[Prognostic significance of textbook outcome in advanced gastric patients who underwent neoadjuvant chemotherapy followed by surgical resection].

Objective: To investigate the risk factors and prognostic value of the textbook outcome (TO) in patients with advanced gastric cancer (AGC) who underwent neoadjuvant chemotherapy followed by surgical resection. Methods: This is a retrospective cohort study. A total of 253 patients with AGC who underwent neoadjuvant chemotherapy combined with gastrectomy and D2 lymphadenectomy in the Department of Gastric Surgery, Fujian Medical University Union Hospital from January 2010 to December 2019 were retrospectively included. There were 195 males and 58 females, aged (60.3±10.0) years (range: 27 to 75 years). The patients were then divided into the TO group (n=168) and the non-TO group (n=85). Multivariate Logistic regression was used to analyze the independent predictors of TO. Univariate and multivariate Cox analysis were used to analyze independent prognosis factors for overall survival (OS) and disease-free survival (DFS). Propensity score matching was performed to balance the TO and non-TO groups, and the Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results: Among the 253 patients, 168 patients (66.4%) achieved TO. The Eastern Cooperative Oncology Group score (OR=0.488, 95%CI: 0.278 to 0.856, P=0.012) and ypN stage (OR=0.626, 95%CI:0.488 to 0.805, P<0.01) were independently predictive of TO. Multivariate analysis revealed that TO was an independent risk factor for both OS (HR=0.662, 95%CI: 0.457 to 0.959,P=0.029) and DFS (HR=0.687, 95%CI: 0.483 to 0.976, P=0.036). After matching, the 5-year OS rate (42.2% vs. 27.8%) and the 5-year DFS rate (37.5% vs. 27.8%) were significantly higher in the TO group than in the non-TO group (both P<0.05). Furthermore, patients in the non-TO group benefited significantly from postoperative chemotherapy (both P<0.05), but those in the TO group did not (both P>0.05). Conclusion: TO is an independent prognosis factor in patients undergoing neoadjuvant chemotherapy and surgery for AGC and is associated with postoperative chemotherapy benefits.

[Establishment of a nomogram prediction model using common preoperative indicators for early weight loss after laparoscopic sleeve gastrectomy].

Objectives: To construct a nomogram prediction model using common preoperative indicators for early weight loss (EWL) 1 year after laparoscopic sleeve gastrectomy (LSG). Methods: Relevant data of obese patients who had undergone LSG from January 2015 to May 2022 in Fujian Medical University Union Hospital and Quanzhou First Hospital Affiliated Fujian Medical University were analyzed. Patients with a history of major abdominal surgery, severe gastroesophageal reflux disease, pregnancy within 1 year after surgery, or who were lost to follow-up were excluded, resulting in a total of 200 patients in the study (190 from Fujian Medical University Union Hospital and 10 from Quanzhou First Hospital Affiliated Fujian Medical University). The participants were 51 men and 149 women of a mean age 29.9±8.2 years and a body mass index (BMI) 38.7±6.5 kg/m2. All patients in this group underwent standardized LSG procedure. Achieving ideal weight (BMI≤25 kg/m2) 1 year after LSG was defined as goal of EWL. Logistic regression analyses were performed to identify factors that independently influenced EWL. These factors were incorporated into the nomogram model. Receiver operating characteristic (ROC) curves (the larger the area under the curve [AUC], the better the predictive ability and accuracy of the model), likelihood ratio test (higher likelihood ratio indicates greater model homogeneity), decision curve analysis (higher net benefit indicates a better model), Akaike information criterion (AIC; smaller AIC indicates a better model), and Bayesian information criterion (BIC; smaller BIC indicates a better model) were used to validate the predictive ability of the column line diagram model. Results: In this study of 200 obese patients who underwent LSG surgery, 136 achieved EWL goal, whereas the remaining 64 did not. The rate of EWL goal achievement of the entire group was 68.0%. Compared with patients who did not achieve EWL goal, those who did had lower BMI, alanine transaminase, aspartate transaminase, triglycerides, and higher cholesterol. Additionally, the proportion of female was higher and the proportions of patients with fatty liver and hypertension lower in those who achieved EWL goal (all P<0.05). Univariate and multivariate logistic regression analysis revealed that preoperative BMI (OR=0.852, 95%CI: 0.796-0.912, P<0.001), alanine transaminase (OR=0.992, 95%CI: 0.985-0.999, P=0.024), presence of fatty liver (OR=0.185, 95%CI: 0.038-0.887, P=0.035) and hypertension (OR=0.374, 95%CI: 0.144-0.969, P=0.043) were independently associated with failure to achieve EWL goal. Cholesterol (OR=1.428, 95%CI: 1.052-1.939, P=0.022) was independently associated with achieving EWL goal. We used the above variables to establish an EWL nomogram model. ROC analysis, the likelihood ratio test, decision curve analysis, and AIC all revealed that the predictive value of the model was better than that of BMI alone (nomogram model vs. BMI: area under the curve 0.840 vs. 0.798, P=0.047; likelihood ratio: 58.785 vs. 36.565, AIC: 193.066 vs. 207.063, BIC: 212.856 vs. 213.660). Conclusion: Our predictive model is more accurate in predicting EWL after LSG compared with using BMI.

