Objective To investigate the role and potential mechanism of secreted phosphoprotein 1 (SPP1)⁺ macrophages in the formation of chronic renal allograft fibrosis. Methods The expression features of SPP1⁺ macrophages in renal allografts of chronic allograft dysfunction (CAD) patients were analyzed based on single-cell transcriptome data of renal tissues from patients with CAD. Transcription factor VIPER analysis and DoRothEA transcription factor activity analysis were performed on the single-cell transcriptome data. Renal tissue samples were collected from kidney transplant recipients, including the CAD group (n=5) and the non-renal allograft fibrosis group (CTL group, n=5). A mouse model of chronic allograft rejection was established and divided into the allogeneic kidney transplantation group (CAD group, n=3) and the syngeneic kidney transplantation group (SYN group, n=3). Hematoxylin-eosin staining was used to detect renal tissue injury in mice, and Masson staining was used to detect renal tissue fibrosis. Immunofluorescence staining was performed to detect SPP1 expression in renal tissues of transplant recipients and mouse renal allografts. Bone marrow-derived macrophages (BMDMs) were extracted from mice and subjected to hypoxia stimulation. The expression of hypoxia-inducible factor (HIF)-1α and SPP1 was detected by Western blot, and SPP1 expression was detected by flow cytometry. BMDMs were transfected with HIF-1α overexpression plasmid and HIF-1α small interfering RNA (siRNA) followed by hypoxia intervention, and the expression of HIF-1α and SPP1 was detected by Western blot. Mouse aortic endothelial cells (MAECs) were co-cultured with the supernatant of BMDMs, and the expression of endothelial-mesenchymal transition (EndMT)-related markers was detected by Western blot and immunofluorescence. Results Single-cell transcriptome analysis showed that the proportion of SPP1⁺ macrophages in renal allograft tissues was significantly higher in the CAD group than in the CTL group (P<0.05). The renal injury score and the percentage of interstitial fibrotic area in the CAD group were significantly higher than those in the SYN group (both P<0.05). Immunofluorescence staining showed that the proportion of SPP1⁺ macrophages was increased in the CAD group compared with the CTL group, and also increased in the CAD group compared with the SYN group (both P<0.05). VIPER analysis and DoRothEA transcription factor activity analysis revealed activation of the hypoxia pathway and upregulated expression of transcription factors such as HIF-1α in SPP1⁺ macrophages. SPP1 expression was elevated in BMDMs under hypoxic conditions. Knockdown of HIF-1α inhibited hypoxia-induced SPP1 protein expression, whereas overexpression of HIF-1α upregulated SPP1 protein levels. After co-culture of hypoxia-induced BMDMs with MAECs, the expression levels of EndMT-related markers were increased. Conclusions SPP1⁺ macrophages differentiated under hypoxia are significantly infiltrated in the formation of chronic renal allograft fibrosis, and may promote renal allograft fibrosis by inducing EndMT in renal vascular endothelial cells.

OBJECTIVE To investigate the clinical characteristics of euglycemic diabetic ketoacidosis （euDKA） induced by empagliflozin， and provide references for safe medication. METHODS Case reports of euDKA induced by empagliflozin were retrieved and analyzed from PubMed， Web of Science， CNKI， and Wanfang Data. The Naranjo’s scale was adopted to assess the causal relationship between empagliflozin and euDKA. RESULTS A total of 29 patients were enrolled， including 16 males and 13 females，with a median age of 58 years. All patients were diagnosed with type 2 diabetes mellitus； 22 patients had at least one comorbidity. The median time to euDKA onset was 60 days after administration， and 7 cases occurred within 2 weeks of treatment. Perioperative periods，fasting，and low-carbohydrate or ketogenic diets were the main predisposing factors. Common presentations included nausea，vomiting， fatigue， tachypnea，and tachycardia. The causal relationship between empagliflozin and euDKA was assessed as “probable” in all cases. According to adverse reaction severity grading， 13 cases were grade 3 （severe） and 16 cases were grade 4 （life-threatening）. All patients discontinued empagliflozin and recovered after corresponding treatment. CONCLUSIONS euDKA is a serious adverse reaction to empagliflozin， which mostly occurs early in treatment. Perioperative periods， fasting， and ketogenic diets are prone to induce euDKA. Elderly patients and those with comorbidities are at higher risk. Risk assessment should be conducted before clinical administration； blood ketones and acid-base monitoring should be strengthened in the early medication period； withhold the drug before elective surgery， avoid prolonged fasting；upon diagnosis， discontinue empagliflozin and initiate intravenous insulin， provide fluid resuscitation promptly， and use other treatments to improve patient prognosis.

