1.Improvement effects of pachymic acid on myocardial injury in coronary heart disease rats by regulating mito-chondrial autophagy mediated by the PINK1/Parkin signaling pathway
Jian XIE ; Bo GAO ; Shanshan LIANG ; Qing YANG ; Siyan GUO ; Longjia GONG
China Pharmacy 2025;36(18):2267-2272
OBJECTIVE To explore whether pachymic acid (Pac) regulates mitochondrial autophagy mediated by the PTEN- induced kinase 1 (PINK1)/Parkin RBR E3 ubiquitin-protein ligase (Parkin) signaling pathway to alleviate myocardial injury in coronary heart disease (CHD) rats. METHODS SD rats were divided into control (Con) group, CHD group, Pac low-dose group (Pac-L group), Pac high-dose group (Pac-H group), Pac-H+PINK1/Parkin signaling pathway inhibitor group (Pac-H+3-MA group), with 10 rats in each group. Except for the Con group, CHD models were established in the remaining groups of rats. After successful modeling, the rats in each group were intraperitoneally injected with the corresponding drugs or normal saline. After continuous intervention for 4 weeks, the left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and mean arterial pressure (MAP) of the rats were detected. The levels of creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), cardiac troponin I (cTnI), and cardiac troponin T (cTnT) in the serum, as well as the levels of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), IL-1β, reactive oxygen species (ROS), malondialdehyde (MDA) in the myocardial tissue, and the activities of catalase (CAT) and superoxide dismutase (SOD), as well as the expression levels of p62, cleaved caspase-3, Parkin, PINK1 proteins and the ratio of microtubule-associated protein 1 light chain 3 Ⅱ (LC3Ⅱ)/LC3Ⅰ ratio were measured. The morphology of myocardial tissue and mitochondrial autophagic vesicles were observed, and the number of mitochondrial autophagic vesicles per unit area and the rate of cardiomyocyte apoptosis were counted. RESULTS Compared with CHD group, LVEF, MAP, IL-10 levels, CAT and SOD activities, p62, Parkin, PINK1 protein expressions, LC3Ⅱ/LC3Ⅰ ratio, the numbers of mitochondrial autophagic vesicles per unit area in the Pac-L and Pac-H E-mail:hzdpft@163.com groups were increased significantly (P<0.05); the levels of LVEDV, LVESV, CK-MB, LDH, cTnI, cTnT, TNF-α, IL-1β, ROS and MDA, cell apoptosis rates, and protein expression of cleaved caspase-3 were all decreased significantly (P<0.05); and the changes in various indicators were more pronounced in the Pac-H group (P<0.05); both groups showed varying degree of improvement in myocardial histopathological morphology. Compared with the Pac-H group, the aforementioned indicators in rats from the Pac-H+3-MA group were all significantly reversed (P<0.05). CONCLUSIONS Pac may promote mitochondrial autophagy in cardiomyocytes of CHD rats by activating the PINK1/ Parkin signaling pathway, thereby reducing inflammatory responses and oxidative stress and improving myocardial injury.
2.Research progress of traditional Chinese and Western medicine non-pharmacological prevention strategies for acute high altitude disease
Li LI ; Peipei LU ; Zhiwen CAO ; Bo WEN ; Shanshan SHEN ; Zirong WANG ; Yong TAN ; Cheng LYU
Chinese Critical Care Medicine 2024;36(6):669-672
Acute high altitude disease (AHAD) is a general term for a series of clinical reactions that occur when the body fails to adapt to the low-pressure hypoxic environment of high altitudes. Mild cases can cause symptoms such as headache, nausea and vomiting, while more severe cases can lead to life-threatening conditions such as pulmonary edema, cerebral edema and other critical conditions that can be fatal. With the increasing demand for high altitudes deployment, understanding the common preventive measures of AHAD can reduce its morbidity or mortality to a certain extent, which is of great benefit to those who reside temporarily at high altitudes. In recent years, as people's health awareness has improved, there has been a growing attention towards non-pharmacological methods of disease prevention. At the same time, non-pharmacological therapy has significant therapeutic effects in preventing and treating high-altitude diseases, which has attracted the attention of researchers in this field. This review summarizes the major non-pharmacological preventive components of modern medicine and outlines the current non-pharmacological approaches to AHAD from the perspective of traditional Chinese medicine, intending to serve clinical purposes and improve the onset and prognosis of AHAD.
