Isorhamnetin ameliorates cisplatin-induced acute kidney injury in mice by activating SLPI-mediated anti-inflammatory effect in macrophage.

OBJECTIVE: Isorhamnetin (IH) has been reported to have significant anti-inflammatory effects in various diseases, but its role and mechanism in AKI remain unclear. This study aimed to explore the potential role and mechanism of isorhamnetin in inhibiting macrophage related inflammation and improving AKI injury. METHODS: We established an AKI mouse model by intraperitoneal injection of cisplatin in vivo, and constructed an inflammatory cell model by stimulating RAW264.7 cells with LPS. Creatinine and urea nitrogen were measured to evaluate the changes of renal function in AKI mice. The changes of renal pathological structure were observed by H&E staining. The inflammatory factor-related proteins and RNA expression levels were detected by Western blot and real time PCR. RESULTS: Isorhamnetin protected the kidney from cisplatin induced AKI and significantly inhibited the mRNA and protein levels of inflammatory cytokines (IL-1ß, IL-6, and TNF-α) both in AKI kidney and LPS-stimulated RAW264.7 cells. Interestingly, the data also demonstrated that isorhamnetin significantly upregulated the expression of secretory leukocyte peptidase inhibitor (SLPI), an anti-inflammatory factor, in AKI kidney and LPS-stimulated macrophages, as well as inhibited the M1 macrophage and activated M2 macrophage in vitro. Blocking of SLPI by siRNA activated Mincle-associated inflammatory signaling in macrophages, and the inhibitory effect of isorhamnetin on inflammation was significantly attenuated. CONCLUSION: Isorhamnetin inhibits macrophage inflammation and protects kidney in AKI may be related to downregulating Mincle/Syk/NF-κB-maintained macrophage phenotype by activating SLPI.

Ixazomib-based frontline therapy followed by ixazomib maintenance in frail elderly newly diagnosed with multiple myeloma: a prospective multicenter study.

Background: Frail elderly patients with newly diagnosed multiple myeloma (NDMM) have inferior survival and less benefit from high-dose therapies. This prospective study aimed to investigate the efficacy, safety, and quality of life (QoL) of induction treatment of ixazomib/lenalidomide/dexamethasone (IRd) and ixazomib/pegylated liposomal doxorubicin/dexamethasone (IDd) followed by ixazomib/dexamethasone (Id) maintenance therapy in frail, elderly patients with NDMM. Methods: From July 2019 to December 2021, this non-randomized concurrent controlled clinical study enrolled 120 NDMM patients aged ≥65 years with frailty defined by the International Myeloma Working Group (IMWG) frailty score or Mayo geriatric scoring system. The enrolled patients received 6-8 cycles of IRd or IDd followed by Id maintenance therapy for a minimum of 2 years at the discretion of physicians based on patient's clinical characteristics (chiCTR1900024917). Findings: The median age was 71 years and 55% of the patients were males. The overall response rate (ORR) was 82% and 77%, complete response (CR) rate was 25% and 12% for IRd and IDd groups, respectively. The difference in ORR of the Idd group minus the IRd group was -5.36% (95% CI: -18.9% to 8.19%), indicating that the ORR of the IDd group was neither inferior nor non-inferior to the IRd group. After a median follow-up of 34.3 months, the median progression-free survival (PFS) was 21.6 and 13.9 months, OS was not reached and 29.2 months in IRd and IDd groups, respectively. 28 and 33 patients discontinued induction therapy, 20 and 19 discontinued maintenance therapy in IRd and IDd groups, respectively. Cumulative Grade 3 or higher hematological adverse events (AEs) occurred in 10 of the 60 patients (17%) and non-hematological AEs occurred in 15 of the 60 patients (25%) in the IRd group, while 13 of the 60 patients (22%) and 21 of the 60 patients (35%) in the IDd group. Patients were observed with clinically significant improvement in QoL when compared with that at baseline in both IRd and IDd groups by evaluation per cycle (P < 0.0001). Interpretation: The results demonstrated that compared with IRd regimen, IDd regimen showed no significant advantage, but the survival of the IDd group was shorter than that of the IRd group, indicating an all-oral outpatient triplet regimen with IRd, which has low toxicity and has improved QoL, could be the viable first-line treatment option for frail NDMM patients. Funding: The Young Elite Scientist sponsorship program by bast of Beijing Association for Science and Technology (No. BYESS2023116) and Beijing Medical Award Foundation (No. YXJL-2018-0539-0073).