Tp47-Induced Monocyte-Derived Microvesicles Promote the Adherence of THP-1 Cells to Human Umbilical Vein Endothelial Cells via an ERK1/2-NF-κB Signaling Cascade.

The Treponema pallidum membrane protein Tp47 induces immunocyte adherence to vascular cells and contributes to vascular inflammation. However, it is unclear whether microvesicles are functional inflammatory mediators between vascular cells and immunocytes. Microvesicles that were isolated from Tp47-treated THP-1 cells using differential centrifugation were subjected to adherence assays to determine the adhesion-promoting effect on human umbilical vein endothelial cells (HUVECs). Intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) levels in Tp47-induced microvesicle (Tp47-microvesicle)-treated HUVECs were measured, and the related intracellular signaling pathways of Tp47-microvesicle-induced monocyte adhesion were investigated. Tp47-microvesicles promoted THP-1 cell adhesion to HUVECs (P < 0.01) and upregulated ICAM-1 and VCAM-1 expression in HUVECs (P < 0.001). The adhesion of THP-1 cells to HUVECs was inhibited by anti-ICAM-1 and anti-VCAM-1 neutralizing antibodies. Tp47-microvesicle treatment of HUVECs activated the extracellular signal-regulated kinase 1/2 (ERK1/2) and NF-κB signaling pathways, whereas ERK1/2 and NF-κB inhibition suppressed the expression of ICAM-1 and VCAM-1 and significantly decreased the adhesion of THP-1 cells to HUVECs. IMPORTANCE Tp47-microvesicles promote the adhesion of THP-1 cells to HUVECs through the upregulation of ICAM-1 and VCAM-1 expression, which is mediated by the activation of the ERK1/2 and NF-κB pathways. These findings provide insight into the pathophysiology of syphilitic vascular inflammation.

Recombinant Treponema pallidum protein Tp47 promoted the phagocytosis of macrophages by activating NLRP3 inflammasome induced by PKM2-dependent glycolysis.

BACKGROUND: Glycolysis is a critical pathway in cellular glucose metabolism that provides energy and participates in immune responses. However, whether glycolysis is involved in NOD-like receptor family protein 3 (NLRP3) inflammasome activation and phagocytosis of macrophages in response to Treponema pallidum infection remains unclear. OBJECTIVES: To investigate the role of glycolysis in activating the NLRP3 inflammasome for regulating phagocytosis in macrophages in response to T. pallidum protein Tp47 and its associated mechanisms. METHODS: Interactions between activation of the NLRP3 inflammasome and phagocytosis and the role of glycolysis in Tp47-treated macrophages were investigated through experiments on peritoneal macrophages and human monocytic cell line-derived macrophages. RESULTS: Activation of phagocytosis and NLRP3 inflammasome were observed in Tp47-treated macrophages. Treatment with NLRP3 inhibitor MCC950 or si-NLRP3 attenuated Tp47-induced phagocytosis. Glycolysis and glycolytic capacity were enhanced by Tp47 stimulation in macrophages, and a change in the levels of glycolytic metabolites (phosphoenolpyruvate, citrate and lactate) was induced by Tp47 in macrophages. Inhibition of glycolysis with 2-deoxy-D-glucose, a glycolysis inhibitor, decreased the activation of NLRP3. Expression of M2 isoform of pyruvate kinase (PKM2), an enzyme catalysing a rate-limiting reaction in the glycolytic pathway, was upregulated in Tp47-stimulated macrophages. Inhibition of PKM2 with shikonin or si-PKM2 decreased glycolysis and NLRP3 activation. CONCLUSION: Tp47 promotes phagocytosis in macrophages by activating the NLRP3 inflammasome, which is induced by the enhancement of PKM2-dependent glycolysis.

