Dust-phase phthalates in university dormitories in Beijing, China: pollution characteristics, potential sources, and non-dietary oral exposure.

This study aimed to determine dust-phase phthalate levels in 112 dormitories of 14 universities during autumn and winter, investigate their potential sources, and estimate phthalate exposure via dust ingestion. Twelve phthalates were detected, among which di-(2-ethylhexyl) phthalate (DEHP) and dicyclohexyl phthalate (DCHP) were the most abundant, followed by di-isobutyl phthalate (DiBP) and di-n-butyl phthalate (DnBP). The median concentrations and contributions of DCHP and DEHP were the highest. The contributions of di-n-octyl phthalate and di-nonyl phthalate were higher in winter than in autumn. Potential sources included iron furniture, chemical fiber textiles, clothes, and personal care products. Medium-density fiberboard furniture is a potential sink for phthalates. In two seasons, DEHP, DCHP, DiBP, and DnBP were the main phthalates ingested by college students . The median oral exposure of ten phthalates was higher in females than in males. College students have a high risk of exposure to DEHP in dormitories.

Approaches for Performance Verification Toward Standardization of Peripheral Blood Regulatory T-Cell Detection by Flow Cytometry.

CONTEXT.­: Regulatory T-cell (Treg) detection in peripheral blood, based on flow cytometry, is invaluable for diagnosis and treatment of immune-mediated diseases. However, there is a lack of reliable methods to verify the performance, which is pivotal towards standardization of the Tregs assay. OBJECTIVE.­: To conduct standardization studies and verify the performance of 3 commercially available reagent sets for the Tregs assay based on flow cytometry and agreement analysis for Treg detection across the different reagent sets. DESIGN.­: The analytical performance of Tregs assay using reagent sets supplied by 3 manufacturers was evaluated after establishing the gating strategy and determining the optimal antibody concentration. Postcollection sample stability was evaluated, as well as the repeatability, reproducibility, reportable range, linearity, and assay carryover. Agreement between the different assays was assessed via Bland-Altman plots and linear regression analysis. The relationship between the frequency of CD4+CD25+CD127low/- Tregs and CD4+CD25+Foxp3+ Tregs was evaluated. RESULTS.­: The postcollection sample stability was set at 72 hours after collection at room temperature. The accuracy, repeatability, reproducibility, and accuracy all met the requirements for clinical analysis. Excellent linearity, with R2 ≥0.9 and no assay carryover, was observed. For reportable range, a minimum of 1000 events in the CD3+CD4+ gate was required for Tregs assay. Moreover, the results for Tregs labeled by antibodies from the 3 manufacturers were in good agreement. The percentage of CD4+CD25+CD127low/- Tregs was closely correlated with CD4+CD25+Foxp3+ Tregs. CONCLUSIONS.­: This is the first study to evaluate systematically the measurement performance of Tregs in peripheral blood by flow cytometry, which provides a practical solution to verifying the performance of flow cytometry-based immune monitoring projects in clinical practice.

Inhibitory receptor CD47 binding to plasma TSP1 suppresses NK-cell IFN-γ production via activating the JAK/STAT3 pathway during HIV infection.

BACKGROUND: Natural killer (NK) cells play an important first-line role against tumour and viral infections and are regulated by inhibitory receptor expression. Among these inhibitory receptors, the expression, function, and mechanism of cluster of differentiation 47 (CD47) on NK cells during human immunodeficiency virus (HIV) infection remain unclear. METHODS: Fresh peripheral blood mononuclear cells (PBMCs) were collected from people living with HIV (PLWH) and HIV negative controls (NC) subjects. Soluble ligand expression levels of CD47 were measured using ELISA. HIV viral proteins or Toll-like receptor 7/8 (TLR7/8) agonist was used to investigate the mechanisms underlying the upregulation of CD47 expression. The effect of CD47 on NK cell activation, proliferation, and function were evaluated by flow cytometry. RNA-seq was used to identify downstream pathways for CD47 and its ligand interactions. A small molecule inhibitor was used to restore the inhibition of NK cell function by CD47 signalling. RESULTS: CD47 expression was highly upregulated on the NK cells from PLWH, which could be due to activation of the Toll-like receptor 7/8 (TLR7/8) pathway. Compared with NC subjects, PLWH subjects exhibited elevated levels of CD47 ligands, thrombospondin-1 (TSP1), and counter ligand signal regulatory protein-α (SIRPα). The TSP1-CD47 axis drives the suppression of interferon gamma (IFN-γ) production and the activation of the Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway in NK cells. After treatment with a STAT3 inhibitor, the NK cells from PLWH showed significantly improved IFN-γ production. CONCLUSIONS: The current data indicate that the binding of the inhibitory receptor CD47 to plasma TSP1 suppresses NK cell IFN-γ production by activating the JAK/STAT3 pathway during HIV infection. Our results suggest that CD47 and its related signalling pathways could be targets for improving NK cell function in people living with HIV.

