1.Gemcitabine long-term maintenance chemotherapy benefits patients with survival: a multicenter, real-world study of advanced breast cancer treatment in China
Jian YUE ; Guohong SONG ; Huiping LI ; Tao SUN ; Lihua SONG ; Zhongsheng TONG ; Lili ZHANG ; Zhenchuan SONG ; Quchang OUYANG ; Jin YANG ; Yueyin PAN ; Peng YUAN
Chinese Journal of Oncology 2024;46(3):249-255
Objective:This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer. Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients.Methods:Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals). The clinicopathological data, the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed. To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy.Results:A total of 224 patients with advanced breast cancer were enrolled in this study, with a median age of 52 years (26-77 years), 55.4%(124/224) was postmenopausal. Luminal type were 83 cases, TNBC were 97 cases, and human epidermal growth factor receptor 2 (HER's-2) overexpression were 44. At the analysis, 224 patients who received the gemcitabine-based regimens were evaluated, included 5 complete reponse (CR), 77 partial response (PR), 112 stable disease (SD) and 27 progressive disease (PD). The objective response rate (ORR) was 36.6%(82/224). Seventy patients had serious adverse diseases, including leukopenia (9), neutrophilia (49), thrombocytopenia (15), and elevated transaminase (2). The median follow-up time was 41 months (26~61 months), and the median PFS was 5.6 months. The reasons of termination treatment were listed: disease progression were 90 patients; personal reasons were 51 patients; adverse drug reactions were 18 patients; completed treatment were 65 patients. It was found that progression-free survival (PFS) was significantly longer in patients receiving >6 cycles than that in patients with ≤6 cycles (8.2 months vs 5.4 months, HR=2.474, 95% CI: 1.730-3.538, P<0.001). Conclusions:Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world. The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.
2.Gemcitabine long-term maintenance chemotherapy benefits patients with survival: a multicenter, real-world study of advanced breast cancer treatment in China
Jian YUE ; Guohong SONG ; Huiping LI ; Tao SUN ; Lihua SONG ; Zhongsheng TONG ; Lili ZHANG ; Zhenchuan SONG ; Quchang OUYANG ; Jin YANG ; Yueyin PAN ; Peng YUAN
Chinese Journal of Oncology 2024;46(3):249-255
Objective:This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer. Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients.Methods:Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals). The clinicopathological data, the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed. To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy.Results:A total of 224 patients with advanced breast cancer were enrolled in this study, with a median age of 52 years (26-77 years), 55.4%(124/224) was postmenopausal. Luminal type were 83 cases, TNBC were 97 cases, and human epidermal growth factor receptor 2 (HER's-2) overexpression were 44. At the analysis, 224 patients who received the gemcitabine-based regimens were evaluated, included 5 complete reponse (CR), 77 partial response (PR), 112 stable disease (SD) and 27 progressive disease (PD). The objective response rate (ORR) was 36.6%(82/224). Seventy patients had serious adverse diseases, including leukopenia (9), neutrophilia (49), thrombocytopenia (15), and elevated transaminase (2). The median follow-up time was 41 months (26~61 months), and the median PFS was 5.6 months. The reasons of termination treatment were listed: disease progression were 90 patients; personal reasons were 51 patients; adverse drug reactions were 18 patients; completed treatment were 65 patients. It was found that progression-free survival (PFS) was significantly longer in patients receiving >6 cycles than that in patients with ≤6 cycles (8.2 months vs 5.4 months, HR=2.474, 95% CI: 1.730-3.538, P<0.001). Conclusions:Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world. The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.
3.Machine learning modeling identifies hypertrophic cardiomyopathy subtypes with genetic signature.
