1.The safety and efficacy of urinary microbiota transplantation in the treatment of interstitial cystitis
Bo LIU ; Yuwei ZHANG ; Lili ZHANG ; Xinyu XU ; Yang WANG ; Hao LIN ; Chaoqun GU ; Peng JIANG ; Yifan SUN ; Ninghan FENG
Chinese Journal of Urology 2025;46(6):421-429
Objective:To investigate the safety and efficacy of urinary microbiota transplantation(UMT)in treating interstitial cystitis(IC).Methods:A retrospective analysis of the clinical data of three patients with IC treated with UMT at the Central Hospital of Jiangnan University from May 2022 to August 2024. Three women(45,62,79 years)presented with urinary frequency(10 - 90 min intervals),urgency,dysuria,lower abdominal pain,and non-organic sleep disorder,with nocturia(2 - 15 episodes)causing sleep difficulty. Disease durations were 3,6,and 21 years. Prior antibiotic therapy failed. Preoperative urinalysis/culture(x2)ruled out bacterial cystitis,and diagnosed as interstitial cystitis(IC),with one of transient positive urine culture. Preoperative scores for case 1 were self-rating depression scale(SDS)of 49,self-rating anxiety scale(SAS)of 31,interstitial cystitis symptom index(ICSI)of 5,interstitial cystitis problem index(ICPI)of 2,brief urological problem scale of 50,genitourinary pain assessment scale of 10,and pain catastrophizing scale(PCS)of 0. For case 2,the scores were 60 of SDS,66 of SAS,9 of ICSI,11 of ICPI,50 of brief urological problem scale,28 of genitourinary pain assessment scale,and 34 of PCS. For case 3,the scores were 44 of SDS,48 of SAS,11 of ICSI,5 of ICPI,33 of brief urological problem scale,27 of genitourinary pain assessment scale,and 21 of PCS. Preoperative bladder hydro-distention showed mucosal hemorrhage including central block hemorrhage(Case 1),numerous spots(Case 2),and distinct sheets(Case 3). Preoperative urine 16S rRNA sequencing revealed low diversity,increased Gardnerella/ Bacteroides(opportunistic),and decreased Bacillus/ Streptococcus(beneficial). Two healthy young female donors had normal comprehensive tests covering blood/urine/stool,coagulation,CRP,immunity,liver/kidney function,lipids,infectious diseases,hormones,tumor markers,urine culture,TOUCH,and expanded quantitative urine culture. Donor urine 16S rRNA showed low pathogenic( Gardnerella/ Bacteroides)abundance. Donor midstream morning urine was catheter-collected,centrifuged,and the bacterial pellet resuspended in saline. Recipients underwent bladder irrigation pre-UMT. On UMT day,donor bacterial suspension was instilled via catheter with adverse event monitoring. Follow-up included clinic visits at 1 month and 1 year for symptom assessment,scale scoring,cystoscopy evaluating mucosal inflammation,hydrodistension checks,and telephone tracking of urinary symptoms every 2 - 3 months. Prognosis was assessed by symptom relief,scale score reduction,and mucosal recovery. Results:No adverse reactions occurred within 24 hours post-UMT in all 3 cases. Two patients showed same-day urinary urgency reduction;three reported relief from urinary frequency/urgency on postoperative day 7,with 2 - 3 hour daytime intervals and 0 - 5 nocturnal voids. Two patients experienced lower abdominal pain alleviation. Postoperative Week 1 urinalysis and urine cultures revealed no abnormalities. The 16S rRNA test showed a decrease in the abundance of harmful bacteria(e.g., Cupriavidus,Ureaplasm,Mycobacterium,Pseudomonas)and an increase in the abundance of beneficial bacteria( Dietzia,Halomonas,and Streptococcus),and the overall urobacterial structure was significantly improved and similar to that of the donor. Case 1 was followed up for 20 months,and the lab tests were normal,with SDS scales of 38,SAS of 20,ICSI of 3,ICPI of 2,brief urological problem scale of 44,genitourinary pain assessment scale of 10,PCS of 0,at 9 months post-op follow-up,indicating physical and mental improvement. The bladder hydro-distention revealed intact mucosa with only mild inflammation,which improved versus preoperative situation. Case 2 was followed up for 15 months,and the lab tests were normal,with SDS scales of 44,SAS of 34,ICSI of 4,ICPI of 2,brief scale of urinary problems of 0,genitourinary pain assessment scale of 9,PCS of 7,at 2 months post-op follow-up,showing improved anxiety/depression and quality of life. The hydro-distention showed decreased scattered hemorrhagic dots and mucosal inflammation. Case 3 was followed up for 13 months,with an increased leukocytes of urine and the other being normal for lab tests,and SDS scales of 35,SAS of 46,ICSI of 13,ICPI of 13,brief scale of urinary problems of 10,genitourinary pain assessment scale of 33,PCS of 11,at 13 months post-op follow-up,indicating physical and mental improvement. The hydro-distention revealed mucosal congestion,marked submucosal vasodilation,and inflammation decreased compared with preoperative situation. Conclusions:UMT alleviates urinary frequency,urgency,and pain in IC patients with sustained effects,significantly improves urine microecology,and shows no adverse events,positioning it as a viable intervention for IC.
