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The Cochrane Database of Systematic... Nov 2019Chronic hepatitis B is associated with high morbidity and mortality. Chronic hepatitis B requires long-term management aiming at reduction of the risks of hepatocellular... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic hepatitis B is associated with high morbidity and mortality. Chronic hepatitis B requires long-term management aiming at reduction of the risks of hepatocellular inflammatory necrosis, liver fibrosis, decompensated liver cirrhosis, liver failure, and liver cancer, and improving health-related quality of life. The Chinese herbal medicine formula Xiao Chai Hu Tang has been used to decrease discomfort and replication of the virus in people with chronic hepatitis B. However, the benefits and harms of Xiao Chai Hu Tang formula have never been established with rigorous review methodology.
OBJECTIVES
To assess the benefits and harms of Xiao Chai Hu Tang formula versus placebo or no intervention in people with chronic hepatitis B.
SEARCH METHODS
We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, and seven other databases to 1 March 2019. We also searched the World Health Organization International Clinical Trials Registry Platform (www.who.int/ictrp), ClinicalTrials.gov (www.clinicaltrials.gov/), and the Chinese Clinical Trial Registry for ongoing or unpublished trials to 1 March 2019.
SELECTION CRITERIA
We included randomised clinical trials, irrespective of publication status, language, and blinding, comparing Xiao Chai Hu Tang formula versus no intervention or placebo in people with chronic hepatitis B. We included participants of any sex and age, diagnosed with chronic hepatitis B according to guidelines or as defined by the trialists. We allowed co-interventions when the co-interventions were administered equally to all the intervention groups.
DATA COLLECTION AND ANALYSIS
Review authors independently retrieved data from reports and after correspondence with investigators. Our primary outcomes were all-cause mortality, serious adverse events, and health-related quality of life. Our secondary outcomes were hepatitis B-related mortality, hepatitis B-related morbidity, and adverse events considered 'not to be serious'. We presented the meta-analysed results as risk ratios (RR) with 95% confidence intervals (CI). We assessed the risks of bias using risk of bias domains with predefined definitions. We used GRADE methodology to evaluate our certainty in the evidence.
MAIN RESULTS
We included 10 randomised clinical trials with 934 participants, but only five trials with 490 participants provided data for analysis. All the trials compared Xiao Chai Hu Tang formula with no intervention. All trials appeared to have been conducted and published only in China. The included trials assessed heterogeneous forms of Xiao Chai Hu Tang formula, administered for three to eight months. One trial included participants with hepatitis B and comorbid tuberculosis, and one trial included participants with hepatitis B and liver cirrhosis. The remaining trials included participants with hepatitis B only. All the trials were at high risk of bias, and the certainty of evidence for all outcomes that provided data for analyses was very low. We downgraded the evidence by one or two levels because of outcome risk of bias, inconsistency or heterogeneity of results (opposite direction of effect), indirectness of evidence (use of surrogate outcomes instead of clinically relevant outcomes), imprecision of results (the CIs were wide), and publication bias (small sample size of the trials). Additionally, 47 trials lacked the necessary methodological information needed to ensure the inclusion of these trials in our review. None of the included trials aimed to assess clinically relevant outcomes such as all-cause mortality, serious adverse events, health-related quality of life, hepatitis B-related mortality, or hepatitis B-related morbidity. The effects of Xiao Chai Hu Tang formula on the proportion of participants with adverse events considered 'not to be serious' is uncertain (RR 0.43, 95% CI 0.02 to 11.98; I = 69%; very low-certainty evidence). Only three trials with 222 participants reported the proportion of people with detectable hepatitis B virus DNA (HBV-DNA), but the evidence that Xiao Chai Hu Tang formula reduces the presence of HBV-DNA in the blood (a surrogate outcome) is uncertain (RR 0.62, 95% CI 0.45 to 0.85; I = 0%; very low-certainty evidence). Only two trials with 160 participants reported the proportion of people with detectable hepatitis B virus e-antigen (HBeAg; a surrogate outcome) (RR 0.72, 95% CI 0.50 to 1.02; I = 38%; very low-certainty evidence) and the evidence is uncertain. The evidence is also uncertain for separately reported adverse events considered 'not to be serious'.
FUNDING
two of the 10 included trials received academic funding from government or hospital. None of the remaining eight trials reported information on funding.
