1.Complement C3 is involved in the recruitment and activation of mast cells during renal interstitial fibrosis
Yanping FENG ; Zhenzhou LI ; Jiong CUI ; Xiaoting WU ; Liyan YANG ; Jianxin WAN
Chinese Journal of Nephrology 2024;40(12):952-960
Objective:To observe the role of complement C3 in the process of renal interstitial fibrosis.Methods:Renal interstitial fibrosis model was established by unilateral ureteral obstruction (UUO) in male C3-deficient (C3KO) mice and age-matched C57BL/6 wild type (WT) mice (8-12 weeks of age). Mice were randomly divided into 4 groups, including sham operation in WT group (WTcontrol) ( n=6), UUO operation in WT group (WTuuo) ( n=6), sham operation in C3-deficient group (C3KOcontrol) ( n=6), and UUO operation in C3-deficient group (C3KOuuo) ( n=6). Tubular interstitial fibrosis was observed by both HE staining and Masson staining. The expression of C3, trypsin (tryptase), angiotensinⅡ (AngⅡ), transforming growth factor β1 (TGF-β1), and matrix metalloproteinase-9 (MMP-9) was detected by immunohistochemical staining. Chymase level were assessed by immunofluorescence staining. The levels of AngⅡ and C3 cleavage fragments C3a and MMP-9 were determined by enzyme-linked immunosorbent assay. The change in renin mRNA was determined by real-time PCR. The changes of chymase, renin, and TGF-β1 were detected by Western blotting. Results:Compared with the WTcontrol group mice, the WTuuo group mice showed significant renal tubular injury, renal interstitial fibrosis, increased infiltration of mast cells, and significantly increased expression of C3, C3a, chymase, renin, AngⅡ, TGF-β1, and MMP-9 in the renal tissue (all P<0.05). Compared with the WTuuo group mice, the renal tubular injury and renal interstitial fibrosis in the C3KOuuo group mice were significantly reduced, and C3 and C3a were not detected in renal tissue. Mast cells infiltration was reduced, and the expression of chymase, renin, AngⅡ, TGF-β1, and MMP-9 was weakened (all P<0.05). Conclusion:C3/C3a can participate in the recruitment and activation of mast cells to release chymase in kidney interstitial fibrosis, and promote the expression of renin, AngⅡ, TGF-β1, MMP 9 and other substances, thus aggravating kidney injury.
2.Complement C3 is involved in the recruitment and activation of mast cells during renal interstitial fibrosis
Yanping FENG ; Zhenzhou LI ; Jiong CUI ; Xiaoting WU ; Liyan YANG ; Jianxin WAN
Chinese Journal of Nephrology 2024;40(12):952-960
Objective:To observe the role of complement C3 in the process of renal interstitial fibrosis.Methods:Renal interstitial fibrosis model was established by unilateral ureteral obstruction (UUO) in male C3-deficient (C3KO) mice and age-matched C57BL/6 wild type (WT) mice (8-12 weeks of age). Mice were randomly divided into 4 groups, including sham operation in WT group (WTcontrol) ( n=6), UUO operation in WT group (WTuuo) ( n=6), sham operation in C3-deficient group (C3KOcontrol) ( n=6), and UUO operation in C3-deficient group (C3KOuuo) ( n=6). Tubular interstitial fibrosis was observed by both HE staining and Masson staining. The expression of C3, trypsin (tryptase), angiotensinⅡ (AngⅡ), transforming growth factor β1 (TGF-β1), and matrix metalloproteinase-9 (MMP-9) was detected by immunohistochemical staining. Chymase level were assessed by immunofluorescence staining. The levels of AngⅡ and C3 cleavage fragments C3a and MMP-9 were determined by enzyme-linked immunosorbent assay. The change in renin mRNA was determined by real-time PCR. The changes of chymase, renin, and TGF-β1 were detected by Western blotting. Results:Compared with the WTcontrol group mice, the WTuuo group mice showed significant renal tubular injury, renal interstitial fibrosis, increased infiltration of mast cells, and significantly increased expression of C3, C3a, chymase, renin, AngⅡ, TGF-β1, and MMP-9 in the renal tissue (all P<0.05). Compared with the WTuuo group mice, the renal tubular injury and renal interstitial fibrosis in the C3KOuuo group mice were significantly reduced, and C3 and C3a were not detected in renal tissue. Mast cells infiltration was reduced, and the expression of chymase, renin, AngⅡ, TGF-β1, and MMP-9 was weakened (all P<0.05). Conclusion:C3/C3a can participate in the recruitment and activation of mast cells to release chymase in kidney interstitial fibrosis, and promote the expression of renin, AngⅡ, TGF-β1, MMP 9 and other substances, thus aggravating kidney injury.
