PART1 facilitates tumorigenesis and inhibits ferroptosis by regulating the miR-490-3p/SLC7A11 axis in hepatocellular carcinoma.

BACKGROUND: Ferroptosis is associated with cancer progression and has a promising application for treating hepatocellular carcinoma (HCC). Long non-coding RNA (lncRNA) participates widely in the regulation of ferroptosis, but the key lncRNA regulators implicated in ferroptosis and their molecular mechanisms remain to be identified. METHODS: Bioinformatic analysis was performed in R based on The Cancer Genome Atlas Program (TCGA) public database. The relative expression of genes was detected by real-time quantitative PCR. Cell viability was assessed by the CCK8 assay. The cell cycle and apoptosis were detected by flow cytometry. Migration and invasion of HCC cells were detected by Transwell assay and wound healing assay. Expression of relevant proteins was detected by Western blotting. A dual-luciferase reporter assay was used to detect interactions between PART1 (or SLC7A11) and miR-490-3p. RESULTS: The PART1/miR-490-3p/SLC7A11 axis was identified as a potential regulatory pathway of ferroptosis in HCC. PART1 silencing reduced HCC cell proliferation, migration, and metastasis and promoted apoptosis and erastin-reduced ferroptosis. Further investigation revealed that PART1 acted as a competitive endogenous RNA (ceRNA) for miR-490-3p to enhance SLC7A11 expression. Overexpression of miR-490-3p downregulated the expression of SLC7A11, inhibiting the proliferation, invasion, and metastasis of HCC cells while promoting apoptosis and erastin-induced ferroptosis. Knockdown of PART1 in HCC cells significantly improved the sensitivity of HCC cells to sorafenib. CONCLUSION: Our results revealed that the PART1/miR-490-3p/SLC7A11 axis enhances HCC cell malignancy and suppresses ferroptosis, which provides a new perspective for understanding of the function of long chain non-coding RNAs in HCC. The PART1/miR-490-3p/SLC7A11 axis may be target for improving sorafenib sensitivity in HCC.

Antimicrobial peptidase lysostaphin at subinhibitory concentrations modulates staphylococcal adherence, biofilm formation, and toxin production.

BACKGROUND: The ability of antimicrobial agents to affect microbial adherence to eukaryotic cell surfaces is a promising antivirulence strategy for combating the global threat of antimicrobial resistance. Inadequate use of antimicrobials has led to widespread instances of suboptimal antibiotic concentrations around infection sites. Therefore, we aimed to examine the varying effect of an antimicrobial peptidase lysostaphin (APLss) on staphylococcal adherence to host cells, biofilm biomass formation, and toxin production as a probable method for mitigating staphylococcal virulence. RESULTS: Initially, soluble expression in E. coli and subsequent purification by immobilized-Ni2+ affinity chromatography (IMAC) enabled us to successfully produce a large quantity of highly pure ~ 28-kDa His-tagged mature APLss. The purified protein exhibited potent inhibitory effects against both methicillin-sensitive and methicillin-resistant staphylococcal strains, with minimal inhibitory concentrations (MICs) ranging from 1 to 2 µg/mL, and ultrastructural analysis revealed that APLss-induced concentration-specific changes in the morphological architecture of staphylococcal surface membranes. Furthermore, spectrophotometric and fluorescence microscopy revealed that incubating staphylococcal strains with sub-MIC and MIC of APLss significantly inhibited staphylococcal adherence to human vaginal epithelial cells and biofilm biomass formation. Ultimately, transcriptional investigations revealed that APLss inhibited the expression of agrA (quorum sensing effector) and other virulence genes related to toxin synthesis. CONCLUSIONS: Overall, APLss dose-dependently inhibited adhesion to host cell surfaces and staphylococcal-associated virulence factors, warranting further investigation as a potential anti-staphylococcal agent with an antiadhesive mechanism of action using in vivo models of staphylococcal toxic shock syndrome.

Human activities have more impacts on the recent discharge reduction of the largest tributary of the Yellow River relative to last three centuries.

