Therapeutic effects and safety of apatinib mesylate on patients with gastric carcinoma peritoneal metastasis in SOX scheme.

OBJECTIVE: The aim of this study was to investigate the diagnostic values of serum tumor markers in gastric carcinoma peritoneal metastasis and the therapeutic efficacy as well as safety of apatinib mesylate combined with Geo+Oxaliplatin (SOX) scheme treatment in gastric carcinoma peritoneal metastasis. PATIENTS AND METHODS: Sixty patients with gastric carcinoma peritoneal metastasis and 11 patients without gastric carcinoma peritoneal metastasis were selected as the research subjects. The levels of serum tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 125, CA211, CA242, CA724, and CA19-9] and abdominal irrigating solution exosome [micro ribonucleic acid (miR)-21 and miR-320c] and the differences in their diagnostic values were compared and analyzed. The patients with gastric cancer peritoneal metastases are then divided into two groups, one for control (30 cases receiving just SOX scheme treatment) and the other for the experiment (30 cases receiving SOX scheme treatment plus apatinib mesylate). Besides, the differences in serum tumor marker level, therapeutic efficacy, overall survival (OS), complication rating, and Quality of Life Questionnaire-Core-30 (QLQ-C30) score among patients after treatment were compared. RESULTS: Demonstrated that serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 125, CA211, CA242, CA724, and CA19-9 levels of patients in the transfer group were remarkably enhanced compared with those of patients in the non-transfer group, and the levels of abdominal irrigating solution exosome (miR-21 and miR-320c) were reduced compared with those in non-transfer group (p<0.05). The area under the curve (AUC) of the diagnosis of gastric carcinoma peritoneal metastasis by each index were 0.553, 0.880, 0.832, 0.619, 0.863, 0.651, 0.918, and 0.903, respectively. Patients in the experimental group's serum levels of CEA, CA125, CA211, CA242, CA724, and CA19-9 were noticeably lower after therapy compared to those in the control group, and their median OS was also noticeably longer (p<0.05). After treatment, the objective remission rate (ORR) and disease control rate (DCR) of the control group and experimental group amounted to 6.7% vs. 30.0% and 50.0% vs. 86.7%, respectively. ORR and DCR of the experimental group were notably higher (p<0.05). Between the patients in the control group and the experimental group, there were no glaring variations in the frequency of problems (hypertension, nausea, vomiting, bone marrow suppression, hand-foot syndrome, and leucopenia) (p>0.05). The cognitive function, emotional function, and life health scores of patients in the experimental group were significantly higher than those in the control group (p<0.05), which suggested that serum tumor markers and miR-21 as well as miR-320c showed high diagnostic efficiency in gastric carcinoma peritoneal metastasis. CONCLUSIONS: Apatinib mesylate combined with SOX scheme treatment was more effective in treating gastric carcinoma peritoneal metastasis and possessed the same safety as single SOX scheme treatment. Hence, it is worthy of clinical promotion.

Potential biomarkers for the prognosis and treatment of HCC immunotherapy.

