1.Association of HER2 expression with clinicopathologic features and prognosis in 519 cases of urothelial carcinoma
Aoling HUANG ; Ting XIE ; Hongfeng ZHANG ; Shuaijun CHEN ; Zhengzhuo CHEN ; Bin LUO ; Feng GUAN ; Hong-lin YAN ; Jingping YUAN
Chinese Journal of Clinical and Experimental Pathology 2025;41(5):602-607,613
Purpose To investigate the immunohistochemical HER2 expression in a large group of patients with urothelial carcinoma and to compare the results with the pathologic features and survival rate.Methods A total of 519 urothelial carcinoma specimens were collected from two centers.HER2 expression was measured by EnVision immuno-histochemistry.HER2 expression was compared with clinicopathological parameters,and further analyzed in relation to patient prognosis.Results The median age of the 519 patients was 66 years with a male to female ratio of 1.93∶1.Among them,160 cases were radical specimens,and 359 were transurethral resection specimens.The overall HER2 positivity rate was 61.7%(320/519),of which 148 cases(28.5%)were HER2 1+,238(45.9%)were HER2 2+,and 82(15.8%)were HER2 3+.In addition,51 cases(9.8%)were HER2-negative.HER2-positive ex-pression was associated with age,tumor location,histological grade,histological type,surgical approach,lymphovas-cular invasion,and neural invasion(all P<0.05),but there was no significant correlation with gender,pT stage,muscular invasion,or lymph node metastasis.Univariate and multivariate logistic regression analysis showed that age≥ 66 years,higher tumor grade,and lymphovascular invasion were risk factors for positive HER2 expression,and high histological grade and lymphovascular invasion were independent risk factors affecting HER2 expression after controlling for confounders.Survival analysis showed no significant difference in recurrence-free survival between patients with HER2-positive and HER2-negative non-muscle-invasive urothelial carcinoma(P=0.274).Conclusion High histologic grade,tumor lymphovascular invasion,and neural invasion were associated with positive HER2 expression in patients with urothelial carcinoma,and higher histologic grade and lymphovascular invasion are important factors affect-ing HER2 expression.However,HER2-positive expression may not affect the prognosis of patients with non-muscle-invasive bladder urothelial carcinoma.
2.Association of HER2 expression with clinicopathologic features and prognosis in 519 cases of urothelial carcinoma
Aoling HUANG ; Ting XIE ; Hongfeng ZHANG ; Shuaijun CHEN ; Zhengzhuo CHEN ; Bin LUO ; Feng GUAN ; Hong-lin YAN ; Jingping YUAN
Chinese Journal of Clinical and Experimental Pathology 2025;41(5):602-607,613
Purpose To investigate the immunohistochemical HER2 expression in a large group of patients with urothelial carcinoma and to compare the results with the pathologic features and survival rate.Methods A total of 519 urothelial carcinoma specimens were collected from two centers.HER2 expression was measured by EnVision immuno-histochemistry.HER2 expression was compared with clinicopathological parameters,and further analyzed in relation to patient prognosis.Results The median age of the 519 patients was 66 years with a male to female ratio of 1.93∶1.Among them,160 cases were radical specimens,and 359 were transurethral resection specimens.The overall HER2 positivity rate was 61.7%(320/519),of which 148 cases(28.5%)were HER2 1+,238(45.9%)were HER2 2+,and 82(15.8%)were HER2 3+.In addition,51 cases(9.8%)were HER2-negative.HER2-positive ex-pression was associated with age,tumor location,histological grade,histological type,surgical approach,lymphovas-cular invasion,and neural invasion(all P<0.05),but there was no significant correlation with gender,pT stage,muscular invasion,or lymph node metastasis.Univariate and multivariate logistic regression analysis showed that age≥ 66 years,higher tumor grade,and lymphovascular invasion were risk factors for positive HER2 expression,and high histological grade and lymphovascular invasion were independent risk factors affecting HER2 expression after controlling for confounders.Survival analysis showed no significant difference in recurrence-free survival between patients with HER2-positive and HER2-negative non-muscle-invasive urothelial carcinoma(P=0.274).Conclusion High histologic grade,tumor lymphovascular invasion,and neural invasion were associated with positive HER2 expression in patients with urothelial carcinoma,and higher histologic grade and lymphovascular invasion are important factors affect-ing HER2 expression.However,HER2-positive expression may not affect the prognosis of patients with non-muscle-invasive bladder urothelial carcinoma.
