Disruption of Sirtuin 1-Mediated Control of Circadian Molecular Clock and Inflammation in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is the fourth most common cause of death, and it is characterized by abnormal inflammation and lung function decline. Although the circadian molecular clock regulates inflammatory responses, there is no information available regarding the impact of COPD on lung molecular clock function and its regulation by sirtuin 1 (SIRT1). We hypothesize that the molecular clock in the lungs is disrupted, leading to increased inflammatory responses in smokers and patients with COPD and its regulation by SIRT1. Lung tissues, peripheral blood mononuclear cells (PBMCs), and sputum cells were obtained from nonsmokers, smokers, and patients with COPD for measurement of core molecular clock proteins (BMAL1, CLOCK, PER1, PER2, and CRY1), clock-associated nuclear receptors (REV-ERBα, REV-ERBß, and RORα), and SIRT1 by immunohistochemistry, immunofluorescence, and immunoblot. PBMCs were treated with the SIRT1 activator SRT1720 followed by LPS treatment, and supernatant was collected at 6-hour intervals. Levels of IL-8, IL-6, and TNF-α released from PBMCs were determined by ELISA. Expression of BMAL1, PER2, CRY1, and REV-ERBα was reduced in PBMCs, sputum cells, and lung tissues from smokers and patients with COPD when compared with nonsmokers. SRT1720 treatment attenuated LPS-mediated reduction of BMAL1 and REV-ERBα in PBMCs from nonsmokers. Additionally, LPS differentially affected the timing and amplitude of cytokine (IL-8, IL-6, and TNF-α) release from PBMCs in nonsmokers, smokers, and patients with COPD. Moreover, SRT1720 was able to inhibit LPS-induced cytokine release from cultured PBMCs. In conclusion, disruption of the molecular clock due to SIRT1 reduction contributes to abnormal inflammatory response in smokers and patients with COPD.

Low serum dehydroepiandrosterone levels are associated with diabetic retinopathy in patients with type 2 diabetes mellitus.

AIMS: This cross-sectional study assessed the association of serum dehydroepiandrosterone levels with the risk of diabetic retinopathy in patients with type 2 diabetes mellitus in China. MATERIALS AND METHODS: Patients with type 2 diabetes mellitus were included in a multivariate logistic regression analysis to assess the association of dehydroepiandrosterone with diabetic retinopathy after adjusting for confounding factors. A restricted cubic spline was also used to model the association of serum dehydroepiandrosterone level with the risk of diabetic retinopathy and to describe the overall dose-response correlation. Additionally, an interaction test was conducted in the multivariate logistic regression analysis to compare the effects of dehydroepiandrosterone on diabetic retinopathy among age, sex, obesity status, hypertension, dyslipidemia, and glycosylated hemoglobin level subgroups. RESULTS: In total, 1,519 patients were included in the final analysis. Low serum dehydroepiandrosterone was significantly associated with diabetic retinopathy in patients with type 2 diabetes mellitus after adjustment for confounding factors (odds ratio [quartile 4 vs quartile 1]: 0.51; 95% confidence interval: 0.32-0.81; P = 0.012 for the trend). Additionally, the restricted cubic spline indicated that the odds of diabetic retinopathy decreased linearly as the dehydroepiandrosterone concentration increased (P-overall = 0.044; P-nonlinear = 0.364). Finally, the subgroup analyses showed that the dehydroepiandrosterone level stably affected diabetic retinopathy (all P for interaction >0.05). CONCLUSIONS: Low serum dehydroepiandrosterone levels were significantly associated with diabetic retinopathy in patients with type 2 diabetes mellitus, suggesting that dehydroepiandrosterone contributes to the pathogenesis of diabetic retinopathy.

Fibroblast growth factor 15, induced by elevated bile acids, mediates the improvement of hepatic glucose metabolism after sleeve gastrectomy.

