An improved alphaviruses-specific RT-qPCR facilitates monitoring and prevention of alphaviruses.

Molecular surveillance is vital for monitoring arboviruses, often employing genus-specific quantitative reverse-transcription polymerase chain reaction (RT-qPCR). Despite this, an overlooked chikungunya fever outbreak occurred in Yunnan province, China, in 2019 and false negatives are commonly encountered during alphaviruses screening practice, highlighting the need for improved detection methods. In this study, we developed an improved alphaviruses-specific RT-qPCR capable of detecting chikungunya virus, eastern equine encephalitis virus, western equine encephalitis virus, Venezuelan equine encephalitis virus, Sindbis virus, Mayaro virus, and Ross River virus with high sensitivity and specificity. The assay identified three chikungunya virus-positive cases out of 188 sera retrospectively. Later genetic characterization suggested that imported cases from neighboring countries may be responsible for the neglected chikungunya fever outbreak of 2019 in Yunnan. Our findings underscore the value of improved alphaviruses-specific RT-qPCR in bolstering alphaviruses surveillance and informing preventive strategies.

DEB-TACE versus cTACE for unresectable HCC with B1-type bile duct invasion after successful biliary drainage: A propensity score matching analysis.

BACKGROUND: Transarterial chemoembolization (TACE) is the standard treatment for intermediate-stage hepatocellular carcinoma (HCC). Given the lack of specific recommendations for conventional TACE (cTACE) and drug-eluting bead TACE (DEB-TACE) in patients having unresectable HCC with tumor infiltrating the common hepatic duct or the first-order branch of the bile ducts (B1-type bile duct invasion; B1-BDI) after biliary drainage, we retrospectively compared the safety and efficacy of DEB-TACE with cTACE in this patient population. MATERIALS AND METHODS: Using data from five tertiary medical centers (January 2017-December 2021), we compared complications, overall survival (OS), time to progression (TTP), and tumor response rate between patients having unresectable HCC with B1-BDI who underwent DEB-TACE or cTACE after successful biliary drainage. X-tile software calculated the pre-TACE total bilirubin (TBil) cutoff value, indicating optimal timing for sequential TACE after drainage. Propensity score matching (PSM) was performed. RESULTS: The study included 108 patients with unresectable HCC (B1-BDI) who underwent DEB-TACE and 114 who received cTACE as initial treatment. After PSM (n = 53 for each group), the DEB-TACE group had a longer TTP (8.9 vs. 6.7 months, p = 0.038) and higher objective response rate (64.2% vs. 39.6%, p = 0.011) than did the cTACE group, although OS was comparable (16.7 vs. 15.3 months, p = 0.115). The DEB-TACE group exhibited fewer post-procedural increments in the mean albumin-bilirubin score, TBil, and alanine aminotransferase (ALT), along with a significantly lower incidence of serious adverse events within 30 days (hepatic failure, ALT increase, and TBil increase) than the cTACE group (all p < 0.05). The pre-TACE TBil cutoff value was 99 µmol/L; patients with higher values (>99 µmol/L) had poorer OS in both groups (p < 0.05). CONCLUSION: DEB-TACE is safe and effective after successful biliary drainage in unresectable HCC with B1-BDI, potentially better than cTACE in terms of liver toxicity, TTP, and ORR. Lowering TBil below 99 µmol/L through successful drainage may create ideal conditions for sequential TACE.

Survival in Patients With Recurrent Intermediate-Stage Hepatocellular Carcinoma: Sorafenib Plus TACE vs TACE Alone Randomized Clinical Trial.