[Effect of splenic hilar lymphadenectomy on locally advanced Siewert type â ¡ and â ¢ adenocarcinoma of esophagogastric junction with a tumor diameter ≥4 cm: a five-year survival analysis].

Objective: To examine the long term outcome of splenic hilar lymphadenectomy (SHL) for locally advanced Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG) with a tumor diameter ≥4 cm. Methods: A total of 489 locally advanced Siewert type Ⅱ and Ⅲ AEG patients with a tumor diameter ≥4 cm who underwent radical resection from January 2010 to April 2016 were included. There were 383 males and 106 females. There were 225 patients aged≥65 years and 264 patients aged <65 years. SHL was conducted in 270 patients(SHL group). Wilcoxon rank-sum test or χ2 test were conducted for inter-group comparison. Cox proportional hazard regression was used to analyze the long term outcome of SHL and the prognosis factors of overall survival. Kaplan-Meier curve was drawn finally. The results of survival analysis were verified by Log-rank test. Results: Followed-up to April 2021,the median follow-up time was 78.0 months (range: 74.0 to 85.0 months), the follow-up rate was 95.5%(467/489). The splenic hilar lymphnode metastasis rate of the SHL group was 12.6% (34/270). Younger patients (<65 years old), less complications, higher proportion of patients received adjuvant chemotherapy were demonstrated in the SHL group (χ2: 5.644 to 6.744, all P<0.05). Multivariate analysis showed that SHL was the independent prognosis factor of overall survival for patients with Siewert type Ⅱ and Ⅲ AEG and a tumor diameter≥4 cm (HR=0.68, 95%CI: 0.52 to 0.88, P=0.004) along with preoperative CA19-9, pathological T stage, pathological N stage, adjuvant chemotherapy and postoperative complication. Further subgroup analysis demonstrated that the SHL group had better 5-year overall survival than non-SHL group (62.4% vs. 39.2%, χ2=17.983, P=0.006) in Siewert type Ⅲ AEG rather than in Siewert type Ⅱ AEG(57.3% vs. 53.7%, χ2=3.031, P=0.805). Conclusion: In experienced center, splenic hilar lymphadenectomy can improve the prognosis of Siewert type Ⅲ AEG with a tumor diameter ≥4 cm.

[Establishment of artificial neural network model for predicting lymph node metastasis in patients with stage â ¡-â ¢ gastric cancer].

