1.Potential target genes for spondylolisthesis:drugable genome analysis based on the European population-based biodatabase
Qingfeng ZHANG ; Chaoyi WANG ; Jingyan YANG ; Hanyu LI ; Yuyang ZHAO ; Huatao HAO ; Dong YU
Chinese Journal of Tissue Engineering Research 2026;30(6):1592-1601
BACKGROUND:Spondylolisthesis is a common disease,and there is a lack of effective drugs to treat it.There is still a need to further define the pathogenesis and screen out more suitable therapeutic targets for spondylolisthesis.Mendelian randomization analysis can be used to explore the drugable genes associated with spondylolisthesis and provide valuable guidance for the development of more effective and targeted therapeutic drugs.OBJECTIVE:To explore potential therapeutic targets and effective drugs for spondylolisthesis by means of pharmaceutically available genome-wide Mendelian randomization analysis.METHODS:Using the Finnish database,eQTLGen consortium,drug signature database,drug-gene interaction database,protein-protein interaction database,organic small molecule biological activity database and protein structure database,which contains genome and health information of half a million Finns,data on druggable genes were subjected to two-sample Mendelian randomization analysis and co-localization analysis with data from genome-wide association studies of spondylolisthesis to identify genes highly associated with spondylolisthesis.In addition,GO and KEGG enrichment analysis,protein network construction,drug prediction and molecular docking were performed to provide valuable guidance for the development of more effective and targeted therapeutic agents.RESULTS AND CONCLUSION:In this study,we identified 34 potential drug target genes that were significantly associated with spondylolisthesis,particularly the gene APOBEC3G.This gene showed a significant association with spondylolisthesis outcomes through Mendelian analysis and co-localization analysis,suggesting that APOBEC3G may be a priority therapeutic target.As for other potential mechanisms and drugs,we still need to conduct more in-depth research to determine their roles.This study used a database from a European population,which can be used as a reference for the study of population genetics in China.
2.Comparison of Wild and Cultivated Bupleurum scorzonerifolium Based on Traditional Quality Evaluation
Changsheng YUAN ; Feng ZHOU ; Xingyu LIU ; Yu SHI ; Yihan WANG ; Huaizhu LI ; Yongliang LI ; Shan GUAN ; Huaizhong GAO ; Yanmeng LIU ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):203-214
ObjectiveTo characterize the quality differences among different germplasm and introduced varieties of Bupleurum scorzonerifolium roots(BSR), and explore the underlying molecular mechanisms, providing a basis for high-quality production and quality control. MethodsWild BSR from Yulin(YLW) served as the quality reference, we conducted comparative analysis among YLW, locally domesticated wild germplasm in Yulin(YLC3), Daqing germplasm introduced and cultivated in Yulin(YLDQC3), and locally cultivated germplasm in Daqing(DQC3). A combination of traditional pharmacognostic methods and modern multi-omics analyses was employed, including macroscopic traits(appearance, odor), microscopic features(proportions of cork, phloem, xylem), cell wall component contents(hemicellulose, cellulose, lignin), carbohydrate contents(starch, water-soluble polysaccharides), marker compound contents(ethanol-soluble extracts, total saponins, liposoluble extracts, and saikosaponins A, B2, C, D), metabolomics, and transcriptomics, in order to systematically characterize quality differences and investigate molecular mechanisms among these samples. ResultsMacroscopically, Yulin-produced BSR(YLW, YLC3, YLDQC3) exhibited significantly greater weight, length, and upper and middle diameters than Daqing-produced BSR(DQC3). Odor-wise, YLW and YLC3 had a a fragrance taste, YLDQC3 had a rancid oil odor, and DQC3 had a sweet and fragrant taste. Microscopically, Yulin germplasm(YLW, YLC3) and Daqing germplasm(YLDQC3, DQC3) shared similar structural features, respectively. However, Yulin germplasm showed significantly higher proportions of cork and phloem, as well as stronger xylem vessel staining intensity compared to Daqing germplasm. Regarding various component