The effect of non-insulin-based insulin resistance indices on the prediction of recurrence in patients with atrial fibrillation undergoing radiofrequency catheter ablation.

BACKGROUND: Atrial fibrillation (AF) is acknowledged as a disease continuum. Despite catheter ablation being recommended as a primary therapy for AF, the high recurrence rates have tempered the initial enthusiasm. Insulin resistance (IR) has been established as an independent predictor for the onset of AF. However, the correlation between non-insulin-based IR indices and late AF recurrence in patients undergoing radiofrequency catheter ablation remains unknown. METHODS: A retrospective cohort of 910 AF patients who underwent radiofrequency catheter ablation was included in the analysis. The primary endpoint was late AF recurrence during the follow-up period after a defined blank period. The relationship between non-insulin-based IR indices and the primary endpoint was assessed using multivariate Cox hazards regression models and restricted cubic splines (RCS). Additionally, the net reclassification improvement and integrated discrimination improvement index were calculated to further evaluate the additional predictive value of the four IR indices beyond established risk factors for the primary outcome. RESULTS: During a median follow-up period of 12.00 months, 189 patients (20.77%) experienced late AF recurrence, which was more prevalent among patients with higher levels of IR. The multivariate Cox hazards regression analysis revealed a significant association between these IR indices and late AF recurrence. Among the four indices, METS-IR provided the most significant incremental effect on the basic model for predicting late AF recurrence. Multivariable-adjusted RCS curves illustrated a nonlinear correlation between METS-IR and late AF recurrence. In subgroup analysis, METS-IR exhibited a significant correlation with late AF recurrence in patients with diabetes mellitus (HR: 1.697, 95% CI 1.397 - 2.063, P < 0.001). CONCLUSION: All the four non-insulin-based IR indices were significantly associated with late AF recurrence in patients undergoing radiofrequency catheter ablation. Addressing IR could potentially serve as a viable strategy for reducing the late AF recurrence rate.

In-Sb Covalent Bonds over Sb2Se3/In2Se3 Heterojunction for Enhanced Photoelectrochemical Water Splitting.

Antimony selenide is a promising P-type photocatalyst, but it has a large number of deep energy level defects, leading to severe carrier recombination. The construction of a heterojunction is a common way to resolve this problem. However, the conventional heterojunction system inevitably introduces interface defects. Herein, we employ in situ synthesis to epitaxially grow In2Se3 nanosheets on Sb2Se3 nanorods and form In-Sb covalent interfacial bonds. This petal-shaped heterostructure reduced interface defects and enhanced the efficiency of carrier separation and transport. In this work, the photocurrent density in the proposed Sb2Se3/In2Se3 photocathode is 0.485 mA cm-2 at 0 VRHE, which is 30 times higher than that of pristine Sb2Se3 and it has prominent long-term stability for 24 h without obvious decay. The results reveal that the synergy of the bidirectional built-in electric field constructed between In2Se3 and Sb2Se3 and the solid In-Sb interfacial bonds together build a high-efficiency transport channel for the photogenerated carriers that display enhanced photoelectrochemical (PEC) water-splitting performance. This work provides efficient guidance for reducing interface defects via the in situ synthesis and construction of interfacial bonds.

Association between elevated preoperative red cell distribution width and mortality after brain tumor craniotomy.