3.Clinical and imaging analysis of COVID-19-related osmotic demyelination syndrome
Yuyue QIU ; Chenhui MAO ; Jialu BAO ; Li SHANG ; Tianyi WANG ; Bo LI ; Yixuan HUANG ; Yuhan JIANG ; Shanshan CHU ; Wei JIN ; Liling DONG ; Feng FENG ; Jing GAO
Chinese Journal of Neurology 2024;57(7):763-769
Objective:To analyze the clinical and imaging features of patients with COVID-19-related osmotic demyelination syndrome (ODS).Methods:COVID-19-related ODS cases diagnosed in the Department of Neurology, Peking Union Medical College Hospital from January 2020 to September 2023 were retrospectively reviewed. And their past medical history, possible triggers, clinical manifestations, imaging manifestations, treatment and prognosis were summarized.Results:A total of 5 patients with COVID-19-related ODS were included. Electrolyte disturbances acted as an inducement of ODS in all patients (5/5),4 of whom with hyponatremia. Four of 5 patients first presented with disturbance of consciousness, followed by predominant dystonia. Imaging of all patients (5/5) showed isolated extrapontine myelinolysis (EPM). With the prolongation of the course of disease, such signal intensity could return to normal, and lesions showed atrophic changes in some patients. The patients′ clinical symptoms were partly relieved within a few days to a few months after treatment.Conclusions:COVID-19-related ODS is mostly associated with hyponatremia, and EPM is more common. COVID-19 should be considered as a risk factor for ODS.
4.Efficacy and Mechanism of Lutongning Granules in Treatment of Trigeminal Neuralgia Induced by Injection of Talc into Infraorbital Foramen of Model Rats Based on P2X7R-mediated Neuroinflammation
Qiyue SUN ; Shuran LI ; Shuangrong GAO ; Shanshan GUO ; Zihan GENG ; Lei BAO ; Ronghua ZHAO ; Jingsheng ZHANG ; Bo PANG ; Yingli XU ; Yu ZHANG ; Shan CAO ; Yaxin WANG ; Xiaolan CUI ; Bing HAN ; Jing SUN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):56-63
ObjectiveTo evaluate the effectiveness of Lutongning granules in the treatment of trigeminal neuralgia in animal models and study its mechanism of action, so as to provide laboratory data support for the clinical application of Lutongning granules and precise treatment. MethodMale SD rats were randomly divided into normal group, model group, carbamazepine group (0.06 g·kg-1·d-1), high-dose Lutongning group (2.70 g·kg-1·d-1), and low-dose Lutongning group (1.35 g·kg-1·d-1) according to the stratified basic mechanical pain thresholds, with 10 rats in each group. A trigeminal neuralgia model of rats was prepared by injecting 30% talc suspension into the infraorbital foramen area of the rat. The drug groups were administered 10 mL·kg-1 of drugs by gavage after 2 h of modeling. The normal group and the model group were administered distilled water by gavage under the same conditions once a day for 10 consecutive days. Von Frey brushes were used to determine the mechanical pain threshold of rats. A fully automated blood and body fluid analyzer was employed to detect the blood routine of rats. Hematoxylin and eosin (HE) staining was utilized to detect the pathological changes in the trigeminal ganglion and medulla oblongata tissue. Transmission electron microscopy was used to scan the ultrastructure of the medulla oblongata tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor (TNF)-α, neuropeptide substance P, and β-endorphins (β-EP) in the serum of rats, and Western blot was used to detect the protein expression levels of IL-1β, purinergic receptor P2X7 (P2X7R), and phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK). ResultCompared with that in the normal group, the pain threshold of rats in the model group was significantly lower (P<0.01). The absolute value of neutrophils (NEUT#) and the percentage of neutrophils (NEUT) were significantly improved, and the percentage of lymphocytes (LYMPH) was significantly reduced (P<0.01). The serum levels of IL-1, IL-6, IL-8, and TNF-α were significantly increased (P<0.01). SP content in brain tissue was significantly increased, and β-EP content was significantly decreased (P<0.01). The relative protein expression of IL-1β, P2X7R, and p-p38 MAPK was significantly increased (P<0.05). HE staining and transmission electron microscopy results of medulla