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Long non‐coding RNAs (LncRNAs), which are more than 200 nucleotides in length and with limited protein‐coding potential, play vital roles in the pathogenesis, tumorigenesis, and angiogenesis of cancers. Aberrant expression of lncRNAs has been detected in various carcinomas and may be correlated with oncogenesis by affecting related genes expression. Recently, an increasing number of studies have reported on long intergenic non‐protein coding RNA 460 (LINC00460) in human tumor fields. LINC00460 is upregulated in diverse cancer tissues and cells. The upregulated expression level of LINC00460 is correlated with larger tumor size, tumor node metastasis (TNM) stage, lymph node metastasis, and shorter overall survival. The regulatory mechanism of LINC00460 was complex and diverse. LINC00460 could act as a competitive endogenous RNA (ceRNA), directly bind with proteins or regulate multiple pathways, which affected tumor progression. Moreover, LINC00460 was also identified to increase drug resistance, and therefore, weaken the effectiveness of tumor treatment. It has become increasingly important to investigate the roles of LINC00460 in various cancers by different mechanisms. Therefore, a more comprehensive understanding of LINC00460 is crucial to expound on the cellular function and molecular mechanism of human cancers. In this review, we refer to studies concerning LINC00460 and provide the basis for the evaluation of LINC00460 as a predicted biomarker or potential therapeutic target in malignancies, and also provide ideas for the future research of lncRNAs similar to LINC00460., In recent years, the regulatory role of long noncoding RNAs (lncRNAs) in human tumors has been gradually recognized. In this review, we respectively showed how lncRNA LINC00460 affected progression of human tumors in different types by multiple mechanisms. A large number of previous researches have demonstrated that LINC00460 as an oncogene plays important roles in tumor growth, development, and metastasis. In view of the important role of LINC00460 in tumorigenesis and development as well as its significance as a biomarker, we summarized the specific role and molecular mechanism of LINC00460 in various tumors, convenient for readers integrally learning about the effect of LINC00460 on diverse cancers. We believe this review is valuable for all the researchers who are interested in human cancers and noncoding RNAs.

Background This study aimed to investigate the associations of sarcopenia and its defining components with cognitive function in community-dwelling oldest old (over 80 years old) in China. Methods Sarcopenia was diagnosed by the 2019 Asian Working Group for Sarcopenia (AWGS) criteria. Cognitive function was evaluated by the Montreal Cognitive Assessment (MoCA). Logistic and linear regression models were used to explore the associations of sarcopenia and its defining components with risk of mild cognitive impairment (MCI), and performance on multiple cognitive domains among 428 adults aged 80 years and older. Results The overall prevalence of sarcopenia was 35.5%, with 40.34% for men and 32.14% for women. The prevalence of MCI was higher among sarcopenic oldest old than non-sarcopenic oldest old (28.95% vs. 17.39%, p = 0.005). Multivariate logistic regression analyses showed that sarcopenia [odds ratio (OR) = 1.86, 95% confidence interval (CI): 1.04–3.33], low handgrip strength (HS) [OR = 2.33, 95% CI: 1.40–3.87] and slow gait speed (GS) [OR = 2.31, 95% CI: 1.13–4.72] were significantly and independently associated with risk of MCI. Multivariate linear regression analyses showed that low HS was associated with worse performance in global cognitive function, visuospatial and executive function, naming and delayed recall. Conclusions Sarcopenia, low HS and low GS was significantly associated with MCI in community-dwelling oldest old. The associations between sarcopenia and its defining components with different cognitive subdomains could be further explored in the future.

Sestrin2 (Sesn2) is a stress-inducible protein that plays a critical role in the response to ischemic stress. We recently recognized that Sesn2 may protect the heart against ischemic insults by reducing the generation of reactive oxygen species (ROS). After 45 min of ischemia followed by 24 h of reperfusion, myocardial infarcts were significantly larger in Sesn2 KO hearts than in wild-type hearts. Isolated cardiomyocytes from wild-type hearts treated with hypoxia and reoxygenation (H/R) stress showed significantly greater Sesn2 levels, compared with normoxic hearts (p 0.05). Intriguingly, the administration of adeno-associated virus 9-Sesn2 into Sesn2 knockout (KO) hearts rescued Sesn2 protein levels and significantly improved the cardiac function of Sesn2 KO mice exposed to ischemia and reperfusion. The rescued levels of Sesn2 in Sesn2 KO hearts significantly ameliorated ROS generation and the activation of ROS-related stress signaling pathways during ischemia and reperfusion. Moreover, the rescued Sesn2 levels in Sesn2 KO cardiomyocytes improved the maximal velocity of cardiomyocyte shortening by H/R stress. Rescued Sesn2 levels also improved peak height, peak shortening amplitude, and maximal velocity of the re-lengthening of Sesn2 KO cardiomyocytes subjected to H/R. Finally, the rescued Sesn2 levels significantly augmented intracellular calcium levels and reduced the mean time constant of transient calcium decay in Sesn2 KO cardiomyocytes exposed to H/R. Overall, these findings indicated that Sesn2 can act as an endogenous antioxidant to maintain intracellular redox homeostasis under ischemic stress conditions.

Background: With the increasing number of cases of breast cancer every year, the exploration of novel biomarkers has drawn attention. miR-331 has been demonstrated to play a role in various cancers, but its role in breast cancer is still unknown. Methods: In this study, we included 121 patients with breast cancer treated at Affiliated Hospital of Weifang Medical University. Breast cancer tissues and adjacent normal tissues were collected during the surgery. The expression of miR-331 in breast cancer tissues and cell lines was detected by qRT-PCR assay. Then, with the help of Kaplan-Meier survival and Cox regression analyses, the role of miR-331 in the prognosis of breast cancer was analyzed. Finally, the effect of miR-331 on cell proliferation, migration, and invasion was investigated with CCK-8 assay and transwell assay. Results: miR-331 was significantly upregulated in breast cancer tissues compared with normal tissues. The overexpression of miR-331 was associated with lymph node metastasis, TNM stage, and poor prognosis. From the results of Cox regression analyses, it was found that miR-331 served as an independent indicator in the prognosis of breast cancer. In addition, miR-331 was also found to be upregulated in breast cancer cells, which promoted cell proliferation, migration, and invasion of breast cancer. Conclusion: As shown from our data, miR-331 may be a potential prognostic biomarker in breast cancer. Moreover, the development and progression of breast cancer may involve miR-331. These findings suggest a novel therapeutic target for the treatment of breast cancer.