Jiaqi DAI ; Tao WANG ; Ke XU ; Yang SUN ; Zongzhe LI ; Peng CHEN ; Hong WANG ; Dongyang WU ; Yanghui CHEN ; Lei XIAO ; Hao LIU ; Haoran WEI ; Rui LI ; Liyuan PENG ; Ting YU ; Yan WANG ; Zhongsheng SUN ; Dao Wen WANG
Frontiers of Medicine 2023;17(4):768-780
Previous studies have revealed that patients with hypertrophic cardiomyopathy (HCM) exhibit differences in symptom severity and prognosis, indicating potential HCM subtypes among these patients. Here, 793 patients with HCM were recruited at an average follow-up of 32.78 ± 27.58 months to identify potential HCM subtypes by performing consensus clustering on the basis of their echocardiography features. Furthermore, we proposed a systematic method for illustrating the relationship between the phenotype and genotype of each HCM subtype by using machine learning modeling and interactome network detection techniques based on whole-exome sequencing data. Another independent cohort that consisted of 414 patients with HCM was recruited to replicate the findings. Consequently, two subtypes characterized by different clinical outcomes were identified in HCM. Patients with subtype 2 presented asymmetric septal hypertrophy associated with a stable course, while those with subtype 1 displayed left ventricular systolic dysfunction and aggressive progression. Machine learning modeling based on personal whole-exome data identified 46 genes with mutation burden that could accurately predict subtype propensities. Furthermore, the patients in another cohort predicted as subtype 1 by the 46-gene model presented increased left ventricular end-diastolic diameter and reduced left ventricular ejection fraction. By employing echocardiography and genetic screening for the 46 genes, HCM can be classified into two subtypes with distinct clinical outcomes.
4.Analysis of the occurrence time and risk factors of anemia in AIDS patients caused by HAART regimen containing zidovudine
Haiyan YAN ; Wenming HE ; Guoxian LI ; Keyu LUO ; Xiangsong QIN ; Huifen WEI ; Peng ZHANG ; Zhongsheng JIANG
China Pharmacy 2023;34(21):2620-2624
OBJECTIVE To investigate the occurrence time and risk factors of anemia in patients with acquired immune deficiency syndrome (AIDS) after taking highly active antiretroviral therapy (HAART) containing zidovudine. METHODS The clinical data of 2 150 AIDS patients who were followed up in the care clinic of Liuzhou People’s Hospital from January 1, 2010 to December 31, 2022 were collected. The occurrence time of anemia was analyzed retrospectively, and the risk factors of anemia were analyzed by univariate analysis and binary Logistic regression analysis. RESULTS A total of 854 AIDS patients receiving HAART containing zidovudine were collected, and 107 patients (12.53%) developed anemia. Most of them (63.55%) developed anemia within 3 months after treatment. Baseline hemoglobin [OR=2.944, 95%CI (1.195, 7.501), P=0.019], baseline CD4+ T lymphocyte count [OR=2.472, 95%CI (1.117, 5.469), P=0.026] and baseline human immunodeficiency virus-ribonucleic acid (HIV-RNA) [OR=4.299, 95%CI (1.905, 9.705), P<0.001] was associated with anemia. CONCLUSIONS The median time of anemia in AIDS patients receiving HAART containing zidovudine is the second month after initiation of treatment. Baseline hemoglobin≤110 g/L, baseline CD4+ T lymphocyte E-mail:1315775863@qq.com count≤100 /mm3, and baseline HIV-RNA≥100 000 copies/mL are independent risk factors for anemia in these patients.
5.Exploration on the Construction Ideas of Software Knowledge Base for Rational Use of TCM Decoction Pieces
Peng ZHOU ; Xiao LING ; Ruixin LIU ; Xuelin LI ; Bo ZHANG ; Xinjing GUI
China Pharmacy 2021;32(10):1272-1276
OBJECTIVE:To provide referenc e for the construction and software development of knowledge base for rational use of TCM decoction pieces. METHODS :By reviewing the literatures on rational drug use software and TCM decoction pieces in recent years ,the clinical characteristics of rational drug use of TCM decoction pieces as well as the characteristics and shortcomings of existing rational drug use software in the detection of rational drug use of TCM decoction pieces were analyzed , and the core contents and difficulties in the construction of knowledge base of rational drug use software of TCM decoction pieces were summarized. RESULTS & CONCLUSIONS :Clinical application of TCM decoction pieces was mainly based on “syndrome differentiation”,which reflected the unity of dialectics ,treatment,prescription selection and medication. Therefore ,the consideration of the rationality of clinical use of TCM decoction pieces could not blindly imitate the evaluation method of chemical medicine. Current rational drug use software was not based on the theoretical system of traditional Chinese medicine ,and it was not comprehensive and mature in the aspect of rational drug use review of TCM decoction pieces ,and lacks the knowledge base that could meet the requirements of rational use of TCM decoction pieces. Therefore ,it is necessary to construct a set of knowledge base which can meet the evaluation requirements of “consistency of principle ,method and prescription use ”of TCM decoction pieces under the guidance of TCM theoretical system. Its contents include that patient information collection ,construction of knowledge base related to diseases and syndromes ,selection of processed products of TCM dec oction pieces ,addition andsubtraction of clinical symptoms ,selection taboo of varieties of TCM decoction pieces , compatibility taboo , combined application of Chinese patent medicine or chemical medicine , dosage of TCM decoction pieces , total dosage and tastquantity of each prescription , special de coction drugs , medication methods and administration frequency ,etc. There are still some difficulties in the development of rational drug use software of TCM decoction pieces ,such as the construction of disease and syndrome related knowledge base and the difficulty in judging the rationality of clinical symptom addition and subtraction.
