Objective To explore the causal relationship between immune cells and heart failure (HF), and the mediating role of serum metabolites, in order to identify potential biomarkers and therapeutic targets. Methods We employed a two-sample Mendelian randomization (MR) analysis method based on genome-wide association study (GWAS) data, analyzing the direct and indirect effects of 731 types of immune cells and 1 400 metabolites on HF. We selected valid instrumental variables and conducted statistical analyses using R software. The primary analysis was performed using the inverse variance weighted method, supplemented by MR-Egger analysis and weighted median method. The stability of the results was assessed through tests such as Cochran’s Q test. Results Our research found a negative causal relationship between PD-L1 on CD14−CD16+ and HF. Sensitivity analysis supported this result. The reverse MR analysis did not find an effect of HF on PD-L1 on CD14−CD16+, indicating that PD-L1 on CD14−CD16+ might play a unidirectional role in reducing the risk of HF. Further mediation MR analysis showed that PD-L1 on CD14−CD16+ might influence the risk of HF onset by regulating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), with a mediation effect ratio of 6.7%. Conclusion PD-L1 on CD14−CD16+ may reduce the risk of HF by elevating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), which provides a new perspective for understanding the pathogenesis of HF.

Puji Xiaoduyin， a specialized formula for the swollen-head epidemic， was recorded in the Catalogue of Ancient Classical Formula （the Second Batch）-Han Medicine， published in September 2023. It had been inherited and developed by medical experts of successive generations and passed down to this day. This paper sorted out the historical evolution of this formula using bibliometric methods. It also comprehensively analyzed key information on the formula name， historical origin， drug dosage， herb origin， processing methods， decocting methods， function， and clinical applications. Additionally， this paper analyzed the application of this formula in both modern and ancient times. Results showed that the formula was first recorded as "Puji Xiaodu Yinzi" in LI Dongyuan's Proven Formulas written by LI Gao from the Jin dynasty. The medicinal composition and dosage were： Scutellariae Radix and Coptidis Rhizoma （20.65 g each）， Ginseng Radix et Rhizoma 12.39 g， Scrophulariae Radix， Citri Reticulatae Pericarpium， and Glycyrrhizae Radix et Rhizoma （8.26 g each）， Forsythiae Fructus， Arctii Fructus， Isatidis Radix， and Lasiosphaera Calvatia （4.13 g each）， Bombyx Batryticatus and Cimicifugae Rhizoma （2.891 g each）， Bupleuri Radix and Platycodonis Radix （8.26 g each）. These medicines were grounded to fine powder. One dose， including 20.65 g of the powder， was mixed with 600 mL of water and decocted to 300 mL. After abandoning slag， the medicine should be taken warm frequently. In the formula， Bombyx Batryticatus is stir-fired. With the effect of dispersing wind and clearing heat， removing stagnation and dissipating mass， the formula is specialized in swollen-head epidemic， pestilence， red and swelling head， face， and neck， dry mouth and tongue， as well as other diseases resulting from toxic heat stagnated in the upper jiao. The formula is widely used in treating diseases involving the respiratory， dermal， ophthalmologic， otolaryngologic， and nervous systems. The formula is most frequently used for respiratory diseases， with a wide range of symptoms including parotitis/mumps （66 times）， followed by tonsillitis （28 times）. In conclusion， the broadly applied formula has accurate efficacy and great development value.