2.The safety and efficacy of urinary microbiota transplantation in the treatment of interstitial cystitis
Bo LIU ; Yuwei ZHANG ; Lili ZHANG ; Xinyu XU ; Yang WANG ; Hao LIN ; Chaoqun GU ; Peng JIANG ; Yifan SUN ; Ninghan FENG
Chinese Journal of Urology 2025;46(6):421-429
Objective:To investigate the safety and efficacy of urinary microbiota transplantation(UMT)in treating interstitial cystitis(IC).Methods:A retrospective analysis of the clinical data of three patients with IC treated with UMT at the Central Hospital of Jiangnan University from May 2022 to August 2024. Three women(45,62,79 years)presented with urinary frequency(10 - 90 min intervals),urgency,dysuria,lower abdominal pain,and non-organic sleep disorder,with nocturia(2 - 15 episodes)causing sleep difficulty. Disease durations were 3,6,and 21 years. Prior antibiotic therapy failed. Preoperative urinalysis/culture(x2)ruled out bacterial cystitis,and diagnosed as interstitial cystitis(IC),with one of transient positive urine culture. Preoperative scores for case 1 were self-rating depression scale(SDS)of 49,self-rating anxiety scale(SAS)of 31,interstitial cystitis symptom index(ICSI)of 5,interstitial cystitis problem index(ICPI)of 2,brief urological problem scale of 50,genitourinary pain assessment scale of 10,and pain catastrophizing scale(PCS)of 0. For case 2,the scores were 60 of SDS,66 of SAS,9 of ICSI,11 of ICPI,50 of brief urological problem scale,28 of genitourinary pain assessment scale,and 34 of PCS. For case 3,the scores were 44 of SDS,48 of SAS,11 of ICSI,5 of ICPI,33 of brief urological problem scale,27 of genitourinary pain assessment scale,and 21 of PCS. Preoperative bladder hydro-distention showed mucosal hemorrhage including central block hemorrhage(Case 1),numerous spots(Case 2),and distinct sheets(Case 3). Preoperative urine 16S rRNA sequencing revealed low diversity,increased Gardnerella/ Bacteroides(opportunistic),and decreased Bacillus/ Streptococcus(beneficial). Two healthy young female donors had normal comprehensive tests covering blood/urine/stool,coagulation,CRP,immunity,liver/kidney function,lipids,infectious diseases,hormones,tumor markers,urine culture,TOUCH,and expanded quantitative urine culture. Donor urine 16S rRNA showed low pathogenic( Gardnerella/ Bacteroides)abundance. Donor midstream morning urine was catheter-collected,centrifuged,and the bacterial pellet resuspended in saline. Recipients underwent bladder irrigation pre-UMT. On UMT day,donor bacterial suspension was instilled via catheter with adverse event monitoring. Follow-up included clinic visits at 1 month and 1 year for symptom assessment,scale scoring,cystoscopy evaluating mucosal inflammation,hydrodistension checks,and telephone tracking of urinary symptoms every 2 - 3 months. Prognosis was assessed by symptom relief,scale score reduction,and mucosal recovery. Results:No adverse reactions occurred within 24 hours post-UMT in all 3 cases. Two patients showed same-day urinary urgency reduction;three reported relief from urinary frequency/urgency on postoperative day 7,with 2 - 3 hour daytime intervals and 0 - 5 nocturnal voids. Two patients experienced lower abdominal pain alleviation. Postoperative Week 1 urinalysis and urine cultures revealed no abnormalities. The 16S rRNA test showed a decrease in the abundance of harmful bacteria(e.g., Cupriavidus,Ureaplasm,Mycobacterium,Pseudomonas)and an increase in the abundance of beneficial bacteria( Dietzia,Halomonas,and Streptococcus),and the overall urobacterial structure was significantly improved and similar to that of the donor. Case 1 was followed up for 20 months,and the lab tests were normal,with SDS scales of 38,SAS of 20,ICSI of 3,ICPI of 2,brief urological problem scale of 44,genitourinary pain assessment scale of 10,PCS of 0,at 9 months post-op follow-up,indicating physical and mental improvement. The