1.Traditional Chinese Medicine Regulates JAK/STAT Signaling Pathway to Treat Colorectal Cancer: A Review
Mingxing WANG ; Wanhui DONG ; Baorui ZHANG ; Tong LAI ; Aixin LIU ; Qingming SUN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):278-287
Colorectal cancer (CRC) ranks as the second leading cause of cancer death worldwide. Although preventive colonoscopy screening has improved the survival rate of CRC patients in the past few years, there are still many patients diagnosed after symptoms appear. The surgery for CRC carries high risks and high recurrence, and ideal therapies remain to be developed. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway has become a focus of research due to its central role in cellular activities. As a classic oncogenic pathway, the JAK/STAT signaling pathway offers new possibilities for diagnosing and treating various malignancies, and it paves a new way for developing therapies for CRC. This pathway not only participates in basic cellular processes, such as proliferation, differentiation, and apoptosis but also plays a crucial role in immune responses and inflammation. Abnormal activation of the JAK/STAT signaling pathway is closely related to the occurrence and development of CRC. Studies have shown that the active components and compound prescriptions of traditional Chinese medicine (TCM) can inhibit the proliferation, invasion, migration, and angiogenesis while promoting the apoptosis and autophagy of CRC cells by interfering with the JAK/STAT signaling pathway. Furthermore, this pathway may also play a role in regulating the sensitivity of tumor cells to chemotherapy and radiotherapy, thus influencing the effectiveness of tumor treatment and impeding the progression of CRC. In recent years, research results have been updated rapidly, and previous literature summaries have failed to incorporate the latest findings, creating obstacles to accessing current literature. Therefore, this article supplements and summarizes information from the definition of the JAK/STAT pathway, association of this pathway with CRC, and TCM intervention of CRC. This review aims to provide references for future development of molecular biology regarding CRC and the research and development of new drugs.
2.Magu Xujin capsule promotes hip fracture healing in aged rats through SDF-1/CXCR4 signaling pathway
Xiuxiu HOU ; Baorui XING ; Yuanchao FENG ; Yadi ZHANG
Tianjin Medical Journal 2025;53(1):19-23
Objective To explore the effects of Magu Xujin capsule on hip fracture healing and stromal cell-derived factor-1/CXC chemokine receptor 4(SDF-1/CXCR4)signaling pathway in elderly hip fracture rats.Methods The hip fracture model of aged rats was established,and successfully modeled rats were randomly separated into the model group,the low-dose Magu Xujin capsule group,the high-dose Magu Xujin capsule group,the high-dose Magu Xujin capsule+pathway inhibitor group(the high-dose Magu Xujin capsule and AMD3100 group),with 12 rats in each group.An additional 12 healthy rats were selected as the control group.X-ray was used to observe the healing of hip fractures in rats,and Garrett score was performed.Enzyme-linked immunosorbent assay(ELISA)was applied to detect serum levels of inflammatory factors related to fracture healing,such as tumor necrosis factor-alpha(TNF-α)and interleukin-10(IL-10).CT scanning analysis was used to determine bone volume fraction(BV/TV)and bone surface area/volume ratio(BS/BV).Immunohistochemistry was applied to detect the expression of fracture healing factor insulin-like growth factor-1(IGF-1)and bone morphogenetic protein-2(BMP-2).Western blot assay was applied to detect the expression of SDF-1/CXCR4 signaling pathway related proteins.Results Garrett score,IL-10 level,BV/TV,BS/BV,the IGF-1,BMP-2,SDF-1 and CXCR4 expression were lower in the model group than those in the control group,while TNF-α level was higher(P<0.05).Garrett score,IL-10 level,BV/TV,BS/BV,IGF-1,BMP-2,SDF-1 and CXCR4 expression were higher in the low-dose and high-dose Magu Xujin capsule groups than those in the model group,while TNF-α level was lower(P<0.05).Garrett score,IL-10 level,BV/TV,BS/BV,IGF-1,BMP-2,SDF-1 and CXCR4 expression were lower in the high-dose Magu Xujin capsule+AMD3100 group than those in the high-dose Magu Xujin capsule group,while TNF-α level was higher(P<0.05).Conclusion Magu Xujin capsule can promote hip fracture healing in aged rats,and its mechanism may be related to the activation of SDF-1/CXCR4 signaling pathway.