3.Analysis of the diagnostic value of Th17/treg cell imbalance in peripheral blood and PD-1+CD3+,miR-146a,miR-122,CRP for postoperative infection of endometrial cancer
Xieyan ZHUANG ; Yan LI ; Linxi JIN ; Hongfeng ZHENG ; Ying LIU
Immunological Journal 2025;41(6):424-432
Objective To analyze the value of peripheral blood helper T cell 17(Th17)/regulatory T cell(Treg),programmed death receptor-1(PD-1)+CD3+,miR-146a,miR-122 and serum C-reactive protein(CRP)in the diagnosis of postoperative infection of endometrial cancer,and to explore the influencing factors of postoperative infection for endometrial cancer.Methods A total of 289 patients with endometrial cancer who underwent surgery from January 2021 to August 2024 were selected and divided into the infection group(n=53)and the non-infection group(n=236)according to the postoperative infection of the patients.Clinical data of two groups were collected and compared.The levels of Th17,Treg and PD-1+CD3+in peripheral blood of the two groups were detected by flow cytometry,and the ratio of Th17/Treg was calculated.The levels of miR-146a and miR-122 in peripheral blood of the two groups were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).The serum CRP levels of the two groups were detected by enzyme-linked immunosorbent assay(ELISA),and the influencing factors of postoperative infection in endometrial cancer were analyzed by multivariate Logistic regression.The receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic value of peripheral blood Th17/Treg,PD-1+CD3+,miR-146a,miR-122 and serum CRP for postoperative infection of endometrial cancer.Results Compared with the non-infection group,the infection group had higher proportions of diabetes,anemia,adjuvant chemoradiotherapy,open abdominal surgery,drainage and catheterization time≥7 d,as well as higher levels of Th17,Th17/Treg,PD-1+CD3+,miR-122,and serum CRP(P<0.01),while the levels of Treg and miR-146a in peripheral blood were lower(P<0.01).Multivariate Logistic regression analysis showed that combined diabetes,anemia,adjuvant chemoradiotherapy,open abdominal surgery,drainage and catheterization time≥7 d,peripheral blood Th17/Treg,PD-1+CD3+,miR-122 and serum CRP levels were all risk factors for postoperative infection of endometrial cancer(P<0.05,P<0.01),while miR-146a in peripheral blood was its protective factor(P<0.05).ROC curve analysis showed that the area under the curve of the combined detection of Th17/Treg,PD-1+CD3+,miR-146a,miR-122 in peripheral blood and serum CRP was higher than that of the individual detection of Th17/Treg,PD-1+CD3+,miR-146a,miR-122 and serum CRP in peripheral blood(P<0.01).Conclusion Postoperative infection of endometrial cancer is closely related to the patients'combined diabetes,anemia,adjuvant chemoradiotherapy,open surgery,and drainage and catheterization time≥7 d.Moreover,Th17/Treg,PD-1+CD3+,miR-122 in peripheral blood and serum CRP are highly expressed in patients with postoperative infection of endometrial cancer,while miR-146a in peripheral blood is expressed at a low level.The combined detection of the five has more advantages in evaluating postoperative infection of endometrial cancer.
