1.Meta-analysis of the effects of ABCB1 genotype on the efficacy and safety of taxanes in the treatment of breast cancer
Shufang ZHANG ; Yan LI ; Lun LIU ; Xiaoning GENG ; Bo ZHOU ; Zhongtao ZHANG ; Fulei LIU
China Pharmacy 2024;35(10):1254-1259
OBJECTIVE To evaluate the effects of ABCB1 genotypes on the efficacy and safety of taxanes in the treatment of breast cancer. METHODS By searching Embase,the Cochrane Library, PubMed, CNKI, and Wanfang databases, cohort studies and case-control studies about taxanes in the treatment of breast cancer were collected from the establishment of the database to July 2023. After screeningliterature, extracting data and evaluating quality, meta-analysis was performed by using RevMan 5.3 software. RESULTS A total of 11 studies were included, involving 1 321 patients. There was no correlation between the three genotypes and effective rate, the incidence of myelosuppression, the incidence of neurotoxicity (except for the allele and recessive model of ABCB1 C1236T), and the incidence of hypersensitivity reactions (P>0.05). The subgroup analysis showed that there was a correlation between ABCB1 C1236T dominant model and effective rate when using anthracyclines+5-fluorouracil+cyclophosphamide+taxanes (P<0.05), there was a correlation between ABCB1 C3435T recessive model and effective rate when using taxanes+trastuzumab (P<0.05). ABCB1 C1236T allele model and recessive model were correlated with sample size ≥100 and using cyclophosphamide+epirubicin+5- fluorouracil+paclitaxel or cyclophosphamide+epirubicin+paclitaxel+trastuzumab or cyclophosphamide+epirubicin+5-fluorouracil+ trastuzumab+paclitaxel regimens; recessive model with sample size <100 and the African region were correlated with the incidence of peripheral neuropathy; recessive model was correlated with cutaneous adverse reactions (P<0.05). ABCB1 C3435T recessive model was correlated with the incidence of reduced neutrophil count with sample size ≥100; the incidence of white blood cell count reduction with sample size <100 and using docetaxel+epirubicin+cyclophosphamide was correlated with both the allele model and the dominant model; the incidence of infections was correlated with the dominant model (P<0.05). The incidence of neutrophil count reduction with the sample size <100 was correlated with allele model of ABCB1 G2677T/A; the incidence of edema with sample size ≥100 was correlated with allele model and recessive model; the incidence of infection was correlated with allele model and dominant model, especially in patients with neutrophil count complicated with fever (P<0.05). CONCLUSIONS ABCB1 genotypes are not correlated with effective rate of taxanes in the treatment of breast cancer, but ABCB1 C3435T genotype is associated with decreased neutrophil counts, decreased white blood cell counts and infections; ABCB1 C1236T genotype is associated with neurotoxicity and cutaneous adverse reactions; ABCB1 G2677T/A genotype is associated with decreased neutrophil counts, infections, and edema.
2.Low-dose ATG combined with low-dose PTCY in preventing GVHD after haploidentical transplantation:a retrospective analysis of 90 cases
Jinmei LEI ; Lin LIU ; Zhongtao YUAN ; Yu LI ; Le LUO ; Xiaoping LI ; Shiqi LI ; Sanbin WANG
Journal of Army Medical University 2024;46(4):326-330
Objective To retrospectively analyze the efficacy and safety of low-dose antithymocyte globulin(ATG)combined with low-dose post transplantation cyclophosphamide(PTCY)in prevention of graft versus host disease(GVHD)after haploidentical transplantation.Methods Clinical data of 90 patients receiving haplotype matched transplantation in No.920 Hospital of PLA Joint Logistic Support Force from January 2022 to February 2023 were collected,and they were divided into study group(n=47)and control group(n=43)according to different GVHD prevention programs.The patients of the study group were given low-dose ATG combined with low-dose PTCY,and those of the control group received standard dose of PTCY.The implantation status,occurrence of GVHD,survival status and other indicators were analyzed between the 2 groups.Results ① Both groups of patients were successfully implanted,the median duration for neutrophil implantation(11 vs 17 d,P<0.05)and platelet implantation(12 vs 20 d,P<0.05)was significantly shorter in the study group than the control group.The incidence of grade Ⅱ~Ⅳ aGVHD(12.8%vs 34.9%,P<0.05)and grade Ⅲ~Ⅳ aGVHD(6.4% vs 20.9%,P<0.05)was significantly lower in the study group than the control group,so was the non-recurrent mortality rate(6.4%vs 20.9%,P<0.05)and the incidence of hemorrhagic cystitis(12.8% vs 34.9%,P<0.05).② By the end of the study,there were no significant differences in the incidence of mild and moderate and severe cGVHD,recurrence rate,reactivation rates of EBV and CMV,overall survival rate or progression-free survival rate between the 2 groups.Conclusion For haploidentical transplantation,low-dose ATG combined with low-dose PTCY has the advantages of lower incidence of GVHD,non-recurrent mortality,incidence of hemorrhagic cystitis and faster implantation.