Omega-3 supplementation improves depressive symptoms, cognitive function and niacin skin flushing response in adolescent depression: A randomized controlled clinical trial.

BACKGROUND: Depressive disorder in adolescents is a major health problem with inadequate treatment. Omega-3 (ω3) polyunsaturated fatty acids are a promising adjuvant therapy in adult depression. The primary objective of this study was to investigate the efficacy of adjuvant ω3 treatment on depressive symptoms in adolescent depression. Secondarily, we explored the effects of ω3 on cognitive function and memory and niacin skin flushing response (NSFR), as their robust associations with adolescent depression. METHODS: A total of 71 adolescents with depression (aged 13-24; 59.2 % female) were randomly assigned to receive ω3 plus Paxil (n = 34) or Paxil alone (n = 37) for 12 weeks. Primary outcome was depression severity according to scores on Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes were cognitive function and memory, and NSFR. RESULTS: Significant improvements in depressive symptoms over time (p = 0.00027 at week 12) were observed in the ω3 + Paxil group compared with Paxil group. Additionally, in the ω3 + Paxil group, significant improvements in memory over time, and greater cognitive function and NSFR were also observed compared with the Paxil group; the NSFR was negatively correlated with MADRS scores at baseline. LIMITATIONS: The trial was open label; thus, the outcome measures should be viewed as preliminary since inherent bias in outcomes due to the potential of a placebo effect. CONCLUSIONS: Our results demonstrate that adjuvant ω3 treatment is effective for reducing depressive symptoms as well as improving cognitive function, memory and the NSFR; these results suggest ω3 is a promising adjuvant treatment for adolescent depression.

Coupling analysis of crane accident risks based on Bayesian network and the N-K model.

Crane usage is pervasive on construction sites, however, it is associated with a notably high accident rate. The analyzing of crane accident risks is essential for accident prevention, control, and ensuring the safety of lifting operations. Hence, significant emphasis should be placed on understanding the interaction among various risk factors. This paper proposes a quantitative coupling method for human, machine, management, and environmental risk factors in crane accidents, leveraging Bayesian networks (BN) and the N-K model. Firstly, text mining technology and fault tree analysis are employed to analyze the causes of crane accidents and categorize the associate risk factors. Secondly, the types of risk coupling resulting from human, machine, management, and environmental risk factors are defined. Thirdly, the BN model is developed based on the analysis of crane accident risksand its N-K model. Fourthly, the parameters of the risk coupling nodes in the developed BN are determined based on the calculation results of the N-K model. Finally, for the risk coupling types with high coupling values and the first-level node and second-level node, the failure probability is analyzed through posterior probability and sensitivity analysis. The results indicate that factors related to man and management significantly impact crane accidents and warrant enhanced attention. The interplay among multiple risk factors significantly influences the probability of crane accidents, necessitating careful attention.

Dynamic Fluorescence Sensing of Bromide Ions by Photochromic Bi(III)-Coordination Polymers Based on a Ligand Integrated by Naphthalene Diimides and Pyridinium in Solution and Films.

Bismuth(III)-based complexes have garnered increasing attention in fluorescence sensing due to their environmentally friendly and sustainable characteristics. A Bismuth(III) coordination polymer (CP),1-Cl based on a naphthalene diimides(NDI)-pyridinium is synthesized by an in situ reaction method. Notable for its sensitivity to visible light, 1-Cl shows excellent photochromic properties, and the integration of NDI and pyridinium in one ligand makes photogenerated radicals more stable. Structural analysis and theoretical calculations are employed to investigate the potential pathway of photoinduced electron transfer (ET) during the photochromic process. Notably, in aqueous solutions, 1-Cl displays an extraordinary fluorescence enhancement response to bromide ion (Br-), resulting in a distinct transition from yellow to orange in color. The potential mechanism of fluorescence sensing has been revealed through single-crystal X-ray diffraction analysis. This insight highlights a continuous substitution process where the Cl- ions are successively replaced by Br- ions. Consequently, a single-crystal-to-single-crystal transformation (SCSC) occurs, yielding the intermediate species, 1-Cl-Br, which ultimately transforms into the final product, 1-Br. Finally, the photochromic film is successfully prepared and applied to practical applications such as ink-free printing, information anti-counterfeiting, and the visual detection of Br- ions. This work combines photochromism with fluorescence sensing, broadening the research field and practical application of photochromic materials.