4.Analysis of the diagnostic value of Th17/treg cell imbalance in peripheral blood and PD-1+CD3+,miR-146a,miR-122,CRP for postoperative infection of endometrial cancer
Xieyan ZHUANG ; Yan LI ; Linxi JIN ; Hongfeng ZHENG ; Ying LIU
Immunological Journal 2025;41(6):424-432
Objective To analyze the value of peripheral blood helper T cell 17(Th17)/regulatory T cell(Treg),programmed death receptor-1(PD-1)+CD3+,miR-146a,miR-122 and serum C-reactive protein(CRP)in the diagnosis of postoperative infection of endometrial cancer,and to explore the influencing factors of postoperative infection for endometrial cancer.Methods A total of 289 patients with endometrial cancer who underwent surgery from January 2021 to August 2024 were selected and divided into the infection group(n=53)and the non-infection group(n=236)according to the postoperative infection of the patients.Clinical data of two groups were collected and compared.The levels of Th17,Treg and PD-1+CD3+in peripheral blood of the two groups were detected by flow cytometry,and the ratio of Th17/Treg was calculated.The levels of miR-146a and miR-122 in peripheral blood of the two groups were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).The serum CRP levels of the two groups were detected by enzyme-linked immunosorbent assay(ELISA),and the influencing factors of postoperative infection in endometrial cancer were analyzed by multivariate Logistic regression.The receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic value of peripheral blood Th17/Treg,PD-1+CD3+,miR-146a,miR-122 and serum CRP for postoperative infection of endometrial cancer.Results Compared with the non-infection group,the infection group had higher proportions of diabetes,anemia,adjuvant chemoradiotherapy,open abdominal surgery,drainage and catheterization time≥7 d,as well as higher levels of Th17,Th17/Treg,PD-1+CD3+,miR-122,and serum CRP(P<0.01),while the levels of Treg and miR-146a in peripheral blood were lower(P<0.01).Multivariate Logistic regression analysis showed that combined diabetes,anemia,adjuvant chemoradiotherapy,open abdominal surgery,drainage and catheterization time≥7 d,peripheral blood Th17/Treg,PD-1+CD3+,miR-122 and serum CRP levels were all risk factors for postoperative infection of endometrial cancer(P<0.05,P<0.01),while miR-146a in peripheral blood was its protective factor(P<0.05).ROC curve analysis showed that the area under the curve of the combined detection of Th17/Treg,PD-1+CD3+,miR-146a,miR-122 in peripheral blood and serum CRP was higher than that of the individual detection of Th17/Treg,PD-1+CD3+,miR-146a,miR-122 and serum CRP in peripheral blood(P<0.01).Conclusion Postoperative infection of endometrial cancer is closely related to the patients'combined diabetes,anemia,adjuvant chemoradiotherapy,open surgery,and drainage and catheterization time≥7 d.Moreover,Th17/Treg,PD-1+CD3+,miR-122 in peripheral blood and serum CRP are highly expressed in patients with postoperative infection of endometrial cancer,while miR-146a in peripheral blood is expressed at a low level.The combined detection of the five has more advantages in evaluating postoperative infection of endometrial cancer.
5.Study on the application value of fecal SDC2 gene methylation detection in colorectal cancer screening of urban residents in Zengcheng District in Guangzhou City
Yan HE ; Fangfang XU ; Haijun ZUO ; Wei CHEN ; Zhibin LIU ; Zebang LIU ; Xuezhen CHEN ; Qingshen HUI ; Gengwen ZOU ; Zhenbin CAI ; Yang LIU ; Haoshun TAN ; Hongfeng ZHOU ; Jianping WANG
Chinese Journal of Preventive Medicine 2024;58(7):1020-1028
Objective:To investigate the application value of fecal Syndecan-2 (SDC2) gene methylated SDC2 (m SDC2) detection in colorectal cancer (CRC) screening among urban residents in Guangzhou City. Methods:A cross-sectional study was conducted in Shitan Town, Zengcheng District, Guangzhou City from July to December 2022. A community-based screening program for CRC was conducted among residents aged 40-74 years old. m SDC2 detection was employed in the participants, and those with positive results should be recommended to receive colonoscopy examination. The positive rate of m SDC2 detection, colonoscopy compliance rate, detection rate of intestinal lesions and clinicopathological characteristics were observed. The relationship between cycle threshold (CT) value of m SDC2 and intestinal lesions was explored. Further, the cost-effectiveness of screening was evaluated. Results:A total of 8 189 fecal samples were collected from 8 877 participants with the recovery rate of 92.25%. 8 048 qualified samples were enrolled in this study, consisted of 3 182 males (39.54%) and 4 866 females (60.46%), with the average age of 56 years old (40-74 years). The positive rate of m SDC2 detection was 7.99% (643/8 048), and the compliance rate of colonoscopy was 73.10% (470/643). 20 cases (4.25%) of colorectal cancer, 109 cases (23.19%) of advanced adenoma, 145 cases (30.85%) of non-advanced adenoma, 79 cases (16.81%) of polyps were detected. The detection rate of intestinal lesions was 75.11% and indicated significant differences in gender and age. 20 CRCs included 15 of stage 0-I, 4 of stage Ⅱ-Ⅲ and 1 of unknown stage. The CT value of m SDC2 was negatively correlated with the proportion of advanced colorectal neoplasms ( χ2=16.063, P<0.001). The total cost of the screening was 4.339 5 million yuan, the screening benefit was 28.506 2 million yuan, and the benefit-cost ratio was 6.57. Conclusion:The CRC screening strategy of fecal m SDC2 detection combined with colonoscopy has high colonoscopy compliance and detection rate of intestinal lesions, which is conducive to the detection of early CRCs, and has good cost-effectiveness. This study suggests that this method may be applied to the general CRC screening in China and contribute to the prevention of CRC. The CT value of m SDC2 may have a certain suggestion on the malignant degree of intestinal tumors.
