1.Clinical study on the combination of the Danzhi Jiangtang Capsule and dapagliflozin for type 2 diabetes mellitus with peripheral vascular disease
Jian LIU ; Zhaohui FANG ; Yingqun NI ; Jindong ZHAO ; Ruimin LU ; Ben WANG ; Yushan YAN
Journal of Beijing University of Traditional Chinese Medicine 2024;47(8):1119-1125
Objective This study aimed to explore the effect of the combined Danzhi Jiangtang Capsule with dapagliflozin on the blood lipid profile and related inflammatory markers in patients with type 2 diabetes mellitus with peripheral vascular disease. Methods 72 patients with type 2 diabetes mellitus with peripheral vascular disease who met the inclusion criteria were admitted to the Department of Endocrinology,The First Affiliated Hospital of Anhui University of Chinese Medicine,from April 2021 to April 2023. The patients were assigned to the experimental group and the control group using the random number table method (36 cases in each group). The control group was treated with dapagliflozin in addition to standard treatment,while the experimental group received the Danzhi Jiangtang Capsule for 12 weeks. Clinical efficacy,glucose and lipid metabolism indicators,hypersensitive C-reactive protein (hs-CRP),body mass index (BMI) levels,and traditional Chinese medicine (TCM) syndrome scores were observed pre-and post-treatment.Results In post-treatment,the clinical efficacy was higher in the experimental group than in the control group. Significant reductions in fasting blood glucose (FPG),2 h postprandial glucose (2 hPG),triglycerides (TG),total cholesterol (TC),low-density lipoprotein cholesterol (LDL-C),hs-CRP,BMI,and increased high-density lipoprotein cholesterol (HDL-C) were observed. Scores for TCM syndrome and individual items also decreased (P<0.05). Comparisons within the groups for pre-and post-treatment showed reductions in FPG,2 hPG,TG,TC,LDL-C,hs-CRP,and an increase in HDL-C,along with a decrease in total scores of TCM syndrome (P<0.05). Conclusion The Danzhi Jiangtang Capsule combined with dapagliflozin in the treatment of type 2 diabetes mellitus with peripheral vascular disease can regulate the blood lipid profile,reduce inflammatory factors,and improve patient's symptoms. Integrated traditional Chinese and Western medicine treatment are more conducive to controlling the disease,and TCM can be used in clinical practice as a combination treatment.
2.A Case Report of Multidisciplinary Diagnosis and Treatment of a Patient with Tuberous Sclerosis Complex and Multi-Organ Involvement
Hua ZHENG ; Yunfei ZHI ; Lujing YING ; Lan ZHU ; Mingliang JI ; Ze LIANG ; Jiangshan WANG ; Haifeng SHI ; Weihong ZHANG ; Mengsu XIAO ; Yushi ZHANG ; Kaifeng XU ; Zhaohui LU ; Yaping LIU ; Ruiyi XU ; Huijuan ZHU ; Li WEN ; Yan ZHANG ; Gang CHEN ; Limeng CHEN
JOURNAL OF RARE DISEASES 2024;3(1):79-86
Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.