BACKGROUND: Fibroblast growth factor (FGF) 15/19, which is expressed in and secreted from the distal ileum, can regulate hepatic glucose metabolism in an endocrine manner. The levels of both bile acids (BAs) and FGF15/19 are elevated after bariatric surgery. However, it is unclear whether the increase in FGF15/19 is induced by BAs. Moreover, it remains to be understood whether FGF15/19 elevations contribute to improvements in hepatic glucose metabolism after bariatric surgery. AIM: To investigate the mechanism of improvement of hepatic glucose metabolism by elevated BAs after sleeve gastrectomy (SG). METHODS: By calculating and comparing the changes of body weight after SG with SHAM group, we examined the weight-loss effect of SG. The oral glucose tolerance test (OGTT) test and area under the curve of OGTT curves were used to assess the anti-diabetic effects of SG. By detecting the glycogen content, expression and activity of glycogen synthase as well as the glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (Pepck), we evaluated the hepatic glycogen content and gluconeogenesis activity. We examined the levels of total BA (TBA) together with the farnesoid X receptor (FXR)-agonistic BA subspecies in systemic serum and portal vein at week 12 post-surgery. Then the histological expression of ileal FXR and FGF15 and hepatic FGF receptor 4 (FGFR4) with its corresponding signal pathways involved in glucose metabolism were detected. RESULTS: After surgery, food intake and body weight gain of SG group was decreased compare with the SHAM group. The hepatic glycogen content and glycogen synthase activity was significantly stimulated after SG, while the expression of the key enzyme for hepatic gluconeogenesis: G6Pase and Pepck, were depressed. TBA levels in serum and portal vein were both elevated after SG, the FXR-agonistic BA subspecies: Chenodeoxycholic acid (CDCA), lithocholic acid (LCA) in serum and CDCA, DCA, LCA in portal vein were all higher in SG group than that in SHAM group. Consequently, the ileal expression of FXR and FGF15 were also advanced in SG group. Moreover, the hepatic expression of FGFR4 was stimulated in SG-operated rats. As a result, the activity of its corresponding pathway for glycogen synthesis: FGFR4-Ras-extracellular signal regulated kinase pathway was stimulated, while the corresponding pathway for hepatic gluconeogenesis: FGFR4- cAMP regulatory element-binding protein- peroxisome proliferator-activated receptor γ coactivator-1α pathway was suppressed. CONCLUSION: Elevated BAs after SG induced FGF15 expression in distal ileum by activating their receptor FXR. Furthermore, the promoted FGF15 partly mediated the improving effects on hepatic glucose metabolism of SG.

Hypoxia-inducible factor 2α plays a critical role in the formation of alveoli and surfactant.

Alveolarization of the developing lung is an important step toward the switch from intrauterine life to breathing oxygen-rich air after birth. The distal airways structurally change to minimize the gas exchange path, and Type II pneumocytes increase the production of surfactants, which are required to reduce surface tension at the air-liquid interface in the alveolus. Hypoxia-inducible factor 2α (Hif2α) is an oxygen-regulated transcription factor expressed in endothelial and Type II cells, and its expression increases toward the end of gestation. We investigated the role of Hif2α in Type II cells by conditionally expressing an oxygen-insensitive mutant of Hif2α in airway epithelial cells during development. Newborn mice expressing the mutant Hif2α were born alive but quickly succumbed to respiratory distress. Subsequent analysis of the lungs revealed dilated alveoli covered with enlarged, aberrant Type II cells and a diminished number of Type I cells. The Type II cells accumulated glycogen in part by increased glucose uptake via the up-regulation of the glucose transporter 1. Furthermore, the cells lacked two crucial enzymes involved in the metabolism of glycogen into surfactant lipids, lysophosphatidylcholine acyltransferase and ATP-binding cassette sub-family A member 3. We conclude that Hif2α is a key regulator in alveolar maturation and the production of phospholipids by Type II cells.

Analysis of Car-Following Behaviors under Different Conditions on the Entrance Section of Cross-River and Cross-Sea Tunnels: A Case Study of Shanghai Yangtze River Tunnel.