oblongata tissue revealed neuronal degeneration, mild proliferation of microglial cells, reduction in the number of myelinated nerves, and obvious demyelination. The trigeminal nerve fibers of rats were disarranged, and some nerve fibers showed vacuolization. Axons were swollen, and Schwann cells proliferated. Demyelination was observed. Compared with the model group, each administration group significantly increased the pain threshold of rats (P<0.05, P<0.01), reduced NEUT# and NEUT, and elevated LYMPH (P<0.05, P<0.01). The administration group significantly decreased the levels of IL-1, IL-6, IL-8, and TNF-α in serum and SP in brain tissue (P<0.01) and increased the level of β-EP (P<0.01). They significantly down-regulated the protein expression of IL-1β, P2X7R, and p-p38 MAPK(P<0.05, P<0.01) and significantly ameliorated the pathological changes in medulla oblongata tissue and trigeminal nerves of rats. ConclusionLutongning Granules had significant therapeutic effects on trigeminal neuralgia induced by injection of talc into the infraorbital foramen of model rats, and the mechanism may be related to amelioration of P2X7R-mediated neuroinflammation and inhibition of demyelination of myelinated nerves.
5.Effect of Influenza A Virus on BEAS-2B in Human Lung Epithelial Cells and Intervention Effect of Shufeng Jiedu Capsule-containing Serum
Shan CAO ; Zihan GENG ; Lei BAO ; Yingli XU ; Bo PANG ; Jingsheng ZHANG ; Yu ZHANG ; Mengping CHEN ; Yaxin WANG ; Ronghua ZHAO ; Shanshan GUO ; Xiaolan CUI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):90-97
ObjectiveTo observe the effect of Shufeng Jiedu capsule (SFJD)-containing serum on human lung epithelial cells infected by influenza A virus, and investigate the protective effect of the drug on the cells and the potential antiviral effect. MethodThe SFJD-containing serum was prepared and used to treat human lung epithelial cells (BEAS-2B) cultured in vitro. The viability of cells treated with different concentrations of SFJD-containing serum was measured by the cell counting kit-8 (CCK-8), and the optimal concentration of SFJD-containing serum was screened for subsequent experiments. BEAS-2B cells were classified into normal control, virus infection, and SFJD-containing serum groups, and the CCK-8 method was used to detect the survival rate of BEAS-2B cells after virus infection and drug administration. The expression of influenza virus nucleic acid in the cells of each group was determined, and the apoptosis of cells in different groups was observed by fluorescence microscopy. Real-time PCR was employed to determine the mRNA levels of influenza virus nucleoprotein (NP), Toll-like receptor 4 (TLR4), and myeloid differentiation primary response gene 88 (MyD88) in each group of cells. The immunofluorescence assay was used to detect the fluorescence intensities of TLR4, MyD88, and phosphorylated nuclear factor-κB (p-NF-κB) in lung epithelial cells. ResultCompared with that in the control group (normal serum), the cell survival rates in the blank serum and the SFJD-containing serum (5%, 10%, and 20%) groups were 100.00%±0.00%, 89.05%±4.80%, 87.13%±5.90%, 93.83%±6.03%, and 99.33%±3.39%, respectively (P<0.01). The SFJD-containing serum of 20% was selected as the optimal treatment for subsequent experiments. Compared with the normal control group, the virus infection group showed reduced cell survival rate (P<0.01), and the reduction was increased by the SFJD-containing serum (P<0.01). Compared with the virus infection group, SFJD-containing serum reduced the virus load (P<0.01) to decrease apoptosis. Compared with the normal control group, the virus infection group showed up-regulated mRNA levels of NP, TLR4, and MyD88 (P<0.01), and the up-regulation was down-regulated by the SFJD-containing serum (P<0.05, P<0.01). The fluorescence intensities of TLR4, MyD88, and p-NF-κB proteins in the cells increased after virus infection compared with those in the normal control (P<0.05, P<0.01), and they were decreased after administration with the SFJD-containing serum (P<0.05). ConclusionThe SFJD-containing serum can inhibit influenza virus in vitro by increasing the survival rate, reducing the apoptosis, and down-regulating the protein levels of TLR4, MyD88, and p-NF-κB in BEAS-2B cells.