Willingness to take long-acting injectable pre-exposure prophylaxis among men who have sex with men who participated in the CROPrEP study: a cross-sectional online study.

INTRODUCTION: Evidence on the willingness of men who have sex with men (MSM) with oral pre-exposure prophylaxis (PrEP) experience, especially those with suboptimal adherence, to take long-acting injectable PrEP (LAI-PrEP) is critical to guide future LAI-PrEP implementation. OBJECTIVE: The objective was to assess the willingness of MSM with oral PrEP experience to take LAI-PrEP. METHODS: MSM who participated in the China Real-world Study of Oral PrEP (CROPrEP) were enrolled in this study. Information on the willingness of MSM to take LAI-PrEP and potential correlates was collected using a structured online questionnaire. The main outcomes were the willingness of MSM to take LAI-PrEP and its association with HIV-related behaviours, sexually transmitted infections, and oral PrEP history. Logistic regression was used to identify correlates of the willingness of MSM to take LAI-PrEP. RESULTS: A total of 612 former CROPrEP participants (FCPs) were included in this study. There were 315 (51.5%) daily oral PrEP (D-PrEP) users and 297 (48.5%) event-driven oral PrEP (ED-PrEP) users at the last follow-up. Most FCPs (77.8%) were willing to take free LAI-PrEP. FCPs with no less than two sexual male partners (aOR = 1.54, [95% CI: 1.04, 2.29], P = 0.031), those with male partners with unknown HIV statuses (aOR = 2.04, [95% CI: 1.31, 3.18], P = 0.002), those with recreational drug use (aOR = 1.58, [95% CI: 1.05, 2.40], P = 0.030), and those with HSV-2 positivity (aOR = 2.15, [95% CI: 1.30, 3.57], P = 0.003) were more willing to take LAI-PrEP, while ED-PrEP users (aOR = 0.66, [95% CI: 0.45, 0.98], P = 0.037) and FCPs with suboptimal oral PrEP adherence (aOR = 0.58, [95% CI: 0.36, 0.94], P = 0.026) were less willing to take LAI-PrEP. CONCLUSION: LAI-PrEP has good prospects for expanding PrEP coverage. However, FCPs with suboptimal oral PrEP adherence are less likely to take LAI-PrEP. Further intervention and implementation efforts are needed to improve the willingness of MSM to use LAI-PrEP, and sexual health should be considered during the discussion about PrEP initiation.

Graphdiyne and Nitrogen-Doped Graphdiyne Nanotubes as Highly Efficient Electrocatalysts for Oxygen Reduction Reaction.

Electrocatalysts with high efficiency and low cost are always urgently needed for oxygen reduction reaction (ORR). As a new carbon allotrope, graphdiyne (GDY) has received much attention due to its unique chemical structure containing sp- and sp2-hybridized carbons, and intrinsic electrochemical activity ascribed to its inherent conductivity. Herein, we prepared two graphdiyne materials named GDY nanotube and nitrogen-doped GDY (NGDY) nanotube via cross-coupling reactions on the surface of Cu nanowires. As metal-free catalysts, their electrocatalytic activities for ORR were demonstrated. The results showed that the NGDY nanotube presents more excellent electrochemical performance than that of the GDY nanotube, including more positive potential and faster kinetics and charge transfer process. The improvement can be ascribed to the greater number of structural electrocatalytic active sites from nitrogen atoms as well as the hollow nanotube morphology, which is beneficial to the adsorption of oxygen and acceleration of the catalytic reaction. This work helps develop high-quality graphdiyne-based electrocatalysts with well-defined chemical structures and morphologies for various electrochemical reactions.