Puji Xiaoduyin， a specialized formula for the swollen-head epidemic， was recorded in the Catalogue of Ancient Classical Formula （the Second Batch）-Han Medicine， published in September 2023. It had been inherited and developed by medical experts of successive generations and passed down to this day. This paper sorted out the historical evolution of this formula using bibliometric methods. It also comprehensively analyzed key information on the formula name， historical origin， drug dosage， herb origin， processing methods， decocting methods， function， and clinical applications. Additionally， this paper analyzed the application of this formula in both modern and ancient times. Results showed that the formula was first recorded as "Puji Xiaodu Yinzi" in LI Dongyuan's Proven Formulas written by LI Gao from the Jin dynasty. The medicinal composition and dosage were： Scutellariae Radix and Coptidis Rhizoma （20.65 g each）， Ginseng Radix et Rhizoma 12.39 g， Scrophulariae Radix， Citri Reticulatae Pericarpium， and Glycyrrhizae Radix et Rhizoma （8.26 g each）， Forsythiae Fructus， Arctii Fructus， Isatidis Radix， and Lasiosphaera Calvatia （4.13 g each）， Bombyx Batryticatus and Cimicifugae Rhizoma （2.891 g each）， Bupleuri Radix and Platycodonis Radix （8.26 g each）. These medicines were grounded to fine powder. One dose， including 20.65 g of the powder， was mixed with 600 mL of water and decocted to 300 mL. After abandoning slag， the medicine should be taken warm frequently. In the formula， Bombyx Batryticatus is stir-fired. With the effect of dispersing wind and clearing heat， removing stagnation and dissipating mass， the formula is specialized in swollen-head epidemic， pestilence， red and swelling head， face， and neck， dry mouth and tongue， as well as other diseases resulting from toxic heat stagnated in the upper jiao. The formula is widely used in treating diseases involving the respiratory， dermal， ophthalmologic， otolaryngologic， and nervous systems. The formula is most frequently used for respiratory diseases， with a wide range of symptoms including parotitis/mumps （66 times）， followed by tonsillitis （28 times）. In conclusion， the broadly applied formula has accurate efficacy and great development value.

Objective: To evaluate the operational efficiency of a single-center platelet genotype database in HLA genotype-matched platelet search and applcation, and to compare the efficiency among different matching strategies, hospitals, and between first-time versus repeat application modes. Methods: Data on platelet genotype-based matching applications from December 1, 2025, to May 31, 2026, at our center were collected. Four time intervals were defined according to the workflow: the time from clinical hospital application to blood center receipt confirmation (Δt ); the time from blood center confirmation to completion of platelet gene database search (Δt ); the time from completion of database searching to availability of compatible platelet products (Δt ); and the time from clinical hospital application to availability of compatible platelet products (Δt ). Applications were classified as first-time or repeat based on application history, and as speed-priority matching strategy or classical matching strategy based on matching approach, with efficiency differences compared across the groups. Results: A total of 1 051 valid matching applications were included. The median values of Δt , Δt , Δt , and Δt were 6.2 h, 0.1 h, 0.2 h, and 11.5 h, respectively. Overall, 55.9% of genotype-based matches resulted in compatible platelets being available on the same day. The median Δt of the speed-priority strategy was significantly shorter than that of the classical strategy (5.2 h vs 39.6 h, P<0.001). Median Δt differed significantly among hospitals (P<0.001), with the shortest being 4.4 h. The median Δt for repeat applications was 6.9 h, significantly shorter than that for first-time applications (27.7 h, P<0.001). Conclusion: The platelet gene database demonstrates sufficient efficiency in HLA genotype-matched platelet searching and application to meet clinical demands. Optimizing matching strategies and hospital application workflows may shorten the time for obtaining compatible platelets.

Objective: To deeply explore the systemic management dilemmas affecting patients with chronic periodontitis in underdeveloped regions, providing practical pathways for achieving oral health equity. Methods: This study has been reviewed and approved by the Medical Ethics Committee, and written informed consent was obtained from the participants. Based on a comprehensive design integrating literature review and theory, an interview guide was developed. Using purposive sampling, semi-structured interviews were conducted with 20 patients diagnosed with chronic periodontitis who were from underdeveloped regions and attended the Stomatological Hospital of Southern Medical University between November 2025 and February 2026. The sample size was determined by data saturation. Data analysis employed Colaizzi’s seven-step method. Results: Through interview with 20 participants, three core themes were extracted, encompassing eight sub-themes: individual cognitive-behavioral dilemmas (cognitive limitations and passive coping, inefficient and superficial self-management, and economic and psychological barriers to seeking care); systemic and environmental structural obstacles (distrust in primary healthcare capabilities, and the limited buffering effect and constraints of medical insurance); and the need for health empowerment and support systems (authoritative knowledge and management skill guidance, aspirations for access to high-quality specialized medical resources, and sustained and reminder-based remote support). Conclusion Patients with chronic periodontitis in underdeveloped regions face a multidimensional dilemma composed of limited health literacy, poor adherence to health behaviors, weak primary care service capacity, uneven medical insurance coverage, and insufficient high-quality specialized medical resources. Patients’ health literacy should be advanced through innovative health education, primary care capacity should be strengthened for periodontal disease prevention and treatment, and it is recommended to prioritize the inclusion of initial periodontal therapy in outpatient coordination or chronic disease management, and a remote medical support system based on digital technology should be established.