BACKGROUND: Red cell distribution width (RDW) has been recognized as a potential inflammatory biomarker, with elevated levels associated with adverse outcomes in various diseases. However, its role in predicting outcomes after brain tumor craniotomy remains unclear. We aimed to assess whether preoperative RDW influences mortality and postoperative complications in patients undergoing brain tumor craniotomy. METHODS: This retrospective cohort study analyzed serum RDW levels in patients undergoing brain tumor craniotomy at West China Hospital. RDW was evaluated in two forms: RDW-CV and RDW-SD, and was categorized into four quartiles for analysis by using logistic regression and multivariate analysis to adjust for confounding. RESULTS: The study encompassed 10,978 patients undergoing brain tumor craniotomy. our analysis revealed no significant difference in 30-day mortality across various RDW-CV levels. However, we observed a dose-response relationship with preoperative RDW-CV levels in assessing long-term mortality risks. Specifically, patients with RDW-CV levels of 12.6-13.2% (HR 1.04, 95% CI 1.01-1.18), 13.2-13.9% (HR 1.12, 95% CI 1.04-1.26), and > 13.9% (HR 1.34, 95% CI 1.18-1.51) exhibited a significantly higher hazard of long-term mortality compared to those with RDW-CV < 12.6%. When preoperative RDW-CV was analyzed as a continuous variable, for each 10% increase in RDW-CV, the adjusted OR of long-term mortality was 1.09 (95% CI 1.05-1.13). we also observed significant associations between preoperative higher RDW-CV levels and certain postoperative complications including acute kidney injury (OR 1.46, 95% CI: 1.10-1.94), pneumonia infection (OR 1.19 95% CI: 1.05-1.36), myocardial infarction (OR 1.32, 95% CI: 1.05-1.66), readmission (OR 1.15, 95% CI: 1.01-1.30), and a prolonged length of hospital stay (OR 1.11, 95% CI: 1.02-1.21). For RDW-SD levels, there was no significant correlation for short-term mortality, long-term mortality, and postoperative complications. CONCLUSIONS: Our study showed elevated preoperative RDW-CV is significantly associated with increased long-term mortality and multiple postoperative complications, but no such association is observed with RDW-SD. These findings show the prognostic importance of RDW-CV, reinforcing its potential as a valuable tool for risk stratification in the preoperative evaluation of brain tumor craniotomy patients.

Association between postoperative changes in natremia and outcomes in patients undergoing elective craniotomy.

Postoperative dysnatremias, characterized by imbalances in serum sodium levels, have been linked to increased resource utilization and mortality in surgical and intensive care patients. The management of dysnatremias may involve medical interventions based on changes in sodium levels. In this study, we aimed to investigate the impact of postoperative changes in natremia on outcomes specifically in patients undergoing craniotomy.We conducted a retrospective analysis of patient records from the Department of Neurosurgery at West China Hospital, Sichuan University, covering the period from January 2011 to March 2021. We compared the highest and lowest sodium values in the first 14 postoperative days with the baseline values to define four categories for analysis: no change < 5 mmol/L; decrease > 5 mmol/L; increase > 5 mmol/L; both increase and decrease > 5 mmol/L. The primary outcome measure was 30-day mortality.A total of 12,713 patients were included in the study, and the overall postoperative mortality rate at 30 days was 2.1% (264 patients). The increase in sodium levels carried a particularly high risk, with a tenfold increase (OR 10.21; 95% CI 7.25-14.39) compared to patients with minimal or no change. Decreases in sodium levels were associated with an increase in mortality (OR 1.60; 95% CI 1.11-2.23).Moreover, the study revealed that postoperative sodium decrease was correlated with various complications, such as deep venous thrombosis, pneumonia, intracranial infection, urinary infection, seizures, myocardial infarction, and prolonged hospital length of stay. On the other hand, postoperative sodium increases were associated with acute kidney injury, deep venous thrombosis, pneumonia, intracranial infection, urinary infection, surgical site infection, seizures, myocardial infarction, and prolonged hospital length of stay.Changes in postoperative sodium levels were associated with increased complications, prolonged length of hospital stay, and 30-day mortality. Moreover, the severity of sodium change values correlated with higher mortality rates.

Lower versus higher oxygen targets for out-of-hospital cardiac arrest: a systematic review and meta-analysis.

