Sex Difference in Characteristics and Predictors of In-Hospital Mortality Among Patients with COVID-19.

INTRODUCTION: With the surge in the prevalence of coronavirus disease (COVID-19) in Beijing starting in October 2022, hospitalisations have increased markedly. The present study aimed to evaluate factors associated with in-hospital mortality in patients with COVID-19. METHODS: Using data from hospitalised patients, sex differences in clinical characteristics, in-hospital management, and in-hospital mortality among patients diagnosed with COVID-19 were evaluated. Additionally, predictive factors associated with mortality in 1091 patients, who were admitted to the Beijing Anzhen Hospital (Beijing, China) for COVID-19 between October 2022 and January 2023, were also evaluated. RESULTS: Data from 1091 patients hospitalised with COVID-19 were included in the analysis. The in-hospital mortality rates were 14.9% and 10.4% for males and females, respectively. Multifactorial logistic analysis revealed that lymphocyte percentage (LYM%) (odds ratio [OR] 0.863 [95% confidence interval (CI) 0.805-0.925]; P<0.001), uric acid (OR 1.004 [95% CI 1.002-1.006]; P=0.001), and high-sensitivity C-reactive protein (hs-CRP) (OR 1.094 [95% CI 1.012-1.183]; P=0.024) were independently associated with in-hospital mortality from COVID-19. Among female patients, multifactorial analysis revealed that LYM% (OR 0.856 [95% CI 0.796-0.920]; P<0.001), older age (OR 1.061 [95% CI 1.020-1.103]; P=0.003), obesity (OR 2.590 [95% CI 1.131-5.931]; P=0.024), and high high-sensitivity troponin I level (OR 2.602 [95% CI 1.157-5.853]; P=0.021) were risk factors for in-hospital mortality. Receiver operating characteristic (ROC) curve analysis revealed that the efficacy of LYM% in predicting in-hospital death and its area under the ROC curve (AUC) for predicting in-hospital death in males was 0.800, with a sensitivity of 63.2% and specificity of 83.2%. The AUC for predicting hospital death in females was 0.815, with a sensitivity of 87.5% and specificity of 64.4%. CONCLUSION: LYM% was a consistent predictor of in-hospital mortality in both sexes. Older age and markers of systemic inflammation, myocardial injury, and metabolic dysregulation were also associated with higher mortality risk. These findings may help identify patients who require closer monitoring and tailored interventions to improve outcomes.

Survival benefit of postoperative radioiodine therapy among patients with intermediate-risk differentiated thyroid carcinoma.

BACKGROUND: The 2015 American Thyroid Association (ATA) guidelines proposed the use of the ATA Risk Stratification System and American Joint Committee on Cancer Tumor-Node-Metastasis (AJCC/TNM) Staging System for postoperative radioiodine decision-making. However, the management of patients with intermediate-risk differentiated thyroid carcinoma (DTC) is not well defined. In this study, we aimed to evaluate the therapeutic efficacy of radioactive iodine therapy (RAIT) among various subgroups of patients with intermediate-risk DTC after surgery. METHODS: This was a retrospective study based on the Surveillance, Epidemiology, and End Results (SEER) database (2010-2015). The DTC patients with intermediate risk of recurrence were divided into two groups (treated or not treated with radioactive iodine (RAI)). As the treatment was not randomly assigned, stabilized inverse probability treatment weighting (sIPTW) was used to reduce selection bias. We used the Kaplan-Meier method and log-rank test to analyze overall survival (OS) and cancer-specific survival (CSS). RESULTS: Kaplan-Meier analysis after sIPTW found a significant difference in OS and CSS between no RAIT and RAIT (log-rank test, P < 0.0001; P = 0.0019, respectively). The Kaplan-Meier curves of CSS in age cutoff of 55 years showed a significant association between no RAIT and RAIT (log-rank test, P = 0.0045). Univariate and multivariate Cox regression showed RAIT was associated with a reduced risk of mortality compared with no RAIT (hazard ratio [HR] 0.59, 95% confidence interval [95% CI 0.44-0.80]). Age (≥ 55) years showed a worse CSS regardless of whether or not a patient was treated or not treated with RAI ([HR] 8.91, 95% confidence interval [95% CI 6.19-12.84]). CONCLUSIONS: RAIT improves OS and CSS in patients with intermediate-risk DTC after surgery. 55 years is a more appropriate prognostic age cutoff for the relevant classification systems and is a crucial consideration in RAI decision-making. Therefore, we need individualized treatment plans.