3.Magu Xujin capsule promotes hip fracture healing in aged rats through SDF-1/CXCR4 signaling pathway
Xiuxiu HOU ; Baorui XING ; Yuanchao FENG ; Yadi ZHANG
Tianjin Medical Journal 2025;53(1):19-23
Objective To explore the effects of Magu Xujin capsule on hip fracture healing and stromal cell-derived factor-1/CXC chemokine receptor 4(SDF-1/CXCR4)signaling pathway in elderly hip fracture rats.Methods The hip fracture model of aged rats was established,and successfully modeled rats were randomly separated into the model group,the low-dose Magu Xujin capsule group,the high-dose Magu Xujin capsule group,the high-dose Magu Xujin capsule+pathway inhibitor group(the high-dose Magu Xujin capsule and AMD3100 group),with 12 rats in each group.An additional 12 healthy rats were selected as the control group.X-ray was used to observe the healing of hip fractures in rats,and Garrett score was performed.Enzyme-linked immunosorbent assay(ELISA)was applied to detect serum levels of inflammatory factors related to fracture healing,such as tumor necrosis factor-alpha(TNF-α)and interleukin-10(IL-10).CT scanning analysis was used to determine bone volume fraction(BV/TV)and bone surface area/volume ratio(BS/BV).Immunohistochemistry was applied to detect the expression of fracture healing factor insulin-like growth factor-1(IGF-1)and bone morphogenetic protein-2(BMP-2).Western blot assay was applied to detect the expression of SDF-1/CXCR4 signaling pathway related proteins.Results Garrett score,IL-10 level,BV/TV,BS/BV,the IGF-1,BMP-2,SDF-1 and CXCR4 expression were lower in the model group than those in the control group,while TNF-α level was higher(P<0.05).Garrett score,IL-10 level,BV/TV,BS/BV,IGF-1,BMP-2,SDF-1 and CXCR4 expression were higher in the low-dose and high-dose Magu Xujin capsule groups than those in the model group,while TNF-α level was lower(P<0.05).Garrett score,IL-10 level,BV/TV,BS/BV,IGF-1,BMP-2,SDF-1 and CXCR4 expression were lower in the high-dose Magu Xujin capsule+AMD3100 group than those in the high-dose Magu Xujin capsule group,while TNF-α level was higher(P<0.05).Conclusion Magu Xujin capsule can promote hip fracture healing in aged rats,and its mechanism may be related to the activation of SDF-1/CXCR4 signaling pathway.
4.Co-inhibiting SHP2 and FGFR2 to treat FGFR2-fused gastric cancer by regulating RAS/ERK and PI3K/AKT signaling pathways
Zhang YUE ; Wang YUE ; Wei YUTAO ; Yu LIXIA ; Liu BAORUI ; Wei JIA
Chinese Journal of Clinical Oncology 2024;51(14):703-709
Objective:In this study,we explored the application prospects and mechanisms of action of co-inhibiting fibroblast growth factor receptor 2(FGFR2)and Src homology region 2-containing protein tyrosine phosphatase 2(SHP2)in gastric cancer with the TACC2-FGFR2 fu-sion gene.Methods:We established human gastric cancer cell lines overexpressing the TACC2-FGFR2 fusion gene(MKN45TACC2-FGFR2 and NUGC4TACC2-FGFR2 cells)or a control lentiviral virus(MKN45NC and NUGC4NC cells).The cells were treated with the FGFR2 inhibitor AZD4547,the SHP2 inhibitor SHP099,or a combination of both.The proliferation and migration of tumor cells were detected using cell counting Kit-8(CCK-8)and scratch assays.After treating MKN45TACC2-FGFR2 and NUGC4TACC2-FGFR2 cells with different formulations for 1 or 48 h,Western blot was used to detect variations in the levels of FGFR2,SHP2,and proteins downstream of the RAS/ERK and PI3K/AKT signaling pathways.Results:Com-pared to monotherapy,the combination of AZD4547 and SHP099 significantly inhibited the proliferation and migration of MKN45TACC2-FGFFR2 and NUGC4TACC2-FGFFR2 cells.After 1 h of treatment,the combination therapy inhibited the RAS/ERK and PI3K/AKT pathways in MKN45TACC2-FGFFR2 cells to a greater extent than the AZD4547 monotherapy.Forty-eight hours of AZD4547 monotherapy resulted in feedback activation of p-FGFR and p-SHP2,but failed to inhibit the RAS/ERK pathway.However,combination therapy continuously suppressed upstream FGFR2 and SHP2 signaling,as well as downstream RAS/ERK and PI3K/AKT pathways.Conclusions:Co-inhibiting FGFR2 and SHP2 further inhibit gastric cancer with the TACC2-FGFR2 fusion gene by suppressing the RAS/ERK and PI3K/AKT pathways.These findings provide a new treatment mode for patients with gastric cancer with the TACC2-FGFR2 fusion gene.