6.Study on influencing factors of empathy fatigue in hospice nurses based on ABC-X model
Yali SUN ; Yun ZHAO ; Zhengjing LI ; Liuliu ZHANG ; Meixiang WANG ; Lagen LIU ; Bo YANG ; Xiujuan JIANG ; Shanshan ZHOU
Chinese Journal of Practical Nursing 2024;40(28):2180-2188
Objective:To analyze the status and influencing factors of empathy fatigue in hospice nurses based on ABC-X model (A: stressor event; B:resources available to a family; C: family sperceptions of the stressor; X: likelihood of crisis), so as to provide a reliable basis for developing comprehensive intervention strategies.Methods:A total of 325 nurses engaged in hospice care in China from April 2022 to June 2022 were selected by convenient sampling method. The influencing factors of empathy fatigue of hospice care nurses were analyzed by ABC-X model (working environment, resilience and coping style). The hospice care nurses were investigated by self-made general questionnaire, Chinese version of Empathy Fatigue Scale, Simplified Coping Style Questionnaire, Coping Style Resilience Scale and Nursing Work Environment Scale. The statistical analysis was performed by SPSS.26.0 statistical software.Results:There were 316 females and 9 males with age of (33.0 ± 7.9) years old. The total score of empathy fatigue in 325 hospice nurses was (91.16 ± 9.60) points, the scores of empathy satisfaction, ocupational burnout and secondary traumatic stress were (31.35 ± 6.01), (28.43 ± 5.86), (31.38 ± 5.76) points respectively. The scores of positive coping style, negative coping style, psychological resilience and nursing working environment were (37.46 ± 5.69), (21.28 ± 6.90), (89.84 ± 16.46), (117.13 ± 19.95) points respectively. The negative predictive factor for empathy satisfaction among nurses with the professional title of palliative care ( t=-4.22, P<0.05), and the positive predictive factors for simple coping strategies, psychological resilience, and nursing work environment ( t=4.52, 3.05, 9.03, all P<0.05), could explain 56.7% of the total variation. Psychological resilience, simplified coping strategies, nursing work environment were negative predictive factors for occupational burnout among hospice nurses ( t=-6.93, -3.54, -2.51, all P<0.05), while work nature was a positive predictive factor ( t=2.36, P<0.05), which could explain 49.4% of the total variation. Simplified coping strategies, psychological resilience, and nursing work environment were all negative predictors of secondary traumatic stress in hospice nurses ( t=-5.40, -3.25, -5.95, all P<0.05), which could explain 48.8% of the total variation. Conclusions:Based on the ABC-X model, it is found that the empathic fatigue of hospice nurses is mainly affected by the nursing work environment, mental resilience and coping styles. It is necessary for nursing managers to actively take measures to improve the working environment and coping styles of nurses, enhance their mental resilience and reduce their empathic fatigue.
