Synergistic Effects of Glutamine Deprivation and Metformin in Acute Myeloid Leukemia.

OBJECTIVE: The metabolic reprogramming of acute myeloid leukemia (AML) cells is a compensatory adaptation to meet energy requirements for rapid proliferation. This study aimed to examine the synergistic effects of glutamine deprivation and metformin exposure on AML cells. METHODS: SKM-1 cells (an AML cell line) were subjected to glutamine deprivation and/or treatment with metformin or bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES, a glutaminase inhibitor) or cytarabine. Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay, and cell apoptosis and reactive oxygen species (ROS) by flow cytometry. Western blotting was conducted to examine the levels of apoptotic proteins, including cleaved caspase-3 and poly(ADP-ribose) polymerase (PARP). Moreover, the human long noncoding RNA (lncRNA) microarray was used to analyze gene expression after glutamine deprivation, and results were confirmed with quantitative RT-PCR (qRT-PCR). The expression of metallothionein 2A (MT2A) was suppressed using siRNA. Cell growth and apoptosis were further detected by CCK-8 assay and flow cytometry, respectively, in cells with MT2A knockdown. RESULTS: Glutamine deprivation or treatment with BPTES inhibited cell growth and induced apoptosis in SKM-1 cells. The lncRNA microarray result showed that the expression of MT family genes was significantly upregulated after glutamine deprivation. MT2A knockdown increased apoptosis, while proliferation was not affected in SKM-1 cells. In addition, metformin inhibited cell growth and induced apoptosis in SKM-1 cells. Both glutamine deprivation and metformin enhanced the sensitivity of SKM-1 cells to cytarabine. Furthermore, the combination of glutamine deprivation with metformin exhibited synergistic antileukemia effects on SKM-1 cells. CONCLUSION: Targeting glutamine metabolism in combination with metformin is a promising new therapeutic strategy for AML.

Utilization of the Caprini risk assessment model(RAM) to predict venous thromboembolism after primary hip and knee arthroplasty: an analysis of the Healthcare Cost and Utilization Project(HCUP).

PURPOSE: This study aims to investigate the potential role of Caprini risk assessment model (RAM) in predicting the risk of venous thromboembolism (VTE) in patients undergoing total hip or knee arthroplasty (THA/TKA). No national study has investigated the role of Caprini RAM after primary THA/TKA. METHODS: Data from The National Sample of Healthcare Cost and Utilization Project (HCUP) in 2019 were utilized for this study. The dataset consisted of 229,134 patients who underwent primary THA/TKA. Deep vein thrombosis (DVT) and pulmonary embolism (PE) were considered as VTE. The incidence of thrombosis was calculated based on different Caprini scores, and the risk of the Caprini indicator for VTE events was evaluated using a forest plot. RESULTS: The prevalence of VTE after primary THA/TKA in the U.S. population in 2019 was found to be 4.7 cases per 1000 patients. Age, body mass index (BMI), and Caprini score showed a positive association with the risk of VTE (P < 0.05). The receiver operating characteristic (ROC) curve analysis indicated that a Caprini score of 9.5 had a sensitivity of 47.2% and a specificity of 82.7%, with an area under the curve (AUC) of 0.693 (95% CI, 0.677-0.710). The highest Youden index was 0.299. Multivariate logistic regression analysis revealed that malignancy, varicose vein, positive blood test for thrombophilia, history of thrombosis, COPD, hip fracture, blood transfusion, and age were significant risk factors for VTE. Based on these findings, a new risk stratification system incorporating the Caprini score was proposed. CONCLUSIONS: Although the Caprini score does not seem to be a good predictive model for VTE after primary THA/TKA, new risk stratification for the Caprini score is proposed to increase its usefulness.

Associations of lifestyle characteristics with circulating immune markers in the general population based on NHANES 1999 to 2014.