5.Surgical efficacy and prognosis influencing factors of hilar cholangiocarcinoma based on multi-disciplinary diagnosis and treatment
Liang MAO ; Yifei YANG ; Alexer ABAYDULLA ; Tie ZHOU ; Xu FU ; Hao CHENG ; Jing ZHANG ; Youjun LIANG ; Yinyin FAN ; Wentao KONG ; Jian HE ; Aimei LI ; Min TANG ; Qun ZHOU ; Qibin HE ; Yi WANG ; Lei WANG ; Weiwei KONG ; Jie SHEN ; Baorui LIU ; Jun CHEN ; Jiong SHI ; Qi LI ; Zhao LIU ; Yudong QIU
Chinese Journal of Digestive Surgery 2023;22(7):873-883
Objective:To investigate the surgical efficacy and prognosis influencing factors of hilar cholangiocarcinoma based on multidisciplinary diagnosis and treatment.Methods:The retrospective cohort study was conducted. The clinicopathological data of 91 patients with hilar cholangiocarcinoma who underwent surgery in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from April 2004 to April 2021 were collected. There were 59 males and 32 females, aged (61±10)years. Patients who were admitted from April 2004 to March 2014 underwent traditional surgical diagnosis and treatment, and patients who were admitted from April 2014 to April 2021 underwent multidisciplinary diagnosis and treatment. Observation indica-tors: (1) surgical situations; (2) postoperative situations; (3) postoperative pathological examina-tions; (4) postoperative prognosis analysis; (5) influencing factors of postoperative prognosis. Follow-up was conducted using telephone interview and outpatient examination. Patients were followed up once every 6 months after surgery to detect survival. The follow-up was up to April 2023. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Comparison of ordinal data was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Kaplan-Meier method was used to draw survival curve and calculate survival rate. The Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard model. Results:(1) Surgical situations. Of the 91 patients, there were 65 cases receiving hemi- or expanded hemi-hepatectomy, 13 cases receiving tri-hepatectomy, 9 cases receiving partial hepatectomy, 4 cases receiving extrahepatic bile duct resection. There were 24 cases receiving combined vein resection and reconstruction, 8 cases receiving combined pancreaticoduodenectomy, 6 cases receiving com-bined hepatic artery resection and reconstruction, including 24 cases receiving extended radical surgery (tri-hepatectomy, hepatic artery resection and reconstruction, hepatopancreaticoduodenec-tomy). The operation time, volume of intraoperative blood loss and intraoperative blood transfusion rate of 91 patients was (590±124)minutes, 800(range, 500?1 200)mL and 75.8%(69/91), respectively. Of the 91 patients, cases receiving extended radical surgery, the volume of intraoperative blood loss were 4, 650(range, 300?1 000)mL in the 31 patients who were admitted from April 2004 to March 2014, versus 20, 875 (range, 500?1 375)mL in the 60 patients who were admitted from April 2014 to April 2021, showing significant differences between them ( χ2=4.39, Z=0.31, P<0.05). (2) Post-operative situations. The postoperative duration of hospital stay and cases with postoperative infectious complications were (27±17)days and 50 in the 91 patients. Cases with abdominal infection, cases with infection of incision, cases with bacteremia and cases with pulmonary infection were 43, 7, 5, 8 in the 91 patients. One patient might have multiple infectious complications. Cases with bile leakage, cases with delayed gastric emptying, cases with chylous leakage, cases with liver failure, cases with pancreatic fistula, cases with intraperitoneal hemorrhage, cases with reoperation, cases dead during the postoperative 90 days were 30, 9, 9, 6, 5, 3, 6, 3 in the 91 patients. Cases with abdominal infection was 10 in the 31 patients who were admitted from April 2004 to March 2014, versus 33 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=4.24, P<0.05). Cases dead during the postoperative 90 days was 3 in the 31 patients who were admitted from April 2004 to March 2014, versus 0 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( P<0.05). (3) Post-operative pathological examinations. Of the 91 patients, cases with Bismuth type as type Ⅰ?