BACKGROUND: Supplemental oxygen is commonly administered to patients after out-of-hospital cardiac arrest. However, the findings from studies on oxygen targeting for out-of-hospital cardiac arrest are inconclusive. Thus, we conducted a systematic review and meta-analysis to evaluate the impact of lower oxygen target compared with higher oxygen target on patients after out-of-hospital cardiac arrest. METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, from inception to February 6, 2023, for randomized controlled trials comparing lower and higher oxygen target in adults (aged ≥ 18 years) after out-of-hospital cardiac arrest. We screened studies and extracted data independently. The primary outcome was mortality at 90 days after cardiac arrest. We assessed quality of evidence using the grading of recommendations assessment, development, and evaluation approach. This study was registered with PROSPERO, number CRD42023409368. RESULTS: The analysis included 7 randomized controlled trials with a total of 1451 participants. Compared with lower oxygen target, the use of a higher oxygen target was not associated with a higher mortality rate (relative risk 0.97, 95% confidence intervals 0.82 to 1.14; I2 = 25%). Findings were robust to trial sequential, subgroup, and sensitivity analysis. CONCLUSION: Lower oxygen target did not reduce the mortality compared with higher oxygen target in patients after out-of-hospital cardiac arrest.

Ginseng-derived panaxadiol ameliorates STZ-induced type 1 diabetes through inhibiting RORγ/IL-17A axis.

Retinoic-acid-receptor-related orphan receptor γ (RORγ) is a major transcription factor for proinflammatory IL-17A production. Here, we revealed that the RORγ deficiency protects mice from STZ-induced Type 1 diabetes (T1D) through inhibiting IL-17A production, leading to improved pancreatic islet ß cell function, thereby uncovering a potential novel therapeutic target for treating T1D. We further identified a novel RORγ inverse agonist, ginseng-derived panaxadiol, which selectively inhibits RORγ transcriptional activity with a distinct cofactor recruitment profile from known RORγ ligands. Structural and functional studies of receptor-ligand interactions reveal the molecular basis for a unique binding mode for panaxadiol in the RORγ ligand-binding pocket. Despite its inverse agonist activity, panaxadiol induced the C-terminal AF-2 helix of RORγ to adopt a canonical active conformation. Interestingly, panaxadiol ameliorates mice from STZ-induced T1D through inhibiting IL-17A production in a RORγ-dependent manner. This study demonstrates a novel regulatory function of RORγ with linkage of the IL-17A pathway in pancreatic ß cells, and provides a valuable molecule for further investigating RORγ functions in treating T1D.

Glucose-albumin ratio as new biomarker for predicting mortality after intracerebral hemorrhage.

OBJECTIVE: This study aims to evaluate the prognostic value of blood-based biomarkers and their combinations, in particular the glucose-albumin ratio (GAR), in patients with spontaneous intracerebral hemorrhage (ICH). METHODS: A retrospective observational study on 2481 patients from one hospital was conducted and validated with 602 patients from another. We assessed 15 biomarkers and focused on GAR to elucidate its prognostic and predictive value for outcomes in both cohorts. The primary outcome was mortality at 90 days. RESULTS: The ratio of glucose-to-albumin, defined as GAR, was superior to other biomarkers for predicting mortality at 90 days in patients with ICH (AUC = 0.72). High GAR (using the best cutoff value of 0.19) was associated with increased mortality at 90 days (odds ratios of 1.90, 95% CI 1.54-2.34) and all-cause mortality in the first 3 years after admission (hazard ratio of 1.62, 95% CI 1.42-1.86). All aforementioned findings for GAR were successfully validated in an external independent cohort. CONCLUSIONS: GAR may be a valuable biomarker for predicting the mortality of patients with ICH.

Association Between Red Blood Cell Distribution width and Long-Term Mortality in Patients with Intracerebral Hemorrhage.

