1.Mechanism of Wendan Ningxin Granules in Modulating Diastolic Calcium Leakage-related Proteins to Improve Inflammation-associated Atrial Fibrillation Susceptibility
Biyue SHANG ; Tingting ZHU ; Shunxin LYU ; Zhiwei ZHANG ; Yufei WANG ; Xiangning CUI ; Yingdong LU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):133-143
ObjectiveTo investigate the protective effect and mechanism of Wendan Ningxin granules (WNG) on susceptibility to atrial fibrillation (AF) in mice with inflammatory injury. Methods100 C57BL/6 mice were divided into a blank control group, a model group, a low-dose WNG group (2.34 g·kg-1·d-1), a high-dose WNG group (4.68 g·kg-1·d-1), and an amiodarone positive control group (0.091 g·kg-1·d-1), with 20 mice in each group. Except for the blank control group, mice in other groups received intraperitoneal injections of lipopolysaccharide (LPS) to establish an inflammatory injury model. Treatment groups received continuous intragastric administration of their respective interventions for four weeks. During the fourth week, the treatment groups received LPS injections concurrently with their treatments. The blank control and model groups received distilled water (10 mL·kg-1·d-1) by gavage, with a gavage volume of 10 mL·kg-1 for all groups, once daily. Hematoxylin-eosin (HE) staining and Sirius red staining were used to observe atrial tissue morphology and fibrosis degree. Immunohistochemistry was used to assess the expression of α-smooth muscle actin (α-SMA) in mouse atrial tissue. Electrophysiological detection was performed using a multi-channel electrophysiology mapping system to measure AF inducibility, AF duration, and atrial effective refractory period (AERP). High-resolution optical mapping was used to measure action potential duration (APD) dispersion, conduction heterogeneity index, and calcium transient (CaT) dispersion. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect mRNA expression of proteins related to diastolic calcium leakage in mouse atria: Ca2+/calmodulin-dependent protein kinase Ⅱ(CaMKⅡ), ryanodine receptor 2(RyR2), sarco/endoplasmic reticulum Ca²⁺-ATPase (SERCA), and sodium-calcium exchanger (NCX). Western blot analysis was performed to detect the expression of CaMKII, RyR2, SERCA, and NCX proteins in myocardial tissue from each group. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). ResultsPathological staining results showed that compared with the blank control group, the model group exhibited disrupted atrial tissue structure, inflammatory cell infiltration, atrial fibrosis, and diffuse infiltration of numerous brown α-SMA positive cells in the atrial interstitium (P<0.01). AF could be induced by electrical stimulation with a longer duration. AERP was shortened, while APD dispersion, conduction heterogeneity index, and CaT dispersion were increased (P<0.01). The expression of proteins associated with diastolic calcium leakage, including CaMKⅡ, RyR2, and NCX1, showed elevated mRNA and protein levels, whereas SERCA2a mRNA and protein expression decreased (P<0.05). Serum levels of inflammatory factors IL-1β and TNF-α were elevated (P<0.01). Compared with the model group, intervention with WNG alleviated cardiac structural damage, reduced inflammatory cell infiltration, improved atrial fibrosis, and reduced the diffuse infiltration of α-SMA positive cells (P<0.01). AF inducibility and AF duration upon electrical stimulation were significantly reduced (P<0.05), AERP was prolonged (P<0.05), mRNA and protein expression of CaMKⅡ, RyR2, and NCX1-proteins associated with diastolic calcium leakage-were reduced, whilst mRNA and protein expression of SERCA2a increased (P<0.05), and serum levels of IL-1β and TNF-α were decreased (P<0.01). ConclusionBoth low‑ and high‑dose WNG can effectively reduce susceptibility to inflammation-related AF. The mechanism by which WNG reduce AF susceptibility may be related to regulating proteins involved in sarcoplasmic reticulum diastolic calcium leak, thereby improving cardiac electrical remodeling, and alleviating inflammation-induced myocardial fibrosis, thus improving cardiac structural remodeling.
