1.The PGAM5-NEK7 interaction is a therapeutic target for NLRP3 inflammasome activation in colitis.
Cheng-Long GAO ; Jinqian SONG ; Haojie WANG ; Qinghong SHANG ; Xin GUAN ; Gang XU ; Jiayang WU ; Dalei WU ; Yueqin ZHENG ; Xudong WU ; Feng ZHAO ; Xindong LIU ; Lei SHI ; Tao PANG
Acta Pharmaceutica Sinica B 2025;15(1):349-370
The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.
2.The clinical value of introducing DSA angiography after extra corporeal membrane oxygenation
Yu DING ; Mengqi PI ; Lei ZHAO ; Weiyang XU ; Miao XU ; Xindong FAN
Journal of Interventional Radiology 2025;34(1):33-36
Objective To discuss the accuracy and effectiveness of digital subtraction angiography(DSA)in determining the cause of limb ischemia after extra corporeal membrane oxygenation(ECMO.Methods The clinical data of 3 child patients,who developed 4 times of acute limb ischemia during perioperative period of ECMO at the Affiliated Children's Hospital of Zhengzhou University of China from July to October of 2023,were retrospectively analyzed.In all the child patients,emergency angiography was carried out to quickly identify the cause,then,appropriate treatment plan was adopted to open the blood vessels of the right lower limb.Results After the child patients entered the operating room and received DSA examination,the causes of the limb ischemia were quickly identified.After treatment,the blood supply to the lower limbs was restored.Except for one child who experienced irreversible necrosis of the distal limb due to repeated ischemia-reperfusion injury and required amputation,the other two child patients recovered well.Conclusion It is of great significance to perform DSA examination as soon as possible when the child patients develop limb ischemic manifestations after ECMO so as to quickly identify the cause,promptly restore blood supply to ischemic limbs and increase limb preservation rate,besides,DSA examination can also be used as a preventive measure for child patients after ECMO.
3.Application of intracavitary semiconductor laser therapy in improving facial appearance for child patients with facial venous malformations after receiving sclerotherapy
Yu DING ; Mengqi PI ; Lei ZHAO ; Weiyang XU ; Miao XU ; Xindong FAN
Journal of Interventional Radiology 2025;34(7):742-745
Objective To discuss the application value of intracavitary semiconductor laser therapy in improving facial appearance for child patients with facial venous malformations(VM)after receiving sclerotherapy.Methods The clinical data of 12 child patients with facial VM after receiving sclerotherapy,for whom the improvement of their facial appearance was difficult and who were admitted to the Affiliated Children's Hospital of Zhengzhou University of China from February 2023 to February 2024,were retrospectively analyzed.Intracavitary semiconductor laser treatment was adopted in all the 12 child patients.All the child patients were followed up to check the degree of appearance improvement and lesion volume reduction,and the curative effect was evaluated.Results Three months after intracavitary semiconductor laser treatment,obvious improvement of facial appearance was obtained in all the 12 child patients.The mean postoperative PAC-QOL psychological discomfort score was(10.4±3.9)points,when compared with the preoperative(23.7±4.3)points the difference was statistically significant(P<0.05).MRI examination showed that after treatment no obvious improvement of the lesion was seen in 0 case,moderate improvement in one case,significant improvement in 4 cases,and cure in 7 cases.Conclusion Intracavitary semiconductor laser therapy has significant therapeutic effect in improving facial appearance for child patients with facial VM after receiving sclerotherapy,for whom the improvement of their facial appearance is difficult,therefore,this therapy has high clinical application value.
4. Expression and clinical significance of CK5/6, DSG3, P40, TTF-1, CK7, NapsinA in small biopsy specimens of non-small cell lung cancer
Xindong ZHANG ; Jing MA ; Xiangge WANG ; Tiantian ZHAO
Chinese Journal of Primary Medicine and Pharmacy 2020;27(2):218-221
Objective:
To detect the expression and the differential significance of CK5/6, DSG3, P40, TTF-1, CK7, NapsinA in small biopsy specimens of non-small cell lung cancer (NSCLC), squamous cell carcinoma (SCC) and adenocarcinoma (AC).
