Laparoscopic partial splenectomy for a giant splenic pseudocyst with elevated CA19-9: a case report.

Introduction and importance: Currently, there is a lack of reliable evidence on the management of splenic cysts, which are rare. Exploring the efficacy of laparoscopic partial splenectomy can aid in the accumulation of treatment-related evidence. Case presentation: Here, we report the case of a 31-year-old female who was diagnosed with a giant splenic cyst with elevated serum CA19-9 and subsequently underwent laparoscopic partial splenectomy. Clinical discussion: The effects of most treatment options for splenic cysts, including percutaneous aspiration and drainage, fenestration, and partial splenectomy, have not been confirmed by high-level evidence. With the development of minimally invasive surgery, laparoscopic partial splenectomy has drawn increasing attention. Additionally, the relationships between tumor markers and splenic cysts need to be further elucidated. Conclusions: Laparoscopic partial splenectomy might be recommended for patients with splenic cysts, especially when the cysts are not completely covered by the splenic parenchyma.

A novel pathogenic splicing mutation of RPGR in a Chinese family with X-linked retinitis pigmentosa verified by minigene splicing assay.

AIM: To report a novel splicing mutation in the RPGR gene (encoding retinitis pigmentosa GTPase regulator) in a three-generation Chinese family with X-linked retinitis pigmentosa (XLRP). METHODS: Comprehensive ophthalmic examinations including best corrected visual acuity, fundus photography, vision field, and pattern-visual evoked potential were performed to identify the disease phenotype of a six-year-old boy from the family (proband). Genomic DNA was extracted from peripheral blood of five available members of the pedigree. Whole-exome sequencing (WES), Sanger sequencing, and pSPL3-based exon trapping were used to investigate the aberrant splicing of RPGR. Human Splice Finder v3.1 and NNSPLICE v0.9 were used for in silico prediction of splice site variants. RESULTS: The proband was diagnosed as having retinitis pigmentosa (RP). He had severe symptoms with early onset. A novel splicing mutation, c.619+1G>C in RPGR was identified in the proband by WES and in four family members by Sanger sequencing. Minigene splicing assays verified that c.619+1G>C in RPGR would result in the formation of a damaging alternative transcript in which the last 91 bp of exon 6 were skipped, leading to the subsequent deletion of 623 correct amino acids (c.529_619del p.Val177Glnfs*16). CONCLUSION: We identify a novel splice donor site mutation causing aberrant splicing of RPGR. Our findings add to the catalog of pathological mutations of RPGR and further emphasize the functional importance of RPGR in RP pathogenesis and its complex clinical phenotypes.

Safety and feasibility of modified duct-to-mucosa pancreaticojejunostomy during pancreatoduodenectomy: A retrospective cohort study.

BACKGROUND: Pancreatoduodenectomy (PD) is the most effective surgical procedure to remove a pancreatic tumor, but the prevalent postoperative complications, including postoperative pancreatic fistula (POPF), can be life-threatening. Thus far, there is no consensus about the prevention of POPF. AIM: To determine possible prognostic factors and investigate the clinical effects of modified duct-to-mucosa pancreaticojejunostomy (PJ) on POPF development. METHODS: We retrospectively collected and analyzed the data of 215 patients who underwent PD between January 2017 and February 2022 in our surgery center. The risk factors for POPF were analyzed by univariate analysis and multivariate logistic regression analysis. Then, we stratified patients by anastomotic technique (end-to-side invagination PJ vs modified duct-to-mucosa PJ) to conduct a comparative study. RESULTS: A total of 108 patients received traditional end-to-side invagination PJ, and 107 received modified duct-to-mucosa PJ. Overall, 58.6% of patients had various complications, and 0.9% of patients died after PD. Univariate and multivariate logistic regression analyses showed that anastomotic approaches, main pancreatic duct (MPD) diameter and pancreatic texture were significantly associated with the incidence of POPF. Additionally, the POPF incidence and operation time in patients receiving modified duct-to-mucosa PJ were 11.2% and 283.4 min, respectively, which were significantly lower than those in patients receiving traditional end-to-side invagination PJ (27.8% and 333.2 minutes). CONCLUSION: Anastomotic approach, MPD diameter and pancreatic texture are major risk factors for POPF development. Compared with traditional end-to-side invagination PJ, modified duct-to-mucosa PJ is a simpler and more efficient technique that results in a lower incidence of POPF. Further studies are needed to validate our findings and explore the clinical applicability of our technique for laparoscopic and robotic PD.

