1.SRSF7 promotes pulmonary fibrosis through regulating PKM alternative splicing in lung fibroblasts.
Tongzhu JIN ; Huiying GAO ; Yuquan WANG ; Zhiwei NING ; Danyang BING ; Yan WANG ; Yi CHEN ; Xiaomu TIAN ; Qiudi LIU ; Zhihui NIU ; Jiayu GUO ; Jian SUN ; Ruoxuan YANG ; Qianqian WANG ; Shifen LI ; Tianyu LI ; Yuhong ZHOU ; Wenxin HE ; Yanjie LU ; Yunyan GU ; Haihai LIANG
Acta Pharmaceutica Sinica B 2025;15(6):3041-3058
Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.
2.Analysis of Serum Furin,TGF-β,VEGF and netrin-1 Levels Expression and Polymorphism of r2071410 C/T Locus in the Furin Gene P1 Promoter Region in Patients with Different r-AFS Stages of Endometriosis
Peng LU ; Tiantian LI ; Shifen LONG ; Yan ZHANG ; Xinmei JI
Journal of Modern Laboratory Medicine 2024;39(4):23-27,82
Objective To investigate Furin,tumor growth factor-β(TGF-β),vascular endothelial growth factor(VEGF),neuron towards axon guidance factor-1(netrin-1)level expressions and polymorphism of Furin gene P1 promoter r2071410 locus C/T in endometriosis(EMT)patients with different r-AFS stages,and explore the correlation with the incidence of EMT in Shenzhen.Methods A total of 102 patients diagnosed with EMT from May 2021 to January 2023 in the People's Hospital of Longhua,Shenzhen were selected as EMT group,and the EMT group was divided into stage Ⅰ to Ⅱ group and stageⅢ to Ⅳ group according to r-AFS staging method.At the same time,78 non-EMT patients were collected as control group.The levels of serum Furin,TGF-β,VEGF and netrin-1 were detected by enzyme-linked immunosorbent assay(ELISA),and the polymorphism of the r2071410 C/T locus in the P1 promoter region of Furin gene was analyzed by reverse transcription-real time quantitative polymerase chain reaction(RT-qPCR).Results The levels of Furin(140.84±47.02pg/ml),TGF-β(376.46±82.36ng/L)and VEGF(167.67±53.02ng/L)in EMT group were higher than those in control group(55.49±13.67pg/ml,216.37±15.04ng/L,102.27±8.45ng/L),while the level of netrin-1(48.37±15.20pg/ml)was lower than that of the control group(165.85±15.63pg/ml),with significant differences(t=28.409,20.347,16.915,36.653,all P<0.05).The levels of Furin(192.41±20.62pg/ml),TGF-β(452.61±72.03ng/L)and VEGF(201.84±28.01ng/L)in patients with stage Ⅲ to Ⅳ were higher than those in patients with stage Ⅰ to Ⅱ(78.05±16.54pg/ml,283.75±56.92ng/L,126.07±19.35ng/L),while the level of netrin-1(37.95±11.34pg/ml)was lower than that of stage Ⅰ to Ⅱ(61.05±9.52pg/ml),with significant differences(t=31.071,18.054,19.183,21.625,all P<0.05).Pearson/Spearman correlation analysis showed that Furin was positively correlated with levels of TGF-β and VEGF and clinical stage(r=0.614 9,0.752 6,0.790 5,均 P<0.05),but negatively correlated with netrin-1 level(r=-0.670 1,all P<0.05).The TT genotype and T allele frequencies at r2071410 C/T locus of Furin gene P1 promoter in EMT group(42.16%,55.39%)were higher than those in control group(7.69%,19.87%),while the TT genotype and T allele frequencies at stages Ⅲ to Ⅳ(51.79%,65.18%)were higher than those at stage Ⅰ to Ⅱ(30.43%,43.48%),and the differences were statistically significant(x2=26.500,46.472,4.721,9.626,all P<0.05).The Furin level of patients with different genotypes in EMT group was different(F=51.286,P<0.001),in which the Furin level of TT genotype(216.29±68.53pg/ml)was higher than that of CC(83.04±21.37pg/ml)and CT genotype,(89.18±20.95pg/ml),and the differences were statistically significant(t=27.146,25.719,all P<0.01),but there was no significant difference between CC and CT genotypes(t=1.326,P>0.05).Conclusion The level of Furin in EMT patients was increased,and it was certainly correlated with the levels of TGF-β,VEGF,netrin-1 and clinical stage.Meanwhile,the r2071410 C/T locus in the promoter region of Furin gene P1 showed a polymorphic distribution,in which the Furin level increased more significantly in patients with TT genotype,which may be related to the incidence of EMT in Shenzhen area.
