Plasma campesterol and ABCG5/ABCG8 gene loci on the risk of cholelithiasis and cholecystitis: evidence from Mendelian randomization and colocalization analyses.

The causal relationships between plasma metabolites and cholelithiasis/cholecystitis risks remain elusive. Using two-sample Mendelian randomization, we found that genetic proxied plasma campesterol level showed negative correlation with the risk of both cholelithiasis and cholecystitis. Furthermore, the increased risk of cholelithiasis is correlating with the increased level of plasma campesterol. Lastly, genetic colocalization study showed that the leading SNP, rs4299376, which residing at the ABCG5/ABCG8 gene loci, was shared by plasma campesterol level and cholelithiasis, indicating that the aberrant transportation of plant sterol/cholesterol from the blood stream to the bile duct/gut lumen might be the key in preventing cholesterol gallstone formation.

An aging-related gene signature to predict the prognosis of hepatocellular carcinoma.

Aging increases the susceptibility of various diseases, including hepatocellular carcinoma (HCC). This study aimed to establish an aging-related prognostic model for HCC and to investigate the role of aging-related genes in HCC progression. Transcriptome and clinical information of HCC cases were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Aging-related prognostic genes were identified through univariate Cox regression analysis, protein-protein interaction analysis, and least absolute shrinkage and selection operator (LASSO) analysis. An aging-related risk signature was then constructed, including LDHA, MMP12, ATAD3A, CD8A, TPI1, CST3, and TPM1. The risk score was inversely associated with the overall survival of patients with HCC and correlated well with known prognostic factors. The area under the curve of 1-, 3-, and 5-year survival in the training dataset was 0.83, 0.83, and 0.84, respectively. Univariate and multivariate cox regression analysis verified that the aging-related risk signature independently predicted the overall survival in HCC. To increase the clinical utility of the prognostic model, a nomogram was developed by incorporating the risk score with key clinical features. Finally, single-cell transcriptomes of HCC were analyzed to elucidate the expression pattern of the prognostic genes across different tissues, pathologic stages, and cell types. Collectively, the aging-related prognostic model shed light on HCC pathogenesis and held potential for optimizing the management of HCC.

Lactobacillus Intestinalis Primes Epithelial Cells to Suppress Colitis-Related Th17 Response by Host-Microbe Retinoic Acid Biosynthesis.

Gut microbiome is integral to the pathogenesis of ulcerative colitis. A novel probiotic Lactobacillus intestinalis (L. intestinalis) exerts a protective effect against dextran sodium sulfate-induced colitis in mice. Based on flow cytometry, colitis-associated Th17 cells are the target of L. intestinalis, which is supported by the lack of protective effects of L. intestinalis in T cell-null Rag1-/- mice or upon anti-IL-17-A antibody-treated mice. Although L. intestinalis exerts no direct effect on T cell differentiation, it decreases C/EBPA-driven gut epithelial SAA1 and SAA2 production, which in turn impairs Th17 cell differentiation. Cometabolism of L. intestinalis ALDH and host ALDH1A2 contributed to elevated biosynthesis of retinoic acid (RA), which accounts for the anti-colitis effect in RAR-α -mediated way. In a cohort of ulcerative colitis patients, it is observed that fecal abundance of L. intestinalis is negatively associated with the C/EBPA-SAA1/2-Th17 axis. Finally, L. intestinalis has a synergistic effect with mesalazine in alleviating murine colitis. In conclusion, L. intestinalis and associated metabolites, RA, have potential therapeutic effects for suppressing colonic inflammation by modulating the crosstalk between intestinal epithelia and immunity.

The role of socioeconomic status and oxidative balance score in erectile dysfunction: A cross-sectional study.