Dietary risk factors for inflammatory bowel disease in Shanghai: A case-control study.

BACKGROUND AND OBJECTIVES: Inflammatory bowel disease (IBD) is a multifactorial condition involving the complex interplay of genomics, microbiota, immunology, environment, and personal behaviors, particularly diet. METHODS AND STUDY DESIGN: A case-control study in a tertiary referral hospital. Fifty patients with IBD and 50 controls without gastrointestinal diseases were enrolled consecutively from October 1, 2016, to December 31, 2017. Sociodemographic and Food Frequency Questionnaires (FFQs) were completed, and dietary risk factors for IBD were identified. RESULTS: Six major foods were associated with the recurrent incidence of IBD (p<0.05): chili, fish, milk, nuts, eggs, and fruit. Logistic regression analysis revealed that eating chili and drinking milk more than three times weekly increased the risk of relapse, as did eating fish and nuts one or two times weekly. Eating fruit more than once weekly reduced the risk of IBD. Fish, seafood, vegetables, nuts, beef, and fruit, along with a history of food allergy, were associated with a high risk of clinically recurrent IBD. Dietary patterns featuring seafood and nuts also increased the risk of relapse. CONCLUSIONS: The consumption of chili, milk, fish, and nuts beyond moderate weekly frequencies increased the risk of IBD, whereas fruit consumption was consistently protective against IBD development. Relapse susceptibility was also associated with a history of food allergy. Thus, IBD risk management can involve more personalized and less restrictive dietary patterns, as well as the enforcement of weekly dose thresholds. Uncertainty remains regarding association differentials between ulcerative colitis (UC) and Crohn's disease (CD).

Pterostilbene pre-treatment reduces LPS-induced acute lung injury through activating NR4A1.

CONTEXT: Pterostilbene (PTE), a common polyphenol compound, exerts an anti-inflammatory effect in many diseases, including acute lung injury (ALI). OBJECTIVE: This study explores the potential mechanism of PTE pre-treatment against lipopolysaccharide (LPS)-induced ALI. MATERIALS AND METHODS: Sixty Sprague-Dawley rats were divided into control, ALI, 10 mg/kg PTE + LPS, 20 mg/kg PTE + LPS, and 40 mg/kg PTE + LPS groups. At 24 h before LPS instillation, PTE was administered orally. At 2 h before LPS instillation, PTE was again administered orally. After 24 h of LPS treatment, the rats were euthanized. The levels of inflammatory cells and inflammatory factors in the bronchoalveolar lavage fluid (BALF), the expression of nuclear receptor subfamily 4 group A member 1 (NR4A1), and the nuclear factor (NF)-κB pathway-related protein levels were detected. NR4A1 agonist was used to further investigate the mechanism of PTE pre-treatment. RESULTS: After PTE pre-treatment, the LPS induced inflammation was controlled and the survival rate was increased to 100% from 70% after LPS treatment 24 h. For lung injury score, it decreased to 1.5 from 3.5 after treating 40 mg/kg PTE. Compared with the control group, the expression of NR4A1 in the ALI group was decreased by 20-40%. However, the 40 mg/kg PTE pre-treatment increased the NR4A1 expression by 20-40% in the lung tissue. The results obtained with pre-treatment NR4A1 agonist were similar to those obtained by pre-treatment 40 mg/kg PTE. CONCLUSIONS: PTE pre-treatment might represent an appropriate therapeutic target and strategy for preventing ALI induced by LPS.

Design, synthesis and mechanistic studies of a TICT based fluorogenic probe for lighting up protein HSA.

Human serum albumin (HSA) in blood serves as an important biomarker for clinical diagnosis, and fluorescence sensing method has attracted extensive attention. In this work, a small organic molecule probe, YS8, involving twisted intramolecular charge transfer (TICT) characteristic, was designed and investigated to detect HSA. YS8 kept silent state in fluorescence under physiological conditions, but the encapsulation of YS8 in the hydrophobic subdomain IB region of HSA inhibited the TICT state and produced a clear light-up fluorescent signal. Especially, YS8 was demonstrated to be an efficient fluorogenic probe to discriminate HSA from other proteins including the bovine serum albumin (BSA). Moreover, YS8/HSA complex could be applied in fluorescence imaging in living cells and is also useful in the study of artificial fluorescent protein (AFP).