Importance: Transarterial chemoembolization (TACE) is commonly used to treat patients with recurrent intermediate-stage hepatocellular carcinoma (HCC) and positive microvascular invasion (MVI); however, TACE alone has demonstrated unsatisfactory survival benefits. A previous retrospective study suggested that TACE plus sorafenib (SOR-TACE) may be a better therapeutic option compared with TACE alone. Objective: To investigate the clinical outcomes of SOR-TACE vs TACE alone for patients with recurrent intermediate-stage HCC after R0 hepatectomy with positive MVI. Design, Setting, and Participants: In this phase 3, open-label, multicenter randomized clinical trial, patients with recurrent intermediate-stage HCC and positive MVI were randomly assigned in a 1:1 ratio via a computerized minimization technique to either SOR-TACE treatment or TACE alone. This trial was conducted at 5 hospitals in China, and enrolled patients from October 2019 to December 2021, with a follow-up period of 24 months. Data were analyzed from June 2023 to September 2023. Interventions: Randomization to on-demand TACE (conventional TACE: doxorubicin, 50 mg, mixed with lipiodol and gelatin sponge particles [diameter: 150-350 µm]; drug-eluting bead TACE: doxorubicin, 75 mg, mixed with drug-eluting particles [diameter: 100-300 µm or 300-500 µm]) (TACE group) or sorafenib, 400 mg, twice daily plus on-demand TACE (SOR-TACE group) (conventional TACE: doxorubicin, 50 mg, mixed with lipiodol and gelatin sponge particles [diameter, 150-350 µm]; drug-eluting bead TACE: doxorubicin, 75 mg, mixed with drug-eluting particles [diameter: 100-300 µm or 300-500 µm]). Main Outcomes and Measures: The primary end point was overall survival by intention-to-treat analysis. Safety was assessed in patients who received at least 1 dose of study treatment. Results: A total of 162 patients (median [range] age, 55 [28-75] years; 151 males [93.2%]), were randomly assigned to be treated with either SOR-TACE (n = 81) or TACE alone (n = 81). The median overall survival was significantly longer in the SOR-TACE group than in the TACE group (22.2 months vs 15.1 months; hazard ratio [HR], 0.55; P < .001). SOR-TACE also prolonged progression-free survival (16.2 months vs 11.8 months; HR, 0.54; P < .001), and improved the objective response rate when compared with TACE alone based on the modified Response Evaluation Criteria in Solid Tumors criteria (80.2% vs 58.0%; P = .002). Any grade adverse events were more common in the SOR-TACE group, but all adverse events responded well to treatment. No unexpected adverse events or treatment-related deaths occurred in this study. Conclusions and Relevance: The results of this randomized clinical trial demonstrated that SOR-TACE achieved better clinical outcomes than TACE alone. These findings suggest that combined treatment should be used for patients with recurrent intermediate-stage HCC after R0 hepatectomy with positive MVI. Trial Registration: ClinicalTrials.gov Identifier: NCT04103398.

Early ontogenesis from embryo to juvenile in Senegalese sole Solea senegalensis under laboratory conditions.

Senegalese sole, Solea senegalensis, is a flatfish of high commercial value in the world. It has been identified as an interesting and promising species for marine commercial aquaculture diversification in Europe for at least four decades and was introduced to China in 2003. Early ontogenesis from embryo to juvenile stages in S. senegalensis was analysed under controlled laboratory conditions to provide morphological information for aquaculture. From 0 to 59 days post hatching (dph), 10-20 larvae were sampled and measured each day (0-17 dph) or every 2-6 days (17-59 dph). Morphological characteristics from the egg to the juvenile stage were described. The eggs were separate and spherical with multiple oil globules. After 3 dph, the yolk sac was completely absorbed, mouth and anus were open, a swim bladder appeared, and larvae began feeding on rotifers (Brachionus plicatilis). The larvae began metamorphosis as the notochord flexed upward and the left eye migrated upward after 10 dph. The left eye migrated to the dorsal midline at 15 dph. At 19 dph, the left eye was translocated to the right-ocular side, and the juveniles adopted a benthic lifestyle. The swim bladder degenerated, and the juveniles completed metamorphosis at 23 dph. The growth patterns of some parameters (TL, SL, BH, BW) during larval and juvenile development stages were identified. The inflection points, which are slopes of growth changes, were calculated in growth curves. Three inflection points occurring in the growth curves of larvae and juveniles were found to be associated with metamorphosis, weaning, and transitions in feeding habits. The basic information of embryo development and ontogenesis in this study represents a valuable contribution to the S. senegalensis industry, especially in artificial breeding and rearing techniques.

Changes in Growth and Feeding Characteristics during Early Ontogenesis in Threadsail Filefish, Stephanolepis cirrhifer.

