1.Metabolite identification and metabolic pathway analysis of pirtobrutinib in rats
Meijuan ZHANG ; Jie LI ; Hang YIN ; Mengyu HOU ; Jiangshuo LI ; Jingxuan WU ; Ruihua DONG
China Pharmacy 2025;36(9):1076-1081
OBJECTIVE To analyze and identify the metabolites of pirtobrutinib (PTN) in rats, and clarify the possible metabolic pathways of PTN in rats. METHODS Six rats were intragastrically administered with 10 mg/kg PTN suspension. Blood samples were collected from the rats 30 minutes before administration and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24 hours after administration. Urine and feces samples were collected 12 hours before administration and 24 hours after administration. UHPLC- Orbitrap Exploris 240 system combined with Compound Discoverer 3.0 and Xcalibur 2.0 software were adopted for structural identification and metabolic pathway analysis of PTN metabolites in rat plasma, urine, and feces. RESULTS A total of 29 PTN metabolites were identified, including 17, 19 and 22 metabolites in plasma, urine and feces, respectively. The metabolic pathways of PTN mainly included oxidation, sulfation, glucuronidation, etc., and its metabolites were mostly combination products of two or more different metabolic forms. In detail, a total of 26 metabolites were associated with phase Ⅰ metabolic reactions (14 oxidation metabolites, 9 reduction/dehydrogenation metabolites, 8 demethylation metabolites, and 5 hydrolysis metabolites). Meanwhile, a total of 20 products were involved in phase Ⅱ metabolites (14 sulfation metabolites and 8 glucuronic acid binding metabolites). CONCLUSIONS PTN exhibits a diverse range of metabolites in rat fecal samples, with the primary metabolic pathways being oxidation, sulfation, glucuronidation, and others.
2.A single-center retrospective study of salvage allogeneic hematopoietic stem cell transplantation pretreated with MeCBA regimen for refractory/relapsed acute myeloid leukemia
Fangfang YUAN ; Yongqi WANG ; Minghui LI ; Gangping LI ; Ziye LI ; Ruihua MI ; Qingsong YIN ; Yuewen FU ; Xudong WEI
Chinese Journal of Hematology 2024;45(5):500-504
Thirty refractory relapsed acute myeloid leukemia (R/R AML) patients who received salvage allo-HSCT with MeCBA conditioning regimen from January 2018 to June 2022 at Henan Cancer Hospital were included, and their clinical data were reviewed. There were 16 males and 14 females among the 30 patients with a median age of 37 (16-53) years. There were 3 sibling allograft donor transplants, 1 unrelated donor transplant, and 26 haplotype transplants. The median course of pre-transplant chemotherapy was 4 (3-22). The time of neutrophil engraftment was 14 (9-22) days and 18 (10-40) days for platelet. The 30-day cumulative incidence of neutrophil engraftment was 100% and the 100-day cumulative incidence of platelet engraftment was 96.7% (95% CI 85.4% -97.5% ). 22 (73.3% ) patients experienced grade 1-2 gastrointestinal reactions, and there was no grade 3-4 organ toxicity. With a median follow-up of 37.1 months, the overall survival (OS) rate, event-free survival (EFS) rate, cumulative recurrence rate (CIR), and non-recurrence mortality (NRM) rate at 3 years after transplantation were 70.0% (95% CI 50.3% -83.1% ), 65.3% (95% CI 44.8% -79.8% ), 21.2% (95% CI 9.2% -44.4% ) and 16.7% (95% CI 7.3% -35.5% ), respectively.
