1.Effects of resveratrol on cGAS-STING signaling pathway in fibroblast-like synoviocytes of patients with rheumatoid arthritis
Taorong Wang ; Yubao Shao ; Nannan Liu ; Wenhao Li ; Meng Li ; Xiaoyu Chen
Acta Universitatis Medicinalis Anhui 2025;60(1):73-78
Objective :
To investigate the effects of resveratrol(Res) on fibroblast-like synoviocytes(FLS) in patients with rheumatoid arthritis(RA), and to explore the possible mechanism of Res inhibiting the release of inflammatory factors from FLS.
Methods :
FLS from RA patients were culturedin vitroand treated with different concentrations of Res(0, 20, 40, 80, 160, 320 μmol/L). The viability of FLS cells was detected by CCK-8 assay after 12 and 24 h. The contents of inflammatory factor interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in cell supernatant were detected by ELISA. The expression levels of cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS) and stimulator of interferon gene(STING) were measured by Western blot; After lentivirus infection with FLS caused the cells to overexpress cGAS, the cells were divided into Control group(blank control), cGAS group(cGAS overexpression), Res+cGAS group(Res 160 μmol/L+cGAS overexpression) and Res group(Res 160 μmol/L). The expression level of STING protein in cells of each group was determined by Western blot, the viability of FLS cells in each group was detected by CCK-8, and the contents of inflammatory factor IL-6 and TNF-α in the supernatant of cells of each group were detected by ELISA method.
Results :
The results of CCK-8 experiment showed that under 40, 80, 160 μmol/L Res treatment, FLS viability decreased significantly after 24 h compared with blank control group(P<0.01). ELISA results showed that the contents of IL-6 and TNF-α in cell supernatant were also significantly decreased after treatment with Res of 40, 80 and 160 μmol/L(P<0.01). Meanwhile, Western blot results showed that Res could significantly decrease the protein expression levels of STING and cGAS in FLS cells after treatment of 40, 80 and 160 μmol/L(P<0.05,P<0.01). Compared with the Control group, the expression level of STING protein in FLS increased after overexpression of cGAS(P<0.05); compared with the Res group, the content of inflammatory factors in the supernatant of FLS and the expression level of STING protein in FLS significantly increased after overexpression of cGAS(P<0.01,P<0.05).
Conclusion
The appropriate concentration of Res can inhibit the release of inflammatory cytokines in FLS cells, which may be related to the blocking of cGAS-STING signaling pathway.
2.Exploratory Study on the Theory of the Spatiotemporal Structure of Visceral Manifestation
Houfang MA ; Xiaoying XU ; Linghao MENG ; Haili ZHANG ; Nannan SHI
Journal of Traditional Chinese Medicine 2025;66(16):1629-1634
The "integrated time-space" perspective of life in traditional Chinese medicine holds that structure and function respectively belong to the realms of space and time. The orderly integration of time and space not only supports the existence and development of life, but also serves as the foundation for biological evolution. Based on this standpoint, this paper proposes the spatiotemporal structural theory of visceral manifestation, characterized by the fusion of time and space, the integration of internal and external dimensions, and the absence of primary or secondary distinctions. Using the individual human body as the boundary, it delineates the man and nature spatiotemporal structure, based on the theory of the "correspondence between man and nature", and the internal spatiotemporal structure of the living body. The man and nature spatiotemporal structure, with yin-yang and the five phases as its core, reveals the correspondence and connectivity between the external environment and the internal zang-fu organs within the spatiotemporal dimension. The internal temporal structure of the body refers to the collective physiological rhythms related to the zang-fu organs, while the spatial structure refers to the tangible forms, spatial positions, and connective structures of the zang-fu organs. The proposal of the spatiotemporal structural theory of visceral manifestation represents a rational reconstruction and practical exploration of the essential connotations of visceral manifestation, aiming to provide new perspectives for subsequent theoretical research and clinical applications.
3.Association between self-rated health status and mortality riskamong the elderly
ZHANG Meng ; ZHANG Li ; LIU Mengya ; SONG Nannan ; ZHOU Jinglei
Journal of Preventive Medicine 2024;36(2):105-108,114
Objective:
To investigate the association between self-rated health status and mortality risk, and to evaluate the predictive value of self-rated health status for mortality risk among the elderly.