Online distribution of HIV self-testing kits to promote HIV testing among men who have sex with men discontinuing pre-exposure prophylaxis after demonstration project completion in China: a multicentre open-label randomized controlled trial.

Background: HIV self-testing (HIVST) offers potential solutions to challenges associated with site-based HIV testing (SBHT). However, the effectiveness of HIVST as an HIV prevention strategy for men who have sex with men (MSM) discontinuing pre-exposure prophylaxis (PrEP) after the completion of PrEP demonstration project has rarely been assessed. Methods: The China Real-world Study of Oral PrEP (CROPrEP) project was conducted in four cities in China. Participants were directed to community resources to continue their PrEP medication after the discontinuation of project-provided PrEP at the last CROPrEP visit. We conducted a multicentre open-label randomized controlled trial among MSM who had discontinued PrEP induced by the completion of CROPrEP. Eligible participants were randomly assigned to either the intervention group or the control group (1:1). Participants received regular health education and behavioural interventions throughout the trial. The intervention group was given a link to order free HIVST kits online, while the control group received information about free SBHT. Both groups completed internet-based follow-up surveys at three and six months. The primary outcome was the proportion of participants who underwent HIV testing during the six-month follow-up period. This trial was registered at chictr.org.cn (ChiCTR2000038416). Findings: Between November 2020 and January 2021, we recruited a total of 620 participants (300 in the intervention group and 320 in the control group). The follow-up completion rates were 99·0% and 95·0% in the intervention and control groups, respectively. At baseline, the median age of participants was 32 (interquartile range: 26-37), and 77·7% underwent HIV testing in the past three months. The proportion of participants who underwent HIV testing in the past three months was higher in the intervention group than in the control group at both the three-month (adjusted risk difference [RD]: 36·7, 95% confidence interval [CI]: 35·1-38·5, p < 0·001) and six-month (RD: 26·7, 95% CI: 24·6-28·7 p < 0·001) follow-up periods. Interpretation: Our study suggests that providing online distribution of HIVST kits for MSM with PrEP discontinuation induced by completion of the PrEP project effectively promoted HIV testing. This digital approach improves access to HIV testing for MSM and can be applicable to other settings where MSM turn to online public health services. Funding: The study was funded by the Fund of National Natural Science Foundation of China; the Mega-Projects of National Science Research for the 13th Five-Year Plan; and the Liaoning Revitalization Talents Program, China.

Recurrent steroid cell tumor not otherwise specified with elevated testosterone and prolactin concentrations and impaired glucose metabolism: a case report.

Steroid cell tumor not otherwise specified (SCT-NOS) is a rare type of sex cord-stromal tumor with malignant potential. A 19-year-old woman underwent laparoscopic bilateral cystectomy, and postoperative pathology showed bilateral ovarian SCT-NOS. She had recurrence of the right tumor 8 years after the surgery, with shortened menstrual cycles, elevated testosterone and prolactin concentrations, and impaired glucose metabolism. We performed a laparoscopic right salpingo-oophorectomy. Testosterone and prolactin concentrations rapidly decreased and returned to the normal range after surgery. Subsequently, she had regular menstrual cycles and good glycemic control. The findings in our case suggest that there is a possibility of late recurrence in SCT-NOS. Therefore, we suggest that the postoperative follow-up period should be 10 years for this condition.

A phthalocyanine-based porous organic polymer for a lithium-ion battery anode.

Porous organic polymers (POPs) are a novel class of polymeric materials with high flexibility and designability for building structures. Herein, a phthalocyanine-based porous organic polymer (PcPOP) was constructed in situ on copper foil from H2Pc(ethynyl)4 [Pc(ethynyl)4 = 2(3),9(10),16(17),23(24)-tetra(ethynyl)phthalocyanine] by the coupling reaction. Benefiting from the uniformly distributed electron-rich nitrogen atoms in the Pc structure and the sp-hybridized carbons in the acetylenic linkage, Li intercalation in the porous organic polymer would be improved and stabilized. As a result, PcPOP showed remarkable electrochemical performance in lithium-ion batteries as the anode, including high specific capacity (a charge capacity of 1172 mA h g-1 at a current density of 150 mA g-1) and long cycling stability (a reversible capacity of 960.1 mA h g-1 can be achieved even after 600 cycles at a current density of 1500 mA g-1). The result indicates that the intrinsic doping of electron-rich sites of the building molecules is beneficial for the electrochemical performance of the porous organic polymer.