contents, Yulin germplasm contained significantly higher levels of ethanol-soluble extracts, total saponins, and saikosaponins A, B2, C, D, while Daqing germplasm had significantly higher levels of hemicellulose, starch, and liposoluble extracts. After introduction to Yulin, the Daqing germplasm(YLDQC3) showed increased starch, water-soluble polysaccharides and liposoluble extracts contents, decreased cell wall component content, but no significant difference in other component contents. Metabolomics revealed that saponins and terpenes accumulated significantly in Yulin germplasm, while alcohols and aldehydes accumulated predominantly in Daqing germplasm. Transcriptomics indicated similar gene expression patterns within the same germplasm but specificity between different germplasms. Integrative metabolomic-transcriptomic analysis identified 145 potential key genes associated with the saikosaponin biosynthesis pathway, including one acetyl-coenzyme A(CoA) acetyltransferase gene(ACAT), one 3-hydroxy-3-methylglutaryl-coenzyme A synthase gene(HMGS), two hydroxymethylglutaryl-CoA(HMG-CoA) reductase genes(HMG), one phosphomevalonate kinase gene(PMK), one 1-deoxy-D-xylose-5-phosphate synthase gene(CLA), one hydroxymethylbuten-1-aldol synthase gene(HDR), two farnesyl pyrophosphate synthase genes(FPPS), one squalene synthase gene(SQS), one β-amyrin synthase gene(BAS), 102 cytochrome P450(CYP450) gene family members, and 32 uridine diphosphate-glucuronosyltransferase(UGT) gene family members. ConclusionAmong the three cultivated types, YLC3 most closely resembles YLW in appearance, microscopic features, contents of major bioactive constituents, metabolomic and transcriptomic profiles. Yulin germplasm exhibits superior saponin synthesis capability compared to Daqing germplasm, and Yulin region is more suitable for the growth of B. scorzonerifolium. Based on these findings, it is recommended that artificial cultivation in northern Shaanxi and similar regions utilize the local Yulin germplasm source cultivated for at least three years.
3.Potential target genes for spondylolisthesis:drugable genome analysis based on the European population-based biodatabase
Qingfeng ZHANG ; Chaoyi WANG ; Jingyan YANG ; Hanyu LI ; Yuyang ZHAO ; Huatao HAO ; Dong YU
Chinese Journal of Tissue Engineering Research 2026;30(6):1592-1601
BACKGROUND:Spondylolisthesis is a common disease,and there is a lack of effective drugs to treat it.There is still a need to further define the pathogenesis and screen out more suitable therapeutic targets for spondylolisthesis.Mendelian randomization analysis can be used to explore the drugable genes associated with spondylolisthesis and provide valuable guidance for the development of more effective and targeted therapeutic drugs.OBJECTIVE:To explore potential therapeutic targets and effective drugs for spondylolisthesis by means of pharmaceutically available genome-wide Mendelian randomization analysis.METHODS:Using the Finnish database,eQTLGen consortium,drug signature database,drug-gene interaction database,protein-protein interaction database,organic small molecule biological activity database and protein structure database,which contains genome and health information of half a million Finns,data on druggable genes were subjected to two-sample Mendelian randomization analysis and co-localization analysis with data from genome-wide association studies of spondylolisthesis to identify genes highly associated with spondylolisthesis.In addition,GO and KEGG enrichment analysis,protein network construction,drug prediction and molecular docking were performed to provide valuable guidance for the development of more effective and targeted therapeutic agents.RESULTS AND CONCLUSION:In this study,we identified 34 potential drug target genes that were significantly associated with spondylolisthesis,particularly the gene APOBEC3G.This gene showed a significant association with spondylolisthesis outcomes through Mendelian analysis and co-localization analysis,suggesting that APOBEC3G may be a priority therapeutic target.As for other potential mechanisms and drugs,we still need to conduct more in-depth research to determine their roles.This study used a database from a European population,which can be used as a reference for the study of population genetics in China.