6.Study on the application value of fecal SDC2 gene methylation detection in colorectal cancer screening of urban residents in Zengcheng District in Guangzhou City
Yan HE ; Fangfang XU ; Haijun ZUO ; Wei CHEN ; Zhibin LIU ; Zebang LIU ; Xuezhen CHEN ; Qingshen HUI ; Gengwen ZOU ; Zhenbin CAI ; Yang LIU ; Haoshun TAN ; Hongfeng ZHOU ; Jianping WANG
Chinese Journal of Preventive Medicine 2024;58(7):1020-1028
Objective:To investigate the application value of fecal Syndecan-2 (SDC2) gene methylated SDC2 (m SDC2) detection in colorectal cancer (CRC) screening among urban residents in Guangzhou City. Methods:A cross-sectional study was conducted in Shitan Town, Zengcheng District, Guangzhou City from July to December 2022. A community-based screening program for CRC was conducted among residents aged 40-74 years old. m SDC2 detection was employed in the participants, and those with positive results should be recommended to receive colonoscopy examination. The positive rate of m SDC2 detection, colonoscopy compliance rate, detection rate of intestinal lesions and clinicopathological characteristics were observed. The relationship between cycle threshold (CT) value of m SDC2 and intestinal lesions was explored. Further, the cost-effectiveness of screening was evaluated. Results:A total of 8 189 fecal samples were collected from 8 877 participants with the recovery rate of 92.25%. 8 048 qualified samples were enrolled in this study, consisted of 3 182 males (39.54%) and 4 866 females (60.46%), with the average age of 56 years old (40-74 years). The positive rate of m SDC2 detection was 7.99% (643/8 048), and the compliance rate of colonoscopy was 73.10% (470/643). 20 cases (4.25%) of colorectal cancer, 109 cases (23.19%) of advanced adenoma, 145 cases (30.85%) of non-advanced adenoma, 79 cases (16.81%) of polyps were detected. The detection rate of intestinal lesions was 75.11% and indicated significant differences in gender and age. 20 CRCs included 15 of stage 0-I, 4 of stage Ⅱ-Ⅲ and 1 of unknown stage. The CT value of m SDC2 was negatively correlated with the proportion of advanced colorectal neoplasms ( χ2=16.063, P<0.001). The total cost of the screening was 4.339 5 million yuan, the screening benefit was 28.506 2 million yuan, and the benefit-cost ratio was 6.57. Conclusion:The CRC screening strategy of fecal m SDC2 detection combined with colonoscopy has high colonoscopy compliance and detection rate of intestinal lesions, which is conducive to the detection of early CRCs, and has good cost-effectiveness. This study suggests that this method may be applied to the general CRC screening in China and contribute to the prevention of CRC. The CT value of m SDC2 may have a certain suggestion on the malignant degree of intestinal tumors.