BACKGROUND: We investigated the growth and feeding characteristics of threadsail filefish, Stephanolepis cirrhifer, during early ontogenesis. METHODS: The growth indices of hatchlings fed compound feed were measured from 0 to 50 days post hatching (dph). The absorption time of the yolk sac and oil globule, as well as the rate of first feeding were measured to characterise the early growth stage and determine the point-of-no-return (PNR). Feeding characteristics and rhythms were investigated under a light/dark cycle and under continuous light. RESULTS: Growth indices increased significantly at 24, 28, 30, 40, 45, and 50 dph. The yolk sac and oil globules were completely absorbed before 4 dph, indicative of a short mixed-nutrition period at 3-4 dph. Under starvation conditions, the first feeding rate was highest (86%) at 0.5 dph and then decreased to 53.3% at 1.5 dph and 26.2% at 2 dph, suggesting that the PNR occurs at 1.5-2 dph. The feeding peak appeared at 15:00-18:00 and under light conditions, while the feeding trough appeared at 0:00-3:00. CONCLUSIONS: Compound feed supplied adequate nutrition for early growth and development. The peaks and troughs of feeding times were indicative of daytime feeding behaviour. These results provide guidance for successful rearing of filefish seedlings and juveniles.

Effects of Bedaquiline Combined with Fluoroquinolone and/or Clofazimine on QT Interval in Patients with Multidrug-Resistant Tuberculosis: a Retrospective Study.

With the application of bedaquiline (Bdq), the success rate of multidrug-resistant tuberculosis (MDR-TB) treatment has been significantly improved; however, the cardiac safety of the patients during treatment cannot be ignored. Hence, this study compared the effects of bedaquiline alone and bedaquiline combined with fluoroquinolones (FQs) and/or clofazimine (CFZ) on the QT interval. This single-center retrospective cohort study analyzed the clinical data of MDR-TB patients treated with bedaquiline for 24 weeks from January 2020 to May 2021 in Xi'an Chest Hospital and compared the changes in QTcF between the two groups. Eighty-five patients were included in the study and grouped by types of anti-TB drugs affecting the QT interval they used. Group A included bedaquiline (n = 33), and group B included bedaquiline in combination with fluoroquinolones and/or clofazimine (n = 52). Out of patients with available corrected QT interval by Fridericia's formula (QTcF) data, 2.4% (2/85) experienced a postbaseline QTcF of ≥500 ms, and 24.7% (21/85) had at least one change of QTcF of ≥60 ms from baseline. In group A, 9.1% (3/33) had at least one ΔQTcF of >60 ms, as did 34.6% (18/52) of group B. Multivariate Cox regression analysis showed that the adjusted risk of QT prolongation was 4.82 times higher in group B (95% confidence interval [CI], 1.406 to 16.488). Bedaquiline combined with other anti-TB drugs affecting QT interval significantly increased the incidence of grade 3 or 4 QT prolongation; however, no serious ventricular arrhythmia and permanent drug withdrawal occurred. The use of bedaquiline combined with fluoroquinolone and/or clofazimine is an independent risk factor affecting QT interval. IMPORTANCE Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis. The emergence of MDR-TB is caused by an organism that is resistant to at least isoniazid and rifampin and is currently considered the major challenge for the global control of TB. Bedaquiline is the first new TB drug in 50 years with a unique mechanism of action, strong anti-M. tuberculosis activity. Yet unexplained excess deaths in the bedaquiline arms have been found in some phase II clinical trials; thus, the FDA has issued a "boxed warning." However, the cardiac safety of the patients during treatment cannot be ignored. Accordingly, further investigations are needed to establish whether bedaquiline combined with clofazimine, fluoroquinolones, or anti-TB drugs affecting the QT interval in a long-course or short-course treatment increases the risk of QT prolongation.

Identification of BRD7 by whole-exome sequencing as a predictor for intermediate-stage hepatocellular carcinoma in patients undergoing TACE.

OBJECTIVE: In the present study, we aimed to identify potential predictors of intermediate-stage hepatocellular carcinoma (HCC) using whole-exome sequencing (WES) in patients undergoing transarterial chemoembolization (TACE). MATERIALS AND METHODS: In A total of 51 patients, newly diagnosed with intermediate-stage HCC between January 2013 and December 2020, were enrolled. Prior to treatment, histological samples were collected for western blotting and immunohistochemistry. The predictive roles of clinical indicators and genes in patient prognosis were analyzed using univariate and multivariate analyses. Finally, the correlation between imaging features and gene signatures was examined. RESULTS: Using WES, we identified that bromodomain-containing protein 7 (BRD7) was significantly mutated in patients with different TACE responses. No significant difference in BRD7 expression was observed between patients with and without BRD7 mutations. HCC tumors exhibited higher BRD7 than normal liver tissues. Multivariate analysis revealed that alpha-fetoprotein (AFP), BRD7 expression, and BRD7 mutations were independent risk factors for progression-free survival (PFS). In addition, Child-Pugh class, BRD7 expression, and BRD7 mutations were independent risk factors for overall survival (OS). Patients with wild-type BRD7 and high BRD7 expression had worse PFS and OS, whereas those with mutated BRD7 and low BRD7 expression exhibited the best PFS and OS. The Kruskal-Wallis test revealed that wash-in enhancement on computed tomography might be an independent risk factor for high BRD7 expression. CONCLUSION: BRD7 expression may be an independent risk factor for prognosis in patients with HCC undergoing TACE. Imaging features such as wash-in enhancement are closely related to BRD7 expression.