AUTHORS' CONCLUSIONS
The clinical effects of Xiao Chai Hu Tang formula for chronic hepatitis B remain unclear. The included trials were small and of low methodological quality. Despite the wide use of Xiao Chai Hu Tang formula, we lack data on all-cause mortality, serious adverse events, health-related quality of life, hepatitis B-related mortality, and hepatitis B-related morbidity. The evidence in this systematic review comes from data obtained from a maximum three trials. We graded the certainty of evidence as very low for adverse events considered not to be serious and the surrogate outcomes HBeAg and HBV-DNA. We found a large number of trials which lacked clear description of their design and conduct, and hence, these trials are not included in the present review. As all identified trials were conducted in China, there might be a concern about the applicability of this review outside China. Large-sized, high-quality randomised sham-controlled trials with homogeneous groups of participants and transparent funding are lacking.
Topics: Drugs, Chinese Herbal; Hepatitis B, Chronic; Herbal Medicine; Humans; Phytotherapy; Randomized Controlled Trials as Topic
PubMed: 31697415
DOI: 10.1002/14651858.CD013090.pub2 -
Medicine Dec 2021DNA damage is a fundamental process that plays a considerable role in generating protein diversity. FANCI, loaded on the altered chromatin, plays a vital role in DNA... (Meta-Analysis)
Meta-Analysis
BACKGROUND
DNA damage is a fundamental process that plays a considerable role in generating protein diversity. FANCI, loaded on the altered chromatin, plays a vital role in DNA damage. Abnormal FANCI expression is potentially associated with carcinogenesis.However, the biological role of FANCI in cervical cancer is yet to be determined.
METHODS
We analyzed FANCI expression via multiple gene expression databases. Genes co-expressed with FANCI and its regulators were identified using LinkedOmics. The correlations between FANCI and cancer immune infiltrates were investigated via Tumor Immune Estimation Resource (TIMER).
RESULTS
FANCI was found upregulated with amplification in tumor tissues of multiple cervical cancer cohorts. High FANCI expression was associated with poorer overall survival (OS). Functional network analysis suggested that FANCI regulates spliceosome, DNA replication, and cell cycle signaling via pathways involving several cancer-related kinases and the E2F family. In additional, FANCI expression was positively correlated with infiltrating levels of CD4+ T and CD8+ T cells, and neutrophils. FANCI expression also showed strong correlations with diverse immune marker sets in cervical cancer.
CONCLUSION
These findings suggested that FANCI is correlated with prognosis of and immune infiltration in cervical cancer, laying a foundation for further study of the immune regulatory role of FANCI in cervical cancer.
Topics: Biomarkers, Tumor; CD8-Positive T-Lymphocytes; Fanconi Anemia Complementation Group Proteins; Female; Gene Expression Regulation; Humans; Lymphocytes, Tumor-Infiltrating; Prognosis; Uterine Cervical Neoplasms
PubMed: 34941027
DOI: 10.1097/MD.0000000000027690 -
Molecular Psychiatry Jul 2022Telomere length may serve as a biomarker of cellular aging. The literature assessing telomere length in schizophrenia contains conflicting results. (Meta-Analysis)
Meta-Analysis
CONTEXT
Telomere length may serve as a biomarker of cellular aging. The literature assessing telomere length in schizophrenia contains conflicting results.
OBJECTIVE
To assess differences in leukocyte telomere length (LTL) in peripheral blood in patients with schizophrenia and related disorders and healthy controls and to explore the effect of potential confounding variables.
DATA SOURCES
A search of Ovid MEDLINE, and Proquest databases was conducted to identify appropriate studies published from database inception through December 2020. The review protocol was registered with PROSPERO-ID: CRD42021233280.
STUDY SELECTION
The initial literature search yielded 192 studies. After study selection in 3 phases, we included 29 samples from 22 studies in the meta-analysis database.
DATA EXTRACTION
We used random effects and meta-regression models to derive Cohen d values with pooled 95% confidence intervals (CI) as estimates of effect size (ES) and to test effects of potential moderators.
RESULTS
The overall meta-analysis included 4145 patients with schizophrenia and related disorders and 4184 healthy controls and showed that LTL was significantly shorter in patients, with a small to medium effect size (ES, -0.388; 95% CI, -0.492 to -0.283; p < 0.001). Subgroup meta-analyses did not find a significant effect of age or illness duration on differences in LTL in patients with psychosis relative to controls. Meta-regression analyses showed that none of the putative moderators had a significant effect on effect size estimates.