Methods:
Based on the China Health and Retirement Longitudinal Study (CHARLS) database, data of sociodemographic information, self-rated health status and mortality of the elderly aged 60 years and older were collected from 2011 to 2018. The association between self-rated health status and mortality risk among the elderly was analyzed using a multivariable Cox proportional risk regression model.
Results:
Totally 4 850 individuals were included, with an median age of 65 (interquartile range, 8) years. There were 2 485 males (51.24%) and 2 365 females (48.76%). There were 877 individuals (18.08%) rated their health as good, 2 078 individuals (42.85%) as general, 1 895 individuals (39.07%) as poor. A total of 28 955 person-years were followed up, with an average follow-up of 5.97 years per person. There were 855 deaths by the end of follow-up in 2018, and the median survival time was 7 (interquartile range, 3) years. Multivariable Cox proportional risk regression analysis showed that there were interactive effects of age, sex and self-rated health status on mortality, respectively (both P<0.05). The results of gender-stratified analysis showed that there was no significant association between self-rated health status and mortality risk in old women (P>0.05). The mortality risk was higher in old men with poor self-rated health than with good self-rated health (<70 years, HR=5.382, 95%CI: 3.263-8.876; 70 to 79 years, HR=3.536, 95%CI: 1.070-11.686; ≥80 years, HR=3.043, 95%CI: 1.827-5.066).
Conclusion
There is an association between self-rated health status and mortality risk among the elderly, the old men with poor self-rated health had a higher mortality risk.
4.Evaluation of apparent diffusion coefficient histogram parameters based on multiplexed sensitivity encoding diffusion weighted imaging in lymph node metastasis of cervical cancer
Nannan BAI ; Tong YE ; Tiebao MENG ; Weijing ZHANG ; Haoqiang HE ; Chuanmiao XIE
Journal of Practical Radiology 2024;40(9):1476-1479
Objective To investigate the application value of apparent diffusion coefficient(ADC)histogram parameters of multi-plexed sensitivity encoding diffusion weighted imaging(MUSE-DWI)in evaluating lymph node metastasis of cervical cancer(CC).Methods A total of 54 patients with CC diagnosed pathologically after extensive hysterectomy and pelvic lymph node dissection were analyzed retrospectively,and 74 lymph nodes were extracted,including 28 metastatic lymph nodes and 46 non-metastatic lymph nodes.All patients underwent routine MRI examination and MUSE-DWI before surgery.Through the T2WI fat suppression images were referenced,the region of interest(ROI)covering the entire lymph nodes were drawn on the b=800 s/mm2 images of MUSE-DWI,and ADC histogram parameters were obtained including minimum,maximum,mean,median,percentiles(10 th,25 th,75 th,90 th),kurtosis,and skewness.The differences of ADC histogram parameters between the metastatic lymph nodes and the non-metastatic lymph nodes were compared.The receiver operating characteristic(ROC)curves were drawn and the area under the curve(AUC)were calculated to evaluate the diagnostic efficacy of different parameters in distinguishing lymph node metastasis.Results The mean,median,25 th and 75 th percentiles of ADC histogram of the metastatic lymph nodes were significantly lower than those of the non-metastatic lymph nodes(P<0.05).However,there were no statistically significant differences in minimum,maximum,10 th percentile,90 th percentile,kurtosis,and skewness(P>0.05).In the evaluation of various parameters for distinguishing lymph node metastasis,the mean had the highest diagnostic efficacy(AUC=0.718),and when the threshold was 963.07×10-6 mm2/s,the sensitivity and specificity were 0.643 and 0.717,respectively.Conclusion The ADC histogram parameters based on MUSE-DWI have high diag-nostic value in differentiating CC lymph node metastasis,and the mean has the highest diagnostic efficiency.
