Correlation of oxidative stress and vascular endothelial dysfunction with hippocampal perfusion in atrial fibrillation patients with cognitive impairment.

Objectives: To evaluate the correlation of oxidative stress and vascular endothelial dysfunction with hippocampal perfusion in patients with atrial fibrillation and cognitive impairment. Methods: In total, 41 atrial fibrillation patients with cognitive impairment were compared to 45 atrial fibrillation patients without cognitive impairment. Oxidative stress, vascular endothelial dysfunction, hippocampal perfusion, and cognitive function were measured. Results: Serum level of oxidized low-density lipoprotein was significantly higher in the atrial fibrillation + cognitive impairment group than in the atrial fibrillation group. Serum levels of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were significantly higher, and nitric oxide was lower, in the atrial fibrillation + cognitive impairment group than in the atrial fibrillation group. The regional cerebral blood volume, mean transit time, and time to peak were significantly higher in the atrial fibrillation + cognitive impairment group than in the atrial fibrillation group. Moreover, regional cerebral blood flow was significantly lower in the atrial fibrillation + cognitive impairment group than in the atrial fibrillation group. Age, left atrial diameter, and regional cerebral blood volume were negatively correlated with the cognitive function score in the atrial fibrillation + cognitive impairment group. Serum levels of oxidized low-density lipoprotein, regional cerebral blood volume, regional cerebral blood flow, mean transit time, and time to peak were significantly correlated with cognitive impairment in atrial fibrillation patients after multivariate logistic regression analysis. Conclusion: Hippocampal perfusion and oxidative stress were significantly correlated with cognitive impairment in atrial fibrillation patients.

Nomogram Based on US and Clinicopathologic Characteristics: Axillary Nodal Evaluation Following Neoadjuvant Chemotherapy in Patients With Node-Positive Breast Cancer.

BACKGROUND: To develop a convenient modality to predict axillary response to neoadjuvant chemotherapy (NAC) in breast cancer patients. MATERIALS AND METHODS: In this multi-center study, a total of 1019 breast cancer patients with biopsy-proven positive lymph node (LN) receiving NAC were randomly assigned to the training and validation groups at a ratio of 7:3. Clinicopathologic and ultrasound (US) characteristics of both primary tumors and LNs were used to develop corresponding prediction models, and a nomogram integrating clinicopathologic and US predictors was generated to predict the axillary response to NAC. RESULTS: Axillary pathological complete response (pCR) was achieved in 47.79% of the patients. The expression of estrogen receptor, human epidermal growth factor receptor -2, Ki-67 score, and clinical nodal stage were independent predictors for nodal response to NAC. Location and radiological response of primary tumors, cortical thickness and shape of LNs on US were also significantly associated with nodal pCR. In the validation cohort, the discrimination of US model (area under the curve [AUC], 0.76) was superior to clinicopathologic model (AUC, 0.68); the combined model (AUC, 0.85) demonstrates strong discriminatory power in predicting nodal pCR. Calibration curves of the nomogram based on the combined model demonstrated that substantial agreement can be observed between the predictions and observations. This nomogram showed a false-negative rates of 16.67% in all patients and 10.53% in patients with triple negative breast cancer. CONCLUSION: Nomogram incorporating routine clinicopathologic and US characteristics can predict nodal pCR and represents a tool to aid in treatment decisions for the axilla after NAC in breast cancer patients.

Spectrum and antibiotic sensitivity of bacterial keratitis: a retrospective analysis of eight years in a Tertiary Referral Hospital in Southwest China.

Purpose: The objective of this study was to investigate the epidemiological characteristics, distribution of isolates, prevailing patterns, and antibiotic susceptibility of bacterial keratitis (BK) in a Tertiary Referral Hospital located in Southwest China. Methods: A retrospective analysis was conducted on 660 cases of bacterial keratitis occurring between January 2015 and December 2022. The demographic data, predisposing factors, microbial findings, and antibiotic sensitivity profiles were examined. Results: Corneal trauma emerged as the most prevalent predisposing factor, accounting for 37.1% of cases. Among these cases, bacterial culture results were positive in 318 cases, 68 species of bacteria were identified. The most common Gram-Positive bacteria isolated overall was the staphylococcus epidermis and the most common Gram-Negative bacteria isolated was Pseudomonas aeruginosa. Methicillin-Resistant Staphylococci accounted for 18.1% of all Gram-Positive bacteria. The detection rate of P. aeruginosa showed an increasing trend over time (Rs=0.738, P=0.037). There was a significant decrease in the percentage of Gram-Negative microorganisms over time (Rs=0.743, P=0.035). The sensitivity of Gram-Positive bacteria to linezolid, vancomycin, tigecycline, quinupristin/dalfopristin, and rifampicin was over 98%. The sensitivity rates of Gram-Negative bacteria to amikacin, meropenem, piperacillin/tazobactam, cefoperazone sodium/sulbactam, ceftazidime, and cefepime were all above 85%. In patients with a history of vegetative trauma, the possibility of BK should be taken into account in addition to the focus on fungal keratitis. Conclusion: The microbial composition primarily consists of Gram-Positive cocci and Gram-Negative bacilli. Among the Gram-Positive bacteria, S. epidermidis and Streptococcus pneumoniae are the most frequently encountered, while P. aeruginosa is the predominant Gram-Negative bacteria. To combat Gram-Positive bacteria, vancomycin, linezolid, and rifampicin are considered excellent antimicrobial agents. When targeting Gram-Negative pathogens, third-generation cephalosporins exhibit superior sensitivity compared to first and second-generation counterparts. As an initial empirical treatment for severe cases of bacterial keratitis and those unresponsive to fourth-generation fluoroquinolones in community settings, the combination therapy of vancomycin and tobramycin is a justifiable approach. Bacterial keratitis can be better managed by understanding the local etiology and antibacterial drug susceptibility patterns.

