κ = 0.728, P < 0.001). Using the SGA as a standard, GLIM had a sensitivity of 97.8%, a specificity of 69.4%, a positive predictive value of 89.2%, and a negative predictive value of 92.6%. Malnutrition was associated with higher rates of unplanned hospital admission independent of other prognostic factors (GLIM: hazard ratio [HR]=2.85, 95% CI=1.22-6.68; SGA: HR=2.07, 95% CI=1.13-3.79). Of the five GLIM criteria-related diagnostic combinations, disease burden or inflammation was the most important to predict unplanned hospital admission in multivariable analysis (HR=3.27, 95% CI=2.03-5.28). CONCLUSION: There was good agreement between the GLIM criteria and the SGA. GLIM-defined malnutrition, as well as all five GLIM criteria-related diagnosis combinations, had the potential to predict unplanned hospital admissions in outpatients with UWL within 2 years.

Organic Acid Accumulation and Associated Dynamic Changes in Enzyme Activity and Gene Expression during Fruit Development and Ripening of Common Loquat and Its Interspecific Hybrid.

Loquats have gained increasing attention from consumers and growers for their essential nutrients and unusual phenology, which could help plug a gap period at market in early spring. Fruit acid is a critical contributor to fruit quality. The dynamic changes in organic acid (OA) during fruit development and ripening of common loquat (Dawuxing, DWX) and its interspecific hybrid (Chunhua, CH) were compared, as well as the corresponding enzyme activity and gene expression. At harvest, titratable acid was significantly lower (p ≤ 0.01) in CH (0.11%) than in DWX loquats (0.35%). As the predominant OA compound, malic acid accounted for 77.55% and 48.59% of the total acid of DWX and CH loquats at harvest, followed by succinic acid and tartaric acid, respectively. PEPC and NAD-MDH are key enzymes that participate in malic acid metabolism in loquat. The OA differences in DWX loquat and its interspecific hybrid could be attributed to the coordinated regulation of multiple genes and enzymes associated with OA biosynthesis, degradation, and transport. The data obtained in this work will serve as a fundamental and important basis for future loquat breeding programs and even for improvements in loquat cultural practices.

Correlation of 3'-phosphoadenosine-5'-phosphosulfate synthase 1 (PAPSS1) expression with clinical parameters and prognosis in esophageal squamous cell carcinoma.

BACKGROUND: In recent years, 3'-phosphoadenosine-5'-phosphosulfate synthase 1 (PAPSS1) has been found to be highly expressed in some cancers and significantly associated with prognosis. Nevertheless, the role of PAPSS1 in esophageal squamous cell carcinoma (ESCC) is poorly understood. METHODS: In this study, PAPSS1 expression in ESCC samples was researched through real-time quantitative polymerase chain reaction (qPCR), immunohistochemistry (IHC), and western blot (WB) techniques. siRNA technology was then used to inhibit PAPSS1 expression in ESCC cells, and cytologic tests were conducted to research gene affection on cell apoptosis, proliferation, and migration. Then, the expression of Bcl2, Ki67, and Snail was detected using qPCR and WB tests. These experimental data were analyzed by GraphPad software, where the P-value<0.05 was statistically significant. RESULTS: The results showed that PAPSS1 expression level in ESCC tissues was higher than in the adjacent tissues. The data also showed that PAPSS1 was significantly correlated with N stage, and that the patients with high expressions had longer survival time. After transfection for 48 hours, the cell apoptosis rate of siRNA-PAPSS1 transfected groups decreased significantly, whereas the cell proliferation rate and migration ability increased relative to the control. At the same time, the expression levels of Bcl2, Ki67 and Snail were all upregulated by siRNA-PAPSS1. PAPSS1, however, was suppressed. CONCLUSIONS: PAPSS1 may be an ESCC suppressor gene, and its specific molecular mechanism in ESCC needs to be further studied.

Dynamic Changes in Cell Wall Polysaccharides during Fruit Development and Ripening of Two Contrasting Loquat Cultivars and Associated Molecular Mechanisms.

