LncRNA NONHSAT227443.1 Confers Esophageal Squamous Cell Carcinoma Chemotherapy Resistance by Activating PI3K/AKT Signaling via Targeting MRTFB.

INTRODUCTION: Esophageal cancer presents significant challenges due to limited treatment options and poor prognosis, particularly in advanced stages. Dysregulated long non-coding RNAs (lncRNAs) are implicated in cancer progression and treatment resistance. This study investigated the roles of dysregulated lncRNA NONHSAT227443.1, identified through lncRNA-seq, and its downstream target gene MRTFB in esophageal squamous cell carcinoma (ESCC). METHODS: Dysregulated lncRNAs were identified through lncRNA-seq in esophageal cancer tissues with varying chemotherapy response. The regulatory interaction of overexpressed NONHSAT227443.1 was assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Functional assays, including cell viability, cell proliferation, and flow cytometry analyses, were performed to comprehensively investigate the influence of NONHSAT227443.1 and its downstream molecules on ESCC. RESULTS: NONHSAT227443.1 was significantly overexpressed in paclitaxel plus platinum chemotherapy non-responders and esophageal cancer cell lines. Chemotherapy exposure led to diminished NONHSAT227443.1 expression. NONHSAT227443.1 negatively regulated MRTFB expression, and their combined dysregulation correlated with increased cancer activity, proliferation, and suppressed apoptosis. Diminished MRTFB expression was associated with PI3K/AKT pathway activation. CONCLUSION: Our study provides insights into NONHSAT227443.1 and MRTFB roles in esophageal cancer, contributing to aggressive traits and treatment resistance. NONHSAT227443.1 and MRTFB may serve as potential therapeutic targets to enhance the response to paclitaxel plus platinum chemotherapy in non-responsive cases.

Transport Pathways of Nitrate in Stormwater Runoff Inferred from High-Frequency Sampling and Stable Water Isotopes.

Storm events can mobilize nitrogen species from landscapes into streams, exacerbating eutrophication and threatening aquatic ecosystems as well as human health. However, the transport pathways and storm responses of different nitrogen forms remain elusive. We used high-frequency chemical and isotopic sampling to partition sources of stormwater runoff and determine transport pathways of multiple nitrogen forms in an agricultural catchment. Bayesian mixing modeling reveals shallow subsurface water as the dominant source of stormwater runoff, contributing 74% of the water flux and 72, 71, and 79% of total nitrogen (TN), total dissolved nitrogen (TDN), and nitrate (NO3-N), respectively. Groundwater, by contrast, contributed 11% of stormwater runoff and 21, 22, and 17% of TN, TDN, and NO3-N, respectively. The remaining 14% of stormwater runoff can be attributed to rainwater, which contains much less TN, TDN, and NO3-N. Surprisingly, during storm events, the dominant nitrogen form was NO3-N rather than dissolved organic nitrogen. Antecedent conditions and runoff characteristics have an important influence on nitrogen loads during storm events. Our results provide insight into hydrological mechanisms driving nitrogen transport during storm events and may help in developing catchment management practices for reducing nitrogen pollution in aquatic ecosystems.

Immunotherapy, prognostic, and tumor biomarker based on pancancer analysis, SMARCD3.

BACKGROUND: SMARCD3 has recently been shown to be an important gene affecting cancer, playing an important role in medulloblastoma and pancreatic ductal adenocarcinoma. Therefore, we conducted this research to investigate the potential involvement of SMARCD3 across cancers and to offer recommendations for future studies. METHODS: Utilizing information on 33 malignancies in the UCSC Xena database, SMARCD3 expression and its prognostic value were assessed. The tumor microenvironment was evaluated with the "CIBERSORT" and "ESTIMATE" algorithms. SMARCD3 and immune-related genes were analyzed using the TISIDB website. The pathways related to the target genes were examined using GSEA. MSI (microsatellite instability), TMB (tumor mutational burden), and immunotherapy analysis were used to evaluate the impact of target genes on the response to immunotherapy. RESULTS: There is heterogeneity in terms of the expression and prognostic value of SMARCD3 among various cancers, but it is a risk factor for many cancers including uterine corpus endometrial cancer (UCEC), renal clear cell carcinoma (KIRC), and gastric adenocarcinoma (STAD). GSEA revealed that SMARCD3 is related to chromatin remodeling and transcriptional activation, lipid metabolism, and the activities of various immune cells. The TMB and MSI analyses suggested that SMARCD3 affects the immune response efficiency of KIRC, LUAD and STAD. Immunotherapy analysis suggested that SMARCD3 may be a potential immunotherapy target. RT-qPCR demonstrated the variation in SMARCD3 expression in KIRC, LUAD, and STAD. CONCLUSION: Our study revealed that SMARCD3 affects the prognosis and immunotherapy response of some tumors, providing a direction for further research on this gene.