BACKGROUND: The association between the red cell distribution width (RDW) and long-term mortality in patients with intracerebral hemorrhage (ICH) has not been clearly established. METHODS: We conducted a retrospective cohort study of patients with ICH admitted to two tertiary hospitals. The primary outcome was long-term mortality, and the effect of elevated RDW (RDW coefficient of variation [RDW-CV]; RDW standard deviation [RDW-SD]) on outcomes was assessed by using logistic regression analysis. Serum RDW levels was divided into four levels by quartiles (the lowest quartile [Q1]; the highest quartile [Q4]). RESULTS: This study included 4223 patients with ICH. After adjustment for potential confounders, admission RDW-CV (Quartile 4 [Q4] vs. Quartile 1 [Q1], adjusted hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.34-1.92) and median RDW-CV within the first month after admission (Q4 vs. Q1, adjusted HR 1.69, 95% CI 1.40-2.04) were both associated with 1-year mortality following ICH. Parallel results were found for RDW-SD. In the receiver operating characteristic analyses, both RDW-CV and RDW-SD outperformed some inflammatory biomarkers, such as albumin, hemoglobin, total cholesterol, platelet count, lymphocyte, and fibrinogen, in predicting long-term mortality following ICH. Additionally, compared with admission RDW, median RDW-CV and RDW-SD (areas under the curve [AUC] 0.668 and 0.652, respectively) was superior to predict long-term mortality, (P < 0.001). Furthermore, median RDW-CV level was a better predictor than RDW-SD (P = 0.03). CONCLUSIONS: In patients with ICH, RDW independently predicted long-term mortality. Median RDW levels within the first month after admission were better predictors of long-term mortality compared with RDW levels on admission. Additionally, median RDW-CV showed superior predictive capacity than median RDW-SD for long-term mortality following ICH.

White Blood Cell Count Predicts Mortality in Patients with Spontaneous Intracerebral Hemorrhage.

BACKGROUND: The association between white blood cell (WBC) counts and mortality in patients with intracerebral hemorrhage (ICH) has not been established. The aim of this study is to determine whether higher WBC is associated with mortality at 90 days. METHODS: A retrospective observational study was conducted at two medical hospitals in China. Baseline WBC count on admission served as the primary predictor variable. Longitudinal WBC counts within the first week after admission were collected to assess the effects of WBC trajectory and the median and maximum WBC counts on outcomes following ICH. Associations of WBC count with outcomes were evaluated in multivariable regression analyses. RESULTS: We identified 3613 patients with ICH who met the inclusion criteria. After adjusting primary confounding variables, patients with increased WBC count had a significantly higher risk of 90-day mortality (p < 0.001 for trend). In the receiver operating characteristic analyses, the capacity for all-cause mortality prediction by WBC count on admission (area under the ROC curve (AUC) = 0.65) was superior to other important inflammatory markers, including neutrophil (AUC = 0.64) , lymphocyte (AUC = 0.57), albumin (AUC = 0.57), and platelet count (AUC = 0.53), p < 0.001 for WBC vs. neutrophil, and the median WBC count (AUC = 0.66) within the first week after admission was a better marker than admission WBC count (p = 0.02). CONCLUSIONS: In patients with ICH, WBC count on admission was associated with all-cause mortality at 90 days. Additionally, the median and maximum WBC counts within the first week after admission showed better predictive ability for the 90-day mortality compared with the WBC count on admission.

1,25-Dihydroxyvitamin D deficiency accelerates male reproductive senescence in aging mice and 1,25(OH)2D3 alleviates oxidative stress via NF-κB/SOD.

1,25(OH)2D3 has been demonstrated to exert direct actions on male reproductive system in humans or in animals. With age, renal synthesis of 1,25(OH)2D3 declines significantly, and vitamin D supplementation has been found to alleviate the manifestations of male reproductive aging. Therefore, the relationship between 1,25(OH)2D3 and male reproductive aging needs further study. To determine whether 1,25(OH)2D3 deficiency accelerates male reproductive senescence in aging mice, wild-type and 1α(OH)ase-/- male mice fed a rescue diet after weaning, and the reproductive phenotypes were evaluated at 12-18 mo of age. We demonstrated that 1,25(OH)2D3 deficiency accelerated male reproductive senescence, representing lower fertility efficiency and gonadal hormone levels, reducing cell proliferation, and increasing cell apoptosis, cellular senescence, and the senescence-associated secretory phenotype (SASP). We confirmed that the increased oxidative stress and DNA damage detected in 1α(OH)ase-/- mice resulted in accelerated reproductive senescence in reproductive system, since exogenous antioxidant pyrroloquinoline quinone (PQQ) supplementation could largely rescue reproductive aging phenotype. We further validated the antioxidant effect of 1,25(OH)2D3 in aging wild-type mice and senescent Leydig cells by treated 18-mo-old wild-type male mice or TM3 cells with 1,25(OH)2D3 or vehicle. We assessed the differential gene expression between grouped senescent TM3 cells using RNA-Seq and verified 1,25(OH)2D3 exerted an antioxidant role by acting NF-κB/SOD. This study suggests that 1,25(OH)2D3 deficiency accelerates male reproductive senescence in aging mice by increasing oxidative stress and 1,25(OH)2D3 plays a role in alleviating oxidative stress via NF-κB/SOD signaling pathway.NEW & NOTEWORTHY Based on this studies, we propose that 1,25(OH)2D3 can delay male reproductive aging, and we also propose that 1,25(OH)2D3 regulates NF-κB to exert antioxidant effect. Therefore, by targeting a fundamental aging mechanism, 1,25(OH)2D3 may be an effective agent in maintaining fertility and postponing male reproductive senescence.

