1.Mechanism of salidroside preventing myocardial fibrosis based on TLR4-mediated pyroptosis pathway
Fangjun WEN ; Lei GAO ; Yimin HU ; Kaihu SHI
China Pharmacy 2023;34(9):1053-1059
		                        		
		                        			
		                        			OBJECTIVE To investigate the effects of salidroside (Sal) on myocardial fibrosis and pyroptosis and its potential mechanism. METHODS The mice were randomly divided into control group, model group and Sal low-dose, medium-dose and high-dose groups, with 10 mice in each group. Except for the control group, the mice in other groups were injected subcutaneously with isoproterenol 5 mg/(kg·d)to prepare the myocardial fibrosis model. Since modeling, mice in the Sal low-dose, medium-dose and high-dose groups were given 10, 30 and 50 mg/kg of Sal by intragastric administration every day; control group and model group were given 10 mL/kg of normal saline by intragastric administration every day, for 14 consecutive days. After the last medication, the mice were sacrificed; hematoxylin-eosin staining was used to observe pathological change of myocardial tissue and calculate the diameter of myocardial cell; Masson and Sirius Red staining were used to observe the degree of myocardial fibrosis in mice and calculate the collagen volume fraction (CVF); quantitative real-time PCR was performed to detect the mRNA expressions of collagen type Ⅰ (Col Ⅰ), α-smooth muscle actin (α-SMA), Toll-like receptor 4 (TLR4), NOD-like receptor pyrin domain containing 3 (NLRP3), caspase-1 andgasdermin D (GSDMD) in myocardial tissues. The total protein expressions of Col Ⅰ, α-SMA, TLR4, NLRP3,caspase-1 and GSDMD in myocardial tissues and protein-positive cell score were measured by Western blot assay and immunohistochemistry. RESULTS Compared with control group, the myocardial cells in the model group were enlarged, the arrangement of myocardial fibers was disordered, the matrix metabolism was significantly increased, the CVF in myocardial tissue was significantly increased, and the mRNA and protein expression levels of Col Ⅰ, α-SMA, TLR4, NLRP3, caspase-1 and GSDMD were elevated and protein-positive cell score was increased significantly (P<0.01). Compared with model group, the myocardial cell morphology was clearer, myocardial fibrosis was alleviated, and the levels of the above indicators in myocardial tissue of Sal medium-dose and high-dose groups had been reversed to varying degrees, especially in Sal high-dose group(P<0.05 or P<0.01). In addition, the Sal low-dose group also reversed some fibrosis and pyroptosis-related indicators to some extent. CONCLUSIONS Sal can significantly prevent the occurrence and development of myocardial fibrosis, and the mechanism of action may be related to the inhibition of TLR4-mediated pyroptosis pathway in myocardial tissue.
		                        		
		                        		
		                        		
		                        	
2.Effect and Mechanism of RBM8A on Proliferation, Migration and Apoptosis of Human Endometrial Cancer HEC-1A Cells
Dongmei TAN ; Jingjing ZHANG ; Yimin SHI ; Sai HAN ; Wei GENG ; Jianyi SUN ; Yayu WANG ; Xiurong ZHANG
Cancer Research on Prevention and Treatment 2023;50(1):27-32
		                        		
		                        			
		                        			Objective To investigate the effect of silenced RBM8A gene on the biological behavior (proliferation, migration, and apoptosis) of human endometrial cancer HEC-1A cells and its possible mechanism. Methods The hairpin shRNA targeted by the RBM8A gene was designed, and the best shRNA silencing fragment was screened. The recombinant lentiviral interference vector carrying the target gene was constructed and used to infect HEC-1A cells. Cells with stable knockdown of RBM8A gene were screened by puromycin as the experimental group (shRBM8A), while the shRNA of nonsense sequence was designed as the control group (shControl). CCK-8 method was used to detect cell proliferation, and flow cytometry was used to detect cell apoptosis. Transwell assay was used to detect cell migration and invasion. Western blot was used to analyze the expression of apoptosis-related proteins and EMT signal transduction pathway related proteins. Results In comparison with the shControl group, after RBM8A knockdown, HEC-1A cell proliferation was reduced, apoptosis was increased, migration and invasion ability were significantly inhibited (
		                        		
