ObjectiveTo explore the mechanism by which the Shenfu Xiongze prescription regulates autophagy in rats with myocardial remodeling through the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsA rat model of myocardial remodeling induced by isoprenaline （ISO） was established. Rats were divided into the blank group，the model group，the low-，medium-， and high-dose groups of Shenfu Xiongze prescription，and the captopril group， 6 rats in each group. Except for the blank group，the rat model of myocardial remodeling was established in the other groups by intraperitoneal injection of 2.5 mg·kg^-1 ISO for 3 consecutive weeks. At the same time of modeling， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription were administered the corresponding doses of Shenfu Xiongze prescription solution （8.4，16.8，and 33.6 g·kg^-1），and the captopril group was administered captopril solution （25 mg·kg^-1）. As for the blank group and the model group， the same volume of normal saline was given. The treatment was continued for 3 weeks. Echocardiography was used to observe the cardiac structure and function，and the heart weight index was detected. Masson staining and hematoxylin-eosin （HE） staining were used to observe the pathological morphology changes of myocardial tissue. The levels of interleukin-6 （IL-6） and B-type natriuretic peptide （BNP） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of type Ⅰ collagen （Collagen Ⅰ），type Ⅲ collagen （Collagen Ⅲ），and microtubule-associated protein 1 light chain 3 （LC3） proteins in myocardial tissue was determined by immunohistochemistry. Autophagy was observed by transmission electron microscopy. The mRNA expression of Collagen Ⅰ，Collagen Ⅲ，α-smooth muscle actin （α-SMA），LC3，yeast Atg6 homolog protein （Beclin-1），AMPK，and mTOR in myocardial tissue was detected by quantitative real-time polymerase chain reaction （real-time PCR）. The protein expression of Collagen Ⅰ，α-SMA，transforming growth factor-β₁ （TGF-β₁），LC3，Beclin-1，p62， phosphorylation（p）-AMPK，p-mTOR，AMPK，and mTOR was detected by Western blot. ResultsCompared with the normal group，rats in the model group exhibited significantly decreased values of ejection fraction （EF） and left ventricular fractional shortening （FS） （P<0.01）， significantly increased values of left ventricular end-diastolic diameter （LVIDd） and left ventricular end-systolic diameter （LVIDs） （P<0.01）. Additionally， the model group also showed increased degrees of inflammatory infiltration and fibrosis of myocardial tissue， significantly elevated levels of serum IL-6 and BNP （P<0.01）， significantly increased mRNA and protein levels of Collagen Ⅰ，Collagen Ⅲ，α-SMA，and mTOR （P<0.01），and markedly decreased mRNA and protein levels of LC3，Beclin-1，and AMPK （P<0.05，P<0.01）. Compared with the model group， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription presented significantly elevated EF and FS values （P<0.01） and lowered LVIDd and LVIDs （P<0.05）. In these groups， the inflammation and fibrosis were alleviated significantly. They also exhibited decreased serum levels of IL-6 and BNP （P<0.01）， significantly reduced protein expression of Collagen Ⅰ， α-SMA， TGF-β₁， p62， and p-mTOR （P<0.01）， significantly decreased mRNA expression of Collagen Ⅰ， Collagen Ⅲ， α-SMA， and mTOR （P<0.01）， and significantly increased mRNA and protein levels of LC3， Beclin-1， and AMPK （P<0.05，P<0.01）. ConclusionThe Shenfu Xiongze prescription can improve the myocardial remodeling induced by ISO in rats by regulating the autophagy level，enhance cardiac function，and reduce inflammatory and fibrotic levels. This effect may be achieved through the AMPK/mTOR signaling pathway.

Objective: To explore whether the long-term and frequent use of citrate anticoagulants negatively affects the bone metabolism balance of female frequent plateletpheresis donors, so as to better protect their health. Methods: A total of 65 female plateletpheresis donors and 55 female whole-blood donors from Guangzhou Blood Center (May to December 2024) were enrolled as experimental and control groups respectively, stratified into age subgroups (18-39 years and 40-60 years). Serum levels of 25-hydroxyvitamin D [25(OH)D], procollagen type I N-terminal propeptide (PINP), osteocalcin (OC), and type I collagen carboxy-terminal telopeptide (CTX) were measured. Differences in bone metabolism markers between experimental and control groups across age subgroups were compared. ANOVA was used to analyze dose-response relationships between donation age, annual apheresis donation frequency, and biochemical indicators. Results: In the 40-60 age subgroup, 25(OH)D levels were significantly lower in the experimental group (P<0.05), exhibiting a linear increase with age and a linear decrease with annual donation frequency. No significant differences in CTX or PINP levels were observed between experimental and control groups in either age subgroup. Conclusion: High-frequency plateletpheresis donation does not disrupt bone metabolic balance in female donors. However, it is associated with reduced vitamin D levels in female donors aged >40 years, potentially increasing the risk of osteoporosis. Vitamin D supplementation is recommended for high-frequency female plateletpheresis donors in this age group.