2.Effect and mechanism of the azo-podophyllotoxin derivative SU056 in a mouse model of carbon tetrachloride-induced liver fibrosis
Qichao GE ; Rui CHEN ; Yufei YANG ; Yuecheng GUO ; Dihanjing ZHANG ; Hui DONG ; Lungen LU
Journal of Clinical Hepatology 2026;42(6):1310-1320
ObjectiveTo investigate the effect of SU056, an azo-podophyllotoxin derivative, on carbon tetrachloride (CCl4)-induced liver fibrosis in mice and related mechanisms of action. MethodsA total of 12 mice were randomly divided into control group, model group (CCl4+normal saline), and treatment group (CCl4+SU056), with 4 mice in each group. Mice were given intraperitoneal injection of CCl4 to establish a model of liver fibrosis, and during the middle stage of modeling, the mice in the treatment group were given daily intraperitoneal injection of SU056. Liver histopathological injury, collagen deposition, and liver function were assessed based on HE staining, Masson staining, Sirius Red staining, the content of hydroxyproline in liver tissue, and the serum levels of alanine aminotransferase and aspartate aminotransferase, and immunofluorescence assay was used to measure the expression levels of smooth muscle actin α (α-SMA), collagen type Ⅰ, and Y-box binding protein 1 (YB1). The human hepatic stellate cell (HSC) line LX-2 and primary mouse HSC were used, and CCK-8 assay was used to measure cell proliferation; Transwell assay was used to observe cell migration; quantitative reverse transcription-polymerase chain reaction and Western Blot were used to measure the expression levels of collagen type Ⅰ, collagen type Ⅲ, YB1, phosphorylated mammalian target of rapamycin (mTOR), and phosphorylated S6K, so as to validate the function of the YB1/mTOR signaling axis. The one-way or two-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsIn the mouse model of liver fibrosis induced by CCl4, compared with the model group, the treatment group had significant alleviation of inflammatory cell infiltration, collagen deposition, and pseudolobule formation in liver tissue and significant reductions in the serum levels of alanine aminotransferase and aspartate aminotransferase and the content of hydroxyproline in liver tissue (all P<0.01). Immunofluorescence assay showed that SU056 significantly inhibited the abnormal high expression of α-SMA, collagen type I, and YB1 in liver tissue (all P<0.01). In vitro experiments showed that SU056 inhibited the transforming growth factor-β1-induced proliferation of LX-2 cells (P<0.01), the migration of LX-2 cells (P<0.05), and the transcriptional up-regulation of collagen type Ⅰ and collagen type Ⅲ (all P<0.05) in a dose-dependent manner, and SU056 could inhibit the spontaneous activation of primary HSC in vitro. Mechanistic studies revealed that transforming growth factor-β1 simultaneously upregulated the expression levels of YB1, phosphorylated mTOR, and phosphorylated S6K in LX-2 cells, and treatment with SU056 (10 and 20 µmol/L) could downregulate the protein expression levels of collagen type I, YB1, phosphorylated mTOR, and phosphorylated S6K. Specific knockdown of YB1 or administration of the mTOR inhibitor rapamycin exerted a similar effect as SU056. SU056 also inhibited the co-upregulation of α-SMA and phosphorylated mTOR in liver tissue of model mice (P<0.01). ConclusionSU056 can effectively inhibit HSC activation, proliferation, migration, and extracellular matrix production both in vivo and in vitro and thus delay the progression of liver fibrosis, by disrupting the YB1/mTOR positive feedback signaling axis.
3.Preoperative short-course radiotherapy followed by chemotherapy and PD-1 inhibitor administration for locally advanced rectal cancer: the initial results of a randomized controlled clinical trial (STELLAR II)
Haoyue LI ; Haitao ZHOU ; Lichun WEI ; Yinggang CHEN ; Wenjue ZHANG ; Feiyan DENG ; Ning LI ; Zheng JIANG ; Zheng LIU ; Jianwei LIANG ; Zhaoxu ZHENG ; Xianyu MENG ; Yufei LU ; Zifa LEI ; Xiaoge SUN ; Gong LI ; Yingjie WANG ; Yongwen SONG ; Shunan QI ; Hao JING ; Yirui ZHAI ; Shulian WANG ; Yexiong LI ; Yuan TANG ; Jing JIN
Chinese Journal of Oncology 2025;47(9):913-921
Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.