		                        	
3.Mechanism of osteoclast stimulatory transmembrane protein promoting silicosis fibrosis by inducing ferroptosis
Jing WU ; Cuiyun ZUO ; Yanyan KE ; Jie WANG ; Yaping XU ; Wei DU ; Yimin SHI ; Yunyang ZHUANG ; Xue YI
Journal of Environmental and Occupational Medicine 2023;40(11):1257-1263
		                        		
		                        			
		                        			Background Osteoclast stimulatory transmembrane protein (OC-STAMP) is involved in silicosis fibrosis induced by silicon oxide (SiO2) exposure. Its role in silicosis fibrosis by inducing ferroptosis of alveolar type II epithelial cells and its related mechanism remain unclear. Objective To explore the effect and possible mechanism of OC-STAMP on ferroptosis of alveolar type II epithelial cells and silicosis fibrosis in rats under SiO2 exposure. Methods Twenty male Wistar rats of SPF grade were randomly divided into two groups: control (Sham) group and SiO2 group, 15 rats in each group. Rats in the SiO2 group were given 1 mL of 50 mg·L−1 SiO2 suspension at one time through the non-exposed intratracheal instillation method to establish an animal model of silicosis, and rats in the Sham group were give 1 mL of 0.9% sodium chloride solution in the same way. Rats were sacrificed after 8 weeks. Samples of lung tissue were fixed in glutaraldehyde or paraformaldehyde for observing ultrastructure of mitochondria by transmission electron microscopy; HE, Masson, VG, and Prussian blue were used to observe changes in lung tissue structure and iron deposition. The expression level of OC-STAMP and the degree of lung fibrosis were evaluated by immunohistochemistry and immunofluorescence. The expression level of OC-STAMP in rat lung tissue was detected and the transfection effect of OC-STAMP was verified by real-time fluorescence quantitative polymerase chain reaction (RT-PCR). Overexpression (OCS group) and inhibition expression (SI-OC group) models were constructed by OC-STAMP plasmid and OC-STAMP small interfering RNA (siRNA) transfection to cultured MLE-12 cells, respectively. The relative expression levels of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and other proteins in lung tissue and MLE-12 were detected by Western blotting. Results The results of HE, Masson, and VG staining showed that the silicosis modeling was successful after 8 weeks of SiO2 exposure. The immunofluorescence results showed that OC-STAMP and ATP binding cassette subfamily A member 3 (ABCA3) co-localized in alveolar type II epithelium. The immunohistochemical results showed that the levels of OC-STAMP and collagen I in the SiO2 group were significantly higher than those in the Sham group (P<0.01). The RT-PCR results showed that the OC-STAMP mRNA in the lung tissue of the SiO2 group was significantly higher than that of the Sham group (P<0.01). The Prussian blue staining in the lung tissue of the SiO2 group showed positive brownish-yellow particles. Compared with the Sham group which showed normal mitochondrial structure, the mitochondrial structure was generally swollen and the mitochondrial cristae dissolved and disappeared in the SiO2 group by transmission electron microscope observation. The Western blotting results showed that the expression levels of SLC7A11 and GPX4 both decreased in the lung tissue of the SiO2 group (P<0.05, P<0.01), and the expression level of Vimentin increased (P<0.01). In the transfected MLE-12 cells, compared with the Sham group, the expression levels of SLC7A11 and GPX4 in the OCS group were significantly reduced (P<0.05, P<0.01). Conclusion OC-STAMP may affect the expression of proteins related to ferroptosis, and promote lung fibrosis induced by SiO2 exposure.
		                        		
		                        		
		                        		
		                        	
4.Correlation between preoperative inflammatory biomarkers and postoperative pneumonia or long-term prognosis in patients with esophageal cancer after neoadjuvant therapy
Xiangyu ZHANG ; Yushang YANG ; Qixin SHANG ; Yimin GU ; Guidong SHI ; Hanlu ZHANG ; Xiaoyang LI ; Longqi CHEN
Chinese Journal of Surgery 2021;59(8):660-666
		                        		