Rutaecarpine Alleviates Early Brain Injury-Induced Inflammatory Response Following Subarachnoid Hemorrhage via SIRT6/NF-[Formula: see text]B Pathway.

Subarachnoid hemorrhage (SAH), a specific subtype of cerebrovascular accident, is characterized by the extravasation of blood into the interstice between the brain and its enveloping delicate tissues. This pathophysiological phenomenon can precipitate an early brain injury (EBI), which is characterized by inflammation and neuronal death. Rutaecarpine (Rut), a flavonoid compound discovered in various plants, has been shown to have protective effects against SAH-induced cerebral insult in rodent models. In our study, we used a rodent SAH model to evaluate the effect of Rut on EBI and investigated the effect of Rut on the inflammatory response and its regulation of SIRT6 expression in vitro. We found that Rut exerts a protective effect on EBI in SAH rats, which is partly due to its ability to inhibit the inflammatory response. Notably, Rut up-regulated Sirtuin 6 (SIRT6) expression, leading to an increase in H3K9 deacetylation and inhibition of nuclear factor-kappa B (NF-[Formula: see text]B) transcriptional activation, thereby mediating the inflammatory response. In addition, further data showed that SIRT6 was proven to mediate the regulation of Rut on the microglial inflammatory response. These findings highlight the importance of SIRT6 in the regulation of inflammation and suggest a potential mechanism for the protective effect of Rut on EBI. In summary, Rut may have the potential to prevent and treat SAH-induced brain injury by interacting with SIRT6. Our findings may provide a new therapeutic strategy for the treatment of SAH-induced EBI.

Pregelatinized hydroxypropyl distarch phosphate-reinforced calcium sulfate bone cement for bleeding bone treatment.

Considering the shortcomings of known medical hemostatic materials such as bone wax for bleeding bone management, it is essential to develop alternative bone materials capable of efficient hemostasis and bone regeneration and adaptable to clinical surgical needs. Thus, in the current work, a calcium sulfate hemihydrate and starch-based composite paste was developed and optimized. Firstly, it was found that the use of hydroxypropyl distarch phosphate (HDP) coupled with pregelatinization could generate an injectable, malleable and self-hardening paste with impressive anti-collapse ability in a dynamic aqueous environment, suggesting its potential applicability in both open and minimally invasive clinical practice. The as-hardened matrix exhibited a compressive strength of up to 61.68 ± 5.13 MPa compared to calcium sulfate cement with a compressive strength of 15.16 ± 2.42 MPa, making it a promising candidate for the temporary mechanical stabilization of bone defects. Secondly, the as-prepared paste revealed superior hemostasis and bone regenerative capabilities compared to calcium sulfate cement and bone wax, with greatly enhanced bleeding management and bone healing outcomes when subjected to testing in in vitro and in vivo models. In summary, our results confirmed that calcium sulfate bone cement reinforced with the selected starch can act as a reliable platform for bleeding bone treatment, overcoming the limitations of traditional bone hemostatic agents.

Measuring the Optical Concurrence of Vector Beams with an Atomic-State Interferometer.

We investigate the transmission of vector beams, correlated in their polarization and spatial degrees of freedom, through cold atoms in the presence of a transverse magnetic coupling field. The resulting phase-dependent dynamics allow us to imprint the spatially varying polarization of a vector beam onto atomic spin polarizations, thereby establishing a direct link between optical space-polarization correlations and atomic-state interference. We find that the resulting absorption profiles show interference fringes whose modulation strength is given by the squared concurrence of the vector beam, letting us identify optical concurrence from a single absorption image. We expect impact across a diverse range of applications, including spintronics, quantum memories, metrology, and clocks.

