1.Evidence that metformin promotes fibrosis resolution via activating alveolar epithelial stem cells and FGFR2b signaling.
Yuqing LV ; Yanxia ZHANG ; Xueli GUO ; Baiqi HE ; Haibo XU ; Ming XU ; Lihui ZOU ; Handeng LYU ; Jin WU ; Pingping ZENG ; Saverio BELLUSCI ; Xuru JIN ; Chengshui CHEN ; Young-Chang CHO ; Xiaokun LI ; Jin-San ZHANG
Acta Pharmaceutica Sinica B 2025;15(9):4711-4729
Idiopathic pulmonary fibrosis (IPF) is a progressive disease lacking effective therapy. Metformin, an antidiabetic medication, has shown promising therapeutic properties in preclinical fibrosis models; however, its precise cellular targets and associated mechanisms in fibrosis resolution remain incompletely defined. Most research on metformin's effects has focused on mesenchymal and inflammatory responses with limited attention to epithelial cells. In this study, we utilized Sftpc lineage-traced and Fgfr2b conditional knockout mice, along with BMP2/PPARγ and AMPK inhibitors, to explore metformin's impact on alveolar epithelial cells in a bleomycin-induced pulmonary fibrosis model and cell culture. We found that metformin increased the proliferation and differentiation of alveolar type 2 (AT2) cells, particularly the recently identified injury-activated alveolar progenitors (IAAPs)-a subpopulation characterized by low SFTPC expression but enriched for PD-L1. Single-cell RNA sequencing revealed a reduction in apoptosis among mature AT2 cells. Interestingly, metformin's therapeutic effects were not significantly affected by BMP2 or PPARγ inhibition, which blocked the lipogenic differentiation of myofibroblasts. However, Fgfr2b deletion in Sftpc lineage cells significantly impaired metformin's ability to promote fibrosis resolution, a process linked to AMPK signaling. In conclusion, metformin alleviates fibrosis by directly activating AT2 cells, especially the IAAPs, through a mechanism that involves AMPK and FGFR2b signaling, but is largely independent of BMP2/PPARγ pathways.
2.Proficiency testing for 11 clinical biobanks in Beijing City: simulation study and result analysis
Qian ZHANG ; Yun ZHANG ; Lu HAN ; Min LIU ; Yongbo YU ; Yan WANG ; Ying HU ; Hui ZHONG ; Dan GUO ; Shipeng SUN ; Jinxi LIN ; Siyuan XU ; Xiaokun TANG ; Gaoyuan SUN ; Chuanbao ZHANG ; Hexin LI
Chinese Journal of Preventive Medicine 2025;59(9):1590-1596
Objective:To evaluate the sample preparation proficiency and storage proficiency of 11 clinical biobanks in Beijing through simulated experiments, and to establish an assessment method for the quality comparability of biological samples.Methods:An exploratory research design was adopted. In November 2023, artificial composite serum quality control materials containing six recombinant human protein markers—recombinant human alanine aminotransferase (rhALT), recombinant human aspartate aminotransferase (rhAST), recombinant human creatine kinase (rhCK), recombinant human creatine kinase-MB (rhCK-MB), recombinant human B-type natriuretic peptide (rhBNP), and recombinant human troponin I (rhTNI)—were distributed to 11 clinical biobanks in Beijing City. Sample preparation and storage followed the standardized operating procedures. Proficiency differences were assessed through statistical analysis.Results:Three-way repeated measures ANOVA revealed all six protein markers showed a declining trend over storage time in ultra-low-temperature environments ( F values 11.68-4 179.66, all P<0.01). However, neither long-term/temporary refrigerator types ( F values 0.01-1.23, all P>0.05)nor placement locations within refrigerators significantly affected the stability of these six proteins ( F valus 0.03-1.47, all P>0.05). The biases in detection results for rhALT, rhAST, rhTNI, and rhBNP at different storage time points were within the allowable bias limits for each item, supporting their use as markers for protein stability in biobank samples. All 11 institutions passed the storage proficiency assessment. In the preparation proficiency assessment, deviations were observed in post-preparation sample results, with a notably high out-of-control rate for rhCK (36.36%). Conclusion:Sample preparation proficiency can serve as a quality control metric for clinical biobanks. Future external quality assessment systems for biobanks should focus on sample preparation rather than storage processes.
