1.Arthroscopic surgery for treatment of sinus tarsi syndrome
Jianchao GUI ; Liming WANG ; Yiqiu JIANG ; Chenyang XU ; Li ZHANG ; Xiangjie GU ; Xin MA ; Xu WANG
Chinese Journal of Trauma 2010;26(12):1078-1081
Objective To investigate the result of arthroscopic surgery in the treatment of sinus tarsi syndrome. Methods The study involved 15 patients (6 males and 9 females) with sinus tarsi syndrome admitted to First Hospital of Nanjing from July 2006 to May 2008. The age of the patients ranged from 23 to 63 years ( average 46.3 years). All the patients had one side involvement, including 10 patients with left side involvement and five with right side involvement. All the operations were performed under the tourniquet control and the patients were placed at the lateral decubitus position. The lateral, anterolateral and posterolateral portals were applied intraoperatively and the medial portal was applied when necessary. Visual analogue scale (VAS) and American orthopedic foot and ankle scale (AOFAS) ankle-hindfoot scale were used for follow-up evaluation. Results More than two lesions were found under arthroscope in all patients. The lesions included scar tissue hypertrophy and inflammation in the sinus tarsal canal, soft tissue impingement in the subtalar joint, synovitis, partial tears of subtalar capsule, interosseous talocalcaneal ligament or cervical ligament, cartilage injury and subtalar degeneration. All patients were followed up for 19-35 months (mean 26. 1 months). At the final follow-up, the VAS score was improved from preoperative 7.6 points ( range 6-9 points) to postoperative 2.5 points (range 1-4 points) (P<0.01 ), and the AOFAS score improved from preoperative 41. 9 points (range 20-67 points) to postoperative 83. 1 points ( range 70-100 points) ( P < 0. 01 ). The excellence rate of the AOFAS score reached 73% at the final follow-up. Conclusion For patients with sinus tarsi syndrome after a failed conservative treatment, arthroscopic surgery should be performed as soon as possible and the clinical result is satisfactory.
2.Correlation between chondrocyte migration and integration capability during autologous chondrocyte transplantation
Yiming LU ; Jianchao GUI ; Yang XU ; Zhaowei YIN ; Xiaofei YANG ; Yiqiu JIANG
Chinese Journal of Tissue Engineering Research 2013;(44):7721-7728
BACKGROUND:In joint surgery, the commonly used autologous chondrocyte transplantation often used to repair cartilage defects, and poor integration is one of the reasons that leading to failure repairing. Chondrocytes migration capability is proven to have correlation with integration and some pathways, such as Src-phosphorylated phospholipase Cγ1-extracellular regulated kinase 1/2 has been confirmed to have correlation with the migration ability of chondrocytes, but the correlation with the integration is stil unknown. OBJECTIVE:To determine the chondrocyte signaling pathways involved in autologous chondrocyte migration and their effects on cartilage integration in autologous chondrocyte implantation. METHODS:Articular chondrocytes were isolated from immature pig knee joints. The cells were divided into four groups:Src group, phosphorylated phospholipase Cγ1 group, extracellular regulated kinase 1/2 group and control group, then the Boyden chambers were used to quantify the chondrocyte migration. The chondrocytes/cartilage ring integration model was developed and cultured for 28 days, and then histology, biochemistry, biomechanics, western blot analysis and celltracking analysis were performed to observe the differences between the control group and the suppression groups. RESULTS AND CONCLUSION:The migration ability of chondrocytes was significantly decreased after pretreated with inhibitors. After the chondrocytes/cartilage ring co-cultured for 28 days, Western blot analysis showed that the pathway inhibitors has been presented in the entire culture cycle. The number and length of chondrocytes migrated into the integration area, col agen secretion level, matrix and mechanical strength in the control group were higher than those in three suppression groups. The results suggest that chondrocyte migration ability can affect the cartilage integration capability through Src-phosphorylated phospholipase Cγ1-extracellular regulating kinase 1/2 signal transduction pathway.
