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IntroductionGestational diabetes mellitus (GDM) is one of the most prevalent diseases during pregnancy, which is closely associated with many short-term and long-term maternal and neonatal complications and can incur heavy financial burden on both families and society. Web-based interventions have been used to manage GDM because of the advantages of high accessibility and flexibility, but their effectiveness has remained inconclusive. This systematic review and meta-analysis aims to comprehensively investigate the multidimensional effectiveness of web-based interventions for pregnant women with GDM, thereby aiding implementation decisions in clinical settings.Methods and analysisThis systematic review protocol strictly adheres to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. Six electronic databases (PubMed, Web of Science, Cochrane Central Register of Controlled Trials, Embase, CINAHL and PsycINFO) will be comprehensively searched from their inception to 26 January 2022 to identify randomised controlled trials and controlled clinical trials regarding the efficacy of web-based interventions for pregnant women with GDM on glycaemic control, behavioural outcomes, cognitive and attitudinal outcomes, mental health, maternal and neonatal clinical outcomes, and medical service utilisation and costs. Two reviewers will independently conduct the study selection, data extraction and quality assessment. The methodological quality of included studies will be assessed using the Effective Public Health Practice Project assessment tool. The overall meta-analyses for each of the interested outcomes will be performed if the outcome data are sufficient and provides similar effect measures, as well as subgroup analyses for glycaemic control indicators based on the different types of intervention format, interactivity and technology. We will conduct a qualitative synthesis for studies that cannot be quantitatively synthesised.Ethics and disseminationEthics approval is not required for this review as no human participants will be involved. The results will be disseminated via a peer-reviewed journal or an academic conference.PROSPERO registration numberCRD42022296625.

Metabolic syndrome (MetS) is characterized by a group of metabolic disturbances which leads to the enhanced risk of cancer development. Elucidating the mechanisms between these two pathologies is essential to identify the potential therapeutic molecular targets for colorectal cancer (CRC). 716 colorectal patients from the First and Second Affiliated Hospital of Wenzhou Medical University were involved in our study and metabolic disorders were proven to increase the risk of CRC. The prognostic value of the MetS factors was analyzed using the Cox regression model and a clinical MetS-based nomogram was established. Then by using multi-omics techniques, the distinct molecular mechanism of MetS genes in CRC was firstly systematically characterized. Strikingly, MetS genes were found to be highly correlated with the effectiveness of targeted chemotherapy administration, especially for mTOR and VEGFR pathways. Our results further demonstrated that overexpression of MetS core gene IL6 would promote the malignancy of CRC, which was highly dependent on mTOR-S6K signaling. In conclusion, we comprehensively explored the clinical value and molecular mechanism of MetS in the progression of CRC, which may serve as a candidate option for cancer management and therapy in the future.

The purpose of this review was to systematically assess the effectiveness of 10-Hz repetitive transcranial magnetic stimulation (rTMS) in fibromyalgia.We searched PubMed, Cochrane Library, Embase, Web of Science, and Ovid databases as of November 6, 2021.The inclusion criteria for this review were randomized controlled trials of 10-Hz rTMS for fibromyalgia, exploring the effects of 10-Hz rTMS on pain, depression, and quality of life in patients with fibromyalgia.Data extraction was performed independently by 2 evaluators according to predefined criteria, and the quality of the included literature was assessed using the Cochrane Bias Risk Assessment Tool. The measurement outcomes include visual analog scale, Hamilton Depression Rating Scale, and Fibromyalgia Impact Questionnaire, and so on.A total of 488 articles were screened, and the final 7 selected high-quality articles with 217 patients met our inclusion criteria. Analysis of the results showed that high-frequency transcranial magnetic stimulation at 10 Hz was significantly associated with reduced pain compared with sham stimulation in controls (standardized mean difference [SMD]=-0.72; 95% confidence interval [CI], -1.12 to -0.33; P.001; IOverall, 10-Hz rTMS has a significant effect on analgesia and improved quality of life in patients with FMS but did not improve depression.

Medication nonadherence is associated with an increased risk of complications in hypertensive patients. We investigated behavioral factors associated with medication nonadherence in hypertensive patients in southern Taiwan. Using questionnaires, we collected data regarding clinicodemographic characteristics and nonadherence behaviors from 238 hypertensive patients. We assessed the self-reported prevalence of specific behaviors of medication nonadherence and investigated factors associated with each behavior using multivariable logistic regression analysis. The most common behavior of medication nonadherence was forgetting to take medication (28.6%), followed by discontinuing medication (9.2%) and reducing the medication dose (8.8%). Age ≥ 65 years (adjusted odds ratio [aOR] = 0.32, 95% confidence interval [CI] = 0.15–0.69) and male sex (aOR = 2.61, CI = 1.31–5.19) were associated with forgetting to take medication. The presence of comorbidities (diabetes, kidney disease, or both) and insomnia (aOR = 3.97, 95% CI = 1.30–12.1) was associated with reducing the medication dose. The use of diet supplements was associated with discontinuing the medication (aOR = 4.82, 95% CI = 1.50–15.5). Compliance with a low oil/sugar/sodium diet was a protective factor against discontinuing medication (aOR = 0.14, 95% CI = 0.03–0.75). The most pervasive behavior associated with medication nonadherence among hypertensive patients was forgetting to take medication. Age &lt, 65 years, male sex, comorbidities, insomnia, noncompliance with diet, and the use of dietary supplements were specifically associated with medication nonadherence.

The grand challenge to meet the increasing demands for food by a rapidly growing global population requires protecting crops from pests. Natural active substances play a significant role in the sustainable pests and pathogenic microbes management. In recent years, natural products- (NPs), antimicrobial peptides- (AMPs), medicinal plant- and plant essential oils (EOs)-related online resources have greatly facilitated the development of pests and pathogenic microbes control agents in an efficient and economical manner. However, a comprehensive comparison, analysis and summary of these existing web resources are still lacking. Here, we surveyed these databases of NPs, AMPs, medicinal plants and plant EOs with insecticidal, antibacterial, antiviral and antifungal activity, and we compared their functionality, data volume, data sources and applicability. We comprehensively discussed the limitation of these web resources. This study provides a toolbox for bench scientists working in the pesticide, botany, biomedical and pharmaceutical engineering fields. The aim of the review is to hope that these web resources will facilitate the discovery and development of potential active ingredients of pests and pathogenic microbes control agents.

Purpose The aim of this study was to ascertain whether ba-duan-jin (BDJ) can improve balance and enhance the quality of life among older adults. Design This pilot study was designed as a single group pre-post comparison test. Methods Sixteen older adults were qualified and recruited for this study at local retirement communities. Assessments for pre- and postintervention among the subjects included Single-Leg Stance, Chair Rising Test, Tinetti Balance Test, Modified Falls Efficacy Scale, and 12-Item Short Form Health Survey Questionnaire for quality of life. Findings After 12 weeks of BDJ training, significant improvements were identified in Single-Leg Stance, Tinetti Balance Test, Modified Falls Efficacy Scale, and 12-Item Short Form Health Survey (all p .05). Conclusion The results indicate that BDJ can improve balance, lower extremity strength, quality of life, and decrease fear of falling among older adults. Clinical relevance BDJ is an effective rehabilitation training method and can improve balance and motor function among older people. Rehabilitation nursing plays a key role in functional rehabilitation of older people.