5.Detection and analysis of allergens in children with allergic diseases in Yangzhou area
Di LIU ; Tingting XU ; Shunying LIU ; Xiaojuan LI ; Nannan MENG ; Jing LI ; Haikang ZHOU ; Wenping WEI
Journal of Clinical Medicine in Practice 2024;28(21):28-32
Objective To analyze the distribution characteristics and clinical significance of allergens in children with allergic diseases in Yangzhou area. Methods A total of 1, 025 children who were treated in the Affiliated Hospital of Yangzhou University from December 2022 to December 2023 and tested for allergens were selected as study objects. The detection results of allergens were collected and the distribution characteristics of allergens were analyzed. Results Among the 1, 025 children with allergy-related diseases, 83.41% (855 cases) tested positive for allergens, with a positive rate of 66.24% (679 cases) for inhalant allergens and 61.17% (627 cases) for food allergens. The most common allergens were milk (36.20%), molds (33.27%), and house dust mites (30.34%). There was no statistically significant difference in the positive rate of allergens among different age groups (
6.Correlation between intrinsic capacity and activities of daily living for old adults in China: based on China Health and Retirement Longitudinal Study
Mengya LIU ; Li ZHANG ; Meng ZHANG ; Nannan SONG ; Jinglei ZHOU
Chinese Journal of Rehabilitation Theory and Practice 2023;29(10):1140-1146
ObjectiveTo explore the weights and comprehensive indices of each field of intrinsic capacity of old adults, and the correlation between intrinsic capacity and activities of daily living (ADL). MethodsThe data of 5 506 cases aged more than 60 years in the 2015 China Health and Retirement Longitudinal Study (CHARLS) were used to collect the assessment of intrinsic capacity and the measurement of ADL. The assessment of intrinsic capacity included cognition, motor, vitality, sensory and psychology; while the ADL scale included six indicators, namely dressing, bathing, eating, getting in or out of bed, going to the toilet, and controlling urine and feces. ResultsA total of 1 343 cases were limited in ADL (24.4%). Women, lower education level, older age, the widowed, greater number of chronic diseases, and poorer self-rated health were the factors more likely to be limited in ADL. Principal component analysis showed that the largest weight value was in psychological domain, followed by the cognitive domain, and the lowest weight value was in the motor domain. After controlling for the effects of age, gender, living environment, economic income, education level, marriage, smoking and drinking, number of chronic diseases, and self-rated health, the Logistic regression analysis showed that low exercise capacity (OR = 0.581, 95%CI 0.501 to 0.674), depression (OR = 0.426, 95%CI 0.368 to 0.493), audile and visual impairment (OR = 0.813, 95%CI 0.699 to 0.947; OR = 0.684, 95%CI 0.578 to 0.809), overweight (OR = 1.203, 95%CI 1.014 to 1.428) and obesity (OR = 1.584, 95%CI 1.312 to 1.912) were independent risk factors for ADL limitation in older adults. ConclusionDecrease of intrinsic capacity is a predictor for ADL limitation in older adults.
7.The 500th case: pain in both hip joints, headache, and diplopia
Nannan ZHANG ; Yanlong DUAN ; Hui WANG ; Ningning ZHANG ; Jing YANG ; Meng ZHANG ; Nan LI ; Shuang HUANG ; Nan ZHANG ; Ling JIN
Chinese Journal of Internal Medicine 2023;62(2):232-236
A male child, aged 5 years and 3 months, was admitted to the Oncology Department with a history of pain in both hip joints, headache, and diplopia lasting for 40 days. Physical examination did not reveal definitive signs or obvious abnormalities in the nervous system. Imaging studies showed only abnormalities in the craniocerebrum and spinal cord. Routine cerebrospinal fluid (CSF) analysis revealed elevation in the total number of white blood cells, mainly mononuclear cells. Biochemical analysis of CSF showed normal glucose and chloride levels, and increased protein concentrations. The possibility of central nervous system (CNS) infection was initially considered. Subsequently, antibacterial and antiviral therapy was administered; however, this treatment was ineffective. Further examination of CSF through immunophenotyping revealed mature B-cell lymphoma with CNS involvement; there were no neoplastic lesions detected elsewhere in the body. Thus, the patient was diagnosed with primary central nervous system lymphoma (PCNSL). Complete remission was achieved after chemotherapy with the CNCL-2017-mature B-cell lymphoma regimen. Thus far, all chemotherapy cycles have been completed, the patient remains in complete remission, and the follow-up is ongoing. Clinicians should pay close attention to PCNSL in children.