3.Construction and verification of prognostic model of bladder cancer costimu-latory molecule-related genes
Zhicheng TANG ; Yueqiao CAI ; Haiqin LIAO ; Zechao LU ; Fucai TANG ; Zeguang LU ; Jiahao ZHANG ; Yongchang LAI ; Shudan YAN ; Zhaohui HE
Chinese Journal of Immunology 2024;40(3):564-571
Objective:To explore genes related to costimulatory molecule related to the prognosis of bladder cancer,and to construct and evaluate prognosis model based on costimulatory molecule-based signature(CMS).Methods:Gene expression matrix and clinical information of bladder cancer patients were downloaded from TCGA database and GEO database(GSE31684),and costimulatory molecule-related genes were retrieved from the literature.The univariate and multivariate Cox analysis were used to screened prognostic-related genes and constructed prognostic model.Forecast accuracy of model was verified in TCGA training group,TCGA validation data group and GEO group by Kaplan-Meier survival analysis and receiver operating characteristic curve(ROC).Considering risk score and clinical characteristics,we constructed a nomogram and evaluated its performance by consistency analysis and ROC.CIBERSORT algorithm was used to analyze immune cell composition of tumor microenvironment infiltration,and gene set enrichment analysis(GSEA)was performed to explore the potential mechanism.Results:Four prognostic-related CMSs were found:TNFRSF14,CD276,ICOS and TMIGD2,of which three were included in the risk score construction.Multivariate Cox regression results showed that the risk score based on CMS was an independent prognostic factor for bladder cancer patients.Consistency analysis and ROC results showed that the nomogram had ideal prognosis prediction accuracy.Immune infiltration analysis showed that the high risk group was likely to be in immunosuppressive state.GSEA results suggested that genes in high risk group were enriched in extracel-lular matrix(ECM)receptors interaction,cell cycle and other pathways.Conclusion:TNFRSF14,CD276 and ICOS may be potential prognostic biomarkers for bladder cancer patients.CMS-based risk score and nomogram could contribute to early prognosis and choice of personalized treatment.
4.Screening of key differentially expressed genes involved in osteogenic differentiation of lower limb vascular smooth muscle cells and validation
Yingqun NI ; Mao YANG ; Di YANG ; Chenglin GUO ; Wenjun ZHU ; Yaqin YU ; Qin LU ; Jinzhi LUO ; Chunqin WU ; Zhaohui FANG
Journal of Jilin University(Medicine Edition) 2024;50(3):620-627
Objective:To screen the differentially expressed genes(DEGs)under high phosphate-induced calcification in the vascular smooth muscle cells(VSMCs)by mRNA high-throughput sequencing technology,and to analyze the key genes and signaling pathways involved in the VSMCs calcification.Methods:The human VSMCs were divided into control group and model group.The cells in model group was exposed to the high-phosphate medium,while the cells in control group were cultured in DMEM supplemented with 10%fetal bovine serum under the same conditions.The VSMCs in two groups,stably transfected,were cultured for 12 d.The morphology of the cells in two groups were observed and photographed under inverted microscope.The DEGs were selected by Hisat2 software,and Gene Ontology(GO)functional and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were performed by Stringtie software from three aspects,such as biological processes(BP),molecular functions(MF),and cellular components(CC).The calcification of the cells in two groups was observed by Von Kossa staining method.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to analyze the expression levels of alkaline phosphatase(ALP),bone morphogenetic protein 2(BMP2),alpha-smooth muscle actin(α-SMA),tumor protein 53(Tp53),glutathione peroxidase 4(GPX4),ferritin light chain 1(Ftl1),and glycosylphosphatidylinositol-specific phospholipase D1(GPLD1)mRNA in the cells in two groups.Results:Compared with control group,there were 2 524 DEGs in the cells in model group,and there were 1 368 upregulated DEGs and 1 156 downregulated DEGs.Clustering of DEGs between the cells in two groups was distinct.The GO functional and KEGG pathway enrichment analysis results showed that the upregulated DEGs were primarily involved in regulating the microtubule cytoskeleton,cell polarity,protein localization,and cell cycle regulation among BPs;in constructing cell membrane,microtubule organization,chromosomes,and kinetochore among CCs;and functioning in phosphatidylinositol phosphate,Rho GTPase protein binding,transmembrane transport,and protein kinase regulatory activity among MFs.Downregulated DEGs were mainly involved in cytoplasmic translation,protein membrane localization,mRNA metabolism,and protein endoplasmic reticulum localization among BPs;in forming ribosome subunits,cell membrane,and autophagy among CCs;and functioning in single-stranded DNA,ribonucleoprotein complex,growth factor binding,regulating protein kinase activity,and catalytic activity among MFs.Seven signaling pathways were significantly enriched in upregulated genes,most notably in the biosynthesis of glycosylphosphatidylinositol(GPI)anchors;whereas 18 signaling pathways were significantly enriched in the downregulated genes,most notably in ferroptosis.The RT-qPCR results showed that compared with control group,the expression levels of GPX4,Ftl1,and Tp53 mRNA in the cells in model group were significantly decreased(P<0.01),while the expression level of GPLD1 mRNA was significantly increased(P<0.01);compared with control group,the expression level of α-SMA mRNA in the cells in model group was significantly decreased(P<0.01),and the expression levels of ALP and BMP2 mRNA were significantly increased(P<0.01).Conclusion:The VSMCs underwent calcification and normal cells exhibit the DEGs.The key signaling pathways in the calcification induced by high phosphate in the VSMCs include ferroptosis and GPI anchor biosynthesis,mediated primarily through GPX4,Ftl1,Tp53,and GPLD1.