3.Control effect of Dasatinib on the treatment of acute myeloid leukemia and adverse events of CD123 targeting CAR-T:a case report and literature review
Chunmin LI ; Yu LI ; Zhongtao YUAN ; Lin LIU ; Le LUO ; Xiaoping LI ; Sanbin WANG ; Shiqi LI
Journal of Army Medical University 2024;46(4):347-351
Objective To preliminarily explore the efficacy of chimeric antigen receptor T cells(CAR-T)targeting CD 123 in the treatment of acute myeloid leukemia(AML)and the role of dasatinib in the treatment of CD123 targeting CAR-T induced side effects.Methods Clinical data of 1 patient with relapsed AML admitted to No.920 Hospital of PLA Joint Logistic Support Force in September,2019 were collected.The patient relapsed after previous multi-line chemotherapy and was treated with CD123 targeting CAR-T therapy.The routine blood changes of the patient after treatment were observed.Dasatinib was used when agranulocytosis occurred,40 mg orally 3 times per day,and was stopped when agranulocytosis was relieved.Changes in blood cells,CAR-T amplification,and disease control were observed.The patient was followed up for over 1 year.Results Flow cytometry for bone marrow showed that minimal residual disease negative result was observed in 30 d after infusion.The patient remained disease-free for over 1 year.After CD 123 CAR-T cells infusion,significant expansion of CAR-T cells was observed,accompanied by granulocyte deficiency and cytokine release syndrome(CRS).After using dasatinib,inhibition of CAR-T cell expansion was observed,accompanied by blood cell recovery,and CRS symptoms were alleviated.After stop of dasatinib,CAR-T cells expanded again and blood cells decreased again.Conclusion CAR-T cells targeting CD 123 have certain efficacy in the treatment for relapsed AML.Dashatinib has a blocking effect on the amplification and function of CAR-T,which can alleviate bone marrow suppression caused by CD 123 targeting CAR-T and avoid severe CRS.
4.Analysis of specimen quality of intersphincteric resection for rectal cancer in the Chinese Transanal Total Mesorectal Excision Registry Collaborative database: a nationwide registered study
Pengyu WEI ; Mingyang REN ; Quan WANG ; Hong ZHANG ; Chienchih CHEN ; Qing XU ; Yi XIAO ; Dan MA ; Zhicong FU ; Dehai XIONG ; Yang LI ; Hongwei YAO ; Zhongtao ZHANG
Chinese Journal of Digestive Surgery 2024;23(6):819-825
Objective:To investigate the specimen quality of intersphincteric resection with transabdominal transanal mixed approach for rectal cancer in the Chinese Transanal Total Mesorectal Excision Registry Collaborative (CTRC) database.Methods:The retrospective case-control study was conducted. Based on the concept of real-world research, the clinicopathological data of 281 pati-ents with rectal cancer in the CTRC database who underwent intersphincteric resection with trans-abdominal transanal mixed approach in 19 medical centers, including the Beijing Friendship Hospital of Capital Medical University et al, from November 15,2017 to December 31,2023 were collected. There were 196 males and 85 females, aged 61(range, 27-87)years. Observation indicators: (1) preoperative examinations; (2) neoadjuvant therapy; (3) postoperative examinations; (4) analysis of influencing factors for positive circumferential margin in surgical specimen of intersphincteric resec-tion for rectal cancer. Measurement data with normal distribution were represented as Mean±SD. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages. The chi-square test was used for univariate analysis. Logistic regression model was used for multivariate analysis. Results:(1) Preoperative examinations. Of the 281 patients, 234 cases underwent preoperative pelvic magnetic resonance imaging (MRI) examina-tion. There were 2 cases in clinical stage T0, 3 cases in clinical stage T1, 58 cases in clinical stage T2, 137 cases in clinical stage T3, 24 cases in clinical stage T4, 3 cases in clinical stage Tx, 7 cases missing clinical T staging data. There were 87 cases in clinical stage N0, 68 cases in clinical stage N1, 60 cases in clinical stage N2, 9 cases in clinical stage Nx, 10 cases missing clinical N staging data. There were 30 cases with mesorectal