Objective: To establish a neural network model for predicting lymph node metastasis in patients with stage II-III gastric cancer. Methods: Case inclusion criteria: (1) gastric adenocarcinoma diagnosed by pathology as stage II-III (the 8th edition of AJCC staging); (2) no distant metastasis of liver, lung and abdominal cavity in preoperative chest film, abdominal ultrasound and upper abdominal CT; (3) undergoing R0 resection. Case exclusion criteria: (1) receiving preoperative neoadjuvant chemotherapy or radiotherapy; (2) incomplete clinical data; (3) gastric stump cancer.Clinicopathological data of 1231 patients with stage II-III gastric cancer who underwent radical surgery at the Fujian Medical University Union Hospital from January 2010 to August 2014 were retrospectively analyzed. A total of 1035 patients with lymph node metastasis were confirmed after operation, and 196 patients had no lymph node metastasis. According to the postoperative pathologic staging. 416 patients (33.8%) were stage Ⅱ and 815 patients (66.2%) were stage III. Patients were randomly divided into training group (861/1231, 69.9%) and validation group (370/1231, 30.1%) to establish an artificial neural network model (N+-ANN) for the prediction of lymph node metastasis. Firstly, the Logistic univariate analysis method was used to retrospectively analyze the case samples of the training group, screen the variables affecting lymph node metastasis, determine the variable items of the input point of the artificial neural network, and then the multi-layer perceptron (MLP) to train N+-ANN. The input layer of N+-ANN was composed of the variables screened by Logistic univariate analysis. Artificial intelligence analyzed the status of lymph node metastasis according to the input data and compared it with the real value. The accuracy of the model was evaluated by drawing the receiver operating characteristic (ROC) curve and obtaining the area under the curve (AUC). The ability of N+-ANN was evaluated by sensitivity, specificity, positive predictive values, negative predictive values, and AUC values. Results: There were no significant differences in baseline data between the training group and validation group (all P>0.05). Univariate analysis of the training group showed that preoperative platelet to lymphocyte ratio (PLR), preoperative systemic immune inflammation index (SII), tumor size, clinical N (cN) stage were closely related to postoperative lymph node metastasis. The N+-ANN was constructed based on the above variables as the input layer variables. In the training group, the accuracy of N+-ANN for predicting postoperative lymph node metastasis was 88.4% (761/861), the sensitivity was 98.9% (717/725), the specificity was 32.4% (44/136), the positive predictive value was 88.6% (717/809), the negative predictive value was 84.6% (44/52), and the AUC value was 0.748 (95%CI: 0.717-0.776). In the validation group, N+-ANN had a prediction accuracy of 88.4% (327/370) with a sensitivity of 99.7% (309/310), specificity of 30.0% (18/60), positive predictive value of 88.0% (309/351), negative predictive value of 94.7% (18/19), and an AUC of 0.717 (95%CI:0.668-0.763). According to the individualized lymph node metastasis probability output by N+-ANN, the cut-off values of 0-50%, >50%-75%, >75%-90% and >90%-100% were applied and patients were divided into N0 group, N1 group, N2 group and N3 group. The overall prediction accuracy of N+-ANN for pN staging in the training group and the validation group was 53.7% and 54.1% respectively, while the overall prediction accuracy of cN staging for pN staging in the training group and the validation group was 30.1% and 33.2% respectively, indicating that N+-ANN had a better prediction than cN stage. Conclusions: The N+-ANN constructed in this study can accurately predict postoperative lymph node metastasis in patients with stage Ⅱ-Ⅲ gastric cancer. The N+-ANN based on individualized lymph node metastasis probability has better accurate prediction for pN staging as compared to cN staging.

[Analysis of characteristics and trends of randomized controlled trials of gastric cancer between 2000 and 2019].

Objectives: To analyze the current development status of gastric cancer (GC) randomized controlled trials (RCT) between 2000 and 2019, and to review the basic characteristics of published RCT. Methods: ClinicalTrials.gov was searched for phase 3 or 4 RCT conducted between January 2000 and December 2019 with the keyword "gastric cancer", and the development trend of different types of RCT during different time periods was described. Basic features of registered RCT such as intervention, study area, single-center or multicenter, sample size, and funding were presented. PubMed and Scopus databases were searched to judge the publication status of studies completed until June 2016. The adequacy of the report was estimated by the Consolidated Standards of Reporting Trials (CONSORT) checklist. Design flaws were evaluated by Cochrane tool and/or whether a systematic literature review was cited. The data was analyzed by χ2 test or Fisher exact test. Results: There were 262 RCT including in the present study. The number of GC-RCT registered on ClinicalTrials.gov had been on the rise from 1 case in 2000 to 30 cases in 2015. The proportion of RCT associated with targeted therapy or immunotherapy increased from 0 during 2000-2004 to 37.1% (36/97) during 2015-2019. The RCT registered in Asia was 191 cases, while that in non-Asia region was 71 cases. The proportion of multi-center RCT from non-Asia was higher than that from Asia (70.4% (50/71) vs. 50.3% (96/191), χ²=8.527, P=0.003). The proportion of RCT published was 59.1% (81/137). Among the published RCT, 65 (80.2%) studies were reported adequately, but 63 (77.8%) studies had avoidable design limitations. Conclusions: Targeted therapy and immunotherapy have become research hotspots in the treatment of GC. At present, there are inadequate multicenter RCT in Asia, and the publication rate of RCT is low. A considerable number of published RCT are reported inadequately and have avoidable design flaws.

[Analysis of characteristics and trends of randomized controlled trials of gastric cancer between 2000 and 2019].