ObjectivesThe prevalence of childhood hypertension is rising in parallel with the increasing prevalence of overweight and obesity in children. How growth trajectories from childhood to puberty relate to high blood pressure (HBP) is not well defined. We aimed to characterise potential body mass index (BMI) dynamic changing trajectories from childhood to puberty and investigate their association with HBP.DesignA dynamic prospective cohort.SettingChina Health and Nutrition Survey 1991–2015.ParticipantsThere were 1907 participants (1027 men and 880 women) in this study.OutcomesThe primary outcome was HBP defined as systolic blood pressure (SBP)/diastolic blood pressure (DBP) exceeding the standards or diagnosis by medical records or taking antihypertensive medication.ResultsA model of cubic parameters with three groups was chosen, labelled as normal increasing group (85.16%, n=1624), high increasing group (9.81%, n=187) and resolving group (5.03%, n=96). Compared with the normal increasing group, the unadjusted HRs (95% CIs) for the resolving and high increasing groups were 0.91 (0.45 to 1.86) and 1.88 (1.26 to 2.81), respectively. After adjusting for baseline age, region, sex, baseline BMI z-score, baseline SBP and baseline DBP in model 3, the HRs (95% CIs) for the resolving and high increasing groups were 0.66 (0.30 to 1.45) and 1.56 (1.02 to 2.38).ConclusionsThese results indicate that the BMI trajectories from childhood to puberty have significant impact on HBP risk. Puberty is a crucial period for the development of HBP.

Perivascular adipose tissue (PVAT) is the connective tissue around most blood vessels throughout the body. It provides mechanical support and maintains vascular homeostasis in a paracrine/endocrine manner. Under physiological conditions, PVAT has anti-inflammatory effects, improves free fatty acid metabolism, and regulates vasodilation. In pathological conditions, PVAT is dysfunctional, secretes many anti-vasodilator factors, and participates in vascular inflammation through various cells and mediators; thus, it causes dysfunction involving vascular smooth muscle cells and endothelial cells. Inflammation is an important pathophysiological event in many vascular diseases, such as vascular aging, atherosclerosis, and hypertension. Therefore, the pro-inflammatory crosstalk between PVAT and blood vessels may comprise a novel therapeutic target for the prevention and treatment of vascular diseases. In this review, we summarize findings concerning PVAT function and inflammation in different pathophysiological backgrounds, focusing on the secretory functions of PVAT and the crosstalk between PVAT and vascular inflammation in terms of vascular aging, atherosclerosis, hypertension, diabetes mellitus, and other diseases. We also discuss anti-inflammatory treatment for potential vascular diseases involving PVAT.

Rationale: Hepatitis B virus (HBV) is a major risk factor for liver cancer, in which HBV covalently closed circular DNA (cccDNA) plays crucial roles. However, the effect of pseudogene-derived long noncoding RNAs (lncRNAs) acting as functional regulators of their ancestral gene expression on HBV replication and hepatocellular carcinoma (HCC) remains unclear. In this study, we speculated that the pseudogene-derived lncRNA PCNAP1 and its ancestor PCNA might modulate HBV replication and promote hepatocarcinogenesis. Methods: We investigated the roles of lncRNA PCNAP1 in contribution of HBV replication through modulating miR-154/PCNA/HBV cccDNA signaling in hepatocarcinogenesis by using CRISPR/Cas9, Southern blot analysis, confocal assays, et al. in primary human hepatocytes (PHH), HepaRG cells, HepG2-NTCP cells, hepatoma carcinoma cells, human liver-chimeric mice model, transgenetic mice model, in vitro tumorigenicity and clinical patients. Results: Interestingly, the expression levels of PCNAP1 and PCNA were significantly elevated in the liver of HBV-infectious human liver-chimeric mice. Clinically, the mRNA levels of PCNAP1 and PCNA were increased in the liver of HBV-positive/HBV cccDNA-positive HCC patients. Mechanistically, PCNA interacted with HBV cccDNA in a HBc-dependent manner. PCNAP1 enhanced PCNA through sponging miR-154 targeting PCNA mRNA 3'UTR. Functionally, PCNAP1 or PCNA remarkably enhanced HBV replication and accelerated the growth of HCC in vitro and in vivo. Conclusion: We conclude that lncRNA PCNAP1 enhances the HBV replication through modulating miR-154/PCNA/HBV cccDNA signaling and the PCNAP1/PCNA signaling drives the hepatocarcinogenesis. Our finding provides new insights into the mechanism by which lncRNA PCNAP1 enhances HBV replication and hepatocarcinogenesis.

Objective The aim of this study was to investigate the underlying mechanism whereby HBx modulates the targeting of NUSAP1 by miR-18b to enhance hepatocarcinogenesis.Methods We employed an integrated approach of bioinformatics analysis and molecular experiments in hepatoma cells, HBV transgenic mice, and clinical liver cancer tissues to investigate the role of HBx-regulated miR-18b in the development of liver cancer.Results In this study, we report that the HBx-mediated tumor suppressor miR-18b modulates hepatocarcinogenesis during the host-HBV interaction. The expression levels of miR-18b were lower in clinical HBV-positive liver cancer tissues and liver tissues of HBV-transgenic mice. Interestingly, HBx inhibited miR-18b expression by inducing the methylation of CpG islands in its promoter. Accordingly, we tested the hypothesis that HBx enhanced hepatocarcinogenesis by increasing the expression of target genes of miR-18b. Moreover, we identified nucleolar spindle-associated protein 1 (NUSAP1) as one of the target genes of miR-18b. NUSAP1 was expressed at high levels in liver cancer tissues. Interestingly, HBx up-regulated NUSAP1 by suppressing miR-18b. Functionally, miR-18b significantly inhibited the proliferation of hepatoma cells by depressing NUSAP1 levels in vivo and in vitro.Conclusions Thus, we conclude that the targeting of NUSAP1 mRNA by the tumor suppressor miR-18b is controlled by HBx-modulated promoter methylation during the host-virus interaction, leading to hepatocarcinogenesis. Our findings provide new insights into the mechanism by which HBx-mediated miRNAs modulate hepatocarcinogenesis.

BackgroundImmunotherapy, adjuvant chemotherapy, and prognosis of colorectal cancer are associated with MSI. Biopsy pathology cannot fully reflect the MSI status and heterogeneity of rectal cancer.PurposeTo develop a radiomic-based model to preoperatively predict MSI status in rectal cancer on MRI.AssessmentThe patients were divided into two cohorts (training and testing) at a 7:3 ratio. Radiomics features, including intensity, texture, and shape, were extracted from the segmented volumes of interest based on T2-weighted and ADC imaging.Statistical TestsIndependent sample t test, Mann-Whitney test, the chi-squared test, Receiver operating characteristic curves, calibration curves, decision curve analysis and multi-variate logistic regression analysisResultsThe radiomics models were significantly associated with MSI status. The T2-based model showed an area under the curve of 0.870 with 95% CI: 0.794–0.945 (accuracy, 0.845; specificity, 0.714; sensitivity, 0.976) in training set and 0.895 with 95% CI, 0.777–1.000 (accuracy, 0.778; specificity, 0.887; sensitivity, 0.772) in testing set. The ADC-based model had an AUC of 0.790 with 95% CI: 0.794–0.945 (accuracy, 0.774; specificity, 0.714; sensitivity, 0.976) in training set and 0.796 with 95% CI, 0.777–1.000 (accuracy, 0.778; specificity, 0.889; sensitivity, 0.772) in testing set. The combined model integrating T2 and ADC features showed an AUC of 0.908 with 95% CI: 0.845–0.971 (accuracy, 0.857; specificity, 0.762; sensitivity, 0.952) in training set and 0.926 with 95% CI: 0.813-1.000 (accuracy, 0.852; specificity, 1.000; sensitivity, 0.778) in testing set. Calibration curve showed that the combined score had a good calibration degree, and the decision curve demonstrated that the combined score was of benefit for clinical use.Data ConclusionRadiomics analysis of T2W and ADC images showed significant relevance in the prediction of microsatellite status, and the accuracy of combined model of ADC and T2W features was better than either alone.