4.Pathogenesis and Syndrome-Differentiated Treatment of Viral Pneumonia in the Lancang-Mekong River Basin from the Perspective of Filthy Dampness as the Affliction and Yang Failing to Be Stored in the You (酉) Position
Shiwen LUO ; Ming CHENG ; Kun LI ; Maorong FAN ; Zijun ZHANG ; Ying LIU ; Yuyang YANG
Journal of Traditional Chinese Medicine 2026;67(21):2354-2358
Viral pneumonia in the Lancang-Mekong River Basin exhibits distinct regional epidemiological characteristics and pathogenic mechanisms. Filthy dampness constitutes the core pathogenic factor of the disease here, and the core pathogenesis lies in the yang failing to be stored in the you (酉) position. Clinically, the fundamental therapeutic principle is established as boosting qi to expel filth and guiding yang qi to descend and converge into the you position. In the early stage, the pathogenesis is characterized by the pervasive diffusion of filthy dampness, yang qi floating externally and failing to be stored, and the lung failing to diffuse qi. The treatment focuses on invigorating yang qi to dispel filth and dredging the you pathways, primarily using modified Ganlu Xiaodu Decoction (甘露消毒丹). In the progressive stage, the pathogenesis involves the tenacious stagnation of filthy dampness, yang constraint transforming into heat, and the rampant spread of heat-toxins. The therapeutic approach shifts to acrid medicinals for opening and bitter medicinals for promoting descent, rectifying healthy qi to expel filth, utilizing modified Dayuan Beverage (达原饮). In the recovery stage, filthy dampness gradually recedes, accompanied by the depletion of qi and yin, and insufficient kidney yang. The treatment emphasizes supplementing qi and nourishing yin, accompanied by warming yang, with modified Yunv Decoction (玉女煎).
5.Progress of research on clinical treatment of renal tuberculosis
Xiaoshan LI ; Yuyang ZHANG ; Xiumei LI ; Tiantian HOU ; Panfeng SHANG
Chinese Journal of Nosocomiology 2025;35(15):2395-2400
Drug therapy and surgical treatment are the two primary methods for treating renal tuberculosis.With the increase in drug-resistant strains,some novel anti-tuberculosis drugs,such as Delamanid and Bedaquiline,are being developed and gradually applied in clinical practice.Surgical treatment is suitable for patients with poor re-sponses to drug therapy and those who develop complications.Surgical methods include nephrectomy and partial nephrectomy.As the goal of preserving renal function as much as possible becomes more important,minimally in-vasive treatments have been adopted,with significant contributions from percutaneous nephrostomy and ureteral stent placement.Additionally,immunotherapy has emerged as a new direction,with immunomodulators such as interferons and interleukins under investigation.This article discusses the status and research progress in the treat-ment of renal tuberculosis,aiming to provide a theoretical basis for future treatments.