6.Design, synthesis and pharmacological evaluation of 4-(3-chloro-4-(3-cyclopropylthioureido)-2-fluorophenoxy)-7-methoxyquinoline-6-carboxamide (WXFL-152): a novel triple angiokinase inhibitor for cancer therapy.
Yuqin YAO ; Zhuowei LIU ; Manyu ZHAO ; Zhengxia CHEN ; Peng LI ; Yang ZHANG ; Yuxi WANG ; Chengjian ZHAO ; Chaofeng LONG ; Xiaoxin CHEN ; Jinliang YANG
Acta Pharmaceutica Sinica B 2020;10(8):1453-1475
Angiokinases, such as vascular endothelial-, fibroblast- and platelet-derived growth factor receptors (VEGFRs, FGFRs and PDGFRs) play crucial roles in tumor angiogenesis. Anti-angiogenesis therapy using multi-angiokinase inhibitor has achieved great success in recent years. In this study, we presented the design, synthesis, target identification, molecular mechanism, pharmacodynamics (PD) and pharmacokinetics (PK) research of a novel triple-angiokinase inhibitor WXFL-152. WXFL-152, identified from a series of 4-oxyquinoline derivatives based on a structure-activity relationship study, inhibited the proliferation of vascular endothelial cells (ECs) and pericytes by blocking the angiokinase signals VEGF/VEGFR2, FGF/FGFRs and PDGF/PDGFR simultaneously . Significant anticancer effects of WXFL-152 were confirmed in multiple preclinical tumor xenograft models, including a patient-derived tumor xenograft (PDX) model. Pharmacokinetic studies of WXFL-152 demonstrated high favourable bioavailability with single-dose and continuous multi-dose by oral administration in rats and beagles. In conclusion, WXFL-152, which is currently in phase Ib clinical trials, is a novel and effective triple-angiokinase inhibitor with clear PD and PK in tumor therapy.
7.Analysis of the efficacy of suctioning flexible ureteroscopy with automatic control of renal pelvic pressure
Xianxin ZHU ; Leming SONG ; Chuance DU ; Zhongsheng YANG ; Guanghua PENG ; Lei YAO ; Xiaolin DENG ; Min ZENG ; Shengfeng LIU ; Hua CHEN
Chinese Journal of Urology 2018;39(4):256-260
Objective To evaluate the efficacy and safety of suctioning flexible ureteroscopy with automatic control of renal pelvic pressure in the treament of intrarenal and proximal ureteral stones.Methods From November 2014 to December 2016,a total of 372 patients,including 200 males and 172 females,with upper urinary tract calculi were studied.The average age of patients was 48.1 years old.The average size of stone was 5-35mm,mean 15.7mm.There were 272 cases of renal calculi,80 cases of ureteral calculi and 20 cases of renal calculi combined with ureteral calculi.There were 252 cases of single calculi and 127 cases of multiple calculi.There were 237 cases of urinary tract infection and 14 cases of bacteremia.All patients were treated by suctioning fiexible uretemscopy with automatic control of renal pelvic pressure by a patented intelligent system including an irrigation and suctioning platform and a ureteral access sheath with a pressuresensitive tip.Statistical analysis was performed regarding renal pelvic pressure,operative time,stone-free rates,and complications.Results Three hundred and thirty of 372 patients only accepted one surgery to remove the stone.There were 12 cases of upper ureteral calculi were converted to ureteroscope lithotripsy.Seventeen cases were converted to percutaneous nephrolithotomy due to significant ureteral stenosis.Seven cases who failed the first surgery due to difficulty in placing the ureteral access sheath but flexible ureteroscopy were successfully performed in these patients after indwelling a D-J stent for 2 weeks.No stone was found in 6 cases,and the soft endoscope of ureter was examined.In all patients,the renal pelvic pressure of the pelvis was controlled within 20 mmHg.The average operative time was 15-180 min(mean 58.9 min).The stone-free rates was 95.55% (322/337),the incidence of postoperative fever was 2.97% (10/337),the sepsis rate was 1.19% (4/337),the incidence of urinary sepsis was 0.89% (3/337),the incidence of lumbago caused by extravasation was 0.59% (2/337),and no peripheral viscera injury or death case.There was no statistically significant difference between preoperative and postoperative white and red blood cells (P > 0.05).Conclusions This new type of suctioning flexible ureteroscopy with intelligent pressure-control has the advantages of perfusion attraction,pressure feedback,intelligent control and visualization of intracavity pressure.It could be a new type of operation with high safety,low complication and high stone free rate.