Objectives: To analyze the current development status of gastric cancer (GC) randomized controlled trials (RCT) between 2000 and 2019, and to review the basic characteristics of published RCT. Methods: ClinicalTrials.gov was searched for phase 3 or 4 RCT conducted between January 2000 and December 2019 with the keyword "gastric cancer", and the development trend of different types of RCT during different time periods was described. Basic features of registered RCT such as intervention, study area, single-center or multicenter, sample size, and funding were presented. PubMed and Scopus databases were searched to judge the publication status of studies completed until June 2016. The adequacy of the report was estimated by the Consolidated Standards of Reporting Trials (CONSORT) checklist. Design flaws were evaluated by Cochrane tool and/or whether a systematic literature review was cited. The data was analyzed by χ2 test or Fisher exact test. Results: There were 262 RCT including in the present study. The number of GC-RCT registered on ClinicalTrials.gov had been on the rise from 1 case in 2000 to 30 cases in 2015. The proportion of RCT associated with targeted therapy or immunotherapy increased from 0 during 2000-2004 to 37.1% (36/97) during2015-2019. The RCT registered in Asia was 191 cases, while that in non-Asia region was 71 cases. The proportion of multi-center RCT from non-Asia was higher than that from Asia (70.4% (50/71) vs. 50.3% (96/191), χ²=8.527, P=0.003). The proportion of RCT published was 59.1% (81/137). Among the published RCT, 65 (80.2%) studies were reported adequately, but 63 (77.8%) studies had avoidable design limitations. Conclusions: Targeted therapy and immunotherapy have become research hotspots in the treatment of GC. At present, there are inadequate multicenter RCT in Asia, and the publication rate of RCT is low. A considerable number of published RCT are reported inadequately and have avoidable design flaws.

Alpha defensin-1 attenuates surgically induced osteoarthritis in association with promoting M1 to M2 macrophage polarization.

OBJECTIVE: Macrophages play an important part in the pathogenesis of osteoarthritis (OA). Our objective was to determine the effects of α-defensin-1 on macrophage polarization and consequently OA. METHODS: OA synovial tissue and synovial fluid were assessed for the presence of M1 (CD68+CD16+CD206-) and M2 (CD68+CD206+CD16-) macrophages by flow cytometry. M0, M1, and M2 macrophages were co-cultured with OA chondrocytes to determine their influence on chondrogenic phenotype. Polarization of THP-1 activated monocytes from M1 to M2 in response to α-defensin-1 was evaluated by flow cytometry, RT-PCR and RNA sequencing. Effects of intra-articular α-defensin-1 in vivo were evaluated in a rat meniscal/ligamentous injury (MLI) model. RESULTS: The quantity of M1 exceeded M2 polarized macrophages in human OA synovial tissue (mean difference 26.1% [13.6-38.6%], P < 0.001) and fluid (mean difference 10.5% [5.0-16.1%], P = 0.003). M1 to M2 polarization in vitro was most effectively promoted with 10 ng/mL α-defensin-1. Compared with untreated macrophages, the α-defensin-1 polarized macrophages modified co-cultured OA chondrocytes from a pro-catabolic state to a pro-anabolic (regenerative-like) state based on expression of COL2A1, ACN, MMP3, MMP13 and ADAMTS5. Intra-articular α-defensin-1 decreased severity of cartilage damage and synovitis in the MLI rat model. RNAseq analyses suggested insulin and Toll-like receptor signaling pathways in the chondroprotective α-defensin-1 mechanism of action. CONCLUSION: α-defensin-1 promotes M1 to M2 macrophage polarization in vitro, has beneficial effects on chondrocytes indirectly via M2 macrophage polarization, and attenuates the severity of OA in vivo, suggesting it might be a candidate treatment for OA.

The correlation between tissue Doppler imaging and N-terminal pro-brain natriuretic peptide concentration during left ventricular diastolic function recovery after coronary artery bypass grafting.

OBJECTIVE: This study aims to evaluate the changes in left ventricular diastolic function after coronary artery bypass grafting through tissue Doppler imaging (TDI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration and the correlation between the two. PATIENTS AND METHODS: A total of 133 patients who underwent coronary artery bypass grafting between January 2016 and December 2018 were included in this study. Echocardiography and NT-proBNP concentration were reviewed pre-operation, 1 month post-operation, and 3-6 months post-operation. The transmitral peak flow velocity (E) of the mitral valve was measured at each of the three-time points using spectral Doppler imaging. The mitral annulus displacement (Ea peak and Aa peak) was then measured at each of the time points using TDI, and the E/Ea ratio was calculated. Subsequently, the correlation of the E value, Ea value, and E/Ea ratio with NT-proBNP concentration was statistically analyzed. RESULTS: The data obtained at the three-time points were compared with the respective concentrations of NT-proBNP. Multiple linear regression analysis revealed a correlation between NT-proBNP concentration and E value, Ea value, and E/Ea ratio. CONCLUSIONS: Left ventricular diastolic function gradually recovered at 1 month and 3-6 months after coronary artery bypass grafting. There was a correlation between TDI-related values and NT-proBNP concentration.