Methods:
Immunohistochemical SP method was used to detect the expressions of CK5/6, DSG3, P40, TTF-1, CK7 and NapsinA in 120 small biopsy specimens of NSCLC hospitalized in the Central People's Hospital of Tengzhou from January 2016 to December 2017, and the results were analyzed combined with the clinical characteristics of NSCLC.
Results:
The positive expression rates of CK5/6, DSG3 and P40 in lung SCC were 100.0%(56/56), 89.3%(50/56) and 96.4%(54/56), respectively, with specificity of 90.6%, 100.0% and 100.0%, respectively.The positive expression rates of NapsinA, TTF-1 and CK7 in lung AC were 81.3%(52/64), 90.6%(58/64) and 93.8%(60/64), respectively, with specificity of 100.0%, 92.9% and 96.4%, respectively.The positive expression rates of CK5/6, DSG3, P40 in SCC had statistically significant differences compared with those in AC (all
5.Relationship between gene amplification status of human epidermal growth factor receptor 2 and clinicopathological features in breast cancer
Cancer Research and Clinic 2020;32(2):103-106
Objective:To explore the relationship between gene amplification status of human epidermal growth factor receptor 2 (HER2) and its clinicopathological features in breast cancer, and to analyze the affecting factors of axillary lymph node metastasis in breast cancer.Methods:The clinicopathological data of 262 patients with breast cancer at Tengzhou Central People's Hospital between January 2016 and March 2019 were collected, including age, tumor diameter, histological grade, pathological type, lymph node metastasis, tumor number, tumor location. The patients had routine pathology examination and the immunohistochemistry (IHC) result of HER2 was ++. The expressions of p53, Ki-67, estrogen receptor (ER), progesterone receptor (PR) were detected by using IHC. The gene amplification status of HER2 was detected by using fluorescence in situ hybridization (FISH). The relationship between gene amplification status of HER2 and clinicopathological features, the relationship between axillary lymph node metastasis and clinicopathological features was respectively analyzed.Results:HER2 gene amplification-positive was detected in 69 cases of 262 breast cancer patients, and the positive amplification rate was 26.3%. The gene amplification status of HER2 was correlated with Ki-67 proliferation index and the expression of ER as well as PR, and the differences were statistically significant (χ 2=13.27, P < 0.01; χ 2= 34.97, P < 0.01; χ 2=38.31, P < 0.01). There was no correlation with age, tumor diameter and other clinicopathological features (all P > 0.05). Among 262 cases of breast cancer, 106 (40.5%) cases had axillary lymph node metastasis. Lymph node metastasis was correlated with tumor diameter (χ 2=29.10, P < 0.01), and there was no correlation with other clinicopathological features (all P > 0.05). Conclusions:HER2 gene amplification of breast cancer is associated with Ki-67 proliferation index, the expression of ER and PR. The tumor diameter is a factor for affecting axillary lymph node metastasis. Accurate judgment of the above indicators can better guide the treatment and evaluate the prognosis of breast cancer.