Background: Erectile dysfunction (ED) is a complex disorder of biopsychosocial etiology. Approximately 3%-77 % of adult men worldwide are more or less affected by ED. Objective: This cross-sectional study investigated the association between ED and socioeconomic status (SES) based on a nationally representative adult male population. Methods: The poverty income ratio (PIR), which refers to household income ratio to the established poverty line, was used to assess SES. Oxidative stress related to diet and lifestyle was reflected by oxidative balance score (OBS). Erectile function was evaluated using a questionnaire. Based on the results of the questionnaire, participants were divided into two groups of those without ED (always or almost always be able to erect and keep erection, usually be able to erect and keep erection) and with ED (sometimes be able to erect and keep erection, never be able to erect and keep erection). Multivariate logistic regression, multiple models, and restricted cubic spline (RCS) were used to analyze and describe the interaction between ED, OBS, and SES. Results: Compared with men without ED, those with ED were more likely to be older in age (43.98 vs 37.74, P＜0.0001), and less educated (P < 0.001), and with a ratio of family income to poverty less than 3.5 (P = 0.02), higher BMI (30.11 vs 27.84, P＜0.0001), lower OBS (21.71 vs 23.17, P = 0.04), having habit of smoking (P = 0.04), with diabetes (P＜0.0001), and with hypertension (P = 0.003). Participants with higher PIR were more likely to report good erectile function than those with lower PIR through multivariate analysis (OR = 0.49, 95 % CI = 0.31-0.78, P = 0.005). The RCS model revealed a negative non-linear correlation of PIR with ED when PIR ≤3.89. It is interesting to note that PIR was＞3.89 showed a positive non-linear relationship with ED. Conclusion: The social determinants of health and intake of oxidants and antioxidants were considered as risk factors for ED and could be studied as a research focus in the future.

Pesticide residues in agricultural end-products and risk assessment for consumers in North China.

This study investigated pesticide residues in market-sold vegetables and fruits in Hebei Province, China, over 5 years (2018-2022). A modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) method was applied to gas chromatography with triple-quadrupole mass spectrometer (GC-MS/MS). The analytical methods were validated with respect to matrix effect (ME), recovery rate (78.9~105.5%), limit of quantitation (LOQ, 2.93~9.73 µg/kg), and linear correlation coefficient (0.9982~0.9997). Residues of 10 pesticides in 12 categories of vegetable and fruit were detected. 31.9% of the samples were detected pesticide residues; 15.5% of samples were detected multi-component pesticide residues. Twenty-seven positive detections of pesticide residues exceeded the corresponding maximum residue limit (MRL), accounting for 2.33%. The most types of pesticide residues were detected in cherry, with the number of 7. Procymidone was the most detected pesticide, and it was detected in 8 categories of samples. The hazard index (HI) of omethoate was the highest and the procymidone was the lowest. The HI of all the vegetables and fruits were less than 100%. The effects of pesticide residues are within an acceptable range for human. Adequate attention and further monitoring are still needed.

Bacterial contamination of medical face mask wearing duration and the optimal wearing time.

Introduction: Bacterial contamination is a critical parameter for how long a medical mask will be worn. Methods: In this study, we used the pour plate method to observe the total bacteria counts in used medical face masks. The bacterial community analysis was detected using bio-Mass spectrometry technology and 16SrRNA gene sequencing technology. The wearing time of the mask from 0.5 hours to 5 hours were studied. Results: These results shown that the total number of bacteria on the inside surface of the mask were higher than the outside. The total number of bacteria on the inner surface of masks worn for 0.5 h, 1 h 2 h, 4 h and 5 h was 69 CFU/m2,91.3 CFU/m2, 159.6 CFU/m2, 219 CFU/m2, and 879 CFU/m2, respectively. The total number of bacteria on the outside surface of masks worn for 0.5 h, 1 h 2 h, 4 h and 5 h was 60 CFU/m2, 82.7 CFU/m2, 119.8 CFU/m2, 200 CFU/m2, and 498 CFU/m2, respectively. The bacterial abundance obtained from bio-Mass spectrometry were consistent with the results of 16SrRNA sequencing. Both the methods discovered the maximum number of Neisseria followed by Corynebacterium species in mask worn 5 hours. The top 100 bacteria isolated from inside and outside surface of mask belong to 11 phyla. Conclusions: We analyzed bacterial penetration efficiency of the bacteria that were detected both on the inside and outside surface of the masks. In the top 10 bacteria, no bacteria were detected both inside and outside the mask worn for four hours, while 6 bacteria species were detected on the inside and outside of the mask after wearing for five hours. Bacterial penetration rates ranged from 0.74% to 99.66% for masks worn continuously for five hours, and the penetration rate of four strains exceeded 10% in the top 10 colonies. We recommend timely replacement of masks worn for more than four hours.

Idiopathic hypereosinophilic syndrome with hepatic sinusoidal obstruction syndrome: A case report and literature review.

