Pausing of RNA polymerase II disrupts DNA-specified nucleosome organization to enable precise gene regulation.

Metazoan transcription is controlled through either coordinated recruitment of transcription machinery to the gene promoter or regulated pausing of RNA polymerase II (Pol II) in early elongation. We report that a striking difference between genes that use these distinct regulatory strategies lies in the "default" chromatin architecture specified by their DNA sequences. Pol II pausing is prominent at highly regulated genes whose sequences inherently disfavor nucleosome formation within the gene but favor occlusion of the promoter by nucleosomes. In contrast, housekeeping genes that lack pronounced Pol II pausing show higher nucleosome occupancy downstream, but their promoters are deprived of nucleosomes regardless of polymerase binding. Our results indicate that a key role of paused Pol II is to compete with nucleosomes for occupancy of highly regulated promoters, thereby preventing the formation of repressive chromatin architecture to facilitate further or future gene activation.

Pan-cancer analysis of the tumorigenic role of Fanconi anemia complementation group D2 (FANCD2) in human tumors.

Monoubiquitination of FANCD2 is a central step in the activation of the Fanconi anemia (FA) pathway after DNA damage. Defects in the FA pathway centered around FANCD2 not only lead to genomic instability but also induce tumorigenesis. At present, few studies have investigated FANCD2 in tumors, and no pan-cancer research on FANCD2 has been conducted. We conducted a comprehensive analysis of the role of FANCD2 in cancer using public databases and other published studies. Moreover, we evaluated the role of FANCD2 in the proliferation, migration and invasion of lung adenocarcinoma cells through in vitro and in vivo experiments, and explored the role of FANCD2 in cisplatin chemoresistance. We investigated the regulatory effect of FANCD2 on the cell cycle of lung adenocarcinoma cells by flow cytometry, and verified this effect by western blotting. FANCD2 expression is elevated in most TCGA tumors and shows a strong positive correlation with poor prognosis in tumor patients. In addition, FANCD2 expression shows strong correlations with immune infiltration, immune checkpoints, the tumor mutation burden (TMB), and microsatellite instability (MSI), which are immune-related features, suggesting that it may be a potential target of tumor immunotherapy. We further found that FANCD2 significantly promotes the proliferation, invasion, and migration abilities of lung adenocarcinoma cells and that its ability to promote cancer cell proliferation may be achieved by modulating the cell cycle. The findings indicate that FANCD2 is a potential biomarker and therapeutic target in cancer treatment by analyzing the oncogenic role of FANCD2 in different tumors.

Tumor microenvironment characteristics association with clinical outcome in patients with resected intestinal-type gastric cancer.

BACKGROUND: Tumor microenvironment (TME) characteristics including tumor stroma ratio (TSR), tumor budding (TB), and tumor-infiltrating lymphocytes (TILs) were examined in resected gastric cancer. These TME features have been shown to indicate metastatic potential in colon cancer, and intestinal-type gastric cancer (IGC) has pathological similarities with that malignancy. METHODS: TSR, TB, and TILs were quantified in routine histological sections from 493 patients with IGC who underwent radical resection at 2 university hospitals in China from 2010 to 2016. TME variables were dichotomized as follows: TSR (50%), TILs (median), TB per international guidelines (4 buds/0.785mm2), and platelet-lymphocyte ratio (PLR) per survival ROC. Association of TME features with patient clinicopathological characteristics, time-to-recurrence (TTR), and cancer-specific-survival (CSS) were examined using univariate and multivariate analysis, including a relative contribution analysis by Cox regression. RESULTS: Patients whose tumors showed high TSR or high TB or low TILs were each significantly associated with increased T and N stage, higher histological grade, and poorer TTR and CSS at 5 years. Only TSR and N stage were independently associated with TTR and CSS after adjustment for covariates. PLR was only independently associated with TTR after adjustment for covariates. Among the variables examined, only TSR was significantly associated with both TTR (HR 1.72, 95% CI, 1.14-2.60, P = .01) and CSS (HR 1.62, 95% CI, 1.05-2.51, P = .03) multivariately. Relative contribution to TTR revealed that the top 3 contributors were N stage (45.1%), TSR (22.5%), and PLR (12.9%), while the top 3 contributors to CSS were N stage (59.9%), TSR (14.7%), and PLR (10.9%). CONCLUSIONS: Among the examined TME features, TSR was the most robust for prognostication and was significantly associated with both TTR and CSS. Furthermore, the relative contribution of TSR to patient TTR and CSS was second only to nodal status.