Early growth response gene (EGR1) is a transcription factor known to be a downstream effector of B-cell receptor signaling and Janus kinase 1 (JAK1) signaling in diffuse large B-cell lymphoma (DLBCL). While EGR1 is characterized as a tumor suppressor in leukemia and multiple myeloma, the role of EGR1 in lymphoma is unknown. Here we demonstrate that EGR1 is a potential oncogene that promotes cell proliferation in DLBCL. IHC analysis revealed that EGR1 expression is elevated in DLBCL compared with normal lymphoid tissues and the level of EGR1 expression is higher in activated B cell–like subtype (ABC) than germinal center B cell–like subtype (GCB). EGR1 expression is required for the survival and proliferation of DLBCL cells. Genomic analyses demonstrated that EGR1 upregulates expression of MYC and E2F pathway genes through the CBP/p300/H3K27ac/BRD4 axis while repressing expression of the type I IFN pathway genes by interaction with the corepressor NAB2. Genetic and pharmacologic inhibition of EGR1 synergizes with the BRD4 inhibitor JQ1 or the type I IFN inducer lenalidomide in growth inhibition of ABC DLBCL both in cell cultures and xenograft mouse models. Therefore, targeting oncogenic EGR1 signaling represents a potential new targeted therapeutic strategy in DLBCL, especially for the more aggressive ABC DLBCL. Implications: The study characterizes EGR1 as a potential oncogene that promotes cell proliferation and defines EGR1 as a new molecular target in DLBCL, the most common non-Hodgkin lymphoma.

Introduction: The objective of this article was to detect the expression pattern and clinical value of miR-425-5p in diabetic retinopathy (DR) patients and investigate its effect on the proliferation and migration of human retinal microvascular endothelial cells (HRMECs) in a high glucose (HG) state. Methods: The serum miR-425-5p level of the subjects was determined using quantitative real-time PCR. The diagnostic value of serum miR-425-5p was validated using the receiver operating characteristic curve. Pearson analysis detected the correlation between clinical indicators and microRNA. The influence of miR-425-5p on cell proliferation and migration under HG conditions was calculated by using Cell Counting Kit-8 and Transwell assay. Results: Serum miR-425-5p levels showed a gradual increasing trend in the healthy control group, the diabetic mellitus patients without DR, and DR patients. Moreover, the levels of miR-425-5p in proliferative DR (PDR) patients were elevated than that of non-PDR (NPDR) patients. Furthermore, upregulated miR-425-5p had a high diagnostic value for DR patients and can distinguish PDR patients from NPDR patients. The expression of miR-425-5p was significantly positively correlated with the fasting plasma glucose, glycosylated hemoglobin (HbA1C), homeostasis model assessment of insulin resistance, and disease course of the patients. Under HG conditions, overexpression of miR-425-5p promoted HRMEC proliferation and migration, while inhibition of miR-425-5p led to opposite results. Conclusion: Present research confirmed that serum miR-425-5p levels in DR are marked by elevation. High expression of miR-425-5p can be used as a feasible diagnostic biomarker for DR patients and can predict the development and severity of DR. Moreover, inhibiting the expression of miR-425-5p levels under the condition of hyperglycemia may be used as a valuable therapeutic strategy for preventing the pathogenesis of DR.

Physiological reactive oxygen species (ROS) play an important role in cellular signal transduction. However, excessive ROS is an important pathological mechanism in most cardiovascular diseases (CVDs), such as myocardial aging, cardiomyopathy, ischemia/reperfusion injury (e.g., myocardial infarction) and heart failure. Programmed cell death, hypertrophy and fibrosis may be due to oxidative stress. Sestrin 2 (Sesn2), a stress-inducible protein associated with various stress conditions, is a potential antioxidant. Sesn2 can suppress the process of heart damage caused by oxidative stress, promote cell survival and play a key role in a variety of CVDs. This review discusses the effect of Sesn2 on the redox signal, mainly via participation in the signaling pathway of nuclear factor erythroid 2-related factor 2, activation of adenosine monophosphate-activated protein kinase and inhibition of mammalian target of rapamycin complex 1. It also discusses the effect of Sesn2's antioxidant activity on different CVDs. We speculate that Sesn2 plays an important role in CVDs by stimulating the process of antioxidation and promoting the adaptation of cells to stress conditions and/or the environment, opening a new avenue for related therapeutic strategies.

As an inevitable biological process, cardiovascular aging is the greatest risk factor for cardiovascular diseases (CVDs). Sestrin 2 (Sesn2), a stress-inducible and age-related protein associated with various stress conditions, plays a pivotal role in slowing this process. It acts as an anti-aging agent, mainly through its antioxidant enzymatic activity and regulation of antioxidant signaling pathways, as well as by activating adenosine monophosphate-activated protein kinase and inhibiting mammalian target of rapamycin complex 1. In this review, we first introduce the biochemical functions of Sesn2 in the cardiovascular aging process, and describe how Sesn2 expression is regulated under various stress conditions. Next, we emphasize the role of Sesn2 signal transduction in a series of age-related CVDs, including hypertension, myocardial ischemia and reperfusion, atherosclerosis, and heart failure, as well as provide potential mechanisms for the association of Sesn2 with CVDs. Finally, we present the potential therapeutic applications of Sesn2-directed therapy and future prospects.

Objective This study aimed to investigate the relationship between BTB/POZ domain-containing protein 7 (BTBD7) and fibronectin (FN) expression in salivary adenoid cystic carcinoma (SACC) and the function of BTBD7 in proliferation, migration, and invasion of SACC cells. Study Design The BTBD7 and FN expression in SACC and nontumor salivary tissues as well as SACC cells were characterized by immunohistochemistry and immunofluorescence. The effect of BTBD7 silencing on the proliferation, migration, and invasion of SACC-LM cells were determined by wound healing and transwell invasion assays. Results The percentages of SACC with positive BTBD7 expression were significantly higher than those of SACC with FN expression. BTBD7 silencing significantly increased the relative levels of FN expression and inhibited the proliferation, migration, and invasion of SACC-LM cells. Conclusions The study data indicated that BTBD7 was inversely associated with FN expression in SACC. BTBD7 may inhibit FN expression, but it promotes the proliferation, migration, and invasion of SACC-LM cells. Hence, BTBD7 may be associated with metastasis and a new therapeutic target for intervention of SACC.