3.Inhibitory Effects of Suramin in Combination with PG-Rg3 on the Growth of Lung Adencarcinoma in Mice
Jianbin HE ; Yiqiu ZHANG ; Zhi XIANG ; Jianxin TANG ; Xiahui XU ; Ping ZHANG
Tianjin Medical Journal 2013;(9):887-890
Objective To observe the effect of suramin combinated with PG-Rg3 on xenograft growth of lung adeno-carcinoma in mice, and the related mechanism thereof. Methods Forty C57BL/6J mice bearing Lewis cells were random-ized into five groups:control group, cisplatin (DDP) group, suramin group, PG-Rg3 group and combination group. Appropri-ate interventions were given in five groups of mice. Mice were sacrificed at day 24 after tumor inoculation. The subcutaneous tumors were stripped for histological examination. The tumor inhibitory rate was measured. The expressions of erythropoietin-producing hepatoma amplified sequences (Eph) B4 protein, Bcl-2 and tumors microvessel density (MVD) were determined by immunohistochemistry method with image analyze system. The apoptosis of tumor cells was measured by biotinyated dUTP nick and labeling (TUNEL) method. Results There were significantly lower values in subcutaneous tumor volume and weight in drug-treated groups than those in control group (P<0.05). The inhibitory rates were 39.20%, 49.11%, 54.86%and 62.49%in cisplatin group, suramin group, PG-Rg3 group and combined group (P<0.05). The values of EphB4, MVD and Bcl-2 grey values were significantly decreased, the apoptotic index was significantly increased, in suramin group, PG-Rg3 group and combined group than those of control group and DDP group (P<0.05). The values of EphB4, MVD and Bcl-2 grey values were significantly increased, the apoptotic index was significantly decreased, in suramin group and PG-Rg 3 group than those of combined group (P<0.05). Conclusion Suramin combinated with PG-Rg3 can produce a synergetic inhibitory activity against tumor growth of lung adenocarcinoma, which may be associated with the effect of suppressing the expression of EphB4 and angiogenesis, and the promotion of tumor cell apoptosis.
4.An integrated model for tissue engineered cartilage repair in vitro
Jianxin ZHOU ; Feng GAO ; Jianchao GUI ; Zhaowei YIN ; Xiaofei YANG ; Yang XU ; Yiming LU ; Yang LI ; Yiqiu JIANG
Chinese Journal of Tissue Engineering Research 2014;(27):4324-4329
BACKGROUND:With the development of tissue engineering, autologous chondrocyte implantation is often used to repair cartilage defects. And poor integration is one of the common reasons that lead to failure repairing. Many models in vitro are used for related studies.
OBJECTIVE:To develop an interface integrated model of tissue engineered cartilage repair in vitro and to evaluate the effect.
METHODS:Cartilage integration model in vitro was established in pigs. Total y 21 cartilaginous rings were obtained and divided into agarose gel group (n=18) and control group (n=3). In agarose gel group, cartilage rings were covered with agarose gel. Chondrocytes were separated and implanted into the ring. The leakage of cells around the cartilage rings was observed. The sections were stained for histological observation at 1, 2, 4 weeks. The average area of neochondrocytes was measured and compared.
RESULTS AND CONCLUSION:The results from the control group were not processed, because there was no chondrocyte aggregate formation in the center of the explant ring due to earlier chondrocyte leakage outside the explant. While no chondrocytes were found outside the explant ring in the agarose gel group. Tissue sections of the agarose gel group were stained by hematoxylin and eosin, alcian blue, Safranin-O and col agen type II immunohistochemistry at 1, 2, 4 weeks. Neochondrocytes proliferated within cartilage ring, and produced extracellular matrix. After 2 weeks of incubation, these inserted chondrocytes were significantly increased. There was no statistical y significant increment between 2 weeks and 4 weeks (P>0.05), although the area was further increased by 4 weeks. This model provides a convenient simulation of the cartilage integration process in vitro and has a potential application in studies of cartilage integration and cartilage tissue engineering.
5.Estrogen receptor beta suppresses the androgen receptor oncogenic effects in triple-negative breast cancer
Feng XU ; Kun XU ; Lingling FAN ; Xintong LI ; Yiqiu LIU ; Fang YANG ; Chengjun ZHU ; Xiaoxiang GUAN
Chinese Medical Journal 2024;137(3):338-349
Background::Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer associated with poor prognosis and limited treatment options. The androgen receptor (AR) has emerged as a potential therapeutic target for luminal androgen receptor (LAR) TNBC. However, multiple studies have claimed that anti-androgen therapy for AR-positive TNBC only has limited clinical benefits. This study aimed to investigate the role of AR in TNBC and its detailed mechanism.Methods::Immunohistochemistry and TNBC tissue sections were applied to investigate AR and nectin cell adhesion molecule 4 (NECTIN4) expression in TNBC tissues. Then, in vitro and in vivo assays were used to explore the function of AR and estrogen receptor beta (ERβ) in TNBC. Chromatin immunoprecipitation sequencing (ChIP-seq), co-immunoprecipitation (co-IP), molecular docking method, and luciferase reporter assay were performed to identify key molecules that affect the function of AR. Results::Based on the TNBC tissue array analysis, we revealed that ERβ and AR were positive in 21.92% (32/146) and 24.66% (36/146) of 146 TNBC samples, respectively, and about 13.70% (20/146) of TNBC patients were ERβ positive and AR positive. We further demonstrated the pro-tumoral effects of AR on TNBC cells, however, the oncogenic biology was significantly suppressed when ERβ transfection in LAR TNBC cell lines but not in AR-negative TNBC. Mechanistically, we identified that NECTIN4 promoter –42 bp to –28 bp was an AR response element, and that ERβ interacted with AR thus impeding the AR-mediated NECTIN4 transcription which promoted epithelial–mesenchymal transition in tumor progression. Conclusions::This study suggests that ERβ functions as a suppressor mediating the effect of AR in TNBC prognosis and cell proliferation. Therefore, our current research facilitates a better understanding of the role and mechanisms of AR in TNBC carcinogenesis.