[Risk factors of allogeneic red blood transfusion following enhanced recovery hip and knee arthroplasty].

Objective: To Explore the current status and risk factors of perioperative allogenic red blood cell transfusion following enhanced recovery hip and knee joint arthroplasty. Methods: Patients who have taken their primary unilateral total hip and knee arthroplasty (THA, TKA) or simultaneous primary THA were retrospectively included from January, 2019 to December, 2019 in West China Hospital. The baseline characteristics were compared between patients with allogeneic transfusion and those without. And logistic regression were used to analyze the risk factors of perioperative allogeneic red blood cell transfusion. Results: A total of 2 034 patients (2072 arthroplasties) were included, 705 males and 1 329 females, aged (60±24) years. Of all, 1 137 patients received primary THA (38 simultaneous THA), 897 patients received primary unilateral TKA. Eleven (0.54%) patients received allogeneic red blood cell transfusion, and the mean volume was (2.6±1.2) U. Deep venous thrombosis occurred in 2 patients (0.09%) undergoing primary TKA. The transfusion rate in primary THA patients was 0.79% (9/1 137), and 0.22% (2/897) in TKA. Lower preoperative hemoglobin level (P=0.041) and more hematological comorbidities (P=0.005) were detected in transfused patients. And logistic analysis further revealed that preoperative substandard hemoglobin level was the most important risk factor for transfusion (OR=5.663, P=0.018). Conclusions: Under the intervention of enhanced recovery after surgery concept and modern blood management strategies, the transfusion requirement has been significantly reduced following primary joint arthroplasty. Pre-operative hemoglobin level should be an important threshold for perioperative blood management.

[Staging of occupational medicamentosa-like dermatitis due to trichloroethylene].

Objective: To explor staging of the general course of occupational medicamentosa-like dermatitis due to trichloroethylene (OMDT) to better understand the characteristics of OMDT course, and to provide reference for clinical diagnosis and treatment and related studies. Methods: We collected main clinical manifestation and auxiliary examination data during hospitalization to May 2019 from 35 OMDT patients with complete course record who were hospitalized from January 2014 to December 2018. Continuous monitoring indicators with changing trends including main clinical manifestation indicators, peripheral white blood cell counts, liver function indicators such as serum alanine aminotransferase activity, myocardial enzyme indicators such as serum lactate dehydrogenase activity were selected and used with their standardized values to do cluster analysis on time point (week as unit) of the course of each patient. The clustering results combined with changing trends of the indicators were used to determine the stages of course of each patient, and therefore the staging of general course of OMDT was calculated. Positive rates or average levels of the indicators were compared between different stages, and the correlation of duration of each stage was analyzed with physical characteristics, disease characteristics and treatment measures of the patients. Results: General course of OMDT could be divided into acute phase (3.0±1.5) weeks and chronic phase (11.0±4.4) weeks, while chronic phase could be further divided into early period (5.0±3.0) weeks and later period (6.5±3.7) weeks. Compared with chronic phase, clinical manifestation indicators, white blood cell counts (except eosinophil count) , liver function indicators (except total protein and albumin concentration) , and myocardial enzyme indicators were all increased (all P<0.01) , while total protein and albumin concentration decreased (P<0.05 and P<0.01, respectively) in acute phase. Compared with later period of the chronic phase, clinical manifestation indicators (except fever) , white blood cell counts (except lymphocyte count) , liver function indicators (except total protein and albumin concentration) , and creatine kinase isoenzyme activity were all increased (all P<0.01) , while total protein, albumin concentration and creatine kinase activity decreased (all P<0.01) . Duration of acute phase were positively correlated with the time before glucocorticoid treatment (r(spearman)=0.62, P(adjust)<0.01) , and early and later periods of chronic phase were both positively correlated with corresponding duration of glucocorticoid treatment (r(spearman)=0.96, P(adjust)<0.01, r(spearman)=0.91, P(adjust)<0.01, respectively) . Conclusion: For the first time, the study objectively determined stages of general course of OMDT based on combination of multiple indicators, and analyzed characteristics of main indicators in each phase and potential factors related to the duration of each phase.

