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lncRNAs–miRNAs–mRNAs networks play an important role in Gastric adenocarcinoma (GA). Identification of these networks provide new insight into the role of these RNAs in gastric cancer. Biological information databases were screened to characterize and examine the regulatory networks and to further investigate the potential prognostic relationship this regulation has in GA. By mining The Cancer Genome Atlas (TCGA) database, we gathered information on GA-related lncRNAs, miRNAs, and mRNAs. We identified differentially expressed (DE) lncRNAs, miRNAs, and mRNAs using R software. The lncRNA–miRNA–mRNA interaction network was constructed and subsequent survival examination was performed. Representative genes were selected out using The Biological Networks Gene Ontology plug-in tool on Cytoscape. Additional analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms were used to screen representative genes for functional enrichment. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) were used to identify the expression of five candidate differential expressed RNAs. Information of samples from 375 cases of gastric cancer and 32 healthy cases (normal tissues) were downloaded from the TCGA database. A total of 1632 DE-mRNAs, 1008 DE-lncRNAs and 104 DE-miRNAs were identified and screened. Among them, 65 DE-lncRNAs, 10 DE-miRNAs, and 10 DE-mRNAs form lncRNAs–miRNAs–mRNAs regulatory network. Additionally, 10 lncRNAs and 2 mRNAs were associated with the prognosis of GA. Multivariable COX analysis revealed that AC018781.1 and VCAN-AS1 were independent risk factors for GA. GO functional enrichment analysis found DE-mRNA was significantly enriched TERM (P

Background and Aims. Gastroesophageal variceal bleeding is a serious complication of portal hypertension in cirrhotic patients and could be predicted by hepatic venous pressure gradient (HVPG). However, whether the presence of ascites affects the prognostic value of HVPG for patients with acute variceal bleeding is still unknown. This retrospective study is aimed at investigating the influence of ascites on predictive performance of HVPG for early rebleeding in cirrhotic patients with acute variceal bleeding. Methods. In this retrospective study, a total of 148 patients with cirrhosis hospitalized for acute variceal bleeding who underwent HVPG measurement and endoscopic variceal ligation (EVL) for the prevention of rebleeding were included. The receiver operating characteristic curve (ROC) and logistical regression method were employed to analyze the predictive performance of HVPG for early rebleeding. The locally weighted scatterplot smoothing approach was adopted to assess the monotonicity between bleeding risk and HVPG. Results. A significantly higher HVPG level was observed in patients with early rebleeding compared to patients without rebleeding in the nonascites cohort. When using HVPG to predict early rebleeding, there was a lower area under curve in the ascites cohort compared to the nonascites cohort. HVPG was recognized as a risk factor for early rebleeding by a logistic regression model only in the nonascites cohort. An overall monotonicity in the trend of change in HVPG and risk for early rebleeding was observed in the nonascites cohort solely. Conclusion. The predictive value of HVPG for early rebleeding in patients with cirrhosis that developed acute variceal bleeding is hindered by the presence of ascites.

BACKGROUND AND AIM Gastroesophageal varices (GEV) present in compensated advanced chronic liver disease (cACLD) and can develop into high-risk varices (HRV). The gold standard for diagnosing GEV is esophagogastroduodenoscopy (EGD). However, EGD is invasive and less tolerant. This study aimed to develop and validate radiomics signatures based on noncontrast-enhanced computed tomography (CT) images for non-invasive diagnosis of GEV and HRV in patients with cACLD. METHODS The multicenter trial enrolled 161 patients with cACLD from six university hospitals in China between January 2015 and September 2019, who underwent both EGD and noncontrast-enhanced CT examination within 14 days prior to the endoscopy. Two radiomics signatures, termed rGEV and rHRV, respectively, were built based on CT images in a training cohort of 129 patients and validated in a prospective validation cohort of 32 patients (ClinicalTrials. gov identifier: NCT03749954). RESULTS In the training cohort, both rGEV and rHRV exhibited high discriminative abilities on determining the existence of GEV and HRV with the area under receiver operating characteristic curve (AUC) of 0.941 (95% confidence interval [CI] 0.904-0.978) and 0.836 (95% CI 0.766-0.905), respectively. In validation cohort, rGEV and rHRV showed high discriminative abilities with AUCs of 0.871 (95% CI 0.739-1.000) and 0.831 (95% CI 0.685-0.978), respectively. CONCLUSIONS This study demonstrated that rGEV and rHRV could serve as the satisfying auxiliary parameters for detection of GEV and HRV with good diagnostic performance.