Methyltransferase-like 3 (METTL3) is involved in RNA metabolism through N6-methyladenosine (m6A) modification. However, whether METTL3 participates in the progression of breast cancer is unclear. Aberrant expression of Mammalian hepatitis B X-interacting protein (HBXIP) drives the aggressiveness of breast cancer. Here, we are interested in the potential links between HBXIP and METTL3 in breast cancer. We showed that the expression of METTL3 was positively related to that of HBXIP in clinical breast cancer tissues. Moreover, HBXIP could up-regulate METTL3 in breast cancer cells. Mechanistically, HBXIP modulated METTL3 by inhibiting miRNA let-7g, which down-regulated the expression of METTL3 by targeting its 3'UTR. Strikingly, we found that METTL3 promoted the expression of HBXIP through m6A modification. Furthermore, overexpressed HBXIP could rescue the inhibited-proliferation and enhanced-apoptosis induced by silencing of METTL3 in breast cancer cells. Thus, we conclude that HBXIP up-regulates METTL3 by suppressing let-7g, in which METTL3 increased HBXIP expression forming a positive feedback loop of HBXIP/let-7g/METTL3/HBXIP, leading to accelerated cell proliferation in breast cancer. Our finding provides new insights into the mechanism of the mutual regulation between HBXIP and METTL3 in the progression of breast cancer.

e23531 Background: Standard treatment for patients with unresectable locally advanced or metastatic soft-tissue sarcoma is chemotherapy based on anthracyclines, while the tolerance of chemotherapy is limited. We assessed if anlotinib, a multitarget tyrosine kinase inhibitor, is efficacy and safety for the first-line treatment of these patients. Methods: This is an open-label, single-arm, multicenter, phase II clinical trial (NCT03792542) including 44 planned subjects. Eligible patients were aged 18-70 years old, diagnosed with locally advanced or metastatic soft-tissue sarcoma and had at least one measurable lesion according to RECIST 1.1. Other inclusion criteria included ECOG PS 0̃2, chemotherapy and anti-angiogenesis treatment naïve. Patients were administrated 12mg anlotinib once daily for 14 days every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Safety assessment was done in patients who received at least one dose of anlotinib. Here we report the results of a planned interim analysis. Results: From April 2019 to December 2020, 29 patients (16 males and 13 females) were enrolled from 7 hospitals in China. The median age is 57 (range 23-69). Pathological types included liposarcoma (n = 8), undifferentiated pleomorphic sarcoma (n = 5), fibrosarcoma (n = 5), synovial sarcoma (n = 4), and others (n = 7). At the data cutoff date on December 31, 2020, the median duration of treatment was 5.3 months, and the median PFS was not reached. 26 patients were eligible for the evaluation of tumor response.1 achieved partial response (PR) and the objective response rate (ORR) was 3.85% (1/26). 24 had stale disease (SD) and the disease control rate (DCR) was 96.2% (25/26). The clinical benefit rate (CBR), defined as the proportion of patients who achieved durable disease control (CR/PR/SD) more than 4 and 6 months, were 65.4% (17/26) and 38.5% (10/26) respectively. Most adverse events (AE) were grade 1 or 2. The most common grade 3 AE was hypertension (17.2%). No grade 4 AEs or treatment related death occurred in this study through the last follow-up. Conclusions: This interim analysis showed anlotinib of promising efficacy and favorable tolerance in the first-line treatment of locally advanced or metastatic soft- tissue sarcoma. Clinical trial information: NCT03792542.

Until now, the relationship of obstructive sleep apnoea (OSA) with diabetic retinopathy (DR) was controversial. This meta-analysis was performed to obtain definitive conclusion on this topic. Relevant articles were searched on databases of Pubmed, Google Scholar, and Chinese National Knowledge Infrastructure (CNKI). The articles were selected according to inclusion and exclusion criteria. Odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the relationship of OSA with risk of DR.I2andPvalue were used to assess the presence of heterogeneity.I2≥ 50% orP<0.05indicated significant heterogeneity. Sensitivity analysis was performed to evaluate the robustness of pooled results. Begg’s funnel plot and Egger’s regression analysis were adopted to assess publication bias. 6 eligible studies were selected in the present meta-analysis. The pooled results indicated that OSA was significantly associated with increased risk of DR (OR = 2.01, 95% CI = 1.49–2.72). Subgroup analysis based on type of diabetes mellitus suggested that OSA was related to DR in both Type 1 and Type 2 diabetes mellitus. Sensitivity analysis demonstrated that pooled results were robust. No significant publication bias was observed (P=0.128). The results indicate that OSA is related to increased risk of DR.

Branched chain α-keto acids (BCKAs) are endogenous metabolites of branched-chain amino acids (BCAAs). BCAA and BCKA are significantly elevated in pathologically stressed heart and contribute to chronic pathological remodeling and dysfunction. However, their direct impact on acute cardiac injury is unknown. Here, we demonstrated that elevated BCKAs significantly attenuated ischemia-reperfusion (I/R) injury and preserved post I/R function in isolated mouse hearts. BCKAs protected cardiomyocytes from oxidative stress-induced cell death in vitro. Mechanistically, BCKA protected oxidative stress induced cell death by inhibiting necrosis without affecting apoptosis or autophagy. Furthermore, BCKAs, but not BCAAs, protected mitochondria and energy production from oxidative injury. Finally, administration of BCKAs during reperfusion was sufficient to significantly attenuate cardiac I/R injury. These findings uncover an unexpected role of BCAAs metabolites in cardioprotection against acute ischemia/reperfusion injury, and demonstrate the potential use of BCKAs treatment to preserve ischemic tissue during reperfusion.

This study aimed to evaluate the efficacy of electroacupuncture (EA) on Ciliao (BL 32) and Zhongliao (BL 33) acupoints at different depths for the treatment of benign prostatic hyperplasia (BPH) through a single-blind randomized controlled trial. All 120 patients diagnosed with BPH were randomly allocated to an experimental group (deep insertion group, DI group, n = 60) and control group (shallow insertion group, SI group, n = 60) 3 times a week for 4 weeks. The observed results included the International Prostate Symptom Score (IPSS), Quality of Life score (QOL), maximum urine flow rate (Qmax), and postvoid residual urine volume (PVR). After treatment, at both depths, the BPH symptoms of patients were improved by EA. There were significant differences between the IPSS, QOL, and the effective rate of the experimental group and the control group (P<0.05). Although the observed PVR and Qmax were better than those before treatment, there was no statistical significance between two groups (P>0.05). Thus, EA with deep insertion can effectively improve the patients’ urinary symptoms and quality of life, and it will be suitable for clinical application.