bladder hydro-distention revealed intact mucosa with only mild inflammation,which improved versus preoperative situation. Case 2 was followed up for 15 months,and the lab tests were normal,with SDS scales of 44,SAS of 34,ICSI of 4,ICPI of 2,brief scale of urinary problems of 0,genitourinary pain assessment scale of 9,PCS of 7,at 2 months post-op follow-up,showing improved anxiety/depression and quality of life. The hydro-distention showed decreased scattered hemorrhagic dots and mucosal inflammation. Case 3 was followed up for 13 months,with an increased leukocytes of urine and the other being normal for lab tests,and SDS scales of 35,SAS of 46,ICSI of 13,ICPI of 13,brief scale of urinary problems of 10,genitourinary pain assessment scale of 33,PCS of 11,at 13 months post-op follow-up,indicating physical and mental improvement. The hydro-distention revealed mucosal congestion,marked submucosal vasodilation,and inflammation decreased compared with preoperative situation. Conclusions:UMT alleviates urinary frequency,urgency,and pain in IC patients with sustained effects,significantly improves urine microecology,and shows no adverse events,positioning it as a viable intervention for IC.
3.Analysis on correlation between serum levels of TAT,t-PAIC,TM and the progress of intracranial atherosclerotic stenosis
Peng WANG ; Chunhe ZHANG ; Jian ZHAO ; Ninghan CHU ; Xinzhe LYU ; Lin ZHANG ; Danlei WU ; Ruiju ZUO ; Rui ZHANG
Chinese Journal of Arteriosclerosis 2024;32(3):243-248
Aim To investigate the serum levels of thrombin-antithrombin complex(TAT),tissue type plas-minogen activator-inhibitor complex(t-PAIC)and thrombomodulin(TM)in patients with intracranial atherosclerotic steno-sis(ICAS),and their correlations with the degree of stenosis.Methods A total of 196 ICAS patients(ICAS group)who underwent treatment in Cangzhou People's Hospital from January 2021 to February 2023 were enrolled as research sub-jects.Based on the degree of vascular stenosis,they were separated into three groups:mild group(n=78),moderate group(n.=64),and severe group(n=54).A group of 196 healthy outpatient with similar clinical basic data to ICAS patients was selected as controls.The serum levels of TAT,t-PAIC,and TM in each group were compared;Spearman method was applied to analyze the correlation between serum levels of TAT,t-PAIC,TM and stenosis severity in ICAS pa-tients;Multivariate Logistic regression was applied to analyze the influencing factors of severe stenosis in ICAS patients;ROC curve was applied to analyze the predictive value of serum TAT,t-PAIC,TM and total cholesterol(TC)levels for se-vere stenosis in ICAS patients.Results Compared with the control group,the serum levels of TAT,t-PAIC,and TM were significantly increased in the ICAS group(P<0.05);the levels of serum TAT,t-PAIC,TM,and TC in the mild,moderate,and severe groups increased accordingly(P<0.05).Spearman analysis showed that the serum levels of TAT,t-PAIC,and TM in ICAS patients were positively correlated with the degree of stenosis(r=0.574,0.695,0.628;all P<0.05).Multivariate Logistic regression analysis showed that TAT,t-PAIC,TM,and TC were independent risk factors for severe stenosis in ICAS patients(P<0.05).The ROC curve showed that the AUC of severe stenosis in ICAS patients predicted by combination of TAT,t-PAIC,TM,and TC was 0.927,with a sensitivity of 83.33%and a specificity of 86.62%,which was superior to the independent prediction of TAT,t-PAIC,TM and TC(Zcombined detection-TAT=4.617,Zcombined deteetion-t-PAIC=4.024,Zcombined detection-TM=4.004,Zcombined detection-TC=7.078,all P=0.000).Conclusion The ser-um levels of TAT,t-PAIC,and TM in the ICAS group were significantly increased,and were positively correlated with the severity of stenosis.The combination of the three and TC has a high predictive value for the occurrence of severe stenosis in ICAS patients.