Hepatic venous pressure gradient (HVPG) is a hemodynamic index widely used for evaluating the severity of portal hypertension. Theoretically, HVPG can be measured in any of the three major (i.e., right, middle and left) hepatic veins (HVs); however, it remains unclear whether HVPGs measured in different HVs are exchangeable, and if not, what factors cause inter-HV HVPG differences? In consideration of the potential limitations of invasive in vivo measurements, we employed a computational model implemented in conjunction with stochastic parameter sampling to simulate and compare HVPG measurements in multiple HVs under various sinusoidal portal hypertensive conditions. Results demonstrated that HVPGs measured in the right and middle HVs were basically exchangeable, whereas those in the left HV were relatively lower due primarily to the smaller proportion of hepatic venous flow through the left HV compared with that through the right or middle HV. Moreover, it was found that hepatic vein-to-vein shunts (HVVS) led to a marked augmentation of inter-HV HVPG differences and significant underestimation of portal pressure gradient with HVPG. These findings suggest that understanding the distribution of hepatic venous flow and status of HVVS is essential for selecting a proper HV for implementing HVPG measurement in clinical practice.

BackgroundCombined hepatocellular carcinoma and cholangiocarcinoma (CHC) is an uncommon subtype of primary liver cancer. Because of limited epidemiological data, prognostic risk factors and therapeutic strategies for patients with CHC tend to be individualized. This study aimed to identify independent prognostic factors and develop a nomogram-based model for predicting the overall survival (OS) of patients with CHC.MethodsWe recruited eligible individuals from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015 and randomly divided them into the training or verification cohort. Univariate and multivariate analyses were performed to identify independent variables associated with OS. Based on multivariate analysis, the nomogram was established, and its prediction performance was evaluated using the consistency index (C-index) and calibration curve.ResultsIn total, 271 patients with CHC were included in our study. The median OS was 14 months, and the 1-, 3-, and 5-year OS rates were 52.3%, 27.1%, and 23.3%, respectively. In the training cohort, multivariate analysis showed that the pathological grade (hazard ratio [HR], 1.26; 95% confidence interval [CI]: 0.96–1.66), TNM stage (HR, 1.21; 95% CI: 1.02 - 1.44), and surgery (HR, 0.26; 95% CI: 0.17 - 0.40) were independent indicators of OS. The nomogram-based model related C-indexes were 0.76 (95% CI: 0.72 - 0.81) and 0.72 (95% CI: 0.66 - 0.79) in the training and validation cohorts, respectively. The calibration of the nomogram showed good consistency of 1-, 3-, and 5-year OS rates between the actual observed survival and predicted survival in both cohorts. The TNM stage (HR, 1.23; 95% CI: 1.01 - 1.49), and M stage (HR, 1.87; 95% CI: 1.14 3.05) were risk factors in the surgical treatment group. Surgical resection and liver transplantation could significantly prolong the survival, with no statistical difference observed.ConclusionsThe pathological grade, TNM stage, and surgery were independent prognostic factors for patients with CHC. We developed a nomogram model, in the form of a static nomogram or an online calculator, for predicting the OS of patients with CHC, with a good predictive performance.

Effects of ubiquitin-proteasome system (UPS) inhibitor MG-132 on the expression levels of tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) in mice with viral myocarditis were investigated to analyze the correlation of myocardial tissue score of mice between TNF-α and TGF-β1. Eighty healthy male SPF mice aged 6 weeks were selected and 20 mice were randomly selected as the blank group. The blank group did not receive any intervention. Mortality rates of each group were recorded and compared on day 8 of modeling, and heart specimens from the remaining mice were histopathologically examined and the expression of mRNA and protein of TNF-α and TGF-β1 in myocardial tissues were detected by western blot analysis. Correlation between mouse myocardial histopathologic scores and expression of protein of TNF-α and TGF-β1 in myocardial tissues, as well as the expression of TNF-α and TGF-β1 in myocardial tissue in VMC mice was analyzed. The expression levels of myocardial histopathological scores, mRNA and protein of TNF-α and TGF-β1 in the blank and control group were significantly lower than those in the VMC and the MG-132 group. The myocardial histopathological scores, mRNA and TNF-α and TGF-β1 protein in the MG-132 group were significantly lower than those in the VMC group (P