Background Diagnosis of tuberculosis (TB) in children is challenging. Epidemiological data of childhood pulmonary tuberculosis (PTB) are urgently needed. Methods We described trends in epidemiology, clinical characteristics, and treatment outcomes in seven cities of Shandong province, China, during 2005–2017. Data were collected from the China Information System for Disease Control and Prevention. Results Among 6283 (2.4% of all PTB) PTB cases aged

Background Oral mucositis (OM), one of the most common side effects for cancer patients who have undergone chemotherapy, can cause severe impairment to patients' functional ability and impact their quality of life, resulting in delayed and/or incomplete treatment. Traditional Chinese medicine offers empirical herbal decoctions to gargle for the prevention of chemotherapy-induced OM; however, evidence for its clinical efficacy and safety is lacking. Therefore, we provide a protocol to evaluate the preventive effect and safety of Chinese herbal medicine mouthwash in chemotherapy-induced OM. Methods We will comprehensively retrieve relevant articles published till August 15, 2020, in the following electronic databases: the Cochrane Library, PubMed, EMBASE, Chinese National Knowledge Infrastructure Database, Chinese Biomedical Literature Database, Chinese Science and Technique Journals Database, and the Wan-fang Database. Only randomized controlled trials will be included. We will use the criteria provided by the Cochrane Handbook for quality assessment and risk assessment of the included studies and use the RevMan 5.3 software for meta-analysis of the preventive effect and safety. Results This study will assess the preventive effect and safety of Chinese herbal medicine mouthwash in chemotherapy-induced OM. Conclusion This systematic review will provide evidence-based medical corroboration for the clinical application of the Chinese herbal medicine mouthwash in chemotherapy-induced OM. Prospero registration number CRD42020206614.

Purpose: To develop and validate a delta-radiomics model for predicting a pathologic response after chemotherapy preoperatively in high-grade osteosarcoma (HOS). Materials and Methods: A total of 191 patients with HOS were enrolled retrospectively from November 2013 to November 2017 and received neoadjuvant chemotherapy. A cutoff time of November 2016 was used to divide the training set and validation set. All patients underwent diagnostic CTs before and after chemotherapy. By quantifying the tumor region on the two-phase CT images, 540 delta-radiomics features were calculated. A delta-radiomics signature was constructed using the lasso algorithm based on the training set. A radiomics nomogram was then developed from the multivariate logistic regression model by combining independent clinical factors and the delta-radiomics signature. The prediction accuracy was assessed according to receiver operating characteristic (ROC) and calibration curves. Results: The delta-radiomics signature, consisting of 8 selected features, showed significant differences between the pathologic good response (pGR) (necrosis fraction ≥90%) group and the non-pGR (necrosis fraction

Hand, foot and mouth disease (HFMD) has been a substantial burden throughout the Asia-Pacific countries over the past decades. For the purposes of disease prevention and climate change health impact assessment, it is important to understand the temperature–disease association for HFMD in different geographical locations. This study aims to assess the impact of temperature on HFMD incidence in an inland city and a coastal city and investigate the heterogeneity of temperature–disease associations. Daily morbidity data and meteorological variables of the study areas were collected for the period from 2007 to 2012. A total of 108,377 HFMD cases were included in this study. A distributed lag non-linear model (DLNM) with Poisson distribution was used to examine the nonlinear lagged effects of daily mean temperature on HFMD incidence. After controlling potential confounders, temperature showed significant association with HFMD incidence and the two cities demonstrated different impact modes ( I2= 96.1%, p &lt, 0.01). The results highlight the effect of temperature on HFMD incidence and the impact pattern may be modified by geographical localities. Our findings can be a practical reference for the early warning and intervention strategies of HFMD.

The glucose metabolism reprogramming is a hallmark of cancer. The oncoprotein hepatitis B X-interacting protein (HBXIP) functions in the development of breast cancer. In this study, we supposed that HBXIP might be involved in the glucose metabolism reprogramming in breast cancer. We showed that HBXIP led to increases in generation of intracellular glucose and lactate, as well as decreases in generation of reactive oxygen species. Expression of synthesis of cytochrome c oxidase 2 (SCO2) and pyruvate dehydrogenase alpha 1 (PDHA1), two factors of metabolic switch from oxidative phosphorylation to aerobic glycolysis, was suppressed by HBXIP. In addition, miR-183/182 and miR-96 directly inhibited the expression of SCO2 and PDHA1 through targeting their mRNA coding sequences (CDSs), respectively. Interestingly, HBXIP elevated the miR-183/96/182 cluster expression through hypoxia-inducible factor 1α (HIF1α). The stability of HIF1α was enhanced by HBXIP through disassociating interaction of von Hippel-Lindau protein (pVHL) with HIF1α. Moreover, miR-183 increased the levels of HIF1α protein through directly targeting CDS of VHL mRNA, forming a feedback loop of HIF1α/miR-183/pVHL/HIF1α. In function, HBXIP-elevated miR-183/96/182 cluster enhanced the glucose metabolism reprogramming in vitro. HBXIP-triggered glucose metabolism reprogramming promoted the growth of breast cancer in vivo. Thus, we conclude that the oncoprotein HBXIP enhances glucose metabolism reprogramming through suppressing SCO2 and PDHA1 in breast cancer.

Objectives: The aim of this study was to quantify the relationship between meteorological factors and the occurrence of hand, foot, and mouth disease (HFMD) among children in Shandong Province, China, at a county level, using spatial panel data models. Methods: Descriptive analysis was applied to describe the epidemic characteristics of HFMD from January 2008 to December 2012, and then a global autocorrelation statistic (Moran's I) was used to detect the spatial autocorrelation of HFMD in each year. Finally, spatial panel data models were performed to explore the association between the incidence of HFMD and meteorological factors. Results: Moran's I at the county level were high, from 0.30 to 0.45 (p

The objective of this study is to evaluate retrospectively the effectiveness of multiple-drug chemotherapeutics regimen that included high-dose methotrexate (HD-MTX) for treating primary osteosarcoma. 148 newly diagnosed patients with Stage I and II osteosarcoma who received HD-MTX/HD-MTX/DDP(cisplatin)/ADM(doxorubicin) and/or HD-MTX/IFO(Ifosfamide)/DDP/ADM before and after the surgery were retrospectively analyzed to measure the efficacy of this regimen. The significance of various variables as predictive prognostic factors of the patient survival rate was also evaluated. The overall 3-year survival rate of the patients was 79.73 %. The survival rate was improved to 85.71 % in the patients who received surgery and a complete 4-cycle chemotherapy. In addition, the rates of disease-free survival (DFS), local recurrence, and distant metastasis were 68.13, 3.30, and 10.81 %, respectively. Our analysis showed that completing 4-cycle chemotherapy produced a significant impact on the overall 3-year survival and DFS rates (P

We have reported that hepatitis B X-interacting protein (HBXIP, also termed LAMTOR5) can act as an oncogenic transcriptional co-activator to modulate gene expression, promoting breast cancer development. Pyruvate kinase muscle isozyme M2 (PKM2), encoded by PKM gene, has emerged as a key oncoprotein in breast cancer. Yet, the regulatory mechanism of PKM2 is still unexplored. Here, we report that HBXIP can upregulate PKM2 to accelerate proliferation of estrogen receptor positive (ER+) breast cancer. Immunohistochemistry analysis using breast cancer tissue microarray uncovered a positive association between the expression of HBXIP and PKM2. We also discovered that PKM2 expression was positively related with HBXIP expression in clinical breast cancer patients by real-time PCR assay. Interestingly, in ER+ breast cancer cells, HBXIP was capable of upregulating PKM2 expression at mRNA and protein levels in a dose-dependent manner, as well as increasing the activity of PKM promoter. Mechanistically, HBXIP could stimulate PKM promoter through binding to the -779/-579 promoter region involving co-activation of E2F transcription factor 1 (E2F1). In function, cell viability, EdU, colony formation, and xenograft tumor growth assays showed that HBXIP contributed to accelerating cell proliferation through PKM2 in ER+ breast cancer. Collectively, we conclude that HBXIP induces PKM2 through transcription factor E2F1 to facilitate ER+ breast cancer cell proliferation. We provide new evidence for the mechanism of transcription regulation of PKM2 in promotion of breast cancer progression.