Sorafenib plus drug-eluting bead transarterial chemoembolization for early intrahepatic stage-progressed advanced hepatocellular carcinoma refractory to conventional transarterial chemoembolization.

PURPOSE: To investigate the effectiveness and safety of the combination of sorafenib and drug-eluting bead transarterial chemoembolization (DEB-TACE) in the treatment of early intrahepatic stage-progressed advanced hepatocellular carcinoma (ISPA-HCC). METHODS: This study was approved by the ethics committees of six tertiary medical centers in China. Between October 2017 and October 2020, 213 patients with advanced HCC received either sorafenib combined with on-demand DEB-TACE (DTS group, n = 103) or sorafenib monotherapy (S group, n = 110). Overall survival (OS), time to progression (TTP), local tumor response, and adverse events (AEs) were compared between the two groups. RESULTS: The incidences of nause/vomiting, abdonimal pain, hyperbilirubinemia, fever and ALT/AST increasing were higher in the DTS group. The post-treatment partial response, objective response, and disease control rates were significantly higher in the DTS group than in the S group (51.5% vs. 23.6%; 56.3% vs. 25.5%; 77.7% vs. 56.4%, respectively). The median OS was significantly longer in the DTS group than in the S group [16.3 vs. 10.0 months; hazard ratio (HR) = 0.43; P < 0.001], as was the TTP (6.7 vs. 4.3 months; HR = 0.60; P = 0.001). In the DTS group, patients who received ≥ 2 sessions of DEB-TACE benefited more than those who received two sessions of DEB-TACE. Multivariate analysis revealed that the α-fetoprotein level and treatment allocation were independent predictors of OS and TTP. CONCLUSION: The combination of sorafenib and DEB-TACE is safe and effective for the treatment of early ISPA-HCC.

Idarubicin-Loaded DEB-TACE plus Lenvatinib versus Lenvatinib for patients with advanced hepatocellular carcinoma: A propensity score-matching analysis.

AIMS: To investigate the efficacy and safety of lenvatinib and idarubicin-loaded drug-eluting beads transarterial chemoembolization (IDADEB-TACE) in primary advanced hepatocellular carcinoma (HCC). METHODS: This retrospective study included patients with primary advanced HCC who received either lenvatinib monotherapy or lenvatinib plus IDADEB-TACE as first-line treatment from September 2019 to September 2020 at three institutes. Overall survival (OS), time to progression (TTP), objective response rate (ORR), and adverse events were compared. Propensity score-matching was used to reduce the influence of confounding factors on the outcomes. RESULTS: The study reviewed 118 patients who received lenvatinib plus IDADEB-TACE (LIDA group) and 182 who received lenvatinib alone (LEN group). After propensity score-matching, 78 pairs of patients remained. Compared to patients in the LEN group, those in the LIDA group had better post-treatment ORR (57.7% vs. 25.6%, p < 0.001, respectively), median OS and TTP (15.7 vs. 11.3 months, hazard ratio [HR] = 0.50, p < 0.001; 8.0 vs. 5.0 months, HR = 0.60, p = 0.003, respectively), 6- and 12-month OS rates (88.5% vs. 71.4%; 67.6% vs. 43.4%, respectively), and progression-free rates at 6 and 12 months (60.3% vs. 42.3%; 21.1% vs. 10.3%, respectively). Vascular invasion, α-fetoprotein level, and treatment type were independent OS predictors, and vascular invasion and treatment type were independent TTP predictors. Incidences of nausea/vomiting, fever, abdominal pain, and increased ALT/AST were higher in the LIDA group than in the LEN group. CONCLUSIONS: Lenvatinib plus IDADEB-TACE is well-tolerated and more effective than lenvatinib monotherapy in patients with advanced HCC.