Background & Aims The development of COVID-19 vaccines has progressed with encouraging safety and efficacy data. Concerns have been raised about SARS-CoV-2 vaccine responses in the large population of patients with non-alcoholic fatty liver disease (NAFLD). The study aimed to explore the safety and immunogenicity of COVID-19 vaccination in NAFLD. Methods This multicenter study included patients with NAFLD without a history of SARS-CoV-2 infection. All patients were vaccinated with 2 doses of inactivated vaccine against SARS-CoV-2. The primary safety outcome was the incidence of adverse reactions within 7 days after each injection and overall incidence of adverse reactions within 28 days, and the primary immunogenicity outcome was neutralizing antibody response at least 14 days after the whole-course vaccination. Results A total of 381 patients with pre-existing NAFLD were included from 11 designated centers in China. The median age was 39.0 years (IQR 33.0–48.0 years) and 179 (47.0%) were male. The median BMI was 26.1 kg/m2 (IQR 23.8–28.1 kg/m2). The number of adverse reactions within 7 days after each injection and adverse reactions within 28 days totaled 95 (24.9%) and 112 (29.4%), respectively. The most common adverse reactions were injection site pain in 70 (18.4%), followed by muscle pain in 21 (5.5%), and headache in 20 (5.2%). All adverse reactions were mild and self-limiting, and no grade 3 adverse reactions were recorded. Notably, neutralizing antibodies against SARS-CoV-2 were detected in 364 (95.5%) patients with NAFLD. The median neutralizing antibody titer was 32 (IQR 8-64), and the neutralizing antibody titers were maintained. Conclusions The inactivated COVID-19 vaccine appears to be safe with good immunogenicity in patients with NAFLD. Lay summary The development of vaccines against coronavirus disease 2019 (COVID-19) has progressed rapidly, with encouraging safety and efficacy data. This study now shows that the inactivated COVID-19 vaccine appears to be safe with good immunogenicity in the large population of patients with non-alcoholic fatty liver disease.

Background Group A rotavirus (RVA), despite being a leading cause of gastroenteritis in infants and young children, is less studied in Shanxi Province, China. The current study was conducted to determine the prevalence and genetic characterization of RVA in hospitalized children younger than 10 years of age with the diagnosis of acute gastroenteritis in Shanxi Province, China. Methods A hospital-based active surveillance of rotavirus gastroenteritis was conducted at Children’s Hospital of Shanxi from Jan 1, 2015, through Dec 31, 2019. Rotavirus was detected in stool samples by real-time quantitative reverse transcription PCR (qRT-PCR). G- and P-genotypes were determined by reverse transcription PCR (RT-PCR) and nucleotide sequencing. Results A total of 961 children younger than 10 years of age was enrolled over the study period, of whom 183 (19.0%) were positive for RVA. The highest RVA-infection frequency (23.7%) was found among children aged 12–23 months, and the seasonal peak was in December. G9P[8] was most prevalent (76.0%), followed by G3P[8] (7.1%), G2P[4] (3.3%), G1P[8] (0.5%) and G9P[4] (0.5%). Conclusions These results report for the first time that RVA was one of the main causes of severe infectious gastroenteritis in children, and a high proportion of G9P[8] strains circulating in most areas of Shanxi Province. While the protective efficacy of the rotavirus vaccines has been demonstrated against G9P[8] strains, our results highlight that the dominant strains have not been effectively controlled in China.

