Objective To systematically analyze the characteristics of the disease burden of hypertensive heart disease (HHD) in the elderly (≥60 years) globally and in China from 1990 to 2021, and to predict its future trends from 2022 to 2040, with the aim of providing data support for optimizing comprehensive prevention and control strategies for HHD. Methods Based on the Global Burden of Disease (GBD) 2021 database, the number of prevalent cases and disability-adjusted life years (DALYs) of HHD in the elderly were extracted for the world, China, and five regions categorized by sociodemographic index (SDI). Joinpoint regression was used to analyze the temporal trends of age-standardized prevalence rate and age-standardized DALYs rate of HHD in the elderly. A three-factor decomposition method was applied to evaluate the relative contributions of aging, population growth, and epidemiological changes to the variations in the elderly HHD burden. Additionally, a Bayesian age-period-cohort model was used to predict the elderly HHD burden from 2022 to 2040. Results In 2021, the number of prevalent elderly HHD cases reached 10 283 000 globally and 3 412 400 in China, representing increases of 179.20% and 159.20% respectively, compared with 1990. The DALYs of elderly HHD were 18 812 700 person-years globally and 4 731 400 person-years in China, rising by 76.08% and 29.45% respectively from 1990. Meanwhile, the growth rates of the number of prevalent cases and DALYs of elderly HHD varied across different SDI regions. From 1990 to 2021, the age-standardized prevalence rate of elderly HHD in China, as well as the age-standardized DALYs rate of elderly HHD both globally and in China, showed significant downward trends (all average annual percentage changes<0, all P<0.001). In 2021, the 70-74 years age group accounted for the highest proportion of prevalent cases and DALYs of elderly HHD, both globally and in China. Decomposition analysis revealed that population growth was the dominant factor driving the increase in the elderly HHD burden across all regions. The prediction model results indicated that the number of prevalent cases and DALYs of elderly HHD would continue to rise globally and in China from 2022 to 2040, with the growth rate of the elderly HHD burden in China between 2021 and 2040 expected to exceed the global average. Conclusion Over the past 32 years, although the age-standardized disease rates of elderly HHD have mainly shown a downward trend globally and in China, the absolute number of the disease burden has increased substantially. The projection model indicates a continued upward trajectory, with the growth rate in China higher than the global average. Therefore, there is an urgent need to implement precise prevention and control strategies to effectively mitigate the disease burden of elderly HHD.

As a traditional nutritional and healthy cash crop in China, tea has certain significance in promoting human health and preventing and controlling chronic diseases. Studies have shown that the nutritional health effect of tea is due to its rich functional components, mainly including tea polyphenols, tea pigments, tea polysaccharides, theanine, alkaloids and other bioactive substances. At present, researchers from the academic circles have continuously carried out animal and human experiments on the health effects of various functional components of tea, which has accumulated abundant research data and materials. Based on this, this article reviews the literature on the nutritional and health effects of the main functional components of tea, and adopts the method of evidence-based research to screen and extract relevant data for qualitative and quantitative meta-analysis. Subsequently, the nutritional health effects of the five functional components of tea, namely tea polyphenols, tea pigments, tea polysaccharides, theanine, and alkaloids, are summarized and outlined. Studies have shown that tea polyphenols, tea pigments, tea polysaccharides, theanine and alkaloids have different health effects and are expected to play their unique roles in promoting human health and preventing and controlling diseases.

ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

BACKGROUND:Currently,exercise therapy is an effective non-pharmacological treatment for low back pain,and exercise therapy can maintain lumbar spine stabilization through mechanical-chemical coupling between bones and muscles,but there is no clear description of the research progress and optimal treatment protocols for exercise therapy to relieve chronic non-specific lower back pain through mechanical-chemical coupling. OBJECTIVE:To review the research progress related to the influence of paravertebral muscles on lumbar spine stabilization during exercise therapy through mechanical-chemical coupling,which in turn relieves chronic non-specific lower back pain,as well as the current optimal treatment protocols of exercise therapy for chronic non-specific lower back pain. METHODS:Literature searches were performed in WanFang database,CNKI,VIP,Web of Science,and PubMed database,with search terms of"chronic non-specific low back pain,lumbar spine stabilization,paravertebral muscles,exercise therapy"in Chinese and English.Relevant literature published from database inception to January 2024 was searched and 93 articles were included for final summarization. RESULTS AND CONCLUSION:Exercise therapy can act on the paravertebral muscles and bones through appropriate mechanical stimulation and produce corresponding changes.Exercise therapy is an important intervention for chronic non-specific lower back pain as it improves the quality of the paravertebral muscles,primarily through mechanical-chemical coupling,and thus maintains lumbar spine stabilization for better relief of chronic non-specific lower back pain.However,there are no clear reports on the exact effective protocols for exercise therapy to treat chronic non-specific lower back pain through lumbar spine stabilization.The development of an individualized exercise program is particularly important for the treatment and prognosis of chronic non-specific low back pain.Muscle mass and bone mass of the same individual are closely related,and imaging assessment of paravertebral muscle mass and quantity is important for disease detection and intervention.