6.Effect of Yishen Zhuyu Tongluo Decoction on chondrocyte pyroptosis and ferroptosis in rats with knee osteoarthritis
Jingya WANG ; Kang YAN ; Jian LI ; Meng WANG ; Yuyang YANG ; Yueyue YU
Chinese Journal of Comparative Medicine 2025;35(1):49-58
Objective To investigate the effects of Yishen Zhuyu Tongluo Decoction on chondrocyte pyroptosis and ferroptosis in rats with knee osteoarthritis(KOA).Methods Forty SD were divided randomly into a sham operation group(n=10)and a modeling group(n=30).A KOA model was established in the modeling group by anterior cruciate ligament transection of the right hind limb knee joint.The drawer test was used to confirm the successful establishment of the model.Post-surgery,the rats were subjected to 30 min of forced activity daily to induce KOA.Lameness and hopping movements were observed after 4 weeks,and hematoxylin and eosin staining confirmed cartilage surface damage,deformation,and inflammatory cell infiltration,indicating successful modeling.The model rats were then assigned randomly to a model group(n=8),celecoxib group(n=8),and Yishen Zhuyu Tongluo Decoction group(n=8).The sham operation and model groups received 10 mL/kg of saline by gavage,the celecoxib group received 12 mg/kg of celecoxib solution,and the Yishen Zhuyu Tongluo Decoction group received 5.4 g/kg of the herbal decoction,once daily for 8 weeks.After the interventions,the rats were anesthetized,blood was collected from the abdominal aorta and serum was separated,and the knee joints were isolated.Three samples were fixed in paraformaldehyde,while the remaining cartilage tissue was reserved.Pathological changes in joint cartilage were observed by hematoxylin and eosin and Safranin O-Fast Green staining.Bone microstructure was analyzed using micro-computed tomography.Serum interleukin(IL)-1β and IL-18 protein levels were detected by enzyme-linked immunosorbent assay.Relative mRNA expression levels of NLRP3,ASC,Caspase-1,GSDMD,IL-1β,IL-18,ACSL-4,FTH-1,GPX-4,and cyclooxygenase(COX)-2 were detected by reverse transcription quantitative real-time PCR,and protein expression of NLRP3,Caspase-1,and COX-2 were detected by immunohistochemistry.Results Compared with the sham operation group,model rats showed surface damage and deformation of cartilage tissue,disordered cell arrangement in all layers,significant loss of Safranin O-Fast Green staining,and sparse and irregular trabecular bone distribution.Serum levels of the inflammatory factors IL-1β and IL-18 were elevated(P<0.01).mRNA expression levels of NLRP3,ASC,Caspase-1,GSDMD,IL-1β,IL-18,ACSL-4,and COX-2 were also significantly increased(all P<0.01),while FTH-1 and GPX-4 mRNA expression levels were decreased(P<0.01).Compared with the model group,rats in the celecoxib and Yishen Zhuyu Tongluo Decoction groups showed smoother and more intact cartilage surfaces,significantly increased cell counts,less loss of Safranin O-Fast Green staining,denser trabecular bone,and thicker cortical bone,with improved bone microstructure.Serum IL-1β and IL-18 levels were reduced(P<0.01),NLRP3(P<0.01,P<0.05),ASC,Capase-1,GSDMD,IL-1β,IL-18,ACSL-4,and COX-2 mRNA levels were decreased(all P<0.01),and relative expression levels of FTH-1 and GPX-4 mRNA were significantly increased(P<0.01).Conclusions Yishen Zhuyu Tongluo Decoction can treat KOA by inhibiting chondroptosis and ferroptosis in chondrocytes,reducing serum IL-1β and IL-18 levels,and improving bone microstructure.
7.Compatibility of cold herb CP and hot herb AZ in Huanglian Ganjiang decoction alleviates colitis mice through M1/M2 macrophage polarization balance via PDK4-mediated glucose metabolism reprogramming.