OBJECTIVE: To develop a user-friendly visualization application for the automatic annotation of Human Phenotype Ontology (HPO) terms based on large language models and retrieval-augmented generation (RAG) technology, and to validate its performance in an authoritative case dataset. METHODS: By integrating the domestic open-source large language model DeepSeek-V3 with RAG technology, an interactive web application was deployed on the Streamlit cloud platform. Using only the latest official HPO dataset as the data source, the lightweight sentence-embedding model BAAI/bge-small-en-v1.5 was employed to construct a FAISS vector index. During the online phase, a four-step closed-loop process is automatically completed: multilingual translation, phenotype phrase extraction, RAG candidate retrieval, term mapping, and official database validation. 121 English case reports publicly released by BMJ Case Reports and Oxford Medical Case Reports (with a gold-standard HPO set of 1 794 terms) were selected for application validation. Precision, recall, and F1 score were calculated and compared horizontally with traditional dictionary tools, standalone large language models, and the similar application "RAG-HPO". Finally, replace the model with the more advanced ChatGPT-5 and evaluate its performance on the newly extracted dataset. RESULTS: An HPO term automatic annotation visualization application named PhenoRAG, based on large language models and RAG technology, was successfully developed. Users can access it directly via a web link. Across the 112 cases, a total of 2 150 HPO terms were generated; 2,064 (96.0%) were fully validated by the official database, with a hallucination rate of 1.3% and an HPO ID-name mismatch rate of 2.7%. After deduplication, 1,906 terms remained for testing. The overall precision was 63.65%, recall was 67.34%, and F1 was 65.44%, significantly outperforming traditional annotation tools (F1: 0.45-0.49, P < 0.001). Although PhenoRAG's F1 was lower than that of RAG-HPO (F1 = 0.78, P < 0.001), which relies on a manually constructed synonym database of 54 000 entries plus the HPO dataset, it requires no additional dictionary maintenance and can be used without any background in computer programming. Moreover, after switching to the GPT-5 model, PhenoRAG exhibited no hallucination rate on the new dataset, and its F1 score significantly increased (P = 0.038). CONCLUSION Without constructing a synonym database, the PhenoRAG achieved high-accuracy automatic mapping from clinical text to standard HPO terms. It features a low usage threshold, free access, and a Chinese-language interface, and can directly serve rare disease diagnosis, genetic counseling, and research scenarios in China and worldwide, warranting further clinical promotion and multicenter validation.
Humans ; Phenotype ; Biological Ontologies ; Language ; Software ; Large Language Models

OBJECTIVE To investigate the mechanism by which Shenfukang capsule （SFK） ameliorates renal interstitial fibrosis （RIF） by regulating macrophage-fibroblast crosstalk via the signal transducer and activator of transcription 3 （STAT3）/Yes-associated protein （YAP） pathway. METHODS RAW264.7 macrophages were induced to polarize with transforming growth factor-β 1 （TGF-β 1 ）. Subsequently， a non-contact co-culture system of macrophages with renal fibroblasts NRK-49F， as well as a non-contact co-culture system of macrophages with YAP-knockdown renal fibroblasts， were established. Cells were treated with low， medium， and high concentrations （4， 8， 16 μg/mL） of SFK， as well as a STAT3 inhibitor （STAT3-I，1.64 μg/mL） and losartan potassium tablets （positive control， 0.28 μg/mL）， for 48 h. After intervention， the protein and mRNA expression levels of CD86， CD163， and STAT3 in macrophages， as well as CD86， F4/80， and STAT3 mRNA， were detected. In co-cultured renal fibroblasts， the protein and mRNA expression levels of α -smooth muscle actin （ α -SMA）， Vimentin， collagen type Ⅰ （Col-Ⅰ）， matrix metalloproteinase-1 （MMP-1）， and YAP were detected. In co-cultured YAP-knockdown renal fibroblasts， the protein and mRNA expression levels of α -SMA， Vimentin， and MMP-1 were also detected. RESULTS Following TGF-β 1 induction， the protein expression levels of CD86， CD163， and STAT3， as well as the mRNA expression levels of CD86， F4/80， and STAT3 in macrophages were significantly increased （ P ＜0.05）. The conditioned medium from polarized macrophages activated renal fibroblasts， as evidenced by significantly increased protein and mRNA expression levels of α -SMA， Vimentin， Col-Ⅰ， and YAP， and significantly decreased protein and mRNA expression levels of MMP-1 in renal fibroblasts （ P ＜0.05）. Treatment with SFK and STAT3-I reversed the changes in the above indicators， with the medium concentration SFK group showing stronge r effects on some indicators than the low and high concentration groups. In the non-contact co-culture experiment of macrophages and YAP-knockdown renal fibroblasts， there were no statistically significant differences in the protein and mRNA expression of α-SMA， Vimentin， and MMP-1 among the groups. CONCLUSIONS SFK can inhibit macrophage-renal fibroblast crosstalk by blocking the STAT3/YAP pathway， thereby delaying the progression of RIF.

ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.

Protein-protein interactions play an extremely important role in the biochemical functions of cells,and in-depth analysis of protein interactions is the key to understanding cellular life activities.In this study,we systematically mined the interacting proteins of Golgi protein 73(GP73)using classical immunoprecipitation combined with mass spectrometry,and sought to further analyze the molecular func-tion of GP73.Hepatocellular carcinoma cell line HepG2 was selected,and a stable cell line overexpress-ing GP73-3Flag was constructed using lentiviral infection technology.A total of 78 high-confidence GP73 interacting proteins were identified by immunoprecipitation coupled with mass spectrometry.Bioinformat-ics analyses suggested that GP73 interacted with nearly 40 cytosolic proteins and participated in the bio-logical processes of RNA transport,splicing,and translation.Further immunofluorescence and cytosolic protein isolation experiments confirmed the cytosolic localization of GP73 in a variety of tumor cells.Based on the 78 interacting proteins,we further screened protein interaction networks related to mRNA splicing and verified the existence of interactions between GP73 and seven proteins,including HNRN-PH3,SMN1,RBM14,andNCBP1,by co-immunoprecipitation experiments.In addition,minigene spli-cing assay results indicated that GP73 inhibited the splicing efficiency of pre-mRNA by cells.This study contributes to the expansion of knowledge regarding the function of GP73 and aids in elucidating its criti-cal role in cell biology and its potential association with diseases.

Objective To compare the effects of quadratus lumborum block at the lateral supra-arcuate ligament(QLB-LSAL)and erector spinae plane block(ESPB)on early postoperative recovery in patients undergoing posterior lumbar surgery.Methods Ninety-three patients,aged 25～70 years,BMI 18～30 kg/m2 and ASA physical status Ⅱ or Ⅲ and scheduled for posterior lumbar surgery,were randomly divided into QLB-LSAL combined with general anesthesia(Group Q),ESPB combined with general anesthesia(Group E),and general anesthesia alone(Group N).Postoperatively,all groups received patient-controlled intravenous analgesia(PCIA).The following parameters were recorded:the scores of Richmond Agitation-Sedation Scale(RASS)and Bergman Comfort Scale(BCS)at awakening,6 h,12 h,and 24 h postoperatively;Likert scale score at PCIA cessation;the scores of Pittsburgh Sleep Quality Index(PSQI)and Early Postoperative Quality of Recovery-15(QoR-15)at 1 day preopera-(P<0.05).(2)Compared with Group N,group Q exhibited lower PSQI scores and higher QoR-15 scores at 1 and 3 days postoperatively(P<0.05).No statistically significant difference in PSQI scores was observed between group E and N(P>0.05),while group E had higher QoR-15 score than group N only at 1 day postoperatively(P<0.05).Both at 1 and 3 days postoperatively,group Q had lower PSQI scores and higher QoR-15 scores than group E(P<0.05).(3)Postoperative awakening time,extubation time,PACU stay time,time to first anal exhaust and time to first ambulation were significantly shorter in group Q than those in group N(P<0.05).Group E only showed shorter time to first anal exhaust compared to group N(P<0.05).Furthermore,group Q had a significantly shorter PACU stay time than group E(P<0.01).(4)There was no statistically significant difference in the incidence of adverse reactions among the three groups of patients.(P>0.05).Conclusions Both QLB-LSAL and ESPB effectively improve postoperative analgesia and early recovery quality.However,QLB-LSAL demonstrates advantages in enhancing patient comfort,analgesia satisfaction,sleep quality,and accelerating overall postoperative recovery.