The liver regenerative capacity is crucial for patients with end-stage liver disease following partial hepatectomy (PHx). The specific bacteria and mechanisms regulating liver regeneration post-PHx remain unclear. This study demonstrated dynamic changes in the abundance of Parabacteroides distasonis (P. distasonis) post-PHx, correlating with hepatocyte proliferation. Treatment with live P. distasonis significantly promoted hepatocyte proliferation and liver regeneration after PHx. Targeted metabolomics revealed a significant positive correlation between P. distasonis and β-hydroxybutyric acid (BHB), as well as hyodeoxycholic acid and 3-hydroxyphenylacetic acid in the gut after PHx. Notably, treatment with BHB, but not hyodeoxycholic acid or 3-hydroxyphenylacetic acid, significantly promoted hepatocyte proliferation and liver regeneration in mice after PHx. Moreover, STAT3 inhibitor Stattic attenuated the promotive effects of BHB on cell proliferation and liver regeneration both in vitro and in vivo. Mechanistically, P. distasonis upregulated the expression of fatty acid oxidation-related proteins, and increased BHB levels in the liver, and then BHB activated the STAT3 signaling pathway to promote liver regeneration. This study, for the first time, identifies the involvement of P. distasonis and its associated metabolite BHB in promoting liver regeneration after PHx, providing new insights for considering P. distasonis and BHB as potential strategies for promoting hepatic regeneration.

[This corrects the article DOI: 10.1016/j.apsb.2024.03.030.].

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

In this comprehensive review, we delve into the evolution of drug delivery systems in reproductive medicine with a focus on the emerging role of exosomes, a class of extracellular vesicles. Exosomes offer unique advantages in overcoming these challenges due to their inherent biocompatibility, stability, and ability to facilitate targeted delivery. This review provides a detailed examination of exosome biogenesis and their function in cellular communication, setting the stage for understanding their potential as drug delivery vehicles. We explore the mechanisms through which exosomes can be loaded with small molecule drugs and the benefits they offer over synthetic nanoparticles. The review highlights groundbreaking case studies that illustrate the successful application of exosome-mediated drug delivery in reproductive health, including enhancing fertility treatments, supporting gamete and embryo development, and facilitating maternal-fetal communication. This study aims to provide a precise understanding of how exosomal drug delivery can revolutionize treatments for reproductive health disorders, paving the way for future therapeutic applications. Lastly, we touch upon the promising therapeutic implications of exosomal delivery for proteins and genes, offering a window into future treatments for reproductive health disorders.