Background Feicheng County is a high-risk area for esophageal cancer in Shandong province, China. It is important to determine the long-term spatio-temporal trends in epidemiological characteristics and the burden of esophageal cancer, especially since the implementation of the national esophageal cancer screening program for early detection and treatment in 2005. Methods The data collected in Feicheng County from 2001 to 2012 was extracted from the whole-population cancer registry system. The incidence, mortality, disability-adjusted life years (DALY) and changing trends in esophageal cancer according to age and sex were calculated and described. Results The incidence rate of esophageal cancer in Feicheng was consistently high, and increased significantly for male, but not for female from 2001 to 2012, according to the joinpoint regression analysis. The highest and lowest yearly crude incidence rates were 160.78 and 95.97 per 100000 for males, and 81.36 and 52.17 per 100000 for females. The highest and lowest crude yearly mortality rates were 122.26 and 94.40 per 100000 for males, and 60.75 and 49.35 per 100000for females. Esophageal squamous cell carcinoma was the main pathology type and the tumor location changed significantly from 2001 to 2012. Overall, the DALY remained roughly stable and was estimated as 11.50 for males and 4.90 for females per 1000 people. The burden was mainly caused by premature death. There is an obvious spatial pattern in the distribution of incidence density and burden. Conclusion Esophageal cancer remains a public health issue in Feicheng County with a high incidence, mortality and disease burden. The incidence and burden have obvious spatial heterogeneity, and further studies should be conducted to identify geographical risk factors for precise local prevention and control measures.

Epileptic seizure detection is the most important part in the diagnosis of epilepsy. The automatic detection and classification of epileptic EEG signals has great clinical significance. This paper proposes a novel method for epileptic seizure detection using empirical mode decomposition (EMD) and sparse representation based classification (SRC). Firstly, EMD was used to decompose EEG into multiple Intrinsic Mode Function (IMF) components. Secondly, the features like variation coefficient, fluctuation index, relative energy and relative amplitude were extracted from the IMFs. Finally, in the framework of sparse representation based classification (SRC), the feature vectors of test sample were represented as a linear combination of the feature vector of training samples with sparse coefficients. Experimental results show that the time consumed by one epileptic EEG test sample is not more than 5.9 s, and the accuracy is up to 97.5%. In SRC, the raw EEG signals were replaced by extracted features, which could reduce data dimension and computational cost. The algorithm has a good performance in the recognition of ictal EEG. The higher recognition rate and fast speed make the method suit for the diagnosis of epilepsy in clinical application.

Anaplastic thyroid carcinoma (ATC) is a severe thyroid malignancy with poor prognosis, due to its early metastasis and unresponsiveness to both radiation and chemotherapy. Nevirapine, a non-nucleoside reverse transcriptase inhibitor, has been used as a re-differentiation agent to treat cancers in several human cancer models. So far, the effects of nevirapine on human thyroid anaplastic carcinoma cells have not been documented. The aim of this study was to evaluate the therapeutic potential of nevirapine in treatment of human thyroid anaplastic carcinoma. Cell proliferation was determined by methly thiazolyl tetrazolium (MTT) assay. Cell apoptosis was analyzed by Hoechst 33258 staining. The mRNA expression of NIS and TSHR was determined by real-time quantitative reverse transcription-polymerase chain reaction (real time RT-PCR). Iodine uptake was determined by (125)I radioactivity assay. At all doses (100, 200, 350, 500 μmol/L) tested, nevirapine significantly inhibited cell proliferation after 48 h treatment. At high dose (500 μmol/L), nevirapine significantly increased the percentage of apoptotic cells compared with control (P

It has been reported that over-expression of GRP75 can protect cells under different types of stress. In this study, we investigated the protective effect of GRP75 on the liver both in vivo and in vitro. To evaluate the effect of GRP75 over-expression on oxidative damage in the liver in vitro, cell viability and the mitochondrial function of GRP75-overexpressing HL-7702 cells and control transfected cells were monitored during H(2)O(2) treatment. In vivo, liver fibrosis was induced in rats by carbon tetrachloride (CCl(4)) injection for 8 weeks. The GRP75-overexpressing vector was randomly injected into rats before fibrosis was established to study the inhibitory effect of GRP75 on hepatic fibrosis. Liver injury and mitochondrial function were assessed. On H(2)O(2) treatment, GRP75-overexpressing HL-7702 cells exhibited more moderate cell damage than control HL-7702 cells. Both groups of cells showed a decrease in ATP following an early increase on H(2)O(2) treatment, and the mitochondrial membrane potential also decreased similarly in these two groups of cells. Control HL-7702 cells showed an immediate and rapid increase in reactive oxygen species accumulation after the onset of H(2)O(2) treatment, and this accumulation was slowed and reduced in GRP75-overexpressing cells. Western blotting revealed that cytochrome c was greater in control HL-7702 cells than in GRP75-overexpressing HL-7702 cells. Compared with the CCl(4)-only rats, serum alanine transaminase and aspartate aminotransferase were significantly lower in CCl(4)-treated rats transfected with the GRP75 vector (P < 0.01). ATP concentrations decreased in both groups of rats treated with CCl(4), but were higher in the GRP75-overexpressing CCl(4)-treated group than in CCl(4)-only rats. Cytochrome c expression was lower in GRP75-overexpressing rats than in CCl(4)-only rats.

Chronic infection of hepatitis B virus (HBV) is closely associated with the development of hepatocellular carcinoma (HCC). Meta-analyses show that adjuvant anti-HBV therapy is effective for HBV-related HCC patients in clinical. However, the significance that anti-HBV drugs depress HCC is poorly understood. Here, we investigated the effects of telbivudine (LdT), entecavir (ETV) and interferon-α2b (IFN-α2b) on HBV-related HCC. Our data showed that the treatment with the drugs significantly suppressed the growth of HBV-expressing hepatoma cells in vitro and in vivo, but failed to work in HBV-free liver cells. We present the hypothesis that HBx may be involved in the event. As expected, we observed that the expression of HBx was down-regulated by the agents. Meanwhile, the expression of HBx downstream factors was significantly down-regulated. Interestingly, LdT, ETV and IFN-α2b lost the anti-proliferation effects on HBV-related hepatoma cells when the cells were treated with HBx siRNA. Moreover, combination of those drugs enhanced the anti-proliferation effects. In conclusion, LdT, ETV and IFN-α2b suppress the growth of HBV-related HCC through down-regulation of HBx. Our finding provides new insights into the mechanisms of anti-HBV drugs in HCC therapy.