3.Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial.
Chengyuan GU ; Zengjun WANG ; Tianxin LIN ; Zhiyu LIU ; Weiqing HAN ; Xuhui ZHANG ; Chao LIANG ; Hao LIU ; Yang YU ; Zhenzhou XU ; Shuang LIU ; Jingen WANG ; Linghua JIA ; Xin YAO ; Wenfeng LIAO ; Cheng FU ; Zhaohui TAN ; Guohua HE ; Guoxi ZHU ; Rui FAN ; Wenzeng YANG ; Xin CHEN ; Zhizhong LIU ; Liqiang ZHONG ; Benkang SHI ; Degang DING ; Shubo CHEN ; Junli WEI ; Xudong YAO ; Ming CHEN ; Zhanpeng LU ; Qun XIE ; Zhiquan HU ; Yinhuai WANG ; Hongqian GUO ; Tiwu FAN ; Zhaozhao LIANG ; Peng CHEN ; Wei WANG ; Tao XU ; Chunsheng LI ; Jinchun XING ; Hong LIAO ; Dalin HE ; Zhibin WU ; Jiandi YU ; Zhongwen FENG ; Mengxiang YANG ; Qifeng DOU ; Quan ZENG ; Yuanwei LI ; Xin GOU ; Guangchen ZHOU ; Xiaofeng WANG ; Rujian ZHU ; Zhonghua ZHANG ; Bo ZHANG ; Wanlong TAN ; Xueling QU ; Hongliang SUN ; Tianyi GAN ; Dingwei YE
Chinese Medical Journal 2023;136(10):1207-1215
BACKGROUND:
LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer.
METHODS:
We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels.
RESULTS:
On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]).
CONCLUSION:
LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT04563936.
Humans
;
Male
;
Antineoplastic Agents, Hormonal/therapeutic use*
;
East Asian People
;
Gonadotropin-Releasing Hormone/agonists*
;
Goserelin/therapeutic use*
;
Prostate-Specific Antigen
;
Prostatic Neoplasms/drug therapy*
;
Testosterone
4.Effect of behavioral intervention based on social media to promote HIV/syphilis testing in young men who have sex with men
Zhenzhou LUO ; Weiying CHEN ; Yi DING ; Jianghao CHEN ; Qiuhong WU ; Weiming TANG ; Lishan TIAN ; Bo LI
Chinese Journal of Epidemiology 2022;43(6):892-897
Objective:To evaluate the effect of social media based behavioral intervention on promoting joint testing of HIV and syphilis in young men who have sex with men (MSM).Methods:After the recruitment, the participants who met the inclusion criteria were randomly divided (1∶1) into two groups, i.e. social media intervention group and control group. The control group was given routine voluntary counseling and testing (VCT) services. The intervention group was also given VCT services, besides; the comprehensive strategies through social media, including regular health education message and testing information sending, were given to them to strengthen the behavioral intervention. Follow up was conducted for the participants for 12 months after the intervention. The number and the proportion of young MSM receiving HIV and syphilis testing, and the reported proportion of the young MSM with sexually transmitted diseases (STD) symptoms between the intervention group and the control group were compared to evaluate the effect of the intervention.Results:A total of 315 young MSM were recruited (158 in the intervention group and 157 in the control group), in whom 248 young MSM completed the follow up. The follow-up rate was 78.7%. There was no significant difference in baseline characteristics between the intervention group and the control group (all P>0.05). The proportion of young MSM receiving more than one joint testing in the intervention group was slightly higher than that in the control group (53.2% vs. 48.4%, rate difference (RD): 4.8%, 95% CI: -7.5%-17.0%, P=0.448) without significant difference. However, in the young MSM who used condoms in the last anal sex, the proportion of those receiving more than one joint testing in the intervention group was higher than that in the control group (63.8% vs. 46.1%, RD: 17.7%, 95% CI: 1.5%-32.6%, P=0.035). In addition, the reported proportion of young MSM with STD symptoms in the intervention group was significantly lower than that in the control group (6.3% vs. 18.0%,RD: -11.7%, 95% CI: -20.6%- -3.0%, P=0.005). Conclusion:Compared with routine VCT, social media based behavioral intervention might promote joint HIV and syphilis testing in the young MSM who used condom in the study. It could significantly reduce the reporting proportion of STD symptoms, suggesting that this method can promote the AIDS and STD prevention related behaviors in young MSM.