ObjectiveTo investigate the molecular mechanisms by which the receptor for advanced glycation end products（RAGE）-signal transducer and activator of transcription 3（STAT3） signaling pathway mediates mitochondrial injury in striosome/matrix compartment neurons under dopaminergic depletion in Parkinson's disease （PD）. MethodsA 6-hydroxydopamine （6-OHDA）-induced rat model of PD was established and treated with the RAGE inhibitor FPS-ZM1. Immunohistochemistry， double immunofluorescence staining， transmission electron microscopy （TEM）， Western blotting， and quantitative real-time PCR （qRT-PCR） were performed to evaluate RAGE and STAT3 expression as well as mitochondrial ultrastructure alterations in the striosome/matrix compartment. ResultsThe density of RAGE-positive structures and the protein expression level of RAGE in the striosome/matrix compartment were significantly increased in PD rats compared with controls （P<0.05）. Immunohistochemical and double immunofluorescence analyses demonstrated widespread STAT3 expression in striatal neurons， while the number of NeuN/STAT3 double-positive cells was significantly elevated in the PD group （P<0.05）. Western blotting and qRT-PCR further confirmed significant upregulation of STAT3 protein and mRNA expression in PD rats （P<0.05）. TEM analysis revealed marked mitochondrial abnormalities in PD neurons， including reduced mitochondrial density， enlarged mitochondrial area， decreased cristae number， cristae membrane disruption， and outer membrane damage （all P<0.05）. Notably， FPS-ZM1 treatment partially reversed these mitochondrial ultrastructural alterations. ConclusionActivation of the RAGE-STAT3 signaling pathway contributes to mitochondrial structural disruption in striosome/matrix compartment neurons in PD. These findings suggest that the striosome/matrix compartment may represent a novel pathological target for investigating mitochondrial dysfunction and neurodegeneration in PD.

Facing the requirements of promoting the healthy China initiative and improving people's health, the "bone health program" was proposed in 2024. In-depth development of a traditional Chinese medicine(TCM) prevention and control system is of strategic significance to the implementation of the "bone health program". Focusing on osteoporosis(OP), a representative disease affecting people's bone health, this paper concludes that accelerating the research on the prevention and control of OP by TCM is conducive to enhancing the knowledge and awareness of OP among the public, and it is beneficial to revealing the evolutionary pattern of OP and improving the understanding and management of this disease. Additionally, it can provide an overall framework for and strengthen the systematicity and completeness of the research on the prevention and treatment of OP by TCM. Meanwhile, it can help to explore new research paradigms and optimize the existing research model, so as to promote innovative breakthroughs in the prevention and treatment of bone health-related diseases by TCM. Under the overall layout of the "bone health program", importance should be attached to the early prevention and the innovation of very early diagnosis and intervention of OP. Emphasis should be put on the discovery of the target network of disease and treatment mechanism for revealing the core pathogenesis of OP and the therapeutic mechanism of TCM. In addition to local lesions of the bone and its clinical outcomes, attention should be paid to the development of multiple metabolic complications. The fusion of advanced interdisciplinary technologies should be promoted for OP and its complications, and thus a research and development system based on clinical application scenarios and driven by big data can be built. The measures above will facilitate the progress in the prevention and treatment of OP and other bone diseases by TCM and provide new momentum for enriching and deepening the research connotation of the "bone health program".
Osteoporosis/therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/therapeutic use* ; China ; Bone and Bones/drug effects*