OBJECTIVE: The liver is a unique organ containing large populations of immune cells. Immunotherapy for liver cancer is a promising yet particularly challenging method. Therefore, it harbors great significance for the identification of immune-related subtypes and the potential therapeutic targets for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Firstly, we classified the HCC samples downloaded from the dataset of Cancer Genome Atlas (TCGA) into two clusters based on the immune cell infiltration. Thereafter, we identified the significant module and regulatory factors using the weighted gene co-expression network analysis (WGCNA). The immune competence of the regulatory factors was delineated through the ESTIMATE algorithm, the analysis of the tumor microenvironment, and pan-cancer analysis. In the single-cell RNA sequencing analysis, we further explored the immune competence of regulatory factors. We also collected the potential drugs targeting the regulatory factors. In addition, we constructed lncRNA-miRNA-mRNA interaction regulatory networks. Finally, western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were conducted to verify the protein expression of regulatory genes in HCC cell lines and tissues. RESULTS: According to the immune cell infiltration, two immune-related subtypes-cluster 1 and cluster 2-were found. Patients in cluster 2 had a more significant immune infiltration than in cluster 1. Afterward, six significant regulatory genes were identified through WGCNA, and the expression in cluster 2 was high in cluster 1. We performed a comprehensive analysis to clarify the immune signature. The results showed that the six genes had significant immunological competence. Moreover, the expression of the six genes was similar to the subtypes' classification. In the analysis of the prognosis value, patients in cluster 2 had a better prognosis. In addition, the lncRNA in the lncRNA-miRNA-mRNA interaction regulatory networks was located in the nucleus and cytoplasm. In the single-cell RNA sequencing analysis, the six genes were related to the immune cell. We also identified potential drugs for CD6 and CLEC12A, which may provide potential therapeutic drugs. Finally, the regulatory genes were verified in the western blot and quantitative real-time polymerase chain reaction. CONCLUSIONS: The classification into two clusters based on the immune cell infiltration may provide a promising prospect for HCC through immunotherapy. The six regulatory genes may be potential therapeutic targets in the treatment of HCC.

Impact of COVID-19 on acute ischemic stroke presentation and prognosis in a county-level stroke center.

OBJECTIVE: The COVID-19 pandemic has influenced regular medical procedures and health-seeking behaviors. In this study, we aimed to investigate the influence of the COVID-19 pandemic on the presentation and prognosis of acute ischemic stroke (AIS) patients in county-level stroke centers. PATIENTS AND METHODS: We retrospectively collected AIS patients during the strict lockdown period (January 24, 2020, to March 27, 2020) and the corresponding "new normal" period (2021) of the COVID-19 pandemic. Patients seen during the same timeframe in 2019 were enrolled as controls. Statistical analysis was conducted to compare the clinical characteristics of AIS patients who presented during the lockdown and new normal periods and those who presented during the pre-COVID-19 pandemic period. RESULTS: A total of 134 AIS patients presented during the lockdown period (the 2020 group), 207 patients in the pre-COVID-19 period (the 2019 group) and 201 patients in the "new normal" period (the 2021 group). Compared to the 2019 group, there was approximately 1/3 reduction in the number of patients who presented during the lockdown period, while the number of patients who received IVT or EVT was similar between the two groups. The number of patients, baseline characteristics, workflow intervals and clinical outcomes presented during the "new normal" period were similar between the 2019 and 2021 groups. Logistic regression showed that lockdown or new normal status were not risk factors associated with a poor outcome at 90 days. CONCLUSIONS: In county-level city stroke centers, the COVID-19 lockdown resulted in a reduction in the number of patients with AIS admitted to the hospital but had no effect on patients treated with IVT or EVT. Lockdown or new normal status did not influence the prognosis of AIS patients.

Effects of miR-155 on proliferation and apoptosis by regulating FoxO3a/BIM in liver cancer cell line HCCLM3.

The article "Effects of miR-155 on proliferation and apoptosis by regulating FoxO3a/BIM in liver cancer cell line HCCLM3, by W.-W. Liao, C. Zhang, F.-R. Liu, W.-J. Wang, published in Eur Rev Med Pharmacol Sci 2018; 22 (5): 1277-1285. DOI: 10.26355/eurrev_201803_14468. PMID: 29565484." has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/14468.

LncRNA HANR aggravates the malignant progression of glioma via targeting miRNA-335.