7.Simulated Microgravity can Promote the Apoptosis and Change Inflammatory State of Kupffer Cells
Ge JUN ; Liu FEI ; Nie HONGYUN ; Yue YUAN ; Liu KAIGE ; Lin HAIGUAN ; Li HAO ; Zhang TAO ; Yan HONGFENG ; Xu BINGXIN ; Sun HONGWEI ; Yang JIANWU ; Si SHAOYAN ; Zhou JINLIAN ; Cui YAN
Biomedical and Environmental Sciences 2024;37(10):1117-1127
Objective In this study,we analyzed the transcriptome sequences of Kupffer cells exposed to simulated microgravity for 3 d and conducted biological experiments to determine how microgravity initiates apoptosis in Kupffer cells. Methods Rotary cell culture system was used to construct a simulated microgravity model.GO and KEGG analyses were conducted using the DAVID database.GSEA was performed using the R language.The STRING database was used to conduct PPI analysis.qPCR was used to measure the IL1B,TNFA,CASP3,CASP9,and BCL2L11 mRNA expressions.Western Blotting was performed to detect the level of proteins CASP3 and CASP 9.Flow cytometry was used to detect apoptosis and mitochondrial membrane cells.Transmission electron microscopy was used to detect changes in the ultrastructure of Kupffer cells. Results Transcriptome Sequencing indicated that simulated microgravity affected apoptosis and the inflammatory state of Kupffer cells.Simulated microgravity improved the CASP3,CASP9,and BCL2L11 expressions in Kupffer cells.Annexin-V/PI and JC-1 assays showed that simulated microgravity promoted apoptosis in Kupffer cells.Simulated microgravity causes M1 polarization in Kupffer cells. Conclusion Our study found that simulated microgravity facilitated the apoptosis of Kupffer cells through the mitochondrial pathway and activated Kupffer cells into M1 polarization,which can secrete TNFA to promote apoptosis.
8.A multicenter, randomized controlled clinical trial of Pseudomonas aeruginosa injection for prevention of recurrent urinary tract infections
Zhen DU ; Liang CUI ; Zhan GAO ; Yi ZHI ; Gang CUI ; Peng ZHANG ; Hongfeng GUO ; Shan ZHONG ; Benkang SHI ; Yan LI ; Yong ZHANG ; Yifei XING ; Shan CHEN ; Ludong QIAO
Chinese Journal of Urology 2024;45(12):925-931
Objective:To investigate the clinical efficacy and safety of Pseudomonas aeruginosa injection in preventing reurrent urinary tract infection in women. Methods:This was a multicenter, randomized, open, positive-controlled, non-inferiority trial involving female patients with recurrent urinary tract infections (rUTIs) who were admitted to 11 medical centers in China. Inclusion criteria: ①Aged 18-70 years, with verifiable clinical data showing at least 3 episodes of acute UTIs within 1 year and at least 2 episodes within 6 months, and cured by antimicrobial therapy; ② At the time of enrollment, the patients had no obvious symptoms of urinary tract irritation, normal white blood cell count in midstream urine routine (within the normal range of laboratory standards of each unit) or ≤3HP by centrifuge microscopy, negative leucocyte esterase and nitrite, and negative urine culture; ③No abnormal urinary anatomic function (such as urinary obstruction, calculus or congenital urinary malformation) and residual urine volume ≤50 ml were detected by B-ultrasound of urinary system; ④Informed consent signed by the person or agent; ⑤Clear consciousness, able to answer questions independently, according to the requirements of the test plan to complete the research questionnaire. Exclusion criteria: ①Patients allergic to the above drugs; ②Any complex signs of urinary tract infection or pyelonephritis (manifested as low back pain, fever ≥37.3℃, systemic symptoms); ③Drugs affecting immune function were used within 7 days before randomization; ④Patients with basic diseases of urinary system such as obstruction, calculus, urinary stenosis, vesicoureteral reflux or other functional abnormalities, urine diversion, indwelling catheter or stent tube or intermittent catheterization; ⑤Combined with or existing systemic