Objective To compare the effects of quadratus lumborum block at the lateral supra-arcuate ligament(QLB-LSAL)and erector spinae plane block(ESPB)on early postoperative recovery in patients undergoing posterior lumbar surgery.Methods Ninety-three patients,aged 25～70 years,BMI 18～30 kg/m2 and ASA physical status Ⅱ or Ⅲ and scheduled for posterior lumbar surgery,were randomly divided into QLB-LSAL combined with general anesthesia(Group Q),ESPB combined with general anesthesia(Group E),and general anesthesia alone(Group N).Postoperatively,all groups received patient-controlled intravenous analgesia(PCIA).The following parameters were recorded:the scores of Richmond Agitation-Sedation Scale(RASS)and Bergman Comfort Scale(BCS)at awakening,6 h,12 h,and 24 h postoperatively;Likert scale score at PCIA cessation;the scores of Pittsburgh Sleep Quality Index(PSQI)and Early Postoperative Quality of Recovery-15(QoR-15)at 1 day preopera-(P<0.05).(2)Compared with Group N,group Q exhibited lower PSQI scores and higher QoR-15 scores at 1 and 3 days postoperatively(P<0.05).No statistically significant difference in PSQI scores was observed between group E and N(P>0.05),while group E had higher QoR-15 score than group N only at 1 day postoperatively(P<0.05).Both at 1 and 3 days postoperatively,group Q had lower PSQI scores and higher QoR-15 scores than group E(P<0.05).(3)Postoperative awakening time,extubation time,PACU stay time,time to first anal exhaust and time to first ambulation were significantly shorter in group Q than those in group N(P<0.05).Group E only showed shorter time to first anal exhaust compared to group N(P<0.05).Furthermore,group Q had a significantly shorter PACU stay time than group E(P<0.01).(4)There was no statistically significant difference in the incidence of adverse reactions among the three groups of patients.(P>0.05).Conclusions Both QLB-LSAL and ESPB effectively improve postoperative analgesia and early recovery quality.However,QLB-LSAL demonstrates advantages in enhancing patient comfort,analgesia satisfaction,sleep quality,and accelerating overall postoperative recovery.

Objective:To investigate the effects of traditional Chinese curve-correcting and rotation-reducing spinal manipulation on biomechanical parameters and factors influencing herniated disc resorption in lumbar disc herniation(LDH).Methods:A retrospective analysis of 51 LDH patients treated between January 2022 and May 2024 was conducted.Lumbosacral parameters(vertebral rotation angle[α],disc angle[β],sacral slope[SS],lumbar lordosis[LL])were measured via MRI before treatment and at final follow-up.Disc resorption was assessed using Michigan State University(MSU)classification.Multivariate logistic regression identified factors associated with resorption.Results:Post-treatment α angle significantly decreased(3.02°→1.86°,P=0.002),while SS(28.4°→30.0°,P＜0.001)and LL angles(31.0°→35.12°,P＜0.001)increased;Disc resorption occurred in 56.86％(29/51)of patients.Longer disease course(OR=0.79,95％CI:0.69-0.91)and disc calcification(OR=0.03,95％CI:0.00-0.25)were independent inhibitors of resorption(P＜0.001).Conclusion:Spinal manipulation restores lumbosacral biomechanics by reducing vertebral rotation and increasing lumbar curvature,with higher resorption rates in patients with short duration(≤6 months),non-calcified discs,and MSU type 2-3 herniations.

Objective To investigate the relationship between vertical laminar fracture(VLF)in thoracolumbar burst fractures and both neurological injury and dural tear.Methods A retrospective analysis was conducted on the clinical data and multi spiral computed tomography(MSCT)coronal images of 255 patients of thoracolumbar burst fractures.The patients were divided into three groups based on the presence of VLF[Ⅰ group(complete VLF group),Ⅱ group(partial VLF group),and Ⅲ group(normal lamina group)].Statistical analysis was performed using analysis of variance and Fisher's exact test to compare radiological parameters,inci-dence of dural tear,and neurological injury among the groups.Results The Ⅰ group showed significant differences in spinal canal sagittal diameter,pedicle distance,and spinal canal area compared with the other two groups(P<0.05).However,there was no sig-nificant difference in vertebral body compression rate between the Ⅰ group and the Ⅱ group(P>0.05).The Ⅰ group had the high-est incidence of severe neurological injury[American Spinal Injury Association(ASIA)impairment scale grades A and B]and dural tear(P<0.05).Conclusion The severity of VLF is closely related to dural tear and neurological injury.MSCT coronal images can clearly display the extent of VLF,providing an important basis for clinical evaluation and treatment plan.