Socioeconomic disparities and regional environment are associated with cervical lymph node metastases in children and adolescents with differentiated thyroid cancer: developing a web-based predictive model.

Purpose: To establish an online predictive model for the prediction of cervical lymph node metastasis (CLNM) in children and adolescents with differentiated thyroid cancer (caDTC). And analyze the impact between socioeconomic disparities, regional environment and CLNM. Methods: We retrospectively analyzed clinicopathological and sociodemographic data of caDTC from the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2019. Risk factors for CLNM in caDTC were analyzed using univariate and multivariate logistic regression (LR). And use the extreme gradient boosting (XGBoost) algorithm and other commonly used ML algorithms to build CLNM prediction models. Model performance assessment and visualization were performed using the area under the receiver operating characteristic (AUROC) curve and SHapley Additive exPlanations (SHAP). Results: In addition to common risk factors, our study found that median household income and living regional were strongly associated with CLNM. Whether in the training set or the validation set, among the ML models constructed based on these variables, the XGBoost model has the best predictive performance. After 10-fold cross-validation, the prediction performance of the model can reach the best, and its best AUROC value is 0.766 (95%CI: 0.745-0.786) in the training set, 0.736 (95%CI: 0.670-0.802) in the validation set, and 0.733 (95%CI: 0.683-0.783) in the test set. Based on this XGBoost model combined with SHAP method, we constructed a web-base predictive system. Conclusion: The online prediction model based on the XGBoost algorithm can dynamically estimate the risk probability of CLNM in caDTC, so as to provide patients with personalized treatment advice.

Persistent bacteremia caused by Ralstonia pickettii and Microbacterium: a case report.

BACKGROUND: Ralstonia pickettii is a low virulent, gram-negative bacillus that is rarely associated with human infections and may cause bacteremia. Microbacterium species are gram-positive coryneforms that are generally considered as a contaminant in Gram staining of blood cultures, especially when the time to positivity is longer than 48 h. Both these bacterial species are emerging opportunistic pathogens that may occasionally cause serious infections and even life-threatening health conditions. CASE PRESENTATION: Here, we report the case of a patient with bacteremia caused by both R. pickettii and Microbacterium. We advocate for providers to order rapid antibiotic susceptibility testing, since our patient's suffered two kinds of rare pathogens with the opposite of drug sensitivity results to imipenem. CONCLUSIONS: Our case present a patient suffered septic shock caused by R. pickettii and Microbacterium. Improving the antibiotic management based on the result of antimicrobial susceptibility tests is the key of successful treatment.

Association Between Dietary Antioxidant Quality Score (DAQS) and All-Cause Mortality in Hypertensive Adults: A Retrospective Cohort Study from the NHANES Database.

This study aimed to explore the association between the dietary antioxidant quality scores (DAQS) and all-cause mortality in hypertensive adults. In this retrospective cohort study, participants aged ≥ 18 years with hypertension were extracted from the National Health and Nutrition Examination Survey (NAHNES) 2007-2018. Outcome was all-cause mortality of hypertensive participants. DAQS was the exposure variable calculated based on the intake of vitamin A, C, E, zinc, selenium, and magnesium. The weighted univariable and multivariable COX proportional hazards regression models were utilized to explore the association between the DAQS and the all-cause mortality in hypertensive patients and were described as hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses based on different age, gender, diabetes, and cardiovascular disease (CVD) history were further assessed this association. A total of 16,240 participants were finally included in this study. Until 12 December 2019, 2710 (16.69%) all-cause deaths were documented. After adjustment for confounding variables, high DAQS was associated with the lower all-cause mortality (HR = 0.83, 95%CI: 0.72-0.96) in hypertensive patients. Subgroup analyses suggested that the association between DAQS and the all-cause mortality in hypertensive patients remain robust, especially in patients with female (HR = 0.77, 95%CI: 0.63-0.95), aged ≥ 60 years (HR = 0.81, 95%CI: 0.69-0.96). High DAQS was associated with the lower odds of all-cause mortality in adults with hypertension and are a promising intervention to be further explored in hypertensive patients.