fascia invasion, 53 cases with extramural venous invasion. The distance from lower margin of tumor to anal margin was 41.9(range, 1.0-80.0)mm. (2) Neoadjuvant therapy. Of the 281 patients, 125 cases underwent neoadjuvant therapy, including 39 cases receiving chemo-therapy alone, 6 cases receiving short-course simultaneous chemoradiotherapy, 5 cases receiving short-course simultaneous chemoradiotherapy and delayed surgery, 48 cases receiving long-course simultaneous chemoradiotherapy, 2 cases receiving other treatments, and 25 cases missing neoadju-vant therapy data. (3) Postoperative examinations. Of the 281 patients, 249 cases achieved R 0 resection, 9 cases achieved R 1 resection, and there were 23 cases missing surgical margin data. The maximum tumor diameter, the number of lymph nodes harvested and positive rate of vessel carcinoma embolus were 30.0(range, 0.5-200.0)mm, 13(range, 0-70) and 27.55%(73/265) in 281 patients. There were 252 patients with circumferential margin records, showing positive in 15 cases, with a positive rate as 5.95%(15/252). The minimum distance from deep part of tumor to circumferential margin was 7.0(range, 0-150.0)mm in 252 patients. There were 85 cases with distal margin records, showing positive in 1 case, and the distance from lower margin of tumor to distal margin was 10.0(range, 0-202.0)mm. There were 273 patients with specimen integrity records, which showed intact specimen in 208 cases, fair specimen in 58 cases, poor specimen in 4 cases, unevaluated specimen in 3 cases. There were 7 cases with rectal perforation. Of the 281 patients, cases in pathological stage T0, Tis, T1, T2, T3, T4 were 14, 5, 22, 107, 113, 12, respectively, and there were 8 cases missing pathological T staging data. Of the 281 patients, cases in pathological stage N0, N1a, N1b, N1c, N2a, N2b were 176, 27, 27, 11,20, 12, respectively, and there were 8 cases missing pathological N staging data. Of the 281 patients, there were 4 cases with distant metastasis, 262 cases without distant metastasis, 5 cases not evaluated, and 10 cases missing tumor metastasis data. Of the 125 patients undergoing neoadjuvant therapy, there were 85 cases with tumor regression grade records, including 16 cases as grade 1, 27 cases as grade 2, 19 cases as grade 3, 15 cases as grade 4, 8 cases as grade 5. (4) Analysis of influencing factors for positive circumferential margin in surgical specimen of intersphincteric resection for rectal cancer. Results of univariate analysis showed that preoperative T staging on preoperative pelvic MRI, mesorectal fascia invasion, extramural venous invasion, pathological T staging, and pathological N staging were related factors for positive circumferential margin in surgical specimen of intersphincteric resection for rectal cancer ( P<0.05). Conclusions:Intersph-incteric resection with transabdominal transanal mixed approach has good specimen quality and low positive rate of surgical margin. T staging on preoperative pelvic MRI may be related to positive circumferential margin after intersphincteric resection for rectal cancer.
5.The mechanism of bariatric surgery in the treatment of non-alcoholic fatty liver disease
Yiyang MIN ; Peng ZHANG ; Peirong TIAN ; Mengyi LI ; Jingyu ZHANG ; Guanda LU ; Zhongtao ZHANG
Chinese Journal of Digestive Surgery 2024;23(9):1231-1236
Non-alcoholic fatty liver disease (NAFLD), as a metabolic disease, has shown a constant upward trend in prevalence among the people in recent years. In addition to changing lifestyles and conventional drug treatment, bariatric surgery, represented by Roux-en-Y gastric bypass surgery and sleeve gastrectomy, has gradually become one of the treatment options for NAFLD. However, the mechanism of bariatric surgery in treating NAFLD remains to be studied. The "multiple-hit theory", which has gradually been recognized in recent years, believes that NAFLD is formed by the combined effect of multiple mechanisms such as insulin resistance, bile acid metabolism pathway, and intestinal flora. Based on relevant literatures and clinical practices, the authors explore the relevant mechanisms of bariatric surgery for direct or indirect treatment of NAFLD.