Triptolide enhances the sensitivity of pancreatic cancer PANC-1 cells to gemcitabine by inhibiting TLR4/NF-κB signaling.

BACKGROUND: This study aimed to investigate roles of Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling in triptolide (TPL)-induced sensitivity of pancreatic cancer cells to gemcitabine (GEM). METHODS: In vitro, pancreatic cancer PANC-1 cells were treated with lipopolysaccharide (LPS) to activate TLR4, TLR4-siRNA, GEM alone, or GEM plus TPL. In vivo, nude mice bearing PANC-1 cell xenografts were treated with GEM, TPL, or both. Cell proliferation was detected by MTT assay and Ki-67 staining. Apoptosis was assessed by flow cytometry and TUNEL assay. A double luciferase reporter gene was used to detect NF-κB activity. RESULTS: The sensitivity of PANC-1 cells to GEM was reduced by LPS but enhanced by TLR4-siRNA. TPL inhibited expression of TLR4/NF-κB signaling components, which was reversed by LPS. The TPL+GEM group showed more apoptosis than the LPS+TPL+GEM group. Moreover, the activity of NF-κB and the expression of TLR4, p-p65 Survivin, CyclinD1 and Bcl-2 in the TPL+GEM group were lower than in the LPS+TPL+GEM group, whereas Bax expression was higher. The volume of transplanted tumors in the TPL+GEM group was lower than that in the TPL or GEM group. Phospho-p65, Survivin, CyclinD1 and Bcl-2 expression in transplanted tumors was lower in TPL+GEM group than in either single drug group. The Ki-67 staining score of the TPL+GEM group was lower and tumor cells apoptosis rate was increased when compared with TPL or GEM alone. CONCLUSIONS: TPL enhances the sensitivity of pancreatic cancer PANC-1 cells to GEM by inhibiting TLR4/NF-κB signaling.

Validation in China of a non-invasive salivary pepsin biomarker containing two unique human pepsin monoclonal antibodies to diagnose gastroesophageal reflux disease.

OBJECTIVES: Peptest is a new non-invasive reflux diagnostic test based on lateral flow technology that containing two highly specific human pepsin monoclonal antibodies for detecting pepsin, a biomarker for reflux disease. The primary aim of this multicenter clinical study was to validate the efficacy of Peptest in patients diagnosed with gastroesophageal reflux and healthy controls in China. METHODS: Patients with suspected gastroesophageal reflux underwent an endoscopy and were classified into non-erosive reflux disease and erosive esophagitis subgroups. A healthy control group was also recruited. All participants were given a reflux disease questionnaire-patients scoring greater than 12 and controls scoring zero. All participants provided a postprandial saliva sample and most patients gave an additional post-symptom sample for pepsin analysis. RESULTS: Altogether 1032 participants aged between 19 and 78 years were recruited. They consisted of 488 patients with non-erosive reflux disease, 221 with erosive esophagitis and 323 healthy controls. The number of postprandial and post-symptom samples analyzed totaled 1031 and 692, respectively. The results across all centers showed an overall pepsin-positive sensitivity of 85%, a specificity of 60%, a positive predictive value of 82%, a negative predictive value of 65% and a positive likelihood ratio of 2.12. CONCLUSION: The sensitivity of Peptest was high, but the specificity achieved in some centers was low, resulting overall in only a moderate specificity. Further diagnostic investigative studies are warranted.

Ginsenoside Re Improves Isoproterenol-Induced Myocardial Fibrosis and Heart Failure in Rats.

Objective. Panax ginseng is used widely for treatment of cardiovascular disorders in China. Ginsenoside Re is the main chemical component of P. ginseng. We aimed to investigate the protective effect of ginsenoside Re on isoproterenol-induced myocardial fibrosis and heart failure in rats. Methods. A model of myocardial fibrosis and heart failure was established by once-daily subcutaneous injection of isoproterenol (5 mg/kg/day) to rats for 7 days. Simultaneously, rats were orally administrated ginsenoside Re (5 or 20 mg/kg) or vehicle daily for 4 weeks. Results. Isoproterenol enhanced the heart weight, myocardial fibrosis, and hydroxyproline content in rat hearts. Ginsenoside Re inhibited (at least in part) the isoproterenol-induced increase in heart weight, myocardial fibrosis, and hydroxyproline content. Compared with the isoproterenol group, treatment with ginsenoside Re ameliorated changes in left ventricular systolic pressure, left ventricular end diastolic pressure, and the positive and negative maximal values of the first derivative of left ventricular pressure. Ginsenoside Re administration also resulted in decreased expression of transforming growth factor (TGF)-ß1 in serum and decreased expression of Smad3 and collagen I in heart tissue. Conclusion. Ginsenoside Re can improve isoproterenol-induced myocardial fibrosis and heart failure by regulation of the TGF-ß1/Smad3 pathway.