Objectives COVID-19 has rapidly become a major health emergency worldwide. Patients with IBD are at increased risk of infection, especially when they have active disease and are taking immunosuppressive therapy. The characteristics and outcomes of COVID-19 in patients with IBD remain unclear. Design This Italian prospective observational cohort study enrolled consecutive patients with an established IBD diagnosis and confirmed COVID-19. Data regarding age, sex, IBD (type, treatments and clinical activity), other comorbidities (Charlson Comorbidity Index (CCI)), signs and symptoms of COVID-19 and therapies were compared with COVID-19 outcomes (pneumonia, hospitalisation, respiratory therapy and death). Results Between 11 and 29 March 2020, 79 patients with IBD with COVID-19 were enrolled at 24 IBD referral units. Thirty-six patients had COVID-19-related pneumonia (46%), 22 (28%) were hospitalised, 7 (9%) required non-mechanical ventilation, 9 (11%) required continuous positive airway pressure therapy, 2 (3%) had endotracheal intubation and 6 (8%) died. Four patients (6%) were diagnosed with COVID-19 while they were being hospitalised for a severe flare of IBD. Age over 65 years (p=0.03), UC diagnosis (p=0.03), IBD activity (p=0.003) and a CCI score >1 (p=0.04) were significantly associated with COVID-19 pneumonia, whereas concomitant IBD treatments were not. Age over 65 years (p=0.002), active IBD (p=0.02) and higher CCI score were significantly associated with COVID-19-related death. Conclusions Active IBD, old age and comorbidities were associated with a negative COVID-19 outcome, whereas IBD treatments were not. Preventing acute IBD flares may avoid fatal COVID-19 in patients with IBD. Further research is needed.

Background The clinical characteristics and disease course in COVID-19 patients with pre-existing decompensated cirrhosis has not been described so far. Methods In this case series, we report three patients with confirmed COVID-19 and pre-existing decompensated cirrhosis from three hospitals in Hubei, the epicenter of the outbreak in China. Result Patient 1 was a 53-year-old man with hepatitis B virus-related cirrhosis, portal hypertension, and ascites. Though receiving intensive support, he died of irreversible multiple organ dysfunction syndrome 48 days after the onset of the illness. Patient 2 was a 75-year-old woman with a history of schistosomiasis-related cirrhosis, portal hypertension, and ascites. Her family members requested that invasive rescue measures not be undertaken, and she died of acute respiratory distress syndrome 40 days after presenting with COVID-19 infection. Patient 3 was an 87-year-old man with alcohol-related cirrhosis, portal hypertension, and esophageal variceal hemorrhage. He was discharged from the hospital 29 days after illness onset. Conclusion The case series raise the possibility that decompensated cirrhosis may be a risk factor for a poor outcome in patients with COVID-19.

BACKGROUND: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has outbreak in the world. Little is known about the clinical characteristics of patients with SARS-CoV-2 infection in the high-altitude region of China. We reported the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) in Gansu province, China. METHODS: In this retrospective study, patients with laboratory-confirmed SARS-CoV-2 infection were consecutively enrolled from January 21, 2020 to February 11, 2020. The information on the epidemiological, clinical characteristics, laboratory tests, radiological features on admission, treatment and outcome were obtained with the final follow-up of March 13, 2020. On the basis of the median length of hospital stay, patients were further analyzed in two groups (long- vs. short-hospital stay). RESULTS: Of the 86 patients of COVID-19 in 11 cities of Gansu Province, the median hospital stay was 14.0 days (interquartile rang, 11.0-19.0 days). In the overall cohort, the median age was 41.0 years (interquartile rang, 31.0-54.3 years), and 48 (55.8%) patients were female. Forty (46.5%) had a history of exposure to epidemic regions, but none exposed to the Huanan seafood market in Wuhan. Common symptoms included fever (41, 47.7%), and cough (37, 43.0%). On admission, 30 (34.9%) and 58 (67.4%) patients had leukopenia and lymphopenia. According to chest CT scans, 53 (66.3%) of 80 patients showed bilateral pneumonia, and 19 (23.8%) of 80 patients showed unilateral pneumonia. Of the 15 asymptomatic cases, 10 (66.6%) cases were found CT findings of pneumonia. Besides, there were 65 (75.6%) patients with mild and moderate type of COVID-19. All 86 patients received antiviral and traditional Chinese medicine therapy, 53 (61.6%) received antibacterial therapy, and 3 (3.5%) patients received invasive ventilator mechanical ventilation. The proportion of patients received antibiotic treatment in long-hospital stay group was significantly higher than that in the short-hospital stay group (P=0.045). As of March 13, 2020, 84 (97.7%) patients were discharged, and two (2.3%) cases died. CONCLUSIONS: In the Gansu province cohort of 86 patients of COVID-19, most patients were with mild or moderate type, and most asymptomatic cases showed CT imaging findings of SARS-CoV-2 related pneumonia.