4.Efficacy and safety of cryoablation combined with Camrelizumab monoclonal antibody in treatment of hepatocellular carcinoma
Changwang ZHANG ; Ninghan WU ; Cong WANG ; Zheng ZHENG ; Siming GAO ; Changpeng ZOU ; Sujing ZHANG ; Na LI
Journal of Clinical Hepatology 2024;40(6):1169-1174
Objective To investigate the efficacy and safety of cryoablation combined with Camrelizumab monoclonal antibody in the treatment of hepatocellular carcinoma(HCC).Methods A total of 103 HCC patients who were admitted to our hospital from June 2020 to June 2023 were enrolled and randomly divided into combined treatment group with 53 patients and control group with 50 patients.The patients in the control group received percutaneous argon-helium cryoablation,and those in the combined treatment group received percutaneous argon-helium cryoablation combined with Camrelizumab monoclonal antibody.The two groups were compared in terms of short-term response,changes in T lymphocyte subsets after treatment,changes in liver function and alpha-fetoprotein(AFP)after treatment,and progression-free survival and overall survival during follow-up.The t-test was used for comparison of normally distributed continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to plot survival curves,and the log-rank test was used for comparison of survival time between the two groups.Results The combined treatment group had significantly higher overall response rate and disease control rate than the control group(χ2=4.156 and 4.348,P=0.042 and 0.037).After treatment,the combined treatment group had significant increases in the percentages of CD3+and CD4+T lymphocytes and CD4+/CD8+ratio(P<0.05)and a significant reduction in the percentage of CD8+T lymphocytes(P<0.05),while the control group had no significant changes in T lymphocyte subsets after treatment(P>0.05),and compared with the control group after treatment,the combined treatment group had significantly higher percentages of CD3+and CD4+T lymphocytes and CD4+/CD8+ratio(all P<0.05)and a significantly lower percentage of CD8+T lymphocytes(P<0.05).After treatment,both groups had significant reductions in the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and AFP(all P<0.05)and a significant increase in the level of albumin(Alb)(P>0.05),and compared with the control group after treatment,the combined treatment group had significantly lower levels of ALT,AST,and AFP(all P<0.05)and a significantly higher level of Alb(P<0.05).There were no significant differences in the incidence rates of grade Ⅲ—Ⅳ(moderate to severe)adverse reactions between the two groups(P>0.05).Compared with the control group,the combined treatment group had significantly better median progression-free survival(21.32 months vs 15.31 months,χ2=4.689,P=0.030)and median overall survival(28.36 months vs 20.75 months,χ2=5.030,P=0.025).Conclusion Argon-helium cryoablation combined with Camrelizumab monoclonal antibody can effectively improve short-term response,enhance immune function,and prolong survival time,with a favorable safety profile.