4.Preoperative short-course radiotherapy followed by chemotherapy and PD-1 inhibitor administration for locally advanced rectal cancer: the initial results of a randomized controlled clinical trial (STELLAR II)
Haoyue LI ; Haitao ZHOU ; Lichun WEI ; Yinggang CHEN ; Wenjue ZHANG ; Feiyan DENG ; Ning LI ; Zheng JIANG ; Zheng LIU ; Jianwei LIANG ; Zhaoxu ZHENG ; Xianyu MENG ; Yufei LU ; Zifa LEI ; Xiaoge SUN ; Gong LI ; Yingjie WANG ; Yongwen SONG ; Shunan QI ; Hao JING ; Yirui ZHAI ; Shulian WANG ; Yexiong LI ; Yuan TANG ; Jing JIN
Chinese Journal of Oncology 2025;47(9):913-921
Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.
5.Role of PINK1/Parkin mediated mitochondrial autophagy in radiation-induced mesenchymal transition of lung epithelial cells
Gaofeng DING ; Qingke DUAN ; Wen WANG ; Yufei LU
Chinese Journal of Radiological Medicine and Protection 2025;45(7):629-636
Objective:To investigate the role of ionizing radiation in regulating mitochondrial autophagy and epithelial mesenchymal transaction (EMT) in lung, in order to provide experimental evidence for further elucidating the pathogenesis and clinical treatment of radiation-induced pulmonary fibrosis (RIPF).Methods:Beas-2B cells were irradiated with 6 Gy X-rays, and their morphological changes were observed at 0, 12, 24 and 48 h after irradiation. The changes of mitochondrial autophagy and EMT-related proteins in PINK1/Parkin pathway were detected by Western blot assay. The changes of mitochondrial membrane potential were detected by JC-1 staining. TEM was used to observe the changes of cell ultrastructure 48 h after radiation. Beas-2B cells were then divided into control group, irradiation group (RI), RI + vector plasmid group (RI+ oeNC), RI+ PINK1 overexpression group (RI+ oePINK1), and the protein changes of FN1 and LC3 were detected by immunofluorescence. Flow cytometry was used to detect the change of reactive oxygen species (ROS) in each group. The changes of mitochondrial autophagy and EMT-related protein contents were detected by immunofluorescence, flow cytometry and Western blot, respectively.Results:After X-ray irradiation, the cell morphology of human epithelial cells Beas-2B was changed from irregular polygon to spindle shape along with the time increase after irradiation, showing EMT appearance. JC-1 staining showed that, along with the time after irradiation, the red fluorescence was weakened, and the green fluorescence was enhanced, so that the red/green fluorescence ratio was decreased. TEM observation indicated that the cell morphology changed to spindle shape and the number of autophagic lysosomes decreased significantly at 48 h after irradiation. Western blot assay showed that the protein expression levels of PINK1, Parkin and Beclin1 were significantly decreased, while the expression of p62 protein was significantly increased after irradiation. Moreover, the expressions of E-cad and CK19 were significantly decreased, while the expressions of N-cad and Vim were significantly increased ( t = 6.48, 3.72, 6.06, -18.71, P<0.05). Immunofluorescence assay showed that LC3 expression was increased and FN1 expression was decreased in the oePINK1 group ( t = 6.06, -21.49, -9.58, 3.58, P < 0.05). Flow cytometry assay showed that ROS in the oePINK1 group was significantly decreased ( t = -342.54, 88.01, 25.48, P<0.05). After PINK1 overexpression, the expression levels of PINK1, Parkin and Beclin1 were significantly increased, while the expression of p62 protein was significantly decreased ( t = -25.57, -8.76, -11.24, 34.81, P<0.05); meanwhile, the expressions of E-cad and CK19 were significantly increased, while the expressions of N-cad and Vim were significantly decreased ( t =-7.12, 12.04, 67.92, -7.64, P<0.05). Conclusions:X-ray irradiation promoted EMT and impaired mitochondrial function of Beas-2B cells, and weakened mitochondrial autophagy mediated by PINK1/Parkin pathway. Overexpression of PINK1 promoted mitochondrial autophagy, which improved mitochondrial function and effectively inhibited cell EMT, thus alleviating pulmonary fibrosis.