8.Ulinastatin Combined with Xingnaojing Injection in Treatment of Acute Cerebral Hemorrhage and Serum hs-CRP, D-D and NSE Levels
Zhongsheng LU ; Lichao ZHANG ; Peng YANG ; Qiang ZHANG ; Xiaojie CONG
Progress in Modern Biomedicine 2017;17(24):4719-4722
Objective:To investigate ulinastatin (UTI) combined with Xingnaojing injection in the treatment of acute cerebral hemorrhage (ACH) and its effect on the serum high sensitivity C reactive protein (hs-CRP),D-dimer (D-D) and neuron specific enolase(NSE) levels.Methods:110 cases of ACH patients admitted in our hospital from January 2015 to December 2016 were selected and divided into two groups according to the random number table method.The control group was given UTI treatment,while the observation group was given UTI combined with Xingnaojing treatment.Then the brain edema absorption effect,NIHSS score,serum hs-CRP,D-D and NSE levels before and after the treatment of the two groups were recorded and compared;the safety ofmedicidstion of the two groups was evaluated.Results:At the 14th day after treatment,the total effective rate of cerebral hematoma absorption in the observation group was 89.1%,which was significantly higher than 67.3% of the control group (P<0.01).At the 14th day after treatment,the NIHSS scores of both groups were significantly lower than those before the treatment (P<0.01);compared with that of the control group of the same time period,at the 14th day after treatment,the improvement effect of NIHSS score in the observation group was more significant (P<0.01).Compared with those before the treatment,the serum hs-CRP,D-D and NSE levels of both groups at the 14th day after treatment were significantly decreased (P<0.01);at the 14th day after treatment,the serum indicators of the observation group improved more significantly than those of the control group (P<0.01).The incidence rate of adverse reaction in the observation group was 3.6% compared with 5.5% of the control group (P>0.05).Conclusion:Ulinastatin combined with Xingnaojing Injection could rapidly relieve or eliminate hematoma in the treatment of acute cerebral hemorrhage,control the inflammatory response,improve the blood coagulation system and fibrinolytic system,protect the nerve cells and reduce the neurological damagee.