Yanyang LI ; Chang LIU ; Yi WANG ; Peiqi CHEN ; Shihua XU ; Yequn WU ; Lingzhi REN ; Yang YU ; Lei YANG
Chinese Journal of Natural Medicines (English Ed.) 2025;23(10):1183-1194
Ulcerative colitis (UC) is a chronic and non-specific inflammatory bowel disease (IBD). Huanglian Ganjiang decoction (HGD), derived from ancient book Beiji Qianjin Yao Fang, has demonstrated efficacy in treating UC patients traditionally. Previous research established that the compatibility of cold herb Coptidis Rhizoma + Phellodendri Chinensis Cortex (CP) and hot herb Angelicae Sinensis Radix + Zingiberis Rhizoma (AZ) in HGD synergistically improved colitis mice. This study investigated the compatibility mechanisms through which CP and AZ regulated inflammatory balance in colitis mice. The experimental colitis model was established by administering 3% dextran sulphate sodium (DSS) to mice for 7 days, followed by CP, AZ and CPAZ treatment for an additional 7 days. M1/M2 macrophage polarization levels, glucose metabolites levels and pyruvate dehydrogenase kinase 4 (PDK4) expression were analyzed using flow cytometry, Western blot, immunofluorescence and targeted glucose metabolomics. The findings indicated that CP inhibited M1 macrophage polarization, decreased inflammatory metabolites associated with tricarboxylic acid (TCA) cycle, and suppressed PDK4 expression and pyruvate dehydrogenase (PDH) (Ser-293) phosphorylation level. AZ enhanced M2 macrophage polarization, increased lactate axis metabolite lactate levels, and upregulated PDK4 expression and PDH (Ser-293) phosphorylation level. TCA cycle blocker AG-221 and adeno-associated virus (AAV)-PDK4 partially negated CP's inhibition of M1 macrophage polarization. Lactate axis antagonist oxamate and PDK4 inhibitor dichloroacetate (DCA) partially reduced AZ's activation of M2 macrophage polarization. In conclusion, the compatibility of CP and AZ synergistically alleviated colitis in mice through M1/M2 macrophage polarization balance via PDK4-mediated glucose metabolism reprogramming. Specifically, CP reduced M1 macrophage polarization by restoration of TCA cycle via PDK4 inhibition, while AZ increased M2 macrophage polarization through activation of PDK4/lactate axis.
Animals
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Drugs, Chinese Herbal/chemistry*
;
Mice
;
Macrophages/immunology*
;
Glucose/metabolism*
;
Pyruvate Dehydrogenase Acetyl-Transferring Kinase/genetics*
;
Male
;
Mice, Inbred C57BL
;
Humans
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Colitis/drug therapy*
;
Disease Models, Animal
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Colitis, Ulcerative/drug therapy*
;
Metabolic Reprogramming
8.Effect of Yishen Zhuyu Tongluo Decoction on chondrocyte pyroptosis and ferroptosis in rats with knee osteoarthritis
Jingya WANG ; Kang YAN ; Jian LI ; Meng WANG ; Yuyang YANG ; Yueyue YU
Chinese Journal of Comparative Medicine 2025;35(1):49-58
Objective To investigate the effects of Yishen Zhuyu Tongluo Decoction on chondrocyte pyroptosis and ferroptosis in rats with knee osteoarthritis(KOA).Methods Forty SD were divided randomly into a sham operation group(n=10)and a modeling group(n=30).A KOA model was established in the modeling group by anterior cruciate ligament transection of the right hind limb knee joint.The drawer test was used to confirm the successful establishment of the model.Post-surgery,the rats were subjected to 30 min of forced activity daily to induce KOA.Lameness and hopping movements were observed after 4 weeks,and hematoxylin and eosin staining confirmed cartilage surface damage,deformation,and inflammatory cell infiltration,indicating successful modeling.The model rats were then assigned randomly to a model group(n=8),celecoxib group(n=8),and Yishen Zhuyu Tongluo Decoction group(n=8).The sham operation and model groups received 10 mL/kg of saline by gavage,the celecoxib group received 12 mg/kg of celecoxib solution,and the Yishen Zhuyu Tongluo Decoction group received 5.4 g/kg of the herbal decoction,once daily for 8 weeks.After the interventions,the rats were anesthetized,blood was collected from the abdominal aorta and serum was separated,and the knee joints were isolated.Three samples were fixed in paraformaldehyde,while the remaining cartilage tissue was reserved.Pathological