3.Study on occupational stress response of orphans and disabled children care workers in Nanjing
Shifen JIA ; Honger TIAN ; Yang WANG ; Liping ZHOU ; Li ZHANG ; Shuhang XU ; Lu LIU ; Jinhua TIAN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2020;38(3):199-202
Objective:To explore the status quo of occupational stress and its influencing factors of nursing staff for orphaned and disabled children in Nanjing, and to put forward measures for adverse reactions to occupational stress, so as to ensure the psychological health of this occupational population.Methods:From February to May 2017, 236 nursing assistants for orphans and disabled children in Nanjing social welfare home were selected by cluster sampling method. The occupational stress index(occupational stress indictor, OSI) was used to investigate occupational stress response and occupational stress factors. Partial correlation and multiple linear regression were used for statistical analysis.Results:The scores of job satisfaction, mental health and depressive symptoms in occupational stress reaction were (43. 99±6. 83) , (36. 09±4. 59) and (17. 31±2. 44) re- spectively. In terms of job satisfaction, work monotony, logic and compound change were the contributing fac- tors ( P<0. 05) , task strategy and task control were negative factors ( P<0. 05) ; on mental health, opportunities were raised and participation in decision-making Self-esteem, technology utilization, environmental control, time management, task strategy and support of colleagues as contributing factors ( P<0. 05) , ambition and role conflicts as negative factors ( P<0. 05) ; on depression, work input, participation Decision-making, promotion opportunities and behavioral characteristics were protective factors ( P<0. 05 ) . Conclusion:Occupational stress among caregivers of orphans and disabled children cannot be ignored. Occupational stress reaction is serious. Occupational stress factors should be reduced and individual stress coping ability should be enhanced.
4.The current situation of occupational burnout and its influencing factors among orphan child care workers in Nanjing
Lu LIU ; Honger TIAN ; Yang WANG ; Shuhang XU ; Shifen JIA ; Li ZHANG ; Liping ZHOU ; Jinhua TIAN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2020;38(4):268-270
Objective:To explore the status of job burnout of nurses for orphans and disabled children in Nanjing and its influencing factors, so as to provide reference for promoting the mental health of nurses for orphans and disabled children.Methods:From February to May, 2017, a cross-sectional survey was conducted among 236 nurses working in social welfare institutions for orphans and disabled children in Nanjing, using Occupational Stress Indicator (OSI) and Maslach Burnout Inventory (MBI) . It investigated the status of job burnout among nurses of orphans and disabled children, logistic regression analysis was used to explore the effect of occupational stress on the incidence of job burnout of nurses for orphans and disabled children.Results:The results showed that the incidence of job burnout was 67.37% (159/236) , the incidence of job burnout was negatively correlated with behavioral characteristics and family support, the incidence of emotional exhaustion was positively correlated with task control and job monotony ( P<0.05) , and negatively correlated with role ambiguity and job satisfaction ( P<0.05) . The incidence of depersonalization was negatively correlated with job monotony and peer support ( P<0.05) . Conclusion:The nurses of orphans and disabled children have serious job burnout. Occupational stress factors, personality characteristics and relieving factors have influence on the incidence of job burnout.
5.Study on occupational stress response of orphans and disabled children care workers in Nanjing
Shifen JIA ; Honger TIAN ; Yang WANG ; Liping ZHOU ; Li ZHANG ; Shuhang XU ; Lu LIU ; Jinhua TIAN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2020;38(3):199-202
Objective:To explore the status quo of occupational stress and its influencing factors of nursing staff for orphaned and disabled children in Nanjing, and to put forward measures for adverse reactions to occupational stress, so as to ensure the psychological health of this occupational population.Methods:From February to May 2017, 236 nursing assistants for orphans and disabled children in Nanjing social welfare home were selected by cluster sampling method. The occupational stress index(occupational stress indictor, OSI) was used to investigate occupational stress response and occupational stress factors. Partial correlation and multiple linear regression were used for statistical analysis.Results:The scores of job satisfaction, mental health and depressive symptoms in occupational stress reaction were (43. 99±6. 83) , (36. 09±4. 59) and (17. 31±2. 44) re- spectively. In terms of job satisfaction, work monotony, logic and compound change were the contributing fac- tors ( P<0. 05) , task strategy and task control were negative factors ( P<0. 05) ; on mental health, opportunities were raised and participation in decision-making Self-esteem, technology utilization, environmental control, time management, task strategy and support of colleagues as contributing factors ( P<0. 05) , ambition and role conflicts as negative factors ( P<0. 05) ; on depression, work input, participation Decision-making, promotion opportunities and behavioral characteristics were protective factors ( P<0. 05 ) . Conclusion:Occupational stress among caregivers of orphans and disabled children cannot be ignored. Occupational stress reaction is serious. Occupational stress factors should be reduced and individual stress coping ability should be enhanced.