Single-nuclei RNA-seq reveals skin cell responses to Aeromonas hydrophila infection in Chinese longsnout catfish Leiocassis longirostris.

As the primary natural barrier that protects against adverse environmental conditions, the skin plays a crucial role in the innate immune response of fish, particularly in relation to bacterial infections. However, due to the diverse functionality and intricate anatomical and cellular composition of the skin, deciphering the immune response of the host is a challenging task. In this study, single nuclei RNA-sequencing (snRNA-seq) was performed on skin biopsies obtained from Chinese longsnout catfish (Leiocassis longirostris), comparing Aeromonas hydrophila-infected subjects to healthy control subjects. A total of 19,581 single nuclei cells were sequenced using 10x Genomics (10,400 in the control group and 9,181 in the treated group). Based on expressed unique transcriptional profiles, 33 cell clusters were identified and classified into 12 cell types including keratinocyte (KC), fibroblast (FB), endothelial cells (EC), secretory cells (SC), immune cells, smooth muscle cells (SMC), and other cells such as pericyte (PC), brush cell (BC), red blood cell (RBC), neuroendocrine cell (NDC), neuron cells (NC), and melanocyte (MC). Among these, three clusters of KCs, namely, KC1, KC2, and KC5 exhibited significant expansion after A. hydrophila infection. Analysis of pathway enrichment revealed that KC1 was primarily involved in environmental signal transduction, KC2 was primarily involved in endocrine function, and KC5 was primarily involved in metabolism. Finally, our findings suggest that neutrophils may play a crucial role in combating A. hydrophila infections. In summary, this study not only provides the first detailed comprehensive map of all cell types present in the skin of teleost fish but also sheds light on the immune response mechanism of the skin following A. hydrophila infection in Chinese longsnout catfish.

The Correlation of Inflammation, Oxidative Stress, and Hippocampal Perfusion in Patients with Atrial Fibrillation.

Atrial fibrillation (AF) is closely related to abnormal cerebral blood flow. Inflammation and oxidative stress have always been important factors in the pathophysiology of AF. It remains unknown whether inflammation and oxidative stress are correlated to hippocampal perfusion in patients with AF.Sixty-three patients with AF with normal hippocampal blood perfusion (NHBP) were compared to 71 patients with AF with abnormal hippocampal blood perfusion (AHBP) using a case-control study design. The serum levels of inflammation and oxidative stress were measured. The hippocampal perfusion was detected. (1) The serum levels of high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), and oxidized low-density lipoprotein (ox-LDL) were statistically higher in the AHBP group than in the NHBP group. In the AHBP subgroup analysis, the serum levels of hs-CRP and IL-6 were statistically higher in patients with persistent AF than those with paroxysmal AF. (2) The relative cerebral blood volume (rCBV), mean transit time (MTT), and the time-to-peak (TTP) were statistically higher in the AHBP group than in the NHBP group. Moreover, cerebral blood flow (rCBF) was statistically lower in the AHBP group than in the NHBP group. (3) relative cerebral blood volume (rCBV), rCBF, MTT, and TTP were passively associated with serum hs-CRP and IL-6; rCBV, rCBF, and MTT were positively associated with ox-LDL. The serum levels of hs-CRP, IL-6, and ox-LDL were associated with AHBP in patients with AF after multivariate logistic regression analysis.Oxidative stress and inflammatory biomarkers were increased in patients with AF with AHBP, in which the serum levels of hs-CRP and IL-6 in the persistent AF group were statistically higher than those in the paroxysmal AF group. The serum levels of hs-CRP, IL-6, and ox-LDL were associated with AHBP in patients with AF.

