1.Role of mitochondrial biogenesis in rat model of coal workers' pneumoconiosis based on PGC-1α-NRF1-TFAM signaling pathway
Mei ZHANG ; Xiaoqiang HAN ; Lulu LIU ; Yan WANG ; Xin MA ; Yu XIONG ; Huifang YANG ; Na ZHANG
Journal of Environmental and Occupational Medicine 2025;42(12):1429-1437
Background Mitochondrial biogenesis is pivotal in coal workers' pneumoconiosis fibrosis, yet the role of the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)-nuclear respiratory factor 1 (NRF1)-mitochondrial transcription factor A (TFAM) pathway inmitochondrial biogenesis remains elusive, warranting further investigation. Objective To elucidate the role of the PGC-1α-NRF1-TFAM pathway in mitochondrial biogenesis in a rat coal workers' pneumoconiosis model through in vivo and in vitro experiments. Methods (1)n vivo: twelve SPF male SD rats (200-220 g) were randomized into a control group and a coal dust group (n=6 per group). After acclimatization, the coal dust group received 1 mL 50 mg·mL−1 coal dust suspension via intratracheal instillation; the controls received saline. Lung tissues were harvested after two months for histopathology [HE, Masson, and transmission electron microscopy (TEM) ], protein and mRNA analysis, and mitochondrial DNA (mtDNA) quantification by quantitative real-time polymerase chain reaction (qPCR). (2) In vitro: rat lung type II epithelial cells (RLE-6TN) cells were exposed to coal dust (50, 100, 200, and 400 mg·L−1, 24 h). CCK-8 assay determined optimal doses. Ultrastructural changes were analyzed by TEM. Cells were transfected with OE-PGC-1α (PGC-1α overexpression) or shRNA-PGC-1α plasmids (PGC-1α knockdown), and the transfection efficiency was determined by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). The expression levels of alpah-smooth muscle actin (α-SMA), citrate synthase (CS), PGC-1α, NRF1, TFAM, and fibronectin (Fn) proteins and their corresponding mRNA were detected using Western blot and RT-qPCR, respectively. The relative content of mtDNA was determined by qPCR. Results In vivo: the control group lung samples exhibited soft, pink parenchyma, while the coal dust-exposed lungs showed blackened surfaces with soft texture. The histopathological evaluation revealed intact alveolar walls in the controls versus structural destruction, micro-nodules, and fibrotic areas in the coal dust group. After Masson staining, coal dust deposits were found surrounded by blue collagen fibers in the exposed lungs, but absent in the controls. The coal dust group displayed significant upregulation of fibrotic marker α-SMA and downregulation of mitochondrial biogenesis markers (CS, PGC-1α, NRF1, TFAM) and mtDNA compared to the controls (P<0.05). In vitro: coal dust exposure reduced cell density and induced morphological alterations. TEM revealed evenly distributed normal mitochondria in controls versus mitochondrial swelling, disrupted cristae, and reduced numbers in exposed cells. The mitochondrial biogenesis markers were elevated in the coal dust + OE-PGC-1α group compared to the coal dust + OE-NC group (P<0.05); in contrast, they were decreased in the coal dust + shRNA-PGC-1α group compared to the coal dust + shRNA-NC group (P<0.05). Compared to the control group, the expression levels of the fibrosis marker α-SMA mRNA and protein were increased in the coal dust group (P<0.05). Overexpression of PGC-1α reduced α-SMA expression, while downregulation of PGC-1α increased its expression (P<0.05). Conclusion Coal dust exposure induces mitochondrial dysfunction and pulmonary fibrosis in vivo and in vitro via the PGC-1α-NRF1-TFAM pathway dysregulation. Targeting this pathway may mitigate coal dust-induced fibrosis by restoring mitochondrial biogenesis.
2.Long-term hypomethylating agents in patients with myelodysplastic syndromes: a multi-center retrospective study
Xiaozhen LIU ; Shujuan ZHOU ; Jian HUANG ; Caifang ZHAO ; Lingxu JIANG ; Yudi ZHANG ; Chen MEI ; Liya MA ; Xinping ZHOU ; Yanping SHAO ; Gongqiang WU ; Xibin XIAO ; Rongxin YAO ; Xiaohong DU ; Tonglin HU ; Shenxian QIAN ; Yuan LI ; Xuefen YAN ; Li HUANG ; Manling WANG ; Jiaping FU ; Lihong SHOU ; Wenhua JIANG ; Weimei JIN ; Linjie LI ; Jing LE ; Wenji LUO ; Yun ZHANG ; Xiujie ZHOU ; Hao ZHANG ; Xianghua LANG ; Mei ZHOU ; Jie JIN ; Huifang JIANG ; Jin ZHANG ; Guifang OUYANG ; Hongyan TONG
Chinese Journal of Hematology 2024;45(8):738-747
Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.