Compared to highway road tunnels, the entrance section of cross-river and cross-sea tunnels feature long and steep slopes. Along with a complicated traffic environment and harmful weather conditions, traffic congestion and rear-end crashes occur frequently during car-following in cross-river and cross-sea tunnels. It is necessary to examine the impact of traffic flow and weather conditions on car-following behavior at the entrance section of cross-river and cross-sea tunnels. To this end, this paper first extracted the vehicle speed data based surveillance video at the entrance of the Shanghai Yangtze River Tunnel. Moreover, the actual average speed under different traffic flow conditions was obtained through the clustering algorithm, which was used as the basis for setting the experimental parameters. Then, in the driving simulation experiment, three traffic flow conditions (free flow, congested flow, and jam flow) were set up in three weather conditions (sunny, rainy, and snowy), and a risk situation was set up in each condition. Distance headway, time headway, acceleration, lateral offset, and driver's emergency response time were collected. Moreover, seven slopes of 2% to 5% were set, and the relationship of slope on longitudinal speed and lateral offset was analyzed. ANOVA and post-hoc analyses were applied. The result indicates that traffic flow conditions have a significant effect on the car-following behavior, while weather conditions mainly influence the time headway. Moreover, drivers tend to adopt more cautious driving behavior as the distance between the vehicle and the tunnel entrance decreases. The results also show that the slope of the cross-river and cross-sea tunnel entrance section has a major influence on vehicle speed.

Comparison Between Linear Stapler and Circular Stapler After Laparoscopic-Assisted Distal Gastrectomy in Patients With Gastric Cancer.

Background and Aim: To evaluate the safety and efficacy of laparoscopy distal gastrectomy using a linear stapler compared with a circular stapler in patients with gastric cancer. Methods: We retrospectively reviewed 173 patients who underwent laparoscopic distal gastrectomy for gastric cancer at a single center from January 2018 to December 2020. Patients were categorized into the linear stapler group and the circular stapler group. General data, intraoperative and postoperative outcomes, postoperative pathological results, postoperative complications, and postoperative follow-up in the two groups were compared and analyzed. Results: The operation time (208.76 ± 32.92 vs. 226.69 ± 26.92 min, p < 0.05), anastomosis time (71.87 ± 9.50 vs. 90.56 ± 3.18 min, p < 0.05), time to first flatus (68.60 ± 25.96 vs. 76.16 ± 21.05 h, p < 0.05), time to the first sip of water (3.66 ± 0.61 vs. 4.07 ± 0.77 days, p < 0.05), and time to the first liquid diet (4.43 ± 1.02 vs. 5.03 ± 1.70 days, p < 0.05) were significantly shorter in the linear stapler group. In addition, the highest postoperative body temperature within 3 days (37.4 ± 0.61 vs. 37.7 ± 0.61, p < 0.05) after the operation, white blood cell count (WBC) on the 3rd day (9.07 ± 2.52 vs. 10.01 ± 2.98 × 10∧9/L, p < 0.05), and average gastric tube drainage within 3 days (36.65 ± 24.57 vs. 52.61 ± 37 ml, p < 0.05) were also significantly lower in the linear stapler group. Conclusions: Both circular and linear staplers are safe and feasible for gastrointestinal reconstruction in laparoscopic distal gastrectomy. In contrast, a linear stapler has advantages over a circular stapler in shortening operation time and accelerating the postoperative recovery of patients.

Ox-LDL-mediated ILF3 overexpression in gastric cancer progression by activating the PI3K/AKT/mTOR signaling pathway.

