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PURPOSE The optimal surgical procedure, whether total gastrectomy (TG) or proximal gastrectomy (PG), for Siewert type II/III adenocarcinoma of esophagogastric junction (AEG) has not been standardised, primarily because the optimal extent of lymph node (LN) dissection for AEG based on the metastatic rate of perigastric LNs remains under debate. The aim of this study was to investigate the metastatic incidence and prognostic significance of lower perigastric lymph nodes (LPLN), including No.4d, 5, 6 and 12a LN stations, in Siewert type II/III AEG. METHODS A total of 701 patients with Siewert type II/III AEG who received transabdominal open gastrectomy (425 patients with TG and 276 patients with PG) from 2010 to 2015 in West China Hospital were retrospectively included. Based on the clinicopathological information of TG patients, the risk factors of LPLN-positive patients were evaluated, and the metastatic incidence as well as the therapeutic value (TV) index of each LN station was assessed. Moreover, the 5-year overall survival (OS) rates between LPLN-positive and LPLN-negative groups were compared in TG patients, and the postoperative survival difference between TG and PG patients was also compared, using propensity score matching (PSM) method. RESULTS Tumour size (≥ 5 cm, OR = 1.481, p = 0.002) and pT stage (pT4, OR = 2.755, p = 0.024) were significant risk factors for patients with LPLN metastasis. For patients with tumour size more than 5 cm or pT4 stage, the metastatic rates of LPLN for Siewert type II, III and II/III AEG were 31.67%, 34.69% and 33.03%, whereas the TV indexes of LPLN for them were 5.76, 5.62 and 5.38, respectively. LPLN was a significant independent prognostic factor (HR = 1.422, p = 0.028), and positive LPLN was related to worse prognosis (p

Gastric cancer (GC) is the fourth leading cause of cancer-related death worldwide. Our study aimed to investigate the prognostic value of preoperative inflammatory, nutritional and tumor markers and develop an effective prognostic score system to predict the prognosis of GC patients. We retrospectively analyzed 1587 consecutive GC patients who received curative gastrectomy from two medical centers. A novel prognostic score system was proposed based on independently preoperative markers associated with overall survival (OS) of GC patients. A nomogram based on prognostic score system was further established and validated internally and externally. Based on multivariate analysis in the training set, a novel BLC (body mass index-lymphocyte-carbohydrate antigen 19-9) score system was proposed, which showed an effective predictability of OS in GC patients (log-rank P

The AP-2 family of transcription factors consist of DNA-binding proteins: AP-2α to AP-2ε. Members and homologs of this family are also known in frogs, fish and invertebrates. These proteins have the same central basic region and a helix-span-helix dimerization motif, which is necessary for dimerization and DNA binding. This family have been found to influence facial, limbs and kidney development in embryogenesis while regulating differentiation and apoptosis. These proteins are also involved in regulation of endocrine processes. In addition to their influence on growth and development, this family have also been reported to correlate with tumorigenesis and development of cancer. At present, this family have been related to tumors of ovary, melanoma, lung, nasopharynx, breast, glioma, neuroblastoma, colon, etc. They regulate expression of many cancer-related genes and affect the occurrence, development, invasiveness and therapeutic response of cancers. Different expression levels of AP-2s are also related to different survival rate. These findings may bring new idea to the diagnosis, classification, treatment and prognosis of cancer.

The role of intraoperative use of indocyanine green (ICG) fluorescence angiography (ICGFA) to prevent anastomotic leakage (AL) in rectal cancer surgery remains controversial. The systematic review for studies evaluating ICGFA in patients undergoing rectal cancer surgery in PubMed, Embase, Web of Science, and the Cochrane Library was performed up to April 30, 2020. The primary outcome was the incidence of AL. The analysis was performed using RevMan v5.3 and Stata v12.0 software. Eighteen studies comprising 4038 patients were included. In the present meta-analysis, intraoperative use of ICGFA markedly reduced AL rate (OR = 0.33; 95% CI: 0.24–0.45; P

To investigate the physiological responses of Oreochromis aureus to salinity fluctuations at the molecular level. We used RNA-seq to explore the differentially expressed genes (DEGs) in the liver and spleen of O. aureus at 0, 3, 7 and 11 ppt (parts per thousand) salinity levels. Herein, De novo assembly generated 71,009 O. aureus unigenes, of which 34,607 were successfully mapped to the four major databases. A total of 120 shared DEGs were identified in liver and spleen transcripts, of which 83 were up-regulated and 37 were down-regulated. GO and KEGG analysis found a total of 26 significant pathways, mainly including energy metabolism, immune response, ion transporters and signal transduction. The trend module category of DEGs showed that the genes (e.g., FASN, ODC1, CD22, MRC, TRAV and SLC7 family) involved in the change-stable-change (1) and the constant-change categories (2) were highly sensitive to salinity fluctuations, which were of great value for further study. Based on these results, it would help provide basic data for fish salinity acclimation, and provide new insights into evolutionary response of fish to various aquatic environments in the long-term stress adaptation mechanism.

BackgroundDue to the controversy over the prognostic significance of Borrmann type in patients with gastric cancer (GC), the present study was to investigate the clinical value of Borrmann type in advanced GC.MethodsWe retrospectively evaluated 2092 patients with advanced GC and subsequently examined the clinicopathological characteristics and prognosis of patients stratified by Borrmann type.ResultsPatients were divided into three groups according to Borrmann type (Borrmann types I+II, III, and IV). Patients with Borrmann types III and IV had larger size, more poorly differentiated tumor type, more advanced tumor stage, and higher chance of involving the entire stomach. The overall survival (OS) rates were significantly different among the three groups (p< 0.001). Stratification analysis revealed significant OS rates among the three groups in tumor-node-metastasis (TNM) stage III (p< 0.001) and TNM stage IV (p= 0.008). Multivariate analysis revealed that Borrmann types, adjuvant chemotherapy, curative resection, and TNM stage were all independent predictors of OS among GC patients. The subgroup analysis indicated that Borrmann type was an independent predictor of OS among GC patients who undergone curative resection and with TNM stage III cancer. However, curative resection and postoperative chemotherapy failed to prolong the survival of patients with Borrmann type IV.ConclusionsThe clinicopathological characteristics and prognosis of patients with three Borrmann types of GC were different. Borrmann type can be simply used as a valuable factor to predict survival in advanced GC patients, especially in those TNM stage III undergoing curative resection. Additionally, more attention should be paid to the treatment for Borrmann type IV GC.

Bifidobacterium animalis subsp. lactis BB-12 (BB-12) was microencapsulated using co-extrusion technology with chitosan coating and the incorporation of mannitol as prebiotic. Optimization of coating material chitosan concentration (0–0.5% w/v) and mannitol concentration (0–5% w/v) as prebiotic were performed to determine the formulation that produces beads with desired properties. The microencapsulation efficiency (MEE) of free and microencapsulated BB-12 (with and without mannitol) were determined. All forms of BB-12 further subjected to sequential digestion in simulated gastric juice (SGJ, pH 2.0) for 2 hours and simulated intestinal juice (SIJ, pH 7.5) for 3 hours. The results indicated that 0.4% (w/v) of chitosan coating and 3% (w/v) of mannitol were the optimum concentrations to produce microencapsulated BB-12 with the highest MEE of 89.15% and the average bead size of 805 µm. The BB-12 beads produced through co-extrusion were spherical with a smooth surface. Throughout the five hours sequential gastrointestinal digestion, both microencapsulated BB-12 with and without mannitol were able to maintain their viable cell count at least 106 CFU/g at the end of the incubation. The presence of prebiotic mannitol showed a significant protective effect on the microencapsulated BB-12 during gastrointestinal transit.

