AIM:To investigate the therapeutic effects of bone marrow mesenchymal stem cell-derived exosomes(BMSC-Exos)on diabetic retinopathy(DR)in rats, with a focus on their ability to modulate oxidative stress and inflammatory responses through the TLR4/NF-κB signaling pathway.METHODS:Streptozotocin(STZ)-induced diabetic Sprague-Dawley(SD)rats were randomly divided into four groups: Group 1 [normal+phosphate-buffered saline(PBS)], Group 2(normal+Exos), Group 3(DR+PBS), and Group 4(DR+Exos). At the 8th week after modeling, BMSC-Exos or PBS were injected intravitreally. Retinal tissues were collected at the 16th week for histological analysis [hematoxylin and eosin(HE)staining], apoptosis detection(TUNEL). Oxidative stress markers [8-OHdG, superoxide dismutase(SOD), and glutathione(GSH)] were assessed, and inflammatory cytokines [enzyme-linked immunosorbent assay(ELISA)for interleukin(IL)-6 and tumor necrosis factor-alpha(TNF-α)], and molecular profiling [quantitative polymerase chain reaction(qPCR)for TLR4, NF-κB, and VEGF] were measured.RESULTS:The BMSC-Exos treatment significantly suppressed the activation of the TLR4/NF-κB pathway in DR rats(P<0.01), which was accompanied by reduced retinal vascular leakage(Evans blue assay, P<0.001), decreased apoptosis(TUNEL, P<0.05), and attenuated oxidative stress(elevated SOD and GSH, reduced 8-OHdG, P<0.05). The levels of inflammatory cytokines(IL-6 and TNF-α)were markedly decreased(P<0.01).CONCLUSION:BMSC-Exos alleviate DR by suppressing the TLR4/NF-κB axis, thus reducing oxidative damage, inflammation, and microvascular dysfunction. This research offers a novel therapeutic approach for early-stage DR.

Cremastrae Pseudobulbus Pleiones Pseudobulbus is a Chinese medicinal material used for clearing heat， detoxicifying， resolving phlegm， and dissipating nodules. It is derived from Cremastra appendiculata， Pleione bulbocodioides， or Pleione yunnanensis， as recorded in the 2025 edition of the Pharmacopoeia of the People′s Republic of China， with the former known as Maocigu and the latter two known as Bingqiuzi. Current antitumor studies mainly focus on polysaccharides， water-extracted alcohol-precipitated fractions， and purified extracts of C. appendiculata. Structurally characterized glucomannans suppress breast and liver tumor xenografts and exhibit immunomodulatory effects. The water-extracted alcohol-precipitated fractions inhibit tumor angiogenesis in hepatoma-bearing mice. A purified C. appendiculata extract standardized to five phenanthrene and bibenzyl constituents induces mitochondrial apoptosis in hepatocellular carcinoma cells. Reported pharmacological effects involve cell-cycle regulation， apoptosis， epithelial-mesenchymal transition， angiogenesis， autophagy， and the tumor immune microenvironment， with phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR）， Wnt/β-catenin， and Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3） signaling pathways being the major mechanism links. Quality evaluation of Cremastrae Pseudobulbus Pleiones Pseudobulbus has progressed from single-marker assays to an integrated approach involving botanical authentication， chromatographic fingerprinting， multicomponent analysis， and evaluation of associations between blood-absorbed constituents and antitumor effects. Militarine and dactylorhin A can be used for botanical identification and batch evaluation， and in vivo exposure data from related orchids are concentrated on militarine. Quantitative associations between these constituents and antitumor effects remain to be established. Clinical evidence mainly focuses on formula-based applications and expert experience. Comparative antitumor data in hepatoma models are available for the commercial specifications of Maocigu and Bingqiuzi， whereas parallel evaluations of pharmacological effects， safety windows， and drug interactions among the three official botanical origins remain insufficient. The major limitations are the incomplete standardization of botanical origins and preparations and the lack of quantitative links among quality markers， systemic exposure， antitumor effects， and toxicity endpoints， which constrain reproducible pharmacological evaluation and clinical translation of Cremastrae Pseudobulbus/Pleiones Pseudobulbus.