Integrated application of transcriptomics and metabolomics provides insight into the mechanism of Eimeria tenella resistance to maduramycin.

Avian coccidiosis, caused by Eimeria parasites, continues to devastate the poultry industry and results in significant economic losses. Ionophore coccidiostats, such as maduramycin and monensin, are widely used for prophylaxis of coccidiosis in poultry. Nevertheless, their efficacy has been challenged by widespread drug resistance. However, the underlying mechanisms have not been revealed. Understanding the targets and resistance mechanisms to anticoccidials is critical to combat this major parasitic disease. In the present study, maduramycin-resistant (MRR) and drug-sensitive (DS) sporozoites of Eimeria tenella were purified for transcriptomic and metabolomic analysis. The transcriptome analysis revealed 5016 differentially expressed genes (DEGs) in MRR compared to DS, and KEGG pathway enrichment analysis indicated that DEGs were involved in spliceosome, carbon metabolism, glycolysis, and biosynthesis of amino acids. In the untargeted metabolomics assay, 297 differentially expressed metabolites (DEMs) were identified in MRR compared to DS, and KEGG pathway enrichment analysis indicated that these DEMs were involved in 10 pathways, including fructose and mannose metabolism, cysteine and methionine metabolism, arginine and proline metabolism, and glutathione metabolism. Targeted metabolomic analysis revealed 14 DEMs in MRR compared to DS, and KEGG pathway analysis indicated that these DEMs were involved in 20 pathways, including fructose and mannose metabolism, glycolysis/gluconeogenesis, and carbon metabolism. Compared to DS, energy homeostasis and amino acid metabolism were differentially regulated in MRR. Our results provide gene and metabolite expression landscapes of E. tenella following maduramycin induction. This study is the first work involving integrated transcriptomic and metabolomic analyses to identify the key pathways to understand the molecular and metabolic mechanisms underlying drug resistance to polyether ionophores in coccidia.

Zhi-Zi-Hou-Po decoction alleviates depressive-like behavior and promotes hippocampal neurogenesis in chronic unpredictable mild stress induced mice via activating the BDNF/TrkB/CREB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhi-Zi-Hou-Po decoction (ZZHP), a traditional Chinese medicine (TCM) classic recipe, has been extensively applied for the remedy of depression. However, the underlying mechanism of ZZHP hasn't been fully elucidated and it needs to be further clarified. AIM OF STUDY: The aim of the study is to uncover the mechanisms of ZZHP's effect on depression. MATERIALS AND METHODS: C57BL/6 mice were employed to establish Chronic Unpredictable Mild Stress (CUMS) models. Behavioral tests were conducted for evaluating the antidepressant effects of ZZHP. Then, the monoamine neurotransmitters in the hippocampus through High Performance Liquid Chromatography Electrochemical Detection (HPLC-ECD) were utilized to assess the effect of ZZHP on the maintenance of monoamine neurotransmitter homeostasis. Immunofluorescence staining and Golgi staining were detected to analyze the effects of ZZHP on neuroplasticity in the hippocampus. Western Blot (WB) was utilized to examine the effects of ZZHP on BDNF/TrkB/CREB pathways. Finally, behavioral tests, WB and immunofluorescence staining were repeated after TrkB receptor antagonist was added to further confirm the underlying mechanism. RESULTS: Our results shown that ZZHP attenuated depressive-like symptoms in CUMS mice. Moreover, ZZHP remarkably reversed the reduction and maintained the homeostasis of monoamine neurotransmitters in the hippocampus. Simultaneously, ZZHP protected neuronal synaptic plasticity and promoted hippocampal neurogenesis. Furthermore, ZZHP stimulated the BDNF/TrkB/CREB pathway in the hippocampus. The addition of TrkB receptor antagonist inhibited the antidepressant effects of ZZHP, suggesting that ZZHP could not work without triggering the BDNF/TrkB/CREB pathway. CONCLUSION: This study demonstrates that ZZHP can alleviate depressive-like behavior and promote hippocampal neurogenesis in CUMS mice via activating the BDNF/TrkB/CREB pathway.