Proteomics reveals defective peroxisomal fatty acid oxidation during the progression of acute kidney injury and repair.

Acute kidney injury (AKI) is characterized by a rapid decrease in renal function with high mortality and risk of progression to chronic kidney disease (CKD). Ischemia and reperfusion injury (IRI) is one of the major causes of AKI. However, the cellular and molecular responses of the kidney to IRI are complex and not fully understood. Herein, we conducted unbiased proteomics and bioinformatics analyses in an IRI mouse model on days 3, 7, and 21, and validated the results using IRI, unilateral ureteral obstruction (UUO), and biopsies from patients with AKI or CKD. The results indicated an obvious temporal expression profile of differentially expressed proteins and highlighted impaired lipid metabolism during the progression of AKI to CKD. Acyl-coenzyme A oxidase 1 (Acox1), the first rate-limiting enzyme of peroxisomal fatty acid beta-oxidation, was then selected, and its disturbed expression in the two murine models validated the proteomic findings. Accordingly, Acox1 expression was significantly downregulated in renal biopsies from patients with AKI or CKD, and its expression was negatively correlated with kidney injury score. Furthermore, in contrast to the decreased Acox1 expression, lipid droplet accumulation was remarkably increased in these renal tissues, suggesting dysregulation of fatty acid oxidation. In conclusion, our results suggest that defective peroxisomal fatty acid oxidation might be a common pathological feature in the transition from AKI to CKD, and that Acox1 is a promising intervention target for kidney injury and repair.

PacBio single-molecule long-read sequencing provides new insights into the complexity of full-length transcripts in oriental river prawn, macrobrachium nipponense.

BACKGROUND: Oriental river prawn (Macrobrachium nipponense) is one of the most dominant species in shrimp farming in China, which is a rich source of protein and contributes to a significant impact on the quality of human life. Thus, more complete and accurate annotation of gene models are important for the breeding research of oriental river prawn. RESULTS: A full-length transcriptome of oriental river prawn muscle was obtained using the PacBio Sequel platform. Then, 37.99 Gb of subreads were sequenced, including 584,498 circular consensus sequences, among which 512,216 were full length non-chimeric sequences. After Illumina-based correction of long PacBio reads, 6,599 error-corrected isoforms were identified. Transcriptome structural analysis revealed 2,263 and 2,555 alternative splicing (AS) events and alternative polyadenylation (APA) sites, respectively. In total, 620 novel genes (NGs), 197 putative transcription factors (TFs), and 291 novel long non-coding RNAs (lncRNAs) were identified. CONCLUSIONS: In summary, this study offers novel insights into the transcriptome complexity and diversity of this prawn species, and provides valuable information for understanding the genomic structure and improving the draft genome annotation of oriental river prawn.

Impact of a novel prognostic model on allogeneic hematopoietic stem cell transplantation outcomes in patients with CMML.

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable treatment. The outcomes after transplant are influenced by both disease characteristics and patient comorbidities. To develop a novel prognostic model to predict the post-transplant survival of CMML patients, we identified risk factors by applying univariable and multivariable Cox proportional hazards regression to a derivation cohort. In multivariable analysis, advanced age (hazard ratio [HR] 3.583), leukocyte count (HR 3.499), anemia (HR 3.439), bone marrow blast cell count (HR 2.095), and no chronic graft versus host disease (cGVHD; HR 4.799) were independently associated with worse survival. A novel prognostic model termed ABLAG (Age, Blast, Leukocyte, Anemia, cGVHD) was developed and the points were assigned according to the regression equation. The patients were categorized into low risk (0-1), intermediate risk (2, 3), and high risk (4-6) three groups and the 3-year overall survival (OS) were 93.3% (95%CI, 61%-99%), 78.9% (95%CI, 60%-90%), and 51.6% (95%CI, 32%-68%; p < .001), respectively. In internal and external validation cohort, the area under the receiver operating characteristic (ROC) curves of the ABLAG model were 0.829 (95% CI, 0.776-0.902) and 0.749 (95% CI, 0.684-0.854). Compared with existing models designed for the nontransplant setting, calibration plots, and decision curve analysis showed that the ABLAG model revealed a high consistency between predicted and observed outcomes and patients could benefit from this model. In conclusion, combining disease and patient characteristic, the ABLAG model provides better survival stratification for CMML patients receiving allo-HSCT.

Evaluating the trilemma nexus of digital finance, renewable energy consumption, and CO2 emission: evidence from nonlinear ARDL model.

