1.Study on the role and mechanism of SPP1+ macrophages in the formation of chronic renal allograft fibrosis
Zexin YANG ; Zeping GUI ; Junqi ZHANG ; Gang ZHANG ; Hao CHEN ; Li SUN ; Shuang FEI ; Min GU ; Zijie WANG
Organ Transplantation 2026;17(3):413-421
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.
2.Literature analysis of euglycemic diabetic ketoacidosis induced by empagliflozin
Zhenzhen LEI ; Wei RUI ; Yanling SHI ; Jiayue ZHU ; Ying GANG ; Xiaodi SUN ; Hao ZHAN ; Junnan WANG ; Yukun NIU ; Wenxiang ZHANG
China Pharmacy 2026;37(14):1874-1879
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.
3.Analysis of Animal Models of Lumbar Spinal Stenosis Based on Clinical Characteristics of Traditional Chinese and Western Medicine
Miao HE ; Xuxing ZHANG ; Gang WU ; Yi ZHOU ; Hao RAO ; Xiangyu HU
Laboratory Animal and Comparative Medicine 2026;46(4):541-552
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.
4.The therapeutic effects of newly formulated Tadalafil tablets on rats with pathological cardiac hypertrophy through regulation of NF-κB signaling pathway
Xue-di ZHANG ; Ye-ding SONG ; Li-mei LI ; Hao-yan CHEN ; Hua-sui CUI ; Zheng-gang ZHAO ; Zi-jian ZHAO ; Yun-ping MU ; Fang-hong LI
Chinese Pharmacological Bulletin 2025;41(8):1485-1492
Aim To investigate the therapeutic effects of a newly developed Tadalafil tablets on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,as well as its influence on the activation of the NF-κB signaling pathway in myo-cardial cells.Methods SD rats were randomly divid-ed into 4 groups:the sham operation group(Sham),the model group(AAC),the tadalafil new tablet treat-ment group(N-Tad,5 mg·kg-1),and the positive control drug treatment group(Cialis,10 mg·kg-1g).The AAC model group and treatment group rats under-went blunt dissection and constrictive ligation of the abdominal aorta at the left renal artery branch point during surgery,while the Sham group rats only had their arteries separated without any constrictive liga-tion.Rats in the treatment groups received either N-Tad or Cialis via gavage three days after modeling,while rats in the sham group and the model group re-ceived physiological saline daily for 8 weeks.Small an-imal ultra-high-resolution echocardiography and hemo-dynamic assessment were applied to evaluate left ven-tricular function in each group of rats,and the calcula-tion of the left ventricular mass index was conducted.By employing Western blot and RT-PCR.we assessed the impact of this treatment on the expression of the hy-pertrophy factor atrial natriuretic peptide(ANP),phosphorylated NF-κB p65 protein(p-NF-κB p65),and phosphorylated IκB-α in the left heart tissue of rats and in H9c2 cardiomyocytes.Results Compared to the Sham group,the AAC rats exhibited a significant decrease in left heart function,an increase in left ven-tricular mass index,and a notable increase in ANP and p-p65 expression in the left heart tissue(P<0.05).Both N-Tad and Cialis treatments could significantly enhance left ventricular function,decrease left ventric-ular mass index,and inhibit the expression of ANP and phosphorylated NF-κB p65 in rats with myocardial hy-pertrophy(P<0.05).Notably,the therapeutic effect of low-dose N-Tad was comparable to that of high-dose Cialis.At the cellular level,Tadalafil significantly in-hibited the activation of the NF-κB signaling pathway and reduced the expression of associated proteins in H9c2 cardiomyocytes.Conclusions N-Tad can sig-nificantly inhibit p65 and IκB-α phosphorylation,and the activation of the NF-κB signaling pathway,reduce ANP expression,and improve pathological myocardial hypertrophy,as well as mitigate left heart function damage caused by abdominal aortic constriction.
5.Current understanding and challenges of myelin oligodendrocyte glycoprotein antibody-associated diseases
Guohuan YING ; Bing WU ; Xin WANG ; Hongdan QI ; Mingying HE ; Hao QIAN ; Shangyu WANG ; Gang ZHANG
Chinese Journal of Applied Clinical Pediatrics 2025;40(4):316-320
In 2023, new diagnostic criteria were proposed to distinguish myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) from other inflammatory diseases of the central nervous system.With typical clinical presentation and neuroimaging features, the seropositive status of anti-myelin oligodendrocyte glycoprotein-IgG (MOG-IgG) is essential for the diagnosis of MOGAD.Advances in cell transfection immunofluorescence assays have improved diagnostic accuracy in the last few years, but there are differences in the positive predictive value of serum MOG-IgG titers in the context of different MOGAD prevalence.Therefore, alternative diagnostic methods need to be further explored, and the clinical significance of low MOG-IgG titers should be carefully interpreted.In this review, the main clinical features, current understanding and challenges of MOGAD were discussed, including uncertainties about the specificity and pathogenicity of myelin oligodendrocyte glycoprotein autoantibodies and the need to identify immunopathological targets for future therapies.Moreover, it is necessary to search for and validate biomarkers that can help diagnose and detect disease activity, and it is important to identify MOGAD patients who need long-term immunotherapy.