Associations of Bone Mineral Density and Bone Metabolism Indices with Urine Albumin to Creatinine Ratio in Chinese Patients with Type 2 Diabetes.

OBJECTIVE: To identify correlations of bone mineral density (BMD) and bone metabolism indices with the urine albumin to creatinine ratio (ACR) as an indicator of nephropathy in Chinese patients with type 2 diabetes (T2D). METHODS: In this retrospective analysis, 297 patients with T2D were divided into 3 groups according to the urine ACR. Patients' data were analyzed to identify associations of general conditions, blood glucose level, lipid levels, and uric acid level with BMD and bone metabolism indices. RESULTS: BMD at every location tested (femoral neck, trochanter, inside hip, Ward's triangle, total hip, and lumbar vertebrae) was negatively correlated with the urine ACR (all p<0.05). Osteocalcin, beta-C-terminal telopeptide (ß-CTX), and procollagen type 1 N- peptide (P1NP) were positively correlated with urine ACR (all p<0.05). Finally, 25-hydroxyvitamin D [25(OH)D] was negatively correlated with urine ACR (p<0.05). Multiple regression analysis with adjustment for age, body mass index, disease duration, and other clinical measurements revealed no significant correlation between urine ACR and BMD measurements or ß-CTX (p>0.05). However, significant correlations remained between urine ACR and osteocalcin, P1NP, and 25(OH)D (p<0.05). The same results were obtained for postmenopausal women specifically, with the exception of a significant correlation between the ACR and ß-CTX (p<0.05). CONCLUSION: In the early stage of diabetic nephropathy, BMD changes and bone transformation acceleration may occur, and the acceleration of bone transformation may occur before the change in BMD. Therefore, it is important to monitor bone metabolism indices in the early stage of diabetic nephropathy in T2D patients.

Ginsenoside Re Attenuates Isoproterenol-Induced Myocardial Injury in Rats.

Objective. Panax ginseng is widely used for treatment of cardiovascular disorders in China. Ginsenoside Re is the main chemical component of Panax ginseng. This study aimed to investigate the protective effect of Ginsenoside Re on isoproterenol-induced myocardial injury in rats. Methods. Male Wistar rats were orally given Ginsenoside Re (5, 20 mg/kg) daily for 7 days. Isoproterenol was subcutaneously injected into the rats for two consecutive days at a dosage of 20 mg/kg/day (on 6th and 7th day). Six hours after the last isoproterenol injection, troponin T level and creatine kinase-MB (CK-MB) activity were assayed. Histopathological examination of heart tissues was performed. The levels of malondialdehyde (MDA) and glutathione (GSH) in heart tissues were measured. The nuclear factor erythroid 2-related factor 2 (Nrf2) content in nucleus and the proteins of glutathione cysteine ligase catalytic subunit (GCLC) and glutathione cysteine ligase modulatory subunit (GCLM) in heart tissues were assayed by western blotting method. Results. Treatment with Ginsenoside Re at dose of 5, 20 mg/kg reduced troponin T level and CK-MB activity of rats subjected to isoproterenol. The cardioprotective effect of Ginsenoside Re was further confirmed by histopathological examination which showed that Ginsenoside Re attenuated the necrosis and inflammatory cells infiltration. Ginsenoside Re inhibited the increase of MDA content and the decrease of GSH in heart tissues. Moreover, the Nrf2 content in nucleus and the expressions of GCLC and GCLM were significantly increased in the animals treated with Ginsenoside Re. Conclusion. These findings suggested that Ginsenoside Re possesses the property to attenuate isoproterenol-induced myocardial ischemic injury by regulating the antioxidation function in cardiomyocytes.