Lifestyles maybe associated with the immune and inflammatory state of human body. We aimed to comprehensively explore the relationship between lifestyles and circulating immune-inflammatory markers in the general population. Data from NHANES 1999-2014 was used. Lifestyle factors included leisure-time physical activity (LTPA), diet quality (Healthy Eating Index-2015, HEI-2015), alcohol consumption, cigarettes smoking, sleep hour and sedentary time. Immune makers included C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet-lymphocyte ratio (PLR) and monocyte-lymphocyte ratio (MLR). Generalized linear regression models were used to adjust confounders. Regressions of restricted cubic splines were utilized to evaluate the potentially non-linear relationships between exposures and outcomes. As results, HEI was negatively associated with CRP (P < 0.001), SII (P < 0.001), and NLR (P < 0.001). Cigarettes per day was positively associated with CRP (P < 0.001), SII (P < 0.001), and NLR (P = 0.008). Alcohol consumption was negatively associated with CRP (P < 0.001), but positively associated with PLR (P = 0.012) and MLR (P < 0.001). Physical activity was negatively associated with CRP (P < 0.001), SII (P = 0.005), and NLR (P = 0.002), but positively associated with PLR (P = 0.010). Participants with higher healthy lifestyle score had significantly lower CRP, SII and NLR (all P values < 0.05). Most of the sensitivity analyses found similar results. In conclusion, we found significant associations between lifestyles and immune markers in the general population, which may reflect a systemic inflammatory response to unhealthy lifestyles.

Efficiency of transurethral en-bloc resection vs. conventional transurethral resection for non-muscle-invasive bladder cancer: An umbrella review.

BACKGROUND: En-Bloc transurethral resection of bladder tumor (ERBT) was clinically used to resect non-muscle-invasive bladder cancer (NMIBC). However, discrepancies persist regarding the comparisons between ERBT and conventional transurethral resection of bladder tumor (cTURBT). METHODS: We conducted a comprehensive search in PubMed, Embase, Web of Science, Cochrane Database of Systematic Reviews, and performed manual searches of reference lists to collect and extract data. Data evaluation was carried out using Review Manager 5.4.0, Rx64 4.1.3, and relevant packages. RESULTS: There were nine eligible meta-analyses and nine eligible RCTs in our study. NMIBC patients undergoing ERBT were significant associated with a lower rate of bladder perforation and obturator nerve reflex compared to those receiving cTURBT. Our pooled result indicated that ERBT and cTURBT required similar operation time. Regarding postoperative outcomes, ERBT demonstrated superior performance compared to cTURBT in terms of detrusor muscle presence, catheterization time, and residual tumor. ERBT exhibited a higher rate of three-month recurrence-free survival (RFS) compared to those receiving cTURBT (p < 0.05; I2 = 0%). In bipolar subgroup, ERBT had a significant better 12-month RFS than cTURBT (p < 0.05; I2 = 0%). Simultaneously, the exclusion of Hybrid Knife data revealed a significant improvement in 12-month RFS associated with ERBT (p < 0.05; I2 = 50%). CONCLUSION: Using a combination of umbrella review and meta-analysis, we demonstrated that ERBT had better or comparable perioperative outcome and improved 3 and 12 month RFS than cTURBT. We suggest that ERBT maybe a better surgical method for patients with NMIBC compared with cTURBT.

DLL1/NOTCH1 signaling pathway maintain angiogenesis in meniscus development and degeneration.