8.Evidence-based guidelines for food allergy of children in China
Wei ZHOU ; Jing ZHAO ; Huilian CHE ; Jianguo HONG ; Li HONG ; Hong LI ; Zailing LI ; Juan MENG ; Li SHA ; Jie SHAO ; Kunling SHEN ; Lianglu WANG ; Li XIANG ; Huan XING ; Sainan BIAN ; Nannan JIANG ; Hong JING ; Ling LIU ; Pengxiang ZHOU ; Weiwei ZHU
Chinese Journal of Applied Clinical Pediatrics 2022;37(8):572-583
The diagnosis of food allergy in children is one hotspot attracting people′s attention in recent years.The incidence of it shows an increasing trend which exposes problems in the understanding of children′s food allergy in China, especially in the misdiagnosis and missed diagnosis.To further standardize the diagnosis and treatment of food allergy in children, based on the current domestic, foreign guidelines and relevant research evidence, the guideline recommends 16 clinical hot-button issues in the 4 aspects of diagnosis, treatment, prognosis, and prevention.Finally, a diagnosis flowchart has been formulated.The guideline aims to improve the standard diagnosis and treatment of food allergies in children in China.
9.Role of epidermal growth factor in repair of lung tissues in mice with acute respiratory distress syndrome
Yongqian JIAO ; Chen MENG ; Wen ZENG ; Yiming WANG ; Silu WANG ; Xue WANG ; Nannan ZOU ; Xianyu WANG
Chinese Journal of Anesthesiology 2022;42(3):347-353
Objective:To evaluate the role of epidermal growth factor (EGF) in repair of lung tissues in mice with acute respiratory distress syndrome (ARDS).Methods:Fifty SPF male C57BL/6 mice, aged 6-8 weeks, weighing 21-23 g, were divided into 5 groups ( n=10 each) using a random number table method: control group (group C), EGF group, LPS+ PBS group, LPS+ EGF group and AG1478+ LPS+ EGF group.PBS 0.1 ml was intraperitoneally injected in group C. EGF 10 μg (0.1 ml) was intraperitoneally injected in group EGF.The equal volume of PBS and EGF 10 μg was intraperitoneally injected at 12 h after tracheal infusion of LPS in group LPS+ PBS and group LPS+ EGF, respectively.EGF receptor (EGFR) antagonist AG1478 1 mg was intraperitoneally injected, 30 min later LPS was tracheally instilled, and 12 h later EGF 10 μg was intraperitoneally injected in group AG1478+ LPS+ EGF.ARDS model was developed by endotracheal instillation of LPS 3 mg/kg.The mice were sacrificed on the 1st and 5th days after development of the model, and lung tissues were obtained for microscopic examination of the pathological changes which were scored after HE staining.Bronchoalveolar lavage was performed on 5th day after development of the model and before sacrifice, and bronchoalveolar lavage fluid (BALF) was collected to detect total protein concentration (by BCA method) and IL-6 and TNF-α concentrations (by enzyme-linked immunosorbent assay). Lung tissues were obtained for determination of the wet/dry lung weight ratio (W/D ratio), expression of lung surfactant associated protein C (SP-C) and proliferating nuclear antigen (PCNA) (by immunofluorescence method), and expression of EGFR, phosphorylated EGFR (p-EGFR), protein kinase B (Akt), and phosphorylated Akt (p-Akt) (by Western blot). Results:Compared with group C, the pathological score, W/D ratio, concentrations of total protein, IL-6 and TNF-α in BALF and neutrophil count were significantly increased, the number of cells co-expressing SP-C and PCNA was increased, and p-EGFR/EGFR and p-Akt/Akt ratios were increased in group LPS+ PBS ( P<0.01), and no significant change was found in the indexes mentioned above in group EGF ( P>0.05). Compared with group LPS+ PBS, the pathological score, W/D ratio, concentrations of total protein, IL-6 and TNF-α in BALF and neutrophil count were significantly decreased, the number of cells co-expressing SP-C and PCNA was increased, and p-EGFR/EGFR and p-Akt/Akt ratios were increased in group LPS+ EGF ( P<0.01). Compared with group LPS+ EGF, the pathological score, W/D ratio, concentrations of total protein, IL-6 and TNF-α in BALF and neutrophil count were significantly increased, the number of cells co-expressing SP-C and PCNA was decreased, and p-EGFR/EGFR and p-Akt/Akt ratios were decreased in group AG1478+ LPS+ EGF ( P<0.01). Conclusions:EGF can promote the repair of lung tissues in mice with ARDS, and the mechanism may be related to activation of EGFR signaling pathway and promotion of proliferation of alveolar epithelial cell type Ⅱ.