How to quantitatively decouple the impacts of climate change and human activities on river discharge changes is a challenge in current global change research. As the largest tributary of the Yellow River (YR), the Weihe River (WR) is a typical river whose discharge is influenced by climate change and human activities. Here, we first attempt to obtain the normal-flow season and high-flow season discharge in the lower reaches of the WR by using tree rings and historical documents, respectively. The relationship between natural discharge in the two seasons is unstable and complex since 1678. Using an innovative method, we reconstructed the natural discharge from March to October (DM-O), which explains >73 % of the variance in the observed DM-O during the modeling period 1935-1970. There were 44 high-flow years, 6 extremely high-flow years, 48 low-flow years and 8 extremely low-flow years from 1678 to 2008. The contribution of WR annual discharge to the YR is 17 % over the past three centuries, and their natural discharge changes synchronously rise and fall. Human activities, such as the construction of reservoirs and check-dams, agricultural irrigation and domestic and industrial water consumption, have more impacts than climate change on the decrease in the observed discharge. In total, 53.5 % of the discharge reduction since 1971 is due to human activities, and 46.5 % is due to climate change. In addition, this study provides an important model for how to quantify the influences of human activities and nature on discharge reduction and to reconstruct seasonal resolution climate in global change studies.

Estimates of the prevalence of occult HBV infection in Asia: a systematic review and meta-analysis.

PURPOSE: Occult Hepatitis B virus infection (OBI) is of great significance to the transmission of Hepatitis B virus (HBV) and the evolution of the patient's clinical outcome. We conducted a systematic review and meta-analysis to estimate the prevalence of OBI in Asia. METHODS: Literature search was conducted in PubMed, Cochrane Library database, Web of Science and Embase with the keywords of 'Hepatitis B virus', 'occult infection', 'prevalence'. 70 studies were included in the meta-analysis. Meta-analysis was performed using random-effects models to calculate the pooled prevalence of OBI and 95% confidence interval (CI). The data were analyzed in R 4.1.2. RESULTS: The overall prevalence of OBI was 4% (95%CI: 0.03-0.06) in Asia. Subgroup analysis based on geographic region showed a prevalence of 3% (95%CI 0.02-0.06) in East Asia, 9% (95%CI 0.05-0.15) in West Asia, 3% (95%CI 0.01-0.11) in Southern Asia and 9% (95%CI 0.05-0.15) in Southeast Asia. Subgroup analysis demonstrated a prevalence of 1% (95%CI 0.00-0.02) in general population, 5% (95%CI: 0.03-0.08) in high-risk population, 9% (95%CI: 0.03-0.22) in the human immunodeficiency virus (HIV)-infected patient, 18% (95%CI: 0.09-0.32) in the hepatopathy patients. CONCLUSION: Based on the meta-analysis of the prevalence of OBI in different populations, we concluded that the prevalence of OBI in the high-risk population, hepatopathy patients, and HIV-infected patients was higher than that in the general population. A systematic review showed that OBI was associated with disease progression and prognosis. Therefore, these populations should be routinely screened for OBI and promptly intervened to avoid promoting disease progression.

Molecular Tools for Guiding Therapy in Patients With Staphylococcal Bone and Joint Infections: A Diagnostic Test Accuracy Meta-analysis.

Background: Timely detection of causative pathogens and their antimicrobial resistance are essential for guiding targeted therapies in bone and joint infections (BJI) patients. We performed a systematic review and meta-analysis to assess the diagnostic value of testing osteoarticular samples with the nucleic acid amplification tests (NAAT) for effective staphylococcal strain identification and the administration of appropriately targeted antimicrobial agents in BJI patients. Methods: Five databases, including PubMed, Embase, Scopus, Web of Science, and the Cochrane Library, were searched for related publications from inception to July 24, 2021. Studies comparing the diagnostic accuracy of NAAT to a microbiological culture reference standard of osteoarticular specimens were eligible. Pooled summary values of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) of NAAT compared to the microbiological culture reference standard were calculated using bivariate random-effects meta-analyses. Results: From 906 citations, 11 studies were included. Eleven studies comprising 13 datasets (n = 1047) evaluated NAAT accuracy for methicillin-sensitive Staphylococcus aureus (MSSA) identification, while seven studies comprising nine datasets (n = 727) evaluated methicillin-resistant Staphylococcus aureus (MRSA) identification. Against the microbiological culture reference standard, the pooled summary estimates for detection of both MSSA [sensitivity: 0.89 (95% confidence interval [CI] 0.84-0.93), specificity: 0.99 (95% CI 0.97-0.99), PLR: 34.13 (95% CI 20.54-56.73), NLR: 0.19 (95% CI 0.12-0.3), and DOR: 283.37 (95% CI 129.49-620.1)] and MRSA [sensitivity: 0.81 (95% CI 0.67-0.91), specificity: 1.0 (95% CI 0.99-1.0), PLR: 62.1 (95% CI 24.5-157.6), NLR: 0.33 (95% CI 0.16-0.69), and DOR: 300.25 (95% CI 85.01-1060.5)] were comparable. Heterogeneity was moderate. GeneXpert was frequently used among NAA tests, and its diagnostic accuracy was in line with the overall pooled summary estimates. The heterogeneity in diagnostic efficacy (P >0.05) could not be explained by a meta-regression and subgroup analysis of the research design, sample condition, and patient selection technique. Conclusions: Our study suggested that NAAT can be applied as the preferred prescreening test for the timely diagnosis of staphylococcal strains associated with BJI in osteoarticular samples for successful antimicrobial therapy.