6.Efficacy and safety of infliximab in the treatment of pediatirc Crohn′s disease
Xu XU ; Yuan XIAO ; Yi YU ; Jia LI ; Yiqiu HUANG ; Wei CAO ; Hui HU ; Ting ZHANG ; Chundi XU ; Xinqiong WANG
Chinese Journal of Pediatrics 2021;59(7):557-562
Objective:To analyze the efficacy and safety of the biological agent infliximab (IFX) in the treatment of pediatric Crohn′s disease.Methods:A total of 86 children with Crohn′s disease who had received IFX in three hospitals (Ruijin Hospital, Ruijin Hospital North and Shanghai Children's Hospital) in Shanghai from January 2007 to December 2017 were included in this retrospective study. The efficacy of IFX was assessed by comparing clinical and laboratory data before and after IFX treatment. Student t test, Mann-Whitney U test or chi-square test were used to analyze the data of the two groups. Logistic reggression analysis were used to analyze the effects of variables such as age, clinical characteristics, disease behavior and combined medications on the efficacy and safety of IFX. Results:Among the 86 children with Crohn′s disease in the study, 50 were males and 36 females. The IFX treatment was initiated at 12.0 (7.1, 13.6) years of age, and the follow-up period was 94.1 (47.8, 185.5) weeks. Efficacy analysis showed that in the induction remission phase, the clinical response rate was 97% (79/81) and the remission rate was 74% (60/81). In the maintenance remission phase, the clinical response rate was 75% (51/68) and the remission rate was 68% (46/68). After 34 weeks of treatment with IFX, pediatric Crohn′s disease activity index (PCDAI) (5 (0, 10) vs. 36 (26, 45)), C-reactive protein (3 (1, 8) vs. 8 (3, 31) mg/L), erythrocyte sedimentation rate (10 (6, 10) vs. 35 (20, 50) mm/1 h), platelet ( (327±107)×10 9vs. (438±159) ×10 9/L), albumin ((37±6) vs. (30±6) g/L), hemoglobin ((116±16) vs. (103±18) g/L), change of body weight (-0.5±1.2 vs. -1.0±0.9), anemia (29% (20/68) vs. 75% (51/68)), and perianal disease (13/21 vs. 0) were significantly improved (all P<0.05). By the end of 34 weeks of IFX treatment, 25% (17/68) of children experienced secondary loss of response to IFX. Logistic reggression analysis showed that PCDAI>30 was positively correlated with secondary loss of response ( OR=3.823, 95% CI 1.015 -15.328, P=0.048), and combined with azathioprine was conducive to maintaining efficacy of IFX ( OR=0.440, 95% CI 0.106 -1.033, P=0.044). The IFX-related adverse events included infusion reactions in 17% (15/86) and infections in 42% (36/86) of children. Analysis showed that age<6 years was a risk factor for infusion reactions (χ 2=6.556, P=0.010), and combined use of steroids (χ 2=5.230, P=0.022) may increase the incidence of infection. Conclusions:IFX is effective in the treatment of pediatric Crohn′s disease with favorable safety. Reducing secondary loss of response to IFX is an urgent issue that need to be addressed. At the same time, it is necessary to pay close attention to the adverse events during IFX treatment.