Ⅱ, type Ⅲ, type Ⅳ, cases with T staging as Tis stage, T1 stage, T2a?2b stage, T3 stage, T4 stage, cases with N staging as N0 stage, N1 stage, N2 stage, cases with M staging as M0 stage, M1 stage, cases with TNM staging as 0 stage, Ⅰ stage, Ⅱ stage, Ⅲ stage, ⅣA stage, ⅣB stage, cases with R 0 radical resection, cases with R 1 or R 2 resection were 15, 46, 30, 1, 9, 25, 30, 26, 49, 36, 6, 85, 6, 1, 7, 13, 58, 6, 6, 63, 28. Cases with R 0 radical resection, cases with R 1 or R 2 resection were 15, 16 in the 31 patients who were admitted from April 2004 to March 2014, versus 48, 12 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=9.59, P<0.05). (4) Postoperative prognosis analysis. Of the 91 patients, 3 cases who died within 90 days after surgery were excluded, and the 5-year overall survival rate and median overall survival time of the rest of 88 cases were 44.7% and 55 months. The 5-year overall survival rate was 33.5% in the 28 patients who were admitted from April 2004 to March 2014, versus 50.4% in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=5.31, P<0.05). Results of further analysis showed that the corresponding 5-year overall survival rate of cases without lymph node metastasis was 43.8% in the 16 patients who were admitted from April 2004 to March 2014, versus 61.6% in the 31 patients who were admitted from April 2014 to April 2021. There was a significant difference in the 5-year overall survival rate between these patients without lymph node metastasis ( χ2=3.98, P<0.05). The corresponding 5-year overall survival rate of cases with lymph node metastasis was 18.5% in the 12 patients who were admitted from April 2004 to March 2014, versus 37.7% in the 29 patients who were admitted from April 2014 to April 2021. There was no significant difference in the 5-year overall survival rate between these patients with lymph node metastasis ( χ2=2.25, P>0.05). (5) Influencing factors of postoperative prognosis. Results of multivariate analysis showed that poorly differentiated tumor and R 1 or R 2 resection were inde-pendent risk factors influencing prognosis after surgical treatment of hilar cholangiocarcinoma ( hazard ratio=2.62, 2.71, 95% confidence interval as 1.30?5.29, 1.30?5.69, P<0.05). Conclusions:Compared with traditional surgical diagnosis and treatment, treatment of hilar cholangiocarcinoma based on multidisciplinary diagnosis and treatment can expand surgical indications, reduce proportion of dead patients within 90 days after surgery, improve proportation of radical resection and long-term survival rate. Poorly differentiated tumor and R 1 or R 2 resection are independent risk factors influencing prognosis after surgical treatment of hilar cholangiocarcinoma.
6.Progress in the application of pathogen vaccine in tumor immunotherapy
Hanxi ZHANG ; Baorui LIU ; Rutian LI
Tumor 2023;43(2):122-131
Immunosuppressive tumor microenvironment is an important obstacle to tumor immunotherapy.Therefore,improving tumor microenvironment to enhance immune response is the key to improve the efficacy of immunotherapy.Based on the basic principle of immunology that the body has a strong response to"foreign"antigens and a weak response to preexisting antigens,pathogen infection can be combined with innate immune-related receptors to enhance the anti-tumor immune response.Pathogen vaccines can induce a"hot"tumor microenvironment with stronger antigen presentation and T lymphocyte activation,showing higher response to immunotherapy and having better security.In this review,we summarized the related studies on pathogen vaccine enhancing tumor immune response,including mixed bacterial vaccine,BCG vaccine,OK-432,synthetic vaccines based on tetanus toxin,modified vaccinia virus,influenza vaccine,Epstein-Barr virus and COVID-19 vaccine.The feasibility,application prospect and challenge of pathogen vaccine in tumor immunotherapy were discussed.
7.Radiotherapy for the head and neck soft tissue sarcomas: review and prospect
Zhifan ZHANG ; Luxin XUE ; Xiaolu WANG ; Baorui LIU ; Rutian LI
Chinese Journal of Radiation Oncology 2023;32(9):843-847
Soft tissue sarcoma (STS) is a highly heterogeneous group of malignant tumors originating from mesenchymal tissues. The most common sites of STS are limbs (45%), viscera (21%) and retroperitoneum (17%). The incidence of head and neck soft tissue sarcomas (HNSTS) is the lowest (5%) compared with other areas of the body. Due to numerous functional organs and delicate and complex anatomical structures of the head and neck, it is often difficult to perform radical surgical treatment. Therefore, radiotherapy plays an important role in the treatment of HNSTS. Due to its low incidence, radiotherapy for HNSTS has been rarely studied and captivated little attention. In this article, the present situation and clinical evidence of radiotherapy for HNSTS were summarized, aiming to provide reference for clinical practice.