Research on the development methodology for clinical practice guidelines for organic integration of traditional Chinese and Western medicine.

Integrated traditional Chinese medicine (TCM) and Western medicine (WM) is a new medical science grounded in the knowledge bases of both TCM and WM, which then forms a unique modern medical system in China. Integrated TCM and WM has a long history in China, and has made important achievements in the process of clinical diagnosis and treatment. However, the methodological defects in currently published clinical practice guidelines limit its development. The organic integration of TCM and WM is a deeper integration of TCM and WM. To realize the progression of "integration" to "organic integration", a targeted and standardized guideline development methodology is needed. Therefore, the purpose of this study is to establish a standardized development procedure for clinical practice guidelines for the organic integration of TCM and WM to promote the systematic integration of TCM and WM research results into clinical practice guidelines in order to achieve optimal results as the whole is greater than the sum of the parts.

Xuebijing injection, a Chinese patent medicine, against severe pneumonia: Current research progress and future perspectives.

Severe pneumonia is one of the most common infectious diseases and the leading cause of sepsis and septic shock. Preventing infection, balancing the patient's immune status, and anti-coagulation therapy are all important elements in the treatment of severe pneumonia. As multi-target agents, Xuebijing injection (XBJ) has shown unique advantages in targeting complex conditions and saving the lives of patients with severe pneumonia. This review outlines progress in the understanding of XBJ's anti-inflammatory, endotoxin antagonism, and anticoagulation effects. From the hundreds of publications released over the past few years, the key results from representative clinical studies of XBJ in the treatment of severe pneumonia were selected and summarized. XBJ was observed to effectively suppress the release of pro-inflammatory cytokines, counter the effects of endotoxin, and assert an anticoagulation effect in most clinical trials, which are consistent with experimental studies. Collectively, this evidence suggests that XBJ could play an important and expanding role in clinical medicine, especially for sepsis, septic shock and severe pneumonia. Please cite this article as: Zhang M, Zheng R, Liu WJ, Hou JL, Yang YL, Shang HC. Xuebijing injection, a Chinese patent medicine, against severe pneumonia: Current research progress and future perspectives. J Integr Med. 2023; 21(5): 413-422.

Clinical evidence of three traditional Chinese medicine drugs and three herbal formulas for COVID-19: A systematic review and meta-analysis of the Chinese population.

BACKGROUND: The coronavirus disease 2019 (COVID-19) continues to spread worldwide. Integrated Chinese and Western medicine have had some successes in treating COVID-19. OBJECTIVE: This study aims to evaluate the efficacy and safety of three traditional Chinese medicine drugs and three herbal formulas (3-drugs-3-formulas) in patients with COVID-19. SEARCH STRATEGY: Relevant studies were identified from 12 electronic databases searched from their establishment to April 7, 2022. INCLUSION CRITERIA: Randomized controlled trials (RCTs), non-RCTs and cohort studies that evaluated the effects of 3-drugs-3-formulas for COVID-19. The treatment group was treated with one of the 3-drugs-3-formulas plus conventional treatment. The control group was treated with conventional treatment. DATA EXTRACTION AND ANALYSIS: Two evaluators screened and selected literature independently, then extracted basic information and assessed risk of bias. The treatment outcome measures were duration of main symptoms, hospitalization time, aggravation rate and mortality. RevMan 5.4 was used to analyze the pooled results reported as mean difference (MD) with 95% confidence interval (CI) for continuous data and risk ratio (RR) with 95% CI for dichotomous data. RESULTS: Forty-one studies with a total of 13,260 participants were identified. Our analysis suggests that compared with conventional treatment, the combination of 3-drugs-3-formulas might shorten duration of fever (MD = -1.39; 95% CI: -2.19 to -0.59; P < 0.05), cough (MD = -1.57; 95% CI: -2.16 to -0.98; P < 0.05) and fatigue (MD = -1.36; 95% CI: -2.21 to -0.51; P < 0.05), decrease length of hospital stay (MD = -2.62; 95% CI -3.52 to -1.72; P < 0.05), the time for nucleic acid conversion (MD = -2.92; 95% CI: -4.26 to -1.59; P < 0.05), aggravation rate (RR = 0.49; 95% CI: 0.38 to 0.64; P < 0.05) and mortality (RR = 0.34; 95% CI: 0.19 to 0.62; P < 0.05), and increase the recovery rate of chest computerized tomography manifestations (RR = 1.22; 95% CI: 1.14 to 1.3; P < 0.05) and total effectiveness (RR = 1.24; 95% CI: 1.09 to 1.42; P < 0.05). CONCLUSION: The 3-drugs-3-formulas can play an active role in treating all stages of COVID-19. No severe adverse events related to 3-drugs-3-formulas were observed. Hence, 3-drugs-3-formulas combined with conventional therapies have effective therapeutic value for COVID-19 patients. Further long-term high-quality studies are essential to demonstrate the clinical benefits of each formula. Please cite this article as: You LZ, Dai QQ, Zhong XY, Yu DD, Cui HR, Kong YF, Zhao MZ, Zhang XY, Xu QQ, Guan ZY, Wei XX, Zhang XC, Han SJ, Liu WJ, Chen Z, Zhang XY, Zhao C, Jin YH, Shang HC. Clinical evidence of three traditional Chinese medicine drugs and three herbal formulas for COVID-19: A systematic review and meta-analysis of the Chinese population. J Integr Med. 2023; 21(5): 441-454.