Acute pancreatitis in intraductal papillary mucinous neoplasm: a single-center retrospective cohort study with systematic review and meta-analysis.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is a cystic tumor of the pancreas arising from abnormal papillary proliferation of ductal epithelial cells, and is a precancerous lesion of pancreatic malignancy. This study aimed to evaluate associations between acute pancreatitis (AP) and histologic subtypes of IPMN. METHODS: In the clinical study, patients with IPMN confirmed by surgical resection specimens at our institute between 2009 and 2021 were eligible for inclusion. Associations and predictive accuracy of AP on the presence of HGD were determined by logistic regressions. In addition, a systematic review and meta-analysis was conducted through literatures upon search in PubMed, Embase, CENTRAL, China National Knowledge Infrastructure (CKNI), and Wanfang database, up to June, 2023. Pooled effects of the associations between AP and HGD and intestinal epithelial subtype subtype, shown as odds ratios (ORs) with 95% confidence intervals (CIs), were calculated using random effects model. RESULTS: The retrospective cohort study included 47 patients (32 males, 15 females) diagnosed with IPMN at our center between 2009 and 2021, including 11 cases with AP (median 62 years) and 36 cases (median 64.5 years) without. Accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of AP in predicting HGD were 78.7%, 57.1%, 82.5%, 36.4%, and 91.7%, respectively. Univariate logistic regression analysis showed that AP group had greater odds of presence of HGD (OR: 6.29,95% CI: 1.14-34.57) than non-AP group. Meta-analysis of five case-control studies in the literature included 930 patients and showed that AP-IPMN patients had higher odds for HGD (OR: 2.13, 95% CI 1.38-3.29) and intestinal epithelial subtype (OR: 5.38, 95% CI: 3.50-8.27) compared to non-AP IPMN. CONCLUSIONS: AP is predictive of malignancy in patients with IPMN.

The Role of P53 in Myocardial Ischemia-Reperfusion Injury.

PURPOSE: P53 is one of the key tumor suppressors. In normal cells, p53 is maintained at low levels by the ubiquitination of the ubiquitinated ligase MDM2. In contrast, under stress conditions such as DNA damage and ischemia, the interaction between p53 and MDM2 is blocked and activated by phosphorylation and acetylation, thereby mediating the trans-activation of p53 through its target genes to regulate a variety of cellular responses. Previous studies have shown that the expression of p53 is negligible in normal myocardium, tends to increase in myocardial ischemia and is maximally induced in ischemia-reperfused myocardium, demonstrating a possible key role of p53 in the development of MIRI. In this review, we detail and summarize recent studies on the mechanism of action of p53 in MIRI and describe the therapeutic agents targeting the relevant targets to provide new strategies for the prevention and treatment of MIRI. METHODS: We collected 161 relevant papers mainly from Pubmed and Web of Science (search terms "p53" and "myocardial ischemia-reperfusion injury"). After that, we selected pathway studies related to p53 and classified them according to their contents. We eventually analyzed and summarized them. RESULTS AND CONCLUSION: In this review, we detail and summarize recent studies on the mechanism of action of p53 in MIRI and validate its status as an important intermediate affecting MIRI. On the one hand, p53 is regulated and modified by multiple factors, especially non-coding RNAs; on the other hand, p53 regulates apoptosis, programmed necrosis, autophagy, iron death and oxidative stress in MIRI through multiple pathways. More importantly, several studies have reported medications targeting p53-related therapeutic targets. These medications are expected to be effective options for the alleviation of MIRI, but further safety and clinical studies are needed to convert them into clinical applications.

Nobiletin alleviates myocardial ischemia-reperfusion injury via ferroptosis in rats with type-2 diabetes mellitus.