6.Safety and efficacy of donor-derived chimeric antigen receptor T-cell therapy in patients with relapsed B-cell acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation
Yaqi ZHUO ; Sanfang TU ; Xuan ZHOU ; Jilong YANG ; Lijuan ZHOU ; Rui HUANG ; Yuxian HUANG ; Meifang LI ; Bo JIN ; Bo WANG ; Shiqi LI ; Zhongtao YUAN ; Lihua ZHANG ; Lin LIU ; Sanbin WANG ; Yuhua LI
Chinese Journal of Hematology 2024;45(1):74-81
Objective:To investigated the safety and efficacy of donor-derived CD19+ or sequential CD19+ CD22+ chimeric antigen receptor T-cell (CAR-T) therapy in patients with B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:The data of 22 patients with B-ALL who relapsed after allo-HSCT and who underwent donor-derived CAR-T therapy at the Zhujiang Hospital of Southern Medical University and the 920th Hospital of Joint Logistics Support Force of the People’s Liberation Army of China from September 2015 to December 2022 were retrospectively analyzed. The primary endpoint was overall survival (OS), and the secondary endpoints were event-free survival (EFS), complete remission (CR) rate, and Grade 3-4 adverse events.Results:A total of 81.82% ( n=18) of the 22 patients achieved minimal residual disease-negative CR after CAR-T infusion. The median follow-up time was 1037 (95% CI 546–1509) days, and the median OS and EFS were 287 (95% CI 132-441) days and 212 (95% CI 120-303) days, respectively. The 6-month OS and EFS rates were 67.90% (95% CI 48.30%-84.50%) and 58.70% (95% CI 37.92%-79.48%), respectively, and the 1-year OS and EFS rates were 41.10% (95% CI 19.15%-63.05%) and 34.30% (95% CI 13.92%-54.68%), respectively. Grade 1-2 cytokine release syndrome occurred in 36.36% ( n=8) of the patients, and grade 3-4 occurred in 13.64% of the patients ( n=3). Grade 2 and 4 graft-versus-host disease occurred in two patients. Conclusion:Donor-derived CAR-T therapy is safe and effective in patients with relapsed B-ALL after allo-HSCT.
7.Clinical study of the efficacies of ruxolitinib plus low-dose PTCY for acute GVHD prevention after haploidentical transplantation in malignant hematological diseases
Xiaoping LI ; Yu LI ; Lin LIU ; Zhongtao YUAN ; Youcheng WANG ; Yancheng DONG ; Dingsong ZHANG ; Jing FENG ; Yingnian CHEN ; Sanbin WANG
Chinese Journal of Hematology 2024;45(2):128-133
Objective:To investigate and verify a novel acute graft versus host disease (aGVHD) prevention protocol in the context of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) .Methods:Patients who underwent haplo-HSCT in our center between January 2022 and December 2022 were included. All patients received reduced doses of cyclophosphamide, Rabbit anti-human tymoglobulin, ruxolitinib, methotrexate, cyclosporine, and MMF to prevent aGVHD. The transplantation outcomes, complications, and survival rate of all patients were investigated.Results:A total of 52 patients with haplo-HSCT were enrolled, 29 (55.8%) male and 23 (44.2%) female, with a median age of 28 (5-59) years. There were 25 cases of acute myeloid leukemia, 17 cases of acute lymphocyte leukemia, 6 cases of myelodysplastic syndrome, 2 cases of chronic myeloid leukemia and 2 cases of myeloproliferative neoplasms. 98.1% of patients had successful engraftment. The incidence of Ⅱ-Ⅳ aGVHD and Ⅲ-Ⅳ aGVHD was 19.2% (95% CI 8.2% -30.3% ) and 7.7% (95% CI 0.2% -15.2% ), respectively. No patients experienced severe gastrointestinal mucositis. The Epstein-Barr virus and CMV reactivation rates were 40.4% and 21.3%, respectively. 9.6% of patients relapsed during followup, with 1-year overall survival, progression-free survival, and non-relapse mortality rates of 86.5% (95% CI 76.9% -96.1% ), 78.8% (95% CI 67.4% -90.3% ) and 11.5% (95% CI 2.6% –20.5% ), respectively. Conclusion:Ruxolitinib combined with a low dose of PTCY is a safe and effective first-line aGVHD prevention strategy.