Introduction This qualitative research explores the experience of partner caregivers and how their partner’s dementia impacts on their daily living and occupational lives, with the aim of informing the sustainability of homecare and decreasing the likelihood of formal care. Method Ten participants were recruited through Alzheimer’s Society groups. They were interviewed using the same semi-structured interview process and asked questions about their daily activities and caregiving role. The data was analysed using Braun and Clarke’s thematic analysis process and themes generated using inductive coding and reasoning. Findings Three main themes were identified: (1) losing occupational activities and roles; (2) adapting to a new occupational life and (3) adjusting to a new relationship in the trajectory of their partner’s illness. Conclusion This study highlights the complex occupational challenges experienced by partner caregivers of people with dementia. It suggests that there is a role for occupational therapists in sustaining homecare by working with partner caregivers as ‘expert service users’. Involvement should be provided at critical points of the caregiving journey and include co-creating technology solutions for social inclusion, sustaining adaptive engagement in personal occupations, creating opportunities for restoration and supporting caregivers to preserve their partner’s personhood.

BackgroundThis study aimed to evaluate the impact of postoperative complication and its etiology on long-term survival for gastric cancer (GC) patients with curative resection.MethodsFrom January 2009 to December 2014, a total of 1,667 GC patients who had undergone curative gastrectomy were analyzed. Patients with severe complications (SCs) (Clavien–Dindo grade III or higher complications or those causing a hospital stay of 15 days or longer) were separated into a “complication group.” Univariate and multivariate analyses were performed to reveal the relationship between postoperative complications and long-term survival. A 2:1 propensity score matching (PSM) was used to balance baseline parameters between the two groups.ResultsSCs were diagnosed in 168 (10.08%) patients, including different etiology: infectious complications (ICs) in 111 (6.66%) and non-infectious complications (NICs) in 71 (4.26%) patients. Multivariate analysis showed that presence of SCs (P=0.001) was an independent prognostic factor for overall survival, and further analysis by complication type demonstrated that the deteriorated overall survival was mainly caused by ICs (P=0.004) rather than NICs (P=0.068). After PSM, patients with SCs (p=0.002) still had a significantly decreased overall survival, and the presence of ICs (P=0.002) rather than NICs (P=0.067) showed a negative impact on long-term survival.ConclusionSerious complications, particularly of an infectious type, may have a negative impact on overall survival of GC patients. However, additional multicenter prospective studies with larger sample size are required to verify this issue.

Prolonged prenatal or adult exposure to ethanol is detrimental to mental and physical well-being, resulting in developmental abnormalities, progressive addiction and ultimate death. A growing number of studies have shown the therapeutic potential of cannabinoids in ethanol-related behaviors in mammals. However, the potential pharmacological actions of cannabinoids in ethanol responses have not been examined in the model organism Drosophila melanogaster. Here, we systematically investigated the effects of various cannabinoids on ethanol preference, ethanol sensitivity and tolerance, and ethanol-induced developmental defect in Drosophila. We showed that treatment with the phytocannabinoid cannabidiol (CBD) displayed a significant decrease in preference for consuming ethanol in adult flies. Interestingly, cannabinoids exhibited differential roles in short- and long-term ethanol tolerance in flies. Although cannabinoids had no detectable effects on short-term ethanol tolerance, CBD and the endocannabinoid anandamide (AEA) suppressed long-term tolerance to ethanol. Moreover, ethanol exposure delayed larval-to-pupal development and increased larval/pupal size. Unexpectedly, treatment with CBD or endocannabinoids did not attenuate ethanol-induced developmental delay, instead, exacerbated its detrimental effect. Thus, our systematical study reveals, for the first time, a differential role of the cannabinoids in the modulation of ethanol-related responses in Drosophila.

BackgroundGiven the expanding clinical applications of laparoscopic surgery and neoadjuvant chemotherapy in advanced gastric cancer treatment, there is an emerging need to summarize the few evidences that evaluated the safety and efficacy of laparoscopic versus open gastrectomy in patients with advanced gastric cancer (AGC) following neoadjuvant chemotherapy (NAC).MethodsFrom January 1 to 2, 2021, we searched Ovid Embase, PubMed, Cochrane central register Trials (Ovid), and web of science to find relevant studies published in English, and two authors independently performed literature screening, quality assessment of the included studies, data extraction, and data analysis. This study was registered with PROSPERO (CRD42021228845).ResultsThe initial search retrieved 1567 articles, and 6 studies were finally included in the meta-analysis review, which comprised 2 randomized control trials and 4 observational studies involving 288 laparoscopic gastrectomy (LG) and 416 open gastrectomy (OG) AGC patients treated with NAC. For intraoperative conditions, R0 resection rate, blood transfusion, intraoperative blood loss, number of lymph nodes dissected, proximal margin, and distal margin were comparable between LG group and open OG group. For postoperative short-term clinical outcomes, LG has significantly less postoperative complications (OR = 0.65, 95%CI: 0.42–1.00, p = 0.05) and shorter postoperative time to first aerofluxus (WMD = -0.57d, 95%CI: -0.89–0.25, p = 0.0004) than OG, and anastomotic leakage, pulmonary infection, pleural effusion, surgical site infection, thrombosis, intestinal obstruction, peritoneal effusion or abscess formation, postoperative time to first defecation, postoperative time to first liquid diet, and postoperative length of stay were comparable between the two groups. For postoperative survival outcomes, there were no significant differences in disease-free survival (DFS) and overall survival (OS) between the two groups.ConclusionThe available evidences indicated that LG is an effective and feasible technology for the treatment of AGC patients treated with NAC, and LG patients have much less postoperative complications and faster bowel function recovery than OG patients.Systematic Review RegistrationPROSPERO database (identifier, CRD42021228845).

It has long been thought that microtubule disassembly, one of the earliest cellular events, contributes to neuronal pruning and neurodegeneration in development and disease. However, how microtubule disassembly drives neuronal pruning remains poorly understood. Here, we conduct a systematic investigation of various microtubule‐destabilizing factors and identify exchange factor for Arf6 (Efa6) and Stathmin (Stai) as new regulators of dendrite pruning in ddaC sensory neurons during Drosophila metamorphosis. We show that Efa6 is both necessary and sufficient to regulate dendrite pruning. Interestingly, Efa6 and Stai facilitate microtubule turnover and disassembly prior to dendrite pruning without compromising the minus‐end‐out microtubule orientation in dendrites. Moreover, our pharmacological and genetic manipulations strongly support a key role of microtubule disassembly in promoting dendrite pruning. Thus, this systematic study highlights the importance of two selective microtubule destabilizers in dendrite pruning and substantiates a causal link between microtubule disassembly and neuronal pruning.