Background— Although metabolic reprogramming is critical in the pathogenesis of heart failure, studies to date have focused principally on fatty acid and glucose metabolism. Contribution of amino acid metabolic regulation in the disease remains understudied. Methods and Results— Transcriptomic and metabolomic analyses were performed in mouse failing heart induced by pressure overload. Suppression of branched-chain amino acid (BCAA) catabolic gene expression along with concomitant tissue accumulation of branched-chain α-keto acids was identified as a significant signature of metabolic reprogramming in mouse failing hearts and validated to be shared in human cardiomyopathy hearts. Molecular and genetic evidence identified the transcription factor Krüppel-like factor 15 as a key upstream regulator of the BCAA catabolic regulation in the heart. Studies using a genetic mouse model revealed that BCAA catabolic defect promoted heart failure associated with induced oxidative stress and metabolic disturbance in response to mechanical overload. Mechanistically, elevated branched-chain α-keto acids directly suppressed respiration and induced superoxide production in isolated mitochondria. Finally, pharmacological enhancement of branched-chain α-keto acid dehydrogenase activity significantly blunted cardiac dysfunction after pressure overload. Conclusions— BCAA catabolic defect is a metabolic hallmark of failing heart resulting from Krüppel-like factor 15–mediated transcriptional reprogramming. BCAA catabolic defect imposes a previously unappreciated significant contribution to heart failure.

Background Multidrug-resistant tuberculosis (MDR-TB) resulting from various factors has raised serious public health concerns worldwide. Identifying the ecological risk factors associated with MDR-TB is critical to its prevention and control. This study aimed to explore the association between the development of MDR-TB and the risk factors at the group-level (ecological risk factors) in China. Methods Data on MDR-TB in 120 counties were obtained from the National Tuberculosis Information Management System, and data on risk-factor variables were extracted from the Health Statistical Yearbook, provincial databases, and the meteorological bureau of each province (municipality). Partial Least Square Path Modeling was used to detect the associations. Results The median proportion of MDR-TB in new TB cases was 3.96% (range, 0–39.39%). Six latent factors were extracted from the ecological risk factors, which explained 27.60% of the total variance overall in the prevalence of MDR-TB. Based on the results of PLS-PM, TB prevention, health resources, health services, TB treatment, TB detection, geography and climate factors were all associated with the risk of MDR-TB, but socioeconomic factors were not significant. Conclusions The development of MDR-TB was influenced by TB prevention, health resources, health services, TB treatment, TB detection, geography and climate factors. Such information may help us to establish appropriate public health intervention strategies to prevent and control MDR-TB and yield benefits to the entire public health system in China.

Tumor angiogenesis plays an important role in the development of cancer. Previously, we reported that hepatitis B X-interacting protein (HBXIP) functioned as an oncoprotein in breast cancer. However, the role of HBXIP in angiogenesis in breast cancer remains poorly understood. In the present study, we show that the oncoprotein HBXIP plays crucial roles in the event. We observed that the expression levels of HBXIP were positively correlated with those of fibroblast growth factor 8 (FGF8) or vascular endothelial growth factor (VEGF) in clinical breast cancer tissues. Then, we demonstrated that HBXIP was able to upregulate FGF8 through activation of its promoter involving direct binding to cAMP response element-binding protein (CREB) in breast cancer cells and thereby increased its secretion. Strikingly, we identified another pathway that HBXIP upregulated FGF8 and VEGF through inhibiting miRNA-503, which directly targeted 3' untranslated region of FGF8 or VEGF mRNA in the cells. Moreover, we revealed that HBXIP-induced FGF8 could upregulate VEGF expression through activating phosphoinositide 3-kinase (PI3K)/Akt/hypoxia-inducible factor 1-alpha (HIF1α) signaling and increase its secretion. In function, matrigel angiogenesis assay and hemoglobin content analysis uncovered that HBXIP-enhanced FGF8/VEGF boosted tumor angiogenesis and growth in breast cancer in vitro and in vivo in a paracrine/autocrine manner. Thus, we conclude that HBXIP enhances angiogenesis and growth of breast cancer through modulating FGF8 and VEGF. Our finding provides new insights into the mechanism of tumor angiogenesis in breast cancer. Therapeutically, HBXIP may serve as a novel target of tumor angiogenesis.

Background Hand, foot, and mouth disease (HFMD) has caused major public health concerns worldwide, and has become one of the leading causes of children death. China is the most serious epidemic area with a total of 3,419,149 reported cases just from 2008 to 2010, and its different geographic areas might have different spatial epidemiology characteristics at different spatial-temporal scale levels. We conducted spatial and spatial-temporal epidemiology analysis to HFMD at county level in Shandong Province, China. Methods Based on the China National Disease Surveillance Reporting and Management System, the spatial-temporal database of HFMD from 2007 to 2011 was built. The global autocorrelation statistic (Moran’s I) was first used to detect the spatial autocorrelation of HFMD cases in each year. Purely Spatial scan statistics combined with Space-time scan statistic were used to detect epidemic clusters. Results The annual average incidence rate was 93.70 per 100,000 in Shandong Province. Most HFMD cases (93.94%) were aged within 0–5 years old with an average male-to-female sex ratio 1.71, and the incidence seasonal peak was between April and July. The dominant pathogen was EV71 (47.35%), and CoxA16 (26.59%). HFMD had positive spatial autocorrelation at medium spatial scale level (county level) with higher Moran’s I from 0.31 to 0.62 (P

Background Traditional herbal therapies have been used for a long time to treat gastrointestinal disorders including irritable bowel syndrome, and their effectiveness from clinical research evidence needs to be systematically reviewed. Objectives To assess the effectiveness and safety of herbal medicines in patients with irritable bowel syndrome. Search methods We searched the following electronic databases till July 2004: The Cochrane Library (CENTRAL), MEDLINE, EMBASE, AMED, LILACS, the Chinese Biomedical Database, combined with hand searches of Chinese journals and conference proceedings till end of 2003. No language restriction was used. Selection criteria Randomised controlled trials of herbal medicines compared with no treatment, placebo, pharmacological interventions were included. Data collection and analysis Data were extracted independently by two authors. The methodological quality of trials was evaluated using the components of randomisation, allocation concealment, double blinding, and inclusion of randomised participants. Main results Seventy-five randomised trials, involving 7957 participants with irritable bowel syndrome, met the inclusion criteria. The methodological quality of three double-blind, placebo-controlled trials was high, but the quality of remaining trials was generally low. Seventy-one different herbal medicines were tested in the included trials, in which herbal medicines were compared with placebo or conventional pharmacologic therapy. Herbal medicines were also combined with conventional therapy and compared to conventional therapy alone. Compared with placebo, a Standard Chinese herbal formula, individualised Chinese herbal medicine, STW 5 and STW 5-II, Tibetan herbal medicine Padma Lax, traditional Chinese formula Tongxie Yaofang, and Ayurvedic preparation showed significantly improvement of global symptoms. Compared with conventional therapy in 65 trials testing 51 different herbal medicines, 22 herbal medicines demonstrated a statistically significant benefit for symptom improvement, and 29 herbal medicines were not significantly different than conventional therapy. In nine trials that evaluated herbal medicine combined with conventional therapy, six tested herbal preparations showed additional benefit from the combination therapy compared with conventional monotherapy. No serious adverse events from the herbal medicines were reported. Authors' conclusions Some herbal medicines may improve the symptoms of irritable bowel syndrome. However, positive findings from less rigorous trials should be interpreted with caution due to inadequate methodology, small sample sizes, and lack of confirming data. Some herbal medicines deserve further examination in high-quality trials.