Susceptibility to myocardial ischemia-reperfusion (IR) injury in type-2 diabetes (T2DM) remains disputed, although studies have reported that ferroptosis is associated with myocardial IR injury. Nobiletin, a flavonoid isolated from citrus peels, is an antioxidant that possesses anti-inflammatory and anti-diabetic activities. However, it remains unknown whether nobiletin has any protective effects on susceptibility to myocardial IR injury during T2DM in rats via ferroptosis. To investigate the effects and underlying mechanisms of nobiletin on myocardial IR injury during T2DM, we induced myocardial IR model in rats at T2DM onset vs mature disease. We also established a high-fat high-glucose (HFHG) and hypoxia-reoxygenation (H/R) model in H9c2 cells to imitate abnormal glycolipid metabolism during T2DM. Myocardial injury, oxidative stress and ferroptosis towards myocardial IR in rats with mature T2DM but not at T2DM onset were increased. These changes were restored under treatment with ferrostain-1 or nobiletin. Both ferrostain-1 and nobiletin decreased the expression of ferroptosis-related proteins including Acyl-CoA synthetase long chain family member 4 (ACSL4) and nuclear receptor coactivator 4 (NCOA4) but not glutathione peroxidase 4 (GPX4) in rats with mature T2DM and cells with HFHG and H/R injury. Nobiletin strengthened the effect of si-ACSL4 on inhibiting ACSL4 expression, and also inhibited the effect of Erastin or oe-ACSL4 on increasing ACSL4 expression. Taken together, our data indicates that ferroptosis involves in susceptibility to myocardial IR injury in rats during T2DM. Nobiletin has therapeutic potential for alleviating myocardial IR injury associated with ACSL4- and NCOA4-related ferroptosis.

The role of circadian clock-controlled mitochondrial dynamics in diabetic cardiomyopathy.

Diabetes mellitus is a metabolic disease with a high prevalence worldwide, and cardiovascular complications are the leading cause of mortality in patients with diabetes. Diabetic cardiomyopathy (DCM), which is prone to heart failure with preserved ejection fraction, is defined as a cardiac dysfunction without conventional cardiac risk factors such as coronary heart disease and hypertension. Mitochondria are the centers of energy metabolism that are very important for maintaining the function of the heart. They are highly dynamic in response to environmental changes through mitochondrial dynamics. The disruption of mitochondrial dynamics is closely related to the occurrence and development of DCM. Mitochondrial dynamics are controlled by circadian clock and show oscillation rhythm. This rhythm enables mitochondria to respond to changing energy demands in different environments, but it is disordered in diabetes. In this review, we summarize the significant role of circadian clock-controlled mitochondrial dynamics in the etiology of DCM and hope to play a certain enlightening role in the treatment of DCM.

Diagnostic performance and prognostic value of circulating tumor DNA methylation marker in extranodal natural killer/T cell lymphoma.

Circulating tumor DNA (ctDNA) carries tumor-specific genetic and epigenetic variations. To identify extranodal natural killer/T cell lymphoma (ENKTL)-specific methylation markers and establish a diagnostic and prognosis prediction model for ENKTL, we describe the ENKTL-specific ctDNA methylation patterns by analyzing the methylation profiles of ENKTL plasma samples. We construct a diagnostic prediction model based on ctDNA methylation markers with both high specificity and sensitivity and close relevance to tumor staging and therapeutic response. Subsequently, we built a prognostic prediction model showing excellent performance, and its predictive accuracy is significantly better than the Ann Arbor staging and prognostic index of natural killer lymphoma (PINK) risk system. Notably, we further establish a PINK-C risk grading system to select individualized treatment for patients with different prognostic risks. In conclusion, these results suggest that ctDNA methylation markers are of great value in diagnosis, monitoring, and prognosis, which might have implications for clinical decision-making of patients with ENKTL.

Intravenous Administration of Hypertonic Glucose Solution to Prevent Dizziness in Patients Undergoing Gastrointestinal Endoscopy Under General Anesthesia: A Randomized Clinical Trial.