Comparison of power spectra from overnight electroencephalography between patients with Down syndrome and matched control subjects.

Electroencephalograms can capture brain oscillatory activities during sleep as a form of electrophysiological signals. We analysed electroencephalogram recordings from full-night in-laboratory polysomnography from 100 patients with Down syndrome, and 100 age- and sex-matched controls. The ages of patients with Down syndrome spanned 1 month to 31 years (median 4.4 years); 84 were younger than 12 years, and 54 were male. From each electroencephalogram, we extracted relative power in six frequency bands or rhythms (delta, theta, alpha, slow sigma, fast sigma, and beta) from six channels (frontal F3 and F4, central C3 and C4, and occipital O1 and O2) during five sleep stages (N3, N2, N1, R and W)-180 features in all. We examined differences in relative power between Down syndrome and control electroencephalograms for each feature separately. During wake and N1 sleep stages, alpha rhythms (8.0-10.5 Hz) had significantly lower power in patients with Down syndrome than controls. Moreover, the rate of increase in alpha power with age during rapid eye movement sleep was significantly slower in Down syndrome than control subjects. During wake and N1 sleep, delta rhythms (0.25-4.5 Hz) had higher power in patients with Down syndrome than controls. During N2 sleep, slow sigma rhythms (10.5-12.5 Hz) had lower power in patients with DS than controls. These findings extend previous research from routine electroencephalogram studies demonstrating that patients with Down syndrome had reduced circadian amplitude-the difference between wake alpha power and deep sleep delta power was smaller in Down syndrome than control subjects. We envision that these brain oscillatory activities may be used as surrogate markers for clinical trials for patients with Down syndrome.

GADGETS: a genetic algorithm for detecting epistasis using nuclear families.

MOTIVATION: Epistasis may play an etiologic role in complex diseases, but research has been hindered because identification of interactions among sets of single nucleotide polymorphisms (SNPs) requires exploration of immense search spaces. Current approaches using nuclear families accommodate at most several hundred candidate SNPs. RESULTS: GADGETS detects epistatic SNP-sets by applying a genetic algorithm to case-parent or case-sibling data. To allow for multiple epistatic sets, island subpopulations of SNP-sets evolve separately under selection for evident joint relevance to disease risk. The software evaluates the identified SNP-sets via permutation testing and provides graphical visualization. GADGETS correctly identified epistatic SNP-sets in realistically simulated case-parent triads with 10 000 candidate SNPs, far more SNPs than competitors can handle, and it outperformed competitors in simulations with many fewer SNPs. Applying GADGETS to family-based oral-clefting data from dbGaP identified SNP-sets with possible epistatic effects on risk. AVAILABILITY AND IMPLEMENTATION: GADGETS is part of the epistasisGA package at https://github.com/mnodzenski/epistasisGA. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Effect of the gut microbiota and their metabolites on postoperative intestinal motility and its underlying mechanisms.

Gut microbiota is closely related to human health and disease because, together with their metabolites, gut microbiota maintain normal intestinal peristalsis. The use of antibiotics or opioid anesthetics, or both, during surgical procedures can lead to dysbiosis and affect intestinal motility; however, the underlying mechanisms are not fully known. This review aims to discuss the effect of gut microbiota and their metabolites on postoperative intestinal motility, focusing on regulating the enteric nervous system, 5-hydroxytryptamine neurotransmitter, and aryl hydrocarbon receptor.

Comparison of specimen extraction site and another site for protective loop ileostomy in laparoscopic low anterior rectal resection: a retrospective comparative study.