CONCLUSIONS
This meta-analysis find further support for the hypothesis of accelerated cellular aging in schizophrenia and related disorders and highlights the need for large longitudinal studies with repeated LTL measurements over time and appropriate assessments of associated factors.
Topics: Case-Control Studies; Humans; Leukocytes; Psychotic Disorders; Schizophrenia; Telomere; Telomere Shortening
PubMed: 35393557
DOI: 10.1038/s41380-022-01541-7 -
Indian Journal of Otolaryngology and... Mar 2023The histopathological investigations of oral lesions are a basic approach for diagnosing ongoing cancer or pre-cancer associated pathological attributes in the dissected...
UNLABELLED
The histopathological investigations of oral lesions are a basic approach for diagnosing ongoing cancer or pre-cancer associated pathological attributes in the dissected biopsy. The early detection and management of potentially malignant disorders of the lip and oral cavity that require intervention may reduce malignant transformations, or in case any malignancy is detected during surveillance, the appropriate treatment may improve survival rates. This would guide the clinicians to decide the appropriate treatment modality or lesion to achieve a more favorable prognosis. MCM2 protein is involved in DNA replication providing additional information about the prognosis of neoplasms. Some authors have pointed out that MCM proteins have been inversely correlated with salivary tumour differentiation and therefore could be an indicator of proliferation potential. Therefore, it is essential to find the expression of the MCM2 gene in oral leukoplakia and oral squamous cell carcinoma. Electronic databases like Ebscohost, Livivo, Google Scholar and PubMed were searched. Based on the inclusion and exclusion criteria, 2 reviewers (MS and SN) independently selected the relevant articles. Any disagreement was discussed until a consensus was reached. We used the QUADAS-2 tool to assess the quality of the included studies over four key domains: patient selection, index test, reference standard and flow and timing of participants through the study. 10 out of 57 titles were found to meet the eligibility criteria. Biopsied tissue with immunohistochemical staining or advanced diagnostic studies were included. A total of 901 samples were included in the study and different groups were normal oral mucosa (NOM), oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). MCM2 proteins are useful diagnostic markers for distinguishing malignant from benign epithelial dysplasia and for early detection and diagnosis of OSCC as an adjunct to clinicopathological parameters.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s12070-022-03296-7.
PubMed: 37007886
DOI: 10.1007/s12070-022-03296-7 -
AIDS Reviews Oct 2020Antiretroviral therapy (ART) inhibits HIV replication but does not eradicate the latent reservoir. The previous research suggests that earlier ART initiation provides...
Antiretroviral therapy (ART) inhibits HIV replication but does not eradicate the latent reservoir. The previous research suggests that earlier ART initiation provides benefit on limiting reservoir size, but timing and extent of this effect remain unclear. Analytic treatment interruption (ATI) may be used to demonstrate HIV remission, but whether early ART also improves likelihood or duration of even temporary virologic remission is unclear. This review seeks to answer both questions. We performed a systematic review and analysis following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and included 21 interventional or observational studies with sufficient HIV reservoir outcomes. We also aggregated reservoir outcomes and transformed data into approximate measurements of total HIV DNA per million peripheral blood mononuclear cells and analyzed the correlation between timing of ART initiation and reservoir size. People living with HIV who initiate ART in primary infection maintain smaller reservoirs on suppressive ART than those who initiate treatment during chronic infection. The reduction of reservoir is most pronounced when ART is started within 2 weeks of HIV acquisition. Across studies, we found a moderately strong association between longer time to ART initiation and reservoir size, which was strongest when measured after 1 year on ART (Pearson's r = 0.69, p = 0.0003). After ATI, larger pre-ATI reservoir size predicts shorter time to viral rebound. Early ART may also facilitate long-term control of viremia. Although achieving sustained HIV remission will require further interventions, initiating ART very early in infection could limit the extent of the reservoir and also lead to post-ATI control in rare cases.
Topics: Anti-Retroviral Agents; HIV Infections; HIV-1; Humans; Leukocytes, Mononuclear; Viral Load; Virus Latency
PubMed: 33105471
DOI: 10.24875/AIDSRev.20000001 -
Neuropsychopharmacology : Official... Mar 2022We searched PubMed for primary research quantifying drug modification of light-induced circadian phase-shifting in rodents. This search, conducted for work published...