OBJECTIVE: The aim of this study was to uncover the role of lncRNA HANR in the progression of glioma and the underlying mechanism. PATIENTS AND METHODS: HANR expression level in 36 matched glioma tissues and adjacent non-tumoral tissues was determined by qRT-PCR. The relationship between HANR expression and pathological indexes of the glioma patients was analyzed. The Kaplan-Meier method was introduced to investigate the survival of glioma patients. After the knockdown of HANR, the proliferative, migratory, and invasive changes of U251 and SHG44 cells were determined. Bioinformatics and Dual-Luciferase Reporter Gene Assay were applied to predict and verify the downstream target of HANR, respectively. Furthermore, the rescue experiments were conducted to clarify the role of HANR/miRNA-335 regulatory loop in the progression of glioma. RESULTS: HANR was significantly upregulated in glioma tissues and cell lines. Glioma patients with a high expression level of HANR presented remarkably higher rates of lymphatic metastasis and distant metastasis, as well as worse prognosis. The silence of HANR remarkably attenuated the proliferative, migratory, and invasive capacities of U251 and SHG44 cells. MiRNA-335 was the direct target of HANR and was significantly downregulated in glioma tissues. Meanwhile, the miRNA-335 level was negatively regulated by HANR. In addition, the knockdown of miRNA-335 partially reversed the regulatory effects of HANR on cellular behaviors of glioma. CONCLUSIONS: LncRNA HANR is upregulated in glioma, which is closely correlated with metastasis and poor prognosis of glioma patients. In addition, HANR aggravates the progression of glioma by negatively regulating miRNA-335.

Circ_0005075 stimulates the proliferation and metastasis of glioma via downregulating SIRT1.

OBJECTIVE: The aim of this study was to uncover the potential influence of circ_0005075 on the malignant progression of glioma and the underlying mechanism. PATIENTS AND METHODS: Circ_0005075 level in glioma tissues and cell lines was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relation between circ_0005075 expression and metastasis of glioma patients was analyzed. Prognostic potential of circ_0005075 in glioma was assessed by calculating overall survival (OS) and progression-free survival (PFS). After knockdown or overexpression of circ_0005075, changes in the viability, migration, and wound closure percentage of T98-G and U87 cells were examined, respectively. Subsequently, expression pattern and prognostic value of SIRT1 in glioma patients were determined. Furthermore, the involvement of SIRT1 in glioma progression affected by circ_0005075 was evaluated through rescue experiments. RESULTS: Circ_0005075 was significantly up-regulated in glioma tissues and cell lines. Meanwhile, its expression level was significantly higher in glioma patients with lymphatic metastasis or distant metastasis when compared with those with negative metastasis. OS and PFS were both remarkably worse in glioma patients with high expression level of circ_0005075. Knockdown of circ_0005075 decreased the viability, migration, and wound closure percentage of T98-G cells. However, overexpression of circ_0005075 in U87 cells yielded the opposite trends. SIRT1 expression level was negatively regulated by circ_0005075 in glioma. QRT-PCR results demonstrated that SIRT1 was significantly down-regulated in glioma tissues and cell lines. High level of SIRT1 predicted better prognosis of glioma patients. Rescue experiments confirmed that SIRT1 was responsible for the regulatory role of circ_0005075 in the malignant progression of glioma. CONCLUSIONS: Circ_0005075 is up-regulated in glioma tissues and correlated with distant metastasis and poor prognosis of glioma patients. Furthermore, it aggravates the malignant progression of glioma by down-regulating SIRT1.

Association between SOST gene polymorphisms and response to alendronate treatment in postmenopausal Chinese women with low bone mineral density.

The aim of this study was to explore the allelic association between SOST polymorphisms and the variance of clinical effects of alendronate in postmenopausal Chinese women with osteoporosis or osteopenia. In the study, 500 postmenopausal women in Shanghai area with osteoporosis or osteopenia were included. All participants were treated with weekly oral alendronate 70 mg, daily calcium 600 mg and vitamin D 125 IU for 12 months. Nine tagging single-nucleotide polymorphisms (SNPs) in SOST gene were genotyped. Bone mineral density of lumbar spine (L1-L4), left femoral neck and total hip were measured at baseline and after 1 year of treatment, respectively. In the study, 450 subjects completed the 1-year follow-up. The rs865429 was significantly associated with the % change of BMD at the femoral neck (P = 0.007). GG carriers seemed to be at an advantage after treatment of alendronate. Compared with AG and AA heterozygote, GG homozygote had the highest % change of BMD (3.100 ± 2.899%) at femoral neck. The odds ratio (95% confidence) of GG homozygote to be responders at femoral neck was 1.921 (1.211-3.048). Two haplotypes GG and AC constituted by rs865429 and rs851057 were associated with the % change of BMD at femoral neck and total hip, respectively. Therefore, the common variation of SOST gene contribute to the therapeutic response to alendronate treatment in Chinese women with osteoporosis or osteopenia.