Clinically significant portal hypertension (CSPH) is associated with an incremental risk of esophageal varices and overt clinical decompensations. However, hepatic venous pressure gradient (HVPG) measurement, the gold standard for defining CSPH (HVPG≥10 mm Hg) is invasive and therefore not suitable for routine clinical practice. This study aims to develop and validate a radiomics-based model as a noninvasive method for accurate detection of CSPH in cirrhosis. The prospective multicenter diagnostic trial (CHESS1701, ClinicalTrials.gov identifier: NCT03138915 ) involved 385 patients with cirrhosis from five liver centers in China between August 2016 and September 2017. Patients who had both HVPG measurement and contrast-enhanced CT within 14 days prior to the catheterization were collected. The noninvasive radiomics model, termed rHVPG for CSPH was developed based on CT images in a training cohort consisted of 222 consecutive patients and the diagnostic performance was prospectively assessed in 163 consecutive patients in four external validation cohorts. rHVPG showed a good performance in detection of CSPH with a C-index of 0·849 (95%CI: 0·786–0·911). Application of rHVPG in four external prospective validation cohorts still gave excellent performance with the C-index of 0·889 (95%CI: 0·752–1·000, 0·800 (95%CI: 0·614–0·986), 0·917 (95%CI: 0·772–1·000), and 0·827 (95%CI: 0·618–1·000), respectively. Intraclass correlation coefficients for inter- and intra-observer agreement were 0·92–0·99 and 0·97–0·99, respectively. A radiomics signature was developed and prospectively validated as an accurate method for noninvasive detection of CSPH in cirrhosis. The tool of rHVPG assessment can facilitate the identification of CSPH rapidly when invasive transjugular procedure is not available.

In recent years it was found that the synthesis and biological activity of ribosomes are closely associated with tumor cell growth, tumorigenesis, and malignant transformation. However, the role of regulator of ribosome synthesis 1 (RRS1) in hepatocellular carcinoma (HCC) has not yet been reported. In the present study, we aimed to examine the potential role of RRS1 in tumor cell growth by using a lentivirus-mediated RNA interference (RNAi) system in the HCC cell line SMMC-7721 in vitro. Compared with that of the negative control group (Lv-shCon), the mRNA and protein expression levels of RRS1 in SMMC-7721 cells transfected with Lv-shRRS1 were significantly decreased. Further experiments found that silencing of RRS1 gene expression in SMMC-7721 cells significantly suppressed cell proliferation, inhibited colony formation capacity, increased apoptosis and arrested cells in the G1 phase. These results suggest that the RRS1 gene plays a critical role in cell proliferation, colony formation, cell apoptosis and cell cycle distribution in human HCC cells, and that silencing of RRS1 by RNAi is a promising therapeutic approach for the treatment of HCC, and should be further developed.