5.Characteristics of fine lymphocyte typing in myelodysplastic syndrome
Yu SHI ; Min WANG ; Ninghan ZHANG ; Fang LIU ; Chun QIAO ; Yan WANG ; Rong WANG ; Huimin JIN ; Yujie WU
Chinese Journal of Laboratory Medicine 2024;47(12):1403-1410
Objective:To investigate the characteristics of fine lymphocyte typing in patients with myelodysplastic sydrome (MDS) and evaluate the changes of immune status during the course of MDS.Methods:A retrospective study was conducted on 73 patients with MDS, including 47 males and 26 females, aged 66 (56, 73) years old, diagnosed at the First Affiliated Hospital of Nanjing Medical University from February 1, 2022 to January 31, 2024. Besides, 30 healthy individuals from the Health Management Center were selected as the control group. The deep lymphocyte typing was detected by flow cytometry. The differences of lymphocyte subset distribution among the groups were compared; Spearman′s rank correlation coefficient was used to analyze the correlation between lymphocyte subpopulation and blast cells or CD34 +cells. Results:As the risk level of revised International Prognostic Scoring System(IPSS-R)increased, the proportion of helper T(Th) cells ( P=0.047) and naivesubpopulation (CD4+CD45RA+CD62L+) ( P=0.021) in the low-risk group, middle-risk group, and high-risk group increased gradually, while memory subpopulation(CD4+CD45RA-) ( P=0.007) gradually decreased; compared to the group with the low amount of gene mutations, the proportion of B lymphocyte cells (8.76% vs 18.41%, P=0.005) and late activated cytotoxic T lymphocyte (Tc) cells (CD8+HLADR+)(21.21% vs 31.69%, P=0.020) decreased in the high group, and natural killer (NK) cells increased (14.98% vs 8.94%, P=0.032). There was a correlation between the percentage of blast cells and the proportion of Th cells ( P=0.022), naive subpopulation ( P=0.045), memory subpopulation ( P=0.017), and highly activated Tc cells(CD8 +CD38 +HLADR +) ( P=0.013). Conclusions:In patients with MDS, the proportion of Th cells and naive subpopulations is increased, while that of memory subpopulations is decreased, which may indicate an increased risk of IPSS-R; the decreased proportion of B cells, late activated Tc cells, and the increased proportion of NK cells may suggest the accumulation of gene mutations. The differences of lymphocyte subpopulation distribution among MDS patients with different IPSS-R risk level and different amount of gene mutations, indicate that there is immune dysregulation during the course of MDS. Fine lymphocyte typing is helpful to evaluate the changes in immune function in MDS patients.
6.Characteristics of fine lymphocyte typing in myelodysplastic syndrome
Yu SHI ; Min WANG ; Ninghan ZHANG ; Fang LIU ; Chun QIAO ; Yan WANG ; Rong WANG ; Huimin JIN ; Yujie WU
Chinese Journal of Laboratory Medicine 2024;47(12):1403-1410
Objective:To investigate the characteristics of fine lymphocyte typing in patients with myelodysplastic sydrome (MDS) and evaluate the changes of immune status during the course of MDS.Methods:A retrospective study was conducted on 73 patients with MDS, including 47 males and 26 females, aged 66 (56, 73) years old, diagnosed at the First Affiliated Hospital of Nanjing Medical University from February 1, 2022 to January 31, 2024. Besides, 30 healthy individuals from the Health Management Center were selected as the control group. The deep lymphocyte typing was detected by flow cytometry. The differences of lymphocyte subset distribution among the groups were compared; Spearman′s rank correlation coefficient was used to analyze the correlation between lymphocyte subpopulation and blast cells or CD34 +cells. Results:As the risk level of revised International Prognostic Scoring System(IPSS-R)increased, the proportion of helper T(Th) cells ( P=0.047) and naivesubpopulation (CD4+CD45RA+CD62L+) ( P=0.021) in the low-risk group, middle-risk group, and high-risk group increased gradually, while memory subpopulation(CD4+CD45RA-) ( P=0.007) gradually decreased; compared to the group with the low amount of gene mutations, the proportion of B lymphocyte cells (8.76% vs 18.41%, P=0.005) and late activated cytotoxic T lymphocyte (Tc) cells (CD8+HLADR+)(21.21% vs 31.69%, P=0.020) decreased in the high group, and natural killer (NK) cells increased (14.98% vs 8.94%, P=0.032). There was a correlation between the percentage of blast cells and the proportion of Th cells ( P=0.022), naive subpopulation ( P=0.045), memory subpopulation ( P=0.017), and highly activated Tc cells(CD8 +CD38 +HLADR +) ( P=0.013). Conclusions:In patients with MDS, the proportion of Th cells and naive subpopulations is increased, while that of memory subpopulations is decreased, which may indicate an increased risk of IPSS-R; the decreased proportion of B cells, late activated Tc cells, and the increased proportion of NK cells may suggest the accumulation of gene mutations. The differences of lymphocyte subpopulation distribution among MDS patients with different IPSS-R risk level and different amount of gene mutations, indicate that there is immune dysregulation during the course of MDS. Fine lymphocyte typing is helpful to evaluate the changes in immune function in MDS patients.