Autologous oxygen release nano bionic scaffold composite miR-106a induced BMSCs enhances osteoblast conversion and promotes bone repair through regulating BMP-2.

OBJECTIVE: Suitable seed cells and selection of bioactive scaffold materials are the main research contents of bone tissue engineering. It was showed that autologous oxygen release nano bionic scaffold could promote the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The role of microRNA-106a (miR-106a) in regulating BMSCs differentiation has not been reported. We intend to investigate the role of autologous oxygen release nano bionic scaffold composite miR-106a in inducing BMSCs constructing tissue engineering bone. MATERIALS AND METHODS: Rat BMSCs were isolated and transfected by using miR-106a scramble or miR-106a inhibitor. Healthy male Sprague-Dawly (SD) rats were randomly divided into three groups, including bone fracture group established as rat tibial fracture model, negative control group implanted by autologous oxygen release nano bionic scaffold composite miR-106a scramble BMSCs, and miR-106a inhibitor group implanted by autologous oxygen release nano bionic scaffold composite miR-106a inhibitor BMSCs. Callus growth was observed. Alkaline phosphatase (ALP) activity was detected. Bone morphogenetic protein 2 (BMP-2) expression was tested by Real-time PCR (RT-PCR) and Western blot assay. Collagen II production was determined by RT-PCR. RESULTS: Autologous oxygen release nano bionic scaffold composite BMSCs significantly increased local bone mineral density, promoted callus healing, facilitated ALP secretion, elevated collagen II expression, and up-regulated BMP-2 mRNA and protein levels compared with fracture group (p<0.05). Autologous oxygen release nano bionic scaffold composite miR-106a induced BMSCs exhibited more significant effect on bone repair (p<0.05). CONCLUSIONS: Autologous oxygen release nano bionic scaffold composite miR-106a induced BMSCs enhanced osteoblast conversion and promoted bone repair through regulating BMP-2.

Dietary supplementation with Clostridium butyricum helps to improve the intestinal barrier function of weaned piglets challenged with enterotoxigenic Escherichia coli K88.

AIMS: The objective of this study was twofold: (i) to examine the effect of Clostridium butyricum on intestinal barrier function and (ii) to elucidate the mechanisms involved in enhanced intestinal barrier function. METHODS AND RESULTS: Forty-eight weaned piglets were assigned randomly to either a basal diet or a C. butyricum-supplemented diet. On day 15, all pigs were orally challenged with enterotoxigenic Escherichia coli (ETEC) K88 or saline. Clostridium butyricum decreased serum diamine oxidase activity and d-lactic acid concentration, as well as increased intestinal tight junction proteins (ZO-1, claudin-3 and occludin) expression in ETEC K88-infected pigs. Moreover, C. butyricum decreased IL-1ß and IL-18 levels in serum and gut, whereas it increased IL-10 levels. Furthermore, C. butyricum downregulated NLRP3 and caspase-1 expression in ETEC K88-challenged pig gut, but did not affect apoptosis-associated speck-like protein expression. CONCLUSIONS: Clostridium butyricum enhanced intestinal barrier function and inhibited apoptosis-associated speck-like protein-independent NLRP3 inflammasome signalling pathway in weaned piglets after ETEC K88 challenge. SIGNIFICANCE AND IMPACT OF THE STUDY: The novelty of this study lies in the beneficial effects of C. butyricum on intestinal health, likely by improving intestinal barrier function and alleviating inflammatory reactions.