Clinical relevance of molecular testing methods in the diagnosis and guidance of therapy in patients with staphylococcal empyema: a systematic review and meta-analysis.

Background: Efficient detection tools for determining staphylococcal pleural infection are critical for its eradication. The objective of this meta-analysis was to assess the diagnostic utility of nucleic acid amplification tests (NAAT) in suspected empyema cases to identify staphylococcal strains and avoid unnecessary empiric methicillin-resistant Staphylococcus aureus (MRSA) therapy. Methods: From inception to July 24, 2021, relevant records were retrieved from PubMed, Embase, Scopus, Web of Science, and the Cochrane Library. The quality of studies was determined using the QUADAS-2 tool. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and hierarchical summary receiver operating characteristic (HSROC) curve for NAAT's diagnostic performance were evaluated using an HSROC model. Results: Eight studies comprising 424 samples evaluated NAAT accuracy for Staphylococcus aureus (SA) identification, while four studies comprising 317 samples evaluated methicillin-resistant Staphylococcus aureus (MRSA) identification. The pooled NAAT summary estimates for detection of both SA (sensitivity: 0.35 (95% CI 0.19-0.55), specificity: 0.95 (95% CI 0.92-0.97), PLR: 7.92 (95% CI 4.98-12.59), NLR: 0.44 (95% CI 0.14-1.46), and DOR: 24.0 (95% CI 6.59-87.61) ) and MRSA (sensitivity: 0.45 (95% CI 0.15-0.78), specificity: 0.93 (95% CI 0.89-0.95), PLR: 10.06 (95% CI 1.49-67.69), NLR: 0.69 (95% CI 0.41-1.15), and DOR: 27.18 (95% CI 2.97-248.6) ) were comparable. The I2 statistical scores for MRSA and SA identification sensitivity were 13.7% and 74.9%, respectively, indicating mild to substantial heterogeneity. PCR was frequently used among NAA tests, and its diagnostic accuracy coincided well with the overall summary estimates. A meta-regression and subgroup analysis of country, setting, study design, patient selection, and sample condition could not explain the heterogeneity (meta-regression P = 0.66, P = 0.46, P = 0.98, P = 0.68, and P = 0.79, respectively) in diagnostic effectiveness. Conclusions: Our study suggested that the diagnostic accuracy of NAA tests is currently inadequate to substitute culture as a principal screening test. NAAT could be used in conjunction with microbiological culture due to the advantage of faster results and in situations where culture tests are not doable.

Insight into spatial-temporal patterns of hydroclimate change on the Chinese Loess Plateau over the past 250 years, using new evidence from tree rings.

The climate aridity since the mid-20th century has raised concerns about water resources on the Chinese Loess Plateau (CLP). A lack of extended observation-like precipitation records for the eastern CLP (ECLP) means that it remains unclear whether or not the current arid state of the CLP is unprecedented, and the spatial-temporal characteristics of hydroclimatic variability across the CLP over past centuries are not well understood. Here we present a regional hydrological-year precipitation reconstruction for the Heichashan Mountains, which successfully captures hydroclimate changes on the ECLP since 1773 CE. The reconstruction explains 48.72 % of the observed variance for 1957-2019 CE and reveals a wetting trend since the early 2000s and shows 2014-2020 CE to have been the second wettest period over the past 248 years. 1910-1932 CE was the longest and driest period over the past centuries. Furthermore, the 19th century was relatively wet, whereas the 20th century was dry. We demonstrate that droughts tend to occur in warm periods. Combining our new reconstruction with previously published hydroclimatic reconstructions, we find that hydroclimate has changed synchronously on the ECLP and the western CLP (WCLP) for most of the past two centuries. Some regional differences do exist, for example in the 1890s-1920s, when aridity gradually intensified across the ECLP, no similar drying is evident in records for the WCLP, although the 1920s megadrought occurred in both the ECLP and WCLP. Another difference is in the onset of the 20th-century aridity, which began in the 1950s on the ECLP, around 20 years later than it began on the WCLP. In addition to the known influences of the Asian Summer Monsoon and related large-scale circulations, this work highlights a major finding that the 1920s megadrought may be related to a regime shift in Northern Hemisphere temperature.