7.The expressional characteristics and diagnostic values of TRBC1 in mature T-cell lymphoma
Ninghan ZHANG ; Xiao CHEN ; Sishu ZHAO ; Chun QIAO ; Lu LIU ; Jianyong LI ; Yujie WU
Chinese Journal of Hematology 2022;43(7):575-580
Objective:To investigate the expression characteristics of TRBC1 protein in mature T-cell lymphoma (TCL) , and compare with T-cell receptor (TCR) -Vβ repertoire analysis and TCR gene rearrangement results, to explore the value of TRBC1 in the diagnosis of TCL.Methods:The expression of TRBC1 was detected by multi-parameter flow cytometry in 30 cases of TCL, 40 cases of normal controls and 50 cases of patients without T lymphocyte proliferative diseases (non-TCL) admitted to the Department of Hematology, The First Affiliated Hospital of Nanjing Medical University. The diagnostic value of TCRVβ repertoire analysis, TCR gene rearrangement and TRBC1 restricted expression detection in TCL was evaluated.Results:The positive rates of CD4 +T and CD8 +T cell subsets TRBC1 in normal control group were (39.6±6.5) % and (39.3±4.4) %. The positive rates of CD4 +T and CD8 +T cell subsets TRBC1 in non-TCL were (39.1±3.8) % and (36.0±8.4) %. All 30 cases of TCL were CD3 +TCRγδ -, and the positive rate of TRBC1 was >92.3% or <12.7%. All cases showed restrictive expression pattern (monoclonal expression) , which was significantly different from those of the normal control and the non-TCL cases ( P<0.001) . In terms of the diagnostic performance of T cell clonality, the sensitivity of TRBC1 was 100%, the positive detection rate of TCR gene rearrangement was 92.8%, and the sensitivity of TCRVβ detection was 94.1%. Kappa test showed high consistency among the three detective methods. Conclusion:Multi-parameter flow cytometry detection of TRBC1 expression level can quickly and efficiently diagnose mature T-cell lymphoma, which has good clinical application value.
8.Association of macrophage migration inhibitory factor gene-173 locus polymorphism and prostate cancer
Guanxiong DING ; Lixin HUA ; Zheng XU ; Ninghan FENG ; Ninghong SONG ; Wei ZHANG ; Hongfei WU
Chinese Journal of Urology 2009;30(6):379-381
Objective To study the association of MIF-173 locus polymorphism and the risk of prostate cancer (PCa) in China. Methods A case control study including 259 PCa patients and 301 age-matched controls was conducted. The polymorphisms of MIF-173 locus were analyzed by poly-merase chain reaction restriction fragment length polymorphism (PCR-RFLP) technique using genomic DNA isolated from peripheral blood lymphocytes. The correlations between the susceptibility to PCa and different genotypes were compared. The effect of age, smoking method and family history of canc-er were also analyzed. Results The rate of the MIF-173 * C variant allele of the PCa patients(n=259) was significantly higher than that of the controls (n=301) (36.0% vs 15.0%). The MIF-173 *C variant allele could significantly increase the risk of PCa (OR=2.96,95%CI: 1.92-4.57). Peo-ple with older age (age>70) or family history of cancer, who carried MIF-173 * C allele demonstra-ted a significantly increased risk in comparison with those carrying wild genotype of G/G(OR=3.66, 95%CI=2.02-6.62;OR=3.26, 95%CI=1.24-8.55). Conclusion These results suggested that polymorphisms of MIF-173 locus appear to influence the risk of PCa and may have synergistic effect with age and family history of cancer.

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