3.Proficiency testing for 11 clinical biobanks in Beijing City: simulation study and result analysis
Qian ZHANG ; Yun ZHANG ; Lu HAN ; Min LIU ; Yongbo YU ; Yan WANG ; Ying HU ; Hui ZHONG ; Dan GUO ; Shipeng SUN ; Jinxi LIN ; Siyuan XU ; Xiaokun TANG ; Gaoyuan SUN ; Chuanbao ZHANG ; Hexin LI
Chinese Journal of Preventive Medicine 2025;59(9):1590-1596
Objective:To evaluate the sample preparation proficiency and storage proficiency of 11 clinical biobanks in Beijing through simulated experiments, and to establish an assessment method for the quality comparability of biological samples.Methods:An exploratory research design was adopted. In November 2023, artificial composite serum quality control materials containing six recombinant human protein markers—recombinant human alanine aminotransferase (rhALT), recombinant human aspartate aminotransferase (rhAST), recombinant human creatine kinase (rhCK), recombinant human creatine kinase-MB (rhCK-MB), recombinant human B-type natriuretic peptide (rhBNP), and recombinant human troponin I (rhTNI)—were distributed to 11 clinical biobanks in Beijing City. Sample preparation and storage followed the standardized operating procedures. Proficiency differences were assessed through statistical analysis.Results:Three-way repeated measures ANOVA revealed all six protein markers showed a declining trend over storage time in ultra-low-temperature environments ( F values 11.68-4 179.66, all P<0.01). However, neither long-term/temporary refrigerator types ( F values 0.01-1.23, all P>0.05)nor placement locations within refrigerators significantly affected the stability of these six proteins ( F valus 0.03-1.47, all P>0.05). The biases in detection results for rhALT, rhAST, rhTNI, and rhBNP at different storage time points were within the allowable bias limits for each item, supporting their use as markers for protein stability in biobank samples. All 11 institutions passed the storage proficiency assessment. In the preparation proficiency assessment, deviations were observed in post-preparation sample results, with a notably high out-of-control rate for rhCK (36.36%). Conclusion:Sample preparation proficiency can serve as a quality control metric for clinical biobanks. Future external quality assessment systems for biobanks should focus on sample preparation rather than storage processes.
4.Effect of "medical clown" assisted anesthesia intervention in pediatric surgery
Guili ZHANG ; Hongli GUO ; Xiaokun TAO ; Yalei LI
Chinese Journal of Modern Nursing 2021;27(29):4024-4028
Objective:To explore the effect of "medical clown" assisted anesthesia intervention in pediatric surgery.Methods:From May 2018 to May 2020, a total of 1 200 surgical children admitted to the First Affiliated Hospital of Zhengzhou University were selected as the research object. The children were divided into a control group and an observation group with the random number table method, each with 600 cases. The control group completed anesthesia intervention according to the conventional method, and the observation group was given "medical clown" assisted anesthesia intervention. The mean arterial pressure (MAP) , heart rate (HR) , and the modified Face, Legs, Activity, Crying, Consolability (FLACC) score of the two groups of children at different time points were compared. At the same time, the anesthesia Induction Compliance Checklist (ICC) score, and the modified Yale Preoperative Anxiety Scale-Short Form (mYPAS) score of the two groups of children and the satisfaction of the family members with the operation when the child came to the hospital for review one month later were recorded.Results:The MAP, HR, and FLACC scores of the two groups were compared at different time points, and the differences were statistically significant ( P<0.05) . After the intervention, the ICC and mYPAS scores of the observation group were lower than those of the control group, and the satisfaction of the family members of the children was higher than that of the control group, and the differences were statistically significant ( P<0.05) . Conclusions:The application of "medical clown" assisted anesthesia intervention in pediatric surgery can stabilize the basic indicators of children, reduce anxiety, and have a high degree of cooperation in anesthesia.
5.A case report of mucinous tubular and spindle cell carcinoma of the kidney
Xuezhou ZHANG ; Yonghua WANG ; Junxiang LIU ; Zhihan GUO ; Xiaokun YANG ; Ke WANG ; Haitao NIU
Chinese Journal of Urology 2021;42(8):633-634
Mucinous tubular and spindle cell carcinoma of the kidney is a rare subtype of renal carcinoma. In July 2019, one case of mucinous tubular and spindle cell carcinoma of the kidney was admitted to our hospital, The laparoscopic partial nephrectomy was performed, and there was no recurrence or metastasis during the follow-up period of 13 months. The disease has no obvious clinical manifestations and its diagnosis depends on pathological and immunohistochemical features. Surgical treatment is the main treatment for this disease, and most patients have a good prognosis.Howerer, the possibility of progression remains in the late stage of the disease.