Clinical Relevance of Xpert MRSA/SA in Guiding Therapeutic Decisions for Staphylococcal Infections: A Diagnostic Test Accuracy Analysis.

INTRODUCTION: Rapid identification of the causal organism and antibiotic resistance is crucial for guiding targeted therapy in patients with suspected staphylococcal infection. A meta-analysis was carried out to evaluate the diagnostic relevance of Xpert™ MRSA/SA (Xpert) from clinical samples of various origins for limiting the use of unnecessary empirical methicillin-resistant Staphylococcus aureus (MRSA) therapy. METHODS: Five databases, including the Cochrane Library, Scopus, PubMed, Web of Science, and Embase, were comprehensively inspected from inception to October 12, 2021. The pooled summary estimates were evaluated using a bivariate random-effects model. RESULTS: Our inclusion criteria were met by 49 publications containing 68 datasets out of 735 citations. A total of 21 studies (n = 4996) examined the accuracy of Xpert in detecting methicillin-sensitive S. aureus (MSSA), while 47 studies (n = 45,430) examined the accuracy of Xpert in detecting MRSA. As compared to MRSA, Xpert's diagnostic performance for MSSA detection was markedly higher [sensitivity: 0.97 (0.96-0.98), specificity: 0.97 (0.97-0.98), area under curve (AUC): 0.99 (0.99-1.0)]. Xpert's pooled sensitivity and specificity differed marginally across sample types, including screening of colonization, lower respiratory tract (LRT), osteoarticular, and bloodstream samples. Notably, the Xpert pooled specificity was consistently ≥ 92% against microbiological culture across all sample types. The diagnostic efficiency heterogeneity was not explained by a meta-regression and subgroup analysis of research design, sample conditions, and sampling methods (P > 0.05). CONCLUSION: Our findings suggest that Xpert could be used as the favoured screening test for the early detection of staphylococcal infection in a variety of sample types, with the goal of guiding therapeutic decisions.

The relationship between NTCP gene varieties and the progress of liver disease after HBV infection: an updated systematic review and meta-analysis.

BACKGROUND: The aim of this study was to analyze the relationship between sodium taurocholate cotransporting polypeptide (NTCP) gene varieties and hepatitis B virus (HBV) infection and the progress of HBV-related liver disease. METHODS: PubMed, EMBASE, Web of Science and Cochrane library were used to search eligible studies. STATA software was performed to combine results. Pooled odds ratios (OR) was used to assess the potential genetic relationships. RESULTS: A total of 18 eligible case-control studies with 24960 cases and 28342 controls were included in this meta-analysis. The A allele of rs2296651 polymorphism was found to be significantly linked to a protection of HBV infection in the whole combined analysis (P = 0.000). Meanwhile, this allele was significantly associated with a decreased risk of hepatocellular carcinoma (HCC) (A vs. G: OR = 0.668, 95% CI: 0.571-0.782, P = 0.000), and was significantly associated with HBV nature clearance (A vs. G: OR = 0.744, 95% CI: 0.585-0.946, P = 0.016; AA+GA vs. GG: OR = 0.775, 95% CI: 0.613-0.980, P = 0.033; GA vs. GG: OR = 0.748, 95% CI: 0.588-0.952, P = 0.018). However, rs4646287 genetic varieties had no statistical differences in all models with HBV infection or HBV-related disease progress, liver cirrhosis, acute-on-chronic liver failure and HCC, as well as rs7154439, rs4646285, rs4646296. CONCLUSIONS: Rs2296651 polymorphism (A allele) may protect from HBV infection and the progress of HBV-related disease (HBV-related HCC). Future research about other single nucleotide polymorphisms (SNPs) (rs4646287, rs7154439, rs4646285, rs4646296) of NTCP may be needed to clarify the relationship of NTCP gene varieties with HBV infection and HBV-related disease.

THRSP identified as a potential hepatocellular carcinoma marker by integrated bioinformatics analysis and experimental validation.