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.

Investigating and analyzing three cohorts of mushroom poisoning caused by Amanita exitialis in Yunnan, China.

Amanita exitialis is a lethal mushroom found in China. Knowledge regarding taxonomic characterization, toxin detection, general poisoning conditions, clinical manifestations, laboratory examinations, and clinical treatments for this species is currently lacking. We investigated three A. exitialis mushroom poisoning cohorts in Yunnan Province in 2014 and 2015, involving 10 patients. Mushroom samples were identified by morphological and molecular studies. Ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry was used to detect the peptide toxins in the mushroom samples. Epidemiological information, clinical data, and results of laboratory examinations were collected and analyzed. The mushroom samples were all identified as A. exitialis. The average toxin concentration decreased from the cap to the stipe to the volva, and the average concentration of the peptide toxins decreased in the order of α-amanitin > phallacidin > ß-amanitin > γ-amanitin. The latency period between ingestion and the onset of symptoms was 13.9 ± 2.1 h, and the time from ingestion to hospitalization was 49.6 ± 8.5 h. The most common symptoms were nausea and vomiting (100%). Four patients died from fulminant hepatic failure. Laboratory examinations showed that the alanine transaminase, aspartate transaminase, prothrombin time, and activated partial thromboplastin time levels peaked on the third day post-ingestion. Total bilirubin and direct bilirubin values peaked on day 7. The death group and the survival group had a similar variation trend of serological indexes, but the death group had a greater change. A. exitialis is an extremely dangerous mushroom and there is a need to educate the public to avoid picking and eating wild mushrooms that have not been definitively identified.

Development of a nomogram for predicting the risk of anastomotic leakage after a gastrectomy for gastric cancer.

AIMS: To investigate the incidence of and factors associated with anastomotic leakage (AL) following gastrectomy for gastric cancer. METHODS: We retrospectively analyzed 3632 patients who underwent a laparoscopic gastrectomy or open gastrectomy for gastric cancer. A logistic regression model was used to identify the determinant variables, and a nomogram for AL was developed. RESULTS: A total of 3632 patients were included in the study, 50 of whom (1.4%) developed AL. Postoperative deaths occurred in 6 (0.2%) patients with AL failure to rescue. Esophagojejunal AL (27/50) and Billroth I AL (20/50) were the most common types of AL. Gastrografin swallow was the main diagnostic method. The diagnosis was made a median of 9 days postoperatively. The median healing time for AL was 34.5 days. Of the 50 AL patients, 56% of patients could be managed nonsurgically, whereas 28% of patients required percutaneous radiologic drainage, 6% of patients were treated by endoscopy, and 10% of patients required a second surgery. A multivariate analysis showed the following adverse risk factors for AL: age ≥65 years, hemoglobin ≤8.0 g/dL and malnourishment. A multivariable model for AL showed a strong optimism-adjusted discrimination (concordance index, 0.675). The 5-year overall survival rates for patients without or with AL were 59.4% and 67.4%, respectively (p = 0.354). CONCLUSIONS: AL was infrequent but was more prevalent in patients with age ≥65 years, hemoglobin ≤8.0 g/dL and malnourishment. We created a novel nomogram that can provide individualized prediction of AL in patients after a gastrectomy for gastric cancer, which may help clinicians in making treatment decisions.

[Surgical outcomes after laparoscopy-assisted distal gastrectomy and open distal gastrectomy for patients with advanced gastric cancer: a case-control study using a propensity score method].

Objective: To investigate the surgical outcomes after the laparoscopy-assisted distal gastrectomy (LADG) for patients with advanced gastric cancer. Methods: The data of 213 patients who underwent LADG and 213 treated by open distal gastrectomy (ODG) were selected using the propensity score matching method from a prospectively constructed database of 641 patients who underwent radical distal gastrectomy between January 2005 and June 2012 in Department of Gastric Surgery, Fujian Medical University Union Hospital. The baseline characteristics and surgical outcomes were compared using a paired t-test or the Wilcoxon signed ranks test for continuous variables. The cumulative survival rates were compared using the Kaplan-Meier method and log-rank test. Results: Among all patients, there were significant differences in tumor location, digestive tract reconstruction, histologic type, pT stage, and pTNM stage between LADG and ODG group (P<0.05). After propensity score matching, patient distributions were closely balanced. There was no significant difference in clinicopathologic characteristics between the two groups (P>0.05). Regarding perioperative characteristics, the time to first flatus, and time to resumption of diet, did not differ between the two groups (P>0.05), while there were significant differences in the operation time (t=-11.28, P=0.000), blood loss (t=-5.674, P=0.000), number of dissected lymph nodes (t=4.727, P=0.000), and post-operative hospital stay (t=-2.193, P=0.038). LADG group has less morbidity than ODG group (χ2=4.777, P=0.029). Multivariate analysis revealed that the laparoscopic surgery (RR=0.392, P=0.009) was the protected factor for determining postoperative complications. There was no significant difference in the cumulative survival rate at total and each UICC stage between the two groups, either (P>0.05). Conclusion: LADG is an oncological safe minimally invasive procedure for advanced gastric cancer yields comparable oncological outcomes with ODG.