BACKGROUND: This study aimed to investigate the relationship of dyslipidemia and interleukin-enhancer binding factor 3 (ILF3) in gastric cancer, and provide insights into the potential application of statins as an agent to prevent and treat gastric cancer. METHODS: The expression levels of ILF3 in gastric cancer were examined with publicly available datasets such as TCGA, and western blotting and immunohistochemistry were performed to determine the expression of ILF3 in clinical specimens. The effects of ox-LDL on expression of ILF3 were further verified with western blot analyses. RNA sequencing, Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Gene Set Enrichment Analysis (GSEA) pathway analyses were performed to reveal the potential downstream signaling pathway targets of ILF3. The effects of statins and ILF3 on PI3K/AKT/mTOR signaling pathway, cell proliferation, cell cycle, migration and invasion of gastric cancer cells were investigated with Edu assay, flow cytometry and transwell assay. RESULTS: Immunohistochemistry and western blot demonstrated that the positive expression rates of ILF3 in gastric cancer tissues were higher than adjacent mucosa tissues. The ox-LDL promoted the expression of ILF3 in a time-concentration-dependent manner. ILF3 promoted the proliferation, cell cycle, migration and invasion by activating the PI3K/AKT/mTOR signaling pathway. Statins inhibited the proliferation, cell cycle, migration and invasion of gastric cancer by inhibiting the expression of ILF3. CONCLUSIONS: These findings demonstrate that ox-LDL promotes ILF3 overexpression to regulate gastric cancer progression by activating the PI3K/AKT/mTOR signaling pathway. Statins inhibits the expression of ILF3, which might be a new targeted therapy for gastric cancer.

Efficacy and Safety of Totally Laparoscopic Gastrectomy Compared with Laparoscopic-Assisted Gastrectomy in Gastric Cancer: A Propensity Score-Weighting Analysis.

Objectives: To compare the short- and long-term outcomes of totally laparoscopic gastrectomy (TLG) with laparoscopic-assisted gastrectomy (LAG) in gastric cancer (GC) patients and evaluate the efficacy and safety of TLG. Methods: This retrospective study was based on GC patients who underwent laparoscopic radical gastrectomy in the Qilu Hospital from January 2017 to December 2020. The groups' variables were balanced by using the propensity score-based inverse probability of treatment weighting (PS-IPTW). The primary outcomes were 3-year relapse-free survival (RFS) and 3-year overall survival (OS). Postoperative recovery and complications were the secondary outcomes. Results: A total of 250 GC patients were included in the study. There were no significant differences in baseline and pathological features between the TLG and the LAG groups after the PS-IPTW. TLG took around 30 min longer than LAG, while there were more lymph nodes obtained and less blood loss throughout the procedure. TLG patients had less wound discomfort than LAG patients in terms of short-term prognosis. There were no significant differences between groups in the 3-year RFS rate [LAG vs. TLG: 78.86% vs. 78.00%; hazard ratio (HR) = 1.14, 95% confidence interval (CI), 0.55-2.35; p = 0.721] and the 3-year OS rate (LAG vs. TLG: 78.17% vs. 81.48%; HR = 0.98, 95% CI, 0.42-2.27; p = 0.955). The lymph node staging was found to be an independent risk factor for tumor recurrence and mortality in GC patients with laparoscopic surgery. The subgroup analysis revealed similar results of longer operation time, less blood loss, and wound discomfort in totally laparoscopic distal gastrectomy, while the totally laparoscopic total gastrectomy showed benefit only in terms of blood loss. Conclusion: TLG is effective and safe in terms of short- and long-term outcomes, with well-obtained lymph nodes, decreased intraoperative blood loss, and postoperative wound discomfort, which may be utilized as an alternative to LAG.

An intron mutation of HNF1A causes abnormal splicing and impairs its activity as a transcription factor.

Mutations in HNF1A are associated with Maturity Onset Diabetes of the Young type 3 (MODY3) and most of them are in the coding region. Herein, we identified an intron mutation at the 6th nucleotide upstream of the end of intron 7 of HNF1A, named IVS7-6G > A, in a patient with early-onset diabetes. The "minigene" assay showed that IVS7-6G > A produced two aberrant mRNA variants translating into two truncated proteins: L502S fs* and G437A fs*, both affecting HNF1A transactivation domain (TAD). To determine functional consequences of IVS7-6G > A mutation, we made plasmids encoding truncated HNF1A containing different portions of HNF1A TAD and found that the TAD of HNF1A is important not only for its regulatory activities, but also for its nuclearization, and the residues 282-501 was more essential than 502-631. Our data suggested IVS7-6G > A impaired HNF1A splicing and may contribute to the pathogenesis of MODY3.

Clinical Application of Indocyanine Green Fluorescence Technology in Laparoscopic Radical Gastrectomy.