7.An optimal medicinal and edible Chinese herbal formula attenuates particulate matter-induced lung injury through its anti-oxidative, anti-inflammatory and anti-apoptosis activities.
Huan ZHANG ; Jun KANG ; Wuyan GUO ; Fujie WANG ; Mengjiao GUO ; Shanshan FENG ; Wuai ZHOU ; Jinnan LI ; Ayesha T TAHIR ; Shaoshan WANG ; Xinjun DU ; Hui ZHAO ; Weihua WANG ; Hong ZHU ; Bo ZHANG
Chinese Herbal Medicines 2023;15(3):407-420
OBJECTIVE:
Identifying novel strategies to prevent particulate matter (PM)-induced lung injury is crucial for the reduction of the morbidity of chronic respiratory diseases. The combined intervention represented by herbal formulae for simultaneously targeting multiple pathological processes can provide a more beneficial effect than the single intervention. The aim of this paper is therefore to design a safe and effective medicinal and edible Chinese herbs (MECHs) formula against PM-induced lung injury.
METHODS:
PM-induced oxidative stress, inflammatory response and apoptosis A549 cell model were used to screen anti-oxidant, anti-inflammatory and anti-apoptotic MECHs, respectively. A network pharmacology method was utilized to rationally design a novel herbal formula. Ultra performance liquid chromatography-mass spectrometer was utilized to assess the quality control of MECHs formula. The excretion of magnetic iron oxide nanospheres of the MECHs formula was estimated in zebrafish. The MECH formula against PM-induced lung injury was investigated with mice experiments.
RESULTS:
Five selected herbs were rationally designed to form a new MECH formula, including Citri Exocarpium Rubrum (Juhong), Lablab Semen Album (Baibiandou), Atractylodis Macrocephalae Rhizoma (Baizhu), Mori Folium (Sangye) and Polygonati Odorati Rhizoma (Yuzhu). The formula effectively promoted the magnetic iron oxide nanospheres excretion in zebrafish. The mid/high dose formula significantly prevented PM-induced lung damage in mice by enhancing the activity of SOD and GSH-Px, reducing the MDA and ROS level and attenuating the upregulation of pro-inflammatory cytokine (IL-6, IL-8, IL-1β and TNF-α), down regulating the protein expression of NF-κB, STAT3 and Caspase-3.
CONCLUSION
Our findings suggest that the effective MECHs formula will become a novel strategy for preventing PM-induced lung injury and provide a paradigm for the development of functional foods using MECHs.
8.TRIB3 promotes pulmonary fibrosis through inhibiting SLUG degradation by physically interacting with MDM2.
Xiaoxi LV ; Shanshan LIU ; Chang LIU ; Yunxuan LI ; Tingting ZHANG ; Jie QI ; Ke LI ; Fang HUA ; Bing CUI ; Xiaowei ZHANG ; Yuxin LIU ; Jiaojiao YU ; Jinmei YU ; Li LI ; Xia LI ; Zhigang YAO ; Bo HUANG
Acta Pharmaceutica Sinica B 2023;13(4):1631-1647
Pulmonary fibrosis (PF) is the pathological structure of incurable fibroproliferative lung diseases that are attributed to the repeated lung injury-caused failure of lung alveolar regeneration (LAR). Here, we report that repetitive lung damage results in a progressive accumulation of the transcriptional repressor SLUG in alveolar epithelial type II cells (AEC2s). The abnormal increased SLUG inhibits AEC2s from self-renewal and differentiation into alveolar epithelial type I cells (AEC1s). We found that the elevated SLUG represses the expression of the phosphate transporter SLC34A2 in AEC2s, which reduces intracellular phosphate and represses the phosphorylation of JNK and P38 MAPK, two critical kinases supporting LAR, leading to LAR failure. TRIB3, a stress sensor, interacts with the E3 ligase MDM2 to suppress SLUG degradation in AEC2s by impeding MDM2-catalyzed SLUG ubiquitination. Targeting SLUG degradation by disturbing the TRIB3/MDM2 interaction using a new synthetic staple peptide restores LAR capacity and exhibits potent therapeutic efficacy against experimental PF. Our study reveals a mechanism of the TRIB3-MDM2-SLUG-SLC34A2 axis causing the LAR failure in PF, which confers a potential strategy for treating patients with fibroproliferative lung diseases.