6.Expression of Bone Marrow Stromal Antigen 2 in Advanced Non-Small Cell Lung Cancer Tissues and Its Impact on the Prognosis of Cisplatin Chemotherapy
Xiang FU ; Hao-qian XU ; Ling-ping ZHU ; Zhi-gang CHEN ; Yuan-ya ZHANG
Progress in Modern Biomedicine 2025;25(20):3322-3328
Objective:To explore the expression of bone marrow stromal antigen 2(BST2)in advanced non-small cell lung cancer(NSCLC)tissues and its impact on the prognosis of cisplatin chemotherapy.Methods:This study was a prospective study,127 advanced NSCLC patients who received treatment at Shangrao People's Hospital from January 2022 to December 2023 were prospective selected,all patients received cisplatin+gemcitabine chemotherapy regimen.They were divided into survival group(n=85)and death group(n=42)according to the prognosis.The relationship between expression of BST2 and clinicopathological characteristics was analyzed.The survival situation was analyzed by Kaplan-Meier method.Influencing factors of prognosis after cisplatin chemotherapy were discussed by univariate and multivariate COX regression analyses.Results:The positive expression rate of BST2 in cancer tissues(34.65%)in advanced NSCLC tissues was significantly higher than that in adjacent tissues(7.09%)(P<0.05).Expression of BST2 was associated with tumor TNM staging,lymph node metastasis and differentiation degree(P<0.05).The 1-year survival rate of patients with high expression of BST2(56.98%)was significantly lower than that of patients with low expression(87.80%)(P<0.05).High expression of BST2 and TNM stage Ⅳ were independent prognostic risk factors for cisplatin chemotherapy in patients with advanced NSCLC(P<0.05).Conclusion:The expressed of BST2 is highly in patients with advanced NSCLC tissues and closely related to cisplatin chemotherapy poor prognosis,suggesting its potential as a prognostic biomarker.
7.Expression of Bone Marrow Stromal Antigen 2 in Advanced Non-Small Cell Lung Cancer Tissues and Its Impact on the Prognosis of Cisplatin Chemotherapy
Xiang FU ; Hao-qian XU ; Ling-ping ZHU ; Zhi-gang CHEN ; Yuan-ya ZHANG
Progress in Modern Biomedicine 2025;25(20):3322-3328
Objective:To explore the expression of bone marrow stromal antigen 2(BST2)in advanced non-small cell lung cancer(NSCLC)tissues and its impact on the prognosis of cisplatin chemotherapy.Methods:This study was a prospective study,127 advanced NSCLC patients who received treatment at Shangrao People's Hospital from January 2022 to December 2023 were prospective selected,all patients received cisplatin+gemcitabine chemotherapy regimen.They were divided into survival group(n=85)and death group(n=42)according to the prognosis.The relationship between expression of BST2 and clinicopathological characteristics was analyzed.The survival situation was analyzed by Kaplan-Meier method.Influencing factors of prognosis after cisplatin chemotherapy were discussed by univariate and multivariate COX regression analyses.Results:The positive expression rate of BST2 in cancer tissues(34.65%)in advanced NSCLC tissues was significantly higher than that in adjacent tissues(7.09%)(P<0.05).Expression of BST2 was associated with tumor TNM staging,lymph node metastasis and differentiation degree(P<0.05).The 1-year survival rate of patients with high expression of BST2(56.98%)was significantly lower than that of patients with low expression(87.80%)(P<0.05).High expression of BST2 and TNM stage Ⅳ were independent prognostic risk factors for cisplatin chemotherapy in patients with advanced NSCLC(P<0.05).Conclusion:The expressed of BST2 is highly in patients with advanced NSCLC tissues and closely related to cisplatin chemotherapy poor prognosis,suggesting its potential as a prognostic biomarker.
8.An Epithelial Senescence Model Induced by Doxorubicin in MCF 10A Cells
Zeng-Sheng WANG ; Zu-Biao NIU ; Bo ZHANG ; Jia-Hui HAO ; Yi-Chao ZHU ; Rui-Gang YANG ; He REN ; Chen-Yu LIU ; Qiang SUN ; Li-Cheng REN
Chinese Journal of Biochemistry and Molecular Biology 2025;41(1):147-155
This research aims to construct a stable epithelial cell senescence model for screening and e-valuation of senolytics.We explored the optimal conditions for doxorubicin-induced senescence of non-transformed epithelial cells MCF 10A,including the optimal induction concentration,the optimal inter-vention time,and the optimal senescence duration,and confirmed the feasibility of MCF 10A as an epi-thelial senescence model by multiple ways.The optimal condition for Doxorubicin-induced senescence of MCF 10A cells was treatment with 0.6 μmol/L Doxorubicin for 16 h to achieve the best senescence state on the 8th day.Under the optimal induction conditions,the positive rate of senescence-associated β-gal-actosidase(SA-β-gal)staining in the treated group reached 97%.At the same time,biochemical results of detecting the expression of mRNA,proteins,and immunofluorescence demonstrated that the expression levels of senescence-associated secretory phenotype(SASP),p16,p21 and p53 in the treated group were significantly higher than those in the control cells,and Lamin B1 was significantly decreased(P<0.001),which were consistent with the specific characteristics of senescence.In summary,an epithelial senescence model was successfully induced in MCF 10A cells by Doxorubicin in this study,which will promote the screening of senolytics for senescent epithelial cells.