Loquats have drawn much attention due to their essential nutrients and unusual phenology, which fills a market gap in early spring. Fruit firmness (FF) is one of the most important quality attributes. Dynamic changes in FF, cell wall (CW) polysaccharides, CW hydrolase activity, and expression of CW metabolism-related genes during the fruit development and ripening stages of two contrasting loquat cultivars were compared. Although the two cultivars possessed similar FF at the initial fruitlet stage, Dawuxing was significantly firmer than Ninghaibai at all subsequent time points. FF was positively correlated with the contents of covalent-soluble pectin and hemicellulose, activity of peroxidase, and gene expressions of PME, EG, CAD6, and POD; and negatively correlated with the contents of water-soluble pectin, activities of polygalacturonase, endo-glucanase, cellobiohydrolase, and xylanase, and gene expressions of PG, EG2, PAL1, PAL3, and CAD5. Identifying molecular mechanisms underlying the differences in FF is useful for fundamental research and crop improvement in future.

[Regulation of Toll-like receptors and their downstream factors by butyrate].

Butyrate, normally produced by probiotics in the gut, not only provides energy for cells, but also changes the phosphorylation, acetylation and methylation levels of many proteins in cells. As a result, it affects the expression of many genes and the transmission of cell signals. Through G protein-coupled receptors, butyrate promotes the secretion of intestinal mucus and the formation of epithelial barriers, and attenuates the impacts of the pathogenic bacteria and their metabolites on human body. The Toll-like receptors (TLRs) are a group of pattern recognition receptors, and their activation causes the translocation of nuclear factor κB (NF-κB) from the cytoplasm to the nucleus and eventually leads to expression and secretion of various pro-inflammatory factors and chemokines. The expression of TLRs is also involved in the pathogenesis of some inflammatory diseases and tumors. The purpose of this review is to summarize the effects of butyrate on TLRs and their downstream signaling pathways. We not only summarized the production of butyrate, the expression of TLRs and the influence of their interaction on the body under the conditions of inflammation and tumor, but also discussed the potential role of butyrate as a bacterial metabolite in the treatments of some human diseases.

Immunometabolism in the tumor microenvironment and its related research progress.

The tumor immune microenvironment has been a research hot spot in recent years. The cytokines and metabolites in the microenvironment can promote the occurrence and development of tumor in various ways and help tumor cells get rid of the surveillance of the immune system and complete immune escape. Many studies have shown that the existence of tumor microenvironment is an important reason for the failure of immunotherapy. The impact of the tumor microenvironment on tumor is a systematic study. The current research on this aspect may be only the tip of the iceberg, and a relative lack of integrity, may be related to the heterogeneity of tumor. This review mainly discusses the current status of glucose metabolism and lipid metabolism in the tumor microenvironment, including the phenotype of glucose metabolism and lipid metabolism in the microenvironment; the effects of these metabolic methods and their metabolites on three important immune cells Impact: regulatory T cells (Tregs), tumor-associated macrophages (TAM), natural killer cells (NK cells); and the impact of metabolism in the targeted microenvironment on immunotherapy. At the end of this article,the potential relationship between Ferroptosis and the tumor microenvironment in recent years is also briefly described.

A potential biomarker of esophageal squamous cell carcinoma WTAP promotes the proliferation and migration of ESCC.

This study focuses on the function of WTAP in esophageal squamous cell carcinoma (ESCC) samples and cell lines. The results showed that WTAP expression in ESCC tissues was significantly upregulated in 78.1% (57 of 73) of the ESCC tissues at the protein level compared with adjacent non-cancerous tissues via immunohistochemical staining. The WTAP protein expression level was positively correlated with the lymph node metastasis and TNM stage, and patients with higher WTAP protein expression level exhibited a shorter overall survival interval. Knocking down WTAP significantly reduced cell proliferation and migration but promoted cell apoptosis of TE-1and KYSE150 cells. Moreover, WTAP inhibition reduced the expression of ki67 and Snail related to cell proliferation and migration but increased the expression of Bax and Caspase-3 which were involved in cell apoptosis. In conclusion, our results suggest that the WTAP, a potential biomarker of ESCC, maybe play an important role in ESCC-genesis through regulating expression of genes related to cell proliferation, migration and apoptosis.

Exogenous Ethylene Promotes Peel Color Transformation by Regulating the Degradation of Chlorophyll and Synthesis of Anthocyanin in Postharvest Mango Fruit.