We searched PubMed for primary research quantifying drug modification of light-induced circadian phase-shifting in rodents. This search, conducted for work published between 1960 and 2018, yielded a total of 146 papers reporting results from 901 studies. Relevant articles were those with any extractable data on phase resetting in wildtype (non-trait selected) rodents administered a drug, alongside a vehicle/control group, near or at the time of exposure. Most circadian pharmacology experiments were done using drugs thought to act directly on either the brain's central pacemaker, the suprachiasmatic nucleus (SCN), the SCN's primary relay, the retinohypothalamic tract, secondary pathways originating from the medial/dorsal raphe nuclei and intergeniculate leaflet, or the brain's sleep-arousal centers. While the neurotransmitter systems underlying these circuits were of particular interest, including those involving glutamate, gamma-aminobutyric acid, serotonin, and acetylcholine, other signaling modalities have also been assessed, including agonists and antagonists of receptors linked to dopamine, histamine, endocannabinoids, adenosine, opioids, and second-messenger pathways downstream of glutamate receptor activation. In an effort to identify drugs that unduly influence circadian responses to light, we quantified the net effects of each drug class by ratioing the size of the phase-shift observed after administration to that observed with vehicle in a given experiment. This allowed us to organize data across the literature, compare the relative efficacy of one mechanism versus another, and clarify which drugs might best suppress or potentiate phase resetting. Aggregation of the available data in this manner suggested that several candidates might be clinically relevant as auxiliary treatments to suppress ectopic light responses during shiftwork or amplify the circadian effects of timed bright light therapy. Future empirical research will be necessary to validate these possibilities.
Topics: Circadian Rhythm; Pharmaceutical Preparations; S Phase; Serotonin; Suprachiasmatic Nucleus
PubMed: 34961774
DOI: 10.1038/s41386-021-01251-8 -
Advances in Nutrition (Bethesda, Md.) May 2020Diet, physical activity, and other lifestyle factors have been implicated in the pathophysiology of several chronic diseases, but also in a lower total mortality and...
Diet, physical activity, and other lifestyle factors have been implicated in the pathophysiology of several chronic diseases, but also in a lower total mortality and longer life expectancy. One of the mechanisms in which diet can reduce the risk of disease is with regard to its impact on telomeres. Telomere length (TL) is highly correlated to chronological age and metabolic status. Individuals with shorter telomeres are at higher risk of chronic diseases and mortality. Diet may influence TL by several mechanisms such as regulating oxidative stress and inflammation or modulating epigenetic reactions. The present systematic review aims to examine the results from epidemiologic and clinical trials conducted in humans evaluating the role of nutrients, food groups, and dietary patterns on TL. We also discuss the possible mechanisms of action that influence this process, with the perspective that TL could be a novel biomarker indicating the risk of metabolic disturbances and age-related diseases. The available evidence suggests that some antioxidant nutrients, the consumption of fruits and vegetables, and Mediterranean diet are mainly associated with longer telomeres. However, most of the evidence is based on high heterogenic observational studies and very few randomized clinical trials (RCTs). Therefore, the associations summarized in the present review need to be confirmed with larger prospective cohort studies and better-designed RCTs.
Topics: Cohort Studies; Humans; Nutritional Status; Randomized Controlled Trials as Topic; Telomere; Telomere Shortening
PubMed: 31688893
DOI: 10.1093/advances/nmz107 -
International Journal of Molecular... Aug 2019Telomere length (TL) has long been associated with aging, as telomeres serve as protective caps of chromosomes, and are thus deeply involved in the preservation of...
Telomere length (TL) has long been associated with aging, as telomeres serve as protective caps of chromosomes, and are thus deeply involved in the preservation of genome integrity and are vital to cellular functions. Traditionally, a strong link connects aging and infertility in both sexes, with an earlier onset in females. Over the past decade, telomeres have attracted increasing attention due to the role they play in fertility. In this review, we investigated the potential positive or negative association between relative TL and different factors of female and male infertility. A systematic search of the PubMed database was conducted. Out of the 206 studies identified, 45 were reviewed as they fulfilled the criteria of validity and relevance. Following an analysis and a comparison of the study outcomes, several clear trends were observed. The majority of female infertility factors were associated with a shorter TL, with the exception of endometriosis, premature ovarian failure and clear cell carcinoma that were associated with a longer TL and polycystic ovary syndrome (PCOS), which revealed conflicting results among several studies, leading to ambiguous conclusions. Male infertility factors were associated with a shorter TL. Although this review can provide an outline of general trends in the association of TL with infertility factors, further epidemiological and original research studies are required to focus on investigating the basis of these varying lengths of telomeres.