Organic Integration of Traditional Chinese and Western Medicines-Future of Clinical Practice Guidelines of Integrated Traditional Chinese and Western Medicines.

The transformation and implementation of clinical practice guidelines for integrated traditional Chinese medicine (TCM) and Western medicine (WM) is crucial to the adoption of medical science and technological findings and is an important way for TCM to be made available to the world. First, clinical practice guidelines (CPGs) of TCM and WM integration in recent years was analyzed to clarify the current situation and problems in the existing guidelines according to the following four perspectives: (1) perspective of TCM and WM integration in guidelines, (2) diagnosis Using integrated TCM and WM, (3) integration of TCM and WM treatment, (4) promoting TCM and WM integration. Secondly, the information and quality evaluation of CPGs for integrated Chinese and Western medicine in 2020-2022 were analyzed to explore the degree and methods of integration of Chinese and Western medicine guidelines. And last this study aimed to lay a foundation for the further establishment of Chinese characteristic, repeatable, and calculable clinical practice guidelines of TCM and WM integration.

Effectiveness and safety of community-led assisted partner service among HIV-diagnosed men who have sex with men: a multicentre, randomized controlled trial in China.

Background: No randomized controlled trials have involved established HIV-diagnosed men who have sex with men (MSM) diagnosed for more than 6 months into the assisted partner service (aPS). We compared voluntary aPS involving community-based organizations (CBOs) and HIV self-testing (aPSST) with regular partner service (rPS) in HIV-diagnosed MSM irrespective of diagnosis time. Methods: In this unblinded, multicentre trial, we enrolled HIV-diagnosed MSM irrespective of diagnosis time in three cities in northern China. Index patients were randomly assigned to aPSST or rPS. Index patients in the aPSST group were additionally provided a comprehensive intervention package including HIV self-testing and CBO-based aPS compared with rPS group. The primary outcome was the number of index patients whose any sexual partner tested for HIV during the 6-month study. Completion of HIV testing was defined as sexual partners taking a clinic-based HIV test or HIV self-testing. Safety was assessed preliminary at the end of the 6-month follow-up. This study has been registered at chictr.org.cn (ChiCTR2000038784). Findings: From March to December 2021, 325 of HIV-diagnosed MSM were enrolled (90⋅2% were established HIV-diagnosed MSM) and randomly assigned to receive aPSST (n = 167) or rPS (n = 158). At 6 months, 110 (65⋅9%) index patients in the aPSST group had at least one sexual partner tested for HIV compared with 50 (31⋅6%) in the rPS group (hazard ratio 2⋅86; 95% confidence interval 2⋅03-4⋅03; p < 0⋅001). No significant difference was observed in effects of aPSST on HIV testing promotion between established and newly HIV-diagnosed MSM. Self-reported harms were infrequently observed in both groups (approximately 2⋅0%). Interpretation: Among HIV-diagnosed MSM regardless of diagnosis time, voluntary aPS involving CBOs and HIV self-testing was effective and safe for promoting partner HIV testing. Funding: This work was supported by the Mega-Projects of National Science Research, the National Natural Science Foundation of China and the Liaoning Revitalization Talents Program, China.