Due to geographical location and climatic factors, postharvest storage and preservation of tropical fruits and vegetables are still facing huge challenges. Ethephon (ETH) is widely used as an ethylene donor to achieve the commercial color and flavor of climacteric fruits. However, the effect of ETH on fruit coloration was affected by many factors, such as fruit species, plant hormones, and storage conditions. In this study, the main mango variety "Guifei" in Hainan, China, was used to study the effects of different concentrations of ETH on fruit ripening and coloration during storage at 25°C. Results showed that postharvest treatment with ETH (300, 500, and 900 mg·L-1) enhanced the activities of ACS and ACO, stimulated the release of endogenous ethylene, and accelerated fruit softening and color transformation. Compared with control, ETH treatment not only accelerated the breakdown of chlorophyll with higher activities of Chlase and MDCase but also induced the synthesis of carotenoid and anthocyanin with higher activities of PAL, CHI, DFR, and UFGT. Moreover, the changes in DFR and UFGT activities coincided with the increase in ETH concentration. Further, correlation analysis showed that the production of endogenous ethylene induced by ETH was significantly negatively correlated with firmness and chlorophyll content, whereas positively correlated with MDA content and anthocyanin content. This study suggests that the positive effect of ETH on "Guifei" mango color transformation is concentration-dependent within a certain concentration range. Anthocyanin is the main pigment for the red formation of "Guifei" mango, and DFR and UFGT may play critical roles in anthocyanin synthesis. ETH promoted the red coloration by promoting the release of endogenous ethylene and enhancing the activities of anthocyanin synthesis enzymes.

A phase III trial of neoadjuvant intraperitoneal and systemic chemotherapy for gastric cancer with peritoneal metastasis.

Although recent advances in systemic chemotherapy have improved the clinical outcomes of gastric cancer patients with peritoneal metastasis, the peritoneum still represents a common site of treatment failure and disease recurrence. Neoadjuvant intraperitoneal-systemic chemotherapy has been acknowledged as a more aggressive treatment for gastric cancer patients with peritoneal metastasis. In this multicenter phase III randomized controlled trial, 238 patients will be randomly separated into two groups in a 2:1 ratio after laparoscopic exploration. The experimental arm will receive the proposed neoadjuvant intraperitoneal-systemic chemotherapy regimen, whereas the control group will receive a Paclitaxel + S-1 (PS) chemotherapy regimen. The endpoints for the study are overall survival, response rate, gastrectomy radicality rate, progression-free survival and adverse events.

Recent advances in technology have improved the outcomes of stomach cancer patients. However, there are still many patients who die of cancer that has spread from another part of the body. Neoadjuvant intraperitoneal­systemic chemotherapy has been acknowledged as a more aggressive treatment for stomach cancer patients with peritoneal metastasis (cancer that has spread to the very thin layer of tissue on the inside of the abdomen that covers the stomach and other organs). In this study, 238 patients will be randomly separated into two groups in a 2:1 ratio after evaluation. The experimental group will receive the proposed neoadjuvant intraperitoneal­systemic chemotherapy regimen, whereas the control group will receive a Paclitaxel + S-1 (PS) chemotherapy regimen. The endpoints for the study are how long patients live, number of patients who respond to treatment, number of patients who undergo surgery, how long patients live without their disease getting worse and problems caused by treatment. Trial registration number: ChiCTR-IIR-16009802.

Pre-hospital mild therapeutic hypothermia for patients with severe traumatic brain injury.

BACKGROUND: We aimed to assess the effects of pre-hospital mild therapeutic hypothermia (MTH) on patients with severe traumatic brain injury (sTBI). METHODS: Eighty-six patients with sTBI were prospectively enrolled into the pre-hospital MTH group and the late MTH group (initiated in hospital). Patients in the pre-hospital MTH group were maintained at a tympanic temperature of 33°C-35°C before admission and continued to be treated with a therapeutic hypothermia device for 4 days. Patients in the late MTH group were treated with the same MTH parameters. Intracranial pressure (ICP), complications and Glasgow Outcome Scale (GOS) scores were monitored. RESULTS: ICP was significantly lower for patients in the pre-hospital MTH group 24, 48, and 72 h after treatment (17.38 ± 4.88 mmHg, 18.40 ± 4.50 mmHg, and 16.40 ± 4.13 mmHg, respectively) than that in the late MTH group (20.63 ± 3.00 mmHg, 21.80 ± 6.00 mmHg, and 18.81 ± 4.50 mmHg) (P < .05). The favorable prognosis (GOS scores 4-5) rate in the pre-hospital MTH group was higher tha n the late MTH group (65.1% vs. 37.2%, respectively; P < .05) without complications . CONCLUSION: Pre-hospital MTH for patients with STBI can reduce ICP and improve neurological outcomes.