changes in joint cartilage were observed by hematoxylin and eosin and Safranin O-Fast Green staining.Bone microstructure was analyzed using micro-computed tomography.Serum interleukin(IL)-1β and IL-18 protein levels were detected by enzyme-linked immunosorbent assay.Relative mRNA expression levels of NLRP3,ASC,Caspase-1,GSDMD,IL-1β,IL-18,ACSL-4,FTH-1,GPX-4,and cyclooxygenase(COX)-2 were detected by reverse transcription quantitative real-time PCR,and protein expression of NLRP3,Caspase-1,and COX-2 were detected by immunohistochemistry.Results Compared with the sham operation group,model rats showed surface damage and deformation of cartilage tissue,disordered cell arrangement in all layers,significant loss of Safranin O-Fast Green staining,and sparse and irregular trabecular bone distribution.Serum levels of the inflammatory factors IL-1β and IL-18 were elevated(P<0.01).mRNA expression levels of NLRP3,ASC,Caspase-1,GSDMD,IL-1β,IL-18,ACSL-4,and COX-2 were also significantly increased(all P<0.01),while FTH-1 and GPX-4 mRNA expression levels were decreased(P<0.01).Compared with the model group,rats in the celecoxib and Yishen Zhuyu Tongluo Decoction groups showed smoother and more intact cartilage surfaces,significantly increased cell counts,less loss of Safranin O-Fast Green staining,denser trabecular bone,and thicker cortical bone,with improved bone microstructure.Serum IL-1β and IL-18 levels were reduced(P<0.01),NLRP3(P<0.01,P<0.05),ASC,Capase-1,GSDMD,IL-1β,IL-18,ACSL-4,and COX-2 mRNA levels were decreased(all P<0.01),and relative expression levels of FTH-1 and GPX-4 mRNA were significantly increased(P<0.01).Conclusions Yishen Zhuyu Tongluo Decoction can treat KOA by inhibiting chondroptosis and ferroptosis in chondrocytes,reducing serum IL-1β and IL-18 levels,and improving bone microstructure.
9.Bioinformatics analysis and experimental verification of ferroptosis in phospholipase A2 receptor associated membranous nephropathy
Manxia HUANG ; Yuyang HE ; Yangpu LI ; Zhuoting LIU ; Yanqing WANG ; Youjia ZENG
Chinese Journal of Nephrology 2025;41(2):81-89
Objective:To identify and validate the key genes of ferroptosis in phospholipase A2 receptor (PLA2R) associated membranous nephropathy through bioinformatics analysis and in vitro experiments, and to explore the potential role of ferroptosis in PLA2R associated membranous nephropathy (PMN). Methods:The GSE115857 dataset obtained by retrieving the Gene Expression Omnibus (GEO) database and the ferroptosis-related genes obtained by retrieving the FerrDb database were intersected. The intersected genes were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The key ferroptosis genes associated with PMN were identified by intersecting genes selected using support vector machines-recursive feature elimination and least absolute shrinkage and selection operator regression. The results were validate by real-time PCR, cell counting kit-8, Western blotting and immunofluorescence in human renal podocyte line AB 8/13 from both the control group and model group.Results:A total of 25 genes related to ferroptosis of PMN were obtained, and GO and KEGG analysis showed that these genes were mainly involved in cell ferroptosis metabolism. The key ferroptosis genes of PMN obtained by machine learning method were activating transcription factor 3 ( ATF3) and coiled coil domain containing 6 ( CCDC6). The results of in vitro experiments showed that the human renal podocyte line AB 8/13 in the model group was significantly deformed and retracted compared with the control group. The surface area density of foot processes was significantly reduced, and the podocyte cytoskeleton was allosteric. The morphology of F-actin was disordered and the expression of synaptopodin was decreased. The cell proliferation activity was significantly decreased ( P<0.05). The expression of PLA2R protein was increased ( P<0.05), and the expression of GPX4 protein was decreased ( P<0.01). The protein and mRNA levels of ATF3 and CCDC6 were significantly up-regulated (all P<0.05). Conclusions:Ferroptosis may be one of the key mechanisms in the occurrence and development of PMN. In vitro experiments show that ATF3 and CCDC6 are the key genes in the ferroptosis of PMN podocytes, which provides new insights and ideas for the pathogenesis of PMN.