Background: This study aimed to observe the application and evaluate the feasibility and safety of indocyanine green (ICG) fluorescence technology in laparoscopic radical gastrectomy (LRG). Methods: Patients who underwent LRG & D2 lymphadenectomy at Qilu Hospital of Shandong University were included between January 2018 and August 2019. According to whether endoscopic injection of ICG was performed, patients were assigned to the ICG group (n=107) and the control group (n=88). The clinicopathologic features, retrieved lymph nodes, postoperative recovery, and follow-up data were compared between the two groups. Results: Baseline characteristics are comparable. The ICG group had a significantly larger number of lymph nodes retrieved (49.55 ± 12.72 vs. 44.44 ± 10.20, P<0.05), shorter total operation time (min) (198.22 ± 13.14 vs. 202.50 ± 9.91, P<0.05), shorter dissection time (min) (90.90 ± 5.34 vs. 93.74 ± 5.35, P<0.05) and less blood loss (ml) (27.51 ± 12.83 vs. 32.02 ± 17.99, P<0.05). The median follow-up time was 29.0 months (range 1.5-43.8 months), and there was no significant difference between the ICG group and the control group in 2-year OS (87.8% vs. 82.9%, P>0.05) or DFS (86.0% vs. 80.7%, P>0.05). Conclusions: ICG fluorescence technology in laparoscopic radical gastrectomy has advantages in LN dissection, operation time, and intraoperative blood loss. The 2-year OS and 2-year DFS rates between the two groups were comparable. In conclusion, ICG fluorescence technology is feasible and safe.

The incidence of second primary cancer in male and female patients with initial colorectal cancer: a SEER population-based study.

BACKGROUND: Second primary cancer (SPC) after primary colorectal cancer (CRC), emerges as a novel challenge for cancer prevention with pronounced differences between female and male patients. METHODS: This was a retrospective study of 140 907 CRC survivors from the surveillance, epidemiology, and end results program database. Competing risk models and nomograms were constructed to predict the risk of SPCs, which were assessed with the C-Index, calibration and decision curve analysis. RESULTS: The 10-year cumulative incidence of SPC was higher in male than in female CRC survivors. The top five common SPCs in female CRC survivors were colorectal, breast, lung and bronchus, corpus and uterus and pancreatic cancers, while in male were prostate, colorectal, lung and bronchus, urinary cancer and melanoma of the skin. Breast and prostate were the most common sites for the development of SPCs after CRC. Older age, stage I and surgery were common risk factors for SPCs in both female and male. The nomogram for predicting the risk of developing SPC-breast cancer in female patients included age, race, site, histology grade, surgery, chemotherapy and stage. However, the model of predicting SPC-prostate cancer in male patients included age, race, site, size, surgery, chemotherapy, radiation and stage. Notably, the nomograms were validated to have a precise discriminative ability, accuracy and clinical effectiveness. CONCLUSIONS: The study surveyed the characteristics of CRC survivors with a particular focus on the incidence of SPC. The models could help supervise the development of a second breast or prostate cancer in female or male CRC survivors.

Alternative splicing of mRNA in colorectal cancer: new strategies for tumor diagnosis and treatment.

Alternative splicing (AS) is an important event that contributes to posttranscriptional gene regulation. This process leads to several mature transcript variants with diverse physiological functions. Indeed, disruption of various aspects of this multistep process, such as cis- or trans- factor alteration, promotes the progression of colorectal cancer. Therefore, targeting some specific processes of AS may be an effective therapeutic strategy for treating cancer. Here, we provide an overview of the AS events related to colorectal cancer based on research done in the past 5 years. We focus on the mechanisms and functions of variant products of AS that are relevant to malignant hallmarks, with an emphasis on variants with clinical significance. In addition, novel strategies for exploiting the therapeutic value of AS events are discussed.

Lymph node status and its impact on the prognosis of left-sided and right-sided colon cancer: A SEER population-based study.