OBJECTIVES: The decline in vascular capacity within the meniscus is a well-documented phenomenon during both development and degeneration. Maintaining vascular integrity has been proposed as a potential therapeutic strategy for osteoarthritis. Therefore, our study aims to investigate the characteristics of endothelial cells and blood vessels in embryonic and degenerated meniscus tissues. METHODS: Human embryonic and mature menisci were used for histological analyses. Single-cell RNA sequencing was used to identify cell clusters and their significant genes in embryo meniscus to uncover characteristic of endothelial cells. Computer analysis and various staining techniques were used to characterize vessels in development and osteoarthritis meniscus. RESULTS: Vessels structure first observed in E12w and increasing in E14w. Vessels were veins majorly and arteries growth in E35w. Endothelial cells located not only perivascular but also in the surface of meniscus. The expression of DLL1 was observed to be significantly altered in endothelial cells within the vascular network that failed to form. Meniscus tissues affected by osteoarthritis, characterized by diminished vascular capacity, displayed reduced levels of DLL1 expression. Experiment in vitro confirmed DLL1/NOTCH1 be vital to angiogenesis. CONCLUSION: Lack of DLL1/NOTCH1 signaling pathway was mechanism of vascular declination in development and degenerated meniscus.

Single-cell and bulk RNA-sequencing reveals mitosis-involved gene HAUS1 is a promising indicator for predicting prognosis and immune responses in prostate adenocarcinoma (PRAD).

It was imperative to identify latent biomarkers pertinent to malignancies, given the pivotal role targeted molecular therapies play in tumor treatment investigations. This study aimed to assess the validity of HAUS1 as an indicator for survival prognosis and immune responses in prostate adenocarcinoma (PRAD) via single-cell and bulk RNA-sequencing. Related data on HAUS1 expression in PRAD were obtained from online databases, followed by comprehensive analyses to delineate its associations with survival prognosis, implicated pathways, and immune responses. Besides, the expression pattern of HAUS1 in PRAD was also verified in vitro, by using qRT-PCR, Western blot analysis, and immunohistochemistry. We found HAUS1 was downregulated in PRAD compared with normal tissues, as verified in vitro by qRT-PCR, Western blot, and immunohistochemistry (p < 0.05). Single-cell RNA-sequencing analysis indicated that HAUS1 had relatively higher expressions in B cells, Mono/Macro cells, and Endothelial cells compared with other cell types. Cox regression analysis revealed HAUS1 could serve as an independent indicator for the overall survival prognosis of PRAD (p < 0.05). Spearman correlation analyses revealed HAUS1 was closely related to the tumor microenvironment, immune cell infiltration levels, immune checkpoints, and immune cell pathways (p < 0.05). Furthermore, HAUS1 expression was found to be closely related to the immunotherapeutic response of patients receiving clinical intervention (p < 0.05). Collectively, our findings underscored the significant role of HAUS1 in PRAD prognosis and immune response, thereby presenting a novel and promising avenue for investigating the clinical utility of immunotherapy in PRAD.

Efficiency of bladder-sparing strategies for bladder cancer: an umbrella review.

Bladder preservation (BP) has emerged as a clinical alternative to radical cystectomy (RC) for alleviating the substantial physical and psychological burden imposed on localized bladder cancer patients. Nevertheless, disparities persist in the comparative evaluations of BP and RC. We aimed to address the disparities between BP and RC. An umbrella review and meta-analysis were conducted to explore these disparities. We extracted data from meta-analyses and randomized controlled trials (RCTs) selected after searching PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews. Review Manager 5.4.0 and R x64 4.1.3 were used to evaluate the collected data. Our study included 11 meta-analyses and 3 RCTs. In terms of progression-free survival, all the meta-analyses reported that patients with localized bladder cancer who underwent BP exhibited outcomes comparable to those who underwent RC. Meta-analyses regarding the outcomes of cancer-specific survival (CSS) and overall survival (OS) are controversial. To solve these issues, we conducted a pooled analysis of CSS data, which supported the similarity of CSS between BP and RC with no significant heterogeneity [odds ratio (OR): 1.2; 95% confidence interval (CI): 0.71-2.02; I2 = 26%]. Similarly, the pooled OS results extracted from three RCTs indicated the comparability of OS between BP and RC with no significant heterogeneity (OR: 1.12; 95% CI: 0.41-3.07; I2 = 33%). A combination of umbrella review and meta-analysis results suggested that BP had survival rates comparable to those of RC. We suggest that BP may be a more eligible therapy than RC for patients with localized muscle-invasive bladder cancer. This conclusion warrants further validation through randomized controlled trials.