10.Staging system for renal tuberculosis and prognostic analysis of treatment at different stages
Chenhao GUO ; Xiao LU ; Yuyang ZHANG ; Rui ZHANG ; Wei QIN ; Linping QI ; Xiumei LI ; Panfeng SHANG
Chinese Journal of Urology 2025;46(8):581-586
Objective:To investigate the staging criteria of renal tuberculosis,and to analyze the diagnostic and therapeutic characteristics as well as prognostic outcomes at different stages.Methods:A retrospective analysis was conducted on the clinical data of 134 patients with renal tuberculosis who were admitted to the Second Hospital of Lanzhou University between January 2019 and December 2023.The study cohort included 62 males and 72 females,with a mean age of(46.63 ± 13.52)years and a mean body mass index(BMI)of(22.85 ± 3.73)kg/m 2. A total of 107 patients resided in rural areas. Sixty patients had a history of pulmonary tuberculosis. Tuberculous lesions were located in the left kidney in 72 cases and in the right kidney in 62 cases. The main presenting complaints included irritative lower urinary tract symptoms in 85 patients and systemic symptoms in 92 patients. Ureteral involvement was observed in 97 patients,bladder involvement in 32 patients,and genital involvement in 9 patients. Based on computed tomography(CT)findings,the number,extent,and degree of renal destruction caused by tuberculous lesions were comprehensively evaluated in axial,coronal,and sagittal planes. The primary staging criteria included lesion diameter(2 cm)and the proportion of renal volume involved by the lesion(one-third,one-half,and two-thirds). Renal tuberculosis was classified into three stages and six subtypes:Stage Ⅰa,a solitary lesion with a diameter ≤ 2 cm;Stage Ⅰb,a solitary lesion >2 cm or multiple lesions confined within one-third of the renal volume;Stage Ⅱa,lesions involving more than one-third but confined within one-half of the renal volume;Stage Ⅱb,lesions involving more than one-half but confined within two-thirds of the renal volume;Stage Ⅲa,lesions involving more than two-thirds of the renal volume with a glomerular filtration rate(GFR)of the affected kidney <10 ml/min;and Stage Ⅲb,complete renal calcification,presenting as an “autonephrectomy”. Among the 134 patients included in this study,7 were classified as Stage Ⅰa,17 as Stage Ⅰb,20 as Stage Ⅱa,19 as Stage Ⅱb,62 as Stage Ⅲa,and 9 as Stage Ⅲb. The severity of hydronephrosis was graded as follows:mild,renal pelvic separation <2 cm;moderate,2-3 cm;and severe,>3 cm. Prior to treatment,the mean renal pelvic separation was(1.76 ± 0.92)cm in Stage Ⅰa,(1.69 ± 0.81)cm in Stage Ⅰb,and(1.10 ± 0.82)cm in Stage Ⅱa,corresponding to mild to moderate hydronephrosis. All 7 patients in Stage Ⅰa underwent ureteroscopic examination and double-J stent placement,combined with a 6-month short-course anti-tuberculosis regimen consisting of isoniazid,rifampicin,pyrazinamide,and ethambutol for 2 months(intensive phase),followed by isoniazid and rifampicin for 4 months(continuation phase). Among the 17 patients in Stage Ⅰb,13 presented with hydronephrosis and underwent ureteroscopic examination and double-J stent placement in combination with 6 months of anti-tuberculosis therapy,while 4 patients with isolated renal tuberculosis received anti-tuberculosis therapy alone for 6 months.Of the 20 patients in Stage Ⅱa,4 with hydronephrosis underwent ureteroscopic examination and double-J stent placement plus 6 months of anti-tuberculosis therapy,whereas 16 underwent nephroureterectomy. All 19 patients in Stage Ⅱb underwent nephroureterectomy. Among the 62 patients in Stage Ⅲa,60 underwent nephroureterectomy,while 2 refused surgery and were treated with the 6-month short-course anti-tuberculosis regimen. Of the 9 patients in Stage Ⅲb,8 underwent nephroureterectomy;in 1 patient,surgery was not performed due to severe adhesions in the operative field,and the patient received the 6-month short-course anti-tuberculosis regimen instead. Follow-up assessments included clinical