Effects of miR-155 on proliferation and apoptosis by regulating FoxO3a/BIM in liver cancer cell line HCCLM3.

OBJECTIVE: MiR-155 has been shown to be up-regulated in hepatocellular carcinoma (HCC) patients. B-cell lymphoma-2 (Bcl-2) interacting mediator of cell death (BIM) regulates cell proliferation and apoptosis, as its down-regulation is involved in HCC onset. Transcriptional factor FoxO3a mediates BIM expression and is related to HCC pathogenesis. Bioinformatics analysis showed targeted regulation of FoxO3a by miR-155. This study aims to investigate whether miR-155 plays a role in mediating FoxO3a/BIM signal pathway and HCC occurrence. PATIENTS AND METHODS: HCC patients were collected for tumor and adjacent tissues, in which microRNA-155 (miR-155) and FoxO3a expressions were examined. In vitro cultured HCCLM3, HepG2 and L-02 cells were tested for basal apoptotic rate by flow cytometry and were compared for miR-155 and FoxO3a expression. Dual-luciferase reporter gene assay demonstrated the targeted relationship between miR-155 and FoxO3a. HCCLM3 cells were treated with miR-155 inhibitor and/or FoxO3a-pMD18-T. Cell apoptosis and proliferation were examined by using flow cytometry and MTT assays, respectively. Western blot and spectrometry assay were employed to quantify the FoxO3a, BIM expressions, and caspase activity. RESULTS: Compared to adjacent tissues, HCC tissues had significantly higher miR-155 and significantly lower FoxO3a expression (p<0.05). HCCLM3 and HepG2 cells had significantly lower FoxO3a expression and basal apoptotic rate compared to L02 cells, whilst miR-155 level was significantly higher (p<0.05). MiR-155 targeted and inhibited 3'-UTR of FoxO3a, increasing BIM expression, caspase-3, and caspase-9 activities, and enhancing cell apoptosis and weakening proliferation. CONCLUSIONS: HCC tissues elevated the miR-155 and suppressed the FoxO3a expressions. MiR-155 targeted and inhibited FoxO3a expression to suppress the BIM, depress caspase-3 and caspase-9 activities, therefore inhibiting the HCC cell apoptosis and facilitating proliferation.

B-cell deficiency: a de novo IKZF1 patient and review of the literature

No disponible

Effect of a rosmarinic acid supplemented hemodialysis fluid on inflammation of human vascular endothelial cells.

Chronic systemic inflammation and repetitive damage of vascular endothelia by incompatible dialysis system are probable causes of cardiovascular disease in patients on dialysis. The present study aimed to assess in vitro biocompatibility and anti-inflammatory effect of hemodialysis fluid supplemented with rosmarinic acid (RA) using human umbilical vein endothelial cells (HUVEC). HUVECs (5×106 cells/mL) were pre-exposed to 1 µg/mL of lipopolysaccharides (LPS) and incubated with RA-supplemented hemodialysis fluid (HDF). Cytotoxicity was assessed qualitatively by morphologic assessment and quantitatively by MTT assay. Expressions of proinflammatory mediators were assessed using quantitative real-time PCR and production of NO was quantified. Phosphorylation of AKT and nuclear localization of nuclear factor kappa B (NF-κB) were examined using western blotting. Exposure of HUVECs to RA-supplemented HDF had no influence on morphology and viability. Inhibition of proinflammatory mediator production in HUVECs by RA supplementation to HDF was significant in a dose-dependent manner. Exposure to RA-supplemented HDF resulted in a decrease in nitric oxide synthase expression and reduction of NO production in LPS-stimulated HUVECs. RA supplementation of HDF suppressed Akt activation in LPS-stimulated HUVECs. In addition, the level of cellular IκB was increased in parallel to a reduced nuclear translocation of NF-κB in LPS-induced endothelial cells. Our results suggest that RA-supplemented HDF is biocompatible and significantly suppressed inflammation induced in endothelial cells. In this respect, the use of HDF supplemented with RA could alleviate inflammation and improve long-term treatment of patients with renal failure on dialysis. Further clinical studies are required to confirm the effects.

