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.Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine: Threatened Abortion
Xinchun YANG ; Shuyu WANG ; Huilan DU ; Songping LUO ; Zhe JIN ; Rong LI ; Xiangyan RUAN ; Qin ZHANG ; Xiaoling FENG ; Shicai CHEN ; Fengjie HE ; Shaobin WEI ; Qun LU ; Yanqin WANG ; Yang LIU ; Qingwei MENG ; Zengping HAO ; Ying LI ; Mei MO ; Xiaoxiao ZHANG ; Ruihua ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):241-246
Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine (TCM). The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology, Western medicine obstetrics and gynecology, and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion, the experts concluded that chromosome, endocrine, and immune abnormalities were the key factors for the occurrence of threatened abortion, and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion, TCM has advantages in preventing miscarriages, alleviating clinical symptoms and TCM syndromes, relieving anxiety, regulating reproductive endocrine and immune abnormalities, personalized and diversified treatment, enhancing efficiency and reducing toxicity, and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.
3.Advances in biomarkers for diagnosing congenital heart disease
Yuquan LU ; Guixiang TIAN ; Wei SHENG
International Journal of Pediatrics 2024;51(2):73-76
Congenital heart disease(CHD)is a common congenital anomaly that is the leading cause of death among children under the age of five years with birth defects in both developed and developing countries. With the increasing prevalence of CHD,the importance of early diagnosis and intervention of CHD is well accepted. Prenatal ultrasonography is routinely applied for the screening of CHD but many factors influence its diagnostic accuracy. Biomarker testing is a simple and rapid method that can be used as an adjunct to prenatal screening for CHD. This review aims to provide new ideas for the early diagnosis of children with CHD by exploring the pathogenesis of biomarkers in CHD. In recent years,many studies have been devoted to the exploration of biomarkers related to CHD,and the studies on biomarkers in CHD are summarized from three aspects:epigenetics,proteomics and environmental factors.
4.Occlusion with Bronchial Covered Stent in the Management of Bronchial Stump Fistula after Right Middle and Lower Lobectomy: A Case Report and Literature Review.
Miao HUANG ; Fangliang LU ; Shaolei LI ; Yuquan PEI ; Liang WANG ; Yue YANG
Chinese Journal of Lung Cancer 2021;24(4):299-304
BACKGROUND:
Bronchopleural fistula (BPF) is one of the most serious and rare postoperative complications, especially the bronchial stump fistula after lobectomy/pneumonectomy. Common treatment options include conservative medical treatment combined with surgery. However, due to the delayed healing of the fistula, the chest cavity continues to communicate with the outside world, and the patient is prone to complicated with severe thoracic infection and respiratory failure, so that the physical condition can hardly tolerate the second surgical procedure. Endoscopic treatment provides a new option for the treatment of this complication.
METHODS:
A case of right pulmonary squamous cell carcinoma was admitted to the Department of Thoracic Surgery II, Peking University Cancer Hospital in June 2016. The diagnosis and treatment was retrospectively analyzed, and the literature was reviewed.
RESULTS:
A 65 year old male patient was admitted to hospital because of "cough with blood in sputum for 3 months". Chest computed tomography (CT) showed soft tissue density mass shadow in the right lower lobe. A tumor could be seen in the opening of the right middle lobe and basal segment of lower lobe. Biopsy confirmed squamous cell carcinoma. Diagnosis consideration: squamous cell carcinoma of the middle and lower lobe of the right lung (cT2aN2, IIIa). Patients received gemcitabine plus cisplatin neoadjuvant chemotherapy for 2 cycles, and the effect of chemotherapy showed stable disease (SD). Four weeks after chemotherapy, the patient underwent video-assisted thoracic surgery (VATS) assisted right middle and lower lobectomy and mediastinal lymph node dissection. On the 5th day after operation, the patient developed acute respiratory distress syndrome (ARDS) and was transferred to intensive care unit (ICU) again after endotracheal intubation. On the 7th day after operation, the patient developed a right intermediate trunk bronchial stump fistula, but due to ARDS, the patient's physical condition could not tolerate the second operation. Under the support of extracorporeal membrane oxygenation (ECMO), a membrane covered, expandable, hinged stent was inserted into the intermediate trunk bronchial stump through rigid bronchoscope, and was successfully blocked. Due to no improvement in ARDS and irreversible pulmonary interstitial fibrosis, the patient received double lung transplantation successfully after systemic anti-infection treatment.
CONCLUSIONS
Endoscopic implantation of covered stent is a simple, safe and effective method for closure of bronchial stump fistula. When the patient's clinical situation is not suitable for immediate surgery, endoscopic stent implantation can be used as a preferred treatment method to create opportunities for follow-up treatment.