8.Frequency of JK (a-b-) in Yichang: genetic pedigree analysis of Jk (a-b-) and Jka weak expression
Juncui GAO ; Yurong YUAN ; Yuxiang LIN ; Haojun ZHANG ; Shangen ZHENG
Chinese Journal of Blood Transfusion 2022;35(2):154-156
【Objective】 To explore the molecular hereditary and frequency of Jk(a-b-) in blood donors in Yichang. 【Methods】 A total of 49 999 samples from Yichang Red Cross Central Blood Station were screened for Jk(a-b-) by urea hemolysis test(2 mol /L). The phenotypes of JK (a-b -) probands and their families were confirmed by monoclonal anti-Jka and anti-Jkb, and the whole exon of SLC14A1 gene was sequenced. 【Results】 The frequency of Jk(a-b-) in Yichang blood donors was 0.004% (2/49 999), and the exon sequencing of SLC14A1 gene confirmed that both two probands were JK*02N.01 caused by c. 342-1G>A homozygous mutation.Besides, JK*01W.01 allele was observed in the pedigree analysis, and weak expression of Jka was found in 4 out of 11 family members. 【Conclusion】 The frequency of JK (a-b -) in Yichang blood donors is similar to those in Shanghai 0.004%(2/48 400), and both caused by JK * 02N.01 allele with high frequency in Southeast Asia. The epidemiological survey of JK * 01w.01 allele frequency should be further performed.
9.Three platelet antibody detection methods: a comparative study
Dongmin ZHANG ; Jing LI ; Lijia SHI ; Tao LIU ; Yueping DING
Chinese Journal of Blood Transfusion 2022;35(11):1164-1166
【Objective】 To compare three kinds of platelet antibody detection methods used to identify alloantibodies in patients with platelet transfusion refractory(PTR). 【Methods】 The 83 samples from PTR patients were analyzed base on three different methods, including solid phase ELISA, Luminex, and capture. The sensitivity, reproducibility, and consistency of different kits were evaluated. 【Results】 A total of 71 (62 positive and 9 negative) out of 83 samples showed consistent results by three methods. The consistency between Luminex and solid phase ELISA was 95.2% (Kapp value=0.829, P<0.05), between solid phase ELISA and capture method was 85.5% (Kapp value=0.512, P<0.05), and between Luminex and capture method was 90.3% (kappa value=0.636, P<0.05). Among the 12 samples with inconsistent results, 3 cases presented positive results by capture method alone and negative by other methods, which had incompatible cross-matching results with 6 random blood donors; 5 cases with HLA antibodies showed negative results by capture method alone and positive by both Luminex and solid phase ELISA; the other 4 cases were positive in both capture and Luminex, but negative in solid phase ELISA. 【Conclusion】 The consistency of three methods was 85.5%, and each has its limitations. The capture method is rapid, economic and registered domestically, which can be used for preliminary screening.Luminex has the optimal diagnostic performance, which can be used for high-throughput and HPA/HLA antibody analysis. The solid phase ELISA is convenient. The combination of them can detect platelet antibodies effectively.
10.Analysis of surveillance results of brucellosis in Lushan County, Pingdingshan City, Henan Province from 2011 to 2019
Yanyan LI ; Junjie ZHANG ; Qimin GUO ; Baorui LI ; Qingmei XIE ; Zongjin LI ; Xiping MA
Chinese Journal of Endemiology 2021;40(9):738-741
Objective:The surveillance results of brucellosis in Lushan County, Pingdingshan City, Henan Province are analyzed to provide basis for formulating prevention and control strategies.Methods:Retrospective analysis method was used to collect the surveillance data from Lushan County Center for Disease Control and Prevention and Animal Husbandry Department from 2011 to 2019. Descriptive statistical analysis was made on the serological, pathogenic of brucellosis.Results:From 2011 to 2019, 15 943 high-risk people were investigated, and 10 834 were serologically tested, with a positive detection rate of 23.11% (2 504/10 834). Among them, the positive detection rate of brucellosis serum increased rapidly in 2013 and decreased after 2016. The positive detection rate was 25.87% (1 593/6 157) in men and 19.48% (911/4 677) in women. The age of positive detection was mainly 40-< 70 years old, accounting for 70.45% (1 764/2 504). The positive detection rate of farmers in all occupations was the highest, which was 25.97% (2 242/8 634). There were significant differences in the positive detection rates among different gender, age and occupation (χ 2=61.163, 27.855, 257.412, P < 0.01). A total of 578 blood samples from patients with acute brucellosis were isolated and cultured, 215 strains of Brucella were detected, and the positive detection rate was 37.20%. Conclusions:The high-risk group of human brucellosis in Lushan County, Pingdingshan City is middle-aged and elderly male farmers engaged in aquaculture. It is suggested that the joint prevention and control measures should be strengthened, the health education of high-risk groups should be strengthened, and comprehensive prevention and control measures should be taken to control the occurrence and prevalence of brucellosis.

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