5.Identification of pathogenic variant in a Chinese pedigree affected with non-syndromic cleft lip and palate.
Mingjie ZHANG ; Jia HUANG ; Feifei SHI ; Jiahuan HE ; Hai XIAO ; Dong WU ; Hongdan WANG ; Hongyan LIU
Chinese Journal of Medical Genetics 2021;38(1):52-55
OBJECTIVE:
To explore the genetic basis for a Chinese pedigree affected with non-syndromic cleft lip and cleft palate (NSCLP).
METHODS:
With informed consent obtained, members of the pedigree were subjected to clinical examination and history taking to exclude syndromic cleft lip and palate. One affected member was subjected to whole-exome sequencing and bioinformatics analysis. Candidate variant was verified by Sanger sequencing and co-segregation analysis of her family members and 100 unrelated healthy individuals.
RESULTS:
Whole-exome sequencing and co-segregation analysis showed that all affected members of this pedigree have carried a heterozygous missense c.253A>G (p.Cys85Arg) variant in exon 4 of the IRF6 gene, which has co-segregated with the phenotype and was not found among the 100 unrelated healthy individuals.
CONCLUSION
The missense c.253A>G variant in exon 4 of the IRF6 gene probably underlay the NSCLP in this pedigree.
Brain/abnormalities*
;
China
;
Cleft Lip/genetics*
;
Cleft Palate/genetics*
;
Female
;
Humans
;
Interferon Regulatory Factors/genetics*
;
Mutation, Missense
;
Pedigree
;
Whole Exome Sequencing
6.The effect of adjuvant radiotherapy on postoperative complications of immediate deep inferior epigastric artery perforator flap breast reconstruction
Yingying ZHANG ; Xiaoli YU ; Ayong CAO ; Zhen HU ; Guangyu LIU ; Zhenzhou SHEN ; Zhimin SHAO ; Jiong WU
Chinese Journal of Surgery 2021;59(9):777-781
Objective:To examine the effect of adjuvant radiotherapy on postoperative complications of immediate deep inferior epigastric artery perforator (DIEP) flap breast reconstruction.Methods:Data was collected from 185 patients underwent immediate DIEP reconstruction during November 2006 to March 2020 Department of Breast Surgery, Fudan University Shanghai Cancer Center. All the patients were female, aging (43.0±7.8) years (range: 29 to 61 years). The series included with a total of 187 flaps (2 bilateral, 183 unilateral). Included patients were divided into 2 groups: immediate DIEP reconstruction requring or not requring post-mastectomy radiation therapy (71 cases (71 flaps) in PMRT group, 114 cases (116 flaps) in control group). The aesthetic outcome were measured by Kroll score system and compared between the groups by t test. The complications included partial flap loss, minor necrosis were analyzed between the groups by χ 2 test, while the influence of the other correlation factors on complication occurrence was analyzed by Logistic analysis. Results:The controll groups showed better aesthetic results (2.21±0.55 vs. 2.47±0.82, t=-2.593, P=0.010). Complication rate in PMRT group was higher than that in control group (19.7% (15/71) vs. 4.2% (4/116), χ2=15.079, P<0.01). The complication rate was not correlated with age, body mass index, perforator number, neoadjuvant chemotherapy and adjuvant chemotherapy. Conclusions:Correlation was observed between adjuvant radiotherapy and post-operative complication of the DIEP flap. However, the complication occurrence and aesthetic results remain in the acceptable range. The other factors such as age, body mass index, perforator number, neoadjuvant chemotherapy and adjuvant chemotherapy should not be considered as prognosis factor of post-operative complication of the DIEP flap.