5.Correlation between Lymph Node Ratio and Clinicopathological Features and Prognosis of IIIa-N2 Non-small Cell Lung Cancer.
Shanyuan ZHANG ; Liang WANG ; Fangliang LU ; Yuquan PEI ; Yue YANG
Chinese Journal of Lung Cancer 2019;22(11):702-708
BACKGROUND:
IIIa-N2 non-small cell lung cancer was significant different in survival, although N stage of lung cancer based on anatomic location of metastasis lymph node. Lymph node ratio considered of prognostic factor might be the evaluation index for IIIa-N2 non-small cell lung cancer prognosis. Therefore, the aim of the study was to evaluate the correlation between lymph node ratio and clinicopathological features and prognosis of IIIa-N2 non-small cell lung cancer prognosis.
METHODS:
A total of 288 cases of pathological IIIa-N2 non-small cell lung cancer were enrolled who received radical resection at the Department of Thoracic Surgery II, Peking University Cancer Hospital from January 2006 to December 2016. The univariate analysis between clinicopathological variables and lymph node ratio used Pearson's chi-squared test. Cox regression was conducted to identify the independent prognosis factors for IIIa-N2 non-small cell lung cancer.
RESULTS:
There were 139 cases in the lower lymph node ratio group, another 149 cases in the higher lymph node ratio group. Adenocarcinoma (χ²=5.924, P=0.015), highest mediastinal lymph node metastasis (χ²=46.136, P<0.001), multiple-number N2 metastasis (χ²=59.347, P<0.001), multiple-station N2 metastasis (χ²=77.387, P<0.001) and skip N2 lymph node metastasis (χ²=61.524, P<0.001) significantly impacted lymph node ratio. The total number of lymph node dissection was not correlated with the lymph node ratio (χ²=0.537, P=0.464). Cox regression analysis confirmed that adenocarcinoma (P=0.008), multiple-number N2 metastasis (P=0.025) and lymph node ratio (P=0.001) were the independent prognosis factors of disease free survival. The 5-year disease free survival was 18.1% in the higher lymph node ratio group, and 44.1% in the lower. Lymph node ratio was the independent prognosis factor of overall survival (P<0.001). The 5-year overall survival was 36.7% in the higher lymph node ratio group, and 64.1% in the lower.
CONCLUSIONS
Lymph node ratio was correlative with the pathology, highest mediastinal lymph node metastasis, multiple-number N2 metastasis, multiple-station N2 metastasis and skip N2 lymph node metastasis. Lymph node ratio was the independent prognosis factor for IIIa-N2 non-small cell lung cancer.
6.The structure differences of Japanese encephalitis virus SA14 and SA14-14-2 E proteins elucidate the virulence attenuation mechanism.
Xinyu LIU ; Xin ZHAO ; Rui NA ; Lili LI ; Eberhard WARKENTIN ; Jennifer WITT ; Xu LU ; Yongxin YU ; Yuquan WEI ; Guohong PENG ; Yuhua LI ; Junzhi WANG
Protein & Cell 2019;10(2):149-153
7. Effect of multimodal analgesia using periprostatic nerve block anesthesia combined with flurbiprofen in transperineal template-guided prostate biopsy
Xuefei DING ; Yang LUAN ; Shengming LU ; Tianbao HUANG ; Fei YAN ; Jianan XU ; Yuquan ZHOU ; Fei WANG ; Yaozong XU
Chinese Journal of Surgery 2019;57(6):428-433
Objective:
To evaluate the effect of multimodal analgesia using periprostatic nerve block anesthesia (PNB) combined with flurbiprofen in patients undergoing transperineal template-guided prostate biopsy (TTPB).