6.Clinical observation of decitabine combined with low-dose cytarabine in treatment of high-risk myelodysplastic syndrome
Yujiao CUI ; Xindong ZHAO ; Shaoling WU ; Chunying DUAN ; Haifeng YUAN ; Qiao SONG
Journal of Leukemia & Lymphoma 2020;29(5):279-283
Objective:To observe the clinical efficacy and safety of decitabine combined with low-dose cytarabine in treatment of high-risk myelodysplastic syndrome.Methods:The data of 47 newly treated MDS patients who had high-risk or above scores according to revised international prognostic scoring system (IPSS-R) in the Affiliated Hospital of Qingdao University from January 2016 to September 2018 were retrospectively analyzed. The patients were divided into decitabine combined with low-dose cytarabine group (15 cases) and decitabine group (32 cases). The clinical efficacy and adverse reactions in two groups were compared.Results:After 4 courses of treatment, the bone marrow remission rate, partial remission rate and hematologic remission rate was 20.0% (3/15), 6.7% (1/15), and 13.3% (2/15), respectively in decitabine combined with low-dose cytarabine group, and was 28.1% (9/32), 3.1% (1/32), and 9.4% (3/32), respectively in decitabine group, and there were no statistically differences of both groups (both P > 0.05). The overall response rate in decitabine combined with low-dose cytarabine group was higher than that in decitabine group [93.3% (14/15) vs. 62.5% (20/32), P = 0.037], and the complete remission rate in decitabine combined with low-dose cytarabine group was higher than that in decitabine group [53.3% (8/15) vs. 21.9% (7/32), P = 0.046]. The 1-year overall survival (OS) rate of decitabine combined with low-dose cytarabine group was 86%; and the median OS time of decitabine combined with low-dose cytarabine group was 24 months (95% CI 15.5-32.5 months), which was higher than that of decitabine group (20 months), but there was no statistically significant difference ( χ2 = 0.058, P = 0.810). The incidence of grade Ⅲ-Ⅳ bone marrow suppression and infection in decitabine combined with low-dose cytarabine group was higher than that in decitabine group, but there were no statistically significant differences of both groups (both P > 0.05). Grade Ⅲ-Ⅳ bone marrow suppression and infection were commonly found within the first 2 courses of treatment in decitabine combined with low-dose cytarabine group, and the adverse reactions gradually decreased in the subsequent treatment. Conclusions:Decitabine combined with low-dose cytarabine can achieve better remission rate and prolong survival time for MDS patients with high-risk and above. There is no significant increase in the incidence of grade Ⅲ-Ⅳ bone marrow suppression and infection. For high-risk MDS patients who are not suitable or unable to receive hematopoietic stem cell transplantation, it can be the preferred option.
7.Research progress of neoadjuvant intraperitoneal-systemic chemotherapy for conversion therapy of peritoneal metastasis in gastric cancer
Xindong ZHOU ; Fei LONG ; Xiaochun ZHAO ; Lang CHEN ; Jiangping DENG
Chinese Journal of Digestive Surgery 2019;18(6):607-610
In China,peritoneal metastasis of gastric cancer has main characteristics of high incidence,late staging and poor prognosis.However,the proposal of conversion therapy has brought hope to patients.Conversion therapy of peritoneal metastasis in gastric cancer is a novel concept,which aims at down-staging of the gastric cancer's primary lesion and effectively controlling the peritoneal metastases at the same time through valid chemotherapy and other means.Then the surgeons strive for performing radical gastrectomy and lymph node dissection (D2) to prolong survival time of the patients with advanced gastriccancer and improve their life quality.Systemic chemotherapy is the core of the methods of conversion therapy,while the local intraperitoneal chemotherapy can be used as a supplement.Neoadjuvant intraperitoneal-systemic chemotherapy (NIPS) is the most promising technique as conversion therapy due to the comprehensive advantages of the systemic chemotherapy and local intraperitoneal chemotherapy.In recent years,there were many clinical studies reporting NIPS for conversion therapy of peritoneal metastasis in gastric cancer.Therefore,this paper systematically reviews experiences of clinical application in order to provide references for clinical practice of conversion therapy in gastric cancer.
8. An study on the incidence of heat stroke and explore it's prediction model in Pudong New Area of Shanghai from 2013-2017
Yijing ZHAO ; Xindong HU ; Yunbiao HUANG ; Wenpeng WANG ; Minjuan YANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2018;36(4):285-287
Objective:
To know the incidence of heat stroke and explore it's prediction model in Pudong New Area of Shanghai.
Methods:
An epidemiological investigation was conducted on heat stroke cases in Pudong New Area of Shanghai from 2013 to 2017. Daily temperature data during this period were collected to explore it’s influence.