A phase II study of perioperative treatment in gastric cancer with No.16a2/b1 lymph node metastasis: DRAGON-06 trial.

Although gastric cancer with para-aortic lymph node (PAN) metastasis is commonly regarded as unresectable, surgeons have explored the optimal treatment for patients with PAN metastases limited to No.16a2/b1 in the past few decades. Preoperative systemic therapy combined with D2 gastrectomy plus PAN dissection may improve the prognosis of these patients. In this multicenter phase II trial, 29 gastric cancer patients with PAN metastasis limited to No.16a2/b1 will receive preoperative treatment with nab-paclitaxel, oxaliplatin, S-1 (nab-POS: nab-paclitaxel, oxaliplatin, S-1) and sintilimab followed by D2 gastrectomy plus PAN dissection; and postoperative treatment with oral S-1, intravenous sintilimab and intraperitoneal paclitaxel. The end points for the study are 3-year overall survival, 3-year disease-free survival, pathological response rate, incidence of postoperative complications and adverse events.

Stomach cancer with metastases in the para-aortic lymph nodes is usually considered inoperable. Chemotherapy combined with resection of the stomach and more extensive lymph node dissection may prolong the life of these patients. In this multicenter study, 29 stomach cancer patients with para-aortic lymph node metastases will receive preoperative treatment with nab-paclitaxel, oxaliplatin, S-1 and sintilimab, followed by resection of the stomach combined with para-aortic lymph node dissection and use of continued oral, intravenous and intraperitoneal chemotherapy. The study's end points are 3-year overall survival, 3-year disease-free survival, pathological response rate, incidence of postoperative complications and adverse events. Clinical Trial Registration: ChiCTR2200061125 (ChiCTR.org.cn).

Oxaliplatin plus S-1 with intraperitoneal paclitaxel for the treatment of Chinese advanced gastric cancer with peritoneal metastases.

BACKGROUND: In this study, we tried to access the efficacy and safety of oxaliplatin plus S-1 with intraperitoneal paclitaxel (PTX) for the treatment of Chinese advanced gastric cancer with peritoneal metastases. PATIENTS AND METHODS: Thirty patients diagnosed with advanced gastric cancer underwent laparoscopic exploration and were enrolled when macroscopic disseminated metastases (P1) were confirmed. PTX was diluted in 1 l of normal saline and IP administered through peritoneal port at an initial dose of 40 mg/m2 over 1 h on day1,8, respectively. Oxaliplatin was administered intravenously at an initial dose of 100 mg/m2 on day1, and S-1 was administered orally at an initial dose of 80 mg/m2 for 14 days followed by 7 days rest, repeated by every 3 weeks. RESULTS: Of all these 30 patients, the median number of cycles was 6 (range 2-16) due to the limitation of hematotoxicity and peripheral neuropathy by oxaliplatin. There were 11 (36.7%) patients received conversion surgery. The median progression free survival (PFS) was 6.6 months (95% CI = 4.7-8.5 months) and the median overall survival (OS) was 15.1 months (95% CI = 12.4-17.8 months). The grade 3-4 hematological toxicities were leucopenia (23.3%), neutropenia (23.3%), anemia (16.7%), and thrombocytopenia (20%), respectively. The grade 3-4 non-hematological toxicities were tolerated, most of which were peripheral sensory neuropathy (40%) due to oxaliplatin, diarrhea (20%), nausea and vomiting (26.7%). CONCLUSIONS: SOX+ip PTX regimen was effective in advanced gastric cancer with peritoneal metastasis. Survival time was significantly prolonged by conversion surgery. Grade 3-4 toxicities were uncommon. Large scale clinical trial is necessary to get more evidence to identify its efficacy. TRAIL REGISTRATION: ChiCTR, ChiCTR-IIR-16009802 . Registered 9 November 2016.

Neoadjuvant Chemotherapy Versus Direct Surgery for Locally Advanced Gastric Cancer With Serosal Invasion (cT4NxM0): A Propensity Score-Matched Analysis.