Methods:
Totally 166 patients (aged (68.2±9.1) years, range: 47 to 81 years) who received TTPB from October 2017 to June 2018 at Department of Urology, Northern Jiangsu People′s Hospital Affiliated to Yangzhou University were enrolled prospectively. All the patients were randomly divided into 2 groups. The observation group (
8.Effects of oral-muscle biofeedback system training on rehabilitation of cognitive impairment in patients with obstructive sleep apnea after ischemic stroke
Jun HE ; Tongbo LU ; Jinmei ZHU ; Xue QIAN ; Suqin JIAO ; Lixiang YAN ; Yuquan DING ; Lixia ZHANG ; Tong WANG
Chinese Journal of Behavioral Medicine and Brain Science 2018;27(12):1100-1104
Objective To explore the effect of oral-muscle biofeedback system training on the rehabilitation of cognitive dysfunction in patients with obstructive sleep apnea (OSA) after ischemic stroke.Methods A total of 60 cases of poststroke OSA patients with cognitive dysfunction admitted to the rehabilitation center of deAn hospital in changzhou city from June 2017 to March 2018 were selected.On the basis of routine rehabilitation treatment,the control group was given positive pressure ventilation treatment,and the observation group was given oral muscle biofeedback system training.The changes of polysomnography (PSG) parameters,Montreal cognitive assessment (MoCA) score,serum matrix metalloproteinase-9 (MMP-9) and plasma homcysteinemia (Hcy) expression levels in the two groups before and after treatment were compared.Results Apnea hypopnea index and maximum apnea time of the two groups were significantly decreased after treatment compared with those before treatment,and the lowest SpO2 and average SpO2 were significantly higher than those before treatment(P<0.05).After treatment,MoCA total score and the dimensions score of patients in the observation group were significantly higher than those in the control group at the same time (P<0.05).After treatment,the levels of Hcy((12.38±4.54) μmol/L) and MMP-9((124.52± 12.94) μg/L) in the observation group were significantly lower than those in the control group at the same time(Hcy(17.52±6.27) μmol/L,MMP-9(268.25±20.5 7)μg/L),and the difference was statistically significant (Hcy:t=3.637,P<0.05;MMP-9:t =32.395,P<0.05).Conclusions Positive pressure ventilation and oral muscle biofeedback system training have the same effect on OSA after stroke,but oral muscle biofeedback system training can also effectively improve patients' cognitive function.
9.Hematopoietic stem cell injury in mice induced by busulfan
Chengcheng LI ; Bowen GUAN ; Lu SU ; Nv DANG ; Yuquan WANG ; Aimin MENG
Chinese Journal of Comparative Medicine 2018;28(2):26-32
Objective To study the hematopoietic stem cell injury(HSC)induced by busulfan. Methods C57BL/6 mice were treated with i.p. injection of 20 mg/kg or 40 mg/kg busulfan. All mice were euthanized at 15 days and 30 days after busulfan treatment for analysis of the peripheral blood cell counts, bone marrow cellularity and HPC (LKS-, lineage-sca1 -c-kit+), HSC(LSK, lineage-sca1 +c-kit+)and long-term HSC(CD34 - LSK, CD34 - lineage-sca1 +c-kit+)frequency. The colony-forming unit-granulocyte and macrophage(CFU-GM)ability of HPC was measured by colony-forming cell(CFC)assay,and the HSC self-renewal capacity was analyzed by single-cell colony-forming assay. Results The busulfan administration decreased the WBC,RBC and PLT compared with control mice. The HPC function (CFU-GM)was impaired(P < 0.05), and the HSC colony forming ability was decreased at 15 days after busulfan treatment(P < 0.05), whereas the body weight of the mice didn't change significantly after busulfan treatment. Conclusions Our findings suggest that busulfan can induce hematopoietic stem cell injury,and provide a support for the study of hematopoietic stem cell injury mechanism.
10.Surgical treatment of hepatic hemangiomas: a study of 908 patients
Xun WANG ; Mingyi CHEN ; Yongwei CHEN ; Ying LUO ; Wenbin JI ; Jing WANG ; Xiaoqiang HUANG ; Yuquan FENG ; Wenzhi ZHANG ; Wanqing GU ; Shichun LU
Chinese Journal of Hepatobiliary Surgery 2018;24(7):442-445
Objective To study the surgical treatment of hepatic hemangiomas and the timing of surgery.Methods A retrospective study was conducted on 908 patients with giant hemangiomas who underwent surgery between December 1997 and December 2017.The clinical data,surgical indications,surgical outcomes,lesion size,and the effect of TAE were compared.Results The diameter (mean + /-S.D.)of the resected hepatic cavernous hemangiomas was (11.1 ± 6.2) cm (the longest diameter was 60 cm).585 patients (64.4%) underwent enucleation of hepatic hemangiomas and 323 patients (35.6%) underwent anatomical hepatectomy.Six patients died perioperatively (mortality rate 0.7%).The incidence of severe complication (Clavien-Dindo grade 3 ~ 5) was 3.8%.The incidence of severe postoperative complication for enucleation (2.7%) was significantly less than anatomic liver resection (5.6%,P <0.05).When the lesion was more than 20 cm,the complication and mortality rates were significantly higher than those less than 20 cm (P < 0.05).The complication and mortality rates in patients who underwent TAE before surgery were significantly higher than those without TAE (P < 0.05).Conclusions Surgical enucleation of hemangiomas was superior to anatomical hepatectomy.With increase in tumor size,the risk of surgery increased.Surgical treatment was safe and effective for giant hepatic hemangiomas.For giant hepatic hemangiomas with significant increase in size,prompt surgical treatment is recommended.

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