Evaluation of clinicopathological factors related to the prognosis of gastric neuroendocrine carcinoma.

BACKGROUND: Research on the clinicopathology and prognosis of gastric neuroendocrine carcinoma (GNEC) is rare, and a uniform standard for treatment has not been established. Therefore, we retrospectively analyzed the clinical data of 132 cases of GNEC to investigate the factors influencing prognosis. METHODS: A total of 132 patients diagnosed with GNEC at Fujian Medical University Union Hospital from January 2006 to December 2013 were enrolled. This study was performed to analyze the factors related to patient prognosis. RESULTS: In total, 58 men and 74 women whose ages ranged from 38 to 83 years old (62 ± 10) were enrolled. The 1- and 3-year survival rates for these patients were 83.9% and 47.6%, respectively. Of these patients, 100 underwent radical resection, 22 underwent palliative resection, and 10 received chemotherapy alone. The median survival times following radical resection, palliative resection and chemotherapy alone were 48, 20 and 12 months, respectively (P < 0.01). Univariate and multivariate survival analyses of patients who underwent radical resection showed that tumor size, N stage, Ki-67 labeling index, mitotic index and the application of postoperative adjuvant chemotherapy were independent factors affecting patient prognosis. The correlation analysis of the Ki-67 labeling index and mitotic index with prognosis showed that patient survival decreased significantly when the Ki-67 labeling index increased (P < 0.05). CONCLUSIONS: Patients who underwent radical resection had the best prognosis among GNEC. For these patients, tumor size, N stage, Ki-67 labeling index, mitotic index and the application of postoperative adjuvant chemotherapy were the clinicopathological factors significantly associated with patient prognosis.

[Transplantation of adipose derived mesenchymal stem cells alleviated osteoarthritis induced with anterior cruciate ligament transection].

OBJECTIVE: To explore the therapeutic potential of transplantation of adipose derived mesenchymal stem cells (ADMSCs) in rats osteoarthritis caused by anterior cruciate ligament transection. METHODS: Rats peritoneal adipose tissues were used to extract ADMSCs.Cell morphological appearance was documented and flow cytometric cell cycle was used to identify ADMSCs. Anterior cruciate ligament transection was used to induce knee osteoarthritis in rats. ADMSCs were injected into the knee cavities. Knee joint pathology was performed to observe the treatment effects. QRT-PCR and Western blot were used to identify the targets of ADMSCs. RESULTS: ADMSCs were successfully extracted, separated, cultured and identified. Two and eight weeks after ADMSCs transplantation, pathology showed significantly attenuation of arthritis including osteophyte and synovitis, reflecting in significantly improvement of both osteophyte and synovitis grading compared to the controls. QRT-PCR and Western blot revealed that collagen Ⅱ expression was significantly up-regulated after ADMSCs transplantation compared to the controls.MMP-13, but not other MMP-1, MMP-3 or MMP-9 was reduced when ADMSCs were co-cultured with primary chondrocytes. DDR-2 expression in chondrocyte was heavily up-regulated when stimulated by TNF-α in vitro. However, ADMSCs could reverse the effect when co-cultured with chondrocyte, implying that ADMSCs may suppress the expression of DDR-2. IL-1ß suppressed the cartilage differentiation of ADMSCs, and Actinomycin D (DDR-2 inhibitor) could reverse the effect. CONCLUSION: ADMSCs can attenuate osteoarthritis induced by anterior cruciate ligament transection in rats by suppressing the expression of MMP-13, and the upstream target spot may be DDR-2.