6.Effects of lipopolysaccharide-induced toll-like receptor 4 on endoplasmic reticulum stress in atherosclerotic plaques of polipoprotein E gene knockout mice
Xiaokun GUO ; Xiaoshuang XIA ; Peilu WANG ; Lin WANG ; Xin LI
Chinese Journal of Geriatrics 2020;39(6):695-699
Objective:To investigate the effects of endoplasmic reticulum(ER)stress on the stability of atherosclerotic plaques in mice by examining the action of lipopolysaccharide(LPS)-induced Toll-like receptor 4(TLR4)on the protein expression levels in the ER stress pathway in atherosclerotic plaques of polipoprotein E gene knockout (ApoE -/-) mice. Methods:From October 2015 to February 2016, 24 ApoE -/-mice were randomly divided into the control group, the LPS group and the TAK group after 10 weeks of high-fat feeding(n=8, each group). After 10 weeks of intervention, peripheral blood was extracted by removing the eyeballs for the measurement of total cholesterol(TC), triglycerides(TG)and oxidized low density lipoprotein(ox-LDL). Then mice were sacrificed to obtain carotid and aortic specimens.Immunohistochemistry was used to detect the expression of carotid plaque macrophages(MOMA-2), smooth muscle actin(α-actin), TLR4, interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor-α(TNFα)and nuclear factor-κ-gene binding(NFκB). Western blotting was used to determine the expression of PKR-like eukaryotic initiation factor 2αkinase(PERK), C/EBP-homologous protein(CHOP)and glucose-regulated protein 78(GRP78). Results:The levels of TC, TG and ox-LDL were elevated in the LPS group, compared with the control and TAK groups[(25.0±2.3) mmol/L vs. (20.2±1.6) mmol/L and (20.8±2.6) mmol/L, (1.3±0.1) mmol/L vs.(1.3±0.1) mmol/L and (1.0±0.1) mmol/L, (17.4±1.3) mmol/L vs.(15.8±1.6) mmol/L and (12.1±1.1) mmol/L, P<0.05]. The comparison of plaque morphology and pathology showed that the LPS group had a wider range of atherosclerotic plaques, more macrophages and fewer vascular smooth muscle cells than the control and TAK groups( P<0.05). The expression of TLR4, IL-1β, IL-6, TNFα, NFκB, PERK, CHOP and GRP78 was higher in the LPS group than in the control and TAK groups( P<0.05). Compared with the control group, the expression of PERK, CHOP and GRP78 was lower in the TAK group( P<0.05). The expression of TLR4, PERK, CHOP and GRP78 was higher in the LPS group. Conclusions:LPS-induced TLR4 can up-regulate the expression of proteins in the ER stress pathway, increase the secretion of inflammatory cytokines downstream of the ER stress pathway, aggravate lipid metabolism disorders and increase the instability of atherosclerotic plaques.
7. The effect of rock salt aerosol on the prevention of silicosis in rats
Shuang WANG ; Xiaokun ZHAO ; Jiali ZHU ; Qiumin XU ; Xinying LI ; Jinsong ZHANG ; Xiaohui HAO ; Lingli GUO ; Heliang LIU
China Occupational Medicine 2020;47(02):147-153
OBJECTIVE: To investigate the preventive effect of rock salt aerosol on the development of silicosis in rats. METHODS: The specific pathogen free adult male SD rats were randomly divided into normal control group, rock salt control group, silicosis model group and rock salt intervention group, 18 rats in each group. Rats in the silicosis model group and the salt rock intervention group were treated with silica dust at the concentration of 2 000.0 mg/m~3 by dynamic dusting method for 3 hours daily. Rats in the rock salt control group and the rock salt intervention group inhaled the rock salt aerosols with the mass concentration of 20.0 mg/m~3 for 30 minutes daily. The normal control group was not treated with the dust or rock salt aerosol. At the time points of 14, 28 and 56 days after exposure to dust or rock salt aerosol, 6 rats were randomly selected from each group and samples were collected. The pathological change of lung was observed, the total cell count in the bronchoalveolar lavage fluid(BALF) was performed, the enzyme-linked immunosorbent assay was used to detect the change of transforming growth factor-β(TGF-β) in BALF, surfactant D(SP-D) and superoxide dismutase(SOD) in lung tissue. RESULTS: The results of hematoxylin-eosin and Masson staining showed that the inflammatory changes of lung tissue and the pulmonary interstitial fibrosis in the rock salt intervention group were less severer than that in the silicosis model group. At 14, 28, and 56 days after dust exposure, the total cell counts in BALF and SP-D levels in lung tissue of rats in silicosis model group and rock salt intervention group were higher(P<0.05), the SOD activities in lung tissue were lower(P<0.05), as well as the TGF-β levels in BALF in silicosis model group were higher(P<0.05),compared with the normal control group and rock salt control group. The total cell counts and TGF-β levels in BALF, and SP-D levels in lung tissue of rock salt intervention group were lower(P<0.05), the SOD activities in lung tissue were higher(P<0.05), compared with the silicosis model group. CONCLUSION: Rock salt aerosol intervention may delay the pathogenesis of silicosis by improving the inflammatory response, regulating oxidative stress and reducing interstitial fibrosis of lungs.