Relying on the Biomedical Big Data Center of West China Hospital, this paper makes an in-depth research on the construction method and application of breast cancer-specific database system based on full data lifecycle, including the establishment of data standards, data fusion and governance, multi-modal knowledge graph, data security sharing and value application of breast cancer-specific database. The research was developed by establishing the breast cancer master data and metadata standards, then collecting, mapping and governing the structured and unstructured clinical data, and parsing and processing the electronic medical records with NLP natural language processing method or other applicable methods, as well as constructing the breast cancer-specific database system to support the application of data in clinical practices, scientific research, and teaching in hospitals, giving full play to the value of medical big data of the Biomedical Big Data Center of West China Hospital.

The infectious disease Coronavirus 2019 (COVID-19) continues to cause a global pandemic and, thus, the need for effective therapeutics remains urgent. Global research targeting COVID-19 treatments has produced numerous therapy-related data and established data repositories. However, these data are disseminated throughout the literature and web resources, which could lead to a reduction in the levels of their use. In this review, we introduce resource repositories for the development of COVID-19 therapeutics, from the genome and proteome to antiviral drugs, vaccines, and monoclonal antibodies. We briefly describe the data and usage, and how they advance research for therapies. Finally, we discuss the opportunities and challenges to preventing the pandemic from developing further.

Background. Lung cancer (LC) has the highest mortality rate among all the other types of cancer in the world. T cells are known to be the key factor in inducing the immune response during LC. Objective. In this study, we aimed to screen and analyze RNAs associated with CD8(+) T cells and activated memory CD4(+) T cells in lung adenocarcinomas, a subtype of non-small-cell lung cancer (NSCLC-LUAD). Methods. Gene expression RNA-seq data and clinical data of NSCLC-LUAD were downloaded from the XENA database. The data were divided into low scores and high scores based on the Stromal and Immune scores. Then, all the genes were screened for identifying those specifically associated with CD8(+) T cells and activated memory CD4(+) T cells. The screened genes were used for the construction of the protein-protein interaction (PPI) network and for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis along with prognosis analysis. Based on the results of the prognostic analysis, the prognostic-related genes were used to analyze long noncoding (lnc)RNA-micro(mi)RNA-mRNA networks and to predict small chemical molecules. Results. According to the Immune and Stromal scores, a total of 885 upregulated and 29 downregulated RNAs were identified. A total of 90 differentially expressed genes (DEGs) were found to be related to CD8(+) T immune cells, and 48 DEGs were related to activated memory CD4(+) T cells. GPR174 and CD226 suggested a favorable prognosis. For CD8(+) and activated memory CD4(+) T cells, 112 and 113 PPI edges were obtained, respectively. GPR174 was found to be regulated by hsa-miR-19b-5p and hsa-miR-19b-2-5p, and both of these two miRNAs were regulated by lncRNA PCED1B-AS1. CD226 was regulated by hsa-miR-379-5p, which was in turn regulated by lncRNA RP11-81H14.2. Conclusion. Our findings provide a deeper understanding of the T cell-related ceRNA regulatory mechanism in NSCLC-LUAD pathogenesis.

Objective The malignant phenotypes of cancer are defined not only by its intrinsic tumor cells but also by the tumor-infiltrating immune cells activated and recruited to the cancer microenvironment. However, a comprehensive introduction of gastric cancer immune cell infiltration has not been identified so far. Methods In this study, we comprehensively analyzed the tumor-infiltrating immune cells abundance in gastric cancer for the first time by CIBERSORT. The meta-analysis, single-sample gene set enrichment analysis and hierarchical agglomerative clustering were used to measure and evaluate the respective proportions of 22 cell types of immune infiltration using normalized gene expression data. The fraction of tumor-infiltrating immune cells subpopulations was also evaluated to determine the associations with clinical features and molecular subtypes. Results Tumor-infiltrating immune cells are extensively involved in the pathogenesis and development of the gastric cancer. We discovered Tfh and activated CD4+ memory T cells were associated with poorer overall survival and Progression-free survival (PFS), but that naïve B cells were opposite for PFS. Unsupervised clustering analysis revealed there existed three tumor-infiltrating immune cells subgroups with distinct survival patterns. Specially, cluster 1 showed significantly better clinical outcome than other two clusters. Conclusions Collectively, our data explored the differences of tumor-infiltrating immune cells in gastric cancer, and these variations were likely to be important clues for prognosis and management of its future clinical implementation.

Objective To explore training-related independent factors affecting the awareness of cardiopulmonary resuscitation (CPR) in senior high school students in Shanghai. Methods Questionnaires measuring CPR-related knowledge were distributed to 430 senior high school students in Shanghai. Results The overall CPR qualification rate was 7.7%. Qualification rate increased significantly with training frequency (5.5% vs. 9.3% vs. 20%), personal willingness to perform CPR (3.7% vs. 9.5%) and smaller training intervals (12.8% vs. 5.3% vs. 1.8%). After adjustment, training interval

PURPOSE: To validate the feasibility and efficacy of intratumoral radiofrequency hyperthermia (RFH)-enhanced herpes simplex virus (HSV) thymidine kinase (TK) and ganciclovir (GCV) (hereafter, HSV-TK/GCV) gene therapy for non–small-cell lung cancer (NSCLC). MATERIALS AND METHODS: This study was performed from November 11, 2015, to April 14, 2017, and included (a) in vitro experiments with human NSCLC cells to establish the proof of principle, (b) in vivo experiments using mice with subcutaneous NSCLC to further demonstrate the principle, and (c) in vivo experiments using rats with orthotopic NSCLC to validate the technical feasibility. Cells, nude mice, and nude rats were randomly divided into four groups (six animals per group): (a) combination therapy (HSV-TK/GCV combined with RFH), (b) RFH, (c) HSV-TK/GCV, and (d) phosphate-buffered saline. Data were analyzed by using the Dunnett t test or Kruskal–Wallis test. RESULTS: For in vitro experiments, the cell proliferation assay showed significantly diminished viable cells with combination therapy (mean, 0.56; 95% confidence interval [CI]: 0.44, 0.68) versus RFH (mean, 0.89; 95% CI: 0.82, 0.97), HSV-TK/GCV (mean, 0.71; 95% CI: 0.56, 0.86), and phosphate-buffered saline (mean, 1; 95% CI: 1, 1) (P < .05 for all). For in vivo experiments, optical imaging showed significantly decreased relative bioluminescence signal with combination therapy (mean, 0.71 [95% CI: 0.03, 1.39] in mice; 1.29 [95% CI: 0.51, 2.06] in rats) compared with RFH (mean, 2.66 [95% CI: 1.73, 3.59] in mice; 2.26 [95% CI: 1.51, 3.01] in rats), HSV-TK/GCV (mean, 1.37 [95% CI: 0.65, 2.08] in mice; 1.76 [95% CI: 1.20, 2.31] in rats), and phosphate-buffered saline (mean, 3.07 [95% CI: 2.50, 3.65] in mice; 2.94 [95% CI: 2.29, 3.58] in rats) (P < .001 for all). US showed that the smallest relative tumor volumes occurred with combination therapy (mean, 0.60; 95% CI: 0.15, 1.05) versus RFH (mean, 2.43; 95% CI: 1.80, 3.06), HSV-TK/GCV (mean, 1.32; 95% CI: 0.75, 1.89), and phosphate-buffered saline (mean, 2.56; 95% CI: 1.75, 3.38) (P < .05 for all) in the mouse subcutaneous model. CONCLUSION: Intratumoral radiofrequency hyperthermia–enhanced herpes simplex virus thymidine kinase and ganciclovir gene therapy for non–small-cell lung cancer is feasible and can be guided by molecular imaging. © RSNA, 2018