BACKGROUND: Protective loop ileostomy is commonly performed in laparoscopic low anterior rectal resection to prevent the serious complications of anastomotic fistula. It is usually created at the right lower quadrant of the abdomen and another wound is required for stoma. The study aimed to evaluate the outcomes of ileostomy at the specimen extraction site (SES) and another site (AS) beside the auxiliary incision. METHODS: A retrospective analysis was conducted on 101 eligible patients with pathologically diagnosed adenocarcinoma of the rectum from January 2020 to December 2021 in the study center. According to whether the ileostomy was at the specimen extraction site, patients were divided into SES group (40 patients) and AS group (61 patients). Clinicopathological characteristics, the intraoperative details, and postoperative outcomes of the two groups were measured. RESULTS: Univariate analysis showed that the operative time was significantly shorter and the blood loss was significantly less in the SES group than in the AS group during laparoscopic low anterior rectal resection, the time to first flatus was significantly shorter, and the pain was significantly less in the SES group than in the AS group during ileostomy closure. The postoperative complications were similar in both groups. Multivariable analysis showed that ileostomy at the specimen extraction site was a significant factor influencing the operative time and blood loss of rectal resection, and influencing the pain and the time to first flatus during ileostomy closure. CONCLUSION: Compared to ileostomy at AS, protective loop ileostomy at SES was time-saving and less bleeding during laparoscopic low anterior rectal resection, and more quick to first flatus and less pain during stoma closure, and did not lead to more postoperative complications. The median incision of the lower abdomen and the left lower abdominal incision were both good sites for ileostomy.

Effects of CPAP and Mandibular Advancement Devices on depressive symptoms in patients with obstructive sleep apnea: a meta-analysis of randomized controlled trials.

PURPOSE: Studies show that patients with obstructive sleep apnea (OSA) are more likely than the general population to have psychological disorders such as depression. However, it is less clear how OSA treatment affects this association. This meta-analysis aimed to assess whether or not continuous positive airway pressure (CPAP) and mandibular advancement devices (MADs) reduce depression symptoms in patients with OSA. METHODS: We searched Pubmed, Embase, Web of Science, and Cochrane Library from creating the databases until November 2022. Our analysis included RCTs that examined CPAP and MAD treatment effectiveness for depression in patients with OSA. RESULTS: We identified 17 CPAP studies comprising 1,931 patients for inclusion in the meta-analysis. The results of the meta-analysis using a fixed effects model found that CPAP improved depressed mood in patients with OSA relative to controls (SMD = 0.27;95% CI:0.18,0.36), with small heterogeneity among trials (I2 = 8.1% < 50%, P = 0.359). We performed subgroup analyses on three factors: the length of trial follow-up, patient adherence data, and depression assessment scales. The meta-analysis also identified six MAD studies involving 315 patients. According to this analysis, there was no heterogeneity between studies (I2 = 0%, P = 0.748). MADs did not significantly improve depression symptoms compared to controls, indicating a combined effect of SMD = 0.07 (95% CI: - 0.15,0.29), P > 0.05. CONCLUSION: The present findings confirm that CPAP may improve depressive symptoms in patients with OSA. However, the review results suggest that MADs have no significant effect on depressive symptoms in patients with OSA, a finding that is different from the results of previous meta-analyses.

Increased Hemichannel Activity Displayed by a Connexin43 Mutation Causing a Familial Connexinopathy Exhibiting Hypotrichosis with Follicular Keratosis and Hyperostosis.

Mutations in the GJA1 gene that encodes connexin43 (Cx43) cause several rare genetic disorders, including diseases affecting the epidermis. Here, we examined the in vitro functional consequences of a Cx43 mutation, Cx43-G38E, linked to a novel human phenotype of hypotrichosis, follicular keratosis and hyperostosis. We found that Cx43-G38E was efficiently translated in Xenopus oocytes and localized to gap junction plaques in transfected HeLa cells. Cx43-G38E formed functional gap junction channels with the same efficiency as wild-type Cx43 in Xenopus oocytes, although voltage gating of the gap junction channels was altered. Notably, Cx43-G38E significantly increased membrane current flow through the formation of active hemichannels when compared to wild-type Cx43. These data demonstrate the association of increased hemichannel activity to a connexin mutation linked to a skeletal-cutaneous phenotype, suggesting that augmented hemichannel activity could play a role in skin and skeletal disorders caused by human Cx43 mutations.