10.Efficacy of low-dose uric acid oxidase in the treatment of 106 pediatric patients with aggressive mature B-cell non-Hodgkin lymphoma and hyperuricemia
Meng ZHANG ; Yanlong DUAN ; Ling JIN ; Jing YANG ; Shuang HUANG ; Xiaolu NIE ; Nan LI ; Nan ZHANG ; Nannan ZHANG ; Yonghong ZHANG
Chinese Journal of Applied Clinical Pediatrics 2022;37(18):1377-1381
Objective:To investigate the efficacy of low-dose uric acid oxidase in treating children with aggressive mature B-cell non-Hodgkin lymphoma accompanied by hyperuricemia.Methods:Clinical data of children with primary aggressive mature B-cell non-Hodgkin lymphoma and hyperuricemia, who were treated in Beijing Children′s Hospital, Capital Medical University from January 2016 to June 2021 were retrospectively analyzed.The serum uric acid concentration was monitored in all pediatric patients from the day before chemotherapy to the seventh day of chemotherapy.Low-dose uric acid oxidase [0.05-0.10 mg/(kg·dose)] was intravenously injected into the patients when the serum uric acid level exceeded the upper limit of the normal range.The therapeutic effect and clinical medication experience of uric acid oxidase were summarized.The change of serum uric acid levels with time before and after the application of different doses of uric acid oxidase was analyzed by a repeated measures ANOVA. Results:A total of 106 children with primary aggressive mature B-cell non-Hodgkin lymphoma and hyperuricemia were enrolled in this study.There were 88 males and 18 females, with a median age of 6.5 (3.5, 10.0) years.The pathological subtypes comprised Burkitt′s lymphoma in 95 cases (89.6%), high-grade B-cell lymphoma in 7 cases (6.6%), and diffuse large B-cell lymphoma in 4 cases (3.8%). Additionally, 39 cases (36.8%) were in clinical stage Ⅲ and 67 cases (63.2%) were in stage Ⅳ.All cases had high tumor burden, including renal involvement in 52 cases (49.1%), tumor lysis syndrome in 42 cases (39.6%), and acute kidney injury in 27 cases (25.5%). Totally, one dose of uric acid oxidase was intravenously injected into 41 children (38.7%), 41 children (38.7%) were given 2 dosages, 20 children (18.9%) were given 3 dosages, and 4 children (3.8%) received 4 dosages.Moreover, 9 cases (8.5%) were supplemented with continuous renal replacement therapy.Serum uric acid concentrations before chemotherapy and 12 hours after injecting the first dose of uric acid oxidase were (741.4±312.9) μmol/L and (210.8±148.6) μmol/L, respectively.The difference was statistically significant ( t=5.288, P<0.001). The change of serum uric acid levels over time before and after the application of different doses of uric acid oxidase in children was compared, and no significant difference was found ( F=0.225, P=0.879). No delay in chemotherapy or death arising from tumor lysis syndrome and acute kidney injury occurred within 28 days after chemotherapy. Conclusions:Low-dose and on-demand application of uric acid oxidase can rapidly and effectively reduce serum uric acid levels in children with aggressive mature B-cell non-Hodgkin lymphoma in the early stage of chemotherapy.


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