6.The current situation of occupational burnout and its influencing factors among orphan child care workers in Nanjing
Lu LIU ; Honger TIAN ; Yang WANG ; Shuhang XU ; Shifen JIA ; Li ZHANG ; Liping ZHOU ; Jinhua TIAN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2020;38(4):268-270
Objective:To explore the status of job burnout of nurses for orphans and disabled children in Nanjing and its influencing factors, so as to provide reference for promoting the mental health of nurses for orphans and disabled children.Methods:From February to May, 2017, a cross-sectional survey was conducted among 236 nurses working in social welfare institutions for orphans and disabled children in Nanjing, using Occupational Stress Indicator (OSI) and Maslach Burnout Inventory (MBI) . It investigated the status of job burnout among nurses of orphans and disabled children, logistic regression analysis was used to explore the effect of occupational stress on the incidence of job burnout of nurses for orphans and disabled children.Results:The results showed that the incidence of job burnout was 67.37% (159/236) , the incidence of job burnout was negatively correlated with behavioral characteristics and family support, the incidence of emotional exhaustion was positively correlated with task control and job monotony ( P<0.05) , and negatively correlated with role ambiguity and job satisfaction ( P<0.05) . The incidence of depersonalization was negatively correlated with job monotony and peer support ( P<0.05) . Conclusion:The nurses of orphans and disabled children have serious job burnout. Occupational stress factors, personality characteristics and relieving factors have influence on the incidence of job burnout.
7. Analysis of occupational stress and occupational exhaustion of primary caregivers
Shuhang XU ; Honger TIAN ; Liping ZHOU ; Yang WANG ; Li ZHANG ; Shifen JIA ; Lu LIU ; Xiaobo LI
Chinese Journal of Industrial Hygiene and Occupational Diseases 2019;37(3):197-201
Objective:
To investigate the occupation stress and job burnout of orphan child care workers in Nanjing and nursing staff in Yangzhong primary hospital, to compare the differences of occupational stress and job burnout between the two social service workers.
Methods:
From February to May 2017, a cross- sectional survey was conducted. Cluster sampling method was used to investigate the occupation stress and job burnout of orphan child care workers in Nanjing and nursing staff in Yangzhong primary hospital, totally 403 people, by a combination of the Internet of things assessment system of occupational stress and traditional questionnaire.
Results:
There were statistically significant differences of occupational stress and job burnout scores of both social service workers (
8. The influence of demographic characteristics on occupational stress of orphan child care workers
Li ZHANG ; Honger TIAN ; Liping ZHOU ; Yang WANG ; Shuhang XU ; Shifen JIA ; Liu LIU ; Xiaobo LI
Chinese Journal of Industrial Hygiene and Occupational Diseases 2018;36(12):908-911
Objective:
To investigate the occupation stress of orphan child care workers in Nanjing, to explore the influence of different demographic characteristics on occupational stress of orphan child care workers and propose measures.
Methods:
Cluster sampling method was used to investigate the occupation stress of 236 people of orphan child care workers in Nanjing by a combination of the Internet of things assessment system of occupational stress and traditional questionnaire.