Lumbar spinal stenosis (LSS) is a common disabling condition in the elderly, and its clinical assessment relies not only on imaging and neurofunctional indicators but also on traditional Chinese medicine (TCM) syndrome differentiation. To evaluate the concordance between existing LSS animal models and clinical characteristics of TCM and Western medicine, clarify their advantages and limitations, and explore their translational potential, Chinese and English databases, including CNKI, Wanfang Data, PubMed, and Web of Science, are searched using combinations of the terms "lumbar spinal stenosis," "model," "guideline," "consensus," and "norm" from inception to the end of June 2025. After screening, a total of 21 publications are included, of which 15 report animal experimental studies, and 6 are guidelines, consensus statements, or normative documents. Based on these, the existing modeling methods are summarized, diagnostic indicators are extracted from clinical guidelines and expert consensus, and clinical concordance is evaluated using an assessment system proposed in the relevant literature. The results show that the existing animal models are categorized into three concordance levels: high (laminectomy/spinous process removal with filling; laminectomy/spinous process + ligament/muscle removal with filling; autologous bone backfilling), moderate (nylon tape dural binding method, adjustable screws, fixation combined with removal of ligament/muscle), and low (balloon compression method, adjustable balloon compression method, bipedal standing, ligament/muscle resection, steel wire cerclage method). Overall, current animal models of LSS generally perform well in terms of structural construction but show clear limitations in replicating clinical diagnostic logic and TCM syndromes. Future research should enhance syndrome phenotype collection and enrich TCM-based evaluation systems based on existing models. Additionally, multifactorial integrated modeling strategies should be introduced to extend the depth of syndrome-level simulation. This study aims to analyze LSS animal models that can faithfully recapitulate disease pathogenesis, conform to clinical realities of both Western medicine and TCM clinical practice, and have broad application potential, so as to narrow the translational gap between experimental findings and clinical practice.