BACKGROUND AND OBJECTIVE: Dizziness is a common complication of gastrointestinal endoscopy under general anesthesia. Dizziness is primarily caused by a lack of energy and blood volume following fasting and water deprivation. Hypertonic glucose solution (HGS) is an intravenous energy replenishment, that increases blood volume due to its hyperosmotic characteristics and can be directly absorbed from blood circulation. This study aimed to HGS can prevent dizziness after gastrointestinal endoscopy. METHODS: This was a double-blind, randomized, controlled study. Eligible patients were randomly allocated into two groups based on the intravenous agent administered before gastrointestinal endoscopy: Group A, saline (0.9%; 20 mL); and group B, HGS (50%; 20 mL). Overall, 840 patients were included in the statistical analysis. The scores and incidence of dizziness were assessed. RESULTS: The dizziness score were higher in group A than in group B (1.92 ± 0.08 vs. 0.92 ± 0.06; p < 0.01). The incidence of mild dizziness and moderate-to-severe dizziness was significantly lower in group B than in group A (40.10% vs. 51.78% and 3.10% vs. 19.72%, respectively; p < 0.01). The incidence and score of dizziness were significantly lower in males than in females (30.81% vs. 51.82% and 0.64 ± 0.08 vs. 1.12 ± 0.08, respectively; p < 0.01) after pretreatment with HGS. CONCLUSION: Pretreatment with HGS effectively prevents dizziness after gastrointestinal endoscopy under general anesthesia. The mechanism of action is unclear but might be related to body energy replacement and an increase in blood volume following HGS administration.

Hederagenin improves psoriasis skin lesions by inhibiting macrophage mincle-mediated inflammation / 中国临床药理学与治疗学

AIM: To observe the effects and mechanisms of hederagenin (HDG) in improving psoriasis skin lesions and inflammation in mice. METHODS: A mouse model of psoriasis was established by depilation of the back and continuous application of imiquimod for 7 days in C57 mice. After modeling, HDG was administered orally (low dose: 25 mg · kg

Analysis of typical experiences of public hospital salary system reform in Sichuan province / 中华医院管理杂志

Objective:To analyze the experiences and practice in the reform of public hospital salary system in Sichuan province, summarize the typical modes of such reform in the province, and provide references for further reform.Methods:As of October 29, 2021, the research group received 77 sets of typical experience materials submitted by the health commissions and public hospitals in Sichuan province on enforcing the reform of the public hospital salary system. The analysis framework was based on the five main elements proposed in the Guidance to Deepening the Reform of the Salary System of Public Hospitals for the purpose of furthering the reform. These five elements refer to " reasonably determining the level of salary in public hospitals" " fully implementing the autonomy of internal distribution in public hospitals " " establishing and improving the incentive and restraint mechanism for the remuneration of public hospital leaders" " improving the assessment and evaluation mechanism oriented to public welfare" and " funding sources ". A quantitative analysis was made on the typical experience materials using the social network analysis method, while a qualitative analysis was made on the typical experience materials using the content analysis method. Results:The results of social network analysis showed that the network density was 0.272; the highest point centrality was " fully implement the autonomy of internal distribution in public hospitals" (0.935), and the highest intermediary centrality was " improving the assessment and evaluation mechanism oriented to public welfare" (0.870), while the closeness to centrality of " establishing and improving the incentive and constraint mechanism for the salary of public hospital leaders" (0.434) and " funding sources" (0.421) were relatively low. The results of content analysis showed that the ones with higher frequency among all the typical experience materials were " fully implementing the autonomy of internal distribution of hospitals" (72 times) and " improving the assessment and evaluation mechanism oriented to public welfare" (67 times), while the ones with lower frequency were " establishing and improving the salary incentive and constraint mechanism for public hospital leaders" (17 times) and " funding sources" (14 times). In terms of unity and synergy, the typical models of public hospital salary system reform in the province could be categorized as the fine standard mode, the fair value mode, the autonomous synergy mode and the circular symbiosis mode.Conclusions:Deepening the reform of the salary system of public hospitals should unify the standards and improve the fair and refined assessment and evaluation mechanism; explore various forms of distribution and build an internal autonomous and synergistic incentive mechanism; pay attention to the weak remuneration incentive mechanism for hospital leaders and the problem of a relatively single source of funding.