Vectorized dataset of silted land formed by check dams on the Chinese Loess Plateau.

Check dams on the Chinese Loess Plateau (CLP) have captured billions of tons of eroded sediment, substantially reducing sediment load in the Yellow River. However, uncertainties persist regarding the precise sediment capture and the role of these dams in Yellow River flow and sediment dynamics due to the lack of available spatial distribution datasets. We produced the first vectorized dataset of silted land formed by check dams on the CLP, combining high-resolution and easily accessible Google Earth images with object-based classification methods. The accuracy of the dataset was verified by 1947 collected test samples, and the producer's accuracy and user's accuracy of the dam lands were 88.9% and 99.5%, respectively. Our dataset not only provides fundamental information for accurately assessing the ecosystem service functions of check dams, but also helps to interpret current changes in sediment delivery of the Yellow River and plan future soil and water conservation projects.

Prognostic Significance of the Highest Mediastinal Lymph Node Involvement in Patients with Stage III-N2 Non-small Cell Lung Cancer.

BACKGROUND: Highest mediastinal lymph node (HMLN) involvement is a category of uncertain resection, yet the prognostic significance of HMLN involvement remains controversial. METHODS: A total of 486 patients with pathological stage III-N2 disease who underwent radical resection were enrolled from January 2015 to December 2018. Patients were allocated into two groups-HMLN involvement (219 cases) and HMLN-negative (249 cases) groups. Kaplan-Meier analysis and Cox proportional hazard regression models were used to evaluate the impact of HMLN involvement on 5-year recurrence-free survival (RFS) and overall survival (OS). RESULTS: The proportion of patients with multiple N2 diseases (72.1% vs. 23.7%; p < 0.001) and stage IIIA (87.2% vs. 77.5%; p < 0.009) were greater in the HMLN-involvement group than in the HMLN-negative group, and the survival rates of the HMLN-involvement group were significantly lower than those of the HMLN-negative group (RFS: 27.2% vs. 49.8%, p < 0.001; OS: 42.1% vs. 59.2%, p = 0.001). HMLN status was an independent factor for OS only (RFS: adjusted hazard ratio [aHR] 1.26, 95% confidence interval CI 0.94-1.68; OS: aHR 1.45, 95% CI 1.07-1.99) in the entire stage III cohort. After stratification of patients according to stage, the involvement of HMLN decreased both RFS and OS in the stage IIIA group (RFS: aHR 1.46, 95% CI 1.06-2.02; OS: aHR 1.70, 95% CI 1.19-2.42); however, no such difference was observed within the stage IIIB group. CONCLUSIONS: HMLN involvement is a prognostic factor of deteriorating survival in highly advanced N2 disease only in patients with stage IIIA.

Abdominal obesity in Chinese patients undergoing hemodialysis and its association with all-cause mortality.

Introduction: Obesity in patients undergoing hemodialysis is common. However, there is limited information on the relationship between obesity types defined by the combined body mass index (BMI) and waist circumference (WC) classification criteria and all-cause mortality in Chinese hemodialysis patients. Our objective was to determine the association between obesity types and all-cause mortality in hemodialysis patients. Methods: We conducted a prospective cohort study including patients from 11 hemodialysis centers in Beijing. According to the World Health Organization's standards, patients were classified into 2 categories with WC and 4 categories with BMI and then followed up for 1 year. Kaplan-Meier survival analysis was used to compare the difference in the cumulative survival rate in different BMI and WC groups. A multivariate Cox regression analysis was used to determine the association between different types of obesity and all-cause mortality. Results: A total of 613 patients were enrolled, the mean age was 63.8 ± 7.1 years old, and 42.1% were women. Based on the baseline BMI, there were 303 (49.4%) patients with normal weight, 227 (37.0%) with overweight, 37(6.0%) with obesity, and 46 (7.5%) with underweight. Based on the baseline WC, 346 (56.4%) patients had abdominal obesity. During a median follow-up of 52 weeks, 69 deaths occurred. Kaplan-Meier plots demonstrated a significant association of BMI categories (log-rank χ2 = 18.574, p<0.001) and WC categories (log-rank χ2 = 5.698, p=0.017) with all-cause death. With normal BMI and non-abdominal obesity as a reference, multivariate Cox regression analysis results showed that obesity (HR 5.36, 95% CI, 2.09-13.76, p<0.001), underweight (HR, 5.29, 95% CI, 2.32-12.07, p<0.001), normal weight combined with abdominal obesity (HR 2.61, 95% CI, 1.20-5.66, p=0.016), and overweight combined with abdominal obesity (HR 1.79, 95% CI, 1.03-3.73, p=0.031, respectively) were significantly associated with higher risks of all-cause mortality. Conclusion: Our study indicated that abdominal obesity is common and associated with all-cause mortality among Chinese hemodialysis patients.