6.Expert consensus on hypofractionated radiotherapy for breast cancer (2025 edition)
Yufei LU ; Hong GE ; Ting WANG ; Hao WANG ; Chengliang YANG ; Ye-xiong LI ; Hao JING ; Lu CAO ; Chi ZHANG
Chinese Journal of Radiation Oncology 2025;34(12):1171-1182
Breast cancer is one of the most common malignant tumors, and postoperative radiotherapy remains an essential component of its treatment. In recent years, hypofractionated radiotherapy has gradually become the recommended approach for postoperative breast cancer treatment. Compared with conventional fractionated radiotherapy, hypofractionated regimens shorten the overall treatment duration, enhance patient convenience, and reduce treatment costs, while achieving comparable long-term efficacy and maintaining good quality of life. Based on relevant domestic and international studies and clinical experience, this consensus establishes expert recommendations regarding indications, prescribed doses, dose constraints for organs at risk (OAR), implementation methods, and plan evaluation for hypofractionated radiotherapy after breast cancer surgery, with a particular focus on moderately hypofractionated (MHF) and ultrahypofractionated (UHF) regimens. MHF radiotherapy is applicable to whole-breast irradiation, chest wall irradiation, and regional nodal irradiation, and is suitable for most breast cancer patients. UHF radiotherapy, which employs a higher dose per fraction to further shorten the treatment course, is suitable for patients requiring rapid therapy or prioritizing treatment convenience. Although the short-term efficacy of UHF radiotherapyis similar to that of MHF radiotherapy, its long-term efficacy and safety require further clinical validation. Meanwhile, potential adverse effects of UHF, such as breast induration and atrophy, should be carefully assessed. Therefore, radiotherapy dose and fractionation regimen should be individualized according to patient-specific factors, particularly considering OAR dose constraints. Rational selection of radiotherapy regimens can minimize adverse effects while maintaining therapeutic efficacy, ultimately improving patient outcomes and quality of life. This consensus provides scientific guidance for the clinical and research application of hypofractionated radiotherapy in breast cancer.
7.A survey of clinical application of stereotactic radiotherapy technology in China in 2024
Xiaoxue KOU ; Jiayi YU ; Jingwei ZHANG ; Nan BI ; Xuwei CAI ; Guanghui CHENG ; Yufei LU ; Yanyang WANG ; Ligang XING ; Yonggang XU ; Jianxin XUE ; Li ZHANG ; Hongqing ZHUANG ; Anhui SHI
Chinese Journal of Radiation Oncology 2025;34(9):897-904
Objective:To investigate the current status of application of stereotactic body radiation therapy (SBRT) in China, aiming to provide reference for promoting the development of this technology.Methods:From January to March 2024, a questionnaire was designed and distributed online, targeting member units of the Professional Committee of Stereotactic Radiosurgery Treatment, which covers 175 radiotherapy units in 30 provinces and regions nationwide. The survey focused on the current application of SBRT technology and its utilization in the treatment of early-stage non-small cell lung cancer (NSCLC). A statistical description of the survey results was presented.Results:Of 175 questionnaires distributed, a total of 130 valid responses were collected, with an effective response rate of 74.3%. A total of 81.5% (106/130) of the units had implemented SBRT technology, and 99.1% of the respondents believed it was necessary to further promote SBRT technology, yet the actual training rate was only 67.0%. SBRT equipment configuration: there were a total of 267 SBRT equipment, featuring a diverse range of types, with traditional linear accelerators as the mainstays, accounting for 76.0% ( n=203), followed by 12.0% ( n=32) for TOMO, 6.4% ( n=17) for Cyber knife, 3.7% ( n=10) for Gamma knife, and proton/heavy ion equipment at 1.5% ( n=4), respectively. The percentage of units with multi-leaf collimator leaf widths ≤0.5 cm was 93.4% (99/106). The application of SBRT: the first radiotherapy unit commenced SBRT in 2000, and this technology entered a period of rapid growth after 2015, sustaining a steady increase over the past decade; SBRT technology was mainly applied in the brain, lung, liver, bone, adrenal gland, and kidney, with application rates of 97.2%, 94.3%, 86.8%, 71.7%, 56.6%, and 27.4%, respectively, while the application rates for the pancreas, metastatic lymph nodes, and other parts were less than 5%. Current status of SBRT technology application in early-stage NSCLC: 90.6% (96/106) of units had implemented SBRT; pre-treatment multi-disciplinary diagnosis and treatment accounted for 77% (74/96); the proportion of application units for peripheral and central type lung cancer lesions both exceeded 57.3%, whereas the application rate for ultra-central type and lesions > 5 cm lung cancer was less than 30%; there was significant variability in the selection of reference guidelines, dose fractionation patterns, and the concept of central type among units. Conclusions:The development of SBRT technology in China is in a period of steady growth, but several issues such as low training rate and lack of standardization still exist. The survey results provide important reference for clinical training and promotion of SBRT technology in China.