Background The prognostic significance of preoperative plasma fibrinogen in patients with operable gastric cancer remains under debate. This study aimed to elucidate the prognostic value of fibrinogen in gastric cancer patients underwent gastrectomy. Methods A total of 4351 patients with gastric cancer collected from three comprehensive medical centers were retrospectively evaluated. Patients were categorized by minimum P value using X-tile, while the baseline confounders for fibrinogen was balanced through propensity score matching (PSM). The relationships between fibrinogen and other clinicopathologic features were evaluated, and nomogram was constructed to assess its prognostic improvement compared with TNM staging system. Results Fibrinogen was significantly correlated with macroscopic type, tumor differentiation, tumor size, and T and N stage. The factors, fibrinogen and T stage as well as N stage, were identified to be independent prognostic factors after PSM. Nomogram based on fibrinogen demonstrated a smaller Akaike information criterion (AIC) and a larger concordance index (C-index) than TNM staging system, illustrating that fibrinogen might be able to improve the prognostic accuracy. Conclusions Preoperative plasma fibrinogen levels in gastric cancer patients were significantly correlated with tumor progression, which could be regarded as a reliable marker for survival prognostic prediction.

Obesity may impact surgical outcomes of gastrectomy. Whether visceral fat area (VFA) is a better obesity parameter than body mass index (BMI) is still controversial. The aim of this study is to compare the accuracy and effectiveness of VFA and BMI in predicting the short-term surgical outcomes of gastrectomy. Patients who were diagnosed with gastric cancer were measured for BMI and VFA preoperatively and then divided into a VFA-H (VFA-high) group and VFA-L (VFA-low) group, at the cutoff point of 100 cm2, and a BMI-H (BMI-high) group and BMI-L (BMI-low) group, at the cutoff point of 25 kg/m2. The short-term surgical outcomes were compared between the different groups. In total, 276 patients were enrolled in this study; 55 (19.9%) patients were classified into the BMI-H group, and 122 (44.2%) patients were classified into the VFA-H group. There was a significant correlation between BMI and VFA (r = 0.652, p

The plasma very low-density lipoprotein (VLDL) concentration is an effective blood biochemical indicator that could be used to select lean chicken lines. In the current study, we used Genome-wide association study (GWAS) method to detect SNPs with significant effects on plasma VLDL concentration. As a result, 38 SNPs significantly associated with plasma VLDL concentration were identified using at least one of the three mixed linear model (MLM) packages, including GRAMMAR, EMMAX and GEMMA. Nearly, all these SNPs with significant effects on plasma VLDL concentration (except Gga_rs16160897) have significantly different allele frequencies between lean and fat lines. The 1-Mb regions surrounding these 38 SNPs were extracted, and twelve important regions were obtained after combining the overlaps. A total of 122 genes in these twelve important regions were detected. Among these genes, LRRK2, ABCD2, TLR4, E2F1, SUGP1, NCAN, KLF2 and RAB8A were identified as important genes for plasma VLDL concentration based on their basic functions. The results of this study may supply useful information to select lean chicken lines.

Background:There is controversy about the characteristics and prognostic implications of signet ring cell gastric cancers and non-signet ring cell gastric cancers.Objective:This study aims to evaluate clinicopathological characteristics and prognoses of signet ring cell carcinoma (SRCC) and non-signet ring cell carcinoma (NSRCC) of stomach.Methods:Studies compared between SRCC and NSRCC of the stomach after gastrectomy and published before September 1st, 2020, in the PubMed, Cochrane, and Embase databases, were identified systematically.Results:A total of 2,865 studies were screened, and 36 studies were included, with 19,174 patients in the SRCC group and 55,942 patients in the NSRCC group. SRCC patients were younger in age (P< 0.001), less likely to be male patients (P< 0.001), more afflicted with upper third lesions (P< 0.001), and presenting with more Borrmann type IV tumors (P= 0.005) than NSRCC patients. Lymph nodes metastasis was similar between SRCC and NSRCC patients with advanced tumor stage (OR: 0.86, 95% CI: 0.67–1.10,P= 0.23), but lower in the SRCC than NSRCC patients with early tumor stage (OR: 0.73; 95% CI: 0.56–0.98,P= 0.02). SRCC patients had comparable survival outcomes with NSRCC patients for early gastric cancers (HR: 1.05, 95% CI: 0.65–1.68,P< 0.001) but had significantly poor prognosis for patients with advanced tumor stage (HR: 1.50, 95% CI: 1.28–1.76,P< 0.001).Conclusions:Signet ring cell carcinomas of the stomach are an increasingly common histopathological subtype of gastric cancers. These kinds of patients tend to be younger in age and more often female. Although, signet ring cell gastric cancer is a negative prognostic factor for patients with advanced stage. The difference is that for early stage of signet ring cell gastric cancers, it has low lymph nodes metastasis rate and comparable prognosis with non-signet ring cell cancers.

Diabetic bladder dysfunction (DBD) afflicts nearly half of diabetic patients, but effective treatment is lacking. In this study, IR-61, a novel heptamethine cyanine dye with potential antioxidant effects, was investigated to determine whether it can alleviate DBD. Rats were intraperitoneally injected with IR-61 or vehicle after diabetes was induced with streptozotocin. Before evaluating the effects of IR-61 in improving DBD by filling cystometry, we detected its distribution in tissues and subcellular organelles by confocal fluorescence imaging. Near infrared (NIR) imaging showed that IR-61 could accumulate at high levels in the bladders of diabetic rats, and confocal images demonstrated that it was mainly taken up by bladder smooth muscle cells (BSMCs) and localized in mitochondria. Then, filling cystometry illustrated that IR-61 significantly improved the bladder function of diabetic rats. The histomorphometry results showed that IR-61 effectively mitigated the pathological changes in bladder smooth muscle (BSM) in diabetic rats. Furthermore, IR-61 remarkably reduced the number of apoptotic BSMCs and the unfavorable expression of proteins related to the mitochondrial apoptotic pathway (Bcl-2, BAX, Cytochrome C, and cleaved Caspase-9) in diabetic rats. Moreover, the frozen section staining and transmission electron microscopy results proved that IR-61 significantly reduced the reactive oxygen species (ROS) levels and prevented the mitochondrial mass and morphology damage in the BSM of diabetic rats. In addition, IR-61 upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its associated antioxidant proteins in the BSM of diabetic rats. Together, these results indicate that IR-61 can improve the voiding function of rats with DBD by protecting the mitochondria of BSMCs from oxidative stress, which is possibly mediated through the activation of the Nrf2 pathway.

This study aimed to evaluate the therapeutic effect of IR-61, a novel mitochondrial heptamethine cyanine dye with antioxidant effects, on diabetes mellitus-induced erectile dysfunction (DMED). Eight-week-old male Sprague–Dawley rats were intraperitoneally injected with streptozotocin (STZ) to induce type 1 diabetes. Eight weeks after STZ injection, all rats were divided into three groups: the control group, DM group, and DM + IR-61 group. In the DM + IR-61 group, the rats were administered IR-61 (1.6 mg kg−1) twice a week by intravenous injection. At week 13, erectile function was evaluated by determining the ratio of the maximal intracavernous pressure to mean arterial pressure, and the penises were then harvested for fluorescent imaging, transmission electron microscopy, histological examinations, and Western blot analysis. Whole-body imaging suggested that IR-61 was highly accumulated in the penis after intravenous injection. IR-61 treatment significantly improved the maximal ICP of diabetic rats. Additionally, IR-61 ameliorated diabetes-induced inflammation, apoptosis, and phenotypic transition of corpus cavernosum smooth muscle cells (CCSMCs) in penile tissue. IR-61 also attenuated mitochondrial damage, reduced reactive oxygen species production in the corpus cavernosum and upregulated sirtuin1 (SIRT1), sirtuin3 (SIRT3), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and heme oxygenase expression in penile tissue. In conclusion, IR-61 represents a potential therapeutic option for DMED by protecting the mitochondria of CCSMCs, which may be mediated by activation of the SIRT1, SIRT3, and Nrf2 pathways.