7.The effect of adjuvant radiotherapy on postoperative complications of immediate deep inferior epigastric artery perforator flap breast reconstruction
Yingying ZHANG ; Xiaoli YU ; Ayong CAO ; Zhen HU ; Guangyu LIU ; Zhenzhou SHEN ; Zhimin SHAO ; Jiong WU
Chinese Journal of Surgery 2021;59(9):777-781
Objective:To examine the effect of adjuvant radiotherapy on postoperative complications of immediate deep inferior epigastric artery perforator (DIEP) flap breast reconstruction.Methods:Data was collected from 185 patients underwent immediate DIEP reconstruction during November 2006 to March 2020 Department of Breast Surgery, Fudan University Shanghai Cancer Center. All the patients were female, aging (43.0±7.8) years (range: 29 to 61 years). The series included with a total of 187 flaps (2 bilateral, 183 unilateral). Included patients were divided into 2 groups: immediate DIEP reconstruction requring or not requring post-mastectomy radiation therapy (71 cases (71 flaps) in PMRT group, 114 cases (116 flaps) in control group). The aesthetic outcome were measured by Kroll score system and compared between the groups by t test. The complications included partial flap loss, minor necrosis were analyzed between the groups by χ 2 test, while the influence of the other correlation factors on complication occurrence was analyzed by Logistic analysis. Results:The controll groups showed better aesthetic results (2.21±0.55 vs. 2.47±0.82, t=-2.593, P=0.010). Complication rate in PMRT group was higher than that in control group (19.7% (15/71) vs. 4.2% (4/116), χ2=15.079, P<0.01). The complication rate was not correlated with age, body mass index, perforator number, neoadjuvant chemotherapy and adjuvant chemotherapy. Conclusions:Correlation was observed between adjuvant radiotherapy and post-operative complication of the DIEP flap. However, the complication occurrence and aesthetic results remain in the acceptable range. The other factors such as age, body mass index, perforator number, neoadjuvant chemotherapy and adjuvant chemotherapy should not be considered as prognosis factor of post-operative complication of the DIEP flap.
8.Safety analysis of laparoscopic radical resection for colorectal cancer in patients aged over 70 years old
Zhenzhou TAO ; Yang LI ; Guang CAO ; Jiexiong LIANG ; Jixiang WU
Clinical Medicine of China 2019;35(1):1-4
Objective To analyze the safety and efficacy of laparoscopic radical resection of colorectal cancer for elderly patients over 70 years old. Methods From January 2014 to January 2017,a retrospective analysis of the patients with radical surgery for colorectal cancer in Department of General Surgery,Beijing Anzhen Hospital,Capital Medical University was performed. According to the patient′s age, the patients were divided into ≥70 years old group (68 cases) and<70 years old group (84 cases). The preoperative clinical data of the two groups were analyzed. The surgeons strictly followed the standard lymph node cleaning and the principle of no tumor for colorectal cancer radical operation. The surgical conditions, pathology,short-term efficacy and the follow-up conditions of the two groups were compared. Statistical analysis was performed using SPSS 20. 0. The normal distribution of the data was expressed as Mean±SD,and the t-test was used for comparison between the group. The count data was compared using the χ2 test or the Fisher exact probability method. Results The operation was successfully completed in both groups. In the group of≥70 years old,2 cases were converted to open due to extensive adhesion of the abdominal cavity,no perioperative death. Compared with the<70 years old group,≥70 years old group had more hypertension and coronary heart disease, respectively ( 38. 2%( 26/68 ) vs. 14. 3%( 12/84 )), and the difference was statistically significant ( P<0. 05 ) . There was no significant difference in intraoperative blood loss and operation time between the two groups (P>0. 05) . There was statistically significant difference in incidence of postoperative cardiovascular events between the groups (26. 4%(18/68) vs. 7. 14%(6/84)χ2= 6. 428, P=0. 010) . However,there were no significant differences between the two groups in implications,rate of death and the time stayed in hospital. (P>0. 05). Conclusion Laparoscopic radical resection for colorectal cancer patients over 70 years old is safe and feasible with strict indications and attention to perioperative management.