It has been established in 2030 sustainability objectives as per SDGs that highlight the critical importance of access to affordable, renewable energy, robust, long-term industrial progress, and digital financing in CO2 emission. The intent of study is to test the trilemma nexus between digital finance, renewable energy consumption, and carbon emission reduction with nonlinear ARDL tests. The study acquired the data and applied the nonlinear ARDL test, split analysis tests, and vector-error correction model (VECM) tests. The results of the study highlighted that the increase of digital finance positively enhances the renewable energy and negatively reduces the CO2 emissions which we calculate to be 11.4% of the digital finance funding on renewable energy goods. For this, a 39% increase in digital financing is noticed by the research findings during the COVID-19 crisis period. Such robust study findings present the latest insights that digital financing is an eminent and viable source of financing for the trilemma nexus with renewable energy consumption and the CO2 emissions. Following these, multiple research implications are also presented for the key stakeholders.

Metabolomics of the anti-inflammatory effect of Pueraria lobata and Pueraria lobata var. Thomsonii in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Pueraria lobata (Willd.) Ohwi and Pueraria lobata var. Thomsonii (Benth.) Maesen are essential medicinal and edible homologous plants widely cultivated in Asian countries. Therefore, P. lobata and P. thomsonii are widely used in the food, health products and pharmaceutical industries and have significant domestic and international market potential and research value. P. lobata and P. thomsonii have pharmacological effects in the clinic, such as antipyretic, analgesic, anti-inflammatory and antioxidant effects. These plants are commonly used in the treatment of inflammatory diseases and other related diseases. However, the potential mechanisms of the anti-inflammatory effects of P. lobata and P. thomsonii have not been elucidated. AIM OF THE STUDY: This study aimed to confirm the anti-inflammatory effects of P. lobata and P. thomsonii on inflammatory model diseases and to investigate the mechanism of their anti-inflammatory effects from the perspective of plasma metabolomics. MATERIALS AND METHODS: First, P. lobata and P. thomsonii were identified by high‒performance liquid chromatography (HPLC). Second, we established the following three inflammation models: an acute inflammation model of auricular swelling in mice induced by xylene, an acute inflammation model of foot swelling in rats induced by carrageenan gum, and a chronic inflammation model of cotton ball granuloma in rats. Then we examined the weight and swelling rate of auricular swelling in mice; the residence time, contact area, and mean contact pressure in rats on the gait meter; and the weight of granulomas in rats and the content of IL-1ß and TNF-α in plasma to investigate the anti-inflammatory pharmacodynamics of P. lobata and P. thomsonii. Third, we used LC‒MS‒based plasma metabolomics techniques to obtain potential biomarkers of P. lobata and P. thomsonii related to inflammation. Then, the potential biomarkers were enriched by MetaboAnalyst and KEGG metabolomics analysis tools to obtain metabolic pathways related to inflammation. Finally, we tested the indicators of COX-2, 5-LOX, GSH, GSSG and γ⁃GCL in rat plasma from the granuloma model by enzyme-linked immunosorbent assays (ELISAs) to verify the inflammation-related metabolic pathway. RESULTS: The experimental results showed that P. lobata and P. thomsonii could reduce the swollen weight and swelling rate of the auricle in mice, and could increase the residence time, contact area and mean contact pressure in rats on the gait meter. Moreover, P. lobata and P. thomsonii could inhibit the growth of granulomas and reduce the content of IL-1ß and TNF-α in plasma in rats. The above results preliminarily verified that P. lobata and P. thomsonii have different anti-inflammatory effects. We identified eighteen plasma biomarkers associated with P. lobata and sixteen plasma biomarkers related to P. thomsonii in regulating inflammation by a plasma metabolomics analysis. The following two major metabolic pathways were further screened and enriched: arachidonic acid metabolism and glutathione metabolism. Then we noted that P. lobata and P. thomsonii could reduce the COX-2, 5-LOX and GSSG levels and increase the GSH, GSH/GSSG and γ⁃GCL levels based on the ELISA results, which demonstrated that P. lobata and P. thomsonii affect the anti-inflammatory mechanism through arachidonic acid metabolism and glutathione metabolism. CONCLUSIONS: The results of this study further elucidate the anti-inflammatory mechanism of action of P. lobata and P. thomsonii, providing a scientific basis for developing new drugs for the treatment of inflammation-related diseases and laying a foundation for the development of herbal resources, such as P. lobata and P. thomsonii.