9.2023 ESMO express: research on changing clinical practice for prostate cancer
Bo DAI ; Shanshan WANG ; Dingwei YE
Chinese Journal of Urology 2023;44(12):885-888
The 2023 European Society for Medical Oncology (ESMO) was held recently. In this conference, numbers of cutting-edge studies were discussed and published including advances in diagnosis and treatment, especially in prostate cancer. Studies that may influence clinical treatment decisions were summarized in this article, including timing of radiotherapy after radical prostatectomy, Enzalutamide in biochemically recurrent prostate cancer, predictive factors of novel hormonal therapies in metastatic hormone-sensitive prostate cancer, and the value of osteoprotective agent. The purpose of this article was to help clinicians make better clinical decisions.
10.Application of sequential flap transfer technique for the reconstruction of extensive faciocervical scar
Zixiang CHEN ; Yuanbo LIU ; Miao WANG ; Shan ZHU ; Bo CHEN ; Shanshan LI ; Tinglu HAN ; Mengqing ZANG
Chinese Journal of Plastic Surgery 2023;39(5):472-478
Objective:To investigate the effectiveness of sequential flap transfer technique in the reconstruction of extensive faciocervical scar.Methods:The clinical data of patients with extensive faciocervical scar admitted to the Scar Comprehensive Treatment Center of Plastic Surgery Hospital of Chinese Academy of Medical Sciences from June 2010 to April 2022 were retrospectively analyzed. Pre-expanded medial arm flap or supraclavicular artery perforator plus flap were harvested and used as the first flap to repair the defects left by faciocervical scar resection. Latissimus dorsi myocutaneous flaps or thoracodorsal artery perforator flaps were harvested from the ipsilateral back and used as the second flap to repair the donor sites of the first flap. Donor sites at the back were directly sutured. The survival of flaps, the morphology of donor sites and recipient sites and the scar of donor site were followed up.Results:A total of 13 patients, aged from 5 to 36 years (median age, 14 years), were included, including 8 males and 5 females. Twelve of the 13 cases were post-burn scar, including facial scars in 5 cases, cervical scar in 1 case and faciocervical scar in 6 cases. One case of scar was caused by radiotherapy for facial hemangioma. The size of defects after scar resection and release ranged from 12.0 cm × 8.0 cm to 24.5 cm × 8.0 cm. The operation was successfully completed in all cases. Three pre-expanded supraclavicular artery perforator plus flaps and 10 pre-expanded medial arm flaps, measuring 23.0 cm × 7.0 cm to 27.0 cm ×14.0 cm, were used as the first flap; five latissimus dorsi myocutaneous flaps and eight thoracodorsal artery perforator flaps, measuring 18.0 cm × 7.0 cm to 25.0 cm × 10.0 cm, were used as the second flap. One patient developed hematoma at two days after the pedicle division of medial arm flap and the flap survived completely after removal of the hematoma. Other flaps survived without complications and the incisions were healed in one stage. Patients were followed up for 1 to 48 months, with a median follow-up of 13 months. The color, texture, and thickness of flaps were similar to those of the recipient site. All patients were satisfied with the cosmetic result of recipient sites and donor sites.Conclusion:The sequential flap transfer technique could improve the reconstructive ability of pre-expanded medial arm flap and supraclavicular artery perforator plus flap in surgical treatment of extensive faciocervical scar, minimize the donor site morbidities, assist the closure of donor site and improve the overall outcomes.

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