Genetically engineered mouse model of HPV16 E6-E7 with vaginal-cervical intraepithelial neoplasia and decreased immunity.

Objective: To construct models of high-risk human papillomavirus (HPV) infection with precancerous lesions or cervical cancer and explore the immune function. Methods: Using CRISPR/Cas9, the expression vector HPV16-E6-E7-Rosa26 was microinjected into fertilized eggs of C57BL/6 N mice using homologous recombination, and the F0 generation was obtained for reproduction. Then, the formation of precancerous lesions was promoted via intramuscular injection of estradiol. Presence of precancerous cervical-vaginal intraepithelial lesions, Ki67 and p16 expression levels, and CD8+ T cell proportions in the spleen were evaluated. Results: Two F0 generation mice exhibited correct the homologous recombination. Seven positive mice were identified in the F1 generation. After breeding and mating, 25 homozygous and 11 heterozygous HPV16-E6-E7-engineered mice were obtained from the F2 generation. After estradiol benzoate treatment, the cervical-vaginal epithelium appeared as precancerous lesions with positive Ki67 and p16 expression. The percentage of CD8+ T cells decreased. Conclusion: HPV16-E6-E7-Rosa26 induced low immune function in mice, and provides a good model for the basic research of the mechanisms of action of HPV infection-associated precancerous lesions or cervical cancer.

CD34+ synovial fibroblasts exhibit high osteogenic potential in synovial chondromatosis.

Synovial chondromatosis (SC) is a disorder of the synovium characterized by the formation of osteochondral nodules within the synovium. This study aimed to identify the abnormally differentiated progenitor cells and possible pathogenic signaling pathways. Loose bodies and synovium were obtained from patients with SC during knee arthroplasty. Single-cell RNA sequencing was used to identify cell subsets and their gene signatures in SC synovium. Cells derived from osteoarthritis (OA) synovium were used as controls. Multi-differentiation and colony-forming assays were used to identify progenitor cells. The roles of transcription factors and signaling pathways were investigated through computational analysis and experimental verification. We identified an increased proportion of CD34+ sublining fibroblasts in SC synovium. CD34+CD31- cells and CD34-CD31- cells were sorted from SC synovium. Compared with CD34- cells, CD34+ cells had larger alkaline phosphatase (ALP)-stained area and calcified area after osteogenic induction. In addition, CD34+ cells exhibited a stronger tube formation ability than CD34- cells. Our bioinformatic analysis suggested the expression of TWIST1, a negative regulator of osteogenesis, in CD34- sublining fibroblasts and was regulated by the TGF-ß signaling pathway. The experiment showed that CD34+ cells acquired the TWIST1 expression during culture and the combination of TGF-ß1 and harmine, an inhibitor of Twist1, could further stimulate the osteogenesis of CD34+ cells. Overall, CD34+ synovial fibroblasts in SC synovium have multiple differentiation potentials, especially osteogenic differentiation potential, and might be responsible for the pathogenesis of SC.

The implications of single-cell RNA-seq analysis in prostate cancer: unraveling tumor heterogeneity, therapeutic implications and pathways towards personalized therapy.

In recent years, advancements in single-cell and spatial transcriptomics, which are highly regarded developments in the current era, particularly the emerging integration of single-cell and spatiotemporal transcriptomics, have enabled a detailed molecular comprehension of the complex regulation of cell fate. The insights obtained from these methodologies are anticipated to significantly contribute to the development of personalized medicine. Currently, single-cell technology is less frequently utilized for prostate cancer compared with other types of tumors. Starting from the perspective of RNA sequencing technology, this review outlined the significance of single-cell RNA sequencing (scRNA-seq) in prostate cancer research, encompassing preclinical medicine and clinical applications. We summarize the differences between mouse and human prostate cancer as revealed by scRNA-seq studies, as well as a combination of multi-omics methods involving scRNA-seq to highlight the key molecular targets for the diagnosis, treatment, and drug resistance characteristics of prostate cancer. These studies are expected to provide novel insights for the development of immunotherapy and other innovative treatment strategies for castration-resistant prostate cancer. Furthermore, we explore the potential clinical applications stemming from other single-cell technologies in this review, paving the way for future research in precision medicine.