Objective : To investigate the factors affecting the outcome of high-risk human papillomavirus ( HR- HPV) infection in patients with normal cervix examined by colposcopy in Hefei area and the relationship between persistent HR-HPV infection and cervical cytology． Methods : Data of colposcopy patients were collected from 478 HR-HPV infected patients with normal cervix through colposcopy．Their age，number of sexual partners，contracep- tive methods and other relevant basic information were recorded．Vaginal interferon use，HR-HPV infection at year 1 and year 2，and cervical liquid-based cytology test ( LCT) results were tracked，univariate and multivariate ana- lyses were performed based on basic information，and ROC curves were plotted． Results : The HR-HPV clearance rate at 1 year was 59. 41% ，and the clearance rate at 2 years was 66. 75%．The other 12 types of infection ( 31， 33，35，39，45，51，52，56，58，59，66，68) were more common than the 16 and 18 types．Univariate and mult- ivariate analyses showed that age＞50 years，number of sexual partners ≥2，and history of cervical conectomy in- creased the risk of persistent HR-HPV infection ( χge = 21. 676，P ＜0. 001; χumber of sexual partners = 8. 262，P =0. 004; χistory of cervical conectomy = 11. 267，P = 0. 001 ) ． The risk of HR-HPV infection was significantly lower when condom or vaginal interferon was used ( χondom use = 10. 885，P = 0. 001; χnterferon use = 4. 099，P = 0. 043) ．The area under the ROC curve (AUC) of combined diagnosis of HR-HPV persistent infection was higher than that of single diagnosis，and the AUC of combined diagnosis was 0. 737．Persistent HR-HPV infection was an independent risk factor for abnormal LCT，and the AUC predicted by the model was 0. 755．No cancer was found in patients with persistent HR-HPV infection for 2 years，and the proportion of abnormal LCT was higher than that in patients with negative HR-HPV．The difference was statistically significant ( χ2 = 39. 64，P＜0. 001) ． Conclusion The combined ROC model constructed for patients＞50 years old，with multiple sexual partners，history of cervical surgery， no vaginal interferon use，and no condom use has certain value in predicting persistent HR-HPV infection，and per- sistent HR-HPV infection has predictive value in predicting LCT abnormalities．

Traditional Chinese medicine (TCM) is characterized by complex, multicomponent herbal formulations that challenge the conventional“one drug, one target” paradigm. Network pharmacology, through the construction of multilayered drug-target-disease networks, provides a systematic framework for unraveling TCM’s multitarget and multipathway mechanisms. Recent advancements in artificial intelligence, particularly large language models (LLMs), further enhance data integration, target identification, and clinical decision-making. This review synthesizes current progress in the application of network pharmacology and LLMs in TCM, highlighting their potential to deepen mechanistic insights and optimize drug discovery. By bridging traditional medical wisdom with modern computational tools, this integrative approach aims to advance the scientific validation of TCM and foster innovative healthcare solutions.

Objective:To evaluate the impact of donor characteristics on the prognosis of myelodysplastic syndrome (MDS) patients undergoing haplo-identical transplantation (HIDT) .Methods:A retrospective analysis of 203 MDS patients who received HIDT was conducted to evaluate how donor factors influenced transplant outcomes.Results:In MDS patients undergoing haploidentical transplantation, donors over 50 years were associated with higher EBV reactivation (2-year cumulative incidence 42.9% vs 22.0% for <50 years old; P=0.010). Female donors were linked to increased severe chronic GVHD compared with male donors (2-year incidence 11.9% vs 4.0% ; P=0.017). Additionally, 2-year overall survival (OS) was slightly lower with female donors than male donors (56.6% vs 69.7% ), but the difference was not statistically significant ( P=0.073). Donor-recipient blood type did not affect post-transplant OS or cumulative relapse rates. Donor-recipient kinship analysis revealed that child donors, compared to haploidentical sibling or parent donors, had lower rates of grade Ⅱ–Ⅳ acute GVHD (27.2% vs 45.7% vs 53.5%, P=0.007) and 2-year EBV reactivation (13.9% vs 29.3% vs 38.9%, P=0.001). For donors under 20 years, donor gender did not significantly affect 2-year OS ( P=0.913), relapse-free survival ( P=0.716), or 100-day incidence of grade Ⅱ–Ⅳ acute GVHD ( P=0.359) . Conclusion:For MDS patients undergoing HIDT, donors over 50 should be avoided. Male and child donors are preferred, while donor gender does not significantly affect outcomes if the donor is under 20 years old.