Hepatocellular carcinoma (HCC) is the most common malignant liver tumor with high mortality and poor prognosis worldwide. This study aimed to identify hub genes and investigate the underlying molecular mechanisms in HCC progression by integrated bioinformatics analysis and experimental validation. Based on the Gene Expression Omnibus (GEO) databases and The Cancer Genome Atlas (TCGA), 12 critical differential co-expression genes were identified between tumor and normal tissues. Via survival analysis, we found higher expression of LCAT, ACSM3, IGF1, SRD5A2, THRSP and ACADS was associated with better prognoses in HCC patients. Among which, THRSP was selected for the next investigations. We found that THRSP mRNA expression was negatively correlated with its methylation and closely associated with clinical characteristics in HCC patients. Moreover, THRSP expression had a negative correlation with the infiltration levels of several immune cells (e.g., B cells and CD4+ T cells). qRT-PCR verified that THRSP was lower expressed in HCC tissues and cell lines compared with control. Silencing of THRSP promoted the migration, invasion, proliferation, and inhibited cell apoptosis of HCCLM and Huh7 cell lines. Decreased expression of THRSP promoted HCC progression by NF-κB, ERK1/2, and p38 MAPK signaling pathways. In conclusion, THRSP might serve as a novel biomarker and therapeutic target of HCC.

The Biomarkers for Predicting Viral HepatitisAssociated Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world, and more than half of the newly diagnosed cases are chronic hepatitis B patients. Due to the lack of specific clinical manifestations, many patients are already at an advanced stage at the time of diagnosis and therefore have missed the best time for treatment. Organs in a pathological state usually secrete specific substances into the blood, which can indirectly indicate the pathological state of the organ, so some biological markers in the blood can be used as a tool to predict the incidence of HCC. METHODS: The Research articles related to HCC were collected by searching PubMed databases with the keywords "hepatocellular carcinoma", "serum biomarker", "hepatitis B", "prediction" and "prognosis", and Additional articles were identified by manual search of references found in the primary articles, followed by a summary and review. RESULTS: Viral hepatitis is the main cause of HCC worldwide, and this phenomenon is particularly prominent in Asian and African populations. A variety of serological markers including M2BPGi, IL-6 and COMP can be used to predict the incidence of long-term HCC in patients. The risk of HCC is dynamic rather than constant, and dynamic detection will help improve prediction accuracy. For hepatitis B patients, HBV DNA load and HBcr Ag are important predictive markers of HCC. CONCLUSION: For a high-risk population of HCC, early risk prediction is helpful to guide clinical work, and timely adjustments of the screening frequency and treatment plan are helpful to prolong the survival time of HCC patients.

Indole-3-propionic Acid-aggravated CCl4-induced Liver Fibrosis via the TGF-ß1/Smads Signaling Pathway.

BACKGROUND AND AIMS: The pathogenesis of liver fibrosis involves liver damage, inflammation, oxidative stress, and intestinal dysfunction. Indole-3-propionic acid (IPA) has been demonstrated to have antioxidant, anti-inflammatory and anticancer activities, and a role in maintaining gut homeostasis. The current study aimed to investigate the role of IPA in carbon tetrachloride (CCl4)-induced liver fibrosis and explore the underlying mechanisms. METHODS: The liver fibrosis model was established in male C57BL/6 mice by intraperitoneal injection of CCl4 twice weekly. IPA intervention was made orally (20 mg/kg daily). The degree of liver injury and fibrosis were assessed by serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and histopathology. Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction (qPCR) were used to detect the inflammatory cytokines. The malondialdehyde (MDA), glutathione, glutathione peroxidase, superoxide dismutase, and catalase were determined via commercial kits. Hepatocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. The expression of mRNA and protein was assayed by qPCR, Western blotting, or immunohistochemical staining. RESULTS: After IPA treatment, the ALT and AST, apoptotic cells, and pro-inflammatory factor levels were enhanced significantly. Moreover, IPA intervention up-regulated the expression of collagen I, α-smooth muscle actin, tissue inhibitor of matrix metalloproteinase-1, matrix metalloproteinase-2, transforming growth factor-ß1 (TGF-ß1), Smad3, and phosphorylated-Smad2/3. Additionally, IPA intervention did not affect the MDA level. Attractively, the administration of IPA remodeled the gut flora structure. CONCLUSIONS: IPA aggravated CCl4-induced liver damage and fibrosis by activating HSCs via the TGF-ß1/Smads signaling pathway.

AC093797.1 as a Potential Biomarker to Indicate the Prognosis of Hepatocellular Carcinoma and Inhibits Cell Proliferation, Invasion, and Migration by Reprogramming Cell Metabolism and Extracellular Matrix Dynamics.