This study aimed to compare the ameliorative effects of Lycii Fructus and Chrysanthemi Flos at different ratios on retinal damage in mice and to elucidate the underlying mechanisms. A retinal injury model was established by intraperitoneal injection of sodium iodate(NaIO_3) solution. The mice were divided into the following groups: blank group, model group, positive drug(AREDS 2) group, low-and high-dose groups of Lycii Fructus and Chrysanthemi Flos at 1∶1, low-and high-dose groups at 3∶1, and low-and high-dose groups at 1∶3. Administration was carried out 15 days after modeling. The visual acuity of the mice was assessed using the black-and-white box test. The fundus was observed using an optical coherence tomography device, and retinal thickness was measured. HE staining was used to observe the morphology and pathological changes of the retina. The levels of oxidative factors in serum and ocular tissues were measured using assay kits. The levels of inflammatory factors in serum and ocular tissues were detected by enzyme-linked immunosorbent assay(ELISA), and the expression of Nrf2, HO-1, and NF-κB proteins in ocular tissues was analyzed by Western blot. The results showed that after administration of Lycii Fructus and Chrysanthemi Flos at different ratios, the model group showed improved retinal thinning and disordered arrangement of retinal layers, elevated content of SOD and GSH in the serum and ocular tissues, and reduced levels of MDA, TNF-α, IL-1β, and IL-6. Lycii Fructus and Chrysanthemi Flos at 1∶1 and 1∶3 showed better improvement effects. The combination significantly upregulated the expression levels of Nrf2 and HO-1 and downregulated the expression of NF-κB p65. These results indicate that Lycii Fructus and Chrysanthemi Flos at different ratios can improve retinal damage, reduce oxidative stress, and alleviate inflammation in both the body and ocular tissues of mice. The mechanism may be related to the regulation of the Nrf2/HO-1 and NF-κB signaling pathways in ocular tissues. These findings provide a theoretical basis for the clinical application of Lycii Fructus and Chrysanthemi Flos in the treatment of dry age-related macular degeneration.
Animals ; Mice ; Retina/injuries* ; Male ; Lycium/chemistry* ; Drugs, Chinese Herbal/administration & dosage* ; Chrysanthemum/chemistry* ; NF-kappa B/genetics* ; Humans ; Retinal Diseases/metabolism* ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress/drug effects* ; Flowers/chemistry* ; Heme Oxygenase-1/genetics*

Objective To analyze the differences in bone serum protein between patients with osteoporosis accompanied by obstructive sleep apnea syndrome(OSAS)and those with osteoporosis only using proteomics.Methods A total of 80 osteoporosis patients who attended our hospital between June 2022 and June 2024 were enrolled.Based on their polysomnography results,the participants were divided into an OSAS and osteoporosis comorbidity(OSAS-osteoporosis)group(n=42)and an osteoporosis only group(n=38).Propensity score matching was applied to incorporate covariates in logistic regression so that the individual characteristics of the two groups of patients were generally balanced.Following the matching procedure,a final cohort of 20 matched pairs was obtained and subsequently utilized for further analysis.The mass spectrum was obtained using laser desorption ionization mass spectrometry.Principal component analysis(PCA)was performed to assess differences in metabolic patterns between groups.Partial least squares discriminant analysis(PLS-DA)and orthogonal PLS-DA(OPLS-DA)were employed for further data analysis.Variable importance in projection(VIP)scores of each substance were calculated with OPLS-DA to screen the metabolites showing inter-group differences.Heatmaps were generated to visualize metabolic profile differences between the OSAS-osteoporosis group and the osteoporosis group.Enrichment pathway analysis was conducted on the differential identified metabolites.Results After propensity score matching,individual characteristics between the groups were well balanced.Mass spectrometry revealed significant differences between the OSAS-osteoporosis and osteoporosis groups.In the PCA score plot,the separation trend of the two groups was not significant.The PLS-DA score plot showed a discernible separation trend,with R2 and Q2 lower than those of the corresponding results of the real model,confirming the reliability of the model.OPLS-DA showed that the total R2X of the model was 0.635,R2Y was 0.879,and O2Y was 0.728,showing obvious separation trends between the two groups.A total of 16 differential metabolites were identified,including stearyl-oleyl-glycerol phosphate choline,phosphate choline,L-histidine,erucamide,2'-deoxyuridine,1-palmitoyl glycerol,thymine,tyramine,L-pyroglutamic acid,L-glutamic acid,myristate,glycerol-3-phosphate,caprylic acid,pregnenolone,L-arginine,D-4-hydroxyphenylglycine,and isobutyric acid.Heatmaps showed significant differences in metabolic profiles between the OSAS-osteoporosis group and the osteoporosis group.Pathway enrichment analysis showed that 27 metabolic pathways were involved.27 metabolic pathways.Under the conditions of P<0.05 and pathway impact>0.2,the three most significant metabolic pathways identified included mainly alanine,aspartate,and glutamate metabolism,arginine biosynthesis,and histidine metabolism.Conclusion Significant differences were observed in the metabolic profiles between patients with both OSAS and osteoporosis and those with osteoporosis alone.