Rational Fabrication of Ionic Covalent Organic Frameworks for Chemical Analysis Applications.

The rapid development of advanced material science boosts novel chemical analytical technologies for effective pretreatment and sensitive sensing applications in the fields of environmental monitoring, food security, biomedicines, and human health. Ionic covalent organic frameworks (iCOFs) emerge as a class of covalent organic frameworks (COFs) with electrically charged frames or pores as well as predesigned molecular and topological structures, large specific surface area, high crystallinity, and good stability. Benefiting from the pore size interception effect, electrostatic interaction, ion exchange, and recognizing group load, iCOFs exhibit the promising ability to extract specific analytes and enrich trace substances from samples for accurate analysis. On the other hand, the stimuli response of iCOFs and their composites to electrochemical, electric, or photo-irradiating sources endows them as potential transducers for biosensing, environmental analysis, surroundings monitoring, etc. In this review, we summarized the typical construction of iCOFs and focused on their rational structure design for analytical extraction/enrichment and sensing applications in recent years. The important role of iCOFs in the chemical analysis was fully highlighted. Finally, the opportunities and challenges of iCOF-based analytical technologies were also discussed, which may be beneficial to provide a solid foundation for further design and application of iCOFs.

Phenotypic and genetic features of a novel clinically isolated rough morphotype Candida auris.

Introduction: Candida auris is a newly emerging pathogenic fungus of global concern and has been defined by the World Health Organization (WHO) as a member of the critical group of the most health-threatening fungi. Methods: This study reveals and reports for the first time that a rough morphotype C. auris strain causes urinary tract infections in non-intensive care unit (ICU) inpatients. Furthermore, the morphology, the scanning electronmicroscopy (SEM), Whole-genome resequencing and RNA sequencing of C. auris possessing rough morphotype colonies compared to their smooth morphotype counterparts. Results: The newly identified phenotypic variation of C. auris appears round, convex, dry, and burr-like with a rough texture. SEM shows that rough type C. auris has a rough and uneven colony surface with radial wrinkles and irregular spore arrangement. Cells of the rough morphotype C. auris naturally aggregate into clusters with tight connections in the liquid, and it seems that the cell division is incomplete. A genome-wide analysis of the rough type C. auris confirmed its genetic association with the smooth type of C. auris prevalent in China (Shenyang) two years ago; however, single nucleotide polymorphism (SNP) mutations of five genes (ACE2, IFF6, RER2, UTP20, and CaO19.5847) were identified more recently. RNA-seq revealed IFF2/HYR3, DAL5, PSA31, and SIT1 were notably up-regulated, while multiple cell wall-associated genes (ALS1, MNN1, PUL1, DSE1, SCW11, PGA38, RBE1, FGR41, BGLI, GIT3, CEP3, and SAP2) were consistently down-regulated in rough morphotype C. auris. Discussion: The rough phenotypic variation of C. auris is likely to be related to the structural and functional changes in cell wall proteins. This novel rough morphotype C. auris will provide a basis for further studies concerning the evolutionary characteristics of C. auris.