Results:
246 heat stroke cases were reported and investigated, 70.3% (173/246) of them were male. 170 cases are severe heat stroke, accounting for 69.1%. 28 patients died, accounting for 11.4% of all cases of heat stroke, and 16.5% (28/170) of severe heat stroke cases. Thermoplegia (56.5%, 96/170) was the most popular type among severe heat stroke cases. Heat prostration, heat cramps and mixed type account for 17.1% (29/170) , 12.4% (21/170) and 14.0% (24/170) respectively. Scatter plot and linear regression demonstrated that there was a significant linear relation between number of high temperature days and number of heat stroke cases (
9.Regulatory effect of vitamin D on the expression of occludin in the intestinal epithelial cells of neonatal ;rats with necrotizing enterocolitis
Yongyan SHI ; Jianhua FU ; Li YAO ; Xinyi ZHAO ; Xindong XUE
Chinese Pediatric Emergency Medicine 2017;24(1):60-64
Objective To investigate the expression of occludin in the intestinal epithelial cells of neonatal rats with necrotizing enterocolitis ( NEC) . The influence of vitamin D on NEC and the expression of occludin was also explored. Methods Sixty neonatal Wistar rats from different litters were divided into four groups 48 hours after birth:10 in the breast-fed+ control group,10 in the breast-fed +vitamin D group,20 in the NEC+ control group and 20 in the NEC+ vitamin D group. In groups with NEC,neonatal rats were sep-arated from their mothers and treated with rat milk substitute+hypoxia+hypothermia. In groups with vitamin D treatment,paricalcitol was given through intraperitoneal injection 30 minutes before,one day and two days after the induction of NEC. The tissue was harvested from the ileum of the rats 72 hours after induction of NEC. Microscopically,the tissue was assessed according to the Nadler scoring system. The expression and location of occludin was observed after immunofluorescence staining. Western blotting was performed and quantified to compare the expression of occludin among groups. Results In NEC rats,the intestinal structure was destructed. Separation of the submucosal or muscular layer,discharge or disappearance of the villa was accompanied by necrosis of the intestinal cells. Vitamin D treatment could significantly alleviate those chan-ges,with the Nadler score 1. 70 ± 0. 21 compared to 2. 90 ± 0. 23 without vitamin D treatment ( P<0. 01 ) . The expression of occludin was decreased in NEC rats and vitamin D could partly rescue this decrease (P<0. 01). The distribution of occludin was sparse and discontinuous in NEC rats while after vitamin D treatment,the distribution was maintained even and continuous. Conclusion The expression of occludin in intestinal epithelial cells is significantly reduced in NEC rat. Vitamin D treatment may inhibit the development of NEC by maintaining the expression of occludin.
10.Comparison of single-bundle and double-bundle autografts in anterior cruciate ligament reconstruction
Jie TAN ; Xiaobing FENG ; Jianhua QU ; Changjie WU ; Xindong ZHAO ; Yingxiang LI ; Bangkai YAN
Chinese Journal of Tissue Engineering Research 2014;(42):6817-6821
BACKGROUND:Different weaving methods of autologous tendon lead to various treatment efficacies on cruciate ligament rupture, but the preferred method is stil controversial.
OBJECTIVE:To comparatively analyze the clinical efficacy of single-bundle and double-bundle autografts on anterior cruciate ligament reconstruction.
METHODS:A retrospective analysis of 48 cases of anterior cruciate ligament rupture was performed. According to the composition of graft beam, these 48 patients were divided into two groups:double-bundle group (n=24) and single-bundle group (n=24). Al surgical patients underwent autologous anterior cruciate ligament reconstruction by arthroscopy, and were fol owed up for at least 6 months. The function of knee joint after operation was comprehensively analyzed through IKDC and Lysholm scores.
RESULTS AND CONCLUSION:Al of the patients (n=48) exhibited no joint complications postoperatively, such as intra-articular infection, joint effusion and incision inflammation. The IKDC scores and Lysholm scores in the double-bundle group were better than those in the single-bundle group, but there was no statistical y significant difference (P>0.05). This study demonstrated that single-bundle and double-bundle autografts both have good curative effects on anterior cruciate ligament reconstruction by arthroscopy. But in contrast, the curative effects of double-bundle autografts are better.

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