		                        			
		                        			Objective:To examine the correlation between neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR) and neutrophil-monocyte ratio (NMR) for postoperative pneumonia or long-term overall survival in patients with esophageal cancer after neoadjuvant therapy.Methods:The clinical data of 137 patients, including 111 males and 26 females, with the age of ( M( Q R))61(10) years (range: 45 to 75 years), undergoing radical resection of esophageal cancer after neoadjuvant therapy admitted at Department of Thoracic Surgery, West China Hospital from January 2016 to May 2019 were analyzed retrospectively. The blood routine one or two days before surgery and the occurrence of pneumonia after surgery were collected via hospital information system. The absolute count of neutrophils, lymphocytes and monocytes was recorded, to calculate NLR, LMR and NMR. The survival of patients was recorded systematically via follow-up. In the first part, the influencing factors of postoperative inflammation were analyzed, to group the patients into two groups according to the occurrence of postoperative pneumonia. χ 2 test, t-test or rank-sum test were conducted for inter-group comparison. In the second part, cut-off values of inflammatory biomarkers were obtained with the receiver operating characteristic (ROC) curve and grouped, with postoperative pneumonia as endpoint criteria. Independent factors correlated with postoperative pneumonia were determined through univariate and multivariate Logistic regression analysis. In the third part, the analysis on prognosis factors was carried on, with the survival as endpoint criteria. Cut-off values of inflammatory biomarkers were obtained with X-Tile software and grouped. The survival analysis was carried on with univariate and multivariate Cox proportional hazards regression model, and the Kaplan-Meier curve was drawn finally. The results of survival analysis were verified by Log-rank test. Results:Median follow-up time was 614 (299) days (range: 382 to 1 612 days). Cut-off values of NLR, LMR, and NMR obtained via the ROC curve were 3.0, 3.9, and 6.2, respectively. According to the multivariate Logistic regression analysis, NLR>3.0 ( OR=2.740, 95% CI: 1.221 to 6.152, P=0.015) and LMR>3.9 ( OR=0.140, 95% CI: 0.022 to 0.890, P=0.037) were independent prognosis factors for postoperative pneumonia in patients with esophageal cancer after neoadjuvant therapy. Cut-off values of NLR, LMR, and NMR obtained with X-Tile software were 3.3, 4.2, and 7.2, respectively. Through multivariate Cox proportional risk regression analysis, late tumor ypTNM staging (8th AJCC) ( HR=2.087, 95% CI:1.079 to 4.038, P=0.029), poor pathologic response ( HR=2.251, 95% CI: 1.117 to 4.538, P=0.023), and LMR>4.2 ( HR=0.347, 95% CI: 0.127 to 0.946, P=0.039) could be independent prognosis factors for overall survival. Kaplan-Meier survival analysis indicated that the overall survival of patients with LMR ≤4.2 was worse ( P=0.002), with the 1-year overall survival rate of 82.9%, and the 1-year overall survival rate of patients with LMR>4.2 was 94.6%. Conclusion:Preoperative LMR ≤3.9 and NLR>3.0 can be considered as independent prognosis factors for postoperative pneumonia, while LMR≤4.2 as one of independent prognosis factors for overall survival.
		                        		
		                        		
		                        		
		                        	
5.Correlation between preoperative inflammatory biomarkers and postoperative pneumonia or long-term prognosis in patients with esophageal cancer after neoadjuvant therapy
Xiangyu ZHANG ; Yushang YANG ; Qixin SHANG ; Yimin GU ; Guidong SHI ; Hanlu ZHANG ; Xiaoyang LI ; Longqi CHEN
Chinese Journal of Surgery 2021;59(8):660-666
		                        		