Study on the distribution of ABO blood group in patients with pancreatic cancer / 中国输血杂志

【Objective】 To investigate whether there is a correlation between the differences in ABO blood group distribution in patients with pancreatic cancer, and to evaluate the relative risk. 【Methods】 Patients with pathological diagnosis or discharge diagnosis of pancreatic cancer who underwent ABO blood group typing in our hospital from January 2017 to October 2021 were selected, and the blood group distribution of patients and the correlation were analyzed. 【Results】 There was a statistically significant difference between the pancreatic cancer group and the control group (P<0.05). The study showed that type A may be a relative risk factor for pancreatic cancer patients (χ2=42.44, P<0.001), and type B may play a protective role (χ2=16.28, P<0.01). Significant differences were found in distribution between different gender groups (χ2=64.35, P<0.05). The test results showed that type A may be a risk factor for pancreatic cancer in men (χ2=35.2, OR=1.7, 95%CI=0.59-1.02, P<0.001), and type O may play a protective role in pancreatic cancer(χ2=18.22, OR=0.6, 95%CI=0.25-0.32, P<0.01); type A may be a relative risk factor for female pancreatic cancer patients (χ2=7.06, OR=1.4, 95%CI=0.59-1.02, P<0.001), while type B may play a protective role (χ2=20.32, OR=0.5, 95%CI=0.32-0.43, P<0.01). In pancreatic cancer group, the risk factors of blood type A were higher than those of non-A group, and the protective effect of type B was significantly higher than that of non-B group. 【Conclusion】 The distribution of blood group and relative risk factors in pancreatic cancer patients suggest that A type is predominant; in the population with A blood group, more attention should be paid to early prevention and early treatment, so as to reduce the risk of disease.

Alisma Shugan Decoction attenuates hepatic fibrosis and endoplasmic reticulum stress in mice with carbon tetrachloride-induced fibrosis.

Background: Over the years, Alisma Shugan Decoction (ASD), because of its potent anti-inflammation activity, has been used in traditional Chinese medicine (TCM) for treatment of many inflammation-associated disorders including those of the heart, blood vessel and brain. Methods: Herein, we examined the probable therapeutic effect of ASD in carbon tetrachloride (CCl4)-induced liver injury and fibrosis mice models. Results: Our results demonstrate that ASD dose-dependently reduced the fibrosis-related increased collagen deposition secondary to liver tissue exposure to CCl4. Data from our biochemical analyses showed significantly less liver damage biomarkers including ALT, AST and hydroxyproline in the ASD-treated samples, suggesting hepato-protective effect of ASD. Furthermore, we demonstrated that treatment with ASD significantly reversed CCl4-induced elevation of TNF-α, IL-6, IL-1ß and MP-1. Interestingly, NF-κB signalling, a principal regulator of inflammation was markedly suppressed by ASD treatment. In addition, treatment with ASD deregulated stress signalling pathways by suppressing the expression of markers of unfolded protein response, such as ATF6, IRE and GRP78. Conclusion: In conclusion, the present study provides preclinical evidence for the use of ASD as an efficacious therapeutic option in cases of chemical-induced liver damage and/or fibrosis. Further large-cohort validation of these findings is warranted.

CCRT and aerobic exercise: a randomised controlled study of processing speed, cognitive flexibility, and serum BDNF expression in schizophrenia.

Computerised cognitive remediation therapy (CCRT) and aerobic exercise are often used to rehabilitate social functioning in patients with schizophrenia. However, there is limited knowledge regarding the effects of CCRT combined with aerobic exercise on cognitive function and brain-derived neurotrophic factor (BDNF) levels in patients with schizophrenia and cognitive impairment. Ninety-six patients with schizophrenia and cognitive impairment were included in this study and randomly divided into control, aerobic exercise (AE), and CCRT combined with aerobic exercise (CAE) groups. Changes in processing speed and cognitive flexibility at week 8 were evaluated as primary and secondary cognitive outcomes using the Trail Making Test: Part A, the Brief Assessment of Cognition in Schizophrenia: Symbol Coding Test, and the Stroop Colour-Word Test. Positive and Negative Syndrome Scale (PANSS) scores and serum BDNF expression were determined as other secondary outcomes. The CAE group showed significantly better performance in terms of changes in processing speed and cognitive flexibility than the control and AE groups at week 8 (p < 0.05); however, no significant improvements in processing speed and cognitive flexibility were found between the control and AE groups. The CAE group showed significant improvements in the PANSS negative symptoms than the control group at week 8 (p < 0.05), but the AE group showed no significant difference in the changes of PANSS negative symptoms when compared with the other two groups. The CAE group and AE group showed a greater increase in serum BDNF levels than the control group (p < 0.01), but there was no significant difference in serum BDNF expression between the CAE group and AE group. In conclusion, 8-week CCRT combined with aerobic exercise may improve some cognitive performance and negative symptoms in patients with schizophrenia. Aerobic exercise may have an immediate effect on serum BDNF levels rather than cognitive function.