Objective:To investigate the effect and mechanism of injectable photopolymerizable porous gelatin methacrylate anhydride (Porous GelMA)/methacrylated silk fibroin (SilMA) composite hydrogel (PSE) loaded with human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) in promoting knee joint cartilage regeneration.Methods:The porous GelMA solution (60 g/L) was mixed with SilMA solution (200 g/L) at a volume ratio of 6∶1 . The mixture was ultraviolet-irradiated for 30 seconds to form a cured Porous GelMA/SilMA hydrogel (P/S6). The hUCMSC-Exos was isolated via differential centrifugation coupled with ultrafiltration and then was incorporated into the Porous GelMA/SilMA composite solution at 200 μg/ml, followed by ultraviolet irradiation for 30 seconds to generate Exos-loaded PSE. Primary rat chondrocytes (P1) were divided into control group, P/S6 group, and PSE group to characterize the porosity, compressive strength, and sustained exosome release kinetics of PSE hydrogel. Chondrocytes were allocated to control group, interleukin-1β (IL-1β) group, P/S6 group, and PSE group, among which the last three groups were preconditioned with 10 ng/ml IL-1β for 24 hours, and then cultured in complete medium, P/S6 extract and PSE extract for 3 days, respectively, to establish in vitro cartilage defect models, while the control group remained untreated. Western blot and qRT-PCR analysis were conducted to quantify the expression levels of antibody to aggrecan core protein (ACAN), sex-determining region Y-box transcription factor 9 (SOX9), matrix metalloproteinase-13 (MMP13) and collagen type II (COL II). Murine monocyte-macrophage leukemia cells (RAW264.7) were divided into control group, P/S6 group, and PSE group, which were then cultured in complete medium, PSE extract, and PSE extract medium for 3 days, respectively. qRT-PCR was employed to detect the expression levels of recombinant arginase-1 protein (ARG1), mannose receptor (CD206), and inducible nitric oxide synthase (iNOS). Transcriptomic sequencing was used to identify differentially expressed genes during PSE-mediated chondrocyte regeneration, followed by functional enrichment analysis of key signaling pathways. Twenty-four SD rats were selected to establish cartilage defect models and assigned to injury control group, P/S6 group, and PSE group according to the random number table (8 rats per group). The right knee joints of the rats were surgically exposed, and cylindrical osteochondral defects (a diameter of 2.0 mm× a depth of 1.0 mm) were surgically created in the center of the femoral trochlear groove using a drill bit. The injury control group received phosphate-buffered saline, while the P/S6 group and PSE group were injected with corresponding hydrogels followed by photo-crosslinking. Incisions then were closed in layers. At 6 and 10 weeks after injury, specimens were harvested for HE staining and safranin O-fast green staining to evaluate cartilage regeneration and immunohistochemistry staining to quantify the positive area fractions for COL II, MMP13, ARG1, and CD206 in the defect areas. Results:PSE hydrogel exhibited compressive strength matching native cartilage (0.41 MPa), high porosity (85%), and sustained exosome release capacity (cumulative release rate of approximately 85% over 14 days). In chondrocyte repair experiments, compared to the IL-1β group, the PSE group demonstrated significantly upregulated expression of anabolic markers of cartilage (COL II expression increased by 2.1-fold, ACAN by 1.8-fold, and SOX9 by 1.5-fold) ( P<0.01) as well as significantly suppressed expression of catabolic markers (MMP13 expression decreased by 52%) ( P<0.01). In macrophage polarization assays, the PSE group exhibited ARG1 expression increased by 68% when compared to the control group ( P<0.01), thus promoting M2 polarization of macrophages. Transcriptomic analysis revealed that PSE enhanced extracellular matrix (ECM) synthesis by activating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway and ECM-receptor interaction pathway, as well as by suppressing inflammation-related gene expression. Histological evaluation in animal experiments revealed regeneration of hyaline cartilage with smooth, continuous surfaces in the defect areas in the PSE group. At 10 weeks after surgery, the neocartilage-positive area in the PSE group was (9.94±0.26)%, significantly larger than (1.67±0.11)% in the injury control group ( P<0.01). Besides, the CD206? M2 macrophage-positive area reached (14.44±0.23)% in the PSE group, significantly larger than (3.41±0.36)% in the injury control group ( P<0.01). Conclusions:The PSE hydrogel successfully engineered in the study can significantly promote regenerative repair of knee cartilage defects through a dual mechanism of enhanced ECM anabolism and remodeled inflammatory microenvironment. The core mechanisms involve specific activation of the PI3K/Akt pathway (boosting chondrocyte proliferation and survival) and ECM-receptor interaction pathway (driving ECM synthesis and assembly) by exosome-loaded PSE, while effectively polarizing macrophages toward an anti-inflammatory M2 phenotype so as to coordinately regulate cartilage ECM metabolism and suppress inflammatory responses.

OBJECTIVE: To observe the clinical efficacy of acupuncture based on "status-target coherence" theory combined with Kegel exercises for vaginal laxity syndrome (VLS). METHODS: Sixty-six patients with VLS were randomized into an observation group (33 cases, 2 cases dropped out, 1 case was discontinued) and a control group (33 cases, 5 cases dropped out). The observation group was treated with acupuncture combined with Kegel exercises, acupuncture was applied to bilateral Ciliao (BL32), Zhongliao (BL33), Sanyinjiao (SP6), etc. The control group was treated with Kegel exercises. Both acupuncture and Kegel exercises were performed once every other day, three times a week for 12 weeks. Before and after treatment, the vaginal laxity questionnaire (VLQ) score, pelvic floor muscle strength (vaginal resting pressure, vaginal systolic pressure, vaginal contraction duration), degree of vaginal laxity and sexual satisfaction questionnaire (SSQ) grade were observed in both groups. RESULTS: After treatment, the VLQ score, vaginal resting pressure, vaginal systolic pressure, vaginal contraction duration in the observation group were elevated compared with those before treatment (P<0.05), and SSQ grade was improved (P<0.05); and the above indexes in the observation group were better than those in the control group (P<0.05). There were no significant difference before and after treatment in the degree of vaginal laxity in the two groups (P>0.05). CONCLUSION Acupuncture based on "status-target coherence" theory combined with Kegel exercises can effectively enhance the strength of pelvic floor muscles, improve the symptoms of vaginal laxity, and improve the satisfaction of sexual life, and its therapeutic effect is better than Kegel exercises alone.
Humans ; Female ; Adult ; Vagina/physiopathology* ; Acupuncture Therapy ; Exercise Therapy ; Young Adult ; Middle Aged ; Treatment Outcome ; Acupuncture Points ; Combined Modality Therapy ; Vaginal Diseases/therapy*