AIM To investigate the relationship between non-alcoholic fatty liver disease (NAFLD) and colorectal adenomatous and hyperplastic polyps. METHODS A retrospective cross-sectional study was conducted on 3686 individuals undergoing health checkups (2430 males and 1256 females). All subjects underwent laboratory testing, abdominal ultrasonography, colonoscopy, and an interview to ascertain the baseline characteristics and general state of health. Multinomial logistic regression analysis was performed to examine the association between NAFLD and the prevalence of colorectal adenomatous and hyperplastic polyps. Furthermore, the relationship was analyzed in different sex groups. Subgroup analysis was performed based on number, size, and location of colorectal polyps. RESULTS The prevalence of colorectal polyps was 38.8% in males (16.2% for adenomatous polyps and 9.8% for hyperplastic polyps) and 19.3% in females (8.4% for adenomatous polyps and 3.9% for hyperplastic polyps). When adjusting for confounding variables, NAFLD was significantly associated with the prevalence of adenomatous polyps (OR = 1.28, 95%CI: 1.05-1.51, P < 0.05) and hyperplastic polyps (OR = 1.35, 95%CI: 1.01-1.82, P < 0.05). However, upon analyzing adenomatous and hyperplastic polyps in different sex groups, the significant association remained in males (OR = 1.53, 95%CI: 1.18-2.00, P < 0.05; OR = 1.42, 95%CI: 1.04-1.95, P < 0.05) but not in females (OR = 0.44, 95%CI: 0.18-1.04, P > 0.05; OR = 1.18, 95%CI: 0.50-2.78, P > 0.05). CONCLUSION NAFLD is specifically associated with an increased risk of colorectal adenomatous and hyperplastic polyps in men. However, NAFLD may not be a significant factor in the prevalence of colorectal polyps in women.

Objective To explore stable and functional microRNA (miRNA)–disease relationships using a genome-wide expression profile pattern matching strategy. Methods We applied the ranked microarray pattern matching strategy Gene Set Enrichment Analysis to identify miRNA permutations with similar expression patterns to diseases. We also used quantitative reverse transcription PCR to validate the predicted expression levels of miRNAs in three diseases: inflammatory bowel disease (IBD), oesophageal cancer, and colorectal cancer. Results We found that hsa-miR-200 c was upregulated more than 40-fold in oesophageal cancer. The expression of miR-16 and miR-124 was not consistently upregulated in IBD or colorectal cancer. Conclusions Our results suggest that this expression profile matching strategy can be used to identify functional miRNA–disease relationships.

Chemotherapy is one of the major strategies for cancer treatment. Several antineoplastic drugs including vinorelbine (VRB) are commonly intravenously infused and liable to cause serious phlebitis. The therapeutic drugs for preventing this complication are limited. In this study, the mechanism of baicalein (BCN) was investigated on VRB-induced phlebitis in vivo and vascular endothelial cell injury in vitro. Treatment with BCN obviously attenuated vascular endothelial cell loss, edema, inflammatory cell infiltration and blood clots, and reduced the serum levels of TNF-α, IL-1β, IL-6 and ICAM-1 in the rabbit model of phlebitis induced by intravenous injection of VRB compared with vehicle. Further tests in vitro demonstrated that BCN lessened VRB-induced endothelial cell apoptosis, decreased intracellular ROS levels, suppressed phosphorylation of p38 and eventually inhibited activation of NF-κB signaling pathway. And these effects could be reversed by p38 agonist P79350. These results suggested that BCN exerted the protective effects against VRB-induced endothelial disruption in the rabbit model of phlebitis via inhibition of intracellular ROS generation and inactivation of p38/NF-κB pathway, leading to the decreased production of pro-inflammatory cytokines. Thus, BCN could be used as a potential agent for the treatment of phlebitis.

A novel virus-imprinted polymer for prevention of viral infection was prepared by anchoring molecularly imprinted polymer (MIP) on the surface of poly-dopamine (PDA)-coated silica particles. The imprinting reaction was carried out via self-polymerization of dopamine in the presence of a virus template. Plaque forming assay indicated that the MIP exhibited selective anti-viral infection properties for the template virus in complex media containing different interfering substances, and even other types of viruses. Remarkable dose-dependent and time-dependent inhibition of virus infection was observed due to the MIP’s selective binding to the template virus. When the MIP was incubated with the virus and host cells together, rapid and selective adsorption of template viruses by the MIP prevented the viruses to infect the host cells in a period of 12 h. The MIP was biocompatible and non-toxic, and had excellent stability and reusability. Furthermore, the MIPs prepared using different viruses as templates showed similar anti-viral infection properties. The MIP synthesized using dopamine as monomer and crude virus as template provided an attractive possibility for clinical applications in the field of antiviral therapy. Statement of Significance This is the first report to prepare artificial antibody (molecularly imprinted polymer, MIP) that can selectively prevent virus infection using dopamine self-polymerization system. Only MIP anchoring on the surface of poly-dopamine coated silica particles and polymerized using ammonium persulfate as radical initiator showed dose-dependent and time-dependent inhibition of template virus infection in complex media containing interferences and even other viruses. Viruses bond to MIP lost infectious capability. When incubated with virus and host cells, MIP rebond viruses rapidly and selectively to prevent viruses infecting host cells for 12 h. The achieved MIPs were biocompatibility, non-toxicity with excellent stability and reusability, and can be used to different viruses. The bio-mimic MIPs provided an attractive prospect for clinical applications in antiviral therapy.

BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease worldwide. However, to date, there is no ideal therapy for this disease. AIM To study the effects of Si-Ni-San freeze-dried powder on high fat diet-induced NAFLD in mice. METHODS Twenty-four male C57BL/6 mice were randomized into three groups of eight. The control group (CON) was allowed ad libitum access to a normal chow diet. The high fat diet group (FAT) and Si-Ni-San group (SNS) were allowed ad libitum access to a high fat diet. The SNS group was intragastrically administered Si-Ni-San freeze-dried powder (5.0 g/kg) once daily, and the CON and FAT groups were intragastrically administered distilled water. After 12 wk, body weight, liver index, visceral fat index, serum alanine aminotransferase (ALT), portal lipopoly-saccharide (LPS), liver tumor necrosis factor (TNF)-α and liver triglycerides were measured. Intestinal microbiota were analyzed using a 16S r DNA sequencing technique. RESULTS Compared with the FAT group, the SNS group exhibited decreased body weight, liver index, visceral fat index, serum ALT, portal LPS, liver TNF-α and liver triglycerides (P < 0.05). Intestinal microbiota analysis showed that the SNS group had different bacterial composition and function compared with the FAT group. In particular, Oscillospira genus was a bacterial biomarker of SNS group samples. CONCLUSION The beneficial effects of Si-Ni-San freeze-dried powder on high fat diet-induced NAFLD in mice may be associated with its anti-inflammatory and changing intestinal microbiota effects.

Aim To identify the factors affecting the pharmacokinetics (PKs) of sirolimus in healthy Chinese subjects and renal transplant patients. Methods A population PK model of sirolimus was constructed using dense data from 22 healthy volunteers and sparse data from 105 renal transplant patients. Results The data were well described by a two-compartment model with first-order absorption. The estimates of absorption rate constant (Ka), clearance (CL/F), and central volume of distribution (V2/F) were 0.24 h(-1), 8.81 L/h, and 676 L, respectively. The CL/F in renal transplant patients was 45.5% lower than that in healthy subjects. Based on the final model, CL/F decreased significantly with increasing cyclosporine (CsA) daily dose and age. A decrease of 7.3% in CL/F for every 100-mg increase in the CsA daily dose and a decrease of 34.2% in CL/F for every 20-year increase in age was observed. Moreover, V2/F increased significantly with increasing serum creatinine in our study. However, the range of serum creatinine concentration and the interindividual variability for V2/F are large. Conclusion This is the first study to characterize the population PKs of sirolimus using a two-compartment model in healthy Chinese subjects and renal transplant patients. A decrease of 7.3% in the sirolimus CL/F for every 100-mg increase in the CsA daily dose and a decrease of 34.2% in the sirolimus CL/F for every 20-year increase in age was observed, which allowed us to better optimize sirolimus dosing regimens in Chinese renal transplant patients.

Myeloid‐derived suppressor cells (MDSCs) are a heterogeneous cell population that includes immature myeloid cells and the progenitor cells of macrophages, dendritic cells (DCs), monocytes, and neutrophils. The expansion and functional importance of MDSCs in patients with cancer and noncancer pathogenic conditions has been recognized. As a result, there has been growing interest in understanding their roles in acute graft‐versus‐host disease (aGVHD) after allogenetic hematopoietic stem cell transplantation (allo‐HSCT). In order to evaluate possible effects of MDSCs on aGVHD development and clinical outcomes, this study systematically detected the dynamic changes of MDSCs accumulation in patients during the first 100 days after allo‐HSCT, and investigated the levels of other cell types and relative cytokines during MDSCs accumulation. Results showed that accumulation of MDSCs in the graft and in peripheral blood when engraftment might contribute to patients' overall immune suppression and result in the successful control of severe aGVHD and long‐term survival without influence on risk of recurrence after allo‐HSCT. But MDSCs levels in the graft had more favorable predictive abilities. Furthermore, MDSCs proportion significantly increased in patients developing aGVHD after allo‐HSCT. It might be caused by secondary inflammatory response, especially related to high concentrations of IL‐6 and TNF‐α. But this accumulation would not be able to counterbalance the aggravation of aGVHD and would not have influence on clinical outcomes and risk of relapse. Overall, MDSCs might be considered as potential new therapeutic option for aGVHD and achieve long‐term immunological tolerance and survival.

Background Moyamoya disease or syndrome (MMD or MMS) is a cerebrovascular disease characterized by stenosis or occlusion of the distal portion of the internal carotid arteries, with ultimate spread to the proximal portion of the anterior cerebral arteries and middle cerebral arteries (MCAs). In the present study, we wanted to evaluate the usefulness of conventional computed tomography (CT) and axial magnetic resonance (MR) T2-weighted imaging (T2WI) for the examination of horizontal segments of the MCAs (ie, M1 segments) in patients diagnosed with MMD or MMS. Methods This study enrolled 29 patients (n = 11 men; n = 18 women), who underwent conventional CT and/or MR T2WI. CT angiography, MR angiography, or digital subtraction angiography was used as a reference. CT and MR imaging data were reviewed by 2 experienced radiologists, who analyzed and recorded stenosis or occlusions of the M1 segments. We performed statistical analyses to compare the diagnostic accuracy of both techniques on M1 segments in MMD or MMS. Results Fifty-three steno-occlusive changes of M1 segments were revealed by angiography in the 29 patients. T2W-MRI allowed the identification of moyamoya vessels with 100% success rate. Stenosis and occlusion of M1 segments were better visualized on axial T2W-MRI compared to conventional CT (94.59% versus 71.43%; P = .008). Conclusions Our study showed that conventional CT and axial T2W-MRI could be used to identify the steno-occlusive changes of the horizontal segment of the MCA in MMD or MMS, which may have a significant impact on the accurate diagnosis of this disease at its early stage.

Background The aim of this study was to investigate and interpret the expression level and potential function of TCEA3 in gastric cancer. Material and methods qRT-PCR was used to determine the expression level of TCEA3 in gastric cancer tissues. Pearson χ2 test was performed to clarify the correlation between TCEA3 expression and patients' clinicopathologic characteristics. Biological function of TCEA3 was tested by proliferation assay and colony formation assay. Flow cytometry was used to study the potential function of TCEA3 in apoptosis induction. Results TCEA3 expression was significantly downregulated in gastric cancer tissues compared with paired normal tissues. Poor prognoses were observed in the low TCEA3 expression group of patients in contrast to the high TCEA3 expression group. Functionally, upregulation of TCEA3 inhibited gastric cancer cell proliferation and colony formation. We also found that TCEA3 may attenuate cell growth through apoptosis induction. Conclusions Our findings suggest that TCEA3 attenuates the proliferation and induces apoptosis of gastric cancer cells.