Elevated circulating PCSK9 level is associated with 28-day mortality in patients with sepsis: a prospective cohort study.

OBJECTIVES: Pro-protein convertase subtilisin/kexin 9 (PCSK9) decreases the clearance of the pathogenic lipids, supporting the potential role of PCSK9 in the prognosis of sepsis. METHODS: In this prospective cohort study, patients with sepsis were consecutively recruited from 1 to 2020 to 30 September 2021 at the First People's Hospital of Huaihua, China. All the eligible patients were categorized into low-PCSK9 and high-PCSK9 groups, based on their PCSK9 levels at admission. Time-dependent receiver operating characteristic curves and Cox proportional hazards regression were used to evaluate the association between PCSK9 level and 28-day mortality of sepsis. RESULTS: Of the 203 enrolled patients, 56 (27.59%) died during the 28-day follow-up. The PCSK9 level was positively related to the C-reactive protein level. The cut-off point of PCSK9 levels for 28-day mortality risk was 370 ng/ml. Through comparison between high-PCSK9 (> 370 ng/ml) with low-PCSK9 (≤ 370 ng/ml) groups, the adjusted HR for mortality was 2.56 (95% CI: 1.25-5.23, p = 0.01). CONCLUSIONS: The 28-day mortality of sepsis increased significantly as the baseline circulating PCSK9 level exceeded 370 ng/ml, indicating circulating PCSK9 levels may be a potential biomarker to predict the prognosis of sepsis.

Association between number of dissected lymph nodes and survival in patients undergoing resection for clinical stage IA pure solid lung adenocarcinoma: a retrospective analysis.

BACKGROUND: Lymph node dissection is essential for staging of pure solid lung adenocarcinoma and selection of treatment after surgical resection, particularly for stage I disease since the rate of lymph node metastasis can vary from 0 to 23.7%. METHODS: We retrospectively screened all adult patients (18 years of age or older) who underwent lobectomy for pure solid cT1N0M0 lung adenocarcinoma between January 2015 and December 2017 at our center. Cox proportional hazard regression was used to assess the association between the number of dissected lymph nodes and recurrence-free survival (RFS) and to determine the optimal number of dissected lymph nodes. RESULTS: The final analysis included 458 patients (age: 60.26 ± 8.07 years; 241 women). RFS increased linearly with an increasing number of dissected lymph nodes at a range between 0 and 9. Kaplan-Meier analysis revealed significantly longer RFS in patients with ≥ 9 vs. <9 dissected lymph nodes. In subgroup analysis, ≥ 9 dissected lymph nodes was not only associated with longer RFS in patients without lymph node metastasis (n = 332) but also in patients with metastasis (n = 126). In multivariate Cox proportional hazard regression, ≥ 9 dissected lymph nodes was independently associated with longer RFS (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.26 to 0.73; P = 0.002). CONCLUSIONS: ≥9 Dissected lymph nodes was associated with longer RFS; accordingly, we recommend dissecting 9 lymph nodes in patients undergoing lobectomy for stage IA pure solid lung adenocarcinoma.

Improved LC-MS/MS method for the simultaneous quantification of tacrolimus and cyclosporine A in human blood and application to therapeutic drug monitoring.