9.Mutation and Clinical Feature of IL-7R in Adult Patients with Acute Lymphoblastic Leukemia.
Guo-Mei FU ; Dan-Dan CHEN ; Chuan WU ; Meng WANG ; Zheng-Xi PAN ; Xue-Yang PENG ; Hui SUN ; Ling SUN ; Yan-Fang LIU ; Zhong-Xing JIANG
Journal of Experimental Hematology 2019;27(5):1416-1423
OBJECTIVE:
To investigate the IL-7R gene mutation and clinical features of adult patients with acute lymphoblastic leukemia (ALL).
METHODS:
One hundred sixty-four cases of newly treated adults with ALL from May 2016 to December 2018 were selected. Targeted and specific next-generation sequencing technology was used to detected a total of 16 types of Ph-like ALL mutations, which include IL-7R mutation, and the cilinical features, rate, types and sites of IL-7R were analyzed.
RESULTS:
IL-7R mutation was determined in 10 cases of 164 adult patients with ALL and the total mutation frequency was 13 times (6.1%). Out of 10 cases 5 cases were male (50%), 5 cases were female (50%). 6 cases of B-ALL ( 60% ) and 4 cases of T-ALL (40%). The mutation site of all cases was located at exon 6, among which 6 cases had replacement mutations, 3 cases had deletion mutations and 4 cases had insertion mutations. In addition, 1 triple and 1 double mutation of IL-7R were found. Besides, six mutation sites were newly identified, including: c.720_724del, c.723_726del, c.721_722insAGTG, c.727_728insTAACGGCCCCCTGCT, c.727_728insATGCAGGGAGCGAA and c.728_729insAAGTGTCA.
CONCLUSION
Six novel mutation sites and a poor manifestation of IL-7R have been explored in this research. Thus more samples are required to study the effects of IL-7R mutation on ALL treatment.
Adult
;
Female
;
Humans
;
Interleukin-7 Receptor alpha Subunit
;
genetics
;
Male
;
Mutation
;
Precursor Cell Lymphoblastic Leukemia-Lymphoma
;
Signal Transduction
10.Molecular epidemiological characteristics of genital Chlamydia trachomatis
Lanlan LIU ; Wu LI ; Si SUN ; Li ZHANG ; Tao ZHANG ; Chunfang LYU ; Zhongwei CHEN ; Zhenzhou LUO ; Xiangsheng CHEN
Chinese Journal of Dermatology 2019;52(8):582-585
Chlamydia trachomatis (Ct) is the causative agent of bacterial sexually transmitted diseases (STDs) worldwide.The incidence of Ct infection has exceeded that of Neisseria gonorrhoeae,and becomes the highest in STDs in many countries.Ct infection can lead to urethritis,epididymitis,prostatitis and infertility in males,and cervicitis,endometritis,pelvic inflammatory disease,infertility in females,and neonatal conjunctivitis.Additionally,urogenital Ct infection is always ignored due to its concealed symptoms,leading to a long clinical course,recurrence or repeated infections.Furthermore,Ct infection can increase the risk of human immunodeficiency virus and human papilloma virus infections.Therefore,how to prevent and control the transmission of Ct has become one of the global public health issues.Currently,a growing body of researches have focused on the molecular epidemiological characteristics of Ct,which are aiming to identify the mutant strains,elaborate transmission dynamics,investigate the distribution of Ct serotypes in different populations,so as to provide molecular epidemiological evidence for the prevention and control of Ct infection.This review summarizes the epidemic status and research methods for molecular epidemiological characteristics of Ct,as well as application of Ct serotyping in clinical practice,providing references for the prevention,control and research of Ct infection.

Result Analysis
Print
Save
E-mail