Network pharmacology and molecular docking prediction, combined with experimental validation to explore the potential mechanism of Qishen Yiqi pills against HF-related cognitive dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Qishen Yiqi Pills (QSYQ) is a classical herbal formula for treating heart failure (HF) and has potential efficacy in improving cognitive function. The latter is one of the most common complications in patients with HF. However, there is no study on treating HF-related cognitive dysfunction by QSYQ. AIMS OF THE STUDY: The study aims to investigate the effect and mechanism of QSYQ on treating post-HF cognitive dysfunction based on network pharmacology and experimental validation. MATERIALS AND METHODS: Network pharmacology analysis and molecular docking was used to explore endogenous targets of QSYQ in treating cognitive impairment. Ligation of the anterior descending branch of the left coronary artery and sleep deprivation (SD) were used to induce HF-related cognitive dysfunction in rats. The efficacy and potential signal targets of QSYQ were then verified by functional evaluation, pathological staining, and molecular biology experiments. RESULTS: 384 common targets were identified by intersecting QSYQ 'compound targets' and 'cognitive dysfunction' disease targets. KEGG analysis showed these targets were enriched to the cAMP signal, and four marks responsible for regulating the cAMP signal were successfully docked with core compounds of QSYQ. Animal experiments demonstrated that QSYQ significantly ameliorated cardiac function and cognitive function in rats suffering from HF and SD, inhibited the reduction of cAMP and BDNF content, reversed the upregulation of PDE4 and downregulation of CREB, suppressed the loss of neurons, and restored the expression of synaptic protein PSD95 in the hippocampus. CONCLUSION: This study clarified that QSYQ could improve HF-related cognitive dysfunction by modulating cAMP-CREB-BDNF signals. It provides a rich basis for the potential mechanism of QSYQ in the treatment of heart failure with cognitive dysfunction.

Enhanced Cell Osteogenic Differentiation in Alendronate Acid and Flufenamic Acid Drug-Impregnated Nanoparticles of Mesoporous Bioactive Glass Composite Calcium Phosphate Bone Cement In Vitro.

This study aims to compare the anti-osteoporotic drugs alendronic acid (ALN) and flufenamic acid (FA) alone impregnate into nanoparticles of mesoporous bioactive glass (nMBG), which further composites calcium phosphate cement (CPC) and investigates their in vitro performance. The drug release, physicochemical properties, and biocompatibility of nMBG@CPC composite bone cement are tested, and the effect of the composites on improving the proliferation and differentiation efficiency of mouse precursor osteoblasts (D1 cells) is also investigated. Drug release shows that FA impregnates nMBG@CPC composite, a large amount of FA is released rapidly within 8 h, gradually reaching a stable release within 12 h, followed by a slow and sustained release within 14 days, and then reaches a plateau within 21 days. The release phenomenon confirms that the drug-impregnated nBMG@CPC composite bone cement effectively achieves slow drug delivery. The working time and setting time of each composite are within 4-10 min and 10-20 min, respectively, meeting the operational requirements of clinical applications. The addition of nMBG nanoparticles in the CPC matrix did not prevent the aggregation phenomenon under microstructural observation, thus resulting in a decrease in the strength of the nMBG@CPC composite. However, after 24 h of immersed reaction, the strength of each 5 wt.% nMBG impregnated with different concentrations of FA and ALN is still greater than 30 MPa, which is higher than the general trabecular bone strength. The drug-impregnated nMBG@CPC composites did not hinder the product formation and exhibit biocompatibility. Based on the proliferation and mineralization of D1 cells, the combination of nMBG with abundant FA and ALN in CPC is not conducive to the proliferation of D1 cells. However, when D1 cells are contact cultured for 21 days, alkaline phosphatase (ALP) enzyme activity shows higher ALP secretion from drug-impregnated nMBG@CPC composites than drug-free composites. Accordingly, this study confirms that nMBG can effectively impregnate the anti-osteoporosis drugs FA and ALN, and enhance the mineralization ability of osteoblasts. Furthermore, drug-impregnated nMBG applications can be used alone or in combination with CPC as a new option for osteoporotic bone-filling surgery.

Cardiac MRI-Based Assessment of Myocardial Injury in Asymptomatic People Living With Human Immunodeficiency Virus: Correlation With nadir CD4 Count.