Background: Bladder cancer has a high rate of recurrence and drug resistance due to a lack of effective therapies. IR-780 iodide, a near-infrared (NIR) mitochondria-targeting fluorescent agent, has been demonstrated to achieve higher selectivity than other drugs in different tumor types. In the study, we aimed to investigate the anti-tumor effect of IR-780 combined with hyperbaric oxygen (HBO) on bladder cancer.Methods: Using in vitro cell line data, in vivo model data and clinical data, we tested the ability of IR-780 to selectively accumulate in bladder cancer. We also evaluated the anti-tumor effect of IR-780 combined or not with HBO both in vitro and in vivo, and explored the potential mechanism of its anti-tumor effect. Results: We revealed for the first time that IR-780 selectively accumulated in bladder cancer (bladder cancer cells, xenografts and bladder cancer samples from patients) and could induce cancer cell apoptosis by targeting the mitochondrial complex I protein NDUFS1. Further study displayed that the combination with HBO could significantly enhance the antitumor effect of IR-780 in vitro by promoting cancer cell uptake and inducing excessive mitochondrial reactive oxygen species (ROS) production, while suppressing tumor growth and recurrence in animal models without causing apparent toxicity. Moreover, this combination antitumor strategy was also demonstrated in drug-resistant bladder cancer cells (T24/DDP) and xenografts. Conclusions: These data identify for the first time a combination of IR-780 and HBO (IR-780+HBO), which exhibits mitochondria-targeting and therapeutic capabilities, as a novel treatment paradigm for bladder cancer.

Data about whether laparoscopic gastrectomy (LG) is applicable in serosa-positive (pT4a) gastric cancer patients remain rare. The purpose of this study is to compare the perioperative and long-term outcomes between the laparoscopic and open gastrectomy (OG) in pT4a gastric cancer patients who underwent curative resection. A total of 1086 consecutive pT4a patients (101 patients with LG and 985 with OG) who underwent curative gastrectomy in a high-volume center between 2006 and 2016 were evaluated. Demographics, surgical, and oncologic outcomes were analyzed. Propensity score matching (PSM) analysis was performed to balance baseline confounders, and COX regression analysis was performed to identify independent prognostic factors. After PSM adjustment, a well-balanced cohort comprising 101 patients who underwent LG and 201 who underwent OG was analyzed. Operative time (288.7 vs. 234.2 min; P

Adhesive small bowel obstruction (ASBO) has a significant impact on quality of life and medical costs. However, data about ASBO after gastrectomy remain sparse. From January 2009 to December 2017, 3025 patients who underwent gastrectomy for gastric cancer were retrospectively collected and analyzed. Clinicopathological materials were obtained retrospectively, and univariate and multivariate regression analyses were performed to determine risk factors for ASBO. A nomogram for the prediction of ASBO was generated using the results of multivariable analyses. Bootstraps with 1000 resamples were performed for internal validation. The performance of the model was assessed with its discrimination, calibration, and clinical usefulness. A total of 330 (10.9%) patients experienced at least one ASBO episode with a median follow-up of 57.0 (interquartile range 31.0–85.0) months. Logistic regression analysis showed that independent risk factors for ASBO were previous abdominal surgery (odds ratio, OR = 2.03), open gastrectomy (OR = 3.12), non-Billroth-1 reconstruction (Billroth-2, OR = 2.61; Roux-en-Y, OR = 1.99; esophagogastrostomy, OR = 2.79), D2/D2 + lymphadenectomy (OR = 2.64), combined organ resection (OR = 2.76), and postoperative intraabdominal complication (OR = 2.73). The nomogram showed good discrimination, with a C-index of 0.702 and good calibration. Decision curve analysis demonstrated that the nomogram was clinically useful. Several risk factors associated with ASBO after gastrectomy for gastric cancer were identified. Nomogram generated based on these factors could serve as a reliable tool to predict the probability of ASBO.

Background: It is known that Bacillus Calmette–Guérin (BCG), which serves as an adjuvant immunotherapy, has certain beneficial effects on the prognosis for gastric cancer. However, no existing reports have probed into the impact of old tuberculosis (TB) lesion on patients with gastric cancer. Methods: Using the database from a high-volume center, 2649 consecutive gastric cancer patients admitted to West China Hospital undergoing curative-intent gastrectomy were identified between 2009 and 2016. Patients were divided into TB group and non-tuberculosis (NTB) group based on the presence or absence of a coexistent old pulmonary TB lesion. Then, multinomial logistic regression models tested the risk factors for the postoperative pulmonary complications (PPCs). Kaplan-Meier analyses and Cox regression models tested the effect of old TB lesion on overall survival (OS) rate. The propensity score-matching (PSM) method was used to assemble a well-balanced cohort.Results: Altogether 81 of the enrolled patients had old pulmonary TB lesions. The presence of an old TB lesion was associated with superior overall survival (OS). Besides, the 3-year OS rates were 84.7% in TB group and 69.2% in NTB group, and the difference between two groups was statistically significant (p=0.005). Similarly, in the following analysis on 73 pairs of matched patients, significant differences were also noted between the two cohorts (p=0.001), with the 3-year OS rates of 90.4% and 69.2%, respectively. Further, multivariable Cox regression analysis showed that old TB was an independent positive factor for OS before and after propensity score-matching (PSM) (p=0.002/p<0.001, HR=0.471/0.220, respectively). Additionally, the old TB lesion appeared to be an independent risk factor for postoperative pulmonary complications (PPCs) (both pConclusions: Old TB lesion is a risk factor for PPCs. Despite that, it represented as an independent positive factor for the prognosis of gastric cancer in general. This study may shed light on further immune therapy for gastric cancer.

Objective: The prognostic significance of serum CA19-9 levels in gastric cancer patients remains a matter debate. The aim of this study was to determine the prognostic value of changes in preoperative and postoperative serum CA19-9 levels in patients with gastric cancer.Methods: A total of 1,046 gastric cancer patients who underwent curative gastrectomy in West China Hospital of Sichuan University from January 2011 to December 2016 were analyzed retrospectively. Patients were categorized by minimum P-value using X-tile, while the baseline confounders for CA19-9 changes were balanced through propensity score matching (PSM). The relationships between CA19-9 changes and other clinicopathologic features were measured. Univariate and multivariate analysis were performed to explore the risk factors associated with survival outcomes.Results: We included 653 patients. Changes in CA19-9 levels significantly correlated with age, tumor size, macroscopic type, histological grade, T stage and TNM stage. Kaplan–Meier curves revealed that patients with CA19-9 changes