An endothelial-related prognostic index for bladder cancer patients.

BACKGROUND: Within the tumor microenvironment, endothelial cells hold substantial sway over bladder cancer (BC) prognosis. Herein, we aim to elucidate the impact of endothelial cells on BC patient outcomes by employing an integration of single-cell and bulk RNA sequencing data. METHODS: All data utilized in this study were procured from online databases. R version 3.6.3 and relevant packages were harnessed for the development and validation of an endothelial-associated prognostic index (EPI). RESULTS: EPI was formulated, incorporating six genes (CYTL1, FAM43A, GSN, HSPG2, RBP7, and SLC2A3). EPI demonstrated significant prognostic value in both The Cancer Genome Atlas (TCGA) and externally validated dataset. Functional results revealed a profound association between EPI and endothelial cell functionality, as well as immune-related processes. Our findings suggest that patients with low-risk EPI scores are more likely to respond positively to immunotherapy, as indicated by immune checkpoint activity, immune infiltration, tumor mutational burden, stemness index, TIDE, and IMvigor210 analyses. Conversely, individuals with high-risk EPI scores exhibited heightened sensitivity to cisplatin, docetaxel, and gemcitabine treatment regimens. CONCLUSION: We have effectively discerned pivotal genes from the endothelial cell perspective and constructed an EPI for BC patients, thereby offering promising prospects for precision medicine.

Nonpathogenic E. coli engineered to surface display cytokines as a new platform for immunotherapy.

Given the safety, tumor tropism, and ease of genetic manipulation in non-pathogenic Escherichia coli (E. coli), we designed a novel approach to deliver biologics to overcome poor trafficking and exhaustion of immune cells in the tumor microenvironment, via the surface display of key immune-activating cytokines on the outer membrane of E. coli K-12 DH5α. Bacteria expressing murine decoy-resistant IL18 mutein (DR18) induced robust CD8+ T and NK cell-dependent immune responses leading to dramatic tumor control, extending survival, and curing a significant proportion of immune-competent mice with colorectal carcinoma and melanoma. The engineered bacteria demonstrated tumor tropism, while the abscopal and recall responses suggested epitope spreading and induction of immunologic memory. E. coli K-12 DH5α engineered to display human DR18 potently activated mesothelin-targeting CAR NK cells and safely enhanced their trafficking into the tumors, leading to improved control and survival in xenograft mice bearing mesothelioma tumor cells, otherwise resistant to NK cells. Gene expression analysis of the bacteria-primed CAR NK cells showed enhanced TNFα signaling via NFkB and upregulation of multiple activation markers. Our novel live bacteria-based immunotherapeutic platform safely and effectively induces potent anti-tumor responses in otherwise hard-to-treat solid tumors, motivating further evaluation of this approach in the clinic.

Actively extracting kidney stones combined dusting technique can improve SFR of moderate-complexity kidney stones in fURL.