Identifying optimal candidates for post-TIPS patients with HCC undergoing TACE: a multicenter observational study.

OBJECTIVE: To develop a prognostic model for post-transjugular intrahepatic portosystemic shunt (TIPS) patients with hepatocellular carcinoma (HCC) beyond the Milan criteria treated by transarterial chemoembolization (TACE). DESIGN: Between January 2013 and January 2020, 512 patients with HCC beyond the Milan criteria who underwent TACE after TIPS were retrospectively recruited from 15 tertiary centers. Patients were randomly sorted into a training set (n = 382) and a validation set (n = 130). Medical data and overall survival were assessed. A prediction model was developed using multivariate Cox regression analyses. Predictive performance and discrimination were evaluated and compared with other prognostic models. RESULTS: Vascular invasion, log10(AFP), 1/creatinine, extrahepatic spread, and log10(ALT) were the most significant prognostic factors of survival. These five parameters were included in a new VACEA score. This score was able to stratify patients in the training set into four distinct risk grades whose median overall survival were 25.2, 15.1, 8.9, and 6.2 months, respectively. The 6-month, 1-year, 2-year, and 3-year AUROC values and C-index of the VACEA model were 0.819, 0.806, 0.779, 0.825, and 0.735, respectively, and higher than those of other seven currently available models in both the training and validation sets, as well as in different subgroups. CONCLUSION: The VACEA score could stratify post-TIPS patients with HCC beyond the Milan criteria treated by TACE and help to identify candidates who benefit from this treatment. KEY POINTS: • Vascular invasion, AFP, creatinine, extrahepatic spread, and ALT were independent significant prognostic factors of survival for HCC patients who underwent TACE after TIPS. • Our new model, named VACEA score, can accurately predict prognosis at the individual level and stratify patients into four distinct risk grades. • The VACEA model showed better prognostic discrimination and calibration than other current TACE-/TIPS-specific models Graphical abstract.

Dissecting a hypoxia-related angiogenic gene signature for predicting prognosis and immune status in hepatocellular carcinoma.

Background: Hypoxia and angiogenesis, as prominent characteristics of malignant tumors, are implicated in the progression of hepatocellular carcinoma (HCC). However, the role of hypoxia in the angiogenesis of liver cancer is unclear. Therefore, we explored the regulatory mechanisms of hypoxia-related angiogenic genes (HRAGs) and the relationship between these genes and the prognosis of HCC. Methods: The transcriptomic and clinical data of HCC samples were downloaded from public datasets, followed by identification of hypoxia- and angiogenesis-related genes in the database. A gene signature model was constructed based on univariate and multivariate Cox regression analyses, and validated in independent cohorts. Kaplan-Meier survival and time-dependent receiver operating characteristic (ROC) curves were generated to evaluate the model's predictive capability. Gene set enrichment analysis (GSEA) was performed to explore signaling pathways regulated by the gene signature. Furthermore, the relationships among gene signature, immune status, and response to anti-angiogenesis agents and immune checkpoint blockade (ICB) were analyzed. Results: The prognostic model was based on three HRAGs (ANGPT2, SERPINE1 and SPP1). The model accurately predicted that low-risk patients would have longer overall survival than high-risk patients, consistent with findings in other cohorts. GSEA indicated that high-risk group membership was significantly associated with hypoxia, angiogenesis, the epithelial-mesenchymal transition, and activity in immune-related pathways. The high-risk group also had more immunosuppressive cells and higher expression of immune checkpoints such as PD-1 and PD-L1. Conversely, the low-risk group had a better response to anti-angiogenesis and ICB therapy. Conclusions: The gene signature based on HRAGs was predictive of prognosis and provided an immunological perspective that will facilitate the development of personalized therapies.

Treatment Outcomes and Risk Factors of Multidrug-Resistant Tuberculosis Patients in Xi'an China, a Retrospective Cohort Study.