Background/Aims: Melatonin, synthesized by the pineal gland and released into the blood, appears to have antitumour properties; however, the mechanisms of its anti-cancer effects are largely unknown, especially in stomach cancer. Here, we explore the antitumour activity of melatonin in a gastric cancer cell line (AGS) and analyse its molecular mechanisms. Methods: AGS cells were treated with melatonin, and cell viability was assessed using a CCK-8 assay. Flow cytometry was performed to evaluate apoptosis, and protein expression was examined by Western blotting. Results: Melatonin significantly inhibited cell viability, clone formation, and cell migration and invasion and induced apoptosis in AGS cells. Moreover, MAPK pathways (p38, JNK and ERK) were activated by melatonin treatment, which also significantly increased caspase-3 cleavage and Bax protein expression and decreased Bcl-2 protein expression in a time-dependent manner. Our results demonstrate that p38 and JNK inhibitors (SB203580 and SP600125, respectively) prevented melatonin-induced apoptosis; thus, the propensity of p38 MAPK and JNK to promote apoptosis could be at least partly due to the inhibition of NF-κB p65 activation by p38 and JNK. Finally, melatonin was able to strengthen cisplatin-mediated antitumour effects in human gastric carcinoma cells by up-regulating the expression of Bax, down-regulating the expression of Bcl-2 and activating the caspase-dependent apoptotic pathway. Conclusion: Melatonin induced apoptosis in AGS cells by activating the caspase-dependent apoptotic pathway and by inhibiting the nuclear translocation of NF-κB p65, two processes that are regulated by p38 and JNK. Furthermore, melatonin significantly enhanced the anti-tumour effects of cisplatin, with low systemic toxicity. These new findings suggest that melatonin may act as a potent anti-tumour agent and may have great potential as an adjuvant therapy in the future.

Gene duplication is the main source of genomic novelties and complexities for both eukaryotes and prokaryotes. In contrast, gene duplication appears to be infrequent in the RNA viruses. However, the extent and evolution of gene duplication in DNA viruses remains obscure. Here we perform a genome-wide analysis of gene duplication in the genomes of 250 DNA viruses that represent all known DNA viral genera. While no gene duplication event is identified in single stranded DNA (ssDNA) or reverse transcribing DNA viruses, gene duplication is frequent among double stranded DNA (dsDNA) viruses. For dsDNA viruses, the number of duplicate genes is significantly correlated with the genome complexity. We find that most of duplicate genes experienced purifying selection on average. Our results indicate that gene duplication play an important role in shaping the evolution of dsDNA viruses.

Colorectal neoplasm is considered to have a strong association with nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS), respectively. The relationship among NAFLD, MetS, and colorectal neoplasm was assessed in 1793 participants. Participants were divided into 4 groups based on the status of NAFLD and MetS. Relative excess risks of interaction (RERI), attributable proportion (AP), and synergy index (SI) were applied to evaluate the additive interaction. NAFLD and MetS were significantly correlated with colorectal neoplasm and colorectal cancer (CRC), respectively. The incidence of CRC in NAFLD (+) MetS (+) group was significantly higher than other 3 groups. The result of RERI, AP, and SI indicated the significant additive interaction of NAFLD and MetS on the development of CRC. NAFLD and MetS are risk factors for colorectal neoplasm and CRC, respectively. And NAFLD and MetS have an additive effect on the development of CRC.

Background Whether melatonin receptor 1B (MTNR1B) variants are associated with type 2 diabetes mellitus (T2DM) remains unclear. Therefore, we performed this meta‐analysis to better explore correlations between MTNR1B variants and T2DM. Methods Literature research was performed in PubMed, Medline, and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results Totally 21 studies were enrolled to analyses. Pooled overall analyses showed that MTNR1B rs10830963 variant was significantly correlated with the susceptibility to T2DM (allele model: p = 0.02, OR = 0.97, 95% CI 0.95–1.00). Further subgroup analyses by ethnicity of participants revealed that rs10830963 variant was significantly correlated with the susceptibility to T2DM in South Asians, but not in Caucasians or East Asians. No any other positive results were found in overall and subgroup analyses. Conclusions Our findings indicated that MTNR1B rs10830963 variant might serve as a genetic biomarker of T2DM, especially in South Asians.

Human constitutive androstane receptor (hCAR, NR1I3) is a member of the orphan nuclear receptor family and regulates the transcription of many drug-metabolizing enzymes and drug transporters. Previous studies have shown that the hCAR gene produces a number of different kinds of mRNA splicing variants (SVs) in non-Asian ethnicities. In the present study, we identified 18 hCAR SVs (SV1-SV18), including four novel SVs in Korean human livers. Among the four novel SVs, SV2 showed enhanced transactivation activity when cotransfected with CYP2B6 reporter gene, whereas other SVs were nonfunctional. When profiles of major hCAR SVs were compared among 30 livers from Korean patients and 20 livers from Caucasian patients, the relative composition of each SV showed interethnic variation as well as interindividual variation. The most predominant form of hCAR SV was not wild type, but either SV4 or SV7. The summed relative amounts of SV4 and SV7 ranged from 34.5 to 57.6% in the 30 Korean livers and from 47.2 to 82.6% in the 20 Caucasian livers, suggesting large interindividual variation. The mean relative amount of nonfunctional SV9 was significantly higher in Koreans (29.8%) than in Caucasians (12.8%). The mean relative amount of novel SV2 was 9.7% in Korean livers and 3.5% in Caucasian livers. Expression profiling of hCAR proteins in human livers also supported large interindividual variation in the expressional ratio of wild-type and SVs. Our results describe for the first time the direct comparison of hCAR SV profiles between Koreans and Caucasians. The functional relevance of these interindividual and interethnic variations of hCAR mRNA expression needs to be further characterized.

Magnetic resonance (MR) contrast agents focusing on special functions are required to improve cancer diagnosis, particularly in the early stages. Here, we designed multifunctional solid lipid nanoparticles (SLNs) with simultaneous loading of gadolinium (Gd) diethylenetriaminepentaacetic acid (Gd-DTPA) and octadecylamine fluorescein isothiocyanate (FITC) to obtain Gd-FITC-SLNs as a tumor-absorbable nanoparticle contrast agent for the histological confirmation of MR imaging (MRI) findings. Colorectal tumors were evaluated in vitro and in vivo via direct uptake of this contrast agent, which displayed reasonable T1 relaxivity and no significant cytotoxicity at the experimental concentrations in human colon carcinoma cells (HT29) and mouse colon carcinoma cells (CT26). In vitro cell uptake experiments demonstrated that contrast agent absorption by the two types of cancer cells was concentration-dependent in the safe concentration range. During in vivo MRI, transrectal infusion of Gd-FITC-SLNs showed more significant enhancement at the tumor site compared with the infusion of Gd-DTPA in female C57/BL mice with azoxymethane/dextran sulfate sodium-induced colorectal highgrade intraepithelial neoplasia. Subsequent confocal fluorescence microscopy demonstrated Gd-FITC-SLNs as highly concentrated green fluorescent spots distributed from the tumor capsule into the tumor. This study establishes the "proof-of-principle" of a new MRI technique wherein colorectal tumors are enhanced via direct absorption or uptake of the nanoparticle contrast agent.