lupus erythematosus, AIDS and other diseases that can lead to systemic immune function abnormalities; ⑥Patients who are known or suspected to be pregnant, breastfeeding, or planning a pregnancy within 3 months of stopping the drug; ⑦Patients with malignant tumors and mental patients; ⑧Persons who have received any other investigational drug treatment or participated in another interventional clinical trial within 4 weeks prior to screening; ⑨Failure to comply with the trial protocol or other conditions deemed unsuitable for enrollment by the investigator. Patients were randomly divided into 2 groups. The experimental group was given Pseudomonas aeruginosa injection for 5 times, 0.5 ml for the first time, and 1 ml/ time per week for the following 4 weeks. The control group was given fosfomycin aminotriol 3g orally, once every 10 days, for 9 consecutive times. The patients were followed up for 6 to 8 months, during which urinary tract symptoms developed and routine urine tests showed abnormally elevated white blood cells, which was defined as recurrent UTIs. Urine routine, liver and kidney function, and urinary secretory immunoglobulin A(SIgA) were reviewed 0-2 days (V2) after the 5th administration of the experimental group and the 4th administration of the control group. Urine routine and urine SIgA were reviewed at (90±10) d (V3) and (180±10) d (V4) after treatment. At (270±10) d (V5) after treatment, the recurrence (re-infection caused by the same species of bacteria) or re-infection (re-infection caused by non-same species of bacteria) of the two groups were compared, and non-inferiority analysis was performed, and the non-inferiority threshold was set at 0.2. Results:From March 2021 to May 2022, a total of 152 rUTIs patients were enrolled in this study, including 80 patients in the experimental group, 71 patients in the intention-to-analysis set (ITT) and 66 patients in the protocol analysis set (PPS). In the control group, 72 cases met ITT in 69 cases and PPS in 67 cases. There were no significant differences in age, body mass index, marital status, duration of urinary tract infection, history of diabetes, history of previous major surgery, history of infection, and urinary SIgA between the two groups (all P>0.05). The recurrence rates of the experimental group and the control group at V5 time point were 44.78% (30/67) and 42.65% (29/68), respectively ( P=0.803) (ITT data set analysis results showed that the difference in recurrence rates between the two groups was 0.0213(95% CI-0.1460-0.1886, P=0.0048). PPS data set analysis showed that the difference of recurrence rate between the two groups was -0.0021(95%CI -0.1711-0.1670, P=0.0109), and the recurrence rate of the experimental group was not worse than that of the control group. At V2 time points, there were no significant differences in liver and kidney function indexes between test group and control group ( P>0.05). At V2 to V4 time points, urinary SIgA of test group and control group were 0.90 (0.37, 2.89) mg/L and 1.32 (0.34, 3.08) mg/L, 1.54 (0.44, 3.23) mg/L and 1.71 (0.27, 2.92) mg/L, 1.11 (0.65, 3.42) mg/L and 2.18 (0.43, 3.26) mg/L, there was no statistical significance ( P>0.05). The incidence of adverse events in the experimental group was 30.0% (24/80), including 14 cases of redness, pain and discomfort at the injection site, 5 cases of fever, 2 cases of allergic rash, and 1 case of urticaria, headache and constipation each. The incidence of adverse events in the control group was 5.6% (4/72), all of which were diarrhea, and the difference between the two groups was statistically significant ( P<0.01). No life-threatening serious adverse events occurred in both groups, and all adverse events were self-healing without additional intervention. Conclusions:Compared with fosfomycin aminotriol, Pseudomonas aeruginosa injection has the same clinical effect in preventing rUTI and has good safety.