Background & Aims Noninvasive and accurate methods are needed to identify patients with clinically significant portal hypertension (CSPH). We investigated the ability of deep convolutional neural network (CNN) analysis of computed tomography (CT) or magnetic resonance (MR) to identify patients with CSPH. Methods We collected liver and spleen images from patients who underwent contrast-enhanced CT or MR analysis within 14 days of transjugular catheterization for hepatic venous pressure gradient measurement. The CT cohort comprised participants with cirrhosis in the CHESS1701 study, performed at 4 university hospitals in China from August 2016 through September 2017. The MR cohort comprised participants with cirrhosis in the CHESS1802 study, performed at 8 university hospitals in China and 1 in Turkey from December 2018 through April 2019. Patients with CSPH were identified as those with a hepatic venous pressure gradient of 10 mm Hg or higher. In total, we analyzed 10,014 liver images and 899 spleen images collected from 679 participants who underwent CT analysis, and 45,554 liver and spleen images from 271 participants who underwent MR analysis. For each cohort, participants were shuffled and then sampled randomly and equiprobably for 6 times into training, validation, and test data sets (ratio, 3:1:1). Therefore, a total of 6 deep CNN models for each cohort were developed for identification of CSPH. Results The CT-based CNN analysis identified patients with CSPH with an area under the receiver operating characteristic curve (AUC) value of 0.998 in the training set (95% CI, 0.996–1.000), an AUC of 0.912 in the validation set (95% CI, 0.854–0.971), and an AUC of 0.933 (95% CI, 0.883–0.984) in the test data sets. The MR-based CNN analysis identified patients with CSPH with an AUC of 1.000 in the training set (95% CI, 0.999–1.000), an AUC of 0.924 in the validation set (95% CI, 0.833–1.000), and an AUC of 0.940 in the test data set (95% CI, 0.880–0.999). When the model development procedures were repeated 6 times, AUC values for all CNN analyses were 0.888 or greater, with no significant differences between rounds (P > .05). Conclusions We developed a deep CNN to analyze CT or MR images of liver and spleen from patients with cirrhosis that identifies patients with CSPH with an AUC value of 0.9. This provides a noninvasive and rapid method for detection of CSPH ( ClincialTrials.gov numbers: NCT03138915 and NCT03766880 ).

Background The purpose of this study was to evaluate the mid-term results of an Oxford phase-3 unicompartmental knee arthroplasty (UKA) for medial arthritis in Chinese patients. Methods The study included 64 patients who underwent a minimally invasive Oxford phase-3 UKA for medial knee arthritis. The patients were clinically evaluated preoperatively and at the final follow-up according to the clinical and functional components of the Knee Society Score (KSS), the Hospital for Special Surgery knee score and range of motion. A Kaplan-Meier survivorship analysis was performed with revision surgery as the end point. Results The mean preoperative clinical KSSs increased from 63.2 to 91.4 post-operatively, and the mean functional KSSs increased from 54.9 to 86.5 post-operatively. In addition, the mean Hospital for Special Surgery scores increased from 59.5 to 86.4. The mean active knee flexion increased from 109.1° preoperatively to 123.6° post-operatively. A total of six patients (six knees) required revision surgery at the time of the maximum 10-year follow-up. Four conversions to total knee arthroplasty were performed because of arthritis progression in the lateral compartment. One revision to total knee arthroplasty was performed for aseptic loosening, and one liner exchange was performed for wear. The cumulative survival rates at the 6- and 8-year follow-ups were 97% and 93%, respectively. Conclusion Oxford phase-3 UKA was largely applicable for medial arthritis in Chinese patients. However, the Oxford phase-3 medial UKA selection criteria for young Chinese males need further exploration to obtain the best treatment effect.

Background Glioblastoma is the most common and aggressive brain tumor associated with a poor prognosis. Plant homeodomain finger protein 20 (PHF20) is highly expressed in primary human gliomas and its expression is associated with tumor grade. However, the molecular mechanism by which PHF20 regulates glioblastoma remains poorly understood. Methods Genome wide gene expression analysis was performed to identify differentially expressed genes (DEGs) in U87 cells with PHF20 gene knockdown. Gene ontology (GO) and pathway enrichment analyses were performed to investigate the functions and pathways of DEGs. Pathway-net and signal-net analyses were conducted to identify the key genes and pathways related to PHF20. Results Expression of 540 genes, including FEN1 and CCL3, were significantly altered upon PHF20 gene silencing. GO analysis results showed that DEGs were significantly enriched in small molecule metabolic and apoptotic processes. Pathway analysis indicated that DEGs were mainly involved in cancer and metabolic pathways. The MAPK, apoptosis and p53 signaling pathways were identified as the hub pathways in the pathway network, while PLCB1, NRAS and PIK3 s were hub genes in the signaling network. Conclusions Our findings indicated that PHF20 is a pivotal upstream regulator. It affects the occurrence and development of glioma by regulating a series of tumor-related genes, such as FEN1, CCL3, PLCB1, NRAS and PIK3s, and activation of apoptosis signaling pathways. Therefore, PHF20 might be a novel biomarker for early diagnosis, and a potential target for glioblastoma therapies. Electronic supplementary material The online version of this article (doi:10.1186/s12935-017-0459-x) contains supplementary material, which is available to authorized users.

