1.Effect of salidroside on the immune function of BCG-infected macrophages
Shuyi NI ; Zhao JIANG ; Zhongtao WANG ; Shumei HE
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(4):426-433
Objective·To Investigate the effects of salidroside(SAL)on the immune response of macrophages infected with BCG.Methods·RAW264.7 mouse macrophages were infected with BCG,and the experiments were divided into blank control(BCG),salidroside(SAL+BCG),isoniazid(INH+BCG),and salidroside+isoniazid(SAL+INH+BCG)groups.The effects of SAL and INH on the proliferation of RAW264.7 cells were detected by MTT colorimetric assay,and the experimental concentrations of SAL and INH were screened.After the establishment of the BCG-infected macrophage model,intracellular bacterial survival was detected by bacterial plate count and flow cytometry following salidroside pretreatment.The levels of tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),interleukin-6(IL-6),and interleukin-10(IL-10)in the culture supernatants were measured by enzyme-linked immunosorbent assay,and apoptosis levels were assessed by flow cytometry.Results·SAL at a concentration of 800 μmol/L and INH at 10 μmol/L were selected for subsequent experiments.Compared with the BCG group,SAL pretreatment for 36 h had the best effect,and the growth of BCG in macrophages in the administered group was inhibited.The inhibitory effect of the combined application of SAL and INH was obvious and statistically significant.Compared with the BCG group,SAL alone led to decreased secretion of TNF-α,IFN-γ,IL-6,and IL-10,although the differences were not statistically significant.However,the combination of SAL and INH caused a significant decrease in the levels of TNF-α,IL-6 and IL-10 in the supernatants of the cells(all P<0.05).Compared with the BCG group,in the early stage of the infection,SAL and INH were able to significantly reduce the apoptotic levels of BCG-infected RAW264.7 cells(P=0.008,P=0.032),and the combined application of SAL and INH significantly enhanced the apoptosis levels of BCG-infected RAW264.7 cells in the late stage of infection(P=0.001).Conclusion·In BCG-infected macrophages,SAL can exhibit antimycobacterial effects on the host by enhancing macrophage immune function,suppressing intracellular bacterial survival,and concurrently mitigating the inflammatory response elicited by BCG infection.
2.Effect of salidroside on the immune function of BCG-infected macrophages
Shuyi NI ; Zhao JIANG ; Zhongtao WANG ; Shumei HE
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(4):426-433
Objective·To Investigate the effects of salidroside(SAL)on the immune response of macrophages infected with BCG.Methods·RAW264.7 mouse macrophages were infected with BCG,and the experiments were divided into blank control(BCG),salidroside(SAL+BCG),isoniazid(INH+BCG),and salidroside+isoniazid(SAL+INH+BCG)groups.The effects of SAL and INH on the proliferation of RAW264.7 cells were detected by MTT colorimetric assay,and the experimental concentrations of SAL and INH were screened.After the establishment of the BCG-infected macrophage model,intracellular bacterial survival was detected by bacterial plate count and flow cytometry following salidroside pretreatment.The levels of tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),interleukin-6(IL-6),and interleukin-10(IL-10)in the culture supernatants were measured by enzyme-linked immunosorbent assay,and apoptosis levels were assessed by flow cytometry.Results·SAL at a concentration of 800 μmol/L and INH at 10 μmol/L were selected for subsequent experiments.Compared with the BCG group,SAL pretreatment for 36 h had the best effect,and the growth of BCG in macrophages in the administered group was inhibited.The inhibitory effect of the combined application of SAL and INH was obvious and statistically significant.Compared with the BCG group,SAL alone led to decreased secretion of TNF-α,IFN-γ,IL-6,and IL-10,although the differences were not statistically significant.However,the combination of SAL and INH caused a significant decrease in the levels of TNF-α,IL-6 and IL-10 in the supernatants of the cells(all P<0.05).Compared with the BCG group,in the early stage of the infection,SAL and INH were able to significantly reduce the apoptotic levels of BCG-infected RAW264.7 cells(P=0.008,P=0.032),and the combined application of SAL and INH significantly enhanced the apoptosis levels of BCG-infected RAW264.7 cells in the late stage of infection(P=0.001).Conclusion·In BCG-infected macrophages,SAL can exhibit antimycobacterial effects on the host by enhancing macrophage immune function,suppressing intracellular bacterial survival,and concurrently mitigating the inflammatory response elicited by BCG infection.
3.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.
4.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.
5.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.
6.Practice and exploration of safe export of medical-related scientific research data
Yingshuo HUANG ; Shuilong GUO ; Hongwei YAO ; Lihua WANG ; Xian ZHAO ; Zhenchang WANG ; Zhongtao ZHANG ; Shutian ZHANG
Chinese Journal of Hospital Administration 2024;40(4):310-315
Faced with the increasing demand for technological innovation, how to effectively carry out and regulate the export of medical-related scientific research data has become an urgent issue. The author reviewed the current requirements and status of data export in China and abroad, as well as the relevant requirements for medical data management in China, and introduced the practical experience of the first data compliance export case of medical field in China. In view of the main difficulties in the management of medical-related scientific research data export, such as the lack of multi-professional background members of the project team, the difficulty in writing professional documents, the relatively single template, the lack of personalized templates suitable for different professional field, and the need for homogenization of regulatory standards and requirements, it is proposed to rely on a qualified third-party platform in the form of entrusted business, adopt the optional mode under the general declaration template, establish unified regulatory standards, pay attention to the important data and national core data involved in the data export, pay attention to the ethical issues, and replace the original data with derivative data, and keep to " necessity principle" and " minimization principle", so as to provide reference for medical institutions and management departments to strengthen the standardized management and security guarantee of medical-related scientific research data export.