3.Detection of colorectal advanced neoplasms among the cancer screening population in urban areas of Henan Province and analysis on its influencing factors
Lanwei GUO ; Liyang ZHENG ; Qiong CHEN ; Yin LIU ; Huifang XU ; Ruihua KANG ; Hong WANG ; Xiaoyang WANG ; Shuzheng LIU ; Shaokai ZHANG
Chinese Journal of Oncology 2024;46(8):794-800
Objective:To analyze the detection of colorectal advanced neoplasms in the population who underwent colonoscopy screening in Henan Province as part of the Urban China Cancer Screening Program and its influencing factors.Methods:A cross-sectional study design was employed. Based on the Cancer Screening Program conducted in Henan Province, the study enrolled 7 454 urban residents who manifested no symptoms and were recruited from eight cities in the province, including Zhengzhou, Zhumadian, Anyang, Luoyang, Nanyang, Jiaozuo, Xinxiang, and Puyang from October 2013 to October 2019, and participated in colonoscopy screening. The χ 2 test was used to compare the detection rates of colorectal advanced neoplasms among participants with different characteristics, and a multivariate logistic stepwise regression model was used to analyze the factors affecting the detection rates. Results:A total of 7 454 subjects underwent colonoscopy screening, and 112 cases of colorectal advanced neoplasms were detected. Multivariate logistic regression analysis suggested that older age, smoking, higher meat intake, history of diabetes, and family history of colorectal cancer in a first-degree relative were risk factors for colorectal advanced neoplasms. The detection rate was significantly higher in people aged 60-74 years compared with those aged 40-49 years, with an odds ratio ( OR) of 2.04 (95% CI: 1.23-3.38).The rates were higher in people who smoked than those who did not smoke, with an OR of 2.21 (95% CI: 1.48-3.31), and in people who consumed more meat than those who consumed less, with an OR of 1.53 (95% CI: 1.04-2.26). Those with diabetes had a higher detection rate compared with those without, with an OR of 1.69 (95% CI: 1.07-2.69), and those with a first-degree family history of colorectal cancer had a higher detection rate than those without, with an OR of 1.64 (95% CI: 1.09-2.46). Conclusion:The detection rate of colorectal advanced neoplasms through colonoscopy screening in Henan Province covered by the Urban China Cancer Screening Program is 1.50%. Older age, smoking, higher meat intake, history of diabetes, and family history of colorectal cancer in a first-degree relative are identified as risk factors for colorectal advanced neoplasms.
4.The 5-year relative survival rate among cancer patients in Henan province of China, 2015-2019
Qiong CHEN ; Mingxia ZHANG ; Lanwei GUO ; Liyang ZHENG ; Chunya LIU ; Yixian WANG ; Yin LIU ; Hong WANG ; Huifang XU ; Ruihua KANG ; Xiaoyang WANG ; Shuzheng LIU ; Shaokai ZHANG
Chinese Journal of Oncology 2024;46(10):954-960
Objective:To analyze the 5-year relative survival rate of cancer in Henan province based on cancer registration data.Methods:Cancer survival data were extracted from the cancer registration database of Henan province with the diagnosis date between January 1, 2010 and December 31, 2019 were included. The closing date of follow-up was set as December 31, 2019. The 5-year relative survival rate of cancer was calculated using the period survival analysis method and the Ederer II method in the R package "periodR", and the interest period was between 2015 and 2019.Results:During the period of 2015-2019, the overall 5-year relative survival rate of cancer patients in Henan province was 43.6%, and after age-standardization, it was 40.2%. The overall 5-year relative survival rate showed the characteristics of higher survival rate in females than males (45.9% vs 34.7%, Z=39.60, P<0.001) and higher survival rate in urban areas than rural areas (44.9% vs 39.1%, Z=12.97, P<0.001). The 5-year relative survival rate for cancer patients among children aged 0-14 was 60.2%, and for adults aged 15 and above, it was 43.5%, which was standardized to 40.2% after age adjustment. There are two types of cancers with a standardized 5-year relative survival rate exceeding 70% (thyroid cancer at 82.2% and breast cancer at 71.6%), and four cancers with a rate below 30% (pancreatic cancer at 18.2%, liver cancer at 19.6%, lung cancer at 24.0%, and gallbladder cancer at 26.6%). Conclusion:The cancer 5-year survival rate in Henan Province is lower than that of the national average, indicating the need for continued enhancement of cancer prevention and control measures.
5.Detection of colorectal advanced neoplasms among the cancer screening population in urban areas of Henan Province and analysis on its influencing factors
Lanwei GUO ; Liyang ZHENG ; Qiong CHEN ; Yin LIU ; Huifang XU ; Ruihua KANG ; Hong WANG ; Xiaoyang WANG ; Shuzheng LIU ; Shaokai ZHANG
Chinese Journal of Oncology 2024;46(8):794-800
Objective:To analyze the detection of colorectal advanced neoplasms in the population who underwent colonoscopy screening in Henan Province as part of the Urban China Cancer Screening Program and its influencing factors.Methods:A cross-sectional study design was employed. Based on the Cancer Screening Program conducted in Henan Province, the study enrolled 7 454 urban residents who manifested no symptoms and were recruited from eight cities in the province, including Zhengzhou, Zhumadian, Anyang, Luoyang, Nanyang, Jiaozuo, Xinxiang, and Puyang from October 2013 to October 2019, and participated in colonoscopy screening. The χ 2 test was used to compare the detection rates of colorectal advanced neoplasms among participants with different characteristics, and a multivariate logistic stepwise regression model was used to analyze the factors affecting the detection rates. Results:A total of 7 454 subjects underwent colonoscopy screening, and 112 cases of colorectal advanced neoplasms were detected. Multivariate logistic regression analysis suggested that older age, smoking, higher meat intake, history of diabetes, and family history of colorectal cancer in a first-degree relative were risk factors for colorectal advanced neoplasms. The detection rate was significantly higher in people aged 60-74 years compared with those aged 40-49 years, with an odds ratio ( OR) of 2.04 (95% CI: 1.23-3.38).The rates were higher in people who smoked than those who did not smoke, with an OR of 2.21 (95% CI: 1.48-3.31), and in people who consumed more meat than those who consumed less, with an OR of 1.53 (95% CI: 1.04-2.26). Those with diabetes had a higher detection rate compared with those without, with an OR of 1.69 (95% CI: 1.07-2.69), and those with a first-degree family history of colorectal cancer had a higher detection rate than those without, with an OR of 1.64 (95% CI: 1.09-2.46). Conclusion:The detection rate of colorectal advanced neoplasms through colonoscopy screening in Henan Province covered by the Urban China Cancer Screening Program is 1.50%. Older age, smoking, higher meat intake, history of diabetes, and family history of colorectal cancer in a first-degree relative are identified as risk factors for colorectal advanced neoplasms.