A hospital-based surveillance of shigellosis was conducted in Taiyuan from 2005 to 2015. A total of 2655 stool cultures were collected from patients with diarrhea, 115 were identified as S. flexneri and 107 were S. sonnei. The highest infection rates were found among children under 5 years of age (34.2 %), and during the summer (61.0 %). ​Six serotypes were identified among S. flexneriisolates:1a, 2a, 2b, Xv, X and Y. Serotype 2a and Xv were the dominant serotypes in two periods, 2012–2015 and 2005–2008, respectively. High shigellosis rates over the past decade highlight shigellosis is still a major public health problem in Taiyuan. Keywords: Shigellosis, Shigella, Infection rate, Serotypes, Molecular serotyping

Molecular target anticancer drugs are commonly used in various forms of cancers. It is a concern that the risk of serious adverse events (SAEs) and fatal adverse events (FAEs) of molecular target drugs are increasing. An up-to-date meta-analysis of all Phase II/III/IV randomized trials of molecular target anticancer drugs was conducted to calculate the increased risk of SAEs and FAEs. A systematic search of PubMed, Web of Science, and Cochrane Library up to April 6, 2017, was conducted. The study enrolled Phase II/III/IV randomized trials of cancer that compared molecular target drugs alone versus placebo or performed single-arm analysis of molecular target drugs. Data on SAEs and FAEs were extracted from the included studies and pooled to compute risk ratio (RR), the overall incidence, and 95% confidence interval (CI). In this meta-analysis, a total of 19,965 and 26,642 patients in randomized 53 and 65 Phase II/II/IV trials were included in the analysis of SAEs and FAEs associated with molecular target anticancer drug, respectively. There were significant differences in the relationship of molecular target anticancer drugs with SAEs (RR = 1.57, 95% CI = 1.35–1.82, P < 0.01, I2 = 81%) and FAEs (RR = 1.51, 95% CI = 1.19–1.91, P < 0.01, I2 = 0%) compared to placebo. The overall incidence of SAEs and FAEs was 0.269 (95% CI = 0.262–0.276, P < 0.01) and 0.023 (95% CI = 0.020–0.025, P < 0.01), respectively. Molecular target anticancer drugs significantly increased the risk of SAEs and FAEs. For patients taking molecular target drugs, efforts are needed to prevent the occurrence of SAEs and FAEs.

Objectives Although there is evidence that visfatin is associated with atherogenesis, the effect of visfatin on plaque stability has not yet been explored. Methods In vivo, vulnerable plaques were established by carotid collar placement in apolipoprotein E–deficient (ApoE−/−) mice, and lentivirus expressing visfatin (lenti-visfatin) was locally infused in the carotid artery. The lipid, macrophage, smooth muscle cell (SMC) and collagen levels were evaluated, and the vulnerability index was calculated. In vitro, RAW264.7 cells were stimulated with visfatin, and the MMPs expressions were assessed by western blot and immunofluorescence. And the mechanism that involved in visfatin-induced MMP-8 production was investigated. Results Transfection with lenti-visfatin significantly promoted the expression of visfatin which mainly expressed in macrophages in the plaque. Lenti-visfatin transfection significantly promoted the accumulation of lipids and macrophages, modulated the phenotypes of smooth muscle cells and decreased the collagen levels in the plaques, which significantly decreased the plaque stability. Simultaneously, transfection with lenti-visfatin significantly up-regulated the expression of MMP-8 in vivo, as well as MMP-1, MMP-2 and MMP-9. Recombinant visfatin dose- and time-dependently up-regulated the in vitro expression of MMP-8 in macrophages. Visfatin promoted the translocation of NF-κB, and inhibition of NF-κB significantly reduced visfatin-induced MMP-8 production. Conclusions Visfatin increased MMP-8 expression, promoted collagen degradation and increased the plaques vulnerability index.