In order to facilitate therapeutic drug monitoring of tacrolimus and cyclosporine A in clinical practice, a simple, rapid, robust, sensitive and specific LC-MS/MS assay was developed and validated for the simultaneous determination of tacrolimus and cyclosporine A in human whole blood. Erythrocytes were destroyed using internal standard solution with 10% (w/v) zinc sulfate in water. The analytes were extracted from 100 µl of whole blood by protein precipitation with acetonitrile. Chromatographic separation was conducted on a Kinetex PFP column (60°C) by a gradient elution with a flow rate of 0.450 ml/min in 2.5 min. Quantitative analysis was performed using electrospray ionization and multiple reaction monitoring in positive ionization mode. The method was fully validated as per current guidelines on bioanalytical methodologies of the US Food and Drug Administration and European Medicines Agency. The method developed was applied successfully in analyzing clinical samples from patients administered tacrolimus or cyclosporine A. The sample treatment procedure was rationalized and improved to fulfill the complete target extraction. The chromatography conditions were optimized to achieve rapid and accurate quantification of both analytes. This method may be beneficial as a constructive input for the therapeutic drug monitoring of tacrolimus and cyclosporine A in obtaining individualized therapy.

A novel prognosis prediction of esophageal cancer based on chromatin regulator-related lncRNA.

It has been reported that chromatin regulators (CRs), as one of the essential upstream regulators of tumor development, were screened to construct a prognostic model for predicting the outcome of tumor patients. However, the prognostic model based on CRs-related long noncoding RNAs (lncRNAs) in esophageal cancer (EC) has never been researched. This study aims to construct a novel CRs-related lncRNA signature to evaluate the prognostic ability of EC patients. We obtained the transcriptome data and clinical information of patients with EC from the Cancer Genome Atlas database, 870 CRs-related genes from previous topic research. Univariate, multivariate Cox, the least absolute shrinkage and selection operator regression analyses were used to establish the risk model. The receiver operating characteristic curve, principal component analysis, nomogram, quantitative real-time PCR were performed to evaluate the independence and accuracy of the model. The biological functions and immune microenvironment of the risk model were analyzed by gene set enrichment analyses and R softwares. A novel 3 CRs-related lncRNAs risk model composed of AC079684.1, TMEM75, LINC00365, as an independent and superior factor, was established for prognosis prediction of EC patients. Quantitative real-time PCR analysis verified upregulated AC079684.1 and TMEM75 mRNA levels and downregulated LINC00365 mRNA level in EC tissues compared with normal tissues. Gene set enrichment analysis analysis displayed Kyoto encyclopedia of genes and genomes and gene ontology pathways enriched in risk groups, such as focal adhesion, pathways in cancer, epidermal cell differentiation. Immune cells and immune checkpoints were more likely to be activated in the high-risk group. Finally, we found most of the compounds in the high-risk group exhibited higher sensitivity through therapeutic drug screening. The 3 CRs-related lncRNAs risk model could independently predict the prognosis of EC and provide immunotherapy guidance for patients with EC.

A comprehensive diagnostic scheme of morphological combined molecular methylation under bronchoscopy.

Methylated SHOX2 and RASSF1A genes are potential biomarkers for lung cancer diagnosis. Therefore, we explored the role of methylation detection combined with morphological bronchoscopic evaluation for lung cancer diagnosis. Bronchoscopy, methylation outcome, and pathological data were collected from 585 patients with lung cancer and 101 controls. The methylation status of the SHOX2 and RASSF1A genes were detected using real-time polymerase chain reaction quantification. Further, the sensitivity and area under the receiver operating characteristic curve of the three methods were analyzed. Among 686 patients, 57.1% had new lesions detected through bronchoscopy and 93.1% of these patients were diagnosed with malignant tumors. Besides, 42.9% of patients had no visible changes under bronchoscopy but there were still 74.8% of them diagnosed with malignant tumors. Bronchoscopy revealed that lung adenocarcinoma, lung squamous cell carcinoma, and small cell lung cancer mainly occurred in the upper and middle lobes. The sensitivity and specificity of methylation detection were 72.8% and 87.1% (vs. cytology 10.4% & 100%), respectively. Therefore, methylated SHOX2 and RASSF1A genes may be promising tumor markers in lung cancer diagnosis. Methylation detection can be an excellent supplementary tool for cytological diagnosis and, combined with bronchoscopy, could form a more effective diagnostic process.

Clinical and Genomic Analysis of Patients with Short Survival after Surgery for Esophageal Squamous Cell Carcinoma.