Results:
The scores of workload, job prospects, participation decision-making, anxiety and logical in different age groups among orphan child care workers were statistically different (
9.The establishment and evaluation of three different kinds of animal model of blood stasis syndrome
Yaoyue LIANG ; Jiajia LI ; Shifen DONG ; Rong ZHANG ; Yueying YUAN ; Jianning SUN
Chinese Pharmacological Bulletin 2016;32(10):1468-1473
Aim To establish phlegm and blood stasis, qi-stag-nation and blood stasis, phlegm turbid+qi-stagnation and blood stasis model in rats and to study the characteristics of animal models with different blood stasis. Methods SD rats were ran-domly divided into normal group, high fat diet group, chronic unpredictable mild stress group ( CUMS ) and high fat diet +chronic unpredictable mild stress group. Different states of blood stasis rat models were established by corresponding factors for 6 weeks. Indexes of weight, open field behavior, serum lipids and corticosterone were monitored dynamically at the 2 nd, 4 th, 6 th weeks. At the end of the experiment(6th week), the heart func-tion was detected by small animal ultrasound and the left ventric-ular intubation. The blood rheology indexes were detected by the viscosity tester and red blood cell deformation/aggregation test instrument. Results Compared with the normal group, blood stasis could be induced by high fat diet and chronic unpredicta-ble mild stress, introducing the influence of different degree on animal behavior, blood lipids, heart function and blood viscosi-ty. When the two factors were superimposed, the changes of the indexes about blood stasis were the most significant. Perform-ance as: compared with normal control group, a significant re-duction was observed in body weight ( P < 0. 01 ); horizontal movement, vertical movement and movement time were reduced (P<0. 01 or P<0. 05) at the 2 nd week;at the 2 nd and 4 th week, serum corticosterone was increased ( P <0. 01 or P <0. 05) as well as TG at the 4 th and 6 th week (P<0. 01); at the 6 th week, velocity of blood was slowed down ( P<0. 01 );left ventricular anterior wall and posterior wall thickness at end-systolic was increased ( P<0. 01 or P<0. 05 ); left ventricular diastolic index was increased ( P<0. 01 ); the maximum rate of myocardial contraction was decreased ( P < 0. 05 ); the whole blood viscosity was increased ( P<0. 01 ) . Conclusions Blood stasis could be formed by high fat diet and chronic unpredictable mild stress, which has different characteristics. When the two factors are superimposed, the abnormal behavior, blood viscosi-ty, heart function, blood lipid and other indexes of the animal could obviously appear, which can provide the basis for the stud-y of blood stasis syndrome and related drugs.
10.Treatment effect of gonadotropin releasing hormone agonist-a different drug consolidation therapy time on endometriosis patients received endometriosis laparoscopic surgery
Jing LI ; Tao HOU ; Hui LIANG ; Shifen DAI
Clinical Medicine of China 2016;32(8):735-738
Objective To study the treatment effect of gonadotropin releasing hormone agonist?α( GnRH?α) different drug consolidation therapy time on endometriosis patients received endometriosis laparoscopic surgery?Methods Seventy cases endometriosis patients received endometriosis laparoscopic surgery in the People's Hospital of Meizhou from May 2012 to March 2014 were enrolled for study and randomly divided into 6 months group and 3 months group according to different time of GnRH?αtreatment?Then hormone levels, inflammatory mediators, follow?up condition and treatment outcome were compared between the two groups?Results The total effective rate of 6 months group was 97?14%( 34/35) ,significantly higher than that of 3 months group(80?00%(28/35)),the difference was significant(χ2 =5?081,P<0?05)?Serum follicle stimulating hormone( FSH) ,progesterone( LH) ,estradiol( E2) levels of 6 months group were significantly lower than 3 months group,the differences were significant((2?42±0?33) U/L vs?(3?79±0?42),(3?49±0?45) U/L vs?(5?12±0?60) U/L,(89?48±10?23) ng/L vs? (130?48±16?85) ng/L;t=15?174,12?858,12?305;P<0?05)?Serum TNF?α,IL?6,IL?8 levels of 6 months group were significantly lower than 3 months group,the differences were significant((18?48±2?23) ng/L vs?(31?49±4?05) ng/L,(14?45±2?18) ng/L vs?(23?49 ±2?95) ng/L,(35?29±4?52) ng/L vs? (58?49±7?28) ng/L;t=16?648,14?580,16?017;P<0?05)?The pregnancy rate,pain relief rate of 6 months group were significantly higher than 3 months group(51?43%(18/35) vs?22?86%(8/35),74?29%(26/35) vs?40?00%(14/35)),the recurrence rate was significantly lower than that 3 months group(8?57%(3/35) vs?31?43%(11/35)),the differences were significant(χ2=6?118, 8?400,5?714;P<0?05)?Conclusion 6 months GnRH?α treatment after laparoscopic surgery help to prevent disease relapse,and regulate hormone levels,inhibit inflammatory reaction,then improve the effect of treatment.

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