5.Clinicopathological features of pulmonary mucosa-associated lymphoid tissue lymphoma: analysis of 41 cases
Hui YANG ; Haijian HUANG ; Baicheng LI ; Meiling ZHENG ; Zaifeng LI ; Zhi YANG ; Xin CHEN ; Zhaohui LU
Journal of Leukemia & Lymphoma 2024;33(11):664-670
Objective:To investigate the clinicopathological features of pulmonary mucosa-associated lymphoid tissue lymphoma (MALToma).Methods:A retrospective case series study was conducted. A total of 41 cases of pulmonary MALToma who were admitted to multiple centers from April 2002 to August 2023 were collected, including 33 cases from Fujian Provincial Hospital, 5 cases from Binzhou People's Hospital, 1 case from the Second Hospital of Zhangzhou, 1 case from the People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine, and 1 case from Jinjiang Hospital. The results of pathological morphological examination, immunohistochemical examination and genetic testing of patients were summarized, their clinicopathological characteristics were analyzed, and the relevant literature was reviewed.Results:Among the 41 patients, there were 24 males and 17 females, aged (58±13) years (range: 36-81 years). The longest diameter of the tumor under the gross macroscopic examination was (2.8±2.0) cm, with a range of 0.8-9.7 cm. Under the microscope, diffuse, flakelike and nodular patterns of lymphoid tissue were seen in the lung tissue with small- to medium-sized lymphoid cells including small lymphocytes, centrocyte-like cells, mononuclear cells and plasma cells. A small number of activated cells were noted, and the lymphoid cells grew along the alveoli. In some areas, the lymphoid cells invaded the bronchi, and lymphatic follicular implantation was rare; 1 case was accompanied by large cell transformation. Tumor cells expressed CD20, Pax-5, bcl-2, and CD43, with Ki-67 proliferation index of 2%-20%, and 50% in some areas of 1 case. The positive rate of clonal B-cell receptor gene rearrangement was 100.00% (29/29); the positive rate of MALT1 gene was 18.75% (3/16), and the positive rate of API2-MALT1 fusion was 66.67% (2/3). The treatment methods included surgery, anti-inflammatory therapy, radiotherapy, and chemotherapy. Follow-up for 4-143 months showed that 43.90% (18/41) had disease-free survival, 21.95% (9/41) had tumor bearing survival, 9.76% (4/41) died, and 24.39%, (10/41) were lost to follow-up. The progression-free survival of patients aged ≥ 60 years was worse than that of patients aged < 60 years ( χ2 = 5.39, P = 0.020). Conclusions:Pulmonary MALToma belongs to indolent B-cell lymphoma, and its diagnosis requires a combination of clinical imaging, pathology and immunophenotyping. If necessary, genetic testing can be used to assist in the diagnosis. The differential diagnosis should be made from pneumonia, low-grade B-cell lymphoma, and extrapulmonary MALToma with lung involvement. The treatment methods include anti-inflammatory therapy, surgical resection and chemotherapy, and the prognosis is good.