The synergistic effect of sea cucumber saponins and caffeine on preventing obesity in high-fat diet-fed mice by extending the action duration of caffeine.

BACKGROUND: Sea cucumber saponins (SCSs) exhibit a unique structure and high bioactivities and might have specialized implications on caffeine metabolic process by altering the activity of N-demethylation enzyme CYP1A2. The present study aimed to clarify the effects of SCS on caffeine metabolism in vivo and in vitro, as well as the synergistic anti-obesity effect of SCS and caffeine on high-fat diet-induced obese mice. RESULTS: Results found that SCS administration significantly postponed the elimination rate of caffeine and its metabolites in vivo, and further study found CYP1A2-mediated caffeine metabolism was remarkably inhibited in a dose-dependent manner in vitro. The synergistic effect of the SCS and caffeine combination could decrease the total weight of white adipose tissue by 52% compared with high-fat diet-treated group. CONCLUSION: SCS could prolong caffeine action time, and the combination of the two substances exhibited joint action on high-fat diet-induced obese mice. These findings might provide a basis for the development of functional foods and potential application using the combination of SCS and caffeine. © 2022 Society of Chemical Industry.

Intra-graph and Inter-graph joint information propagation network with third-order text graph tensor for fake news detection.

Although the Internet and social media provide people with a range of opportunities and benefits in a variety of ways, the proliferation of fake news has negatively affected society and individuals. Many efforts have been invested to detect the fake news. However, to learn the representation of fake news by context information, it has brought many challenges for fake news detection due to the feature sparsity and ineffectively capturing the non-consecutive and long-range context. In this paper, we have proposed Intra-graph and Inter-graph Joint Information Propagation Network (abbreviated as IIJIPN) with Third-order Text Graph Tensor for fake news detection. Specifically, data augmentation is firstly utilized to solve the data imbalance and strengthen the small corpus. In the stage of feature extraction, Third-order Text Graph Tensor with sequential, syntactic, and semantic features is proposed to describe contextual information at different language properties. After constructing the text graphs for each text feature, Intra-graph and Inter-graph Joint Information Propagation is used for encoding the text: intra-graph information propagation is performed in each graph to realize homogeneous information interaction, and high-order homogeneous information interaction in each graph can be achieved by stacking propagation layer; inter-graph information propagation is performed among text graphs to realize heterogeneous information interaction by connecting the nodes across the graphs. Finally, news representations are generated by attention mechanism consisting of graph-level attention and node-level attention mechanism, and then news representations are fed into a fake news classifier. The experimental results on four public datasets indicate that our model has outperformed state-of-the-art methods. Our source code is available at https://github.com/cuibenkuan/IIJIPN.

Randomized Controlled Trial Comparing the Short-term Outcomes of Enhanced Recovery After Surgery and Conventional Care in Laparoscopic Distal Gastrectomy (GISSG1901).