Protective effects of Antrodia camphorata extract against hypoxic cell injury and ischemic stroke brain damage.

Ischemic stroke is the most prevalent stroke condition in the world resulted in either a transient ischemic attack or long-lasting neurological problems due to the interrupted or reduced blood flow to the brain. Antrodia camphorata is a well-known medicinal mushroom native to Taiwan and is familiar due to its medicinal effects. The current study investigated the protective effect of A. camphorata-alcohol extracts (AC-AE) against cobalt (II) chloride (CoCl2 )-induced oxidative stress in vitro and ischemia/reperfusion-induced brain injury in vivo. The rats were pre-treated with AC-AE for 4 weeks. Our results showed that AC-AE reduced cell damage and decreased reactive oxygen species (ROS) production in C6 and PC12 cells under CoCl2 -induced hypoxic condition. AC-AE doses (385, 770, 1,540 mg/kg/day, 4 weeks) increased nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) mRNA expressions and decreased inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA expressions in Sprague Dawley rat. Besides, it decreased stroke infarct size and increased the level of antioxidants in both brain and serum. Furthermore, it reduced the formation of malondialdehyde (MDA) after ischemia/reperfusion (I/R). Our results suggested that AC-AE exerted an effective reduction of ischemia stroke by regulating ROS production.

Structural Basis for PPARs Activation by The Dual PPARα/γ Agonist Sanguinarine: A Unique Mode of Ligand Recognition.

Peroxisome proliferator-activated receptors (PPARs) play crucial roles in glucose and lipid metabolism and inflammation. Sanguinarine is a natural product that is isolated from Sanguinaria Canadensis, a potential therapeutic agent for intervention in chronic diseases. In this study, biochemical and cell-based promoter-reporter gene assays revealed that sanguinarine activated both PPARα and PPARγ, and enhanced their transcriptional activity; thus, sanguinarine was identified as a dual agonist of PPARα/γ. Similar to fenofibrate, sanguinarine upregulates the expression of PPARα-target genes in hepatocytes. Sanguinarine also modulates the expression of key PPARγ-target genes and promotes adipocyte differentiation, but with a lower adipogenic activity compared with rosiglitazone. We report the crystal structure of sanguinarine bound to PPARα, which reveals a unique ligand-binding mode of sanguinarine, dissimilar to the classic Y-shaped binding pocket, which may represent a new pharmacophore that can be optimized for selectively targeting PPARα. Further structural and functional studies uncover the molecular basis for the selectivity of sanguinarine toward PPARα/γ among all three PPARs. In summary, our study identifies a PPARα/γ dual agonist with a unique ligand-binding mode, and provides a promising and viable novel template for the design of dual-targeting PPARs ligands.

Induction chemotherapy followed by intensity-modulated radiotherapy versus concurrent chemoradiotherapy in nasopharyngeal carcinoma: A retrospective analysis.