Background The preoperative work-up has limitations on finding peritoneal dissemination (PD) in gastric cancer patients. Laparoscopic exploration (LE) can discover radiographically occult PD, obtain accurate stage and avert futile laparotomy. The aim of our study was to introduce “Four-Step Procedure” LE in West China Hospital and further evaluate its safety and feasibility. Methods We conducted a retrospective analysis on 165 patients from July 2016 to December 2017 who underwent “Four-Step Procedure” LE in gastrointestinal surgery department of West China Hospital. All the patients were diagnosed with gastric adenocarcinoma without explicit distant metastasis through Computed Tomography and/or Gastrointestinal Ultrasonography. Peritoneal lavage cytological examination (CY) was routinely performed during LE in our research. The “Four-Step” technical process of LE was introduced comprehensively. The clinicopathologic features and the presence of PD or CY at LE were analyzed, and the stratified analysis by cT and cN stages on the proportion of P1 and/or CY1 was also reported in this study. Results Total of 165 patients accepted LE in our study, among these patients: 27 (16.4%) patients with P1 and/or CY1: 19 (11.5%) patients were found PD (P1), 17 (10.3%) patients with positive cytological examination (CY1) and 9 (3.6%) patients with P1Cy1. The stratified analysis by cT stage indicated that there was no P1 and/or Cy1 in cT1–cT2 stages, 1 (2.7%) patient with P1 and 1 (2.7%) with Cy1 in cT3 stage, 18 (20.0%) patients with P1 and 16 (17.8%) with Cy1 in cT4 stage. After LE, there were 74 (44.8%) patients underwent laparoscopic assistant gastrectomy, 25 (15.2%) patients with open gastrectomy, 50 (30.3%) patients with neoadjuvant chemotherapy and 16 (9.7%) patients with palliative chemotherapy and/or conversion therapy. Conclusion “Four-Step Procedure” LE is reliable and feasible for gastric cancer. From our study, LE has unique superiority on ascertaining PD and cytological examination and LE should be recommended in cT4 stage gastric cancer before resection. Electronic supplementary material The online version of this article (10.1007/s00464-018-6605-2) contains supplementary material, which is available to authorized users.

// Xin-Zu Chen 1, 2, * , Shao-Yong Wang 1, 3, * , Yin-Su Wang 4 , Zi-Han Jiang 4 , Wei-Han Zhang 1, 2 , Kai Liu 1, 2 , Kun Yang 1, 2 , Xiao-Long Chen 1, 2 , Lin-Yong Zhao 1, 2 , Meng Qiu 5 , Hong-Feng Gou 5 , Zong-Guang Zhou 1, 6 and Jian-Kun Hu 1, 2 1 Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China 2 Institute of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China 3 Department of Gastrointestinal Surgery, Guizhou Provincial People's Hospital, Guiyang, China 4 Faculty of Medicine, West China Medical School, Sichuan University, Chengdu, China 5 Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China 6 Institute of Digestive Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China * These authors equally contributed to this work and are co-first authors Correspondence to: Jian-Kun Hu, email: hujkwch@126.com Keywords: gastric cancer, laparoscopy, gastrectomy, survival, surgical oncology Received: November 14, 2016 Accepted: March 30, 2017 Published: April 10, 2017 ABSTRACT Objectives: The safety and surgical oncology of laparoscopy-assisted total gastrectomy (LATG) remain inconclusive and challenging. This study aimed to compare the short-term and long-term outcomes between LATG and open total gastrectomy (OTG) procedures. Results: In the all-included analyses, there were 69 patients in the LATG group and 268 in the OTG group. LATG was as safe as OTG without increasing postoperative morbidity and mortality. Stage imbalance might introduce differences in the numbers of harvested lymph nodes in LATG (34.4 ± 12.0) and OTG (40.9 ± 16.9), whereas 95.7% of patients underwent D2/D2+ dissection during the LATG procedure. After a median 31 months of follow-up, the overall survival outcomes were comparable between the LATG and OTG procedures (HR = 1.16, 95% CI 0.68–1.97). Sensitivity analysis found comparable node retrieval and stage-specific or treatment-specific overall survival. Materials and Methods: A retrospective case-control study was conducted among gastric cancer patients who underwent either LATG or OTG with curative intention between June 2006 and December 2015. Data retrieval was based on the Surgical Gastric Cancer Patient Registry in the West China Hospital. The primary outcome was overall survival. The secondary outcomes were postoperative complication incidence and severity, operation duration, blood loss, number of harvested lymph nodes, and postoperative hospital stay. Matched pairwise case-control comparisons were performed as a sensitivity analysis. Conclusions: LATG by experienced surgeons possibly has comparable short-term surgical outcomes and long-term survival outcomes compared with OTG for gastric cancer patients. However, high-quality RCTs are necessary before confirmative judgment and recommendation as an optional treatment in general practice.

To solve the contradiction between handling stability and ride comfort of vehicles with interconnected air suspension system (IASS) and reduce the energy consumption of air suspension with adjustable spring stiffness, a coordinated control for dynamic performance was designed based on the logic of switching interconnection modes and game control for the damper. The control system consists of a switching controller for air suspension interconnection modes and a distribution controller for the damping force. The switching controller determines the optimal air suspension interconnection mode by calculating the vehicle dynamic performance index in real-time. The distribution controller achieves a distribution for optimal damping force based on an infinite time differential game. veDYNA software that is a vehicle dynamics analysis software based on MATLAB/Simulink was used to verify the algorithm, and the accuracy was verified by a bench test. Finally, the results show this coordinated system can significantly improve the ride comfort and restrain the pitching motion. Compared with traditional suspension, the vertical acceleration decreases by 18.32% and the dynamic stroke decreases by more than 10% under the straight condition; the vertical acceleration decreases by 12.24% and the roll angle decreases by 1.26% under the steering condition.

Gonadotropin releasing hormone (GnRH) plays an important role in the regulation of vertebrate reproduction. Studies have shown that immunization against GnRHa can induce sexually sterile tilapia. To explore the mechanism behind this, in this study, RNA-seq and data-independent acquisition (DIA) techniques were used to study the transcriptome and proteome of the gonad of tilapia immunized with GnRHa. 644 differentially expressed genes (80 upregulated and 564 downregulated) and 1150 differentially expressed proteins (351 upregulated and 799 downregulated) were identified. There were 209 genes with consistent differential expression patterns in the transcriptomic and proteomic analyses, of which 9 were upregulated and 200 downregulated, indicating that the gonad gene expression was inhibited by GnRHa immunization. The downregulated genes were particularly involved in the functions of single-organism process, binding, cellular process, metabolic process and catalytic activity, and associated with the pathways including ECM-receptor interaction, focal adhesion, cardiac muscle contraction and oxidative phosphorylation. The expression of six differentially expressed genes involved in the GnRH signaling pathway was all downregulated. In addition, several important functional genes related to gonadal development after GnRHa immunization were screened. This study confirmed the expression of corresponding genes was affected by GnRHa on the gonad development in tilapia at the molecular level, and laid a foundation for elucidating the mechanism of GnRHa immunization.

The rearrangement during transfection (RET) encodes a receptor tyrosine kinase (RTK), which is involved in the development of various tissues and cells. The rearrangements and mutations of RET contribute to the development of a variety of human malignancies. Therefore, RET alterations are novel therapeutic targets. Inhibitors for RET and other kinases have been approved for the treatment of RET-altered tumors and have demonstrated their benefits for some types of cancer patients in clinics. However, due to off-target effects, these inhibitors have some adverse effects and dose-limiting toxicity. Therefore, long-term treatment with these inhibitors has potential limitations. Novel highly selective inhibitors (pralsetinib and selpercatinib) that target the RET pathway are well tolerated and have significant and long-lasting antitumor activity. They have been accelerated for approval by the FDA. This article will focus on the role of highly selective inhibitors targeting the RET and their efficacy and safety in therapy for RET-associated cancers.