Objective To explore the potential role and underlying mechanism of the functionally uncharacterized gene Gm49394 on regulating β-cell apoptosis under diabetic conditions.Methods The expression and translational activity of Gm49394 in pancreatic β-cell lines and non-β-cell lines were validated using RNA fluorescence in situ hybridization(RNA-FISH),quantitative real-time PCR(qPCR),Western blotting,and immunofluorescence(IF)assay.The β-cell lines(NIT-1/Min6)with Gm49394 overexpression or knockdown were constructed.The proliferation,apoptosis,mitochondrial function,as well as oxidative stress and endoplasmic reticulum stress markers in these β-cell lines under physiological homeostasis or pathological stress conditions,such as high glucose(30 mmol/L),inflammation(10 ng/mL IFN-γ alone or combined with 10 ng/mL IL-6),and hydrogen peroxide(100 μmol/L H2O2)were detected by flow cytometry and Western blotting.Results RNA-FISH and qPCR indicated that Gm49394 was specifically expressed in pancreatic β-cell lines and up-regulated under high glucose or inflammatory stimulation.IF assay and Western blotting showed that Gm49394 had protein-coding activity.Flow cytometry and Western blotting identified that Gm49394 overexpression did not affect β-cell proliferation,but promoted β-cell apoptosis and increased reactive oxygen species(ROS)and mitochondrial superoxide(MitoSOX)levels in β cells under physiological homeostasis or pathological stress conditions(P<0.05).Under physiological conditions,Gm49394 knockdown failed to induce significant alterations on β-cell apoptosis,ROS,or MitoSOX levels.Under pathological stress conditions,Gm49394 knockdown significantly suppressed β-cell proliferation,apoptosis,as well as oxidative and endoplasmic reticulum stress(P<0.05).Conclusion Gm49394 may promote β-cell apoptosis via oxidative stress and endoplasmic reticulum stress.

By combining the origin and research progress of the combination of disease and syndrome, the core pathogenesis, this article explored the research ideas and methods of the core pathogenesis of TCM. It is found that modern TCM is mostly guided by the idea of classification-staging-syndrome differentiation, the main prescription of the main disease, the special prescription of the special disease, and the idea of "dynamic-fixed sequential". The tongue image syndrome differentiation method, clustering analysis method, drug test syndrome method, compound pathogenesis method, "evidence-based pathogenesis-syndrome treatment system" research model, and the integration of traditional Chinese and Western medicine theory were used to explore the core pathogenesis of TCM under the condition of disease. Combined with the advantages of modern medical disease differentiation and TCM syndrome differentiation, the individualized diagnosis and treatment methods of integrated traditional Chinese and Western medicine have been continuously improved, in order to solve the stage contradictions of different clinical stages, effectively delay the progression of the disease and improve the prognosis of the disease.

Approximately 20% to 30% of the global workforce is engaged in shift work. As a significant cause of circadian disruption, shift work is closely associated with an increased risk for periodontitis. Nevertheless, how shift work-related circadian disruption functions in periodontitis remains unknown. Herein, we employed a simulated shift work model constructed by controlling the environmental light-dark cycles and revealed that shift work-related circadian disruption exacerbated the progression of experimental periodontitis. RNA sequencing and in vitro experiments indicated that downregulation of the core circadian protein brain and muscle ARNT-like protein 1 (BMAL1) and activation of the Gasdermin D (GSDMD)-mediated pyroptosis were involved in the pathogenesis of that. Mechanically, BMAL1 regulated GSDMD-mediated pyroptosis by suppressing NOD-like receptor protein 3 (NLRP3) inflammasome signaling through modulating nuclear receptor subfamily 1 group D member 1 (NR1D1), and inhibiting Gsdmd transcription via directly binding to the E-box elements in its promoter. GSDMD-mediated pyroptosis accelerated periodontitis progression, whereas downregulated BMAL1 under circadian disruption further aggravated periodontal destruction by increasing GSDMD activity. And restoring the level of BMAL1 by circadian recovery and SR8278 injection alleviated simulated shift work-exacerbated periodontitis via lessening GSDMD-mediated pyroptosis. These findings provide new evidence and potential interventional targets for circadian disruption-accelerated periodontitis.
Pyroptosis/physiology* ; ARNTL Transcription Factors/metabolism* ; Animals ; Periodontitis/etiology* ; Mice ; Phosphate-Binding Proteins/metabolism* ; Shift Work Schedule/adverse effects* ; Intracellular Signaling Peptides and Proteins/metabolism* ; Mice, Inbred C57BL ; Male ; Disease Models, Animal ; Gasdermins