Objective:To investigate the clinical efficacy of autologous ear cartilage biomimetic nasal tip framework construction combined with dermal fat dorsal grafting in rhinoplasty.Methods:A retrospective analysis was conducted on clinical data of patients who underwent rhinoplasty at the Department of Plastic Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine from June 2021 to May 2023. Autologous ear cartilage with preserved perichondrium was harvested from patients, and fashioned into a nasal tip framework simulating the natural nasal tip structure. Dermal fat grafts were harvested from the lateral gluteal crease region where the dermis was thicker, and implanted into the nasal dorsum for augmentation rhinoplasty. Postoperative follow-up included observation of incision healing, nasal tip morphology, and complications. Pre- and postoperative photographs were taken to measure nasal length and nasal tip height. Ultrasound was used to measure subcutaneous fat thickness at the nasal root before and after surgery, and absorption rates were calculated. The absorption rate at 6, 12, and 24 months postoperatively = (1 -subcutaneous fat thickness at 6 or 12 or 24 months postoperatively/subcutaneous fat thickness at 1 month postoperatively) × 100%. Aesthetic satisfaction was evaluated based on surgeon assessment, patient self-evaluation, and third-party physician evaluation (satisfaction by all three parties was rated as markedly effective, by two parties as effective, by one party as fair, and by none as poor). The aesthetic satisfaction rate = (markedly effective + effective) cases/total cases × 100%. Comparisons of preoperative and postoperative nasal tip height and nasal length were performed using paired t-tests, with P<0.05 considered statistically significant. Comparisons of subcutaneous fat thickness at the nasal root at different time points and absorption rates at different postoperative time points were performed using repeated measures ANOVA, with post-hoc pairwise comparisons using Bonferroni correction. For subcutaneous fat thickness comparisons, P<0.007 was considered statistically significant; for absorption rate comparisons, P<0.017 was considered statistically significant. Results:A total of 38 patients were included, consisting of 5 males and 33 females, with a mean age of 29.42 years (range 20-38 years). All patients were followed up for 24 months postoperatively. All incisions healed well; nasal appearance was aesthetically pleasing; nasal dorsal height was satisfactory; nasal tip mobility was good; the framework was stable; and no complications occurred. At 24 months postoperatively, nasal tip height [(22.87±0.52) mm vs. (19.94±0.53) mm] and nasal length [(47.18±0.61) mm vs. (44.20±0.55) mm] were significantly increased compared to preoperative measurements (both P<0.01). Comparison of subcutaneous fat thickness at the nasal root between preoperative and postoperative time points (1, 6, 12, and 24 months) showed statistically significant differences ( P<0.007). Post-hoc comparisons revealed statistically significant differences between: postoperative 1 month and 6 months vs. preoperative; postoperative 12 months vs. postoperative 1 and 6 months; and postoperative 24 months vs. postoperative 1 and 6 months (all P<0.007). However, the comparison between postoperative 24 months and 12 months showed no statistically significant difference ( P>0.007). Comparison of absorption rates at postoperative time points (6, 12, and 24 months) showed statistically significant differences ( P<0.017). Comparisons between postoperative 12 months vs. 6 months, and postoperative 24 months vs. 6 months showed statistically significant differences (both P<0.017), while the comparison between postoperative 24 months and 12 months showed no statistically significant difference ( P>0.017). In the aesthetic satisfaction survey, 37 cases were markedly effective and 1 case was fair, achieving an aesthetic satisfaction rate of 97%. Conclusion:The use of autologous ear cartilage for constructing a biomimetic nasal tip framework combined with dermal fat dorsal grafting in rhinoplasty results in natural postoperative appearance and high patient satisfaction, demonstrating significant value for extensive clinical use.

BACKGROUND: The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined. METHODS: All CTO vessels treated with successful anatomical PCI in patients from PANDA III trial were retrospectively measured for post-PCI QFR. The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs, composite of target vessel-related cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization). Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs, and all vessels were stratified by this optimal cutoff value. Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI. RESULTS: Among 428 CTO vessels treated with PCI, 353 vessels (82.5%) were analyzable for post-PCI QFR. 31 VOCEs (8.7%) occurred at 2 years. Mean value of post-PCI QFR was 0.92 ± 0.13. Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91. The incidence of 2-year VOCEs in the vessel with post-PCI QFR < 0.91 (n = 91) was significantly higher compared with the vessels with post-PCI QFR ≥ 0.91 (n = 262) (22.0% vs. 4.2%, HR = 4.98, 95% CI: 2.32-10.70). CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO. Achieving functionally optimal PCI results (post-PCI QFR value ≥ 0.91) tends to get better prognosis for patients with CTO lesions.