Background: Long-term regimens are widely used for multidrug-resistant tuberculosis (MDR-TB) in North-West China; however, risk factors associated with the treatment outcomes are not well known. Methods: This was a retrospective cohort study of MDR-TB patients treated with longer regimen in Xi'an from 2017 to 2019. Risk factors associated with the treatment outcome were analyzed using multiple logistic regression. Results: Of the 446 patients with MDR-TB included, 215 were cured, 84 completed treatment, 23 failed treatment, 108 were lost to follow-up, and 16 died. Unfavorable outcome risk factors were age >40 years (OR = 3.25, 95% CI = 2.12-4.98), male sex (OR = 2.53, 95% CI = 1.52-4.22), and re-treated tuberculosis (OR = 1.70, 95% CI = 1.11-2.61), whereas poor treatment outcome risk factors were age >40 years (OR = 5.51, 95% CI = 2.52-12.07), fluoroquinolones not used in the regimen (OR = 3.31, 95% CI = 1.45-7.51), and smear-positive (OR = 4.0, 95% CI = 1.47-10.8). Conclusion: In Xi'an, MDR-TB treatments with long-term regimens had low success rates, and age, sex, and tuberculosis treatment history were risk factors of MDR-TB treatment outcomes.

Cigarette Smoking Increases the Risk of Type 2 Diabetes Mellitus in Patients with Non-Alcoholic Fatty Liver Disease: A Population-Based Cohort Study.

OBJECTIVE: Cigarette smoke and non-alcoholic fatty liver disease are risk factors for type 2 diabetes mellitus. However, the impact of smoking on diabetes risk among patients with non-alcoholic fatty liver disease remains unclear. METHODS: This study included 15,464 Japanese individuals. We defined non-alcoholic fatty liver disease based on abdominal ultrasound findings where excess alcohol intake and other liver diseases were excluded. We used Cox proportional regression analysis to identify risk factors for type 2 diabetes onset. RESULTS: During 16,446 person-years of follow-up, 223 of 2,714 non-alcoholic fatty liver disease patients developed type 2 diabetes; the cumulative incidence rate of type 2 diabetes was 13.6 per 1,000 person-years. The proportions of never, former, and current smokers (self-report) were 35.3%, 31.1%, and 33.6%, and 88.5%, 5.1%, and 6.4% in men and women, respectively. In a Cox regression model adjusted for sex, age, body mass index, waist circumference, alcohol intake, exercise, and alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, lipid profiles, and blood pressure values, relative to never smokers, current smokers with non-alcoholic fatty liver disease had an increased risk of type 2 diabetes (hazard ratio=2.05; 95% confidence interval: 1.43-2.94). In addition, former smoking affected the risk of type 2 diabetes; however, this effect was not statistically significant. CONCLUSIONS: This longitudinal study showed that current smoking may act as a "second hit" and increase the risk of type 2 diabetes in patients with non-alcoholic fatty liver disease.

Relationship between circadian genes and memory impairment caused by sleep deprivation.

Background: Sleep deprivation (SD)-induced cognitive impairment is highly prevalent worldwide and has attracted widespread attention. The temporal and spatial oscillations of circadian genes are severely disturbed after SD, leading to a progressive loss of their physiological rhythms, which in turn affects memory function. However, there is a lack of research on the role of circadian genes and memory function after SD. Therefore, the present study aims to investigate the relationship between circadian genes and memory function and provide potential therapeutic insights into the mechanism of SD-induced memory impairment. Methods: Gene expression profiles of GSE33302 and GSE9442 from the Gene Expression Omnibus (GEO) were applied to identify differentially expressed genes (DEGs). Subsequently, both datasets were subjected to Gene Set Enrichment Analysis (GSEA) to determine the overall gene changes in the hippocampus and brain after SD. A Gene Oncology (GO) analysis and Protein-Protein Interaction (PPI) analysis were employed to explore the genes related to circadian rhythm, with their relationship and importance determined through a correlation analysis and a receiver operating characteristic curve (ROC), respectively. The water maze experiments detected behavioral changes related to memory function in SD rats. The expression of circadian genes in several critical organs such as the brain, heart, liver, and lungs and their correlation with memory function was investigated using several microarrays. Finally, changes in the hippocampal immune environment after SD were analyzed using the CIBERSORT in R software. Results: The quality of the two datasets was very good. After SD, changes were seen primarily in genes related to memory impairment and immune function. Genes related to circadian rhythm were highly correlated with engagement in muscle structure development and circadian rhythm. Seven circadian genes showed their potential therapeutic value in SD. Water maze experiments confirmed that SD exacerbates memory impairment-related behaviors, including prolonged escape latencies and reduced numbers of rats crossing the platform. The expression of circadian genes was verified, while some genes were also significant in the heart, liver, and lungs. All seven circadian genes were also associated with memory markers in SD. The contents of four immune cells in the hippocampal immune environment changed after SD. Seven circadian genes were related to multiple immune cells. Conclusions: In the present study, we found that SD leads to memory impairment accompanied by changes in circadian rhythm-related genes. Seven circadian genes play crucial roles in memory impairment after SD. Naïve B cells and follicular helper T cells are closely related to SD. These findings provide new insights into the treatment of memory impairment caused by SD.