TRAF3IP3 promotes glioma progression through the ERK signaling pathway.

TRAF3IP3 was reportedly associated with poor prognosis in patients with melanoma; however, its role in glioma is unknown. We aimed to demonstrate the relationship between TRAF3IP3 and glioma and to investigate the potential role of TRAF3IP3 in glioma. Datasets were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We used the Wilcoxon rank-sum test to compared TRAF3IP3 expression in normal and glioma tissues. Kaplan-Meier analysis was performed to evaluate the correlation between TRAF3IP3 and patient survival rate. Gene set enrichment analysis (GSEA) was used to annotate the biological function of TRAF3IP3 in glioma. We also examined the effects of TRAF3IP3 on glioma progression, including characteristics such as cell proliferation, migration, and invasion, using cell proliferation, wound healing, and Transwell assays, respectively, paired with in vitro glioma cell lines and in vivo mouse xenograft models to determine the molecular mechanisms underlying these effects. High TRAF3IP3 expression in glioma tissues was associated with patients with neoplasm cancer tissue source site, and poorer overall survival (OS) (p = 0.03), which was validated using TCGA. GSEA revealed the enrichment of neuroactive ligand-receptor interactions, the olfactory pathway, proteasome pathway, cytokine-cytokine receptor interactions, and calcium signaling pathway in the TRAF3IP3 high-expression phenotype. TRAF3IP3 knockdown markedly suppressed the proliferation, migration, and invasion abilities of U251 glioma cells, whereas TRAF3IP3 overexpression notably promoted the progression of U118 cell tumors. Mechanistic studies revealed that TRAF3IP3 upregulated p-ERK expression in glioma cells. Notably, the ERK signaling pathway inhibitor U0126 drastically attenuated the effects of TRAF3IP3 on p-ERK and markedly blocked its tumor-promoting activity. TRAF3IP3 overexpression also promoted in vivo tumor growth in a nude mouse xenograft model. Collectively, TRAF3IP3 stimulates glioma cell proliferation, migration, and invasion, at least partly by activating the ERK signaling pathway. We hypothesize that TRAF3IP3 may participate in glioma development via the ERK signaling pathway and that elevated TRAF3IP3 expression may serve as a potential biomarker for glioma prognosis.

Targeted metabolomics reveals aberrant profiles of serum bile acids in patients with schizophrenia.

Emerging evidence indicates that bile acids (BAs), which are signaling molecules that regulate metabolism and inflammation, appear to be dysregulated in schizophrenia (SZ). Further investigation is warranted to comprehensively characterize BA profiles in SZ. To address this, we analyzed serum BA profiles in 108 drug-free patients with SZ and in 108 healthy controls (HCs), divided into a discovery set (n = 119) and a validation set (n = 97), using ultraperformance liquid chromatography triple quadrupole mass spectrometry. Forty serum BAs were detected and absolutely quantified using calibration curves. Global BA profiling showed differences in SZ and HC groups in both discovery and validation sets. The concentrations of chenodeoxycholic acid, ursodeoxycholic acid, 3ß-chenodeoxycholic acid, 7-ketolithocholic acid, 3-dehydrocholic acid, total BAs, and unconjugated BAs were significantly lower in patients with SZ compared with HCs in the two sample sets. The BA deconjugation potentials by gut microbiota and the affinity index of the farnesoid X receptor (FXR) were notably decreased in SZ patients compared to those of HCs. Conjugated BAs and BA deconjugation potentials differed in SZ patients with first versus recurrent episodes, although similar BA profiles were observed in both groups. In addition, a panel of 8 BA variables acted as a potential auxiliary diagnostic biomarker in discriminating SZ patients from HCs, with area under the curve values for receiver operating characteristic curves of 0.758 and 0.732 and for precision-recall curves of 0.750 and 0.714 in the discovery and validation sets, respectively. This study has provided compelling evidence of comprehensive characteristics of circulating BA metabolism in patients with SZ and promoted a deeper understanding of the role of BAs in the pathophysiology of this disease, possibly via the gut microbiota-FXR signaling pathway.