BACKGROUND: There are known cardiac manifestations of HIV, but the findings in asymptomatic subjects are still not fully explored. PURPOSE: To evaluate for the presence of subclinical myocardial injury in asymptomatic people living with human immunodeficiency virus (PLWH) by cardiac MRI and to explore the possible association between subclinical myocardial injury and HIV-related clinical characteristics. STUDY TYPE: Cross-sectional. POPULATION: A total of 80 asymptomatic PLWH (age: 53 years [47-56 years]; 90% male) and 50 age- and sex-matched healthy participants. FIELD STRENGTH/SEQUENCE: A 3-T, cine sequence, T1, T2, and T2* mapping. ASSESSMENT: Function analysis was derived from short axis, two-, three-, and four-chamber cine images by feature tracking. Regions of interest were manually selected in the midventricular septum T1, T2, and T2* mapping sequences. PLWH were evaluated for T1 increment (△T1 mapping = native T1 - cutoff values) and HIV-related clinical characteristics, particularly the nadir CD4 count. And PLWH were stratified into two groups according to the cutoff value of native T1: elevated native T1 and normal. STATISTICAL TESTS: T test, Wilcoxon rank-sum test, Chi-square test, Spearman rank correlation, and logistic regression. P <0.05 indicated statistical significance. RESULTS: Asymptomatic PLWH revealed significantly higher native myocardial T1 values (1241 ± 29 msec vs. 1189 ± 21 msec), T2 values (40.7 ± 1.5 msec vs. 37.9 ± 1.4 msec), and lower LVGRS (30.2% ± 6.2% vs. 35.8% ± 6.4%), LVGCS (-18.0% ± 2.5% vs. -19.5% ± 2.0%), and LVGLS (-16.0% ± 3.8% vs. -17.9% ± 2.6%) but showed no difference in T2* values (17.3 msec [16.3-19.1 msec] vs. 18.3 msec [16.5-19.3 msec], P = 0.201). A negative correlation between the native T1 increment in PLWH with subclinical myocardial injury and the nadir CD4 count (u = -0.316). Nadir CD4 count <500 cells/mm3 was associated with higher odds of elevated native T1 myocardial values (odds ratio, 6.12 [95% CI, 1.07-34.91]) in PLWH. DATA CONCLUSION: Subclinical myocardial inflammation and dysfunction were present in asymptomatic PLWH, and a lower nadir CD4 count may be a risk factor for subclinical myocardial injury. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 2.

[Advances in animal models of chronic heart failure and its applications in traditional Chinese medicine].

Chronic heart failure(CHF) is a series of clinical syndromes in which various heart diseases progress to their end stage. Its morbidity and mortality are increasing year by year, which seriously threatens people's life and health. The diseases causing CHF are complex and varied, such as coronary heart disease, hypertension, diabetes, cardiomyopathy and so on. It is of great significance to establish animal models of CHF according to different etiologies to explore the pathogenesis of CHF and develop drugs to prevent and treat CHF induced by different diseases. Therefore, based on the classification of the etiology of CHF, this paper summarizes the animal models of CHF widely used in recent 10 years, and the application of these animal models in traditional Chinese medicine(TCM) research, in order to provide ideas and strategies for studying the pathogenesis and treatment of CHF, and provide ideas for TCM modernization research.

Altered lipid metabolites accelerate early dysfunction of T cells in HIV-infected rapid progressors by impairing mitochondrial function.

The complex mechanism of immune-system damage in HIV infection is incompletely understood. HIV-infected "rapid progressors" (RPs) have severe damage to the immune system early in HIV infection, which provides a "magnified" opportunity to study the interaction between HIV and the immune system. In this study, forty-four early HIV-infected patients (documented HIV acquisition within the previous 6 months) were enrolled. By study the plasma of 23 RPs (CD4+ T-cell count < 350 cells/µl within 1 year of infection) and 21 "normal progressors" (NPs; CD4+ T-cell count > 500 cells/µl after 1 year of infection), eleven lipid metabolites were identified that could distinguish most of the RPs from NPs using an unsupervised clustering method. Among them, the long chain fatty acid eicosenoate significantly inhibited the proliferation and secretion of cytokines and induced TIM-3 expression in CD4+ and CD8+ T cells. Eicosenoate also increased levels of reactive oxygen species (ROS) and decreased oxygen consumption rate (OCR) and mitochondrial mass in T cells, indicating impairment in mitochondrial function. In addition, we found that eicosenoate induced p53 expression in T cells, and inhibition of p53 effectively decreased mitochondrial ROS in T cells. More importantly, treatment of T cells with the mitochondrial-targeting antioxidant mito-TEMPO restored eicosenoate-induced T-cell functional impairment. These data suggest that the lipid metabolite eicosenoate inhibits immune T-cell function by increasing mitochondrial ROS by inducing p53 transcription. Our results provide a new mechanism of metabolite regulation of effector T-cell function and provides a potential therapeutic target for restoring T-cell function during HIV infection.