Topics: Aging; Female; Humans; Infertility, Female; Infertility, Male; Male; Telomere; Telomere Shortening
PubMed: 31173155
DOI: 10.3892/ijmm.2019.4225 -
Allergy Sep 2019The genetic determinants of food allergy have not been systematically reviewed. We therefore systematically reviewed the literature on the genetic basis of food allergy,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The genetic determinants of food allergy have not been systematically reviewed. We therefore systematically reviewed the literature on the genetic basis of food allergy, identifying areas for further investigation.
METHODS
We searched three electronic databases (MEDLINE, EMBASE and PubMed) on 9 January 2018. Two authors screened retrieved articles for review according to inclusion criteria and extracted relevant information on study characteristics and measures of association. Eligible studies included those that reported an unaffected nonatopic control group, had genetic information and were carried out in children.
RESULTS
Of the 2088 studies retrieved, 32 met our inclusion criteria. Five were genome-wide association studies, and the remaining were candidate gene studies. Twenty-two of the studies were carried out in a predominantly Caucasian population with the remaining 10 from Asian-specific populations or unspecified ethnicity. We found FLG, HLA, IL10, IL13, as well as some evidence for other variants (SPINK5, SERPINB and C11orf30) that are associated with food allergy.
CONCLUSIONS
Little genetic research has been carried out in food allergy, with FLG, HLA and IL13 being the most reproducible genes for an association with food allergy. Despite promising results, existing genetic studies on food allergy are inundated with issues such as inadequate sample size and absence of multiple testing correction. Few included replication analyses or population stratification measures. Studies addressing these limitations along with functional studies are therefore needed to unravel the mechanisms of action of the identified genes.
Topics: Age Factors; Alleles; Child; DNA Copy Number Variations; Filaggrin Proteins; Food Hypersensitivity; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Odds Ratio; Polymorphism, Single Nucleotide
PubMed: 30835860
DOI: 10.1111/all.13767 -
PloS One 2021The neuroendocrine stress response allows vertebrates to cope with stressors via the activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis, which ultimately... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The neuroendocrine stress response allows vertebrates to cope with stressors via the activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis, which ultimately results in the secretion of glucocorticoids (GCs). Glucocorticoids have pleiotropic effects on behavior and physiology, and might influence telomere length dynamics. During a stress event, GCs mobilize energy towards survival mechanisms rather than to telomere maintenance. Additionally, reactive oxygen species produced in response to increased GC levels can damage telomeres, also leading to telomere shortening. In our systematic review and meta-analysis, we tested whether GC levels impact telomere length and if this relationship differs among time frame, life history stage, or stressor type. We hypothesized that elevated GC levels are linked to a decrease in telomere length.
METHODS
We conducted a literature search for studies investigating the relationship between telomere length and GCs in non-human vertebrates using four search engines: Web of Science, Google Scholar, Pubmed and Scopus, last searched on September 27th, 2020. This review identified 31 studies examining the relationship between GCs and telomere length. We pooled the data using Fisher's Z for 15 of these studies. All quantitative studies underwent a risk of bias assessment. This systematic review study was registered in the Open Science Framework Registry (https://osf.io/rqve6).
RESULTS
The pooled effect size from fifteen studies and 1066 study organisms shows no relationship between GCs and telomere length (Fisher's Z = 0.1042, 95% CI = 0.0235; 0.1836). Our meta-analysis synthesizes results from 15 different taxa from the mammalian, avian, amphibian groups. While these results support some previous findings, other studies have found a direct relationship between GCs and telomere dynamics, suggesting underlying mechanisms or concepts that were not taken into account in our analysis. The risk of bias assessment revealed an overall low risk of bias with occasional instances of bias from missing outcome data or bias in the reported result.
CONCLUSION
We highlight the need for more targeted experiments to understand how conditions, such as experimental timeframes, stressor(s), and stressor magnitudes can drive a relationship between the neuroendocrine stress response and telomere length.
Topics: Animals; Glucocorticoids; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Telomere Shortening; Vertebrates
PubMed: 34597314
DOI: 10.1371/journal.pone.0257370