BACKGROUND: Hypereosinophilic syndrome (HES) is classified as primary, secondary or idiopathic. Idiopathic HES (IHES) has a variable clinical presentation and may involve multiple organs causing severe damage. Hepatic sinusoidal obstruction syndrome (HSOS) is characterized by damage to the endothelial cells of the hepatic sinusoids of the hepatic venules, with occlusion of the hepatic venules, and hepatocyte necrosis. We report a case of IHES with HSOS of uncertain etiology. CASE SUMMARY: A 70-year-old male patient was admitted to our hospital with pruritus and a rash on the extremities for > 5 mo. He had previously undergone antiallergic treatment and herbal therapy in the local hospital, but the symptoms recurred. Relevant examinations were completed after admission. Bone marrow aspiration biopsy showed a significantly higher percentage of eosinophils (23%) with approximately normal morphology. Ultrasound-guided hepatic aspiration biopsy indicated HSOS. Contrast-enhanced computed tomography (CT) of the upper abdomen showed hepatic venule congestion with hydrothorax and ascites. The patient was initially diagnosed with IHES and hepatic venule occlusion. Prednisone, low molecular weight heparin and ursodeoxycholic acid were given for treatment, followed by discontinuation of low molecular weight heparin due to ecchymosis. Routine blood tests, biochemical tests, and imaging such as enhanced CT of the upper abdomen and pelvis were reviewed regularly. CONCLUSION: Hypereosinophilia may play a facilitating role in the occurrence and development of HSOS.

Pulmonary cryptococcosis after immunomodulator treatment in patients with Crohn's disease: Three case reports.

BACKGROUND: Corticosteroids and anti-tumor necrosis factor α mAbs are widely used to treat Crohn's disease (CD). However, one disadvantage of this treatment is impairment of normal immune function, leading to an increased risk of infection. Cryptococcus infection is an opportunistic infection that occurs mainly in immunocompromised patients and poses a significant diagnostic challenge in patients with CD. CASE SUMMARY: Here, we report three cases of pulmonary cryptococcosis in patients with CD after receiving immunomodulatory treatment. The patients presented with no or mild respiratory symptoms. Chest computed tomography scans revealed pulmonary nodules in the unilateral or bilateral lobes. Diagnoses were made using pathological examination and metagenomic sequencing. The patients were treated with fluconazole 400 mg once daily for 1 to 6 mo, and symptoms were resolved. Literature searches were conducted in PubMed, Web of Science, and Embase to retrieve previously reported cases and summarize patient characteristics. CONCLUSION: The incidence of cryptococcus infection has increased along with immunomodulator use. Clinical vigilance is required for early identification and standardized treatment.

Lactobacillus johnsonii alleviates colitis by TLR1/2-STAT3 mediated CD206+ macrophagesIL-10 activation.

Imbalance of gut microbiota homeostasis is related to the occurrence of ulcerative colitis (UC), and probiotics are thought to modulate immune microenvironment and repair barrier function. Here, in order to reveal the interaction between UC and gut microbiota, we screened a new probiotic strain by 16S rRNA sequencing from Dextran Sulfate Sodium (DSS)-induced colitis mice, and explored the mechanism and clinical relevance. Lactobacillus johnsonii (L. johnsonii), as a potential anti-inflammatory bacterium was decreased colonization in colitis mice. Gavage L. johnsonii could alleviate colitis by specifically increasing the proportion of intestinal macrophages and the secretion of Il-10 with macrophages depleted model and in Il10-/- mice. We identified this subset of immune cells activated by L. johnsonii as CD206+ macrophagesIL-10. Mechanistically, L. johnsonii supplementation enhanced the mobilization of CD206+ macrophagesIL-10 through the activation of STAT3 in vivo and in vitro. In addition, we revealed that TLR1/2 was essential for the activation of STAT3 and the recognition of L. johnsonii by macrophages. Clinically, there was positive correlation between the abundance of L. johnsonii and the expression level of MRC1, IL10 and TLR1/2 in UC tissues. L. johnsonii could activate native macrophages into CD206+ macrophages and release IL-10 through TLR1/2-STAT3 pathway to relieve experimental colitis. L. johnsonii may serve as an immunomodulator and anti-inflammatory therapeutic target for UC.

ß2-adrenergic receptor drives the metastasis and invasion of pancreatic ductal adenocarcinoma through activating Cdc42 signaling pathway.