7.Study on relationship between cervical microecology and cervical squamous intraepithelial lesions
Ye ZHOU ; Dandan YUAN ; Lanfeng SHEN ; Renjing HU ; Yiqiu XU ; Xuewen HUANG
Chinese Journal of Laboratory Medicine 2020;43(4):468-474
Objective:To explore the relationship between cervical microecology and cervical squamous intraepithelial lesions (SIL).Methods:All subjects were recruited from the health care center or gynecology of the Affiliated Wuxi No.2 People′s Hospital of Nanjing Medical University from March to May of 2019, including 12 subjects normal cervix with 37-47 years old, 21 low-grade squamous intraepithelial lesion (LSIL) subjects with 39-48 years old, 5 high-grade squamous intraepithelial lesion (HSIL) subjects with 38-45 years old and 3 cervical squamous cell carcinoma subjects with 42-43 years old. All subjects were required to fill in a questionnaire, and performed cervical examination. Meanwhile, the microecology of cervical secretions was analyzed by the next generation sequencing (NGS) and the NGS results were analyzed by bioinformatics. Subjects were divided into human papilloma virus (HPV)-negative groups, low-risk HPV (lrHPV), 16/18 high-risk HPV (hrHPV) and other hrHPV infection groups based on HPV test results of NGS. The Venn diagram of data, microecology diversity, the relative abundance and co-occurrence of species, and the receiver operating characteristic (ROC) curve were analyzed.Results:A total of 909 species at the species level were obtained from the cervical secretions of all the subjects, and there was overlap among the groups. There was no significant difference in total HPV infection rate, 16/18 hrHPV infection rate and other hrHPV infection rates among subjects with different cervical lesions (all of P>0.05). Grouped by HPV infection, the 16/18 hrHPV-infected and other hrHPV-infected subjects had increased cervical microecology diversity ( U=39.00 and 43.00, all of P<0.05), and the relative abundance of Lactobacillus crispatus (L.crispatus) had no differences among the groups ( H=4.37, P=0.213 6). Grouped by cervical conditions, the cervical microecology diversity of the subjects with cervical lesions increased ( H=14.60, P=0.002 2), while the L.crispatus relative abundance decreased ( H=13.98, P=0.000 8). Among all the detected species, Mycoplasma, Chlamydia and Streptococcus B had a co-occurrence, while Lactobacillus iners, Gardnerella vaginalis, Atopobium vaginae, and Prevotella bivia had a co-occurrence. As the SIL diagnostic index, the area under the ROC curve (AUC) of the relative L.crispatus relative abundance was 0.874 [95% confidence interval ( CI):0.732-0.957]. L.crispatus combined with Lactobacillus jensenii (L.jensenii) and Mycoplasma had an AUC of 0.943 [95 %CI: 0.822-0.991] in the SIL diagnosis. Conclusions:The decreased L.crispatus relative abundance and the increased cervical microecology diversity may be related to HPV infection and cervical lesions; simplified NGS data may be helpful to the SIL diagnosis.
8.Inhibition of MYC suppresses programmed cell death ligand-1 expression and enhances immunotherapy in triple-negative breast cancer
Xintong LI ; Lin TANG ; Qin CHEN ; Xumin CHENG ; Yiqiu LIU ; Cenzhu WANG ; Chengjun ZHU ; Kun XU ; Fangyan GAO ; Jinyi HUANG ; Runtian WANG ; Xiaoxiang GUAN
Chinese Medical Journal 2022;135(20):2436-2445
Background::Cancer immunotherapy has emerged as a promising strategy against triple-negative breast cancer (TNBC). One of the immunosuppressive pathways involves programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), but many patients derived little benefit from PD-1/PD-L1 checkpoint blockades treatment. Prior research has shown that MYC, a master transcription amplifier highly expressed in TNBC cells, can regulate the tumor immune microenvironment and constrain the efficacy of immunotherapy. This study aims to investigate the regulatory relationship between MYC and PD-L1, and whether a cyclin-dependent kinase (CDK) inhibitor that inhibits MYC expression in combination with anti-PD-L1 antibodies can enhance the response to immunotherapy. Methods::Public databases and TNBC tissue microarrays were used to study the correlation between MYC and PD-L1. The expression of MYC and PD-L1 in TNBCs was examined by quantitative real-time polymerase chain reaction and Western blotting. A patient-derived tumor xenograft (PDTX) model was used to evaluate the influence of a CDK7 inhibitor THZ1 on PD-L1 expression. Cell proliferation and migration were detected by 5-ethynyl-2′-deoxyuridine (EdU) cell proliferation and cell migration assays. Tumor xenograft models were established for in vivo verification. Results::A high MYC expression level was associated with a poor prognosis and could alter the proportion of tumor-infiltrating immune cells (TIICs). The positive correlation between MYC and PD-L1 was confirmed by immunostaining samples from 165 TNBC patients. Suppression of MYC in TNBC caused a reduction in the levels of both PD-L1 messenger RNA and protein. In addition, antitumor immune response was enhanced in the TNBC cancer xenograft mouse model with suppression of MYC by CDK7 inhibitor THZ1. Conclusions::The combined therapy of CDK7 inhibitor THZ1 and anti-PD-L1 antibody appeared to have a synergistic effect, which might offer new insight for enhancing immunotherapy in TNBC.