OBJECTIVE: This study aimed to compare the effects of ERAS and conventional programs on short-term outcomes after LDG. SUMMARY OF BACKGROUND DATA: Currently, the ERAS program is broadly applied in surgical areas. Although several benefits of LDG with the ERAS program have been covered, high-level evidence is still limited, specifically in advanced gastric cancer. METHODS: The present study was designed as a randomized, multicenter, unblinded trial. The enrollment criteria included histologically confirmed cT2-4aN0-3M0 gastric adenocarcinoma. Postoperative complications, mortality, readmission, medical costs, recovery, and laboratory outcomes were compared between the ERAS and conventional groups. RESULTS: Between April 2019 and May 2020, 400 consecutive patients who met the enrollment criteria were enrolled. They were randomly allocated to either the ERAS group (n = 200) or the conventional group (n = 200). After excluding patients who did not undergo surgery or gastrectomy, 370 patients were analyzed. The patient demographic characteristics were not different between the 2 groups. The conventional group had a significantly longer allowed day of discharge and postoperative hospital stay (6.96 vs 5.83 days, P < 0.001; 8.85 vs 7.27 days, P < 0.001); a longer time to first flatus, liquid intake and ambulation (3.37 vs 2.52 days, P < 0.001; 3.09 vs 1.13 days, P < 0.001; 2.85 vs 1.38 days, P < 0.001, respectively); and higher medical costs (6826 vs 6328 $, P = 0.027) than the ERAS group. Additionally, patients in the ERAS group were more likely to initiate adjuvant chemotherapy earlier (29 vs 32 days, P = 0.035). There was no significant difference in postoperative complications or in the mortality or readmission rates. Regarding laboratory outcomes, the procalcitonin and C-reactive protein levels on postoperative day 3 were significantly lower and the hemoglobin levels on postoperative day 5 were significantly higher in the ERAS group than in the conventional group. CONCLUSION: The ERAS program provides a faster recovery, a shorter postoperative hospitalization length, and lower medical costs after LDG without increasing complication and readmission rates. Moreover, enhanced recovery in the ERAS group enables early initiation of adjuvant chemotherapy.

hsa-miR-875-5p inhibits tumorigenesis and suppresses TGF-ß signalling by targeting USF2 in gastric cancer.

BACKGROUND: Gastric cancer (GC) is one of the most common malignancies, and an increasing number of studies have shown that its pathogenesis is regulated by various miRNAs. In this study, we investigated the role of miR-875-5p in GC. METHODS: The expression of miR-875-5p was detected in human GC specimens and cell lines by miRNA qRT-PCR. The effect of miR-875-5p on GC proliferation was determined by Cell Counting Kit-8 (CCK-8) proliferation and 5-ethynyl-2'-deoxyuridine (EdU) assays. Migration and invasion were examined by transwell migration and invasion assays as well as wound healing assays. The interaction between miR-875-5p and its target gene upstream stimulatory factor 2(USF2) was verified by dual luciferase reporter assays. The effects of miR-875-5p in vivo were studied in xenograft nude mouse models. Related proteins were detected by western blot. RESULTS: The results showed that miR-875-5p inhibited the proliferation, migration and invasion of GC cells in vitro and inhibited tumorigenesis in vivo. USF2 was proved to be a direct target of miR-875-5p. Knockdown of USF2 partially counteracted the effects of miR-875-5p inhibitor. Overexpression of miR-875-5p could inhibit proliferation, migration and invasion and suppress the TGF-ß signalling pathway by downregulating USF2. CONCLUSIONS: MiR-875-5p can inhibit the progression of GC by directly targeting USF2. And in the future, miR-875-5p is expected to be a potential target for GC diagnosis and treatment.

Ultrasonic surgical and electrosurgical system (USES) with conventional ultrasonic scalpel (CUS) in gastrectomy: a retrospective cohort study.

BACKGROUND: Harmonic ACE +7 Shears with Advanced Hemostasis is an upgraded ultrasonic device, an ultrasonic surgical and electrosurgical system (USES). The study aimed to evaluate the economic and clinical effectiveness of the USES compared with the conventional ultrasonic scalpel (CUS) in gastrectomy. METHODS: We conducted a single-center, retrospective cohort study using the electronic medical records in China. We collected intraoperative and postoperative data from gastric cancer patients who underwent the endoscope-assisted distal gastrectomy from 2018 to June 30, 2019. Procedure-related costs were estimated. We used linear regression by controlling a set of covariates to assess the effect of USES on outcomes. RESULT: Out of 87 eligible patients, the USES group (40 patients) and CUS group (47 patients) were comparable in terms of age, medical history and stages of cancer. Compared with the CUS, the USES saved 4.27 hemoclips per person (95% CI 0.57-7.97, p < 0.05) and 34.18 ml intraoperative blood per person (95% CI 8.74-59.62 ml, p < 0.05), respectively. Postoperative length of stay (LOS) was shorter in the USES group (7.90 ± 1.95 vs. 9.26 ± 2.81 days) but the difference was not statistically significant (p = 0.05). CONCLUSIONS: The USES group was associated with fewer hemoclips use and intraoperative blood loss in patients undergoing laparoscopic gastrectomy at comparable costs.