BACKGROUND: Some significant differences exist between the outcomes of left- and right-sided colon cancer patients. The presence of nodal metastases is a critical prognostic factor, especially in the absence of distant metastasis. Our research studied the lymph nodes status of left- and right-sided colon cancer patients to determine the influence of this factor on prognosis. METHODS: Our data were obtained from the Surveillance, Epidemiology and End Results (SEER) database. We used the chi-square test to analyze the clinicopathological characteristics. The X-tile program was adopted to acquire optimal cutoff points of lymph node index. Kaplan-Meier curves were used to analyze prognosis and multivariate Cox regression models were performed to identify the independent factors associated with survival. Nomograms were built to predict the overall survival of patients, Harrell's C-index and calibration plots were used to validate the nomograms. RESULTS: The study included 189,941 patients with colon cancer without metastasis (left 69,885, right 120,056) between 2004 and 2015. There are more patients with adequate examined lymph nodes in right-sided. Lymph node status in patients with right colon cancer has a more significant impact on the risk of death. LODDS (C-index: 0.583; AIC: 6875.4) was used to assess lymph node status. The nomograms showed that lymph node status was the main factor to predict the outcome in right-sided colon patients. CONCLUSIONS: The influence of lymph node status on predicting prognosis is significantly different between patients with left and right colon cancer without metastasis. The tumor site needs to be considered when lymph node status is used to assess the outcome of patients.

A narrative review of the roles of muscle segment homeobox transcription factor family in cancer.

Deregulation of many homeobox genes has been observed in various cancers and has caused functional implications in the tumor progression. In this review, we will focus on the roles of the human muscle segment homeobox (MSX) transcription factor family in the process of tumorigenesis. The MSX transcription factors, through complex downstream regulation mechanisms, are promoters or inhibitors of diverse cancers by participating in cell proliferation, cell invasion, cell metastasis, cell apoptosis, cell differentiation, drug resistance of tumors, maintenance of tumor stemness, and tumor angiogenesis. Moreover, their upstream regulatory mechanisms in cancers may include: gene mutation and chromosome aberration; DNA methylation and chromatin modification; regulation by non-coding RNAs; regulation by other transcription factors and post-translational modification. These mechanisms may provide a better understanding of why MSX transcription factors are abnormally expressed in tumors. Notably, intermolecular interactions and post-translational modification can regulate the transcriptional activity of MSX transcription factors. It is also crucial to know what affects the transcriptional activity of MSX transcription factors in tumors for possible interventions in them in the future. This systematic summary of the regulatory patterns of the MSX transcription factor family may help to further understand the mechanisms involved in transcriptional regulation and also provide new therapeutic approaches for tumor progression.

The Circumferential Resection Margin Is a Prognostic Predictor in Colon Cancer.

Objective: This study aimed to investigate the potential value of circumferential resection margin (CRM) in colon cancer prognostics. Summary Background Data: CRM has been extensively studied as an important prognostic factor in rectal and esophageal cancer, but not in colon cancer. Methods: Data from 6,681 CRM-positive patients and 25,908 CRM-negative patients diagnosed with colon cancer in 2010-2015 were obtained from the Surveillance, Epidemiology, and End Results database. Statistical analysis methods utilized included the chi-square test, Kaplan-Meier estimates, Cox proportional, and X-tile software analyses. Results: After propensity score matching, CRM positivity was found to be negatively related with survival (P < 0.001). X-tile software identified 0 and 30 mm as optimal cutoff values (P < 0.001) for prognosis, which was applicable only in stage II-IV patients. A 20 and 33% risk decrease were observed in patients with CRM between 0 and 30 mm [95% confidence interval (CI) = 0.76-0.84], and larger than 30 mm (95% CI = 0.62-0.71), respectively. Chemotherapy strongly benefited prognosis with a hazard ratio of 0.36 (95% CI = 0.34-0.38) for overall survival (OS). Patients with a CRM value of 0-30 mm seemed to benefit most from chemotherapy compared with other groups. CRM and number of regional lymph nodes are independent risk factors, and the latter is a good substitute for CRM in AJCC stage I patients. Conclusion: CRM positivity is a strong unfavorable survival indicator for colon cancer patients. A better outcome is expected with CRM values larger than 30 mm. This cutoff value only applied to stage II-IV patients. For stage I patients, number of regional lymph nodes is a good substitute to predict survival. Chemotherapy was another favorable prognostic factor, especially for patients with a CRM value between 0 and 30 mm.