The role of extranodal metastasis (ENM) in TNM stage in gastric carcinoma (GC) is controversial. This study was aimed to make a detailed investigation of the prognostic significance and the role in TNM stage of ENM in GC. The patients with primary GC, who underwent gastrectomy with curative intention in West China Hospital from January 2005 to December 2011, were retrospectively enrolled. The prognosis and clinicopathological traits were compared between ENM positive (ENMP) and negative (ENMN) groups in all patients, TNM I-II, III and IV stages, respectively. The significance of the number and the role in TNM stage of ENM were also assessed. In our study, 1457 patients were enrolled, with 1324 (90.9%) in ENMN group and 133 (9.1%) in ENMP group. ENMP group had significantly more advanced GC and worse prognosis (all p2 subgroup had remarkably larger tumor size (p=0.002) and more advanced N stage (p=0.016) than ENM=1-2 subgroup. The number of ENM was an independent prognostic factor in ENMP group (p=0.029). The prognosis of ENM>2 in TNM I-III stages was significantly worse than ENMN patients in TNM III stage. The C-index of TNM stage plus the number of ENM was significantly higher than that of current TNM stage alone (p=0.005). In conclusion, the patients in ENMP subgroup had more advanced GC and worse prognosis than those in ENMN subgroup. It might be more reasonable to categorize ENM>2 into TNM IV stage.

// Xiao-Long Chen 1, 2, * , Xin-Zu Chen 1, 2, * , Yi-Gao Wang 1, 2, * , Du He 3 , Zheng-Hao Lu 1, 2 , Kai Liu 1, 2 , Wei-Han Zhang 1, 2 , Wei Wang 1, 2 , Chang-Chun Li 1, 2 , Lian Xue 1, 2 , Lin-Yong Zhao 1, 2 , Kun Yang 1, 2 , Jian-Ping Liu 3 , Zong-Guang Zhou 1, 4 , Jian-Kun Hu 1, 2 , Xian-Ming Mo 5 1 Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China 2 Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China 3 Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, China 4 Institute of Digestive Surgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China 5 Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China * These authors have contributed equally to this work Correspondence to: Jian-Kun Hu, email: hujkwch@126.com Keywords: gastric cancer, cancer stem cells, markers, prognosis, nomogram Received: December 22, 2015 Accepted: August 08, 2016 Published: August 19, 2016 ABSTRACT Cancer stem cells (CSCs) are thought as the source of tumor maintaining and many CSCs markers have been identified. Regarding the heterogeneity in gastric cancer (GC), TNM stage is not enough to accurately predict the prognosis. The aim of this study was to investigate the clinical significance of CSCs markers (Lgr5, Oct4, CD133, EpCAM, CD54 and Sox2) and establish a new model based on these markers to accurately predict prognosis of GC. We retrospectively enrolled 377 GC tissues from January 2006 to October 2012 to perform immunohistochemistry (IHC), and 93 pairs of GC tissues and corresponding adjacent normal gastric tissues to perform quantitative PCR (qPCR) from December 2011 to October 2012. The clinicopathological and follow-up characteristics were collected. In IHC, Oct4, CD133 and EpCAM were independently related to tumor progression, while Sox2 were associated with well or moderate differentiation (all p

// Lin-Yong Zhao 1,2,3,* , Xiao-Long Chen 1,2,* , Yi-Gao Wang 1,2,3,* , Yue Xin 3 , Wei-Han Zhang 1,2,3 , Yin-Su Wang 3 , Xin-Zu Chen 1,2 , Kun Yang 1,2 , Kai Liu 1,2 , Lian Xue 1,2,3 , Bo Zhang 1 , Zhi-Xin Chen 1 , Jia-Ping Chen 1 , Zong-Guang Zhou 1 and Jian-Kun Hu 1,2 1 Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China 2 Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China 3 West China School of Medicine, Sichuan University, Chengdu, China * These authors have contributed equally to this work Correspondence to: Jian-Kun Hu, email: // Keywords : predictive model; gastric cancer; tumor size; lymphovascular invasion; lymph nodes count Received : February 15, 2016 Accepted : July 18, 2016 Published : August 04, 2016 Abstract Background: Various factors may affect the clinical prognosis of lymph node-negative gastric cancer (GC) patients. This study aimed to provide evaluable prognostic information of combination of tumor size (Ts), lymph nodes count (LNs) and lymphovascular invasion (LVI) in lymph node-negative GC patients. Methods: A total of 1,019 node-negative GC patients were enrolled in this retrospective study from 2000 to 2010. The cutoff points of Ts and LNs were determined using X-tile and patients were randomly categorized into training and validation sets by the sample size ratio 1:1. The clinicopathologic characteristics were analyzed and survival prognostic factors were identified, whereas the survival prediction accuracy was also compared by C-index during the different independent prognostic factors. Results: The cutoff points for Ts were 3cm and 5cm, while 14 was the cutoff point for LNs. Age, T stage, Ts, LNs and LVI were identified as independent prognostic factors in node-negative GC patients, and a new prognostic predictive model, TsNL staging system which was composed of Ts, LNs and LVI, was proposed in this study. Compared with T staging system, significant improvement of predictive accuracy for TsNL system was found. Furthermore, nomogram based on TsNL was more accurate in prognostic prediction than that based on Ts, LNs and LVI, separately. Conclusions: Age, T stage, Ts, LNs and LVI were independent prognostic factors in lymph node-negative GC patients. The TsNL staging system, composed of Ts, LNs and LVI, which was closely associated with clinicopathologic features, may improve the prognostic prediction accuracy in node-negative GC patients.

// Lin-Yong Zhao 1, 2, 3, * , Yuan Yin 1, * , Xue Li 3 , Chen-Jing Zhu 3 , Yi-Gao Wang 1, 2, 3 , Xiao-Long Chen 1, 2 , Wei-Han Zhang 1, 2, 3 , Xin-Zu Chen 1, 2 , Kun Yang 1, 2 , Kai Liu 1, 2, 3 , Bo Zhang 1 , Zhi-Xin Chen 1 , Jia-Ping Chen 1 , Zong-Guang Zhou 1 , Jian-Kun Hu 1, 2 1 Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, China 2 Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, China 3 West China School of Medicine, Sichuan University, China * These authors have contributed equally to this work Correspondence to: Jian-Kun Hu, email: hujkwch@126.com Keywords: early gastric cancer, nomogram, lymph node metastasis, prediction, tumor markers Received: April 12, 2016 Accepted: July 10, 2016 Published: July 20, 2016 ABSTRACT Predicting lymph node metastasis (LNM) accurately is of great importance to formulate optimal treatment strategies preoperatively for patients with early gastric cancer (EGC). This study aimed to explore risk factors that predict the presence of LNM in EGC. A total of 697 patients underwent gastrectomy enrolled in this study, were divided into training and validation set, and the relationship between LNM and other clinicopathologic features, preoperative serum combined tumor markers (CEA, CA19-9, CA125) were evaluated. Risk factors for LNM were identified using logistic regression analysis, and a nomogram was created by R program to predict the possibility of LNM in training set, while receiver operating characteristic (ROC) analysis was applied to assess the predictive value of the nomogram model in validation set. Consequently, LNM was significantly associated with tumor size, macroscopic type, differentiation type, ulcerative findings, lymphovascular invasion, depth of invasion and combined tumor marker. In multivariate logistic regression analysis, factors including of tumor size, differentiation type, ulcerative findings, lymphovascular invasion, depth of invasion and combined tumor marker were demonstrated to be independent risk factors for LNM. Moreover, a predictive nomogram with these independent factors for LNM in EGC patients was constructed, and ROC curve demonstrated a good discrimination ability with the AUC of 0.847 (95% CI: 0.789-0.923), which was significantly larger than those produced in previous studies. Therefore, including of these tumor markers which could be convenient and feasible to obtain from the serum preoperatively, the nomogram could effectively predict the incidence of LNM for EGC patients.