PDRG1 predicts a poor prognosis and facilitates the proliferation and metastasis of colorectal cancer.

OBJECTIVE: The incidence and mortality of colorectal cancer (CRC) is increasing yearly and CRC patients are becoming younger in global. Evidences have revealed the carcinogenic effect of p53 and DNA damage-regulated gene 1 (PDRG1) in several types of tumors. However, its biological function is yet to be investigated in CRC. This study aimed to unveil the prooncogenic role of PDRG1 in CRC. METHODS: We detected the expression and clinical pathological features of PDRG1 in CRC tissues and paired non-tumor adjacent tissues. The biological role and molecular mechanism of PDRG1 in CRC were characterized through a range of in vitro and in vivo experiments and datasets analysis. RESULT: We identified the significant up-regulated expression of PDRG1 both in CRC tissues and cell, and higher expression of PDRG1 was associated with worse clinicopathological stage and poorer survival outcome. Cox regression analysis revealed that PDRG1 is an independent prognostic factor for CRC patients. Silencing of PDRG1 significantly retarded CRC cell vitality, invasion and migration, induced cell apoptosis and G0/G1 phase arrest. PDRG1 knockdown also attenuated tumor growth and metastasis as evidencing in vivo experiment. The expression of p21 and apoptosis related protein was enhanced with the knockdown of PDRG1 while cell cycle protein was inhibited. CONCLUSION: PDRG1 function as a novel oncogene and participate in malignant progression of CRC by regulating p21-mediated signal pathway, suggesting that it can serve as a valuable predictive biomarker for diagnosing of CRC patient and a promising target for therapy.

Overall Survival Advantage of Omentum Preservation Over Omentectomy for Advanced Gastric Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Since 1910, omentectomy has been an essential component of radical gastrectomy for advanced gastric cancer. However, researchers have recently questioned the benefit of omentectomy in radical gastrectomy. The aim of this meta-analysis was to compare omentectomy and omentum preservation in gastrectomy for advanced gastric cancer in terms of survival outcomes and short-term outcomes. METHODS: The PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched. Studies that compared omentum preservation with omentectomy were included. Overall survival (OS) and relapse-free survival (RFS) were analyzed as primary outcomes. RESULTS: Of 3509 records screened, one randomized clinical trial and five propensity-score matched retrospective studies with 1661 patients were selected. Omentum preservation was associated with improved OS (hazard ratio [HR] = 0.757, 95% confidence interval [CI] = 0.603-0.950, P = 0.016, I2 = 0%), but not with improved RFS (HR = 0.821, 95% CI = 0.668-1.009, P = 0.060, I2 = 9%) compared with omentectomy for advanced gastric cancer. Furthermore, less blood loss and shorter operation time were found in the omentum preservation group than in the omentectomy group. Additionally, the rate of peritoneal recurrence, the number of harvested lymph nodes, and the incidences of postoperative complications and ileus were comparable in the two groups. CONCLUSIONS: Basing on the current literature, gastrectomy with omentum preservation was associated with improved OS and short-term outcomes compared with omentectomy for advanced gastric cancer. Further randomized trials are required to confirm the survival benefit of omentum-preserving gastrectomy.

Development of a Porcine Model to Assess the Effect of In Situ Knee Joint Loading on Site-Specific Cartilage Gene Expression.