8.Chinese national clinical practice guidelines on prevention, diagnosis and treatment of early colorectal cancer
Jingnan LI ; Hongwei YAO ; Yun LU ; Shutian ZHANG ; Zhongtao ZHANG
Chinese Medical Journal 2024;137(17):2017-2039
Background::The incidence and mortality of colorectal cancer (CRC) in China are increasing in recent years. The clarified pathogenesis and detectable precancerous lesions of CRC make it possible to prevent, screen, and diagnose CRC at an early stage. With the development of endoscopic and surgical techniques, the choice of treatment for early CRC is also worth further discussion, and accordingly, a standard follow-up program after treatment needs to be established.Methods::This clinical practice guideline (CPG) was developed following the recommended process of the World Health Organization, adopting Grading of Recommendations Assessment, Development and Evaluation (GRADE) in assessing evidence quality, and using the Evidence to Decision framework to formulate clinical recommendations, thereby minimizing bias and increasing transparency of the CPG development process. We used the Reporting Items for practice Guidelines in HealThcare (RIGHT) statement and Appraisal of Guidelines for Research and Evaluation II (AGREE II) as reporting and conduct guides to ensure the guideline’s completeness and transparency.Results::This CPG comprises 46 recommendations concerning prevention, screening, diagnosis, treatment, and surveillance of CRC. In these recommendations, we have indicated protective and risk factors for CRC and made recommendations for chemoprevention. We proposed a suitable screening program for CRC based on the Chinese context. We also provided normative statements for the diagnosis, treatment, and surveillance of CRC based on existing clinical evidence and guidelines.Conclusions::The 46 recommendations in this CPG are formed with consideration for stakeholders’ values and preferences, feasibility, and acceptability. Recommendations are generalizable to resource-limited settings with similar CRC epidemiology pattern as China.
9.Promote the high-quality development of gastrointestinal surgery with technological concept innovation
Hongwei YAO ; Peng ZHANG ; Chao YAN ; Ziyu LI ; Zhongtao ZHANG
Chinese Journal of Surgery 2024;62(1):10-15
In the past 30 years, gastrointestinal surgery in China has made significant progress, which is reflected in the gradual standardization of clinical diagnosis and treatment, significant improvement in surgical quality, improvement in short-term and long-term postoperative outcomes, and continuous development of high-quality clinical research. At present, the spectrum of disease in gastrointestinal surgery has changed from traditional benign diseases to malignant diseases represented by gastric cancer and colorectal cancer, metabolic diseases represented by obesity and diabetes, and immune diseases represented by inflammatory bowel disease. It is necessary to carry out full-cycle management for patients. In the new era full of opportunities and challenges, surgeons must be driven by innovation in surgical technology, guided by high-quality clinical research and guaranteed by standardized diagnosis and treatment of diseases, to continue to promote the high-quality development of gastrointestinal surgery in China.
10.Promote the high-quality development of gastrointestinal surgery with technological concept innovation
Hongwei YAO ; Peng ZHANG ; Chao YAN ; Ziyu LI ; Zhongtao ZHANG
Chinese Journal of Surgery 2024;62(1):10-15
In the past 30 years, gastrointestinal surgery in China has made significant progress, which is reflected in the gradual standardization of clinical diagnosis and treatment, significant improvement in surgical quality, improvement in short-term and long-term postoperative outcomes, and continuous development of high-quality clinical research. At present, the spectrum of disease in gastrointestinal surgery has changed from traditional benign diseases to malignant diseases represented by gastric cancer and colorectal cancer, metabolic diseases represented by obesity and diabetes, and immune diseases represented by inflammatory bowel disease. It is necessary to carry out full-cycle management for patients. In the new era full of opportunities and challenges, surgeons must be driven by innovation in surgical technology, guided by high-quality clinical research and guaranteed by standardized diagnosis and treatment of diseases, to continue to promote the high-quality development of gastrointestinal surgery in China.

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