OBJECTIVE: To investigate the therapeutic effect of Xiangshao Granules (XSG) on post-stroke depression (PSD) and explore the underlying mechanisms. METHODS: Forty-three C57BL/6J mice were divided into 3 groups: sham (n=15), PSD+vehicle (n=14), and PSD+XSG (n=14) groups according to a random number table. The PSD models were constructed using chronic unpredictable mild stress (CUMS) after middle cerebral artery occlusion (MCAO). The sham group only experienced the same surgical operation, but without MACO and CUMS stimulation. The XSG group received XSG (60 mg/kg per day) by gavage for 4 weeks. The mice in the sham and vehicle groups were given the same volume of 0.9% saline at the same time. The body weight and behavior tests including open field test, sucrose preference test, tail suspension test, and elevated plus-maze test, were used to validate the PSD mouse model. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining were used to evaluate the anti-inflammatory effects of XSG. The potential molecular mechanisms were explored and verified through network pharmacology analysis, Nissl staining, Western blot, ELISA, and RT-qPCR, respectively. RESULTS: The body weight and behavior tests showed that MCAO combined with CUMS successfully established the PSD models. XSG alleviated neuronal damage, reduced the expressions of pro-apoptotic proteins Caspase-3 and B-cell lymphoma-2 (BCL-2)-associated X (BAX), and increased the expression of anti-apoptotic protein BCL-2 in PSD mice (P<0.05 or P<0.01). XSG inhibited microglial activation and the expressions of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin (IL)-1 β, and IL-6 via the toll-like receptor 4/nuclear factor kappa-B signaling pathway in PSD mice (P<0.05 or P<0.01). Furthermore, XSG decreased the expression of indoleamine 2,3-dioxygenase1 (IDO1) and increased the concentration of 5-hydroxytryptamine in PSD mice (P<0.05 or P<0.01). CONCLUSION XSG could reverse the anxiety/depressionlike behaviors and reduce the neuronal injury in the hippocampus and prefrontal cortex of PSD mice, which may be a potential therapeutic agent for PSD.
Animals ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism* ; Depression/etiology* ; Drugs, Chinese Herbal/therapeutic use* ; Hippocampus/metabolism* ; Male ; Mice, Inbred C57BL ; Prefrontal Cortex/pathology* ; Microglia/metabolism* ; Stroke/drug therapy* ; Disease Models, Animal ; Mice ; Behavior, Animal/drug effects*

OBJECTIVE: To characterize a glycosyltransferase (RpUGT1) from Rheum palmatum and investigate its specificity toward flavonoid compounds. METHODS: The RpUGT1 was expressed in Escherichia coli and screened for catalytic activity against a range of flavonoid substrates using a high-throughput HPLC assay method. Mass spectrometry (MS) and nuclear magnetic resonance (NMR) were used to determine the structure of the product. Homology modeling, molecular docking analyses and site-directed mutagenesis studies were conducted to identify key residues responsible for its function. RESULTS: The recombinant RpUGT1 protein exhibited catalytic activity towards various flavonoids. Notably, RpUGT1 catalyzed the glycosylation of isorhamnetin to form 3-O-glucoside and kaempferol to form 7-O-glucoside, utilizing uridine diphosphate (UDP) glucose as the sugar donor. The homology modeling and molecular docking analyses identified key residues responsible for its activity. Subsequent site-directed mutagenesis studies highlighted the crucial role of K307 in catalysis. CONCLUSION These discoveries offer valuable perspectives on the role of the UGT family and establish a groundwork for forthcoming research on the synthesis of flavonoids in plants.

In the context of the development of transplant oncology, it is of great clinical significance to find a drug with both antitumor and immunosuppressive effects for liver transplantation patients with hepatocellular carcinoma (HCC). The antitumor effect of ginkgolic acid (GA) has been confirmed, and some studies suggest that GA may also have an immunosuppressive effect. The immunosuppressive effect of GA was evaluated by histopathology, T-cell subpopulation, and cytokine detection in rat liver transplantation and mouse cardiac transplantation models, and transcriptomic and metabolomic analysis was used to explore the underlying mechanism of the GA immunosuppressive effect. Metabolites, activation, and ferroptosis markers of CD8⁺ T cells were detected in vivo and in vitro. Based on rat liver transplantation and mouse cardiac transplantation models, the immunosuppressive effect of GA was first confirmed by histopathology, T-cell subpopulation, and cytokine detection. In the mouse cardiac transplantation model, transcriptomics combined with metabolomics demonstrated for the first time that GA inhibited lactate dehydrogenase A (LDHA) expression and pyruvate metabolism in CD8⁺ T cells. It was confirmed in vivo and in vitro that GA inhibited pyruvate metabolism of CD8⁺ T cells through LDHA, inhibiting their activation and inducing ferroptosis. Overexpression of LDHA partially reversed the effect of GA on the metabolism, activation, and ferroptosis of CD8⁺ T cells in vitro. GA mediates metabolic reprogramming through LDHA to inhibit the activation and induce ferroptosis of CD8⁺ T cells to exert an immunosuppressive effect, which lays an experimental foundation for the future clinical application of its immunosuppressive effect.