Risk for type 2 diabetes mellitus death attributed to insufficient whole grain intake in seven regions of China, 2005-2018 / 中华流行病学杂志

Objective: To estimate the risk for type 2 diabetes mellitus (T2DM) death attributed to insufficient whole grain intake in seven regions of China from 2005 to 2018. Methods: Based on China National Nutrition and Health Surveys and China Adult Chronic Disease and Nutrition Surveillance, ordinary Kriging method and locally weighted regression were used to estimate the level of whole grain intake of Chinese residents from 2005 to 2018. Based on the results of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 and Chronic Diseases Risk Factors Surveillance in China, we calculated the population attributable fraction (PAF), attributable death number and attributable mortality rate of T2DM due to insufficient whole grain intake in people aged ≥20 years in different regions of China, and we used the 2010 Chinese census data to compare the changes in T2DM deaths attributed to insufficient intake of whole grains in seven regions of China. Results: The whole grain intake levels of Chinese people over 20 years old in 2002, 2010 and 2015 were 19.0 g/d, 14.3 g/d and 19.8 g/d, respectively. The estimated overall whole grain intake level was 20.1 g/d in Chinese residents in 2018, and the intake level was 19.4 g/d in men and 20.8 g/d in women. Among the seven regions, the intake level was highest in northern China (47.4 g/d) and lowest in southwestern China (6.0 g/d). In 2018, the PAF was lowest in northern China (12.8%) and highest in southwestern China (19.3%). From 2005 to 2018, the PAF varied in the seven regions, and the PAF in northeastern China fluctuated around 18.5%. Other regions showed downward trends, especially in northern China and northwestern China, decreased by 26.4% and 21.2%, respectively. Over the past 14 years, the number of attributable deaths in the seven regions showed upward trends, with the highest annual average growth rate of 6.7% in southern China and the lowest annual average growth rate of 2.4% in northern China. In 2018, the standardized T2DM mortality rate attributed to insufficient whole grain intake in China was 3.13/100 000, and the attributable mortality was 3.21/100 000 in men and 3.05/100 000 in women. The standardized attributable mortality rate was highest in southwestern China (3.97/100 000) and lowest in northern China (1.78/100 000). From 2005 to 2018, the standardized attributable mortality rate increased by 11.5% in men and decreased by 8.1% in women. The standardized attributable mortality rate in southwestern, southern and central China increased by 23.7%, 21.3% and 4.2%, respectively. The standardized attributable mortality rate in northern, northwestern, eastern and northeastern China decreased by 20.9%, 11.0%, 4.5% and 3.9%, respectively. Conclusion: The whole grain intake level of Chinese residents was low, and the whole grain intake of residents in all seven regions should be increased, especially in the southwest, and men should have more whole grain intake than women to reduce the death risk in patients with T2DM.

Burden of hemorrhagic stroke and hypertensive heart disease attributed to alcohol consumption in China / 中华流行病学杂志

Objective: To describe the prevalence of alcohol consumption and the burden of hemorrhagic stroke and hypertensive heart disease attributed to alcohol consumption in adults aged ≥20 years in 31 provinces in China from 2005 to 2018. Methods: Data from several national representative surveys was used to estimate provincial alcohol exposure level of adults aged ≥20 years from 2005 to 2018 by using kriging interpolation and locally weighted regression methods. Global disease burden research method and data, and China's death cause surveillance data were used to calculate the population attributable fraction (PAF) of hemorrhagic stroke and hypertensive heart disease and the deaths due to alcohol consumption in men and women aged ≥20 years in 31 provinces in China. China census data of 2010 were used to calculate the attributable standardized mortality rate. Results: In 2005 and 2018, the prevalence of alcohol consumption was 58.7% (95%CI: 57.8%-59.5%) and 58.4% (95%CI: 57.6%-59.3%), respectively, in men and 17.0% (95%CI: 16.6%-17.4%) and 18.7% (95%CI:18.1%-19.3%), respectively, in women. The daily alcohol intake was 24.6 (95%CI: 23.8-25.3) g and 27.7 (95%CI: 26.8-28.7) g, respectively, in men and 6.3 (95%CI: 6.0-6.5) g and 5.3 (95%CI: 5.0-5.6) g, respectively, in women. Alcohol exposure level was higher in the provinces in central and eastern China than in western provinces. The lowest exposure level was found in northwestern provinces. From 2005 to 2018, the PAF of hemorrhagic stroke death due to alcohol consumption increased from 5.5% to 6.8%, the attributable deaths increased from 50 200 to 59 100, while the PAF of hypertensive heart disease death due to alcohol consumption increased from 7.0% to 7.7%, the attributable deaths increased from 15 200 to 29 300. The PAF of hypertensive heart disease and hemorrhagic stroke was higher in men than in women, and in central and eastern provinces than in western provinces. In 2018, the standardized mortality rates of hemorrhagic stroke and hypertensive heart disease attributed to alcohol consumption were 4.58/100 000 and 2.11/100 000, respectively. Conclusions: The prevalence of alcohol consumption in men and daily alcohol intake of drinkers were relatively high in China, especially in eastern provinces. Alcohol exposure level was lower in women than in men. Regional measures should be taken to reduce the alcohol intakes in men and current drinkers in order to reduce the health problems caused by alcohol consumption.