9.A multicenter, randomized controlled clinical trial of Pseudomonas aeruginosa injection for prevention of recurrent urinary tract infections
Zhen DU ; Liang CUI ; Zhan GAO ; Yi ZHI ; Gang CUI ; Peng ZHANG ; Hongfeng GUO ; Shan ZHONG ; Benkang SHI ; Yan LI ; Yong ZHANG ; Yifei XING ; Shan CHEN ; Ludong QIAO
Chinese Journal of Urology 2024;45(12):925-931
Objective:To investigate the clinical efficacy and safety of Pseudomonas aeruginosa injection in preventing reurrent urinary tract infection in women. Methods:This was a multicenter, randomized, open, positive-controlled, non-inferiority trial involving female patients with recurrent urinary tract infections (rUTIs) who were admitted to 11 medical centers in China. Inclusion criteria: ①Aged 18-70 years, with verifiable clinical data showing at least 3 episodes of acute UTIs within 1 year and at least 2 episodes within 6 months, and cured by antimicrobial therapy; ② At the time of enrollment, the patients had no obvious symptoms of urinary tract irritation, normal white blood cell count in midstream urine routine (within the normal range of laboratory standards of each unit) or ≤3HP by centrifuge microscopy, negative leucocyte esterase and nitrite, and negative urine culture; ③No abnormal urinary anatomic function (such as urinary obstruction, calculus or congenital urinary malformation) and residual urine volume ≤50 ml were detected by B-ultrasound of urinary system; ④Informed consent signed by the person or agent; ⑤Clear consciousness, able to answer questions independently, according to the requirements of the test plan to complete the research questionnaire. Exclusion criteria: ①Patients allergic to the above drugs; ②Any complex signs of urinary tract infection or pyelonephritis (manifested as low back pain, fever ≥37.3℃, systemic symptoms); ③Drugs affecting immune function were used within 7 days before randomization; ④Patients with basic diseases of urinary system such as obstruction, calculus, urinary stenosis, vesicoureteral reflux or other functional abnormalities, urine diversion, indwelling catheter or stent tube or intermittent catheterization; ⑤Combined with or existing systemic lupus erythematosus, AIDS and other diseases that can lead to systemic immune function abnormalities; ⑥Patients who are known or suspected to be pregnant, breastfeeding, or planning a pregnancy within 3 months of stopping the drug; ⑦Patients with malignant tumors and mental patients; ⑧Persons who have received any other investigational drug treatment or participated in another interventional clinical trial within 4 weeks prior to screening; ⑨Failure to comply with the trial protocol or other conditions deemed unsuitable for enrollment by the investigator. Patients were randomly divided into 2 groups. The experimental group was given Pseudomonas aeruginosa injection for 5 times, 0.5 ml for the first time, and 1 ml/ time per week for the following 4 weeks. The control group was given fosfomycin aminotriol 3g orally, once every 10 days, for 9 consecutive times. The patients were followed up for 6 to 8 months, during which urinary tract symptoms developed and routine urine tests showed abnormally elevated white blood cells, which was defined as recurrent UTIs. Urine routine, liver and kidney function, and urinary secretory immunoglobulin A(SIgA) were reviewed 0-2 days (V2) after the 5th administration of the experimental group and the 4th administration of the control group. Urine routine and urine SIgA were reviewed at (90±10) d (V3) and (180±10) d (V4) after treatment. At (270±10) d (V5) after treatment, the recurrence (re-infection caused by the same species of bacteria) or re-infection (re-infection caused by non-same species of bacteria) of the two groups were compared, and non-inferiority analysis was performed, and the non-inferiority threshold was set at 0.2. Results:From March 2021 to May 2022, a total of 152 rUTIs patients were enrolled in this study, including 80 patients in the experimental group, 71 patients in the intention-to-analysis set (ITT) and 66 patients in the protocol analysis set (PPS). In the control group, 72 cases met ITT in 69 cases and PPS in 67 cases. There were no significant differences in age, body mass index, marital status, duration of urinary tract infection, history of diabetes, history of previous major surgery, history of infection, and urinary SIgA between the two groups (all P>0.05). The recurrence rates of the experimental group and the control group at V5 time point were 44.78% (30/67) and 42.65% (29/68), respectively ( P=0.803) (ITT data set analysis results showed that the difference in recurrence rates between the two groups was 0.0213(95% CI-0.1460-0.1886, P=0.0048). PPS data set analysis showed that the difference of recurrence rate between the two groups was -0.0021(95%CI -0.1711-0.1670, P=0.0109), and the recurrence rate of the experimental group was not worse than that of the control group. At V2 time points, there were no significant differences in liver and kidney function indexes between test group and control group ( P>0.05). At V2 to V4 time points, urinary SIgA of test group and control group were 0.90 (0.37, 2.89) mg/L and 1.32 (0.34, 3.08) mg/L, 1.54 (0.44, 3.23) mg/L and 1.71 (0.27, 2.92) mg/L, 1.11 (0.65, 3.42) mg/L and 2.18 (0.43, 3.26) mg/L, there was no statistical significance ( P>0.05). The incidence of adverse events in the experimental group was 30.0% (24/80), including 14 cases of redness, pain and discomfort at the injection site, 5 cases of fever, 2 cases of allergic rash, and 1 case of urticaria, headache and constipation each. The incidence of adverse events in the control group was 5.6% (4/72), all of which were diarrhea, and the difference between the two groups was statistically significant ( P<0.01). No life-threatening serious adverse events occurred in both groups, and all adverse events were self-healing without additional intervention. Conclusions:Compared with fosfomycin aminotriol, Pseudomonas aeruginosa injection has the same clinical effect in preventing rUTI and has good safety.