Wafer-Scale Epitaxial Growth of Two-dimensional Organic Semiconductor Single Crystals toward High-Performance Transistors.

The success of state-of-the-art electronics and optoelectronics relies heavily on the capability to fabricate semiconductor single-crystal wafers. However, the conventional epitaxial growth strategy for inorganic wafers is invalid for growing organic semiconductor single crystals due to the lack of lattice-matched epitaxial substrates and intricate nucleation behaviors, severely impeding the advancement of organic single-crystal electronics. Here, an anchored crystal-seed epitaxial growth method for wafer-scale growth of 2D organic semiconductor single crystals is developed for the first time. The crystal seed is firmly anchored on the viscous liquid surface, ensuring the steady epitaxial growth of organic single crystals from the crystal seed. The atomically flat liquid surface effectively eliminates the disturbance from substrate defects and greatly enhances the 2D growth of organic crystals. Using this approach, a wafer-scale few-layer bis(triethylsilythynyl)-anthradithphene (Dif-TES-ADT) single crystal is formed, yielding a breakthrough for organic field-effect transistors with a high reliable mobility up to 8.6 cm2 V-1 s-1 and an ultralow mobility variable coefficient of 8.9%. This work opens a new avenue to fabricate organic single-crystal wafers for high-performance organic electronics.

Anisotropic charge trapping in phototransistors unlocks ultrasensitive polarimetry for bionic navigation.

Being able to probe the polarization states of light is crucial for applications from medical diagnostics and intelligent recognition to information encryption and bio-inspired navigation. Current state-of-the-art polarimeters based on anisotropic semiconductors enable direct linear dichroism photodetection without the need for bulky and complex external optics. However, their polarization sensitivity is restricted by the inherent optical anisotropy, leading to low dichroic ratios of typically smaller than ten. Here, we unveil an effective and general strategy to achieve more than 2,000-fold enhanced polarization sensitivity by exploiting an anisotropic charge trapping effect in organic phototransistors. The polarization-dependent trapping of photogenerated charge carriers provides an anisotropic photo-induced gate bias for current amplification, which has resulted in a record-high dichroic ratio of >104, reaching over the extinction ratios of commercial polarizers. These findings further enable the demonstration of an on-chip polarizer-free bionic celestial compass for skylight-based polarization navigation. Our results offer a fundamental design principle and an effective route for the development of next-generation highly polarization-sensitive optoelectronics.

Exploring the ellipticity dependency on vector helical Ince-Gaussian beams and their focusing properties.

We present a numerical study of the intensity and polarization structure of vector helical Ince-Gaussian (VHIG) modes, which present a distinct subclass of vector Ince-Gaussian modes with defined parameter settings. The intensity profile of VHIG beams has an elliptic hollow structure, while the polarization distribution shows multiple single-charge polarization vortices arranged along a line. By selecting the mode order, phase factor and ellipticity of the VHIG beams, we can control the number of elliptic rings, the number of polarization vortices, and the topology of the vector singularity. Furthermore, we simulate the focusing properties of VHIG beams based on vector diffraction theory. Our results indicate that the ellipticity parameter of VHIG beams could be a valuable degree of freedom to generate attractive transverse profiles and longitudinal distributions under focusing, which may have implications for lithography, material processing, optical communication, and even optical trapping and manipulation.

Transfer and evolution of structured polarization in a double-V atomic system.