Purpose: The risk signature composed of four lncRNA (AC093797.1, POLR2J4, AL121748.1, and AL162231.4.) can be used to predict the overall survival (OS) of patients with hepatocellular carcinoma (HCC). However, the clinical significance and biological function of AC093797.1 are still unexplored in HCC or other malignant tumors. In this study, we aimed to investigate the biological function of AC093797.1 in HCC and screen the candidate hub genes and pathways related to hepatocarcinogenesis. Methods: RT-qPCR was employed to detect AC093797.1 in HCC tissues and cell lines. The role of AC093797.1 in HCC was evaluated via the cell-counting kit-8, transwell, and wound healing assays. The effects of AC093797.1 on tumor growth in vivo were clarified by nude mice tumor formation experiments. Then, RNA-sequencing and bioinformatics analysis based on subcutaneous tumor tissue was performed to identify the hub genes and pathways associated with HCC. Results: The expression of AC093797.1 decreased in HCC tissues and cell lines, and patients with low expressed AC093797.1 had poor overall survival (OS). AC093797.1 overexpression impeded HCC cell proliferation, invasion, and migration in vitro and suppressed tumor growth in vivo. Compared with the control group, 710 differentially expressed genes (243 upregulated genes and 467 downregulated genes) were filtered via RNA-sequencing, which mainly enriched in amino acid metabolism, extracellular matrix structure constituents, cell adhesion molecules cams, signaling to Ras, and signaling to ERKs. Conclusion: AC093797.1 may inhibit cell proliferation, invasion, and migration in HCC by reprograming cell metabolism or regulating several pathways, suggesting that AC093797.1 might be a potential therapeutic and prognostic marker for HCC patients.

[Reconstruction of summer NDVI over the past 339 years based on the tree-ring width of Picea schrenkiana in Bayinbuluke, Central Tianshan, China]. / åŸºäºŽé›ªå²­äº‘æ‰æ ‘è½®å®½åº¦é‡å»ºè¿‡åŽ»339å¹´å¤©å±±ä¸­éƒ¨å·´éŸ³å¸ƒé²å ‹åœ°åŒºå¤å­£NDVI.

The normalized difference vegetation index (NDVI) is widely used in various fields of vegetation research. Due to the short observation time, however, it is difficult to meet the research needs at long time scale. Here, we established a tree-ring width chronology (STD) based on Picea schrenkiana in Bayinbuluke, and calculated the correlation coefficient of chronology and NDVI with meteorological data. The results showed that both tree-ring width index and NDVI were significantly correlated with meteorological data. Combined with the significant positive correlation between width chronology and NDVI in June-August (r=0.7, P<0.01, n=38), summer NDVI (from June to August) was reconstructed over the past 339 years using a regression model. During 1680-2018, the reconstruction series had four dense vegetation periods (1738-1765, 1786-1798, 1964-1973 and 2000-2018) and five sparse vegetation periods (1690-1714, 1825-1834, 1850-1880, 1895-1920 and 1945-1955). The reconstruction reflected the hydrological signals in the central Tianshan Mountains. The comparison with the surrounding reconstructions revealed that when the runoff of Kaidu River increased and the local environment was humid, the vegetation coverage was high; otherwise the vegetation coverage was low. The extreme value of the reconstruction series also captured a series of natural disasters recorded in historical documents. Results of HYSPLT (Hybrid Single-Particle Lagrangian Integrated Trajectory Model) backward trajectory model and wind field analysis showed that NDVI anomalies were affected by the precipitation from Westerlies.

Clinical Utility of Molecular Tests for Guiding Therapeutic Decisions in Bloodstream Staphylococcal Infections: A Meta-Analysis.