6.The 5-year relative survival rate among cancer patients in Henan province of China, 2015-2019
Qiong CHEN ; Mingxia ZHANG ; Lanwei GUO ; Liyang ZHENG ; Chunya LIU ; Yixian WANG ; Yin LIU ; Hong WANG ; Huifang XU ; Ruihua KANG ; Xiaoyang WANG ; Shuzheng LIU ; Shaokai ZHANG
Chinese Journal of Oncology 2024;46(10):954-960
Objective:To analyze the 5-year relative survival rate of cancer in Henan province based on cancer registration data.Methods:Cancer survival data were extracted from the cancer registration database of Henan province with the diagnosis date between January 1, 2010 and December 31, 2019 were included. The closing date of follow-up was set as December 31, 2019. The 5-year relative survival rate of cancer was calculated using the period survival analysis method and the Ederer II method in the R package "periodR", and the interest period was between 2015 and 2019.Results:During the period of 2015-2019, the overall 5-year relative survival rate of cancer patients in Henan province was 43.6%, and after age-standardization, it was 40.2%. The overall 5-year relative survival rate showed the characteristics of higher survival rate in females than males (45.9% vs 34.7%, Z=39.60, P<0.001) and higher survival rate in urban areas than rural areas (44.9% vs 39.1%, Z=12.97, P<0.001). The 5-year relative survival rate for cancer patients among children aged 0-14 was 60.2%, and for adults aged 15 and above, it was 43.5%, which was standardized to 40.2% after age adjustment. There are two types of cancers with a standardized 5-year relative survival rate exceeding 70% (thyroid cancer at 82.2% and breast cancer at 71.6%), and four cancers with a rate below 30% (pancreatic cancer at 18.2%, liver cancer at 19.6%, lung cancer at 24.0%, and gallbladder cancer at 26.6%). Conclusion:The cancer 5-year survival rate in Henan Province is lower than that of the national average, indicating the need for continued enhancement of cancer prevention and control measures.
7.The efficacy of postoperative radiotherapy in stage Ⅲ(N 2) non-small cell lung cancer: a meta analysis
Lixian LING ; Shishi ZHOU ; Hongjuan ZHENG ; Ruihua YIN ; Mengjun TANG ; Jianfei FU
Chinese Journal of Radiation Oncology 2023;32(4):293-300
Objective:To conduct meta analysis to compare the effect of complete resection with or without postoperative radiotherapy (PORT) on survival in stage Ⅲ(N 2) non-small cell lung cancer (NSCLC). Methods:Relevant studies of the efficacy of PORT for stage Ⅲ(N 2) NSCLC were searched from Wanfang Data, PubMed, and Cochrane Library from January 2006 to January 2022. Literature screening, extraction of information and assessment of the risk of bias of the included literature was carried out by two independent researchers. Meta analysis was performed using R4.0.3 software. Results:A total of 12 publications consisting of 2992 patients were included, 1479 cases in the PORT group and 1513 cases in the control group. PORT improved the overall survival (OS) and disease free survival (DFS) compared to the control group. Fixed-effects model meta analysis of 6 randomized controlled trials showed that PORT did not significantly reduce the risk of death ( HR=0.98, 95% CI: 0.80-1.20). Fixed-effects model meta analysis of 6 retrospective studies showed that PORT improved prognosis ( HR=0.68, 95% CI: 0.59-0.79). PORT could improve OS of patients with multiple (station) metastasis of ipsilateral mediastinum and / or submandibular lymph nodes ( HR=0.89, 95% CI: 0.80-0.99). Conclusions:PORT could improve OS and DFS in stage Ⅲ(N 2) NSCLC. A trend towards benefit can be observed in the subgroup with multiple/multi-station N2 metastasis.