Clinical Significance of Peripheral Blood Lymphocyte Subtypes and Cytokines in Patients with Hepatocellular Carcinoma Treated with TACE.

PURPOSE: To examine the clinical significance of circulating lymphocyte subtypes and cytokines in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). PATIENTS AND METHODS: We enrolled 53 patients and assessed lymphocyte subsets (CD4+ T cells, CD8+ T cells, CD4+/CD8+ cell ratio, natural killer cells, and regulatory T cells) and cytokines (interleukin [IL]-2, IL-4, IL-6, IL-10, and interferon [IFN]-γ) on the day before TACE, and 1 day and 4-8 weeks thereafter. The correlation between baseline inflammatory markers and IL-6, the differences between clinical subgroups, and the prognostic baseline inflammatory values and changes therein were analyzed. RESULTS: We found that baseline IL-6 was positively correlated with IL-10 and IFN-γ. Univariate analysis revealed that patients with higher baseline IL-6, IL-10, and IFN-γ levels had worse liver function and greater tumor burden, suggesting a poor prognosis. Multivariate analysis showed that higher baseline IFN-γ levels were associated with a shorter time to tumor progression (hazard ratio [HR] = 1.912; 95% confidence interval [CI] = 1.013-3.607; p = 0.045), and higher IL-10 levels were associated with poor overall survival (HR = 2.576; 95% CI = 1.237-5.364; p = 0.011). Baseline lymphocyte subtypes and changes therein did not have any significant association with prognosis. CONCLUSION: This study confirmed the association between inflammation and poor prognosis. The prognostic significance of IFN-γ was different from previous studies, while the prognostic significance of lymphocyte subtypes remains to be verified.

A 10-Gene Signature Identified by Machine Learning for Predicting the Response to Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma.

BACKGROUND: Transarterial chemoembolization (TACE) is recommended for intermediate-stage HCC patients. Owing to substantial variation in its efficacy, indicators of patient responses to TACE need to be determined. METHODS: A Gene Expression Omnibus (GEO) dataset consisting of patients of different TACE-response status was retrieved. Differentially expressed genes (DEGs) were calculated and variable gene ontology analyses were conducted. Potential drugs and response to immunotherapy were predicted using multiple bioinformatic algorithms. We built and compared 5 machine-learning models with finite genes to predict patients' response to TACE. The model was also externally validated to discern different survival outcomes after TACE. Tumor-infiltrating lymphocytes (TILs) and tumor stemness index were evaluated to explore potential mechanism of our model. RESULTS: The gene set variation analysis revealed enhanced pathways related to G2/M checkpoint, E2F, mTORC1, and myc in TACE nonresponders. TACE responders had better immunotherapy response too. 373 DEGs were detected and the upregulated DEGs in nonresponders were enriched in IL-17 signal pathway. 5 machine-learning models were constructed and evaluated, and a linear support vector machine (SVM)-based model with 10 genes was selected (AQP1, FABP4, HERC6, LOX, PEG10, S100A8, SPARCL1, TIAM1, TSPAN8, and TYRO3). The model achieved an AUC and accuracy of 0.944 and 0.844, respectively, in the development cohort. In the external validation cohort comprised of patients receiving adjuvant TACE and postrecurrence TACE treatment, the predicted response group significantly outlived the predicted nonresponse counterparts. TACE nonresponders tend to have more macrophage M0 cells and lower resting mast cells in the tumor tissue and the stemness index is also higher than responders. Those characteristics were successfully captured by our model. CONCLUSION: The model based on expression data of 10 genes could potentially predict HCC patients' response and prognosis after TACE treatment. The discriminating power was TACE-specific.

Ultrasound-Guided Clavipectoral Fascial Plane Block With Intermediate Cervical Plexus Block for Midshaft Clavicular Surgery: A Prospective Randomized Controlled Trial.