9.Development of SQL-based reporting tools and its application in radiotherapy workflow quality management
Jie NI ; Juying ZHOU ; Wei ZHAN ; Jian GUO ; Long CHEN ; Guanghui GAN ; Yueliang XU ; Yiqiu LI
Chinese Journal of Radiological Health 2021;30(3):309-314
Objective To effectively use the clinical data generated in daily operation and to realize information networking based on the existing resources of radiotherapy department. To improve quality management efficiency in radiotherapy process. Methods The radiotherapy process and required documents were analyzed. The reporting tool Microsoft Report Builder, which is based on SQL database, was applied to design the patient documents by extracting and analyzing a large number of data generated by Aria, the existing network of our radiotherapy department. PDCA Tools was used to analyze the weak links in the process. Reports with quantitative indices have been designed according to corresponding countermeasures, so as to improve quality control level of the process. Results More than one thousand patients were treated in our department since 2020. All patient documents of radiotherapy can be archived and inquired online after registration only once. 13 daily statistical reports, 5 quarters and 3 annual reports were scheduled according to practical demands. The waiting time before radiotherapy was shortened from 16.2 days to 14.8 days after operating the reporting system 3 months later. The staff could master the treatment progress of patients easily and patients who interrupted the treatment were found in time. Conclusion The reporting tools can realize patient information extraction and networked management effectively in radiotherapy process. Staff efficiency of personnel work and communication was improved. The resource allocation was optimized according to the report data in real time, improving the efficiency and quality of radiotherapy. This method is generally applicable and practical to radiotherapy department.
10.Preliminary study on polymerized human cord hemoglobin increasing the chemosensitivity of subcutaneous xenografts of breast cancer in nude mice
Yiqiu GAO ; Kehui ZHU ; Yingcan XU ; Zhengxin SUO ; Hong WANG ; Jiaxin LIU
Chinese Journal of Blood Transfusion 2022;35(5):475-479
【Objective】 To investigate the effect of polymerized human cord hemoglobin (PolyCHb) on the chemosensitivity of human breast cancer MCF-7 cell subcutaneous xenografts in nude mice and its mechanism. 【Methods】 The MCF-7 cells in exponential growth phase were collected and made into suspension cells at a density of 5×107 cells/mL.Subsequently, the cells were inoculated subcutaneously in the right limb of 18 BALB/c-nu nude mice with 0.2 mL cells per mouse to establish subcutaneous xenograft.When the tumor volume reached about 100 mm3, they were randomly divided into chemotherapy group: doxorubicin 5 mg·kg-1, once/week; chemotherapy + PolyCHb group: in addition to doxorubicin (chemotherapy group), PolyCHb 600 mg·kg-1, 3 times/week; the control group: normal saline 90 mg·kg-1, once/week; all were injected through tail vein continuously for 4 weeks.From the day of injection (d 0), the tumor volume of each group of nude mice was measured every 3 days, and the tumor growth curves were drawn accordingly.After 38 days, the tumor growth observation was completed.The tumor was removed and weighed to calculate the tumor inhibition rate.HE staining, immunohistochemistry and TUNEL method were used to observe the pathological changes of tumor tissue, detect the expression of HIF-1α, and detect tumor cell apoptosis respectively.The content of reactive oxygen species (ROS) of each group was determined by fluorescence staining. 【Results】 The tumor volume (mm3) of chemotherapy + PolyCHb group, chemotherapy group and the control group at day 38 were 196.35±103.45 vs 316.29±62.88 vs 519.42±177.33 (P<0.05), and the tumor inhibition rate (%) of chemotherapy + PolyCHb treatment group and chemotherapy group was 62.20 vs 39.11, respectively.HE staining and TUNEL detection showed that cell necrosis and apoptosis in the growth area of tumor tissue increased in chemotherapy + PolyCHb group.Immunohistochemistry and fluorescence staining showed that HIF-1α expression in chemotherapy + PolyCHb group decreased and reactive oxygen species (ROS) content increased. 【Conclusion】 PolyCHb increases the chemosensitivity of subcutaneous xenograft in nude mice with breast cancer, and its mechanism may be related to the increase of ROS in tumor tissue and the promotion of tumor cell apoptosis.