Recent investigations indicate that ß2-adrenergic receptor (ß2-AR) signaling may facilitate the progression of various tumors, whose underlying mechanisms remain largely elusive. In the present study, we showed that ß2-AR recruited Cdc42 in response to isoproterenol (ISO, a ß-AR selective agonist) exposure in pancreatic ductal adenocarcinoma (PDAC) cells. The association of ß2-AR and Cdc42 promoted the activation of Cdc42, as revealed by increased levels of Cdc42-GTP, and co-incubation with ß2-AR antagonist abrogated ISO-induced activation of Cdc42. ß2-AR-mediated Cdc42 activation further led to the phosphorylation of downstream PAK1, LIMK1 and Merlin. Furthermore, we showed that the activation of ß2-AR/Cdc42 signaling facilitated the migration and invasion of PDAC cells. In addition, ß2-AR and Cdc42 were overexpressed in PDAC specimens, compared with adjacent non-tumor tissues. High expression of ß2-AR and Cdc42 were correlated with lymph node metastasis and TNM stage in PDAC patients. Finally, we showed that overexpression of ß2-AR and Cdc42 were indicative of unfavorable prognosis in PDAC patients. Taken together, our findings suggested that ß2-AR might facilitate Cdc42 signaling to drive the migration and invasion of PDAC cells, consequently resulting in the metastasis and dismal prognosis of PDAC. These studies highlight targeting ß2-AR/Cdc42 signaling as a therapeutic strategy against PDAC.

A Bibliometric Analysis of Publications on Endoscopic Ultrasound.

Background: Over the past 40 years, endoscopic ultrasound (EUS) has become a safe and effective tool for both diagnostic and therapeutic applications. A growing number of articles have been published annually. We aimed to explore global scientific outputs and hotspots of EUS published by different countries, organizations, and authors. Methods: The global literature regarding EUS during the 1900-2020 period was identified from the Web of Science (WOS) Core database. "Bibliometrix" and software VOSviewer were applied to perform bibliometric analysis. Results: The annual growth rate of publications from 1980 to 2020 was around 16% and the number of EUS-related articles had experienced a sudden increase in the last decade. Bhutani MS was the most productive author over the past years, with 94 publications. Hawes RH had the highest number of citations, with 6,034 citations. The United States and institutions from United States dominated the EUS research. Among the journals, GASTROINTESTINAL ENDOSCOPY published the highest number of articles, followed by ENDOSCOPY. The majority of top 10 frequently cited references were cited more than 200 times. Carcinoma, diagnosis, fine-needle-aspiration, cytology, and pancreatitis were the important keywords in co-occurrence analysis of keywords. Recent studies focused more on tissue acquisition, size of the needle, lumen-apposing metal stent, and fine-needle- biopsy. Conclusion: Research on EUS has significantly increased in the last decade globally and it will continue to increase. Active collaboration among different authors and countries was observed in the EUS field. Tissue acquisition, size of the needle, apposing metal stent, and fine-needle-biopsy might be the latest research frontiers and should receive more attention.

Association between serum estradiol level, sex hormone binding globulin level, and bone mineral density in middle-aged postmenopausal women.

BACKGROUND: Changes in sex hormones are thought to play an important role in bone health in postmenopausal women. Our aim in this study was to evaluate the association between levels of estradiol (E2), which is the most potent endogenous estrogen, and sex hormone binding globulin (SHBG) and bone mineral density (BMD) among postmenopausal women, 40-59 years of age. METHODS: Using data from the National Health and Nutrition Examination Survey 2013-2016, we performed weighted multivariable linear regression models to evaluate the associations between serum levels of E2 and SHBG and lumbar BMD. A weighted generalized additive model and smooth curve fitting were used to address potential nonlinearity. RESULTS: A total of 608 postmenopausal women were included in the analysis. The serum E2 level was positively associated with lumbar BMD, after adjusting for other covariates (ß 0.65; 95% confidence interval (CI) 0.38-0.93). An inverted U-shaped association between the serum E2 level and lumbar BMD was further identified, with the point of inflection at an E2 level of 70 pg/mL. There was no significant association between the SHBG level and lumbar BMD (ß 0.01; 95% CI - 0.30 to 0.31). However, the association between these two variables was U-shaped, with the point of inflection at an SHBG level of 65 nmol/L. CONCLUSIONS: Based on our findings, it may be beneficial to appropriately increase serum E2 levels to promote bone health in postmenopausal women with low estrogen levels. Considering the inverted U-shaped association, an excessive E2 level may be harmful to BMD. In addition, increasing the SHBG level to within the normal range (65-144 nmol/L) may be considered.