BACKGROUND: This study aimed to investigate the prognosis of Chinese patients with esophageal squamous cell carcinoma (ESCC) after surgery and its correlation with genomic alterations (GAs) to identify potential prognostic markers. METHODS: The clinical information, pathological specimens, and follow-up information of 50 patients with stage II and III primary ESCC who were surgically resected in the Fourth Hospital of Hebei Medical University from January 2011 to December 2015 were collected in the present study. Based on overall survival (OS), these patients were divided into the short OS group (<3 years) and the long OS group (>4 years). GA detection was performed in patients with ESCC using next-generation sequencing. All categories of GAs were evaluated; the landscape of GAs in patients with ESCC was mapped; and the correlations between clinical characteristics, prognosis, and GAs were analyzed. RESULTS: There was no skew in the distribution of gender, smoking, and adjuvant therapy between the long OS group and the short OS group. A total of 372 GAs were detected in the 50 patients with ESCC, with 7 types of GAs, including insertions, deletions, and copy number variations, and missense mutations occurred most frequently, with a frequency of >50.0%. Tumor protein 53 (TP53; 50/50, 100%) was the most commonly mutated gene in the entire cohort followed by cyclin D1, cyclin-dependent kinase inhibitor 2A (CDKN2A), and fibroblast growth factor 19. More CDKN2A loss (p = 0.098) was detected in the short OS group than in the long OS group. The results of the multivariate analysis after adjustment for clinical factors showed a statistically significant difference in the CDKN2A loss between the two groups. Data obtained from The Cancer Genome Atlas for surgical ESCC revealed that the CDKN2A loss may be responsible for the poorer prognosis in postoperative patients with ESCC. CONCLUSION: In patients with progressive primary ESCC, the poor postoperative prognosis may be epiphenomenally associated with the CDKN2A loss.

hsa_circ_0000518 Facilitates Non-Small-Cell Lung Cancer Progression via Moderating miR-330-3p and Positively Regulating SLC1A5.

Background/Aim: Non-small-cell lung cancer (NSCLC) is the principal agent of cancer deaths globally. The goal of this study was to determine how circular RNA_0000518 (circ_0000518) regulates tumor progression. Materials/Methods. circ_0000518 was selected as a study target involved in NSCLC from GEO (Gene Expression Omnibus) database. circ_0000518 level was gauged by qRT-PCR. It was confirmed as circRNA by actinomycin D inhibition and RNase R assay. Subcellular localization of circ_0000518 was identified by FISH. Cell function was determined by CCK-8, Transwell, and western blot. Glutamine metabolic factors were detected by ELISA. The target regulation relationship between genes was clarified by dual-luciferase reporter assay. In vivo models were established to evaluate the impact of circ_0000518 on tumor growth. Immunohistochemical staining for Ki67, vimentin, and E-cadherin was used to detect cell proliferation and metastasis, respectively. Results: circ_0000518 expression was enhanced in NSCLC. si-circ_0000518 inhibited cell proliferation, invasion, and glutamine metabolism. circ_0000518 functioned as a molecular sponge for miR-330-3p, and inhibition of miR-330-3p in cells markedly reversed circ_0000518 interference-mediated antitumor effects. miR-330-3p interacted with 3'-UTR of SLC1A5. miR-330-3p inhibitor-mediated protumor effect was remarkably reversed in cells after the knockdown of SLC1A5. circ_0000518 knockdown reduced glutamine, glutamate, and α-KG by targeting miR-330-3p. Intertumoral injection of circ_0000518 shRNA adeno-associated virus effectively halted xenograft tumor growth. Conclusion: The current study revealed that circ_0000518 may have a prooncogenic function in the formation and progression of NSCLC, which might be achieved through moderating the miR-330-3p/SLC1A5 axis.

Production-Based and Consumption-Based Accounting of Global Cropland Soil Erosion.

The effective control of cropland soil erosion is urgent for all countries because of its threat to global food security. Cropland soil erosion is caused by agricultural production and driven indirectly by consumption. Analyzing the causes and preventive strategies from the consumption side is essential for soil erosion control. However, there is not yet sufficient research or practice. In this study, we estimated global cropland soil erosion with the revised universal soil loss equation, allocated it to specific types of crops, and quantified the cropland soil erosion footprint of the economies with a multiregional input-output analysis model. Our results showed that developed economies, usually importing cropland soil erosion from developing or agriculturally developed economies, are the beneficiaries in the current crop trading system. The European Union is the largest net importer, while Brazil is the largest exporter. The indirect and induced sectors are the main contributors, consuming approximately 70.48% of the total cropland soil erosion. Our results revealed the region- and product-specific contributors that could inform the reduction of global cropland soil erosion for sustainable food production and consumption.