8.Role of PINK1/Parkin mediated mitochondrial autophagy in radiation-induced mesenchymal transition of lung epithelial cells
Gaofeng DING ; Qingke DUAN ; Wen WANG ; Yufei LU
Chinese Journal of Radiological Medicine and Protection 2025;45(7):629-636
Objective:To investigate the role of ionizing radiation in regulating mitochondrial autophagy and epithelial mesenchymal transaction (EMT) in lung, in order to provide experimental evidence for further elucidating the pathogenesis and clinical treatment of radiation-induced pulmonary fibrosis (RIPF).Methods:Beas-2B cells were irradiated with 6 Gy X-rays, and their morphological changes were observed at 0, 12, 24 and 48 h after irradiation. The changes of mitochondrial autophagy and EMT-related proteins in PINK1/Parkin pathway were detected by Western blot assay. The changes of mitochondrial membrane potential were detected by JC-1 staining. TEM was used to observe the changes of cell ultrastructure 48 h after radiation. Beas-2B cells were then divided into control group, irradiation group (RI), RI + vector plasmid group (RI+ oeNC), RI+ PINK1 overexpression group (RI+ oePINK1), and the protein changes of FN1 and LC3 were detected by immunofluorescence. Flow cytometry was used to detect the change of reactive oxygen species (ROS) in each group. The changes of mitochondrial autophagy and EMT-related protein contents were detected by immunofluorescence, flow cytometry and Western blot, respectively.Results:After X-ray irradiation, the cell morphology of human epithelial cells Beas-2B was changed from irregular polygon to spindle shape along with the time increase after irradiation, showing EMT appearance. JC-1 staining showed that, along with the time after irradiation, the red fluorescence was weakened, and the green fluorescence was enhanced, so that the red/green fluorescence ratio was decreased. TEM observation indicated that the cell morphology changed to spindle shape and the number of autophagic lysosomes decreased significantly at 48 h after irradiation. Western blot assay showed that the protein expression levels of PINK1, Parkin and Beclin1 were significantly decreased, while the expression of p62 protein was significantly increased after irradiation. Moreover, the expressions of E-cad and CK19 were significantly decreased, while the expressions of N-cad and Vim were significantly increased ( t = 6.48, 3.72, 6.06, -18.71, P<0.05). Immunofluorescence assay showed that LC3 expression was increased and FN1 expression was decreased in the oePINK1 group ( t = 6.06, -21.49, -9.58, 3.58, P < 0.05). Flow cytometry assay showed that ROS in the oePINK1 group was significantly decreased ( t = -342.54, 88.01, 25.48, P<0.05). After PINK1 overexpression, the expression levels of PINK1, Parkin and Beclin1 were significantly increased, while the expression of p62 protein was significantly decreased ( t = -25.57, -8.76, -11.24, 34.81, P<0.05); meanwhile, the expressions of E-cad and CK19 were significantly increased, while the expressions of N-cad and Vim were significantly decreased ( t =-7.12, 12.04, 67.92, -7.64, P<0.05). Conclusions:X-ray irradiation promoted EMT and impaired mitochondrial function of Beas-2B cells, and weakened mitochondrial autophagy mediated by PINK1/Parkin pathway. Overexpression of PINK1 promoted mitochondrial autophagy, which improved mitochondrial function and effectively inhibited cell EMT, thus alleviating pulmonary fibrosis.