We numerically investigate the transfer of optical information from a vector-vortex control beam to an unstructured probe beam, as mediated by an atomic vapour. The right and left circular components of these beams drive the atomic transitions of a double-V system, with the atoms acting as a spatially varying circular birefringent medium. Modeling the propagation of the light fields, we find that, for short distances, the vectorial light structure is transferred from the control field to the probe. However, for larger propagation lengths, diffraction causes the circular components of the probe field to spatially separate. We model this system for the D1 line of cold rubidium atoms and demonstrate that four wave mixing can lead to correlations between the optical polarization structure and the diffraction of light, generating coupled dynamics of the internal and external degrees of freedom.

Knockout and Double Knockout of Cathepsin K and Mmp9 reveals a novel function of Cathepsin K as a regulator of osteoclast gene expression and bone homeostasis.

Cathepsins play a role in regulation of cell function through their presence in the cell nucleus. However, the role of Cathepsin K (Ctsk) as an epigenetic regulator in osteoclasts remains unknown. Our data demonstrated that Ctsk-/-Mmp9-/- mice have a striking phenotype with a 5-fold increase in bone volume compared with WT. RNA-seq analysis of Ctsk-/- , Mmp9-/- and Ctsk-/-/Mmp9-/- osteoclasts revealed their distinct functions in gene expression regulation, including reduced Cebpa expression, increased Nfatc1 expression, and in signaling pathways activity regulation. Western blots and qPCR data validated these changes. ATAC-seq profiling of Ctsk-/- , Mmp9-/-, and Ctsk-/-/Mmp9-/- osteoclasts indicated the changes resulted from reduced chromatin openness in the promoter region of Cebpa and increased chromatin openness in Nfatc1 promoter in Ctsk-/-/Mmp9-/- osteoclasts compared to that in osteoclasts of WT, Ctsk/- and Mmp9-/- . We found co-localization of Ctsk with c-Fos and cleavage of H3K27me3 in wild-type osteoclasts. Remarkably, cleavage of H3K27me3 was blocked in osteoclasts of Ctsk-/- and Ctsk-/-/Mmp9-/- mice, suggesting that Ctsk may epigenetically regulate distinctive groups of genes' expression by regulating proteolysis of H3K27me3. Ctsk-/-/Mmp9-/- double knockout dramatically protects against ovariectomy induced bone loss. We found that Ctsk may function as an essential epigenetic regulator in modulating levels of H3K27me3 in osteoclast activation and maintaining bone homeostasis. Our study revealed complementary and unique functions of Ctsk as epigenetic regulators for maintaining osteoclast activation and bone homeostasis by orchestrating multiple signaling pathways and targeting both Ctsk and Mmp9 is a novel therapeutic approach for osteolytic diseases such as osteoporosis.

Associations between short-term exposure of ambient particulate matter and hemodialysis patients death: A nationwide, longitudinal case-control study in China.

BACKGROUND: Long-term exposure to particulate air pollutants can lead to an increase in mortality of hemodialysis patients, but evidence of mortality risk with short-term exposure to ambient particulate matter is lacking. This study aimed to estimate the association of short-term exposure to ambient particulate matter across a wide range of concentrations with hemodialysis patients mortality. METHODS: We performed a time-stratified case-crossover study to estimate the association between short-term exposures to PM2.5 and PM10 and mortality of hemodialysis patients. The study included 18,114 hemodialysis death case from 279 hospitals in 41 cities since 2013. Daily particulate matter exposures were calculated by the inverse distance-weighted model based on each case's dialysis center address. Conditional logistic regression were implemented to quantify exposure-response associations. The sensitivity analysis mainly explored the lag effect of particulate matter. RESULTS: During the study period, there were 18,114 case days and 61,726 control days. Of all case and control days, average PM2.5 and PM10 levels were 43.98 µg/m3 and 70.86 µg/m3, respectively. Each short-term increase of 10 µg/m3 in PM2.5 and PM10 were statistically significantly associated with a relative increase of 1.07 % (95 % confidence interval [CI]: 0.99 % - 1.15 %) and 0.89 % (95 % CI: 0.84 % - 0.94 %) in daily mortality rate of hemodialysis patients, respectively. There was no evidence of a threshold in the exposure-response relationship. The mean of daily exposure on the same day of death and one-day prior (Lag 01 Day) was the most plausible exposure time window. CONCLUSIONS: This study confirms that short-term exposure to particulate matter leads to increased mortality in hemodialysis patients. Policy makers and public health practices have a clear and urgent opportunity to pass air quality control policies that care for hemodialysis populations and incorporate air quality into the daily medical management of hemodialysis patients.