BACKGROUND: For locally advanced gastric cancer (LAGC) with serosal invasion (cT4NxM0), adjuvant chemotherapy (AC) after D2 gastrectomy is the standard therapy in Asia. However, perioperative chemotherapy (PCT) combined with D2 gastrectomy is mostly suggested in Europe and America. As a part of PCT, the value of neoadjuvant chemotherapy (NAC) is unclear. We investigated whether NAC could further improve survival and other outcomes for these patients. METHODS: Patients with cT4NxM0 gastric cancer who underwent D2 gastrectomy were analyzed. The patients were divided into two groups based on whether they received NAC: the neoadjuvant chemotherapy (NAC) and direct surgery (S) groups. After propensity score matching (1:1 ratio), survival and perioperative outcomes were analyzed between the two groups. RESULTS: A total of 902 patients met all the eligibility criteria and were enrolled. After propensity score matching, 221 matched pairs of patients were identified. The median overall survival (OS) and disease-free survival (DFS) of all patients were 75.10 and 43.67 months, respectively. The median OS of patients in the NAC and S groups were undefined and 29.80 months, respectively (P<0.0001). The median DFS of patients in the NAC and S groups were undefined and 22.60 months (P<0.0001). There were no significant differences in the radical degrees of operation between the two groups (P=0.07). However, there were significant differences in postoperative hospital stay (P<0.001) and complications (P=0.037) between the two groups. CONCLUSION: This study suggested NAC can further improve prognosis and prevent recurrence in LAGC (cT4NxM0) patients. NAC is feasible and safe for LAGC (cT4NxM0) patients, and does not increase the risk of perioperative surgery.

Is D2 Lymphadenectomy Alone Suitable for Gastric Cancer With Bulky N2 and/or Para-Aortic Lymph Node Metastases After Preoperative Chemotherapy?

BACKGROUND: For gastric cancer (GC) with extensive lymph node metastasis (bulky N2 and/or para-aortic lymph node metastases), there is no standard therapy worldwide. In Japan, preoperative chemotherapy (PCT) followed by D2 gastrectomy plus para-aortic lymph node dissection (PAND) is considered the standard treatment for these patients. However, in China, the standard operation for GC patients with only bulky N2 metastases was D2 gastrectomy. Besides, after PCT, whether doing PAND improves survival or not is debatable for GC patients with para-aortic lymph node (PAN) metastases. Therefore, we conducted this study to investigate whether D2 lymphadenectomy alone is suitable for these patients after PCT. METHODS: We retrospectively collected data on patients from our electronic medical record system. GC patients with bulky N2 and/or PAN metastases who underwent D2 lymphadenectomy alone after PCT were enrolled. The survival outcomes and chemotherapy responses were analyzed and compared with the results of the JCOG0405 study. RESULTS: From May 2009 to December 2017, a total of 83 patients met all eligibility criteria and were enrolled. The median survival duration for all patients was 40.0 months. The 3-year and 5-year OS rates for all patients were 50.3% and 45.6%, respectively. For patients with only bulky N2 metastasis, the 3-year and 5-year OS rates were 77.1% and 71.6%, respectively, which were similar to the results of the JCOG0405 study (82.7% and 73.4%). For patients with only PAN metastases, the 3-year and 5-year OS rates were 50.0% and 50.0%, respectively, which seemed to be lower than those of the JCOG0405 study (64.3% and 57.1%). For patients with bulky N2 and PAN metastases, the 3-year and 5-year OS rates were 7.4% and 0.0%, respectively, which were lower than those of the JCOG0405 study (20.0% and 20.0%). CONCLUSION: The results of our study suggest that D2 lymphadenectomy alone is suitable for GC patients with only bulky N2 metastasis after PCT. However, D2 lymphadenectomy alone perhaps is not suitable for patients with bulky N2 and PAN metastases after PCT.

Prediction Model of Tumor Regression Grade for Advanced Gastric Cancer After Preoperative Chemotherapy.

BACKGROUND: Preoperative chemotherapy (PCT) has been considered an important treatment for advanced gastric cancer (AGC). The tumor regression grade (TRG) system is an effective tool for the assessment of patient responses to PCT. Pathological complete response (TRG = 0) of the primary tumor is an excellent predictor of better prognosis. However, which patients could achieve pathological complete response (TRG = 0) after chemotherapy is still unknown. The study aimed to find predictors of TRG = 0 in AGC. METHODS: A total of 304 patients with advanced gastric cancer from July 2009 to November 2018 were enrolled retrospectively. All patients were randomly assigned (2:1) to training and internal validation groups. In addition, 124 AGC patients receiving PCT from December 2018 to June 2020 were included prospectively in the external validation cohort. A prediction model for TRG = 0 was established based on four predictors in the training group and was validated in the internal and external validation groups. RESULTS: Through univariate and multivariate analyses, we found that CA199, CA724, tumor differentiation and short axis of the largest regional lymph node (LNmax) were independent predictors of TRG = 0. Based on the four predictors, we established a prediction model for TRG = 0. The AUC values of the prediction model in the training, internal and external validation groups were 0.84, 0.73 and 0.82, respectively. CONCLUSIONS: We found that CA199, CA724, tumor differentiation and LNmax were associated with pathological response in advanced gastric cancer. The prediction model could provide guidance for clinical work.