Objective To compare the efficacy and prognostic impact of ruiyun procedure for hemorrhoid(RPH)and procedure for prolapse and hemorrhoid(PPH)in patients with mixed hemor-rhoids.Methods A total of 218 patients with mixed hemorrhoids who underwent surgical treatment in the Gastrointestinal Surgery Department of our hospital from November 2022 to October 2023 were included in this study.According to differed surgical methods,the patients were divided into RPH group(n=108)and PPH group(n=110).The operative time,intraoperative blood loss,length of hospital stay,surgical treatment outcomes,postoperative complication rates,and recurrence rates were compared between the two groups.The Visual Analogue Scale(VAS)was used to assess pain degree of patients before surgery,24 hours after surgery,and during the first defecation.The 36-Item Short Form Health Survey(SF-36)was employed to evaluate the quality of life,and the Patient Satis-faction Questionnaire(PSQ)was used to investigate patients' satisfaction with the surgical treatment.Results The total effective rate of treatment in the RPH group was 88.89％,which was higher than 78.18％in the PPH group(P＜0.05).The operative time,intraoperative blood loss,and length of hospital stay in the RPH group were shorter or less than those in the PPH group(P＜0.05).The VAS scores at 24 hours after surgery and during the first defecation in the RPH group were lower than those in the PPH group,and the differences were statistically significant(P＜0.05).After surgery,the SF-36 and PSQ scores in both the RPH and PPH groups were higher than those before surgery,and the scores in the RPH group were higher than those in the PPH group,with statistically signifi-cant differences(P＜0.05).The incidence of postoperative complications in the RPH group was lower than that in the PPH group,and the difference was statistically significant(P＜0.05).Six months after surgery,there was no significant difference in the recurrence rates between the two groups(P＞0.05).Conclusion Both RPH and PPH are effective surgical methods for the treat-ment of mixed hemorrhoids.RPH is superior to PPH in reducing postoperative complications and shortening the length of hospital stay,but there is no significant difference in the postoperative recur-rence rates between the two methods.

In the context of the development of transplant oncology,it is of great clinical significance to find a drug with both antitumor and immunosuppressive effects for liver transplantation patients with hepatocellular carcinoma(HCC).The antitumor effect of ginkgolic acid(GA)has been confirmed,and some studies suggest that GA may also have an immunosuppressive effect.The immunosuppressive effect of GA was evaluated by histopathology,T-cell subpopulation,and cytokine detection in rat liver transplantation and mouse cardiac transplantation models,and transcriptomic and metabolomic analysis was used to explore the underlying mechanism of the GA immunosuppressive effect.Metabolites,activation,and ferroptosis markers of CD8+T cells were detected in vivo and in vitro.Based on rat liver transplantation and mouse cardiac transplantation models,the immunosuppressive effect of GA was first confirmed by histopathology,T-cell subpopulation,and cytokine detection.In the mouse cardiac transplantation model,transcriptomics combined with metabolomics demonstrated for the first time that GA inhibited lactate dehydrogenase A(LDHA)expression and pyruvate metabolism in CD8+T cells.It was confirmed in vivo and in vitro that GA inhibited pyruvate metabolism of CD8+T cells through LDHA,inhibiting their activation and inducing ferroptosis.Over-expression of LDHA partially reversed the effect of GA on the metabolism,activation,and ferroptosis of CD8+T cells in vitro.GA mediates metabolic reprogramming through LDHA to inhibit the activation and induce ferroptosis of CD8+T cells to exert an immunosuppressive effect,which lays an experimental foundation for the future clinical application of its immunosuppressive effect.