Clinicopathological characteristics and prognosis of colorectal mucinous adenocarcinoma and nonmucinous adenocarcinoma: a surveillance, epidemiology, and end results (SEER) population-based study.

BACKGROUND: Mucinous adenocarcinoma (MC) is a rare histological subtype of colorectal adenocarcinoma. Previous studies investigating the prognosis of MC have conflicting results and the proper treatment of MC remains unclear. METHODS: This retrospective study presents the clinicopathological characteristics and prognosis of MC. This cohort study collected data from April 1 through August 01, 2018. This study used data on 107,735 patients with nonmucinous adenocarcinoma (NMC) and 9,494 with MC between 2009 and 2013 from the Surveillance, Epidemiology, and End Results program (SEER). Clinicopathological features were analyzed by chi-square test and survival curves by the Kaplan-Meier method. We used propensity score matching (PSM) to account for potential bias. Logistic regression and Cox proportional hazards models were used to compare and calculate adjusted risks of MC death. RESULTS: MC was more frequent in patients with older age, large tumor size and moderate tumor grade compared with NMC (P<0.001). Five-year survival was lower for MC patients than NMC patients (P<0.001). Older age, later tumor node metastasis (TNM) stage and multiple tumors indicated a poorer prognosis while surgery gave better survival outcomes [hazard ratio (HR) =0.38; 95% confidence interval (CI), 0.33 to 0.44; P<0.001]. Younger age, left-side colon location and early disease stage were associated with better survival after surgery (P<0.001). CONCLUSIONS: Age, TNM stage, tumor number and treatment were indicators of prognosis and surgery gave better survival for MC patients compared with those without surgery. Our study contributes to their clinical treatment.

Implications of the growing burden of diabetes for premature cardiovascular disease mortality and the attainment of the Sustainable Development Goal target 3.4.

Non-communicable diseases (NCDs) are a major cause of deaths globally, and cardiovascular disease (CVD) is the leading cause of these deaths. 42% of NCD deaths are premature (occurring before the age of 70 years). As part of the United Nations 3rd Sustainable Development Goal (SDG) on health and wellbeing, target 3.4 is to reduce premature mortality from NCDs by one third between 2015 and 2030. This target adds to the World Health Organization (WHO) target of reducing premature deaths from NCDs by 25% between 2010 and 2025. As diabetes is a major risk factor for CVD, it is important to account for the trends in diabetes when considering premature CVD mortality. We aimed to describe the global trends in diabetes prevalence and mortality, critically review the literature on the estimated attainability of the WHO and SDG targets, and determine if and how these studies accounted for trends in diabetes. Worldwide, the prevalence of diabetes is rising, with an estimated 9.0% global prevalence in adults aged 20-69 by 2030, and low- and middle-income countries (LMICs) having the largest increase of the burden in absolute numbers and age-standardized prevalence. There is a lack of data from most LMICs on the excess CVD mortality associated with diabetes and therefore no consensus on the global risk of CVD mortality in people with diabetes. Where data do exist, there are discrepancies between studies on the direction of mortality trends from diabetes over time. We reviewed 12 studies that estimated the attainability of the WHO or SDG targets for premature NCD mortality. Seven of these considered the potential impacts of achieving the 2025 WHO risk factor targets. Six studies modelled the impact of current trends in risk factors, including diabetes, continuing toward the target dates. Four studies compared this 'business as usual' model with the attainment of the risk factor targets for the world as whole and individual regions, 2 studies for NCD mortality overall, and 2 specifically for CVD mortality. On the impact of diabetes with regards to attainment of the WHO or SDG targets for premature CVD mortality, the overall results were inconclusive. Some concluded that none of the countries or regions considered would meet the targets, and others predicted that in some areas, the targets would be met. Examining the potential impact of trends in diabetes on future CVD mortality rates in LMICs is limited by a relative lack of high quality studies, including on the age specific excess mortality associated with diabetes. Filling these data gaps will enable better estimates of the potential impacts on future CVD mortality of the rapidly increasing prevalence of diabetes in LMICs and help to better inform health policy and the attainment of SDG target 3.4.