OBJECTIVES: The optimal treatment strategy of combining systemic chemotherapy and radiotherapy for nasopharyngeal carcinoma (NPC) is controversial. This study aimed to compare the efficacy and toxicities of induction chemotherapy followed by intensity-modulated radiotherapy (IC-RT) versus concurrent chemoradiotherapy (CCRT) in NPC. METHODS: Of 448 stage II-IVb NPC patients treated with IC-RT or CCRT were retrospectively analysed. The primary outcome was overall survival, which was analysed by using Kaplan-Meier curves and log-rank (Mantel-Cox) test. RESULTS: The median follow-up was 66 months (interquartile range, 46-84 months). There was no statistically significant difference in the estimated 5-year overall survival (OS), progression-free survival (PFS), distance metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) between IC-RT group and CCRT group (OS: 89.5% vs 91.7%, P = .568; PFS: 85.2% vs 87.5%, P = .615; DMFS: 90.9% vs 91.7%, P = .847; LRFS: 92.0% vs 96.9%, P = .104). In the multivariate analysis, the treatment group (IC-RT vs CCRT) was not an independent prognostic factor for OS, PFS, DMFS and LRFS. Less advanced tumour stage and lymph node stage were predictive of higher OS. EBV-DNA level was an independent prognostic factor that was only significantly associated with LRFS. CONCLUSIONS: IC-RT achieves similar survival outcomes and treatment-related toxicities as CCRT in OS, PFS, DMFS and LRFS for patients with NPC. We need multicentre randomised controlled trials to reconfirm our data.

Increased versus stable dose of inhaled corticosteroids for asthma exacerbations: A systematic review and meta-analysis.

BACKGROUND: Increasing the dose of inhaled corticosteroids (ICS) is commonly used at early signs of loss of asthma control. However, the potential benefits and harms of this strategy remain unclear. We performed a systematic review and meta-analysis to compare increased dose with stable dose of ICS among adults and children with asthma. METHODS: We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from inception to August 02, 2018. Randomized clinical trials comparing increased doses vs stable doses of ICS for home management of asthma exacerbations in adults or children were included. RESULTS: The analyses included 8 trials totalling 3866 patients. Four trials were judged as low risk of bias, three were unclear risk, and one was ranked as high risk. Increased dose of ICS was associated with a significantly reduced risk of treatment failure compared with stable dose (OR 0.82, 95% CI 0.70-0.97, I2  = 6%; 314 (281 to 351) vs 358 events per 1000 patients; moderate-quality evidence). There was no significant difference in unscheduled physician visits or hospital admission between increased or stable dose of ICS. However, increased dose of ICS increased the risk of non-serious adverse events (OR 3.50, 95% CI 1.93-6.35, I2  = 0%) but not serious adverse events. CONCLUSIONS: Current evidence of moderate quality supports increasing the dose of ICS as part of a self-initiated action plan to reduce risk of requiring a course of systemic corticosteroids in people with an asthma exacerbation. However, we did not find evidence for an impact on hospital admissions or unscheduled physician visits, and increased ICS dose increased risk of non-serious adverse events.

Psychomotor retardation with a 1q42.11-q42.12 deletion.

A 1q42 deletion is a rare structure variation that commonly harbours various deletion breakpoints along with diversified phenotypes. In our study, we found a de novo 1q42 deletion in a boy who did not have a cleft palate or a congenital diaphragmatic hernia but presented with psychomotor retardation. A 1.9 Mb deletion located within 1q42.11-q42.12 was validated at the molecular cytogenetic level. This is the first report of a 1q42.11-q42.12 deletion in a patient with onlypsychomotor retardation. The precise break points could facilitate the discovery of potential causative genes, such as LBR, EPHX1, etc. The correlation between the psychomotor retardation and the underlying genetic factors could not only shed light on the diagnosis of psychomotor retardation at the genetic level but also provide potential therapeutic targets.

Identification and functional analysis of the novel ORF4 protein encoded by porcine circovirus type 2.