The Emerging Role of Circular RNAs in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) ranks the third leading cause of cancer death in the world and has a notably low survival rate. Circular RNAs (circRNAs) are newly classed non-coding RNA (ncRNA) members that are capable of regulating gene expression at transcription or post-transcription levels. Recent studies demonstrate that some circRNAs are differentially expressed in HCC, and the deregulation of these circRNAs is associated with the clinical pathological and prognostic significance. They also play essential roles in HCC progression, and contribute to cell proliferation, migration, invasion and metastasis by targeting different microRNAs (miRNAs) and protein-coding genes. In this review, we concentrate on recent progress of some important circRNAs in HCC, with an emphasis on their deregulation, functions and regulatory mechanisms, and discuss their potential utility as diagnostic and/or prognostic biomarkers or therapeutic targets for HCC.

20(S)-Protopanaxadiol-Induced Apoptosis in MCF-7 Breast Cancer Cell Line through the Inhibition of PI3K/AKT/mTOR Signaling Pathway.

20(S)-Protopanaxadiol (PPD) is one of the major active metabolites of ginseng. It has been reported that 20(S)-PPD shows a broad spectrum of antitumor effects. Our research study aims were to investigate whether apoptosis of human breast cancer MCF-7 cells could be induced by 20(S)-PPD by targeting the Phosphatidylinositol 3-kinase/Protein kinase B/Mammalian target of rapamycin (PI3K/AKT/mTOR) signal pathway in vitro and in vivo. Cell cycle analysis was performed by Propidium Iodide (PI) staining. To overexpress and knock down the expression of mTOR, pcDNA3.1-mTOR and mTOR small interfering RNA (siRNA) transient transfection assays were used, respectively. Cell viability and apoptosis were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-test and Annexin V /PI double-staining after transfection. The antitumor effect in vivo was determined by the nude mice xenograft assay. After 24 h of incubation, treatment with 20(S)-PPD could upregulate phosphorylated-Phosphatase and tensin homologue deleted on chromosome 10 (p-PTEN) expression and downregulate PI3K/AKT/mTOR-pathway protein expression. Moreover, G0/G1 cell cycle arrest in MCF-7 cells could be induced by 20(S)-PPD treatment at high concentrations. Furthermore, overexpression or knockdown of mTOR could inhibit or promote the apoptotic effects of 20(S)-PPD. In addition, tumor volumes were partially reduced by 20(S)-PPD at 100 mg/kg in a MCF-7 xenograft model. Immunohistochemical staining indicated a close relationship between the inhibition of tumor growth and the PI3K/AKT/mTOR signal pathway. PI3K/AKT/mTOR pathway-mediated apoptosis may be one of the potential mechanisms of 20(S)-PPD treatment.

Human Enterovirus 68 Interferes with the Host Cell Cycle to Facilitate Viral Production.

Enterovirus D68 (EV-D68) is an emerging pathogen that recently caused a large outbreak of severe respiratory disease in the United States and other countries. Little is known about the relationship between EV-D68 virus and host cells. In this study, we assessed the effect of the host cell cycle on EV-D68 viral production, as well as the ability of EV-D68 to manipulate host cell cycle progression. The results suggest that synchronization in G0/G1 phase, but not S phase, promotes viral production, while synchronization in G2/M inhibits viral production. Both an early EV-D68 isolate and currently circulating strains of EV-D68 can manipulate the host cell cycle to arrest cells in the G0/G1 phase, thus providing favorable conditions for virus production. Cell cycle regulation by EV-D68 was associated with corresponding effects on the expression of cyclins and CDKs, which were observed at the level of the protein and/or mRNA. Furthermore, the viral non-structural protein 3D of EV-D68 prevents progression from G0/G1 to S. Interestingly, another member of the Picornaviridae family, EV-A71, differs from EV-D68 in that G0/G1 synchronization inhibits, rather than promotes, EV-A71 viral replication. However, these viruses are similar in that G2/M synchronization inhibits the production and activity of both viruses, which is suggestive of a common therapeutic target for both types of enterovirus. These results further clarify the pathogenic mechanisms of enteroviruses and provide a potential strategy for the treatment and prevention of EV-D68-related disease.

Ginsenoside Rg3 Improves Cardiac Function after Myocardial Ischemia/Reperfusion via Attenuating Apoptosis and Inflammation.