9.Clinical treatment controversies and progress in liver cirrhosis: an evidence-based medicine perspective from managing portal hypertension to preventing complications
Yufei YANG ; Junjun WANG ; Guangwen CHEN ; Qichao GE ; Lungen LU
Chinese Journal of Hepatology 2025;33(8):734-737
Liver cirrhosis as the terminal stage of chronic liver disease has seen many new insights and advances in its treatment strategies and perspectives in recent years. However, there are still many controversies about cirrhotic portal hypertension management, prevention, therapy, and complications. This article summarizes the main key controversial points in the current treatment of liver cirrhosis from an evidence-based medicine perspective, including the use of non-selective β-blockers during decompensated stages, exploration of precise strategies for albumin, re-evaluation of the risks of statins, weighing the pros and cons of proton pump inhibitors, new understandings of anticoagulation therapy, breakthroughs in targeting gut microbiota, and nutritional support management. In addition, it combines the latest research data and guideline recommendations to explore future development directions so as to provide clinical practice reference.
10.Clinical efficacy observation of pelvic floor biofeedback combined with electroacupuncture therapy in the treatment of chronic pelvic floor pain syndrome
Siyun LIAO ; Lifang LU ; Jue SHEN ; Jin YU ; Yufei LI
Chinese Journal of Postgraduates of Medicine 2025;48(4):289-294
Objective:To explore the clinical efficacy of pelvic floor biofeedback combined with electroacupuncture therapy in the treatment of chronic pelvic floor pain syndrome (CPPS).Methods:Ninety CPPS patients admitted to the Dongguan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine from August 2022 to July 2023 were selected prospectively, and they were divided into two groups by random number table method, each group with 45 cases. The control group received pelvic floor biofeedback treatment alone, while the observation group received pelvic floor biofeedback combined with electroacupuncture treatment. The two groups were treated once a day, 10 times as a course of treatment. After two courses of treatment, the clinical efficacy, pain degree before and after treatment, inflammatory factor levels, SF-36 health questionnaire (SF-36) scores, pelvic floor surface myoelectric parameters, and incidence of adverse reactions were compared between the two groups.Results:The total effective rate in the observation group after treatment was higher than that in the control group: 95.56% (43/45) vs. 75.56% (34/45), there was statistical difference ( χ2 = 7.28, P<0.05). After treatment, the visual analogue scale (VAS) scores, levels of procalcitonin (PCT), interleukin-6 (IL-6) and C-reactive protein (CRP) in the two groups were decreased, and SF-36 scores were increased, there were statistical differences ( P<0.05); the VAS scores, PCT, IL-6 and CRP levels in the observation group were lower than those in the control group, and SF-36 scores was higher than that in the control group: (2.11 ± 0.24) scores vs. (2.87 ± 0.34) scores, (0.92 ± 0.08) ng/L vs. (1.26 ± 0.09) ng/L, (24.08 ± 2.52) μg/L vs. (28.49 ± 3.10) μg/L, (4.55 ± 0.51) mg/L vs. (6.06 ± 0.63) mg/L, (74.55 ± 7.29) scores vs. (70.18 ± 7.80) scores, there were statistical differences ( P<0.05). After treatment, the surface muscle potential of pelvic floor muscle were increased in the front resting stage, rapid contraction stage, tension contraction stage, endurance contraction stage and post-resting stage, and the above parameters in the observation group were higher than those in the control group: (3.56 ± 0.34)μV vs.(3.20 ± 0.37) μV, (35.26 ± 3.05) μV vs. (31.47 ± 3.08) μV, (34.22 ± 3.25) μV vs. (31.15 ± 3.01)μV, (29.77 ± 3.17) μV vs. (27.04 ± 2.68) μV, (3.21 ± 0.27) μV vs. (3.00 ± 0.34) μV, there were statistical differences ( P<0.05). The incidence rate of adverse reactions in the two groups had no statistical difference ( P>0.05). Conclusions:Pelvic floor biofeedback combined with electroacupuncture in the treatment of CPPS has good clinical effect, and can relief pain response, regulate the inflammatory response and pelvic floor function, and have high safety.

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