CAF-derived exosomes deliver LINC01410 to promote epithelial-mesenchymal transition of esophageal squamous cell carcinoma.

Exosomes mediate cellular communications in cancer by transmitting active molecules. However, the CAFs-derived molecular determinants that regulate esophageal squamous cell carcinoma (ESCC) metastasis have not been fully characterized. The purpose of this study was to investigate the potential roles of exosomal LINC01410 of ESCC cells. The characteristics of exosomes were identified using transmission electron microscope (TEM), Nanoparticle Tracking Analysis (NTA). The expression of LINC01410 and miR-122-5p was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) assay. The biological roles of LINC01410 in ESCC cells were investigated using transwell assay. Western blot assay was employed to detect protein levels. The potential downstream molecular mechanism of LINC01410 was demonstrated with dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull down. CAFs promote the metastasis and epithelial-mesenchymal transition (EMT) of ESCC cells. CAFs exert their roles by transferring exosomes to ESCC cells, leading to a significant increase of LINC01410 level in ESCC cells. Mechanically, LINC01410 secreted by CAFs-Exo could contribute to metastasis and EMT by sponging miR-122-5p and increasing PKM2 level in TE-1 and Eca-109 cells. Additionally, LINC01410/miR-122-5p/PKM2 axis affecting ESCC metastasis and EMT in vitro and in vivo.

Circular RNA MTO1 intercorrelates with microRNA-630, both associate with Enneking stage and/or pathological fracture as well as prognosis in osteosarcoma patients.

OBJECTIVE: Circular RNA-mitochondrial tRNA translation optimization 1 (circ-MTO1) not only involves in bioprocess of various cancers, but also regulates osteosarcoma progression by regulating microRNA-630 (miR-630). However, the clinical role of circ-MTO1 and miR-630 in osteosarcoma is still obscure. This study aimed to assess the correlation of circ-MTO1 and miR-630 with disease features and prognosis and to explore their association with each other in osteosarcoma patients. METHODS: Forty-four osteosarcoma patients who received neoadjuvant chemotherapy to surgical resection were analyzed in this retrospective study. Then, circ-MTO1 and miR-630 expressions were evaluated in tumor and adjacent non-tumor specimens by reverse transcription quantitative polymerase chain reaction. RESULTS: Circ-MTO1 was lower in tumor than in non-tumor tissues (p<0.001); meanwhile, its elevated tumor expression was correlated with less advanced Enneking stage (p=0.049), good neoadjuvant chemotherapy response (p=0.029), and longer disease-free survival (DFS) (p=0.047). However, no association was found between circ-MTO1 and overall survival (OS) (p=0.122). Additionally, miR-630 in tumor was higher than in non-tumor tissues (p<0.001), while its raised tumor expression was associated with pathological fracture occurrence (p=0.003), advanced Enneking stage (p=0.036), poor neoadjuvant chemotherapy response (p=0.035), and shorter DFS (p=0.011). However, no association was found between miR-630 and OS (p=0.066). In addition, tumor circ-MTO1 was negatively associated with miR-630 (r=-0.323, p=0.032). CONCLUSION: Circ-MTO1 and miR-630 expressions are inter-correlated and dysregulated in osteosarcoma patients. Besides, they associate with Enneking stage and/or pathological fracture, as well as neoadjuvant treatment response and accumulating DFS in these patients.

Efficacy and Safety of Triple versus Dolutegravir-based Dual Therapy in Patients with HIV-1 Infection: A Meta-analysis of Randomized Controlled Trials.