8.Relationship between health literacy of primary school teachers and health behavior of students in Baoji city
WEN Jinsuo, NAN Haitao, WU Yanmei, GUO Xiaokun
Chinese Journal of School Health 2019;40(10):1485-1487
Objective:
To understand the current situation and the relationship between the health literacy of primary school teachers and health behavior literacy of students, and to provide some inspiration for the reform of health promotion and education in school.
Methods:
Twelve primary schools were selected from Jintai district, Chencang district and Long county,and we used stratified cluster random sampling method to choose 334 primary school teachers and 622 students of grade 4 and 6 to fill out the questionnaire.
Results:
Nearly 46.71% of all the teachers had adequate health literacy. Multivariate Logistic regression analysis showed that the urban and rural (OR=2.30, 95%CI=1.30-4.07) and gender (OR=2.62, 95%CI=1.36-5.05) were statistically significant for the health literacy among teachers; Adequate health behavior literacy was found in 46.78% of all the students,multivariate Logistic regression analysis also showed the urban and rural (OR=2.07, 95%CI=1.33-3.24)and mother’s education (OR=2.01-2.41, 95%CI=1.25-4.76) were statistically significant. Spearman correlation coefficient between health literacy of the teachers and students was(r=0.69, P<0.05).
Conclusion
The relation between health literacy of the teachers and students is positive. To improve the health literacy of primary school students, health literacy of primary school teachers should be improved first in China.
9. 25-hydroxyvitamin D, sex hormone levels and cardiovascular risk among men in northeast area of Henan province
Jiao WANG ; Xiaojun MA ; Yanling LIU ; Yanyan ZHAO ; Zhizhen LI ; Feng GUO ; Xiaokun MA ; Lina WU ; Weiping TENG ; Guijun QIN
Chinese Journal of Internal Medicine 2019;58(9):673-679
Objective:
To examine associations of 25-hydroxyvitamin D [25(OH)D] concentrations with sex hormone levels and cardiovascular risk factors.
Methods:
A total of 697 male subjects were obtained from the thyroid disorders, lodine status and diabetes: a national epidemiological survey-2014 (TIDE) research--Henan sub-center survey through multistage stratified cluster random sampling from December 2015 to March 2016. The associations between 25(OH)D and sex hormones or cardiovascular risk factors were analyzed by linear regression analyses.
Results:
The age of the subjects was (46.6±15.9) years (19-85 years). Proportions of vitamin D deficient, vitamin D intermediate and vitamin D optimal were 9.3%, 13.1% and 77.6%, respectively. More subjects with vitamin D deficient were in urban area than in rural area (13.3% vs. 5.7%,
10.25?hydroxyvitamin D, sex hormone levels and cardiovascular risk among men in northeast area of Henan province
Jiao WANG ; Xiaojun MA ; Yanling LIU ; Yanyan ZHAO ; Zhizhen LI ; Feng GUO ; Xiaokun MA ; Lina WU ; Weiping TENG ; Guijun QIN
Chinese Journal of Internal Medicine 2019;58(9):673-679
To examine associations of 25?hydroxyvitamin D [25(OH)D] concentrations with sex hormone levels and cardiovascular risk factors. Methods A total of 697 male subjects were obtained from the thyroid disorders, lodine status and diabetes: a national epidemiological survey?2014 (TIDE) research??Henan sub?center survey through multistage stratified cluster random sampling from December 2015 to March 2016. The associations between 25(OH)D and sex hormones or cardiovascular risk factors were analyzed by linear regression analyses. Results The age of the subjects was (46.6 ± 15.9) years (19?85 years). Proportions of vitamin D deficient, vitamin D intermediate and vitamin D optimal were 9.3%, 13.1% and 77.6%, respectively. More subjects with vitamin D deficient were in urban area than in rural area (13.3% vs. 5.7%, P=0.001). After fully adjusting for age, residence area, economic status, education, body mass index, waist circumference, homeostasis model assessment of insulin resistance (HOMA?IR), hypertension, diabetes, triglyceride, high?density lipoproteincholesterol, total cholesterol, low?density lipoprotein cholesterol and uric acid, linear regression analyses showed that every 25 nmol/L increase in 25(OH)D levels increased lg FT(FT=free testosterone) by 0.013ng/L (β=0.013, P=0.036), lg DHT (DHT=dihydrotestosterone) by 0.030 ng/L (β=0.030, P=0.019), and lg AD (AD=androstenedione) by 0.019 μg/L (β=0.019, P=0.008). After fully adjusting for age, residence area, economic status and education, every 25 nmol/L increase in 25(OH)D levels lowered glycosylated hemoglobin A1c (HbA1c) by 0.051% (β=-0.051, P=0.027). Conclusions Higher 25(OH)D concentrations in men were associated with higher FT, DHT, AD and lower HbA1c levels.


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