A retrospective cohort study on blood lipid changes and their influencing factors in HIV/AIDS patients after receiving antiretroviral therapy in Wuhan / 公共卫生与预防医学

Objective To investigate the prevalence and influencing factors of HIV/AIDS patients with hyperlipidemia before and after receiving antiviral therapy in Wuhan. Methods A retrospective cohort study was used to analyze the data of HIV/AIDS patients in Wuhan from 2004 to 2021. Elevated levels of either TG or TC were determined as hyperlipidemia. Logistic regression model was used to analyze the influencing factors of baseline hyperlipidemia, and Cox proportional risk model was used to analyze the influencing factors of new-onset hyperlipidemia after receiving antiviral therapy. Results A total of 7 562 HIV/AIDS patients were enrolled, 30.61% (2 315/7 562) with hyperlipidemia at baseline and 69.39% (5 247/7 562) without hyperlipidemia. The mean person-years of follow-up for those patients without hyperlipidemia at baseline were 3.48, of whom 33.14% (1 739/5 247) developed hyperlipidemia during follow-up, with an overall density of 9.53/100 person-years. Multivariate logistic regression analysis showed that age ≥30 years and BMI ≥24 kg/m2 were positively correlated with baseline hyperlipidemia, while CD4 cell count ≥ 200 μL was negatively correlated with baseline hyperlipidemia. Multivariate Cox model analysis showed that new-onset hyperlipidemia after receiving antiviral therapy was significantly positively correlated with BMI between 18.5-23.9 and ≥24 kg/m2, the initial antiviral treatment regimen containing LPV/r, efavirenz and other factors A baseline CD4 cell count of 200 to 349 cells /μL was negatively correlated with new-onset hyperlipidemia. Conclusion HIV/AIDS patients with high BMI and an initial antiviral regimen including Kaletra or efavirenz have a significantly higher risk of hyperlipidemia. Follow-up monitoring of blood lipid in these patients should be strengthened.

Effects of schedule exercise therapy on chronic insomnia.

Schedule exercise therapy (SET) is a novel nonpharmacological intervention for the treatment of chronic insomnia disorder (CID). The aim of this study was to explore the effects of SET on CID. Methods: One hundred and eighteen CID were recruited and randomized into medication (MED) or medication combined with SET (MSET) groups. Over 12 observational weeks, sleep and mood status were evaluated using the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Self-rating Depression Scale (SDS), and Self-rating Anxiety Scale (SAS). At the end of the observational period, the rates of clinically effective hypnotic use were calculated. At 12 weeks, the PSQI progressively decreased for all subjects combined (P < .001) as well as ISI (P < .001), ESS (P < .001), SDS (P < .001), and SAS (P < .001). The decreases in PSQI (P < .05), ISI (P < .05), SDS (P < .01), and SAS (P < .05) in the MSET group were significantly larger than those in the MED group, but not the same as those in the ESS group (P > .05). At the trial endpoint, the clinically effective rate was significantly higher (P < .05) and the hypnotic usage rate was lower (P < .05) in the MSET group than in the MED group. SET may be an effective treatment for insomnia in patients with CID.

Extracorporeal Life Support and Temporary CentriMag Ventricular Assist Device to Salvage Cardiogenic-Shock Patients Suffering from Prolonged Cardiopulmonary Resuscitation.

Background: The extracorporeal life support (ECLS) and temporary bilateral ventricular assist device (t-BiVAD) are commonly applied in patients with cardiogenic shock. Prolonged cardiopulmonary resuscitation (CPR) has poor prognosis. Herein, we report our findings on a combined ECLS and t-BiVAD approach to salvage cardiogenic-shock patients with CPR for more than one hour. Methods: Fifty-nine patients with prolonged CPR and rescued by ECLS and subsequent t-BiVAD were retrospectively collected between January 2015 and December 2019. Primary diagnoses included ischemic, dilated cardiomyopathy, acute myocardial infarction, post-cardiotomy syndrome, and fulminant myocarditis. The mean LVEF was 16.9% ± 6.56% before t-BiVAD. The median ECLS-to-VAD interval is 26 h. Results: A total of 26 patients (44%) survived to weaning, including 13 (22%) bridged to recovery, and 13 (22%) bridged to transplantation. Survivors to discharge demonstrated better systemic perfusion and hemodynamics than non-survivors. The CentriMag-related complications included bleeding (n = 22, 37.2%), thromboembolism (n = 5, 8.4%), and infection (n = 4, 6.7%). The risk factors of mortality included Glasgow Coma Scale (Motor + Eye) ≤ 5, and lactate ≥ 8 mmol/L at POD-1, persistent ventricular rhythm or asystole, and total bilirubin ≥ 6 mg/dL at POD-3. Mortality factors included septic shock (n = 11, 18.6%), central failure (n = 10, 16.9%), and multiple organ failure (n = 12, 20.3%). Conclusions: Combined ECLS and t-BiVAD could be a salvage treatment for patients with severe cardiogenic shock, especially for those already having prolonged CPR. This combination can correct organ malperfusion and allow sufficient time to bridge patients to recovery and heart transplantation, especially in Asia, where donation rates are low, as well as intracorporeal VAD or total artificial heart being seldom available.