Anastomotic complications such as leakage and bleeding remain among the most serious complications of laparoscopic colorectal surgery. No perfect method exists for accurate and reliable avoidance of these catastrophes. This study aimed to study the usefulness of routine intraoperative endoscopy (RIOE) by comparing the surgical outcomes for RIOE patients with those for selective intraoperative endoscopy (SIOE) patients. A retrospective chart review was performed for consecutive patients who underwent elective laparoscopic colorectal resections with distal anastomosis between January 2004 and May 2007. One surgeon performed RIOE, whereas the other three surgeons performed SIOE as necessary. All the abnormalities of IOE patients were managed with a subsequent salvage procedure, and the postoperative outcomes were compared between the RIOE and SIOE groups. The study included 107 patients in the RIOE group and 137 patients in the SIOE group. Abnormalities were detected in 11 RIOE patients (10.3%) (six with staple line bleeding, three with positive air leak test results, and two with additional pathology identified). All but one abnormality was laparoscopically managed without conversion to laparotomy. Whereas one patient experienced postoperative staple line bleeding that required a second operation, the remaining 10 patients recovered uneventfully. The mean hospital stay was 6 days (range, 4–9) days. The RIOE group had overall rates of 0% for anastomotic leakage and 0.9% for staple line bleeding. Intraoperative endoscopies were performed for 30 (21.9%) of the 137 patients in the SIOE group. The postoperative outcomes comparison between the RIOE and SIOE groups showed a tendency toward more overall anastomotic complications (0.9% vs. 5.1%) in the SIOE group, which due to the small sample size did not translate into significant differences in terms of staple line bleeding and anastomotic leakage. There also were no significant differences in other outcomes such as ileus, abdominal or pelvic sepsis, reoperation, positive distal margin, distance from distal margins, length of hospital stay, or mortality. Routine IOE for patients undergoing elective laparoscopic colorectal surgery with distal anastomosis can detect abnormalities at or around the anastomosis. Although the RIOE group had fewer postoperative anastomotic complications, due to the small sample size, the 5.7-fold increase in anastomotic failure did not translate into significantly better postoperative outcomes than the SIOE group experienced. A larger-scale single or multicenter prospective randomized study or a metaanalysis including similar studies is necessary for further investigation of this issue.

The effect of CYP2C9 and vitamin K epoxide reductase complex subunit 1 (VKORC1) genotypes was evaluated for the early-phase and steady-state warfarin dosing in Korean patients with mechanical heart valve replacement.The genotypes of CYP2C9 variants including CYP2C9*3, CYP2C9*13, and CYP2C9*14, and VKORC1 1173CT were assessed for the association with warfarin dosing in 265 patients whose data were collected for warfarin dose; international normalized ratio (INR), comedication, comorbidity, and other clinical characteristics.In the early phase of warfarin therapy, the combined genotypes of CYP2C9 and VKORC1 caused statistically significant difference in warfarin dose from day 7 of warfarin dosing and the subsequent time course of dose increase showed significant difference among the three different genotypes (P0.001). Compared with patients with CYP2C9 wild type, the patients with heterozygous CYP2C9 variants have delayed time to reach stable dose [adjusted hazard ratio (HRadj): 0.48; 95% confidence interval (CI): 0.27-0.85] and tended to have high risk for the first INR greater than 3.5 (HRadj: 1.64; 95% CI: 0.98-2.75). The patients with the VKORC1 CT genotype showed no significant difference in the time to reach stable dose but statistically significant low HR for time to first INR greater than 3.5 compared with those with VKORC1 TT genotype (HRadj: 0.25; 95% CI: 0.13-0.51). The observed warfarin maintenance dose was best explained by a model including covariates of age, weight, concurrent congestive heart failure/cardiomyopathy, INR-increasing drugs, aspirin, dietary supplements, and CYP2C9 and VKORC1 genotypes (R=0.56).The heterozygous CYP2C9 and VKORC1 genotypes influence warfarin dosing in an early phase as well as steady state of warfarin therapy in Korean patients with mechanical heart valve replacement.

Background Thiopurine S-methyltransferase (TPMT) genetic polymorphisms have been studied intensively in relation to thiopurine toxicity. In the present study, an improved pyrosequencing method was developed for TPMT genotyping and used to investigate the genotype frequency in Korean and Vietnamese populations. Methods Four-hundred Korean and 159 Vietnamese subjects were genotyped by pyrosequencing for TPMT 238G>C, 460G>A, 539A>T, and 719A>G variants, in order to determine the TPMT⁎2, ⁎3A, ⁎3B, ⁎3C, and ⁎6 alleles. Results TPMT⁎3C was found to be the most frequent allele in both the Korean (0.88%) and Vietnamese (2.83%) populations. TPMT⁎2, ⁎3A, and ⁎3B were not found in either of the study populations. Two Korean subjects were genotyped as TPMT⁎1/⁎6 (0.25%), while none of the Vietnamese had this genotype. The direct comparison of the frequencies of functional TPMT⁎1/⁎3C genotype showed significant difference between Korean and Vietnamese populations ( χ 2 test, p = 0.0124). Duplex pyrosequencing methods for the detection of TPMT⁎3C and TPMT⁎6 were developed and validated to show 100% concordance with the results obtained by direct sequencing. Conclusions The functional TPMT alleles in Korean and Vietnamese populations are TPMT⁎3C and TPMT⁎6. Duplex pyrosequencing for these alleles appears to be an accurate, rapid, and cost-effective method for genotyping TPMT in these Asian populations.

Background and aim: The Krüppel-like transcription factor KLF6 is a novel tumor-suppressor gene. It was inactivated in human prostate cancer and other tumors tissue, as the result of frequent mutation and loss of heterozygosity (LOH). However, there is no data reporting the levels of KLF6 both mRNA and protein in hepatocellular carcinomas (HCCs). We therefore detected mutations and expression of KLF6 in HCC tissues and further observed the effect of it on cell growth in HCC cell lines. Methods: We analyzed the exon-2 of KLF6 gene by direct DNA sequencing, and detected the expression of KLF6 by RT-PCR and Western blot in 23 HCC tissues and corresponding nontumorous tissues. Loss of growth suppressive effect of the HCC-derived KLF6 mutant was characterized by in vitro growth curves plotted, flow cytometry and Western blotting. Results: KLF6 mutations were found in 2 of 23 HCC tissues and one of mutations was missense. Expression of KLF6 mRNA or protein was down-regulated in 8 (34.7%) or 9 (39.1%) of 23 HCC tissues. Wild-type KLF6 (wtKLF6) inhibited cellular proliferation and prolonged G1-S transition by inducing the expression of p21WAF1 following stable transfection into cultured HepG2 cells, but tumor-derived KLF6 mutant (mKLF6) had no effects. Conclusion: Our findings suggest that KLF6 may be involved in pathogenesis of HCC.