PURPOSE: To evaluate the necessity and effectiveness of actively extracting kidney stones with different complexity that have been visually dusted in flexible ureteroscopic lithotripsy (fURL). METHODS: We retrospectively reviewed the medical records of patients who underwent fURL with dusting technique in established hospitals. A total of 535 cases were divided into the dusting group or the dusting plus basketing group according to the use of stone basket. Their characteristics and operative parameters were collected and analyzed. We used the R.I.R.S. scoring system to classify the complexity of kidney stones and divided these kidney stones into three subgroups, namely, mild-, moderate-, and severe-complexity group. And then, the effectiveness of stone basket in these subgroups was analyzed. RESULTS: Although using a stone basket significantly reduced re-operation rate (17.8% in dusting group versus 10.2% in dusting plus basketing group, p = 0.013), no significant difference on stone-free rate (SFR) and overall incidence of complications were noticed between groups. After we classified the complexity of kidney stones using the R.I.R.S. scoring system, we found a stone basket was helpful to improve SFR in kidney stones with moderate-complexity that had been visually dusted in fURL (73.5% in dusting group versus 87.3% in dusting plus basketing group, p = 0.002) but had limited influence on SFR in mild (93.8% in dusting group versus 92.6% in dusting plus basketing group, p = 0.783) or severe (28.5% in dusting group versus 34.0% in dusting plus basketing group, p = 0.598)-complexity kidney stones. CONCLUSION: The use of stone basket should be encouraged in moderate-complexity kidney stones which can be visually dusted in fURL.

Chlorogenic acid improves common carp (Cyprinus carpio) liver and intestinal health through Keap-1/Nrf2 and NF-κB signaling pathways: Growth performance, immune response and antioxidant capacity.

In this experiment, we investigated the effects of adding chlorogenic acid (CGA) to the diet on growth performance, immune function, inflammation response, antioxidant capacity and its related mechanisms of common carp (Cyprinus carpio). A total of 600 fish were selected and randomly divided into five treatment groups and fed with CGA containing 0 mg/kg (CK), 100 mg/kg (L100), 200 mg/kg (L200), 400 mg/kg (L400) and 800 mg/kg (L800) for 56 days. The results of the experiment were as follows: addition of CGA significantly increased the WGR, SGR, FER, and PER of common carp (P < 0.05). The addition of 400-800 mg/kg of CGA significantly increased the serum levels of LZM, AKP activity, C3 and C4 concentration, and increased immune function of common carp (P < 0.05). Regarding antioxidant enzyme activities, adding CGA significantly increased SOD, CAT, and GsH-Px activities, while decreasing MDA content (P < 0.05). Compared with the CK group, the mRNA expression levels of NF-κB, TNF-α, and IL-1ß were decreased. The IL-10 and TGF-ß were increased in the liver and intestines of the CGA supplemented group. Meanwhile, the addition of CGA also significantly up-regulated the mRNA expression levels of Nrf2, HO-1, SOD, CAT, and GPX (P < 0.05). CGA also positively contributed to the development of the carp intestinal tract, as demonstrated by decreased serum levels of DAO, D-LA, and ET-1. And the mucosal fold height was increased significantly with increasing levels of CGA. In conclusion, the addition of CGA in the feed can enhance the growth performance, immune function and antioxidant capacity of common carp, and improve the health of the intestine and liver. According to the results of this experiment, the optimal addition amount in common carp diets was 400 mg/kg.

Follow-up study of isolated calf muscular vein thrombosis for anticoagulant therapy after primary hip and knee arthroplasty.

BACKGROUND: Although isolated calf muscular vein thrombosis (ICMVT) is commonly seen after hip and knee arthroplasty, no treatment guidelines for ICMVT after joint replacement are available. The purpose of this study was to evaluate the outcomes of patients with ICMVT for anticoagulant therapy at different time points after primary hip and knee arthroplasty. METHODS: Patients with ICMVT after primary hip and knee arthroplasty were included in the study. Diagnosis was established with Doppler ultrasound. Patients were followed up clinically and with Doppler ultrasound at 1, 2, and 3 months. The outcomes were efficacy (complete resolution) and acceptability (hemorrhagic events). Anticoagulant therapy at curative dosage was prescribed for 1 month and was extended for 2 additional months in case of incomplete resolution at 1 month or if propagation was present. The chi-square test was used to compare the outcomes at different time points. RESULTS: 302 patients were taken hip and knee arthroplasty from January 2021 to May 2022, in which 51 patients presented with 51 ICMVTs postoperatively. The incidence of ICMVT was about 16.89%. Resolution of ICMVT was considered complete at 1, 2, and 3 months at 36.73%, 61.22%, and 91.84%, respectively, with significant differences among the time points (P < 0.05). All patients with ICMVT receiving anticoagulant therapy remained free of propagations and hemorrhagic events within 3 months. CONCLUSION: Our findings provide new insights into the anticoagulant therapy for ICMVT after primary hip and knee arthroplasty, taking oral Rivaroxaban for 3 months is effective and safe, which contributes to provide the reference for clinical practice.