9.Clinical efficacy of anteriorly displaced orbicularis oculi flap and autologous granular fat injection via sub-brow incision for correction of different degrees of sunken upper eyelid
Guoqiang HU ; Shan ZHANG ; Hao CHEN ; Tianqi ZHANG ; Qiuyue FU ; Gang CHEN
Chinese Journal of Medical Aesthetics and Cosmetology 2025;31(2):110-114
Objective:To investigate the clinical results of anteriorly displaced orbicularis oculi flap and autologous granular fat injections via sub-brow incision for correction of different degrees of sunken upper eyelid.Methods:From September 2021 to September 2022, a total of 80 patients with upper eyelid skin laxity and sunken upper eyelid were recruited prospectively from the Department of Plastic Surgery, Jiangsu Province Hospital of Chinese Medicine. There were 18 males and 62 females, aged 28 to 60 years, with a mean age of (42.7±9.2) years. According to Park's method, 59 patients with grade Ⅰ and grade Ⅱ sunken upper eyelid were treated with eyebrow lifting and orbicularis oculi flap correction, and 21 patients with grade Ⅲ upper eyelid sunken were treated with eyebrow lifting combined with autologous particles fat filling. The patients were followed up for 6 months. The depth of sunken upper eyelid was measured before and after operation. The incidence of adverse reactions and patient satisfaction were recorded.Results:The mean depth of depression measured preoperatively was (6.01±2.25) mm in the grades Ⅰ and Ⅱ sunken upper eyelid, which was improved to (2.00±1.06) mm at the 6-month postoperative follow-up ( P=0.001), and the mean depth of depression was (13.15±1.75) mm in the group of grade Ⅲ, which was improved to (4.15±1.49) mm at the 6-month postoperative follow-up ( P=0.001). After 6-month follow-up, the incidence of complications was 6.3% (5/80) and the satisfaction rate was 90.0% (72/80). Conclusions:Different correction methods should be chosen according to the degree of sunken upper eyelid. Grades Ⅰand Ⅱ sunken upper eyelid are corrected with orbicularis muscle flap through sub-eyebrow incision, and grade Ⅲ is corrected with autologous fat injection. Both the clinical effect and patient satisfaction rate are higher.
10.Efficacy and safety of fractional CO 2 laser combined with topical application of radix scutellariae ointment in treatment of hyperplastic scar
Qiuyue FU ; Tianqi ZHANG ; Wei CHEN ; Shan ZHANG ; Hao CHEN ; Lina ZHOU ; Gang CHEN
Chinese Journal of Medical Aesthetics and Cosmetology 2025;31(2):126-130
Objective:To evaluate the clinical efficacy and safety of fractional CO 2 laser combined with topical application of radix scutellariae ointment in the treatment of hyperplastic scar. Methods:This randomized controlled trial prospectively enrolled 90 patients with hyperplastic scar treated with fractional CO 2 laser at the Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine) from January 2020 to December 2021. Participants were randomly divided into a trial group and a control group using a random number table. The trial group ( n=45, 22 males, 23 females, aged 18-54 years) received topical radix scutellariae ointment post-laser treatment, while the control group ( n=45, 23 males, 22 females, aged 19-55 years) received recombinant bovine basic fibroblast growth factor gel. Both groups underwent treatment every 3 months, with scar assessments conducted at 1-month post-treatment. Outcomes included Vancouver scar scale (VSS) scores, scar cosmesis assessment and rating (SCAR) scores, adverse reaction rates, and patients' satisfaction. Results:After the first, second, and third treatments, the trial group showed significantly lower VSS and SCAR scores compared to the control group (all P<0.05). Patients' satisfaction in the trial group was 91.1% (41/45), significantly higher than 77.8% (35/45) in the control group ( P=0.036). The adverse reaction rate in the trial group was 15.6% (7/45), and 28.9% (13/45) in the control group, there was no statistical difference ( P=0.813). Conclusion:Fractional CO 2 laser combined with topical radix scutellariae ointment demonstrate superior clinical efficacy, higher patient satisfaction, and lower adverse reaction rates in the treatment of hyperplastic scar.

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