Screening for Immune-Related RNA Biomarkers of Aneurysmal Subarachnoid Hemorrhage.

PURPOSE: Through comprehensive bioinformatics analysis based on the immune microenvironment, this study aimed to identify immune-related RNA biomarkers that indicate aneurysmal subarachnoid hemorrhage (aSAH). METHODS: The GSE73378 dataset was downloaded from the National Center for Biotechnology Information GEO database, providing blood from 107 normal controls and 103 patients with aSAH. The immune infiltration types in the aSAH blood samples were assessed and RNAs that were differentially expressed (DE) between 1) the aSAH and control groups and 2) the immune infiltration groups (high and low) were identified. The intersecting genes were subjected to weighted gene co-expression network analysis followed by co-expression network construction. The aSAH-related genes and pathways were identified from the Comparative Toxicogenomics Database: update 2019. RESULTS: A total of three DE long non-coding RNAs (lncRNAs) and 301 DE mRNAs were identified. Of the 301 mRNAs, 91 were significantly enriched in three modules. Based on the 91 mRNAs and three lncRNAs, a co-expression network related to the disease pathway was constructed. This pathway consisted of 16 factors, including the 13 mRNAs (e.g., TNFSF13B, TNFSF10, MYD88, GNA12 and NSMAF) and three lncRNAs (FAM66A, LINC00954 and CELF2-AS2), as well as six pathways, including the NF-κB, toll-like receptor, and sphingolipid signalling pathways. CONCLUSION: TNFSF13B, MYD88, GNA12, NSMAF, FAM66A, LINC00954 and CELF2-AS2 may serve as biomarkers for aSAH. The NF-κB, toll-like receptor and sphingolipid signalling pathways may play critical roles in the progression of aSAH.

Decoy receptor 2 mediates the apoptosis-resistant phenotype of senescent renal tubular cells and accelerates renal fibrosis in diabetic nephropathy.

Apoptotic resistance leads to persistent accumulation of senescent cells and sustained expression of a senescence-associated secretory phenotype, playing an essential role in the progression of tissue fibrosis. However, whether senescent renal tubular epithelial cells (RTECs) exhibit an apoptosis-resistant phenotype, and the role of this phenotype in diabetic nephropathy (DN) remain unclear. Our previous study was the first to demonstrate that decoy receptor 2 (DcR2) is associated with apoptotic resistance in senescent RTECs and renal fibrosis. In this study, we aimed to further explore the mechanism of DcR2 in apoptosis-resistant RTECs and renal fibrosis in DN. DcR2 was co-localized with fibrotic markers (α-SMA, collagen IV, fibronectin), senescent marker p16, and antiapoptotic proteins FLIP and Bcl2 but rarely co-localized with caspase 3 or TUNEL. DcR2 overexpression promoted renal fibrosis in mice with streptozotocin (STZ)-induced DN, as evidenced by augmented Masson staining and upregulated expression of fibrotic markers. DcR2 overexpression also enhanced FLIP expression while reducing the expression of pro-apoptotic proteins (caspases 8 and 3) in senescent RTECs, resulting in apoptotic resistance. In contrast, DcR2 knockdown produced the opposite effects in vitro and in vivo. Moreover, quantitative proteomics and co-immunoprecipitation experiments demonstrated that DcR2 interacted with glucose-related protein 78 kDa (GRP78), which has been shown to promote apoptotic resistance in cancer. GRP78 exhibited co-localization with senescent and antiapoptotic markers but was rarely co-expressed with caspase 3 or TUNEL. Additionally, GRP78 knockdown decreased the apoptosis resistance of HG-induced senescent RTECs with upregulated cleaved caspase 3 and increased the percentage of apoptotic RTECs. Mechanistically, DcR2 mediated apoptotic resistance in senescent RTECs by enhancing GRP78-caspase 7 interactions and promoting Akt phosphorylation. Thus, DcR2 mediated the apoptotic resistance of senescent RTECs and renal fibrosis by interacting with GRP78, indicating that targeting the DcR2-GRP78 axis represents a promising therapeutic strategy for DN.

The delivery of miR-21a-5p by extracellular vesicles induces microglial polarization via the STAT3 pathway following hypoxia-ischemia in neonatal mice.