An Autographa californica nucleopolyhedrovirus-encoded microRNA, AcMNPV-miR-4, downregulates the expression of host gene alg-2.

Autographa california multiple nucleopolyhedrovirus (AcMNPV)-encoded microRNAs (miRNAs) that regulate viral genes to achieve infection have been reported previously. Here, we report another AcMNPV encoded miRNA, AcMNPV-miR-4 (Ac-miR-4), which downregulated the host gene, apoptosis-linked gene (alg-2). This regulation was verified by dual-luciferase reporter assays. The effects of Ac-miR-4 on virus infection were assessed. The results showed that the production of infectious budded virions (BV) was decreased and the occlusion-derived virion (ODV) embedding into polyhedra was delayed when Sf9 cells were administered an overdose of Ac-miR-4. All these findings suggest that Ac-miR-4 prolongs cell lifespan and reduces virus virulence at a relatively early stage but increases ODV at a very late stage. This finding may be attributed to the downregulation effects of alg-2, which lead to weakened ALG-2 related functions, such as cell apoptosis, vesicle budding and protein transport.

Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate osteoarthritis of the knee in mice model by interacting with METTL3 to reduce m6A of NLRP3 in macrophage.

BACKGROUND: Osteoarthritis (OA) is a prevalent degenerative joint disease that not only significantly impairs the quality of life of middle-aged and elderly individuals but also imposes a significant financial burden on patients and society. Due to their significant biological properties, extracellular vesicles (EVs) have steadily received great attention in OA treatment. This study aimed to investigate the influence of EVs on chondrocyte proliferation, migration, and apoptosis and their protective efficacy against OA in mice. METHODS: The protective impact of EVs derived from human umbilical cord mesenchymal stem cells (hucMSCs-EVs) on OA in mice was investigated by establishing a mouse OA model by surgically destabilizing the medial meniscus (DMM). Human chondrocytes were isolated from the cartilage of patients undergoing total knee arthroplasty (TKA) and cultured with THP-1 cells to mimic the in vivo inflammatory environment. Levels of inflammatory factors were then determined in different groups, and the impacts of EVs on chondrocyte proliferation, migration, apoptosis, and cartilage extracellular matrix (ECM) metabolism were explored. N6-methyladenosine (m6A) level of mRNA and methyltransferase-like 3 (METTL3) protein expression in the cells was also measured in addition to microRNA analysis to elucidate the molecular mechanism of exosomal therapy. RESULTS: The results indicated that hucMSCs-EVs slowed OA progression, decreased osteophyte production, increased COL2A1 and Aggrecan expression, and inhibited ADAMTS5 and MMP13 overexpression in the knee joint of mice via decreasing pro-inflammatory factor secretion. The in vitro cell line analysis revealed that EVs enhanced chondrocyte proliferation and migration while inhibiting apoptosis. METTL3 is responsible for these protective effects. Further investigations revealed that EVs decreased the m6A level of NLRP3 mRNA following miR-1208 targeted binding to METTL3, resulting in decreased inflammatory factor release and preventing OA progression. CONCLUSION: This study concluded that hucMSCs-EVs inhibited the secretion of pro-inflammatory factors and the degradation of cartilage ECM after lowering the m6A level of NLRP3 mRNA with miR-1208 targeting combined with METTL3, thereby alleviating OA progression in mice and providing a novel therapy for clinical OA treatment.