3.The establishment and application of integrated nursing model for patients with coronary heart disease based on Omaha system under the "Nightingale + " era
Yi ZHUANG ; Yuhong XU ; Huifang HAN ; Mei ZHENG ; Shanshan ZHAO
Journal of Clinical Medicine in Practice 2018;22(12):8-10,26
Objective To study influence of hospital-community-family integrated nursing model for patients with coronary heart disease based on Omaha system under the " Nightingale + " era.Methods A total of 90 coronary heart disease patients were selected as research objects,and were divided into observation group and control group according to digital table method,with 45 cases per group.The control group implemented traditional nursing,while observation group implemented hospital-community-family integrated nursing model based on Omaha system under the " Nightingale +" era.Results The observation group had higher compliance,quality of life after discharge than the control group (P < 0.05).The incidence rates of primary and secondary cardiovascular adverse events were lower than that in the control group (P < 0.05).Conclusion Hospital-community-family integrated nursing model for patients with coronary heart disease based on Omaha system is feasible,and can enhance compliance after discharge coronary heart disease patients,improve the quality of life,reduce the incidence rate of cardiovascular adverse events.
4.The establishment and application of integrated nursing model for patients with coronary heart disease based on Omaha system under the "Nightingale + " era
Yi ZHUANG ; Yuhong XU ; Huifang HAN ; Mei ZHENG ; Shanshan ZHAO
Journal of Clinical Medicine in Practice 2018;22(12):8-10,26
Objective To study influence of hospital-community-family integrated nursing model for patients with coronary heart disease based on Omaha system under the " Nightingale + " era.Methods A total of 90 coronary heart disease patients were selected as research objects,and were divided into observation group and control group according to digital table method,with 45 cases per group.The control group implemented traditional nursing,while observation group implemented hospital-community-family integrated nursing model based on Omaha system under the " Nightingale +" era.Results The observation group had higher compliance,quality of life after discharge than the control group (P < 0.05).The incidence rates of primary and secondary cardiovascular adverse events were lower than that in the control group (P < 0.05).Conclusion Hospital-community-family integrated nursing model for patients with coronary heart disease based on Omaha system is feasible,and can enhance compliance after discharge coronary heart disease patients,improve the quality of life,reduce the incidence rate of cardiovascular adverse events.
5. A preliminary study on the outcome of lower-risk myelodysplastic syndrome by low-dose decitabine
Li YE ; Yanling REN ; Lili XIE ; Yingwan LUO ; Peipei LIN ; Xinping ZHOU ; Liya MA ; Chen MEI ; Weilai XU ; Juying WEI ; Huifang JIANG ; Liming ZHANG ; Hui ZENG ; Hongyan TONG
Chinese Journal of Hematology 2017;38(4):307-312
Objective:
To assess the efficiency and safety of low-dose decitabine in patients with lower-risk myelodysplastic syndrome (MDS) to couple with the clinical significance of MDS-related gene mutations.
Methods:
This study was done in 4 institutions in Zhejiang Province. A total of 62 newly diagnosed patients with lower-risk MDS were assigned to two groups of decitabine (12 mg·m-2·d-1 for 5 consecutive days) and best supportive care (BSC) . Their bone marrow samples were subject to examinations of MDS-related 15 gene mutations. The primary endpoints were the proportion of patients who achieved overall response (ORR) after at least two cycles and progression-free survival (PFS) , and their relevances to the gene mutations.
Results:
Of 62 enrolled patients, and 51 cases were included in the final analysis. 16 of 24 patients (66.7%) in decitabine group achieved ORR versus 8 of 27 (29.6%) in BSC group (
6.The Effects of Continuing Nursing Care on Sexual Quality of Patients after Laparoscopic Subtotal Hysterectomy
Juli SHEN ; Mei GAO ; Huifang JIA ; Mei HUANG ; Zuyan SUN ; Hongwen HU
Journal of Kunming Medical University 2016;37(9):147-150
Objective To explore the influence of continuing nursing care on sexual quality of patients after laparoscopic subtotal hysterectomy.Methods Seventy-eight patients with selective laparoscopic subtotal hysterectomy enrolled from March 2014 to April 2015 were numbered according to their enrollment date,and divided into control group and intervention group randomly.Both groups were conducted laparoscopic subtotal hysterectomy under general anesthesia.After the surgery,the control group was treated with standard nursing care and the intervention group received continuing nursing care beyond the standard nursing care.Participants' sexual quality of 3 months and 6 months after surgery were evaluated using the female sexual function index (FSFI) Results The scores of FSFI of intervention group were significantly higher than those of the control group.Conclusion The continuing nursing care of patients after laparoscopic subtotal hysterectomy can effectively improve patient's short-term sexual quality,which is worth of being applied in gynecology nursing care in the future.