7.Conjecture on the next development direction of colorectal cancer and its minimally invasive surgery
Zhenjun WANG ; Zhongtao ZHANG ; Zhili JI
Chinese Journal of Surgery 2024;62(8):717-719
The surgical treatment of colorectal cancer will be more and more accurate and minimally invasive under the guidance of precision medicine. At the same time, it will derive and evolve non-surgical paths, such as immune checkpoint inhibitors and immune targeted therapy for microsatellite instability high/mismatch repair deficient colorectal cancer, and wait and watch path after neoadjuvant treatment for low advanced rectal cancer. Laparoscopic minimally invasive surgery for colorectal cancer will be gradually iterated by robots, which is the only way to intelligent surgery.
8.Clinical and genetic analysis of a child with Canavan disease due to compound heterozygous variants of ASPA gene
Shasha NIU ; Yanyan MA ; Yuqiang LYU ; Hongmei XIN ; Dong WANG ; Yanxin WANG ; Ya′nan YANG ; Zilong LI ; Yi LIU ; Zhongtao GAI
Chinese Journal of Medical Genetics 2024;41(2):225-229
Objective:To analyze the clinical phenotype and genetic characteristics for a child with Canavan disease.Methods:A child who was admitted to the Children's Hospital Affiliated to Shandong University on April 9, 2021 for inability to uphold his head for 2 months and increased muscle tone for one week was subjected to whole exome sequencing, and candidate variants were verified by Sanger sequencing.Results:Genetic testing revealed that the child has harbored compound heterozygous variants of the ASPA gene, including a paternally derived c. 556_559dupGTTC (p. L187Rfs*5) and a maternally derived c.919delA (p. S307Vfs*24). Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+ PM2_Supporting+ PM3). Conclusion:The c. 556_559dupGTTC (p.L187Rfs*5) and c. 919delA (p.S307Vfs*24) compound heterozygous variants of the ASPA gene probably underlay the pathogenesis of Canavan disease in this child.
9.Application of polymerase chain reaction and metagenomic next generation sequencing in diagnosis of traumatic bone infection
Zhongtao YANG ; Kun ZHANG ; Cheng REN ; Chaofeng WANG ; Yibo XU ; Congming ZHANG ; Deyin LIU ; Erdong SHEN ; Maoqiang FAN ; Teng MA
Chinese Journal of Orthopaedic Trauma 2024;26(12):1094-1099
Trauma-associated bone infection is one of the most serious infectious diseases after surgery, characterized by high incidence, complex pathogenic microorganisms, therapeutic difficulty and poor prognosis. Therefore, early accurate identification of pathogenic microorganisms and sensitivity of related antibiotics is very important to the success of surgery as well as of local and systemic antibiotic support therapies. As traditional detection methods have such shortcomings as complex items, numerous indicators, slow speed, a low positive rate, and inability to detect rare pathogenic microorganisms, there is an urgent need for better detection methods to identify pathogenic microorganisms of bone infection. In recent years, polymerase chain reaction (PCR) and metagenomic next generation sequencing (mNGS) have been used in clinical diagnosis of a variety of infectious diseases because of their advantages in accuracy, speed, efficiency, and detection range of pathogenic microorganisms over traditional cultures. PCR and mNGS can also be used as effective tools to diagnose trauma-associated bone infection. This review explores the advantages, disadvantages, development trends and guiding significance of these two techniques in the diagnosis of trauma-associated bone infection.
10.Co-word cluster analysis of research hotspots at home and abroad on self-management of patients with chronic obstructive pulmonary disease from 2013 to 2023
Zhongtao ZHOU ; Qingyang LI ; Shuoshuo LI ; Runqiu WANG ; Huaiyu BAI ; Ao JIANG ; Jing ZHANG
Chinese Journal of Modern Nursing 2024;30(1):77-82
Objective:To analyze the research hotspots of self-management in patients with chronic obstructive pulmonary disease (COPD) at home and abroad.Methods:Related literature on self-management of COPD patients were searched in China National Knowledge Infrastructure and Web of Science databases, and the searched period was from January 1, 2013 to June 30, 2023. CiteSpace 5.8 software was used for keyword cluster analysis.Results:A total of 641 articles in Chinese and 1 192 in English were obtained. Domestic research hotspots about self-management of COPD patients mainly focused on health education, continuing care, rehabilitation care, etc. Foreign research hotspots about self-management of COPD patients mainly focused on mobile health, telemedicine and so on.Conclusions:This paper analyzes the research hotspots of self-management of COPD patients at home and abroad and provides reference for future research on self-management of COPD patients.

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