Impact of BMI on Long-Term Outcomes in Patients with ST-Segment Elevation Myocardial Infarction after Primary Percutaneous Coronary Intervention.

Aim: Obesity paradox remains a point of debate in ST-segment elevation myocardial infarction (STEMI) patients. The aim of this study was to examine the relationship between body mass index (BMI) and clinical outcomes in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). Methods: Outcomes were assessed in 1429 STEMI patients undergoing PPCI between January 2009 and January 2010 in Beijing. Patients were classified into 6 groups according to age (the younger and elderly groups consisting of patients ≤65 and > 65 years old) and baseline BMI (normal weight, BMI < 24 kg/m2; overweight, 24 kg/m2 ≤BMI < 28 kg/m2; obese, BMI ≥ 28 kg/m2). The primary outcome was death, acute myocardial infarction (AMI), or revascularization. Results: On long-term follow-up (mean follow-up of 59 months), 13.9% of patients experienced the adverse event. Multivariate logistic regression analyses showed that low BMI was a significant predictor of the primary outcome only in the younger group. The odds ratio for overweight in comparison with normal weight was 0.741 (95% CI: 0.413-0.979; p = 0.038), the odds radio for obesity in comparison with normal-weight patients was 0.508 (95% CI: 0.344-0.750; p = 0.016) in the younger group. In the elderly group, diabetes, hypertension, triple disease, regular exercise, angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blockers (ARBs) use after discharge, and bleeding complication were associated with primary outcome. Conclusion: The obesity paradox was recognized only in the younger age group in STEMI patients undergoing PPCI.

Efficacy and safety of Corbrin Capsule on malnutrition, inflammation, and atherosclerosis syndrome in patients with uremia: systematic review and meta-analysis.

BACKGROUND: Uremia is a clinical syndrome caused by the development of chronic renal failure to the end-stage. Corbrin Capsule has the effect of tonifying the lungs and kidneys and improving the essence and qi, which can improve the metabolic disorders of the body. However, there is currently no systematic evaluation of the efficacy of Corbrin Capsule in the treatment of uremia malnutrition, inflammation, and atherosclerosis (MIA) syndrome. This paper aiming to provide a reference for improving the prognosis of uremic MIA patients. METHODS: According to the PICOS principle, the literature inclusion and exclusion criteria were formulated. The databases such as PubMed, Web of Science, Embase, and Cochrane Library were searched by computer using "Corbrin Capsule", "uremia", "MIA syndrome", and "kidney function" as search items. The outcome indicators were body mass index (BMI), C-reactive protein (CRP), blood urea nitrogen (BUN), and serum creatinine (sCr). Subsequently, the Cochrane Reviewer's Handbook 4.2.5 was adopted to assess the literature quality. The conventional treatment combined with Corbrin Capsule was defined as MIA/treatment group, and the conventional treatment was defined as the control group. The Review Manager (RevMan) 5.3 software was used to conduct a meta-analysis of the experimental data. RESULTS: A total of 6 suitable included articles were selected, including 894 patients. The included literature was analyzed and found that there was no obvious publication bias. According to the results of meta-analysis, the total BMI score was mean difference (MD) [95% confidence interval (CI)]: -0.10 (-3.44 to 3.24) with Z=0.06 and P=0.95. The CRP total score was MD (95% CI): 1.40 (0.34 to 2.46) with Z=2.58 and P=0.010. The BUN index was MD (95% CI): -1.15 (-3.05 to 0.75) with Z=1.18, P=0.24. Analysis result of sCr index data was MD (95% CI): -72.82 (-202.16 to 56.52) with Z=1.10 and P=0.27. DISCUSSION: Corbrin Capsule can effectively improve the relevant physiological indicators of patients with uremic MIA syndrome. However, the outcome indicators included in this study were insufficient, and it is necessary to further expand the sample size and outcome indicators in the future.