7.Sphingosine 1-phosphate signaling pathway:a novel target for regulation of epithelial and endothelial barrier function
Huifang MEI ; Lixin SUN ; Zhenzhou JIANG ; Luyong ZHANG
Journal of China Pharmaceutical University 2016;47(6):654-660
Sphingosine 1-phosphate(S1P)is a pleiotropic sphingolipid metabolite that has been shown to regulate important physiological function by activation of its G-protein-coupled receptors S1PRs. S1P has been identified as an important signaling molecule in maintaining epithelial and endothelial barrier function. S1P signaling pathway is involved in epithelial and endothelial barrier function by regulation of adherens junction and tight junction assembly, cytoskeletal reorganization, and focal adhesion formation. Thus, S1P signaling pathway may become a novel therapeutic target for cell barrier dysfunction during some illnesses such as acute lung injury, inflammatory bowel disease and sepsis. In this review, the research progress of S1P signaling pathway in regulating epithelial and endothelial barrier function and the application of S1P in barrier dysfunction-related diseases were summarized, so as to provide references for future research.
8.Exploration and practice on the teaching of clinical skills for medical international students
Gongxian YUAN ; Huifang CHEN ; Jianghua REN ; Ying ZHANG ; Hong LEI ; Mei YE ; Fei GONG
Chinese Journal of Medical Education Research 2012;11(8):848-851
ObjectiveTo explore the appropriate teaching methods for medical international students.MethodsTotally 84 students in grade 2005 and 63 students in grade 2006 took part in clinical skills training in 2010 and 2011.The traditional method was employed in grade 2005 and interactive teaching and imagery training was applied in grade 2006 combined with the traditional methods.ResultsThe scores of clinical skill tests ( posterior thorax puncture test,abdomen puncture test,bone puncture,catheterization test) were significantly higher in grade 2006 than in grade 2005 with statistical differences,P < 0.01.The clinical skill test scores were not statistically different between grade 2005 and 2006 before training,P > 0.05,but the scores were statistically different between grade 2005and 2006 after training,P < 0.05.Conclusion Using polynary teaching methods synthetically is helpful to improve the clinical skill training effect for medical international students.
9.Clinical analysis for 12 cases of severe vulvar intraepithelial neoplasm
Huifang HUANG ; Lingya PAN ; Jiaxin YANG ; Mei YU ; Keng SHEN ; Jinghe LANG
Chinese Journal of General Practitioners 2008;7(1):26-29
Objective To study the clinical characteristics, diagnosis, treatment and its effectiveness of vulvar intraepithelial neoplasm Ⅲ(VIN Ⅲ).Methods Clinical data, including age of the patients, mode of surgical operation, pathological features, results of post-operation follow-up, of 12 cases of VIN Ⅲ admitted to the Peking Union Medical College Hospital(PUMCH)during January 1984 to December2006 were retrospectively analyzed.Results Mean age of the 12 cases was 40.3(ranging from 23 to 56)years.All the patients had symptoms of vulvar itching, three with VUlVar ulcer and one with vulvar pain.There was single neoplasm focus in two cases and multiple focuses in 10 cases, five cases with neoplasm in other sites and five with human papilloma virus(HPV)infection.All the 12 patients received surgical operation, three with simple vulvectomy(one with some residue at perianal incisal edge)and other nine with lumpectomy(four with some residue at incisal edge).Eight cases were followed-up for 9.0 months in average(ranging 1~22 months)after surgical operation, including three with some residue at incisal edge.Relapse was found in two cases three and 11 months after operation, respectively, who received re-operation, including one with residue at incisal edge and one without residue.Conclusions It is necessary to attach more importance to biopsy for the cases of suspected VIN Ⅲ, as well as colposcopic diagnosis for those with vaginal or vulvar neoplasm and testing for HPV infection.Surgical operation, including simple vulvectomy and lumpectomy with or without adjunctive measures, are main treatment for patients of VIN Ⅲ and follow-up is also important for all those with VIN Ⅲ.

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