Unlocking the potential of N-acetylcysteine: Improving hepatopancreas inflammation, antioxidant capacity and health in common carp (Cyprinus carpio) via the MAPK/NF-κB/Nrf2 signalling pathway.

N-acetylcysteine (NAC) positively contributes to enhancing animal health, regulating inflammation and reducing stress by participating in the synthesis of cysteine, glutathione, and taurine in the body. The present study aims to investigate the effects of dietary different levels of NAC on the morphology, function and physiological state of hepatopancreas in juvenile common carp (Cyprinus carpio). 450 common carps were randomly divided into 5 groups: N1 (basal diet), N2 (1.5 g/kg NAC diet), N3 (3.0 g/kg NAC diet), N4 (4.5 g/kg NAC diet) and N5 (6.0 g/kg NAC diet), and fed for 8 weeks. The results indicated that dietary 3.0-6.0 g/kg NAC reduced hepatopancreas lipid vacuoles and nuclear translocation, and inhibited apoptosis in common carp. Simultaneously, the activities of hepatopancreas alanine aminotransferase and aspartate aminotransferase progressively increased with rising dietary NAC levels. Dietary NAC enhanced the non-specific immune function of common carp, and exerted anti-inflammatory effects by inhibiting the MAPK/NF-κB signaling pathway. Additionally, dietary 3.0-6.0 g/kg NAC significantly improved the antioxidant capacity of common carp, which was associated with enhanced glutathione metabolism, clearance of ROS and the activation of Nrf2 signaling pathway. In summary, NAC has the potential to alleviate inflammation, mitigate oxidative stress and inhibit apoptosis via the MAPK/NF-κB/Nrf2 signaling pathway, thereby improving hepatopancreas function and health of common carp. The current findings provide a theoretical basis for promoting the application of NAC in aquaculture and ecological cultivation of aquatic animals.

Comparative Efficacy and Safety of Measures for the Treatment of Adults with Isolated Calf Muscular Vein Thrombosis: A Systematic Review and Network Meta-analysis.

BACKGROUND: Isolated calf muscular vein thrombosis (ICMVT) can result in pulmonary embolism, but the treatment of ICMVT remains controversial. Therefore, the purpose of the present study was to investigate the optimal treatment for the ICMVT by comparing the efficacy and safety of different treatments. METHODS: A network meta-analysis was conducted to search for studies published from database inception to April 30, 2022, that compared the outcomes of 2 or more treatments for ICMVT. The primary outcomes were efficacy (resolution rate) and safety (adverse reactions). Data were extracted following predefined hierarchy and the Cochrane Collaboration risk of bias tool was used to evaluate the methodological quality of the included studies. We estimated summary odds ratios with 95% credibility intervals using Bayesian network meta-analysis with random effects. RESULTS: A total of 16 studies were enrolled in the study. In terms of efficacy and safety, urokinase thrombolysis combined with low-molecular-weight heparin (LMWH) was most effective but had the lowest safety, while physical therapy was safest but had the lowest efficacy. More important, direct oral factor Xa inhibitors were most likely to be second most effective and safe compared with other treatments. For the duration of treatment, anticoagulant therapy for at least 3 months could effectively increase the resolution rate of ICMVT. CONCLUSIONS: Considering both efficacy and safety, taking direct oral factor Xa inhibitors for at least 3 months was the optimal treatment compared to LMWH, urokinase thrombolysis combined LMWH, physical therapy and warfarin for patients with ICMVT.