6.A nationwide multicenter prospective study on the perioperative impact of closure of mesen-teric fissure in laparoscopic right hemicolectomy
Gang LIU ; Weimin XU ; Da LI ; Lei QIAO ; Jieqing YUAN ; Dewei ZHANG ; Yan LIU ; Shuai GUO ; Xu ZHANG ; Wenzhi LIU ; Yingfei WANG ; Hang LU ; Xiaowei ZHANG ; Xin CHEN ; Zhaohui XU ; Xingyang LUO ; Ge LIU ; Cheng ZHANG ; Jianping ZHOU
Chinese Journal of Digestive Surgery 2024;23(6):812-818
Objective:To investigate the perioperative impact of closure of mesenteric fissure in laparoscopic right hemicolectomy.Methods:The prospective randomized controlled trial was conducted. The clinical data of 320 patients who underwent laparoscopic right hemicolectomy in 11 medical centers, including The First Affiliated Hospital of China Medical University et al, from November 2022 to August 2023 were selected. Based on block randomization, patients were alloca-ted into the mesenteric fissure non-closure group and the mesenteric fissure closure group. Observa-tion indicators: (1) grouping of the enrolled patients; (2) intraoperative conditions; (3) postopera-tive conditions. Measurement data with skewed distribution were represented as M( Q1, Q3) and com-parison between groups was conducted using the Mann-Whitney U test. Count data were represen-ted as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher's exact probability. Comparison of ordinal data was conducted using the rank sum test. Comparison of visual analog scores was analyzed using generalized estimating equations. Results:(1) Grouping of the enrolled patients. A total of 320 patients with colon cancer were screened for eligibility, including 156 males and 164 females, aged 68(59,73)years. All the 320 patients were allocated into the mesenteric fissure non-closure group with 164 cases and the mesenteric fissure closure group with 156 cases. There was no significant difference in the age, body mass index, American Society of Anesthesiologist score, maximum tumor diameter, anastomosis location, anastomosis method, surgical approach, range of lymph node dissection, tumor staging between the two groups ( P>0.05) and there was a significant difference in the sex between them ( P<0.05). (2) Intraoperative conditions. There was no significant difference between the mesenteric fissure closure group and the mesenteric fissure non-closure group in the volume of intraoperative blood loss, operation time, conversion to laparotomy, intraoperative complication ( P>0.05). Three patients in the mesenteric fissure non-closure group were converted to laparotomy. One patient in the mesenteric fissure closure group was converted to laparotomy, and 2 cases with intraoperative complication were mesenteric hematoma. (3) Postoperative conditions. There was no significant difference between the mesenteric fissure non-closure group and the mesenteric fissure closure group in the overall postoperative complications ( χ2=0.28, P>0.05). There was no significant difference in the occurrence of postoperative intestinal obstruction, abdominal distension, ascites, pleural effusion, gastric paralysis, anastomotic bleeding, anastomotic leakage, or surgical wound infection between the two groups ( P>0.05). There was no significant difference between the two groups in the reoperation, postoperative gastric tube replacement. There was no significant differ-ence in time to postoperative first flatus, time to postoperative initial liquid food intake, time to post-operative resumption of bowel movements, duration of postoperative hospital stay, total hospital expenses between the two groups ( Z=-0.01, 0.43, 1.04, -0.54, -0.36, P>0.05). One patient in the mesenteric fissure non-closure group received reoperation. No perioperative internal hernia or death occurred in either group. The visual analog score decreased with time in both groups. There was no significant difference in the visual analog score between the mesenteric fissure closure group and the mesenteric fissure non-closure group [ β=-0.20(-0.53,0.13), P>0.05]. Conclusion:Compared with closure of mesenteric fissure, non-closure of mesenteric fissure during laparoscopic right hemi-colectomy dose not increase perioperative complications or postoperative management risk.