Extracellular vesicles (EVs) from mesenchymal stromal cells (MSCs) have previously been shown to protect against brain injury caused by hypoxia-ischemia (HI). The neuroprotective effects have been found to relate to the anti-inflammatory effects of EVs. However, the underlying mechanisms have not previously been determined. In this study, we induced oxygen-glucose deprivation in BV-2 cells (a microglia cell line), which mimics HI in vitro, and found that treatment with MSCs-EVs increased the cell viability. The treatment was also found to reduce the expression of pro-inflammatory cytokines, induce the polarization of microglia towards the M2 phenotype, and suppress the phosphorylation of selective signal transducer and activator of transcription 3 (STAT3) in the microglia. These results were also obtained in vivo using neonatal mice with induced HI. We investigated the potential role of miR-21a-5p in mediating these effects, as it is the most highly expressed miRNA in MSCs-EVs and interacts with the STAT3 pathway. We found that treatment with MSCs-EVs increased the levels of miR-21a-5p in BV-2 cells, which had been lowered following oxygen-glucose deprivation. When the level of miR-21a-5p in the MSCs-EVs was reduced, the effects on microglial polarization and STAT3 phosphorylation were reduced, for both the in vitro and in vivo HI models. These results indicate that MSCs-EVs attenuate HI brain injury in neonatal mice by shuttling miR-21a-5p, which induces microglial M2 polarization by targeting STAT3.

L-Cysteine attenuates osteopontin-mediated neuroinflammation following hypoxia-ischemia insult in neonatal mice by inducing S-sulfhydration of Stat3.

We previously show that L-Cysteine administration significantly suppresses hypoxia-ischemia (HI)-induced neuroinflammation in neonatal mice through releasing H2S. In this study we conducted proteomics analysis to explore the potential biomarkers or molecular therapeutic targets associated with anti-inflammatory effect of L-Cysteine in neonatal mice following HI insult. HI brain injury was induced in postnatal day 7 (P7) neonatal mice. The pups were administered L-Cysteine (5 mg/kg) at 24, 48, and 72 h post-HI. By conducting TMT-based proteomics analysis, we confirmed that osteopontin (OPN) was the most upregulated protein in ipsilateral cortex 72 h following HI insult. Moreover, OPN was expressed in CD11b+/CD45low cells and infiltrating CD11b+/CD45high cells after HI exposure. Intracerebroventricular injection of OPN antibody blocked OPN expression, significantly attenuated brain damage, reduced pro-inflammatory cytokine levels and suppressed cerebral recruitment of CD11b+/CD45high immune cells following HI insult. L-Cysteine administration reduced OPN expression in CD11b+/CD45high immune cells, concomitant with improving the behavior in Y-maze test and suppressing cerebral recruitment of CD11b+/CD45high immune cells post-HI insult. Moreover, L-Cysteine administration suppressed the Stat3 activation by inducing S-sulfhydration of Stat3. Intracerebroventricular injection of Stat3 siRNA not only decreased OPN expression, but also reversed HI brain damage. Our data demonstrate that L-Cysteine administration effectively attenuates the OPN-mediated neuroinflammation by inducing S-sulfhydration of Stat3, which contributes to its anti-inflammatory effect following HI insult in neonatal mice. Blocking OPN expression may serve as a new target for therapeutic intervention for perinatal HI brain injury.

Prostate-specific membrane antigen (PSMA) fusion imaging in prostate cancer: PET-CT vs PET-MRI.

OBJECTIVES: To investigate whether PET-CT or PET-MRI is more appropriate for imaging prostate cancer, in terms of primary tumor detection, local staging and recurrence, as well as lymph nodes and distant metastases. METHODS: A systematic literature search was conducted on Embase, PubMed/MEDLINE, and the Cochrane Library database. Studies evaluating the diagnostic performance of PET-CT vs PET-MRI in prostate cancer patients were emphasized. RESULTS: We reviewed 57 original research articles during the period 2016-2021: 14 articles regarding the radiotracer PSMA; 18 articles regarding the primary tumor detection, local tumor staging, managing local recurrence; 17 articles for managing lymph node metastases; and eight articles for managing bone and other distant metastases. PSMA PET could be complementary to mpMRI for primary prostate cancer localization and is particularly valuable for PI-RADS three lesions. PET-MRI is better than PET-CT in local tumor staging due to its specific benefit in predicting extracapsular extension in MRI-occult prostate cancer patients. PET-MRI is likely superior as compared with PET-CT in detecting local recurrence, and has slightly higher detection rates than PET-CT in lymph node recurrence. PET-CT and PET-MRI seem to have equivalent performance in detecting distant bony or visceral metastases. CONCLUSION: In conclusion, PET-MRI is suitable for local and regional disease, either primary staging or restaging, whereas PET-CT is valuable for managing distant bony or visceral metastasis. ADVANCES IN KNOWLEDGE: We reviewed the emerging applications of PET-MRI and PET-CT in clinical aspects. Readers will gain an objective overview on the strength and shortfalls of PET-MRI or PET-CT in the management of prostate cancer.