Characterizing Pharmacogenomic-Guided Medication Use With a Clinical Data Repository.

The extent to which pharmacogenomic-guided medication use has been adopted in various health systems is unclear. To assess the uptake of pharmacogenomic-guided medication use, we determined its frequency across our health system, which does not have a structured testing program. Using a multisite clinical data repository, we identified adult patients' first prescribed medications between January 2011 and December 2013 and investigated the frequency of germline and somatic pharmacogenomic testing, by the Pharmacogenomics Knowledgebase level of the US Food and Drug Administration label information. There were 268,262 medication orders for drugs with germline pharmacogenomic testing information in their drug labels. Pharmacogenomic testing was detected for 1.5% (129/8,718) of medication orders with recommended or required testing. Of the 3,817 medication orders associated with somatic pharmacogenomic testing information in their drug labels, 20% (372/1,819) of required tests were detected. The low rates of detectable pharmacogenomic testing suggest that structured testing programs are required to achieve the success of precision medicine.

Effect of a rosmarinic acid supplemented hemodialysis fluid on inflammation of human vascular endothelial cells

Chronic systemic inflammation and repetitive damage of vascular endothelia by incompatible dialysis system are probable causes of cardiovascular disease in patients on dialysis. The present study aimed to assess in vitro biocompatibility and anti-inflammatory effect of hemodialysis fluid supplemented with rosmarinic acid (RA) using human umbilical vein endothelial cells (HUVEC). HUVECs (5×106 cells/mL) were pre-exposed to 1 μg/mL of lipopolysaccharides (LPS) and incubated with RA-supplemented hemodialysis fluid (HDF). Cytotoxicity was assessed qualitatively by morphologic assessment and quantitatively by MTT assay. Expressions of proinflammatory mediators were assessed using quantitative real-time PCR and production of NO was quantified. Phosphorylation of AKT and nuclear localization of nuclear factor kappa B (NF-κB) were examined using western blotting. Exposure of HUVECs to RA-supplemented HDF had no influence on morphology and viability. Inhibition of proinflammatory mediator production in HUVECs by RA supplementation to HDF was significant in a dose-dependent manner. Exposure to RA-supplemented HDF resulted in a decrease in nitric oxide synthase expression and reduction of NO production in LPS-stimulated HUVECs. RA supplementation of HDF suppressed Akt activation in LPS-stimulated HUVECs. In addition, the level of cellular IκB was increased in parallel to a reduced nuclear translocation of NF-κB in LPS-induced endothelial cells. Our results suggest that RA-supplemented HDF is biocompatible and significantly suppressed inflammation induced in endothelial cells. In this respect, the use of HDF supplemented with RA could alleviate inflammation and improve long-term treatment of patients with renal failure on dialysis. Further clinical studies are required to confirm the effects.

UPP mediated Diabetic Retinopathy via ROS/PARP and NF-κB inflammatory factor pathways.

Diabetic retinopathy (DR) is a leading cause of blindness in adults at working age. Human diabetic retinopathy is characterized by the basement membrane thick, pericytes loss, microaneurysms formation, retina neovascularization and vitreous hemorrhage. To investigate whether UPP activated ROS/PARP and NF-κB inflammatory factor pathways in Diabetic Retinopathy, human retinal endothelial cells (HRECs) and rats with streptozotocin-induced diabetes were used to determine the effect of UPP on ROS generation, cell apoptosis, mitochondrial membrane potential (ΔΨm) and inflammatory factor protein expression, through flow cytometry assay, immunohistochemistry, Real-time PCR, Western blot analysis and ELISA. The levels of ROS and apoptosis and the expressions of UPP (Ub and E3) and inflammatory factor protein were increased in high glucose-induced HRECs and retina of diabetic rats, while ΔΨm was decreased. The UPP inhibitor and UbshRNA could attenuate these effects through inhibiting the pathway of ROS/PARP and the expression of NF-κB inflammatory factors, and the increased UPP was a result of high glucose-induced increase of ROS generation and NF-κBp65 expression, accompanied with the decrease of ΔΨm. Clinical study showed the overexpression of UPP and detachment of epiretinal membranes in proliferative DR (PDR) patients. It has been indicated that the pathogenic effect of UPP on DR was involved in the increase of ROS generation and NF-κB expression, which associated with the ROS/PARP and NF-κB inflammatory factor pathways. Our study supports a new insight for further application of UPP inhibitor in DR treatment.