7.Study on the relationship between hemoglobin glycosylation index and arteriosclerosis- related blood lipids
Chen ZHANG ; Lu LIN ; Di SUN ; Jingtao DOU ; Anping WANG ; Liguang DONG ; Shuyu WANG ; Zhaohui LYU ; Yiming MU
Chinese Journal of Internal Medicine 2024;63(6):579-586
Objective:To study the relationship between hemoglobin glycation index (HGI) and blood lipid indices such as low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and plasma atherogenic index (AIP).Methods:This cross-sectional study included 16 049 participants from the Beijing Apple Garden community between December 2011 and August 2012. The subjects were divided into three groups based on the HGI quartile: low ( n=5 388), medium ( n=5 249), and high ( n=5 412). The differences in blood lipid indicators between different HGI groups were compared and multivariate logistic regression model was established to analyze the association between HGI and dyslipidemia. And multivariate logistic regression model was established to analyze the relationship between HGI and blood lipid indicators in different glucose metabolism populations. Results:There were 16 049 participants in all (mean age: 56 years), including 10 452 women (65.1%). They were classified into normal glucose tolerance (9 093 cases), prediabetes (4 524 cases), and diabetes (2 432 cases) based on glucose tolerance status. In the general population, with the increase of HGI, LDL-C, non-HDL-C, and AIP gradually increased (all P values for trends were <0.05), and the proportion of abnormalities increased significantly ( χ2=101.40, 42.91, 39.80; all P<0.001). A multivariate logistic regression model was established, which suggested a significant correlation between HGI and LDL-C, non-HDL-C, and AIP (all P<0.05), after adjusting for factors such as age, sex, fasting blood glucose, hypertension, body mass index, smoking, and alcohol consumption. In the overall population, normal glucose tolerance group, and diabetes group, HGI had the highest correlation with non-HDL-C ( OR values of 1.325, 1.678, and 1.274, respectively); in the prediabetes group, HGI had a higher correlation with LDL-C ( OR value: 1.510); and in different glucose metabolism groups, AIP and HGI were both correlated ( OR: 1.208-1.250), but not superior to non-HDL-C and LDL-C. Conclusion:HGI was closely related to LDL-C, non HDL-C, and AIP in the entire population and people with different glucose metabolism, suggesting that HGI may be a predictor of atherosclerotic cardiovascular disease.
8.Proteomic changes of vitreous from rhegmatogenous retinal detachment combined with choroidal detachment using data-independent acquisition
Pingping LI ; Mengyao HAN ; Rui ZHANG ; Fangyu CHEN ; Yanzi LI ; Jing YUAN ; Ning MA ; Zhaohui LI ; Lu LI ; Jianhua WU
Chinese Journal of Ocular Fundus Diseases 2024;40(10):758-765
Objective:To observe the proteomic changes in vitreous fluid samples from patients with rhegmatogenous retinal detachment combined with choroidal detachment (RRDCD).Methods:A prospective cross-sectional clinical study. Vitreous fluid samples were collected from 35 patients with RRDCD (RRDCD group) and 40 patients with rhegmatogenous retinal detachment (RRD group) who were diagnosed at Wuhan Aier Eye Hospital between November 2021 and December 2023. Prior to vitrectomy, 0.3-0.5 ml of vitreous fluid was collected from the affected eyes. Differentially expressed proteins were analyzed using Data-Independent Acquisition (DIA). Three of these proteins were randomly selected for validation using enzyme-linked immunosorbent assay (ELISA). Bioinformatics analyses, including gene ontology functional enrichment and kyoto encyclopedia of genes and genomes pathway enrichment, were performed to explore the functions of the differentially expressed proteins.Results:Significant differences were observed between the RRDCD and RRD groups in intraocular pressure ( t=-12.795), the number of retinal tears ( t=4.601), the extent of retinal detachment ( χ2=39.642), axial length ( t=0.840), postoperative proliferative vitreoretinopathy incidence ( χ2=4.730), single-surgery reattachment rate ( χ2=7.717), and best-corrected visual acuity ( t=7.033) at 6 months postoperatively ( P<0.05). A total of 237 differentially expressed proteins were identified between the RRDCD and RRD groups, with 63 upregulated and 174 downregulated. These proteins were involved in pathways such as extracellular matrix-receptor interaction, complement activation, coagulation, and lysosomal pathways. ELISA validation results showed that the expression trends of the three selected proteins in the RRDCD and RRD groups were consistent with the DIA proteomic analysis. Compared to the RRD group, proteins such as fibrin, coagulation factors, cathepsins, and trypsin inhibitors were significantly upregulated in the RRDCD group. Conclusions:The protein expression profile in vitreous fluid samples from RRDCD patients show significant alterations compared to the RRD group. These differential changes suggest that RRDCD is closely associated with complement and coagulation cascade activation, lysosomal pathways, and extracellular matrix remodeling.