A randomized controlled trial to evaluate omentum-preserving gastrectomy for patients with T1-T3 gastric cancer.

Although complete omentectomy is traditionally performed in patients with gastric cancer as part of radical gastrectomy to ensure the elimination of micrometastases, the prognostic value of omentectomy during gastrectomy remains unclear. Retrospective studies have shown that the incidence of metastases in the greater omentum is very low in T1-T3 gastric cancer. Thus radical gastrectomy with D2 lymphadenectomy and preservation of the greater omentum may be a proper curative treatment for gastric cancer patients with T1-T3 tumors. The aim of this article is to describe the design and rationale for this prospective, randomized controlled DRAGON-05 trial, conducted to evaluate the prognostic value of omentum-preserving gastrectomy for patients with T1-T3 gastric cancer. Clinical trial registration: ChiCTR2000040045 (ClinicalTrials.gov).

Prediction model of objective response after neoadjuvant chemotherapy in patients with locally advanced gastric cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) plays an important role in the therapeutic strategy of locally advanced gastric cancer (LAGC). However, the response of LAGC after NAC varies among different patients. The objective response after NAC has proven to be an excellent indicator for benefiting from NAC, yet effective predictors of objective response are still lacking. The present study aimed to identify potential predictors of objective response in LAGC patients treated with NAC. METHODS: Clinicopathological data from 267 patients with LAGC who received NAC and met the inclusion criteria between July 2009 and December 2018 were retrospectively reviewed. Patients were randomly divided into the training and test sets at a 2:1 ratio. Univariate analysis was used to investigate whether any factors were correlated with objective response in the training set. Multivariate logistic regression analysis was applied to find independent predictors. A risk score model was then constructed based on the independent predictors, and its performance in predicting objective response was validated in the test set. RESULTS: Univariate analysis found that gender, age, short axis diameter of the largest regional lymph node (LNmax), serum total protein content, CEA detection value, tumor location, tumor differentiation, signet ring cell carcinoma component and Borrmann type were potential predictors for objective response. In multivariate logistic regression analysis, gender, LNmax and signet ring cell carcinoma component were independent predictors for objective response. Based on independent predictors, we developed a prediction model for objective response. CONCLUSIONS: We found gender, LNmax and signet ring cell carcinoma component were independent predictors for objective response. The prediction model is a good tool to predict the objective response for LAGC patients treated with NAC, which can be applied to guide clinical practice.

[The regulation of Na+/H+ exchangers by Toll-like receptors under inflammation].

Toll-like receptors (TLRs) can be recognized and activated by different pathogen associated molecular patterns (PAMPs), which induce innate immune response and inflammation of the body. Na+/H+ exchangers (NHEs) not only play roles in the regulation of cellular pH and cell volume, maintenance of the cavity microenvironment and nutrients absorption, but also are related to cell proliferation, migration and apoptosis. The activity and membrane protein expression of NHEs are inhibited under the inflammation condition. It has been shown that the activation of TLR2 in colon epithelial cells can inhibit the activity of NHE1 through MyD88 independent pathway, which involves the recruitment of Src and the phosphorylation of PI3Ks. Other studies on intestinal macrophage showed long-term LPS stimulation can induce TLR4 activation through MyD88-dependent pathway (TLR4/MyD88/NF-κB) and induce inflammation and degeneration of intracellular NHE1, which leads to NHE1 activity inhibition. But short-term LPS exposure increases the activity and protein expression of NHE1. The activation of TLR5 increases the activity of NHE3. The activity and/or expression of NHE3 in intestinal macrophages in colitis patients and model animals were decreased. In renal tubular epithelial cells, basolateral LPS stimulation inhibits luminal NHE3 activation through TLR4/MyD88-dependent MAPK/ERK signaling pathway. And LPS stimulation on the lumen side activates TLR4/MyD88-dependent PI3K-AKT-mTOR signaling pathway, which results in the inhibition of NHE1 activity in basolateral side, and then affects the NHE3 function of the lumen side.