Systematic review with meta-analysis: coffee consumption and the risk of gallstone disease.

BACKGROUND: Epidemiologic evidence on coffee consumption reducing the risk of gallstone disease has been contradictory. AIM: To perform a meta-analysis of observational studies, to investigate an association and dose-response of coffee consumption with gallstone disease. METHODS: We used PubMed and EMBASE databases to identify all published studies before June 2015. A random-effects model was used to compute a pooled relative risk (RR) and corresponding 95% confidence intervals (CIs). RESULTS: One case-control study and five prospective cohort studies (with seven cohorts) involving 227,749 participants and 11,477 gallstone disease cases were included. Coffee consumption was significantly associated with a reduced risk of gallstone disease (RR, 0.83; 95% CI, 0.76 to 0.89; I(2) = 35.9%), based on prospective studies; specifically, we observed an inverse relation in females, but not in males. The case-control study did not reveal any association between coffee and gallstone disease (OR, 0.99; 95% CI, 0.64 to 1.53). In a dose-response analysis, the RR of gallstone disease was 0.95 (95% CI, 0.91 to 1.00; P = 0.049) per 1 cup/day of coffee consumption. A significant nonlinear dose-response association was also identified (P for nonlinearity = 0.0106). For people who drank 2, 4 and 6 cups of coffee per day, the estimated RRs of gallstone disease were 0.89 (95% CI, 0.79 to 0.99), 0.81 (95% CI, 0.72 to 0.92) and 0.75 (95% CI, 0.64 to 0.88), respectively, compared with the lowest level drinkers. CONCLUSION: This study suggests that coffee consumption is related to a significantly decreased risk of gallstone disease.

Transthoracic closure of atrial septal defect and ventricular septal defect without cardiopulmonary bypass.

The minimally invasive surgical transthoracic occlusion of an atrial septal defect (ASD) or a ventricular septal defect (VSD) is an increasingly widespread alternative treatment for congenital heart disease. The aim of this study is to summarize our clinical experience with minimally invasive surgical transthoracic occlusion of ASD and VSD without cardiopulmonary bypass (CPB). Between April 2011 and October 2012, 27 patients with ASD and 95 patients with VSD (78 men and 44 women) were considered for minimally invasive surgical transthoracic occlusion without CPB. A small infrasternal incision (2.0-4.0 cm) was made under general anesthesia, under transesophageal echocardiography (TEE) guidance; the ASD and VSD were closed by using an appropriate occluder; and TEE was performed simultaneously to demonstrate the position of the device, any residual shunting, or encroachment on the atrioventricular valve, coronary sinus, or aortic valve. Successful transthoracic occlusion was performed in all 122 patients without complications. No complications such as third-degree atrioventricular block and residual shunting occurred after the procedures. The ventilation time was 2.2 ± 1.2 h, and the average length of hospital stay was 4.7 ± 1.7 days. All patients received aspirin at 3 mg·kg(-1)·day(-1) (maximum 100 mg/day) 24 h after the procedure. Minimally invasive surgical transthoracic occlusion without CPB is a new treatment that has many advantages such as causing little trauma, promoting quick recovery, having less complications, and avoiding radiation damage. However, the appropriate selection of patients is still key to improving the success rate of the operation.