Objectives. Ginsenoside Rg3 is one of the ginsenosides which are the main constituents isolated from Panax ginseng. Previous study demonstrated that ginsenoside Rg3 had a protective effect against myocardial ischemia/reperfusion- (I/R-) induced injury. Objective. This study was designed to evaluate the effect of ginsenoside Rg3 on cardiac function impairment induced by myocardial I/R in rats. Methods. Sprague-Dawley rats were subjected to myocardial I/R. Echocardiographic and hemodynamic parameters and histopathological examination were carried out. The expressions of P53, Bcl-2, Bax, and cleaved caspase-3 and the levels of TNF-α and IL-1ß in the left ventricles were measured. Results. Ginsenoside Rg3 increased a left ventricular fractional shortening and left ventricular ejection fraction. Treatment with ginsenoside Rg3 also alleviated increases of left ventricular end diastolic pressure and decreases of left ventricular systolic pressure and ±dp/dt in myocardial I/R-rats. Ginsenoside Rg3 decreased apoptosis cells through inhibiting the activation of caspase-3. Ginsenoside Rg3 also caused significant reductions of the contents of TNF-α and IL-1ß in left ventricles of myocardial I/R-rats. Conclusion. The findings suggested that ginsenoside Rg3 possessed the effect of improving myocardial I/R-induced cardiac function impairment and that the mechanism of pharmacological action of ginsenoside Rg3 was related to its properties of antiapoptosis and anti-inflammation.

[Effect of PEG-6000 Simulation Drought Stress on Physiological Characteristics of Guangfeng Medicinal Yam Plantlets].

Objective: In order to provide the theoretical basis for the Guangfeng medicinal yam( Dioscorea opposita) in field transplanting, the effect of PEG-6000 simulation drought stress on physiological characteristics of Guangfeng medicinal yam plantlets was studied. Methods: Using the method of spectrophotometer,the content of total chlorophyll,soluble total sugar, soluble protein and praline,as well as the activities of SOD,CAT and POD of Guangfeng medicinal yam plantlets were tested under PEG-6000 treatment. Results: Under PEG-6000 simulated drought stress, with the increasing of drought stress and the extension of stress time, the total chlorophyll content of Guangfeng medicinal yam plantlets continued to decline, the content of total soluble sugar, proline and MDA of Guangfeng medicinal yam plantlets significantly increased, the content of soluble protein and the activities of CAT,POD and SOD of Guangfeng medicinal yam plantlets increased at first and then decreased. Conclusion: This study reveals the changes of physiological indices of Guangfeng medicinal yam plantlets under PEG-6000 simulation drought stress, which indicated that Guangfeng medicinal yam plantlets have certain drought tolerance.

Prognostic value of c-Met in colorectal cancer: a meta-analysis.

AIM: To assess the prognostic value of c-Met status in colorectal cancer. METHODS: We conducted a search in PubMed, Web of Science, and the Cochrane Library covering all published papers up to July 2014. Only studies assessing survival in colorectal cancer by c-Met status were included. This meta-analysis was performed by using STATA11.0. RESULTS: Ultimately, 11 studies were included in this analysis. Meta-analysis of the hazard ratios (HR) indicated that patients with high c-Met expression have a significantly poorer overall survival (OR) (HR = 1.33, 95%CI: 1.06-1.59) and progression-free survival (PFS) (HR = 1.47, 95%CI: 1.03-1.91). Subgroup analysis showed a significant association between high c-Met expression and poorer overall survival in the hazard ratio reported (HR = 1.41, 95%CI: 1.08-1.74). CONCLUSION: The present meta-analysis indicated that high c-Met expression was associated with poor prognosis in patients with colorectal cancer.

Fish consumption and risk of gastrointestinal cancers: a meta-analysis of cohort studies.