BACKGROUND: Regional anesthesia such as interscalene brachial plexus block (ISBPB) with intermediate cervical plexus block (ICPB) is generally a preferred choice for clavicular surgery. However, various studies have shown that these blocks, especially ISBPB, could cause phrenic nerve paralysis and decrease diaphragmatic motion. The study aimed to evaluate the efficacy of clavipectoral fascial plane block (CPB), an alternative technique to ISBPB, with ICPB, in reducing hemidiaphragmatic paralysis during midshaft clavicular surgery. METHODS: Forty patients scheduled for right midshaft clavicular surgery were randomized (1:1) into an ultrasound-guided ISBPB with ICPB (BC) group or ultrasound-guided CPB with ICPB (CC) group. Five milliliter of 0.375% ropivacaine was used for ICPB, another 20 mL for ISBPB or CPB, and no administration of additional sedative or general anesthetic was planned. Primary outcome was measured by the incidence of hemidiaphragmatic paralysis using M-mode ultrasonography, while secondary outcomes were measured by bedside pulmonary function test, the success rate of block, the time required for the block procedure and onset of block, and motor block score in right upper extremity. RESULTS: In comparison with BC group, the incidence of hemidiaphragmatic paralysis postblock was decreased in CC group (50% vs 0%; P < .001), and measurement of bedside pulmonary function was significantly improved. There was a 100% success rate for anesthetic block in both BC and CC groups, and CC group showed lower motor block score in upper extremity and less block procedure time than BC group (7.1 ± 1.2 vs 3.2 ± 0.6 minutes; P < .001). Moreover, no significant differences were found between time of onset of block and other anesthetic complications in the 2 groups. CONCLUSIONS: Ultrasound-guided CPB with ICPB could significantly reduce hemidiaphragmatic paralysis and provide an adequate surgical anesthesia with fewer complications such as motor block in upper extremity during right midshaft clavicular surgery.

Curcumin Relieves Chronic Unpredictable Mild Stress-Induced Depression-Like Behavior through the PGC-1α/FNDC5/BDNF Pathway.

METHODS: All rats were randomly divided into four groups, namely, control, CUMS, CUMS + CUR, and CUMS + CUR + SR18292 (PGC-1α inhibitor). Behavioral tests were conducted to assess the antidepressant-like effects of CUR. The expressions of PGC-1α, estrogen-related receptor alpha (ERRα), FNDC5, and BDNF were determined to investigate the regulatory effects of CUR on the PGC-1α/FNDC5/BDNF pathway. The PGC-1α inhibitor SR18292 was used to explore the role of PGC-1α in the induction of BDNF by CUR. RESULTS: Daily gavage of 100 mg/kg CUR successfully attenuated the abnormal behaviors induced by CUMS and effectively prevented CUMS-induced reduction of PGC-1α, ERRα, FNDC5, and BDNF expressions. CUR also enhanced PGC-1α and ERRα translocation from cytoplasm to nucleus. Furthermore, we found that CUR supplementation effectively promoted neurocyte proliferation and suppressed neuronal apoptosis induced by CUMS. Of note, the PGC-1α inhibitor SR18292 remarkably reversed the beneficial effects of CUR on depressed rats, indicating an important role of PGC-1α in the antidepressant-like effects of CUR. CONCLUSION: Collectively, our data evaluating the neuroprotective action of CUR in the CUMS rats highlights the involvement of the PGC-1α/FNDC5/BDNF pathway in the antidepressant-like effects of CUR.

The Role of CSR Engagement in Customer-Company Identification and Behavioral Intention During the COVID-19 Pandemic.

The global coronavirus pandemic has reignited a strategic debate among the business community of the necessity for corporate social responsibility (CSR) engagement in the ever-dynamic social media. Considering the global economic downturn introduced by the COVID-19 pandemic, the present research is devoted to investigating whether CSR engagement in social media can help DiDi (a Chinese shared brand) at stake survive this overwhelming crisis. A theoretical model proposed to describe the hypothesized relationships was tested by a Structural Equation Modeling technique through the empirical online questionnaire. Through findings, we demonstrated that there was a positive relationship between CSR engagement of DiDi on WeChat, customer-company identification (C-C identification), and behavioral intention [purchase intention, brand loyalty, and e-word-of-mouth (eWOM)] of customers. With attention to psychological influence, our empirical statistics also evidenced the mediating role of C-C identification between CSR engagement and behavioral intention of customers. This study highlights the significant role of CSR engagement in a critical period theoretically and offers businesses more open innovation strategies to compete against the COVID-19 pandemic-induced market downturn.