8.Expression of CDK5 and its correlation with peripheral inflammation-related cells and prognosis in colon cancer patients
Qinghua WANG ; Ruihua YIN ; Bin HU ; Bingjing JIANG ; Zhihui DAI ; Wanfen TANG ; Xia ZHANG ; Shishi ZHOU ; Jianfei FU
Chinese Journal of General Surgery 2021;36(10):774-778
Objective:To identify the clinical significance of CDK5 in colon cancer tissues.Methods:Two hundred colon cancer tissues were tested for CDK5 expression by immunohistochemistry on tissue microarrays. The correlation between CDK5 expression and clinicopathological features, prognosis and peripheral inflammation-related cells was analyzed.Results:CDK5 was low expressed in 100 cases (50.0%), and high in another 100 cases (50.0%). Longer time to tumor progression ( P=0.026) and overall survival ( P=0.035) were observed in patients with high CDK5 expression. By multivariate analysis , the expression of CDK5 was an independent risk factor for poor prognosis ( HR=0.45,95% CI: 0.21-0.99, P=0.049). The expression of CDK5 was not related to the counts of white blood cells and neutrophils ( P>0.05). Prognosis of patients with a positive lymph node ratio less than 0.15 was significantly better than that of patients with a higher lymph node ratio ( P<0.001). Conclusions:Patients with low CDK5 expression have poor prognosis, and CDK5 expression is not related to the counts of peripheral white blood cells and neutrophils.
9. The safety and efficacy of low dose subcutaneous decitabine combined with arsenic trioxide in patients with inermediate or higer-risk myelodysplastic syndrome
Hao AI ; Xudong WEI ; Qingsong YIN ; Ruihua MI ; Lin CHEN ; Qian WANG ; Yongping SONG
Chinese Journal of Internal Medicine 2019;58(12):908-910
To retrospectively analyze the safety and efficacy of low dose subcutaneous decitabine combined with arsenic trioxide in patients with intermediate or high-risk myelodysplastic syndrome (MDS). Three of the total 11 MDS patients achieved complete remission (CR) and 6 achieved hematological improvement (HI), 1 stable disease (SD), and 1 progressive disease (PD). One patient was treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median follow-up time was 413(90-1 275) d. Nine patients were still alive. Low dose subcutaneous decitabine combined with arsenic trioxide can be an alternative regimen for intermediate or high-risk MDS patients.
10. Effect of lenalidomide combined with interferon and interleukin-2 for treatment of refractory/relapsed or minimal residual disease-positive acute myelogenous leukemia
Ruihua MI ; Lin CHEN ; Hao AI ; Fangfang YUAN ; Qingsong YIN ; Xudong WEI
Journal of Leukemia & Lymphoma 2019;28(12):743-748
Objective:
To analyze the efficacy and safety of lenalidomide combined with interferon (IFN) and interleukin-2 (IL-2) for treatment of refractory/relapsed or minimal residual disease (MRD)-positive acute myelogenous leukemia (AML).
Methods:
Twelve patients with AML who were hospitalized in the Affiliated Cancer Hospital of Zhengzhou University from August 2013 to May 2019 were selected. These patients were previously treated with thalidomide combined with IFN and IL-2, and then treated with combined with IFN and IL-2. According to the Frence-American-British (FAB) classification system, there was 1 case of M0, 1 case of M1, 4 cases of M2a, 3 cases of M2b, 1 case of M4EO, and 2 cases of M5b. There were 2 cases with FLT3-ITD mutation-positive, 1 case with c-kit mutation-positive. There were 2 cases in the low-risk group, 7 cases in the intermediate-risk group, and 3 cases in the high-risk group. Three cases were refractory AML, 7 cases were relapsed AML (including 3 cases of recurrence once, 4 cases of recurrence twice; 5 cases of recent recurrence, 2 cases of long-term recurrence), 2 cases were MRD-positive. The efficacy and adverse reactions of 12 cases were evaluated.
Results:
Twelve patients had received more than one cycle therapy of lenalidomide combined with IFN and IL-2, of which 4 patients achieved morphological complete remission (CR), 2 patients had CR with incomplete recovery of blood cells (CRi), 4 patients had no remission, 1 case had a decrease in MRD, and 1 case had an increase in MRD, and the total effective (CR+ CRi+ partial remission+ MRD decreased) was in 7 cases. There were no adverse reactions such as rash, constipine, bradycardia and peripheral neuritis; six patients had grade Ⅲ or higher experienced myelosuppression. No patients died of complications during the treatment, and the duration of remission of all patients was 2-20 months.
Conclusion
Lenalidomide combined with IFN and IL-2 for treatment of refractory/relapsed or MRD-positive AML is effective, and it can reduce the MRD value in MRD-positive patients, it could be a new treatment method for AML.

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