9.Clinical Efficacy of Danzhi Jiangtang Capsules on Patients with Type 2 Diabetes Mellitus Complicated with Lower-extremity Macroangiopathy and Serum Levels of Hcy and Cys C
Jiping WU ; Zhaohui FANG ; Ruimin LU ; Jindong ZHAO ; Sihai WANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(18):102-108
ObjectiveTo observe the clinical efficacy of Danzhi Jiangtang capsules with the functions of replenishing Qi, nourishing Yin, and dredging collaterals on patients with type 2 diabetes mellitus (T2DM) combined with lower-extremity macroangiopathy and serum levels of homocysteine (Hcy) and cystatin C (Cys C). MethodA total of 80 eligible patients who were treated in the department of endocrinology of the First Affiliated Hospital of Anhui University of Chinese Medicine from May 2017 to December 2019 were randomized into the treatment group (40 cases) and control group (40 cases). Both groups received the basic therapies for diabetes and Danzhi Jiangtang capsules (oral) was added to the treatment group. The levels of glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), 2-hour postprandial glucose (2 hPG), fasting C-peptide (C-P), and 2-hour postprandial C-peptide (2 hC-P), triglycerides (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) and serum levels of Hcy and Cys C were measured and the traditional Chinese medicine(TCM) syndrome scores were calculated before and after treatment in the two groups. ResultAfter 12 weeks of treatment, levels of HbA1c, FPG, and 2 hPG were lower than those before treatment in the two groups (P<0.05). Levels of C-P (P<0.05) and 2 hC-P were higher than those before treatment in the two groups. After treatment, levels of HbA1c, FPG, and 2 hPG in the treatment group were lower than those in the control group (P<0.05), while levels of C-P and 2 hC-P showed no significant difference between two groups. After treatment, the levels of TG, TC, and LDL-C were lower than those before treatment (P<0.05) and HDL-C level was higher than that before treatment (P<0.05) in both groups. After treatment, levels of TG and LDL-C in the treatment group were lower than those in the control group (P<0.05), and levels of TC and HDL-C demonstrated no significant difference between two groups. After the treatment, the TCM syndrome score was lower than that before the treatment in both groups (P<0.05) and lower in the treatment group than in the control group (P<0.05). The overall effective rate of the treatment group was higher than that of the control group (χ2=7.585, P<0.05). The levels of Cys C and Hcy were lower than those before treatment in the two groups (P<0.05) and lower in the treatment group than in the control group (P<0.05). Doppler echocardiography of the lower limbs showed no obvious improvement in the control group after treatment. However, for the treatment group, slight decrease in intima-media thickness of the lower limb arteries and a slight reduction in the plaque area were observed, but the difference was not statistically significant. ConclusionDanzhi Jiangtang capsules has definite therapeutic effect on T2DM combined with lower-extremity macroangiopathy, which can improve glucolipid metabolism and reduce serum levels of Hcy and Cys C. This study can serve a reference for the prevention and treatment of T2DM combined with macroangiopathy.
10.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

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