Background : The current prevalence of tuberculosis (TB) in the People’s Republic of China (P. R. China) demonstrates geographical heterogeneities, which show that the TB prevalence in the remote areas of Western China is more serious than that in the coastal plain of Eastern China. Although a lot of ecological studies have been applied in the exploration on the regional difference of disease risks, there is still a paucity of ecological studies on TB prevalence in P. R. China. Objective : To understand the underlying factors contributing to the regional inequity of TB burden in P. R. China by using an ecological approach and, thus, aiming to provide a basis to eliminate the TB spatial heterogeneity in the near future. Design : Latent ecological variables were identified by using exploratory factor analysis from data obtained from four sources, i.e. the databases of the National TB Control Programme (2001–2010) in P. R. China, the China Health Statistical Yearbook during 2002–2011, the China Statistical Yearbook during 2002–2011, and the provincial government websites in 2013. Partial least squares path modelling was chosen to construct the structural equation model to evaluate the relationship between TB prevalence and ecological variables. Furthermore, a geographically weighted regression model was used to explore the local spatial heterogeneity in the relationships. Results : The latent ecological variables in terms of ‘TB prevalence’, ‘TB investment’, ‘TB service’, ‘health investment’, ‘health level’, ‘economic level’, ‘air quality’, ‘climatic factor’ and ‘geographic factor’ were identified. With the exception of TB service and health levels, other ecological factors had explicit and significant impacts on TB prevalence to varying degrees. Additionally, each ecological factor had different impacts on TB prevalence in different regions significantly. Conclusion : Ecological factors that were found predictive of TB prevalence in P. R. China are essential to take into account in the formulation of locally comprehensive strategies and interventions aiming to tailor the TB control and prevention programme into local settings in each ecozone. Keywords : tuberculosis; prevalence; ecological factor; spatial heterogeneity; P. R. China (Published: 12 June 2014) Citation : Glob Health Action 2014, 7 : 23620 - http://dx.doi.org/10.3402/gha.v7.23620 Supplementary material : To access the supplementary material for this article, please see Supplementary files under Article Tools

Summary Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus. The spatial distribution has continued to expand, while the areas at potential high risk of SFTS have, to date, remained unclear. Methods Using ecological factors as predictors, the MaxEnt model was first trained based on the locations of human SFTS occurrence in Shandong Province. The risk prediction map of China was then created by projecting the training model onto the whole country. The performance of the model was assessed using the known locations of disease occurrence in China. Results The key environmental factors affecting SFTS occurrence were temperature, precipitation, land cover, normalized difference vegetation index (NDVI), and duration of sunshine. The risk prediction maps suggested that central, southwestern, northeastern, and the eastern coast of China are potential areas at high risk of SFTS. Conclusions The potential high risk SFTS areas are distributed widely in China. The epidemiological surveillance system should be enhanced in these high risk regions.

Background Chinese herbal medicines have been used for a long time to treat osteoporosis. The evidence of their benefits and harms needs to be systematically reviewed. Objectives To assess the beneficial and harmful effects of Chinese herbal medicines as a general experimental intervention for treating primary osteoporosis by comparing herbal treatments with placebo, no intervention and conventional medicine. Search methods We searched the following electronic databases to January 2013: the Specialised Register of the Cochrane Complementary Medicine Field, CENTRAL, MEDLINE, EMBASE, LILACS, JICST-E, AMED, Chinese Biomedical Database and CINAHL. Selection criteria Randomised controlled trials of Chinese herbal medicines compared with placebo, no intervention or conventional medicine were included. Data collection and analysis Two authors extracted data and assessed risk of bias independently. Disagreement was resolved by discussion. Main results One hundred and eight randomised trials involving 10,655 participants were included. Ninety-nine different Chinese herbal medicines were tested and compared with placebo (three trials), no intervention (five trials) or conventional medicine (61 trials), or Chinese herbal medicines plus western medicine were compared with western medicine (47 trials). The risk of bias across all studies was unclear for most domains primarily due to inadequate reporting of study design. Although we rated the risk of selective reporting for all studies as unclear, only a few studies contributed numerical data to the key outcomes. Seven trials reported fracture incidence, but they were small in sample size, suffered from various biases and tested different Chinese herbal medicines. These trials compared Kanggusong capsules versus placebo, Kanggusong granule versus Caltrate or ipriflavone plus Caltrate, Yigu capsule plus calcium versus placebo plus calcium, Xianlinggubao capsule plus Caltrate versus placebo plus Caltrate, Bushen Zhuanggu granules plus Caltrate versus placebo granules plus Caltrate, Kanggusong soup plus Caltrate versus Caltrate, Zhuangguqiangjin tablets and Shujinbogu tablets plus calcitonin ampoule versus calcitonin ampoule. The results were inconsistent. One trial showed that Bushenhuoxue therapy plus calcium carbonate tablets and alfacalcidol had a better effect on quality of life score (scale 0 to 100, higher is better) than calcium carbonate tablets and alfacalcidol (mean difference (MD) 5.30; 95% confidence interval (CI) 3.67 to 6.93). Compared with placebo in three separate trials, Chinese herbal medicines (Migu decoction, Bushen Yigu soft extract, Kanggusong capsules) showed a statistically significant increase in bone mineral density (BMD) (e.g. Kanggusong capsules, MD 0.06 g/cm3; 95% CI 0.02 to 0.10). Compared with no intervention in five trials, only two showed that Chinese herbal medicines had a statistically significant effect on increase in BMD (e.g. Shigu yin, MD 0.08 g/cm3; 95% CI 0.03 to 0.13). Compared with conventional medicine in 61 trials, 23 showed that Chinese herbal medicines had a statistically significant effect on increase in BMD. In 48 trials evaluating Chinese herbal medicines plus western medication against western medication, 26 showed better effects of the combination therapy on increase in BMD. No trial reported death or serious adverse events of Chinese herbal medicines, while some trials reported minor adverse effects such as nausea, diarrhoea, etc. Authors' conclusions Current findings suggest that the beneficial effect of Chinese herbal medicines in improving BMD is still uncertain and more rigorous studies are warranted.