Monitoring of Aluminum content in food and assessment of dietary exposure of residents in North China.

Although the Chinese diet has become very abundant in the past 30 years, few people know that traditional Chinese diet is exposed to aluminium (Al). A total of 1232 samples were purchased during 2017-2019 and analysed for Al content with an inductively coupled plasma-mass spectrometry (ICP-MS) method. High Al levels were found in deep-fried dough sticks (mean 219 mg/kg), starch products (mean 84.5 mg/kg), and steam bread (mean 28.6 mg/kg). The average dietary Al exposure of residents in North China was 1.82 mg/kg bw/week, lower than the PTWI (provisional tolerable weekly intake). Deep-fried dough sticks (DFDS) are the main Al contributor in North China, providing 28.2% of the daily intake. The P95 dietary exposure to Al from DFDS was 2.3 mg/kg bw/week, exceeding the PTWI. Therefore, more attention should be paid to the health risk of exposure to Al from DFDS and starch products. Over-use of Al associated with food additives should be effectively controlled.

RORß suppresses the stemness of gastric cancer cells by downregulating the activity of the Wnt signaling pathway.

Gastric cancer (GC) is the third leading cause of cancer­related mortality and the fifth most common type of cancer worldwide. GC stem cells (GCSCs) have been reported to be responsible for the malignant behavior of GC. However, the key molecular mechanism controlling GCSC function remains unclear. The present study aimed to investigate the function of retinoic acid­related orphan receptor ß (RORß) in GC. The expression levels of RORß in GC cells and clinical GC tissues were analyzed using western blotting, reverse transcription­quantitative PCR (RT­qPCR) and immunohistochemistry. The association between RORß expression levels and GCSC markers was analyzed using Gene Set Enrichment Analysis, and GeneChip was performed to identify differentially expressed genes between control and RORß­overexpressing GC cells. CCK­8 and flow cytometric assays were used to evaluate the effect of RORß on cell viability and apoptosis, respectively. The effect of RORß on the self­renewal capacity of GCSCs was measured using a sphere formation assay, the expression levels of induced pluripotent stem (iPS) factors and epithelial­mesenchymal transition (EMT)­related factors were measured by RT­qPCR and western blotting, and the tumorigenic capacity was measured by an in vivo mouse model. Finally, the impact of RORß on the Wnt signaling pathway was determined using western blotting and a TOP/FOP flash assay. The results revealed that the expression levels of RORß were downregulated in GC tissues compared with para­carcinoma tissues, and were inversely associated with the expression levels of GCSC markers. The overexpression of RORß upregulated the expression levels of the pro­apoptotic gene, Bcl­2 like protein 11, which subsequently inhibited the viability and promoted the apoptosis of GC cells. In addition, RORß decreased the sphere forming ability, and downregulated the expression levels of iPS cell­ and EMT­related factors. In vivo, RORß suppressed the tumorigenic capacity and stemness of GC cells. Mechanistically, RORß was revealed to decrease the activity of the Wnt/ß­catenin signaling pathway in GCSCs. In conclusion, the findings of the present study identified RORß as a novel suppressor of GCSCs and highlighted the prospect of RORß as a novel candidate target for stem cell­based GC therapy.

Ubiquitin-specific protease 14 (USP14) promotes proliferation and metastasis in pancreatic ductal adenocarcinoma.

Previous studies have shown aberrant expression of ubiquitin-specific protease 14 (USP14) in multiple malignancies, suggesting an important role of USP14 in tumorigenesis. However, the functional role of USP14 in pancreatic ductal adenocarcinoma (PDAC) has never been elucidated. In this study, we found that USP14 was remarkably upregulated in PDAC tissues compared with normal pancreatic tissues. Notably, Kaplan-Meier curves showed that high expression of USP14 predicted significantly worse prognosis in PDAC patients than low expression of USP14. To determine whether USP14 could regulate the proliferation, apoptosis and metastasis of PDAC cells, we knocked down endogenous USP14 or overexpressed exogenous USP14 in Panc-1 and BxPC-3 cells. Using MTT assays, colony formation analyses, flow cytometry assays, and cell invasion and migration assays, we found that knockdown of USP14 attenuated proliferation, induced apoptosis and restrained invasion and migration of PDAC cells. Overexpression of USP14 could enhance proliferation, prevent apoptosis and promote invasion and migration of PDAC cells. In addition, USP14 could regulate the expression of cyclin D1, PCNA and E-cadherin, three important carcinogenic factors, in PDAC cells. These findings suggest that USP14 might play an important role in promoting the tumorigenesis of PDAC and thus be a promising therapeutic target to prevent PDAC progression.