This study aimed to evaluate the prognostic significance of node ratio (Nr), the ratio of metastatic to retrieved lymph nodes, and to investigate whether a modified staging system based on Nr can improve prognostic ability for gastric cancer patients following gastrectomy. A total of 2572 patients were randomly divided into training set and validation set, and the cutoff points for Nr were produced using X-tile. The relationships between Nr and other clinicopathologic factors were analyzed, while survival prognostic discriminatory ability and accuracy were compared among different staging systems by AIC and C-index in R program. Patients were categorized into four groups as follows: Nr0, Nr1: 0.00-0.15, Nr2: 0.15-0.40 and Nr3: > 0.40. Nr was significantly associated with clinicopathologic factors including macroscopic type, tumor differentiation, lymphovascular invasion, perineural invasion, tumor size, T stage, N stage and TNM stage. Besides, for all patients, Nr and TNrM staging system showed a smaller AIC and a larger C-index than that of N and TNM staging system, respectively. Moreover, in subgroup analysis for patients with retrieved lymph nodes < 15, Nr was demonstrated to have a smaller AIC and a larger C-index than N staging system. Furthermore, in validation analysis, Nr, categorized by our cutoff points, showed a larger C-index and a smaller AIC value than those produced in previous studies. Nr could be considered as a reliable prognostic factor, even in patients with insufficient (< 15) retrieved lymph nodes, and TNrM staging system may improve the prognostic discriminatory ability and accuracy for gastric cancer patients undergoing radical gastrectomy.

Laser treatment has emerged as a common treatment modality for acquired bilateral nevus of Ota-like macules (ABNOM). To identify the ratio of melasma induction and exacerbation before and after laser therapy for ABNOM and to observe the risk factors related to the induction and exacerbation of melasma by laser therapy, we analyzed related factors of 1268 adult Chinese patients who underwent 1064-nm Q-switched neodymium:yttrium-aluminum-garnet (Nd:YAG) laser (QNYL) treatment using case series and case-control studies. Overall, 24.0% of the ABNOM patients had mixed melasma. Among the ABNOM patients without melasma, after laser therapy the development of melasma was more frequently noted in patients older than 35 years (P < 0.0001), as well in patients whose ABNOM was less than 10 cm(2) (P = 0.027), ABNOM were light (similar to yellow-brown) in color (P = 0.021) and skin types were closer to type IV (P < 0.0001). New melasma lesions also appeared most frequently in the zygomatic region (P < 0.0001). Among the ABNOM patients with melasma, 89.5% experienced worsening of their melasma, irrespective of their related factors above. We concluded that the risk of inducing melasma is great after 1064-nm QNYL treatment in ABNOM patients, and particularly in the patients with both ABNOM and melasma. ABNOM patients should be treated as early as possible and before the age of 35 years.

Human echinococcosis has become a major public health problem in most parts of the world. The objective of this article was to study the demographics of patients with hepatic echinococcosis in Ganzi County to elucidate the main risk factors, as well as to report the concurrent prevalence of cerebral echinococcosis and pulmonary echinococcosis. We recruited 195 patients with hepatic echinococcosis from the Datongma area of Ganzi County from January 2018 to November 2018. The patients’ demographics, living environments, supported medical resources, knowledge of echinococcosis prevention and control, and hygienic practices were investigated and analyzed. The prevalence of cerebral echinococcosis and pulmonary echinococcosis were also investigated. The data were analyzed to identify risk factors for human echinococcosis. Our analysis showed that the herding Tibetan population within the 20 to 60 age group, and females, in particular, were at the highest risk of human echinococcosis infection. Having stray dogs around habitations and intimate activities with dogs and livestock were also behavioral risk factors. People with poor health literacy and low educational qualifications had possible risks of infection. In terms of hygiene, not using tap water as the drinking water source and lack of medical staff were significantly correlated with echinococcosis prevalence. Four patients were diagnosed with cerebral echinococcosis. Among them, 1 patient had both cerebral echinococcosis and pulmonary echinococcosis. Possible high-risk factors for echinococcosis were being female, herding population, in the 20 to 60 age group, having stray dogs around habitations, having activities with dogs and livestock, having poor health literacy, having low educational qualifications, and not using tap water as a drinking water source. The detection rate for brain echinococcosis in patients with hepatic echinococcosis was high (2.05%). Effective preventive strategies should be implemented in epidemic areas. Head CT scans should be applied for early detection of cerebral echinococcosis to carry out the treatment.

Changes in the expression and subcellular localization of high mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) molecule, have been implicated in tumorigenesis and tumor cell death in response to cancer therapy. Specifically, HMGB1 release has been shown to occur with a specific form of induced cell death known as necroptosis. In the present study, we examined the role of HMGB1 in the necroptosis of acute myeloid leukemia (AML) cells. In two AML cell lines and primary AML cells from two patients, etoposide induced necroptosis via cIAP1/2 degradation when caspase activity was inhibited by Z-VAD-fmk, but treatment with extracellular HMGB1 prevented this necroptosis. Interestingly, HMGB1 did not prevent the degradation of cIAP1/2, but rather activated the nuclear factor kappa B pathway. The results of the present study provide evidence that extracellular HMGB1 is not only an important DAMP molecule released by cells upon necrosis, but also a regulatory factor that prevents necroptosis in AML cells.

Background The tumor location-modified Lauren classification (mLC) has been proposed recently, but its clinical significance remains under debate. This study aimed to elucidate the clinical relevance of mLC and evaluate its superiority to the Lauren classification (LC) for gastric cancer patients with gastrectomy. Methods This study retrospectively evaluated 2764 consecutive gastric cancer patients from three comprehensive medical institutions. The patients were categorized into training, inner-validation, and independent validation sets. The relationships between mLC and other clinicopathologic factors were analyzed, and independent prognostic factors were identified. Survival prognostic discriminatory ability and predictive accuracy were compared between mLC and LC using the concordance index (C-index) and Akaike’s information criterion (AIC), and a nomogram based on mLC was constructed to compare its prognostic improvement with the tumor-node metastasis (TNM) staging system. Results A significant association between mLC and gender, age, histologic type, T stage, N stage, and M stage was found. The findings showed that mLC, not LC, is an independent prognostic factor, with a smaller AIC and a higher C-index than LC. The nomogram based on mLC showed a better predictive ability than TNM alone. Conclusions Compared with LC, mLC, which could be considered a more reliable prognostic factor, may improve the prognostic discriminatory ability and predictive accuracy for gastric cancer patients with gastrectomy. Electronic supplementary material The online version of this article (10.1245/s10434-018-6654-8) contains supplementary material, which is available to authorized users.