A new strategy of simplification therapy shown the unique benefits in clinical treatment, by reducing pill burden and avoid drug exposure. To provide more evidence for the strategy, we compared the efficacy and safety of dolutegravir (DTG)-containing simplified dual combination antiretroviral therapy (cART) and traditional triple cART for people living with HIV/AIDS. The meta-analysis of randomized controlled trials compared DTG-containing dual therapy with triple cART. The primary outcome was virologic suppression. The secondary outcomes included CD4T cell recovery, lipids change from baseline, and adverse events (AEs). A total of 7 studies, 4852 patients were eligible, 2423 (49.9%) received DTG-based simplified dual cART, and 2429 (50.1%) received triple cART. The viral suppression rate was 94.7% at 24 weeks, 93.0% at 48 weeks, and 96.6% at 96 weeks in dual cART. The viral suppression rate of dual cART was non-inferior to triple cART at 24 weeks (risk difference [RD], -0.00; 95% confidence interval [CI] -0.02-0.01), at 48 weeks (RD, -0.01; 95% CI -0.02-0.01), and at 96 weeks (RD, -0.01; 95% CI -0.02-0.00). Sub-analysis results were consistent with the overall results. With regard to other outcomes (CD4T counts, lipids, any AEs, and AEs grade ≥ 3), there was no significant statistical difference between the two regimens. DTG-based simplified dual cART was non-inferior to triple cART in terms of efficacy and safety. This finding provides strong support for current consensus guidelines recommended the dual regimen as first-line treatment.

Integrase inhibitors versus efavirenz combination antiretroviral therapies for TB/HIV coinfection: a meta-analysis of randomized controlled trials.

BACKGROUND: Integrase inhibitors (INIs)-based antiretroviral therapies (ART) are more recommended than efavirenz (EFV)-based ART for people living with HIV/AIDS (PLWHA). Yet, the advantage of integrase inhibitors in treating TB/HIV coinfection is uncertain. Therefore, the objective of this systematic review is to evaluate the effects and safety of INIs- versus EFV-based ART in TB/HIV coinfection, and demonstrate the feasibility of the regimens. METHODS: Four electronic databases were systematically searched through September 2020. Fixed-effects models were used to calculate pooled effect size for all outcomes. The primary outcomes were virologic suppression and bacteriology suppression for INIs- versus EFV-based ART. Secondary outcomes included CD4+ cell counts change from baseline, adherence and safety. RESULTS: Three trials (including 672 TB/HIV patients) were eligible. ART combining INIs and EFV had similar effects for all outcomes, with none of the point estimates argued against the INIs-based ART on TB/HIV patients. Compared to EFV-based ART as the reference group, the RR was 0.94 (95% CI 0.85 to 1.05) for virologic suppression, 1.00 (95% CI 0.95 to 1.05) for bacteriology suppression, 0.98 (95% CI 0.95 to 1.01) for adherence. The mean difference in CD4+ cell counts increase between the two groups was 14.23 cells/µl (95% CI 0- 6.40 to 34.86). With regard to safety (adverse events, drug-related adverse events, discontinuation for drugs, grade 3-4 adverse events, IRIS (grade 3-4), and death), INIs-based regimen was broadly similar to EFV-based regimens. The analytical results in all sub-analyses of raltegravir- (RAL) and dolutegravir (DTG) -based ART were valid. CONCLUSION: This meta-analysis demonstrates similar efficacy and safety of INIs-based ART compared with EFV-based ART. This finding supports INIs-based ART as a first-line treatment in TB/HIV patients. The conclusions presented here still await further validation owing to insufficient data.

Telecoupling cropland soil erosion with distant drivers within China.

Soil erosion on cropland is a result of the interaction between nature and human activities. The socioeconomic influencing factors of soil erosion have been less studied than the biophysical processes and previous studies have mainly focused on the impacts of local socioeconomic factors on soil erosion in the same region. However, since agricultural activities are densely connected to other socio-economic activities, the need for agricultural products from distant regions could potentially drive local soil erosion accompanying agricultural production. To the best of our knowledge, these telecoupling effects have not been studied. Here, we combined the Revised Universal Soil Loss Equation (RUSLE) and multiregional input-output analysis (MRIO) models to quantify the contribution of China's cross-provincial economic demand to local soil erosion at the provincial, sectoral, and supply chain levels. Our results show that a large amount of soil erosion in the southwest, northeast, and central regions is linked to the economic needs across provinces. Agriculture and food processing are the most important distant driving sectors. The driving effect of household consumption on soil erosion mainly occurs on shorter supply chains, while exports and capital formation drive soil erosion through longer chains. Our results indicate that local soil erosion management must consider the impact of distant agricultural product needs and coordinate food production and supply on a national scale to protect the ecological function of the land.