Background: Treatment of bloodstream staphylococcal infections (BSI) necessitates the prompt initiation of appropriate antimicrobial agents and the rapid de-escalation of excessive broad-spectrum coverage to reduce the risk of mortality. We, therefore, aimed to demonstrate the diagnostic accuracy of nucleic acid amplification tests (NAAT) for the identification of methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) in clinically suspected patients. Methods: Until November 23, 2020, databases including PubMed, Scopus, Embase, and Web of Science were scanned for eligible studies. A bivariate random-effects model was used for meta-analysis of the 33 included studies obtained from 1606 citations, and pooled summary estimates with 95% confidence intervals (CI) were generated. Results: Twenty-three studies (n = 8,547) assessed NAAT accuracy for MSSA detection, while three studies (n = 479) evaluated MRSA detection in adults. The pooled NAAT sensitivity and specificity for MRSA in adults was higher [sensitivity: 0.83 (95% CI 0.59-0.96), specificity: 0.99 (95% CI 0.98-1.0)] as compared to MSSA [sensitivity: 0.76 (95% CI 0.69-0.82), specificity: 0.98 (95% CI 0.98-0.99)]. Similarly, eight studies (n = 4,089) investigating MSSA in pediatric population reported higher NAAT accuracy [sensitivity: 0.89 (95% CI 0.76-0.96), specificity: 0.98 (95% CI 0.97-0.98)] compared to adults. Among NAA tests, SeptiFast (real-time PCR, commercial) was frequently applied, and its diagnostic accuracy corresponded well to the overall summary estimates. A meta-regression and subgroup analysis of study design, sample condition, and patient selection method could not explain the heterogeneity (P > 0.05) in the diagnostic efficiency. Conclusions: NAAT could be applied as the preferred initial tests for timely diagnosis and BSI management.

The effect of CYP2C19 gene polymorphism on the eradication rate of Helicobacter pylori by proton pump inhibitors-containing regimens in Asian populations: a meta-analysis.

Premise: The effects of proton pump inhibitors (PPI) depend on metabolic enzyme CYP2C19 that has different activity due to gene polymorphism. The purpose of this meta-analysis is to determine the potential effects of CYP2C19 polymorphism on the efficiency of PPI-based treatment. Materials & methods: The PubMed, EMBASE, Cochrane Library, etc. were searched for relevant articles published in English or Chinese from inception to 31 May 2020. Finally, 26 randomized controlled trials and 15 cohort studies met the inclusion criteria and used for the meta-analysis via STATA version 15. Results: Poor metabolizer (PM) genotype Helicobacter pylori eradication rates were highest for Asian individuals receiving triple or quadruple first-line therapy based on PPIs (p < 0.05). CYP2C19 polymorphism could influence H. pylori eradication rate only in Mainland China and Japan (p < 0.05). Conclusion: PM genotype facilitates the elimination of H. pylori in Asian populations. Rabeprazole-, esomeprazole- and pantoprazole-based eradication program was less affected by the CYP2C19 polymorphism.

LGALS3BP: A Potential Plasma Biomarker Associated with Diagnosis and Prognosis in Patients with Sepsis.

PURPOSE: This study aimed to screen differentially expressed proteins (DEPs) in plasma of patients with sepsis through data-independent acquisition (DIA) and enzyme-linked immunosorbent assays (ELISAs), and provide convenient and accurate serum markers for determining the condition of septic patients. METHODS: A total of 53 septic patients and 16 normal controls who were admitted to the Affiliated Hospital of Southwest Medical University between January 2019 and December 2020 were enrolled in this study; 6 specimens from the normal group and 15 from the sepsis group were randomly selected for DIA-based quantitative proteomic analysis. The acquired data were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and a protein-protein interaction (PPI) network was constructed to screen potential markers. The selected proteins were further verified through ELISAs. The differences between control and sepsis groups and between survivors and non-survivors were analysed. Receiver operating characteristic (ROC) curves were drawn to explore their diagnostic value and prognostic efficacy. RESULTS: A total of 149 DEPs were identified by bioinformatics methods. The analyses showed that these proteins are mainly involved in biological processes such as cell movement, stress response, cell proliferation, and immune response. Functional pathway analysis showed that they are mainly involved in leukocyte transendothelial migration, protein synthesis and processing, and various bacterial infections. LGALS3BP was selected as a potential plasma biomarker and further verified through an ELISA. Its level in septic patients was significantly higher than that in normal controls, and its level in non-survivors was also higher than that in survivors. The ROC curves suggested its great diagnostic efficacy and prognostic ability in sepsis. CONCLUSION: LGALS3BP levels were significantly different between the normal and sepsis groups; it has good diagnostic value in sepsis, and is related to patient prognosis; thus, it might be a biomarker for sepsis.

Accuracy of Molecular Amplification Assays for Diagnosis of Staphylococcal Pneumonia: a Systematic Review and Meta-analysis.