Signet-ring cell carcinoma (SRCC) has specific epidemiology and oncogenesis in gastric cancer, however, with no systematical investigation for prognostic genomic features. Here we report a systematic investigation conducted in 1868 Chinese gastric cancer patients indicating that signet-ring cells content was related to multiple clinical characteristics and treatment outcomes. We thus perform whole-genome sequencing on 32 pairs of SRC samples, and identify frequent CLDN18-ARHGAP26/6 fusion (25%). With 797 additional patients for validation, prevalence of CLDN18-ARHGAP26/6 fusion is noticed to be associated with signet-ring cell content, age at diagnosis, female/male ratio, and TNM stage. Importantly, patients with CLDN18-ARHGAP26/6 fusion have worse survival outcomes, and get no benefit from oxaliplatin/fluoropyrimidines-based chemotherapy, which is consistent with the fact of chemo-drug resistance acquired in CLDN18-ARHGAP26 introduced cell lines. Overall, this study provides insights into the clinical and genomic features of SRCC, and highlights the importance of frequent CLDN18-ARHGAP26/6 fusions in chemotherapy response for SRCC., Signet-ring cell carcinoma (SRCC) is a unique type of gastric cancer with no prognostic features. Here, the authors report a CLDN18-ARHGAP26/6 gene fusion in patients with a high signet-ring cell content, poor survival outcomes, and who experience no benefit from platinum/fluoropyrimidines-based chemotherapy.

The tumor location-modified Lauren classification (mLC) has been proposed recently, but its clinical significance remains under debate. This study aimed to elucidate the clinical relevance of mLC and evaluate its superiority to the Lauren classification (LC) for gastric cancer patients with gastrectomy.This study retrospectively evaluated 2764 consecutive gastric cancer patients from three comprehensive medical institutions. The patients were categorized into training, inner-validation, and independent validation sets. The relationships between mLC and other clinicopathologic factors were analyzed, and independent prognostic factors were identified. Survival prognostic discriminatory ability and predictive accuracy were compared between mLC and LC using the concordance index (C-index) and Akaike's information criterion (AIC), and a nomogram based on mLC was constructed to compare its prognostic improvement with the tumor-node metastasis (TNM) staging system.A significant association between mLC and gender, age, histologic type, T stage, N stage, and M stage was found. The findings showed that mLC, not LC, is an independent prognostic factor, with a smaller AIC and a higher C-index than LC. The nomogram based on mLC showed a better predictive ability than TNM alone.Compared with LC, mLC, which could be considered a more reliable prognostic factor, may improve the prognostic discriminatory ability and predictive accuracy for gastric cancer patients with gastrectomy.

The prognosis of remnant gastric cancer (RGC) is significantly poor. However, the mechanism and some clinical features of RGC have not been fully understood and are still under debate.From January 2000 to January 2014, 90 RGC patients were enrolled in this retrospective study. Patients were divided into two groups according to primary disease. Clinicopathological features and survival outcomes were compared between two groups.A total of 34 (37.8%) patients were diagnosed with remnant gastric cancer following benign disease (RGCB) and 56 (62.2%) were diagnosed with remnant gastric cancer following malignant disease (RGCM). The mean time interval from the primary operation to the development of RGC was 12.5 ± 13.3 years in all RGC patients. The mean time interval in RGCB was significantly longer than that in RGCM (P 0.01). The 1-, 2-, and 3- year overall survival rates of all patients were 56.1%, 38.2% and 33.2%, respectively. Univariate analysis indicated that tumor size, curability, histology type, serosa invasion, nodal involvement and distant metastasis were prognostic factors for RGC. The multivariate Cox regression analysis revealed that distant metastasis was an independent prognostic factor for RGC.RGC occurred earlier in patients with gastrectomy for primary malignant disease than for primary benign disease, even though the primary disease made no difference to the survival of RGC. Nonetheless, RGC patients experienced dismal overall survival. Therefore, early diagnosis plays a significant role in successfully carrying out curative resection and improving the prognosis for RGC.

Ischemic stroke is a major cause of mortality and morbidity globally. Among the ischemic stroke subtypes, cardioembolic stroke is with poor functional outcome (Modified Rankin score ≥ 2). Early diagnosis of cardioembolic stroke will prove beneficial. This study examined the microRNAs targeting cluster of differentiation 46 (CD46), a potential biomarker for cardioembolic stroke. CD46 mRNA level was shown to be differentially expressed (p < 0.001) between cardioembolic stroke (median = 1.32) and non-cardioembolic stroke subtypes (large artery stroke median = 5.05; small vessel stroke median = 6.45). Bioinformatic search showed that miR-19a, -20a, -185 and -374b were found to target CD46 mRNA and further verified by luciferase reporter assay. The levels of miRNAs targeting CD46 were significantly reduced (p < 0.05) in non-cardioembolic stroke patients (large artery stroke median: miR-19a = 0.63, miR-20a = 0.42, miR-185 = 0.32, miR-374b = 0.27; small artery stroke median: miR-19a = 0.07, miR-20a = 0.06, miR-185 = 0.07, miR-374b = 0.05) as compared to cardioembolic stroke patients (median: miR-19a = 2.69, miR-20a = 1.36, miR-185 = 1.05, miR-374b = 1.23). ROC curve showed that the miRNAs could distinguish cardioembolic stroke from non-cardioembolic stroke with better AUC value as compared to CD46. Endogenous expression of CD46 in Human Umbilical Vein Endothelial Cells (HUVECs) were found to be regulated by miR-19a and miR-20a. Thus implicating that miR-19a and -20a may play a role in pathogenesis of cardioembolic stroke, possibly via the endothelial cells.

Introduction: In 2009, the United Kingdom Department of Health identified the need to assist families so that people with dementia can remain living at home. Occupational therapists could support families and their loved ones at home by understanding the human occupational impact of caregiving. This impact includes how one is influenced by values and motivated to perform activities shaped by experiences and life roles. The purpose of this review was to synthesize qualitative research related to family dementia caregiving, extrapolating information about the human occupational impact on the caregiver. The aim was to inform occupational therapy practice. Method: A search was conducted across a range of electronic databases. A quality appraisal tool was specifically developed for the study appraisal and data extraction process. Data were extracted and analysed within the Model of Human Occupation framework. Findings: Twenty studies were included in this review. Five themes emerged: adapting to dementia; staying motivated and in control; preserving occupational balance and wellbeing; gaining meaning from the caregiver role; and losses and burden. Conclusion: The human occupational impact of caregiving affects the quality and decision-making of care for families. Occupational therapists are well placed to support families through the stages of dementia.

Chinese medicinal plants and their surrounding rhizospheric soil serve as promising sources of actinobacteria. A total of 180 actinobacteria strains were isolated from the rhizosphere soil, leaves, stems, and roots of nine selected plants and have been identified as potential biocontrol agents against Fusarium oxysporum f. sp. cucumerinum. An endophytic strain CNS-42 isolated from Alisma orientale showed the largest zone of inhibition demonstrating a potent effect against F. oxysporum f. sp. cucumerinum and a broad antimicrobial activity against bacteria, yeasts, and other pathogenic fungi. The in vivo biocontrol assays showed that the disease severity index was significantly reduced (P < 0.05), and plant shoot fresh weight and height increased greatly (P < 0.05) in plantlets treated with strain CNS-42 compared to the negative control. This isolate was identified as Streptomyces sp. based on cultural, physiological, morphological characteristics, and 16S rRNA gene analysis. Further bioassay-guided isolation and purification revealed that staurosporine was responsible for its antifungal and plant growth promoting activities and the latter property of staurosporine is reported for the first time. The in vivo assay was further performed and indicated that staurosporine showed good growth promoting effect on the plant shoot biomass of cucumber. This is the first critical evidence identifying CNS-42 as a biocontrol agent for the soil borne pathogen, F. oxysporum f. sp. cucumerinum.