Porcine circovirus type 2 (PCV2) is the primary causative agent of porcine circovirus-associated diseases in pigs. To date, viral proteins Cap, Rep, Rep', and ORF3, encoded by the PCV2 genome, have been described. Here, transcription and translation of a novel viral gene within the PCV2 genome (designated ORF4) was determined and functionally analyzed in vitro and in vivo. Northern blot analysis indicated that the RNA transcribed from the ORF4 gene is about 180 bp in length and overlaps ORF3 in the same direction. Site-directed mutagenesis confirmed that the viral ORF4 protein is not essential for virus replication in PK-15 cells and in mice infected with an ORF4-deficient PCV2 (PCV2Δ). PCV2Δ triggered higher activity levels of caspase-3 and -8 than wild-type PCV2 (wPCV2) in PK-15 cells. The antigenic epitopes of two mouse monoclonal antibodies (MAbs) raised against the viral ORF4 protein were mapped to the same 19KSSASPR25 peptide. Expression of ORF4 was confirmed using the specific MAbs in wPCV2-infected PK-15 cells and mice. Mice infected with PCV2Δ had a higher serum viral load (genomic copies) and more severe lymphoid tissue damage in the spleen than those infected with wPCV2. Meanwhile, flow-cytometric analysis indicated that the PCV2Δ infection caused a significant decrease of CD4(+) and CD8(+) T lymphocytes. Our results demonstrate that ORF4 is a newly discovered viral protein that is not essential for PCV2 replication but plays a role in suppressing caspase activity and regulating CD4(+) and CD8(+) T lymphocytes during PCV2 infection.

Efficacy and Safety of Once-Weekly Insulin Regimes on Glycemic Control for Type 2 Diabetes: A Systematic Review and Network Meta-analysis.

BACKGROUND: Randomized controlled trials have found that once-weekly insulin resulted in greater glycemic control compared to once-daily insulin in patients with type 2 diabetes. However, no direct comparisons have been made between different types of once-weekly insulin thus far. This systematic review and network meta-analysis aimed to evaluate the effect of the two most advanced once-weekly insulin analogues, namely insulin icodec and insulin Fc, in patients with type 2 diabetes. METHODS: We conducted a thorough search in the databases PubMed, Embase, and the Cochrane Central Register of Controlled Trials. The search included articles published from the beginning to October 10, 2023, with no language limitations. Our aim was to conduct a systematic review of randomized controlled trials that investigated the effectiveness and safety of once-weekly insulin in individuals with type 2 diabetes. Our primary outcome was to evaluate excellent glycemic control, defined as patients achieving glycated hemoglobin levels below 7%. RESULTS: We identified a total of 7 trials involving 2829 patients. The results showed that once-weekly insulin icodec is more effective than once-weekly insulin Fc (RR 1.59 [95% CI 1.08-2.38]), once-daily degludec (RR 1.43 [95% CI 1.14-1.83]), and once-daily glargine (RR 1.15 [95% CI 1.00-1.41]). Moreover, the incidence of severe hypoglycemia was lower with once-weekly insulin icodec compared to once-daily degludec (RR 0.00016 [95% CI 0 to 0.41]). However, no significant difference in the incidence of severe hypoglycemia was observed between once-weekly insulin icodec and once-daily glargine (RR 0.39 [95% CI 0.03 to 4.83]). CONCLUSIONS: In patients with type 2 diabetes, once-weekly insulin icodec achieved superior glycemic control compared to once-weekly insulin Fc, with no significant difference in the occurrence of hypoglycemia. The ranking probability results have shown that one weekly icodec seems to be the preferred option in patients with type 2 diabetes. TRIAL REGISTRATION: PROSPERO Identifier: CRD42023470894.

Expression profiles and gene set enrichment analysis of the transcriptomes from the cancer tissue, white adipose tissue and paracancer tissue with colorectal cancer.

Background: Colorectal cancer (CRC) is one of the most common cancers worldwide and is related to diet and obesity. Currently, crosstalk between lipid metabolism and CRC has been reported; however, the specific mechanism is not yet understood. In this study, we screened differentially expressed long non-coding RNAs (lncRNAs) and mRNAs from primary cancer, paracancer, and white adipose tissue of CRC patients. We screened and analyzed the genes differentially expressed between primary and paracancer tissue and between paracancer and white adipose tissue but not between primary and white adipose tissue. According to the results of the biological analysis, we speculated a lncRNA (MIR503HG) that may be involved in the crosstalk between CRC and lipid metabolism through exosome delivery. Methods: We screened differentially expressed long non-coding RNAs (lncRNAs) and mRNAs from primary cancer, paracancer, and white adipose tissue of CRC patients. We screened and analyzed the genes differentially expressed between primary and paracancer tissue and between paracancer and white adipose tissue but not between primary and white adipose tissue. Results: We speculated a lncRNA (MIR503HG) that may be involved in the crosstalk between CRC and lipid metabolism through exosome delivery. Conclusions: In this study, the findings raise the possibility of crosstalk between lipid metabolism and CRC through the exosomal delivery of lncRNAs.