Effect of Cuttlebone on Healing of Indomethacin-Induced Acute Gastric Mucosal Lesions in Rats.

The continuing use of nonsteroidal anti-inflammatory drugs (NSAIDs) usually increases the side effects such as peptic ulcer and acute gastric lesions in the gastrointestinal tract. Cuttlebone (CB), isolated from Sepiella maindroni de Rochebrune, was reported to have antioxidant activities, but its role in the treatment of indomethacin-induced gastric lesions has not yet been confirmed. In this research, we investigate the protective effect of cuttlebone on indomethacin-related ulcers in rats and possible mechanisms. Here, gastric ulcers were induced by oral administration of indomethacin, and then the rats were treated with omeprazole (4 mg/kg) or different doses (750, 1500, and 3000 mg/kg of body weight) of cuttlebone. We evaluated lesion index, inflammation score, and a series of oxidant/antioxidant parameters. The data demonstrated that cuttlebone could protect against gastric ulcers induced by indomethacin in a dose-dependent manner (positive correlation). Also, these effects were associated with attenuating the expression of malonaldehyde (MDA) and increasing the levels of some protective ingredients like epidermal growth factor (EGF), prostaglandin E2 (PGE2), and superoxide dismutase (SOD). Thus, considering its ability to protect indomethacin-induced acute gastric mucosal lesions and the underlying mechanisms, CB might be a potential candidate for treating gastric damage caused by NSAIDs.

Anti-Cancer Effects of 3, 3'-Diindolylmethane on Human Hepatocellular Carcinoma Cells Is Enhanced by Calcium Ionophore: The Role of Cytosolic Ca2+ and p38 MAPK.

Purpose: 3,3'-Diindolylmethane (DIM), derived from indole-3-carbinol (I3C) in the Brassica species of cruciferous vegetables, has anticancer effects, but its exact underlying mechanism of action is unknown. We explored the roles of cytosolic free calcium ([Ca2+]i) and p38 MAPK in the anti-cancer effects of DIM in human hepatocellular carcinoma cells. Methods: Cell proliferation was measured with a Cell Counting Kit-8 (CCK-8) and the clonogenic formation assay. Cell apoptosis was examined by flow cytometric analysis and Hoechst dye staining. Cleaved-caspase3, cleaved-PARP, Bax, total, and phosphorylated p38 MAPK were assayed by western blotting. [Ca2+]i was measured with Fluo-3/AM by fluorescence microscopy. A23187, a calcium ionophore, was used to increase [Ca2+]i levels. Results: DIM inhibited cell proliferation in both SMMC-7721 and HepG2 cells in a concentration- and time-dependent manner. DIM also enhanced phosphorylation of p38 MAPK (p-p38), which was attenuated by SB203580. The proliferation inhibition and apoptosis induction by DIM were also blunted. In addition, DIM increased [Ca2+]i in HCC cells, and this effect was inhibited by the calcium chelator, BAPTA-AM, resulting in reduced p-p38 MAPK activation and apoptosis in DIM-treated cells, though the proliferation inhibition by DIM was unchanged. However, the DIM-induced cell proliferation inhibition and apoptosis were significantly enhanced by A23187, a selective calcium ionophore, which was attributed to exaggerated p-p38 MAPK. Conclusions: The calcium ionophore enhanced DIM-induced anti-cancer effects in hepatocellular carcinoma cells, secondary to [Ca2+]i-dependent activation of p38 MAPK. Treatment with a combination of DIM and calcium ionophore may offer a new approach to enhance the chemotherapeutic efficacy in liver cancer.

The differences in the esophageal motility between liquid and solid bolus swallows: A multicenter high-resolution manometry study in Chinese asymptomatic volunteers.