Objective To explore the construction of α-1,3-galactosyltransferase (GGTA1) gene-knockout (GTKO) Diannan miniature pigs and the kidney xenotransplantation from pigs to rhesus macaques, and to assess the effectiveness of GTKO pigs. Methods The GTKO Diannan miniature pigs were constructed using the CRISPR/Cas9 gene-editing system and somatic cell cloning technology. The phenotype of GTKO pigs was verified through polymerase chain reaction, Sanger sequencing and immunofluorescence staining. Flow cytometry was used to detect antigen-antibody (IgM) binding and complement-dependent cytotoxicity. Kidney xenotransplantation was performed from GTKO pigs to rhesus macaques. The humoral immunity, cellular immunity, coagulation and physiological indicators of the recipient monkeys were monitored. The function and pathological changes of the transplanted kidneys were analyzed using ultrasonography, hematoxylin-eosin staining, immunohistochemical staining and immunofluorescence staining. Results Single-guide RNA (sgRNA) targeting exon 4 of the GGTA1 gene in Diannan miniature pigs was designed. The pGL3-GGTA1-sgRNA1-GFP vector was transfected into fetal fibroblasts of Diannan miniature pigs. After puromycin selection, two cell clones, C59# and C89#, were identified as GGTA1 gene-knockout clones. These clones were expanded to form cell lines, which were used as donor cells for somatic cell nuclear transfer. The reconstructed embryos were transferred into the oviducts of trihybrid surrogate sows, resulting in 13 fetal pigs. Among them, fetuses F04 and F11 exhibited biallelic mutations in the GGTA1 gene, and F04 had a normal karyotype. Using this GTKO fetal pig for recloning and transferring the reconstructed embryos into the oviducts of trihybrid surrogate sows, seven surviving piglets were obtained, all of which did not express α-Gal epitope. The binding of IgM from the serum of rhesus monkey 20# to GTKO pig PBMC was reduced, and the survival rate of GTKO pig PBMC in the complement-dependent cytotoxicity assay was higher than that of wild-type pig. GTKO pig kidneys were harvested and perfused until completely white. After the left kidney of the recipient monkey was removed, the pig kidney was heterotopically transplanted. Following vascular anastomosis and blood flow restoration, the pig kidney rapidly turned pink without hyperacute rejection (HAR). Urine appeared in the ureter 6 minutes later, indicating successful kidney transplantation. The right kidney of the recipient was then removed. Seven days after transplantation, the transplanted kidney had good blood flow, the recipient monkey's serum creatinine level was stable, and serum potassium and cystatin C levels were effectively controlled, although they increased 10 days after transplantation. Seven days after transplantation, the levels of white blood cells, lymphocytes, monocytes and eosinophils in the recipient monkey increased, while platelet count and fibrinogen levels decreased. The activated partial thromboplastin time, thrombin time and prothrombin time remained relatively stable but later showed an upward trend. The recipient monkey survived for 10 days. At autopsy, the transplanted kidney was found to be congested, swollen and necrotic, with a small amount of IgG deposition in the renal tissue, and a large amount of IgM, complement C3c and C4d deposition, as well as CD68⁺ macrophage infiltration. Conclusions The kidneys of GTKO Diannan miniature pigs may maintain normal renal function for a certain period in rhesus macaques and effectively overcome HAR, confirming the effectiveness of GTKO pigs for xenotransplantation.