Hypoxia inducible factor 2α (HIF2α/EPAS1) is associated with development of pulmonary hypertension in severe congenital diaphragmatic hernia patients.

We show that hypoxia inducible factor 2α (HIF2α) is highly expressed in patients with pulmonary hypertension (PH). HIF2α is expressed in every patient with congenital diaphragmatic hernia, while only half of the controls express HIF2α. Our data suggest that HIF2α is a link between hypoxia and the development of PH.

[Effects of aminooxyacetic acid on the learning and memory ability and its possible mechanism in rats with chronic alcoholism].

OBJECTIVE: To investigate the effects of aminooxyacetic acid (AOAA) on learning and memory ability and possible mechanisms in rats with chronic alcoholism. METHODS: Sixty SD male rats were randomly divided into three groups on average.The model group rats and the remedy group rats were fed with the water containing (v/v) 6% alcohol for 28 days.After 14 days, the remedy group rats were treated with AOAA (5 mg/kg·d) by intraperitoneal injection once a day for 14 days and the other two group rats were treated with the equal amount of saline by intraperitoneal injection every day.Five days before the end of the experiment, the water maze test was carried out to test the learning and memory ability of rats for 5 days.Subsequently, the content of H2S, the activity of ATP enzyme and the expression of 5-HT in hippocampus were measured. RESULTS: Compared with the rats in the control group, the latency and the swimming distance of the 2nd to the 4th day, the content of H2S in hippocampus of rats in the model group were all increased, the mitochondrial ATP enzyme activity in hippocampus and the positive expression of 5-HT in hippocampus CA1 and CA3 of rats in the model group were decreased (P<0.01).Compared with the rats in the model group, the latency and the swimming distance of the 2nd to the 4th day, the content of H2S in hippocampus of the rats in the remedy group were decreased, the mitochondrial ATP enzyme activity in hippocampus and the positive expression of 5-HT in hippocampus CA1 and CA3 of rats in the model group were increased (P<0.01). CONCLUSIONS: AOAA could alleviate the symptoms of chronic alcoholism rats, which may be related to the effects of AOAA on the content of H2S, the mitochondrial enzyme activity and the expression of 5-HT in hippocampus.

Hyperbaric oxygen therapy for late radiation-induced tissue toxicity: prospectively patient-reported outcome measures in breast cancer patients.

INTRODUCTION: This study examines patient reported outcome measures of women undergoing hyperbaric oxygen treatment (HBOT) after breast-conserving therapy. METHOD: Included were 57 women treated with HBOT for late radiation-induced tissue toxicity (LRITT) referred in the period January 2014-December 2015. HBOT consisted of (on average) 47 sessions. In total, 80 min of 100 % O2 was administered under increased pressure of 2.4 ATA. Quality of life was assessed before and after treatment using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-BR23, and a NRS pain score. RESULTS: Fifty-seven women were available for evaluation before and after treatment. Before HBOT, patients had severe complaints of pain in the arm/shoulder (46 %), swollen arm/hand (14 %), difficulty to raise arm or move it sideways (45 %), pain in the area of the affected breast (67 %), swollen area of the affected breast (45 %), oversensitivity of the affected breast (54 %), and skin problems on/in the area of the affected breast (32 %); post HBOT, severe complaints were still experienced in 17, 7, 22, 15, 13, 15, and 11 % of the women, respectively. Differences were all significant. The NRS pain score improved at least 1 point (range 0-10) in 81 % of the patients (p < 0.05). CONCLUSION: In these breast cancer patients treated with HBOT for LRITT, the patient-reported outcomes were positive and improvements were observed. HBOT was a well-tolerated treatment for LRITT and its side-effects were both minimal and reversible.