Background Glucose-insulin-potassium (GIK) has been advocated in the setting of acute coronary syndrome (ACS) to reduce ischemia-related arrhythmias and myocardial injury. We conducted a meta-analysis of randomized controlled trials (RCTs) to assess whether the use of GIK infusions >3 or 3 hours after the onset of symptoms, on mortality and/or cardiac arrest. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for each outcome. Results Nine trials were identified and eligible for review. The summary OR for in-hospital mortality was 1.01 (95% CI 0.94 to 1.09), based on 2,542 deaths among 27,294 patients. The subgroup analysis according to the study enrollment time (within 3 hours [OR, 0.77, 95% CI 0.50-1.16], vs. >3 hours [OR, 0.90; 95% CI, 0.67-1.21]) did not reveal any difference in mortality. Conclusions Administration of GIK in ACS patients does not significantly reduce mortality whether or not GIK administration >3 or

BACKGROUND: Several observational studies have shown that statin use may modify the risk of haematological malignancies. To quantify the association between statin use and risk for haematological malignancies, we performed a detailed meta-analysis of published studies regarding this subject. METHODS: We conducted a systematic search of multiple databases including PubMed, Embase, and Cochrane Library Central database up to July 2013. Fixed-effect and random-effect models were used to estimate summary relative risks (RR) and the corresponding 95% confidence intervals (CIs). Potential sources of heterogeneity were detected by meta-regression. Subgroup analyses and sensitivity analysis were also performed. RESULTS: A total of 20 eligible studies (ten case-control studies, four cohort studies, and six RCTs) reporting 1,139,584 subjects and 15,297 haematological malignancies cases were included. Meta-analysis showed that statin use was associated with a statistically significant 19% reduction in haematological malignancies incidence (RR = 0.81, 95% CI [0.70, 0.92]). During subgroup analyses, statin use was associated with a significantly reduced risk of haematological malignancies among observational studies (RR = 0.79, 95% CI [0.67, 0.93]), but not among RCTs (RR = 0.92, 95% CI [0.77, 1.09]). CONCLUSIONS: Based on this comprehensive meta-analysis, statin use may have chemopreventive effects against haematological malignancies. More studies, especially definitive, randomized chemoprevention trials are needed to confirm this association.

Senescence is an irreversible growth arrest which can be triggered by stresses such as oxidative reaction, telomere shortening, DNA damage, or oncogene signaling. Oxidative stress accelerates vascular endothelial cell senescence, and may promote atherosclerosis in humans. Interleukin-8 (IL-8) has been shown to play an important role in tumor growth, angiogenesis, and metastasis, and has close relationship with oxidative stress. The objective of this study was to determine if IL-8 might be able to prevent oxidative stress-induced senescence of endothelial cells and the mechanisms. Human umbilical vein endothelial cells (HUVECs) were cultured and stimulated with hydrogen peroxide in the absence or presence of IL-8. After ex vivo cultivation, HUVECs became senescent as determined by acidic beta-galactosidase staining. IL-8 dose-dependently inhibited the onset of HUVEC senescence. Western blots indicated that IL-8 attenuated the oxidative stress induced high-expression of cell cycle regulation protein and inhibited the activation of p38 and NF-κB pathway. IL-8 also increased telomerase activity which was accompanied with upregulation of the catalytic subunit, telomerase reverse transcriptase (TERT), whereas these effects were significantly attenuated by SB 225002 (selective non-peptide CXCR2 antagonist). In conclusion, IL-8 exerted protective effects against endothelial senescence, which may be related to the activation of telomerase.

cope Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is the principal pungent ingredient in hot red and chili peppers. Many studies have focused on the anticarcinogenic or chemopreventive activities of capsaicin. However, the influence of capsaicin on CYP3A4, its involvement in drug metabolism, and the underlying mechanisms remain unclear. Methods and results Here, we examined the effect of capsaicin on CYP3A4 expression and the metabolism of CYP3A1 substrate, nifedipine in male Sprague–Dawley rats. Capsaicin induced the enzymatic activity and expression of CYP3A4 in HepG2 cells. Treatment with a human pregnane X receptor (hPXR) inhibitor reduced the inductive effects of capsaicin on CYP3A4 expression. Capsaicin also induced the activation of CCAAT/enhancer-binding protein β (C/EBPβ). Moreover, capsaicin increased the activation of the transient receptor potential vanilloid type-1 receptor downstream signaling components Ca2+/calmodulin-dependent protein kinase and Akt. Capsaicin elevated the level of CYP3A1 in rat liver and significantly increased the biotransformation of nifedipine to dehydronifedipine. Conclusion From these data, we conclude that capsaicin induces CYP3A4 expression in vitro and in vivo. This induction was achieved by the activation of hPXR and C/EBPβ. Our results suggest that capsaicin might induce CYP3A4 expression; thus, exposure to capsaicin may increase the metabolism of CYP3A4 substrate and potentially cause food–drug interactions.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT * CYP2C9 single nucleotide polymorphisms (SNPs) are important in safe and effective oral anticoagulation with warfarin use. * Although CYP2C9*2 and *3 are important genetic factors for the warfarin dose, one of the CYP2C9 SNPs, IVS-65GC, has been suggested to be associated with warfarin sensitivity. However, as of yet, there has been no explanation about the possible mechanism and linkage analysis. WHAT THIS PAPER ADDS * New information on CYP2C9 SNPs and their occurrences in common haplotype structures in healthy unrelated Koreans and in individuals who require low warfarin dose after mechanical heart valve replacements (MHVRs) were studied. * Additional evidence showed that an Asian dominant haplotype consisting of -1565CT, -1188TC, IVS3+197GA, IVS3-334CT, IVS3-65GC, IVS4-115AG and IVS5-73AG could be associated with a low warfarin maintenance dose in mechanical heart valve replacement (MHVR) patients. AIMS The objectives of this study were to determine the distribution of CYP2C9 variants in Koreans and investigate their association with warfarin dose requirements in patients who received MHVRs. METHODS All nine exons, intron-exon junction, and promoter region of CYP2C9 were amplified and directly sequenced in 50 healthy normal Koreans. Additional direct DNA sequencing of the CYP2C9 gene was conducted in 36 of the 267 MHVR patients who required low maintenance warfarin doses without carrying CYP2C9*3 and VKORC1 1173T mutations. The effects of CYP2C9 genetics on warfarin maintenance dose were assessed in 267 MHVR patients. RESULTS Thirty-nine single nucleotide polymorphisms (SNPs) including seven previously unidentified SNPs were identified in 50 Koreans by direct DNA sequencing. One of the CYP2C9 haplotypes exhibited an association with warfarin low dose requirement. The adjusted odds ratio for the haplotype between the low dose group and the normal subjects was 2.5 (95% confidence interval 1.05, 6.16). This haplotype consisting of -1565CT, -1188TC, IVS3+197GA, IVS3-334CT, IVS3-65GC, IVS4-115AG, and IVS5-73AG was found in 15% of 36 MHVR patients who required low warfarin doses, while 4% of 50 normal healthy subjects exhibited this haplotype. One of the SNPs comprising this haplotype, -1565CT, apparently changed a protein binding pattern as observed in electrophoretic mobility shift assay. CONCLUSION The haplotype including -1565CT, -1188TC, IVS3+197GA, IVS3-334CT, IVS3-65GC, IVS4-115AG, and IVS5-73AG seems to be associated with low warfarin dose requirement and this haplotype could be considered in the development of a warfarin dose prediction model for Asian populations.