AIM: To assess quantitatively the relationship between fish intake and the incidence of gastrointestinal cancers in a meta-analysis of cohort studies. METHODS: We searched MEDLINE, Embase, Science Citation Index Expanded, and the bibliographies of retrieved articles. Prospective cohort studies were included if they reported relative risks (RRs) and corresponding 95% confidence intervals (CIs) of various cancers with respect to fish intake. When RRs were not available in the published article, they were computed from the exposure distributions. Two investigators extracted the data independently and discrepancies were resolved by discussion with a third investigator. We performed random-effect meta-analyses and meta-regressions of study-specific incremental estimates to determine the risk of cancer associated with a 20-g/d increment of fish consumption. RESULTS: Forty-two studies, comprising 27 independent cohorts, met our inclusion criteria. The studies included 2325040 participants and 24115 incident cases of gastrointestinal cancer, with an average follow-up of 13.6 years. Compared with individuals who did not eat, or seldom ate, fish, the pooled RR of gastrointestinal cancers was 0.93 (95%CI: 0.88-0.98) for regular fish consumers, 0.94 (0.89-0.99) for low to moderate fish consumers, and 0.91 (0.84-0.97) for high fish consumers. Overall, a 20-g increase in fish consumption per day was associated with a 2% reduced risk of gastrointestinal cancers (RR = 0.98; 95%CI: 0.96-1.01). In subgroup analyses, we noted that fish consumption was associated with reduced risk of colorectal (RR = 0.93; 95%CI: 0.87-0.99; P < 0.01), esophageal (RR = 0.91; 95%CI: 0.83-0.99; P < 0.05) and hepatocellular cancers (RR = 0.71; 95%CI: 0.48-0.95; P < 0.01). CONCLUSION: This meta-analysis suggested that fish consumption may reduce total gastrointestinal cancer incidence. Inverse relationships were also detected between fish consumption and specific types of cancers.

20(S)-Protopanaxadiol induces human breast cancer MCF-7 apoptosis through a caspase-mediated pathway.

20(S)-Protopanaxadiol (PPD), a ginsenoside isolated from Pananx quinquefolium L., has been shown to inhibit growth and proliferation in several cancer cell lines. The aim of this study was to evaluate its anticancer activity in human breast cancer cells. MCF-7 cells were incubated with different concentrations of 20(S)-PPD and cytotoxicity was evaluated by MTT assay. Occurrence of apoptosis was detected by DAPI and Annexin V-FITC/PI double staining. Mitochondrial membrane potential was measured with Rhodamine 123. The Bcl-2 and Bax expression were determined by Western blot analysis. Caspase activity was measured by colorimetric assay. 20(S)-PPD dose-dependently inhibited cell proliferation in MCF-7 cells, with an IC50 value of 33.3 µM at 24h. MCF-7 cells treated with 20(S)-PPD presented typical apoptosis, as observed by morphological analysis in cell stained with DAPI. The percentages of annexin V-FITC positive cells were 8.92%, 17.8%, 24.5% and 30.5% in MCF-7 cells treated with 0, 15, 30 and 60µM of 20(S)-PPD, respectively. Moreover, 20(S)-PPD could induce mitochondrial membrane potential loss, up-regulate Bax expression and down-regulate Bcl-2 expression. These events paralleled activation of caspase-9, -3 and PARP cleavage. Apoptosis induced by 20(S)-PPD was blocked by z-VAD-fmk, a pan-caspase inhibitor, suggesting induction of caspase-mediated apoptotic cell death. In conclusion, the 20(S)-PPD investigated is able to inhibit cell proliferation and to induce cancer cell death by a caspase-mediated apoptosis pathway.

Peptic ulcer bleeding in China: a multicenter endoscopic survey of 1006 patients.

OBJECTIVE: We aimed to describe the clinical picture, management and outcomes of Chinese patients with peptic ulcer bleeding (PUB), especially in those with high risks. METHODS: A multicenter endoscopic survey was conducted. All consecutive patients with endoscopy confirmed PUB from October 2010 to June 2011 were enrolled. Data including patients' gender, age, symptoms and endoscopic findings, Forrest classification, and endoscopic and medical treatment were documented. High-risk ulcer was defined as Forrest grades Ia to IIb upon endoscopy. Rates of rebleeding, surgery and mortality were recorded. RESULTS: In all, 1006 patients were included. Of these 437 (43.4%) were categorized with high-risk PUB, among whom 110 (25.2%) received endoscopic treatment, and the success rate was 99.1%. Rebleeding rates 1-3 days, 4-5 days and 6-30 days after treatment in high-risk patients who did and did not receive endoscopic treatment were 10.9% versus 10.4%, 3.6% versus 3.7% and 0.9% versus 1.5%, respectively. The surgery rates of high-risk patients with or without endoscopic treatment were 1.8% (2/110) versus 1.8% (6/327). During the 9-month study period, two patients with high-risk PUB died, therefore, the overall mortality rate of high-risk PUB was 0.5% (2/437). CONCLUSION: The study suggests that the proportions of high-risk PUB in China is 43.4%, while rebleeding and surgery rate after endoscopic treatment as well as the mortality rate of high-risk PUB in China are 15.6%, 1.8% and 0.5%, respectively.