symptoms,erythrocyte sedimentation rate(ESR),serum creatinine,degree of renal pelvic separation,and imaging findings from urinary tract CT. Efficacy was evaluated according to the following criteria:Cure was defined as clinical stability with all of the following conditions:① improvement of systemic symptoms,including absence of flank pain,fever,and lower urinary tract irritative symptoms,with normalization of erythrocyte sedimentation rate(ESR);② negative urine culture for Mycobacterium tuberculosis;and ③ complete calcification of renal lesions and/or no evidence of tuberculous lesions at other sites. Stable disease was defined as no change in the size or extent of renal tuberculosis lesions. Progressive disease was defined as enlargement or increase in the number of tuberculous lesions or involvement of additional sites. Results:Among the 7 patients in Stage Ⅰa,follow-up imaging after treatment showed a mean renal pelvic separation of(0.44 ± 0.56)cm,which was significantly reduced compared with baseline( t = 3.909, P = 0.008). Five patients achieved cure,1 remained stable,and 1 showed disease progression and subsequently underwent nephroureterectomy,resulting in postoperative cure. In Stage Ⅰb,among 13 patients with hydronephrosis,post-treatment imaging showed a mean renal pelvic separation of(0.8 ± 0.75)cm,a statistically significant improvement from baseline( t = 5.633, P < 0.01). Six patients were cured,4 remained stable,and 3 experienced disease progression and underwent nephroureterectomy. Of the 4 patients with isolated renal tuberculosis,2 were controlled,and 2 progressed and underwent nephroureterectomy. In Stage Ⅱa,among 4 patients with tuberculous hydronephrosis,post-treatment renal pelvic separation was(1.20±0.98)cm,with no significant difference from baseline( t = -1.675, P = 0.193);these patients underwent nephroureterectomy 1-2 years later. The remaining 16 patients without hydronephrosis underwent nephroureterectomy and were cured. All 19 patients in Stage Ⅱb underwent nephroureterectomy;17 were cured,and 2 developed ipsilateral perirenal fluid collections 3 months postoperatively,which resolved spontaneously with the standard 6-month anti-tuberculosis regimen. Among 62 patients in Stage Ⅲa,60 underwent nephroureterectomy. Of these,54 were cured;1 developed a urinary tract infection within 2 weeks postoperatively;3 showed contralateral renal disease progression at 3 months;and 1 developed ipsilateral perirenal fluid at 3 months,which resolved spontaneously with standard anti-tuberculosis therapy. One patient developed solitary kidney failure 7 months postoperatively and underwent ureteral stent placement,with disease remaining stable thereafter. Two patients refused surgery and received only anti-tuberculosis therapy;during follow-up,1 patient experienced disease progression and died of disseminated tuberculosis after 1 year,while the other developed contralateral renal involvement at 3 months and received standard 6-month therapy,with disease remaining stable. Among 9 patients in Stage Ⅲb,8 underwent nephroureterectomy and were cured. One patient,with severe adhesions precluding surgery,received anti-tuberculosis therapy alone,and disease remained stable over a 2-year follow-up. Conclusions:The CT-based staging system for renal tuberculosis proposed in this study(three stages and six subtypes)effectively reflects the severity of renal lesions and clearly delineates the clinical characteristics and prognostic outcomes at each stage. Stage Ⅰ patients treated with anti-tuberculosis drugs combined with double-J stent placement demonstrated favorable outcomes and high renal preservation rates. In contrast,Stages Ⅱ and Ⅲ patients showed poor responses to anti-tuberculosis therapy combined with drainage,with a higher risk of disease progression and relatively worse prognosis,highlighting the recommendation for early nephroureterectomy of the affected kidney.

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