10.Causes and prognosis analysis of hyperdynamic left ventricular ejection fraction in intensive care unit patients with sepsis
Feng XIONG ; Hongfeng YANG ; Jun YAN ; Chun WANG ; Zhaochen JIN
Chinese Critical Care Medicine 2023;35(8):834-838
Objective:To analyze the causes of hyperdynamic left ventricular ejection fraction (LVEF) in sepsis patients in the intensive care unit (ICU) and its impact on prognosis.Methods:A retrospective cohort study was conducted. The clinical data of 273 sepsis patients admitted to the department of critical care medicine of the Affiliated People's Hospital of Jiangsu University from January 2018 to October 2021 were collected including gender, age, severity score, comorbidities, source of infection, vital signs, transthoracic echocardiographic (TTE) parameters, fluid intake and output, vasoactive drug dose, therapeutic measures and prognostic indicators. The patients were divided into normal LVEF group (LVEF 0.55-0.70), low LVEF group (LVEF < 0.55) and hyperdynamic LVEF group (LVEF > 0.70) according to the TTE examination results within 7 days of ICU admission. The clinical indicators among the three groups were compared and analyzed, and multivariate Logistic regression analysis was used to screen risk factors for the development of hyperdynamic LVEF in patients with sepsis. Spearman correlation analysis was used to determine the correlation between the mortality of different types of LVEF and clinical variables.Results:Among 273 patients, 20 patients with severe valvular or cardiomyopathy at admission and those who did not completed cardiac ultrasound within 7 days of ICU admission were excluded. A total of 253 patients were finally enrolled, including 169 patients in the normal LVEF group, 40 patients in the low LVEF group, and 44 patients in the hyperdynamic LVEF group. There were statistically significant differences in age, sequential organ failure assessment (SOFA) score, central venous pressure (CVP), heart rate (HR), oxygenation index (PaO 2/FiO 2), blood lactate (Lac), urine output, vasoactive drug dose, ratio of hypertension, ischemic heart disease, chronic liver disease, cancer, invasive mechanical ventilation and renal replacement therapy (RRT), and incidence of septic shock among the different types of LVEF groups. TTE results analysis showed that the hyperdynamic LVEF group had higher stroke volume (SV) and cardiac index (CI) than those in the normal LVEF and low LVEF groups, lower systemic vascular resistance (SVR) than that in the normal LVEF and low LVEF groups, and an increased E/A ratio. The 90-day mortality in the hyperdynamic LVEF group was significantly higher than that in the normal LVEF and low LVEF groups [59.1% (26/44) vs. 24.9% (42/169), 32.5% (13/40), both P < 0.05]. Multivariate Logistic regression analysis showed that chronic liver disease [odds ratio ( OR) = 1.712, 95% confidence interval (95% CI) was 0.912-3.234, P < 0.001], cancer ( OR = 2.784, 95% CI was 1.296-6.151, P < 0.001), HR ( OR = 1.026, 95% CI was 1.014-1.038, P < 0.001), vasoactive drug dose ( OR = 1.133, 95% CI was 1.009-1.291, P < 0.001), and invasive mechanical ventilation ( OR = 2.141, 95% CI was 1.285-3.651, P < 0.001) were independent factors for hyperdynamic LVEF in ICU sepsis patients. Correlation analysis showed that the mortality of hyperdynamic LVEF, normal LVEF and low LVEF patients was positively correlated with vasoactive drug dose ( r value was 0.251, 0.361, 0.289, respectively, all P < 0.001). The mortality of the hyperdynamic LVEF patients was negatively correlated with SVR ( r = -0.545, P < 0.001). Conclusions:Chronic liver disease, cancer, HR, vasoactive drugs dose, and invasive mechanical ventilation are independent risk factors for hyperdynamic LVEF in patients with sepsis. Hyperdynamic LVEF is positively associated with mortality in sepsis patients, which may be due to the the decrease of SVR caused by septic vascular paralysis.

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