Cytochrome P450 2S1 (CYP2S1) is a drug-metabolizing enzyme that shows interindividual variations in response to treatments for psoriasis and is regarded as a putative prognostic marker for colorectal cancer treatment. To gain insight into the genetic basis for the interindividual variations, CYP2S1 gene polymorphisms were analyzed in Korean subjects. Using direct sequencing of the CYP2S1 gene, 12 genetic variations, which included the two novel nonsynonymous mutations CYP2S1 S61N (0.3%) and CYP2S1 L230R (0.8%), were identified in 50 Korean subjects. Homology modeling predicted the location of the L230R change to be near two conserved alpha-helices in the hood of the substrate-binding site. Linkage disequilibrium (LD) analysis with seven common CYP2S1 variations showed two discrete LD blocks in CYP2S1 gene and consequently a limited number of haplotypes. Although the importance of novel CYP2S1 variants and haplotypes remains to be discovered, CYP2S1 polymorphisms would provide useful information on interindividual variations with respect to CYP2S1 function, which facilitates drug response predictions and disease prognosis.

BACKGROUND: With the rapid development of real-time elastography (RTE), a variety of measuring methods have been developed for the assessment of hepatic fibrosis. We evaluated the overall performance of four methods based on RTE by performing meta-analysis of published literature. METHODS: Online journal databases and a manual search from April 2000 to April 2014 were used. Studies from different databases that meet inclusion criteria were enrolled. The statistical analysis was performed using a random-effects model and fixed-effects model for the overall effectiveness of RTE. The area under the receiver operating characteristic curve (AUROC) was calculated for various means. Fagan plot analysis was used to estimate the clinical utility of RTE, and the heterogeneity of the studies was explored with meta-regression analysis. RESULTS: Thirteen studies from published articles were enrolled and analyzed. The combined AUROC of the liver fibrosis index (LFI) for the evaluation of significant fibrosis (F≥2), advanced fibrosis (F≥3), and cirrhosis (F = 4) were 0.79, 0.94, and 0.85, respectively. The AUROC of the elasticity index (EI) ranged from 0.75 to 0.92 for F≥2 and 0.66 to 0.85 for F = 4. The overall AUROC of the elastic ratio of the liver for the intrahepatic venous vessels were 0.94, 0.93, and 0.96, respectively. The AUROC of the elastic ratio of the liver for the intercostal muscle in diagnosing advanced fibrosis and cirrhosis were 0.96 and 0.92, respectively. There was significant heterogeneity in the diagnostic odds ratio (DOR) for F≥2 of LFI mainly due to etiology (p

AIM: To assess the value of plasma melatonin in predicting acute pancreatitis when combined with the acute physiology and chronic health evaluation II (APACHEII) and bedside index for severity in acute pancreatitis (BISAP) scoring systems. METHODS: APACHEII and BISAP scores were calculated for 55 patients with acute physiology (AP) in the first 24 h of admission to the hospital. Additionally, morning (6:00 AM) serum melatonin concentrations were measured on the first day after admission. According to the diagnosis and treatment guidelines for acute pancreatitis in China, 42 patients suffered mild AP (MAP). The other 13 patients developed severe AP (SAP). A total of 45 healthy volunteers were used in this study as controls. The ability of melatonin and the APACHEII and BISAP scoring systems to predict SAP was evaluated using a receiver operating characteristic (ROC) curve. The optimal melatonin cutoff concentration for SAP patients, based on the ROC curve, was used to classify the patients into either a high concentration group (34 cases) or a low concentration group (21 cases). Differences in the incidence of high scores, according to the APACHEII and BISAP scoring systems, were compared between the two groups. RESULTS: The MAP patients had increased melatonin levels compared to the SAP (38.34 ng/L vs 26.77 ng/L) (P = 0.021) and control patients (38.34 ng/L vs 30.73 ng/L) (P = 0.003). There was no significant difference inmelatoninconcentrations between the SAP group and the control group. The accuracy of determining SAP based on the melatonin level, the APACHEII score and the BISAP score was 0.758, 0.872, and 0.906, respectively, according to the ROC curve. A melatonin concentration ≤ 28.74 ng/L was associated with an increased risk of developing SAP. The incidence of high scores (≥ 3) using the BISAP system was significantly higher in patients with low melatonin concentration (≤ 28.74 ng/L) compared to patients with high melatonin concentration (> 28.74 ng/L) (42.9% vs 14.7%, P = 0.02). The incidence of high APACHEII scores (≥ 10) between the two groups was not significantly different. CONCLUSION: The melatonin concentration is closely related to the severity of AP and the BISAP score. Therefore, we can evaluate the severity of disease by measuring the levels of serum melatonin.

Background: With high morbidity, mortality and disability rate, brain infarction brings a huge economic and health burden to the whole society in China. Although some previous studies suggested that telerehabilitation may facilitate rehabilitation for stroke survivors at home, the evidence is insufficient for clinical application; additionally, as yet no trial evaluates efficacy of telerehabilitation for brain infarction patients. Therefore, more high quality trials are needed to provide practice evidence for this novel rehabilitation strategy. Methods/Design: Based on recruitment criteria, this assessor blinded, paralleled randomized controlled trial will recruit 210 brain infarction patients. After being randomly allocated into two groups, participants will receive home-based tele-supervising rehabilitation or conventional rehabilitation. Outcome measurement will be conducted at the end of intervention and 90-day follow-up. Among which, Barthel index assessment will be considered as primary outcome measurement, secondary outcome measurements include NIHSS score, mRS score, 3-oz water swallow test and surface electromyography. Adverse events will also be recorded during the whole process of the trial for safety assessment. Discussion: The HTRBIP trial will evaluate efficacy and safety of home-based tele-supervising rehabilitation for brain infarction patients. It is expected to provide new evidence for telerehabilitation application. Trial registration: Registration date: 17 September 2014; Registration number: ChiCTR-TRC-14005233

We aim to provide a systematic review and meta-analysis of the prevalence rates of mental health symptoms among major African populations during the COVID-19 pandemic. We include articles from PubMed, Embase, Web of Science, PsycINFO, and medRxiv between 1 February 2020 and 6 February 2021, and pooled data using random-effects meta-analyses. We identify 28 studies and 32 independent samples from 12 African countries with a total of 15,071 participants. The pooled prevalence of anxiety was 37% in 27 studies, of depression was 45% in 24 studies, and of insomnia was 28% in 9 studies. The pooled prevalence rates of anxiety, depression, and insomnia in North Africa (44%, 55%, and 31%, respectively) are higher than those in Sub-Saharan Africa (31%, 30%, and 24%, respectively). We find (a) a scarcity of studies in several African countries with a high number of COVID-19 cases; (b) high heterogeneity among the studies; (c) the extent and pattern of prevalence of mental health symptoms in Africa is high and differs from elsewhere—more African adults suffer from depression rather than anxiety and insomnia during COVID 19 compared to adult populations in other countries/regions. Hence, our findings carry crucial implications and impact future research to enable evidence-based medicine in Africa. Refereed/Peer-reviewed