Association of high fibrinogen to albumin ratio with long-term mortality in patients with spontaneous intracerebral hemorrhage.

Background: The association between fibrinogen-to-albumin ratio (FAR) and in-hospital mortality in patients with spontaneous intracerebral hemorrhage (ICH) has been established. However, the association with long-term mortality in spontaneous ICH remains unclear. This study aims to investigate the association between FAR and long-term mortality in these patients. Methods: Our retrospective study involved 3,538 patients who were diagnosed with ICH at West China Hospital, Sichuan University. All serum fibrinogen and serum albumin samples were collected within 24 h of admission and participants were divided into two groups according to the FAR. We conducted a Cox proportional hazard analysis to evaluate the association between FAR and long-term mortality. Results: Out of a total of 3,538 patients, 364 individuals (10.3%) experienced in-hospital mortality, and 750 patients (21.2%) succumbed within one year. The adjusted hazard ratios (HR) showed significant associations with in-hospital mortality (HR 1.61, 95% CI 1.31-1.99), 1-year mortality (HR 1.45, 95% CI 1.25-1.67), and long-term mortality (HR 1.45, 95% CI 1.28-1.64). Notably, the HR for long-term mortality remained statistically significant at 1.47 (95% CI, 1.15-1.88) even after excluding patients with 1-year mortality. Conclusion: A high admission FAR was significantly correlated with an elevated HR for long-term mortality in patients with ICH. The combined assessment of the ICH score and FAR at admission showed higher predictive accuracy for long-term mortality than using the ICH score in isolation.

Association of Postoperative Hypoglycemia With Mortality After Elective Craniotomy.

BACKGROUND AND OBJECTIVES: Hypoglycemia is a known risk of intensive postoperative glucose control in neurosurgical patients. However, the impact of postoperative hypoglycemia after craniotomy remains unexplored. This study aimed to determine the association between postoperative hypoglycemia and mortality in patients undergoing elective craniotomy. METHODS: This study involved adult patients who underwent elective craniotomy at the West China Hospital, Sichuan University, between January 2011 and March 2021. We defined moderate hypoglycemia as blood glucose levels below 3.9 mmol/L (70 mg/dL) and severe hypoglycemia as blood glucose levels below 2.2 mmol/L (40 mg/dL). The primary outcome was postoperative 90-day mortality. RESULTS: This study involved 15 040 patients undergoing an elective craniotomy. Overall, 504 (3.4%) patients experienced moderate hypoglycemia, whereas 125 (0.8%) patients experienced severe hypoglycemia. Multivariable analysis revealed that both moderate hypoglycemia (adjusted odds ratio [aOR] 1.86, 95% CI 1.24-2.78) and severe (aOR 2.94, 95% CI 1.46-5.92) hypoglycemia were associated with increased 90-day mortality compared with patients without hypoglycemia. Moreover, patients with moderate (aOR 2.78, 95% CI 2.28-3.39) or severe (aOR 16.70, 95% CI 10.63-26.23) hypoglycemia demonstrated a significantly higher OR for major morbidity after adjustment, compared with those without hypoglycemia. Patients experiencing moderate (aOR 3.20, 95% CI 2.65-3.88) or severe (aOR 14.03, 95% CI 8.78-22.43) hypoglycemia had significantly longer hospital stays than those without hypoglycemia. The risk of mortality and morbidity showed a tendency to increase with the number of hypoglycemia episodes in patients undergoing elective craniotomy (P for trend = .01, <.001). CONCLUSION: Among patients undergoing an elective craniotomy, moderate hypoglycemia and severe hypoglycemia are associated with increased mortality, major morbidity, and prolonged hospital stays. In addition, the risk of mortality and major morbidity increases with the number of hypoglycemia episodes.