9.Clinical analysis on coinfection in acute gastroenteritis of children
Yong ZHANG ; Zijing ZHANG ; Shaoming ZOU ; Li XIAO ; Xiuqin ZHANG ; Zhongsheng ZHU ; Yongsheng HUANG ; Zhanying MA ; Mingyan ZOU ; Qian PENG ; Yuexin ZENG
International Journal of Pediatrics 2017;44(8):570-573
Objective To investigate the incidence of enteric pathogens causing acute gastroenteritis (AGE) among children to measure the incidence of coinfections,and to compare the clinical characteristics of those infected with one versus multiple agents.Methods A retrospective study was conducted from January 2014 to December 2014.All patients between 1 month and 14 years of age admitted to the Pediatric department with a diagnosis of AGE were eligible for enrollment.Two stool samples for each patient were tested for gastrointestinal pathogens.We summarized the clinical severity of episodes,describing the duration of diarrhea,duration and frequency of vomiting,fever.All patients underwent medical evaluation with estimation of dehydration.Results One or more etiological agents were detected in 3595 out of 4728 patients(76.0%),while we did not detect any etiological agent in 1133 (24.0%).Rotavirus was detected in 1889 (40.0%),adenovirus in 412 (8.7 %),norovirus in 309 (6.5 %),verotoxigenic Escherichia coli (VTEC) in 274 (5.8 %),Salmonella spp.in 276(5.8%),Klebsiella pneumoniae in 123 (2.6%),Shigella spp.in 78 (1.6%),Staphylococcus aureus in 70 (1.5%),C.perfringens in 126(2.7%).In 1370 children out of 4728(29.0%),we found evidence of coinfection.with rotavirus and norovirus was the most common 150 (3.2%),rotavirus and C.perfringens was also common 127(2.7%).Children with coinfection had a more severe clinical presentation.The difference has statistical significance.Conclusion Rotavirus is still the most common pathogen in children with acute diarrhea,followed by NV,adenovirus,Salmonella spp.and VTEC.Rotavirus with norovirus infection was the most common.VTEC combined with three kinds of virus infection had the highest incidence.Children with multiple viral infections were more severe than those of single virus infection in the duration of vomiting and dehydration.There was no significant difference in the duration of fever and diarrhea and the frequency of diarrhea.Children infected by viruses and bacteria had a more severe clinical presentation such as fever,vomiting and diarrhea lasting for a long time,more serious diarrhea and dehydration than those with single bacteria and single virus infection.The difference has no significant difference in degree and duration of diarrhea.
10.A multicenter, randomized, controlled, phase Ⅲ clinical study of PEG-rhG-CSF for preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer.
Binghe XU ; Fuguo TIAN ; Jingrui YU ; Yanqiu SONG ; Jianhua SHI ; Baihong ZHANG ; Yanjun ZHANG ; Zhiping YUAN ; Qiong WU ; Qingyuan ZHANG ; Kejun NAN ; Qiang SUN ; Weilian LI ; Jianbing HU ; Jingwang BI ; Chun MENG ; Hong DAI ; Hongchuan JIANG ; Shun YUE ; Bangwei CAO ; Yuping SUN ; Shu WANG ; Zhongsheng TONG ; Peng SHEN ; Gang WU ; Lili TANG ; Yongchuan DENG ; Liqun JIA ; Kunwei SHEN ; Wu ZHUANG ; Xiaodong XIE ; Youhua WU ; Lin CHEN
Chinese Journal of Oncology 2016;38(1):23-27
OBJECTIVETo explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer (NSCLC), and to provide the basis for clinical application.
METHODSAccording to the principle of open-label, randomized, parallel-group controlled clinical trial, all patients were randomized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 μg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 μg/kg, respectively. The patients with breast cancer received two chemotherapy cycles, and the NSCLC patients received 1-2 cycles of chemotherapy according to their condition. All patients were treated with the combination chemotherapy of TAC (docetaxel+ epirubicin+ cyclophosphamide) or TA (docetaxel+ epirubicin), or the chemotherapy of docetaxel combined with carboplatin, with a 21 day cycle.
RESULTSThe duration of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 μg/kg group (P>0.05 for all). The incidence rate of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group, and G-CSF 5 μg/kg group were 69.7%, 68.4%, and 69.5%, respectively, with a non-significant difference among the three groups (P=0.963). The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg/kg group were 6.1%, 6.4%, and 5.5%, respectively, showing no significant difference among them (P=0.935). The incidence rate of adverse events in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg / kg group were 6.7%, 4.1%, and 5.5%, respectively, showing a non-significant difference among them (P=0.581).
CONCLUSIONSIn patients with breast cancer and non-small cell lung cancer (NSCLC) undergoing TAC/TA chemotherapy, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions. Compared with the continuous daily injection of rhG-CSF 5 μg/kg/d, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia.
Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms ; drug therapy ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cyclophosphamide ; administration & dosage ; adverse effects ; Epirubicin ; administration & dosage ; adverse effects ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Incidence ; Induction Chemotherapy ; Lung Neoplasms ; drug therapy ; Neutropenia ; chemically induced ; epidemiology ; prevention & control ; Polyethylene Glycols ; Recombinant Proteins ; administration & dosage ; Taxoids ; administration & dosage ; adverse effects

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