BACKGROUND: The results of the esophageal body motility differences between liquid and solid swallows from high-resolution manometry (HRM) studies are not consistent. The information of the frequency of ineffective liquid and solid bolus swallows in healthy individuals during HRM procedure is limited. The normative values of the HRM parameters of both liquid and solid swallows for Chinese population are lacking. METHODS: The esophageal HRM data of 101 healthy volunteers from multicenters in China were analyzed. The values of the HRM parameters were summarized and compared between liquid and solid swallows. The frequencies of ineffective liquid and solid swallows were summarized. RESULTS: Esophagus contracted stronger and slower in solid bolus swallows than water swallows with HREM. Ineffective water swallow (DCI < 450 mm Hg.s.cm) and ineffective bread swallow (DCI < 800 mm Hg.s.cm) were frequently seen in asymptomatic individuals. The adding of bread swallows to the HREM procedure might cause diagnostic change in about 15.8% (16/101) of the asymptomatic individuals. CONCLUSIONS: The vigor and velocity of the esophageal peristalsis between liquid and solid bolus swallows are different. Ineffective water and solid bolus swallows are not rare. Adding solid bolus swallows brings diagnostic change, and it may be needed routinely for the HRM procedure.

Risk factors for extremely serious road accidents: Results from national Road Accident Statistical Annual Report of China.

BACKGROUND: In the past decades, extremely serious road accidents with a death toll over ten in each have become a severe public health problem in China. This study investigates risk factors contributing to extremely serious road accidents, which will be crucial for accident prevention. METHODS: Collecting data from The Road Accident Statistical Annual Report openly issued by China's Traffic Management Bureau of the Public Security Ministry for the time period 2004-2015, we used the monthly case number of extreme serious road accidents as the dependent variable. We then selected ten risk factors as primary independent variables: professional driver, driving under influence (alcohol or drug), fatigue, vehicle type, overload, brake problem, weather, road classification, terrain, and region. The method of negative binominal regression was implemented to investigate the association between these risk factors and extremely serious road accidents. RESULTS: A total of 346 extremely serious road accidents were included in our analysis. On a national scale, we found that professional driver [incidence rate ratio (IRR): 1.10, 95% CI: 1.02-1.19], fatigue (IRR: 1.15, 95% CI: 1.03-1.29), large vehicle type (IRR: 1.11, 95% CI: 1.03-1.21), overload (IRR: 1.09, 95% CI: 1.03-1.16), and terrain (IRR: 1.09, 95% CI: 1.01-1.18) were significantly associated with extremely serious road accidents. Besides, separate analyses on western and non-western region indicated that both regions had shared risk factors as well as distinct factors. CONCLUSIONS: Our study identifies professional driver, fatigue, large vehicle type, overload, and terrain as significant risk factors of extremely serious road accidents in China, and targeted and preventative measures could be taken based on our findings.

Cumulative evidence for relationships between multiple variants in the VTI1A and TCF7L2 genes and cancer incidence.

Genetic studies have linked the VTI1A-TCF7L2 region with risk of multiple cancers. However, findings from these studies were generally inconclusive. We aimed to provide a synopsis of current understanding of associations between variants in the VTI1A-TCF7L2 region and cancer susceptibility. We conducted a comprehensive research synopsis and meta-analysis to evaluate associations between 17 variants in this region and risk of seven cancers using data from 32 eligible articles totaling 224,656 cancer cases and 324,845 controls. We graded cumulative evidence of significant associations using Venice criteria and false-positive report probability tests. We also conducted analyses to evaluate potential function of these variants using data from the Encyclopedia of DNA Elements (ENCODE) Project. Eight variants showed a nominally significant association with risk of individual cancer (p < 0.05). Cumulative epidemiological evidence of an association was graded as strong for rs7903146 [odds ratio (OR) = 1.05, p = 4.13 × 10-5 ] and rs7904519 (OR = 1.07, p = 2.02 × 10-14 ) in breast cancer, rs11196172 (OR = 1.11, p = 2.22 × 10-16 ), rs12241008 (OR = 1.13, p = 1.36 × 10-10 ) and rs10506868 (OR = 1.10, p = 3.98 × 10-9 ) in colorectal cancer, rs7086803 in lung cancer (OR = 1.30, p = 3.54 × 10-18 ) and rs11196067 (OR = 1.18, p = 3.59 × 10-13 ) in glioma, moderate for rs12255372 (OR = 1.12, p = 2.52 × 10-4 ) in breast cancer and weak for rs7903146 (OR = 1.11, p = 0.007) in colorectal cancer. Data from ENCODE suggested that seven variants with strong evidence and other correlated variants might fall within putative functional regions. Collectively, our study provides summary evidence that common variants in the VTI1A and TCF7L2 genes are associated with risk of breast, colorectal, lung cancer and glioma and highlights the significant role of the VTI1A-TCF7L2 region in the pathogenesis of human cancers.