Cyclic mechanical loading of cartilage induces stresses and fluid flow, which are thought to modulate chondrocyte metabolism. The uneven surface, plus the heterogeneity of cartilage within a joint, makes stress and fluid pressure distribution in the tissue nonuniform, and gene expression may vary at different sites as a function of load magnitude, frequency, and time. In previous studies, cartilage explants were used for loading tests to investigate biological responses of the cartilage to mechanical loading. In contrast, we used loading tests on intact knee joints, to better reflect the loading conditions in a joint, and thus provide a more physiologically relevant mechanical environment. Gene expression levels in loaded samples for a selection of relevant genes were compared with those of the corresponding unloaded control samples to characterize potential differences. Furthermore, the effects of load magnitude and duration on gene expression levels were investigated. We observed differences in gene expression levels between samples from different sites in the same joint and between corresponding samples from the same site in loaded and unloaded joints. Consistent with previous findings, our results indicate that there is a critical upper and lower threshold of loading for triggering the expression of certain genes. Variations in gene expression levels may reflect the effect of local loading, topography, and structure of the cartilage in an intact joint on the metabolic activity of the associated cells.

Naples prognostic score, a novel prognostic score for patients with high- and intermediate-risk gastrointestinal stromal tumours after surgical resection.

BACKGROUND: A novel multidimensional inflammatory and nutritional assessment system named the Naples prognostic score could serve as an independent prognostic indicator. However, its significance in patients with high- and intermediate-risk gastrointestinal stromal tumours remains unclear. METHODS: We performed this retrospective cohort study based on a prospectively collected database of gastrointestinal stromal tumours (GISTs) between March 2010 and December 2019. The Kaplan-Meier method and log-rank test were used for survival analyses. Least absolute shrinkage and selection operator (LASSO) and Cox proportional hazards regression analysis was used for univariate and multivariate analyses. Time-dependent receiver operating characteristic curves were generated to evaluate the discriminatory ability of the prognostic scoring systems. Differences in the areas under the curve were further compared. RESULTS: A total of 405 patients with regular follow-up were included and analysed in this study. Significant differences in progression-free survival and overall survival were observed between the groups (P < 0.001). Multivariate analysis demonstrated that the NPS was a significant predictor of poor progression-free survival (1 vs 0, HR = 4.622, P = 0.001; 2 vs 0, HR = 12.770, P < 0.001) and overall survival (2 vs 0, HR = 5.535, P = 0.002). Furthermore, time-dependent AUC analyses showed that the NPS was more accurate than other haematologic prognostic systems. CONCLUSIONS: The present study demonstrates that the NPS could independently predict disease progression and survival among patients with high- and intermediate-risk GISTs. The NPS might be regarded and applied as one of the most convenient and effective preoperative risk stratification tools in the future, which should be validated by large-scale multicentre prospective cohort studies.

Risk factors for periappendiceal adhesions in acute appendicitis: a retrospective comparative study.

PURPOSE: Acute appendicitis usually requires immediate surgical treatment, but appendectomies were difficult for some patients with severe periappendiceal adhesions. We investigated risk factors of intraoperative adhesions to help surgeons make better treatment plans for appendicitis. METHODS: We retrospectively analyzed 186 cases diagnosed with acute appendicitis and underwent surgery in Shandong Provincial Hospital affiliated to Shandong First Medical University between January 2018 and December 2019. According to the degree of intraoperative adhesions, they were divided into mild, moderate and severe groups. Then, we analyzed a number of preoperative factors contributed to adhesions, suppuration and perforation during appendectomy in 186 patients. RESULTS: Contrast to the moderate group (MoG) and the mild group (MiG), the severe degree of adhesions group (SG) had a higher intraoperative perforation and suppuration rate, a greater likelihood of conversion to open and more postoperative complications. Multivariable logistic regression analysis showed that recurrent appendicitis and high neutrophil percentage were independently associated with periappendiceal adhesions. The preoperative ultrasonography (US) revealed periappendiceal fluid and high neutrophil percentage were independently associated with appendix suppuration. A high preoperative neutrophil percentage was independently associated with appendix perforation. CONCLUSIONS: Recurrent appendicitis and preoperative high neutrophil percentage were risk factors of periappendiceal adhesions; preoperative US revealed periappendiceal fluid and high neutrophil percentage were risk factors of appendix suppuration; and a high preoperative neutrophil percentage was a risk factor of appendix perforation.

Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): an open-label, superiority and non-inferiority, phase 3 randomised controlled trial.

BACKGROUND: The optimal perioperative chemotherapeutic regimen for locally advanced gastric cancer remains undefined. We evaluated the efficacy and safety of perioperative and postoperative S-1 and oxaliplatin (SOX) compared with postoperative capecitabine and oxaliplatin (CapOx) in patients with locally advanced gastric cancer undergoing D2 gastrectomy. METHODS: We did this open-label, phase 3, superiority and non-inferiority, randomised trial at 27 hospitals in China. We recruited antitumour treatment-naive patients aged 18 years or older with historically confirmed cT4a N+ M0 or cT4b Nany M0 gastric or gastro-oesophageal junction adenocarcinoma, with Karnofsky performance score of 70 or more. Patients undergoing D2 gastrectomy were randomly assigned (1:1:1) via an interactive web response system, stratified by participating centres and Lauren classification, to receive adjuvant CapOx (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day one of each 21 day cycle plus oral capecitabine 1000 mg/m2 twice a day), adjuvant SOX (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day one of each 21 day cycle plus oral S-1 40-60 mg twice a day), or perioperative SOX (intravenous oxaliplatin 130 mg/m2 on day one of each 21 day plus oral S-1 40-60 mg twice a day for three cycles preoperatively and five cycles postoperatively followed by three cycles of S-1 monotherapy). The primary endpoint, assessed in the modified intention-to-treat population, 3-year disease-free survival to assess the superiority of perioperative-SOX compared with adjuvant-SOX and the non-inferiority (hazard ratio non-inferiority margin of 1·33) of adjuvant-SOX compared with adjuvant-CapOx. Safety analysis were done in patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT01534546. FINDINGS: Between Aug 15, 2012, and Feb 28, 2017, 1094 patients were screened and 1022 (93%) were included in the modified intention-to-treat population, of whom 345 (34%) patients were assigned to the adjuvant-CapOx, 340 (33%) patients to the adjuvant-SOX group, and 337 (33%) patients to the perioperative-SOX group. 3-year disease-free survival was 51·1% (95% CI 45·5-56·3) in the adjuvant-CapOx group, 56·5% (51·0-61·7) in the adjuvant-SOX group, and 59·4% (53·8-64·6) in the perioperative-SOX group. The hazard ratio (HR) was 0·77 (95% CI 0·61-0·97; Wald p=0·028) for the perioperative-SOX group compared with the adjuvant-CapOx group and 0·86 (0·68-1·07; Wald p=0·17) for the adjuvant-SOX group compared with the adjuvant-CapOx group. The most common grade 3-4 adverse events was neutropenia (32 [12%] of 258 patients in the adjuvant-CapOx group, 21 [8%] of 249 patients in the adjuvant-SOX group, and 30 [10%] of 310 patients in the perioperative-SOX group). Serious adverse events were reported in seven (3%) of 258 patients in adjuvant-CapOx group, two of which were related to treatment; eight (3%) of 249 patients in adjuvant-SOX group, two of which were related to treatment; and seven (2%) of 310 patients in perioperative-SOX group, four of which were related to treatment. No treatment-related deaths were reported. INTERPRETATION: Perioperative-SOX showed a clinically meaningful improvement compared with adjuvant-CapOx in patients with locally advanced gastric cancer who had D2 gastrectomy; adjuvant-SOX was non-inferior to adjuvant-CapOx in these patients. Perioperative-SOX could be considered a new treatment option for patients with locally advanced gastric cancer. FUNDING: National Key Research and Development Program of China, Beijing Scholars Program 2018-2024, Peking University Clinical Scientist Program, Taiho, Sanofi-Aventis, and Hengrui Pharmaceutical. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.