Rapid and accurate identification of staphylococcal pneumonia is crucial for effective antimicrobial stewardship. We performed a meta-analysis to evaluate the diagnostic value of nucleic acid amplification tests (NAAT) from lower respiratory tract (LRT) samples from suspected pneumonia patients to avoid superfluous empirical methicillin-resistant Staphylococcus aureus (MRSA) treatment. PubMed, Scopus, Embase, Web of Science, and the Cochrane Library Database were searched from inception to 2 September 2020. Data analysis was carried out using a bivariate random-effects model to estimate pooled sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR). Of 1,808 citations, 24 publications comprising 32 data sets met our inclusion criteria. Twenty-two studies (n = 4,630) assessed the accuracy of the NAAT for methicillin-sensitive S. aureus (MSSA) detection, while 10 studies (n = 2,996) demonstrated the accuracy of the NAAT for MRSA detection. The pooled NAAT sensitivity and specificity (with 95% confidence interval [CI]) for all MSSA detection were higher (sensitivity of 0.91 [95% CI, 0.89 to 0.94], specificity of 0.94 [95% CI, 0.94 to 0.95]) than those of MRSA (sensitivity of 0.75 [95% CI, 0.69 to 0.80], specificity of 0.88 [95% CI, 0.86 to 0.89]) in lower respiratory tract (LRT) samples. NAAT pooled sensitivities differed marginally among different LRT samples, including sputum, endotracheal aspirate (ETA), and bronchoalveolar lavage (BAL) fluid. Noticeably, NAAT pooled specificity against microbiological culture was consistently ≥88% across various types of LRT samples. A meta-regression and subgroup analysis of study design, sample condition, and patient selection method could not explain the heterogeneity (P > 0.05) in the diagnostic efficiency. This meta-analysis has demonstrated that the NAAT can be applied as the preferred initial test for timely diagnosis of staphylococcal pneumonia in LRT samples for successful antimicrobial therapy.

Investigational drugs with dual activity against HBV and HIV (Review).

Chronic hepatitis B (CHB) and acquired immunodeficiency syndrome (AIDS) are global public health problems that pose a significant health burden. Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection is common, as these viruses have similar transmission routes, such as blood transmission, sexual transmission and mother-to-child transmission. Coinfection frequently leads to accelerated disease progression. For individuals coinfected with HIV/HBV, combination antiretroviral therapy containing dual anti-HBV drugs is recommended. Certain studies have also indicated the benefits of antiretroviral drugs with anti-HBV activity in patients with coinfection. A total of four Food and Drug Administration-approved HIV drugs also have anti-HBV activity; namely, emtricitabine, lamivudine, tenofovir disoproxil fumarate and tenofovir alafenamide, which are all nucleoside reverse transcriptase inhibitors. However, various issues, including drug resistance and side effects, limit their application. Therefore, it is necessary to develop more drugs with dual activity against HBV and HIV. The present review outlines the mechanisms, safety and efficacy of certain drugs that have been investigated for this purpose.

Association of toll-like receptor polymorphisms with acquisition of HIV infection and clinical findings: A protocol for systematic review and meta-analysis.

BACKGROUND: To find the relationship between toll-like receptor (TLR) gene variants and human immunodeficiency virus (HIV) infection and clinical findings, which could inform clinical decisions and vaccination strategies. METHOD: Four databases were searched for articles that were published on or before Jul.1, 2020. Review Manager 5.3 software was applied to perform meta-analysis to explore. RESULTS: A total of 10 studies involving 20 genes, 3697 cases, and 6498 controls were included in this systematic review. TLR2 -196 to -174 Ins/Del (odds ratio [OR] = 1.562; P = .002), TLR4 rs4986790 (OR = 2.05; P = .002), TLR3 rs3775291 (OR = 0.25; P = .03), TLR7 rs179008 (P = .002), TLR7 rs2074109 (OR = 0.27, P = .019) were found associated with HIV infection. TLR2 -196 to -174, TLR4 rs4986790, TLR7 rs179008, TLR8 rs3764880, TLR9 rs352140 were found associated with clinical findings of HIV infection. We identified 5 case-control studies in meta-analysis, involving 695 cases and 729 controls on TLR7 rs179008 polymorphism, totaling 652 cases and 614 controls on TLR9 rs352140 polymorphism. In meta-analysis, we employed various genetic models. The T allele of TLR7 rs179008 was conferred the risk of HIV infection (T vs A: OR = 1.25, PA = .02). An increased risk of HIV infection was found for individuals with the TLR9 rs352140 GG genotype (GG vs AA: OR = 1.50, PA = .04). CONCLUSIONS: The systematic review indicated that TLR7 rs179008 T allele provides risk effects for HIV infection. TLR9 rs352140 GG genotype may associate with HIV infection.