		                        			
		                        			Objective:To examine the correlation between neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR) and neutrophil-monocyte ratio (NMR) for postoperative pneumonia or long-term overall survival in patients with esophageal cancer after neoadjuvant therapy.Methods:The clinical data of 137 patients, including 111 males and 26 females, with the age of ( M( Q R))61(10) years (range: 45 to 75 years), undergoing radical resection of esophageal cancer after neoadjuvant therapy admitted at Department of Thoracic Surgery, West China Hospital from January 2016 to May 2019 were analyzed retrospectively. The blood routine one or two days before surgery and the occurrence of pneumonia after surgery were collected via hospital information system. The absolute count of neutrophils, lymphocytes and monocytes was recorded, to calculate NLR, LMR and NMR. The survival of patients was recorded systematically via follow-up. In the first part, the influencing factors of postoperative inflammation were analyzed, to group the patients into two groups according to the occurrence of postoperative pneumonia. χ 2 test, t-test or rank-sum test were conducted for inter-group comparison. In the second part, cut-off values of inflammatory biomarkers were obtained with the receiver operating characteristic (ROC) curve and grouped, with postoperative pneumonia as endpoint criteria. Independent factors correlated with postoperative pneumonia were determined through univariate and multivariate Logistic regression analysis. In the third part, the analysis on prognosis factors was carried on, with the survival as endpoint criteria. Cut-off values of inflammatory biomarkers were obtained with X-Tile software and grouped. The survival analysis was carried on with univariate and multivariate Cox proportional hazards regression model, and the Kaplan-Meier curve was drawn finally. The results of survival analysis were verified by Log-rank test. Results:Median follow-up time was 614 (299) days (range: 382 to 1 612 days). Cut-off values of NLR, LMR, and NMR obtained via the ROC curve were 3.0, 3.9, and 6.2, respectively. According to the multivariate Logistic regression analysis, NLR>3.0 ( OR=2.740, 95% CI: 1.221 to 6.152, P=0.015) and LMR>3.9 ( OR=0.140, 95% CI: 0.022 to 0.890, P=0.037) were independent prognosis factors for postoperative pneumonia in patients with esophageal cancer after neoadjuvant therapy. Cut-off values of NLR, LMR, and NMR obtained with X-Tile software were 3.3, 4.2, and 7.2, respectively. Through multivariate Cox proportional risk regression analysis, late tumor ypTNM staging (8th AJCC) ( HR=2.087, 95% CI:1.079 to 4.038, P=0.029), poor pathologic response ( HR=2.251, 95% CI: 1.117 to 4.538, P=0.023), and LMR>4.2 ( HR=0.347, 95% CI: 0.127 to 0.946, P=0.039) could be independent prognosis factors for overall survival. Kaplan-Meier survival analysis indicated that the overall survival of patients with LMR ≤4.2 was worse ( P=0.002), with the 1-year overall survival rate of 82.9%, and the 1-year overall survival rate of patients with LMR>4.2 was 94.6%. Conclusion:Preoperative LMR ≤3.9 and NLR>3.0 can be considered as independent prognosis factors for postoperative pneumonia, while LMR≤4.2 as one of independent prognosis factors for overall survival.
		                        		
		                        		
		                        		
		                        	
7. Preliminary analysis of the factors influencing the secondary external auditory canal carcinoma of nasopharyngeal cancer
Shuang MA ; Liting LI ; Yujia MA ; Juntian SHI ; Changfeng ZHOU ; Yimin LIU ; Jie CHEN
Chinese Journal of Radiation Oncology 2019;28(9):657-659
		                        		
		                        			 Objective:
		                        			In order to investigate the clinical features and influence factors for incidence in patients with radiation-induced external auditory canal carcinoma (RIEACC).
		                        		
		                        			Methods:
		                        			The nasopharyngeal carcinoma (NPC) 16 patients who were diagnosised RIEACC after radiotherapy in the Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University from January 1990 to December 2017 were retrospectively analysis. The influence factors analysis were used 
		                        		
		                        	
8.Analysis of the characteristics of multi-drug resistant acinetobacter baumannii infection in elderly patients with severe respiratory
Mei JING ; Baimei XIE ; Xiulian GU ; Yimin HU ; Jiali XU ; Huaqin WANG ; Songli XU ; Chunyan SHI
Chinese Journal of Geriatrics 2017;36(5):533-536
		                        		
		                        			
		                        			Objective To investigate the clinical characteristics of multiple drug resistant Acinetobacter baumannii infection in respiratory elderly patients.Methods A total of 102 elderly patients infected with multidrug-resistant Acinetobacter baumannii were enrolled in our hospital from January 2014 to December 2015.At the same time,no multiple drug-resistant Acinetobacter baumannii infection elderly patients was selected as a control group.The gender,age,antimicrobial use,white blood cell count,mechanical ventilation time and other differences between the two groups of elderly patients were compared.Results There were significant differences in the days of hospitalization [(18.7±7.5) d vs.(10.0±2.7)d],the time of application of invasive ventilator[(24.6±10.3) d vs.(11.6±6.9)d] and the time of application of antimicrobial agents[(26.2±13.1) d vs.(8.0±2.6)d] (t=19.463、15.436、26.905,all P< 0.05).There was no significant difference in immunosuppressant use,white blood cell count,serum protein level and APACHEⅡ score (all P>0.05).Conclusions Reasonable scientific application of antimicrobial agents,reducing invasive mechanical ventilation time and improving patient immunity can help to reduce the risk of respiratory infection in elderly patients with multiple drug resistance to Acinetobacter baumannii.
		                        		
		                        		
		                        		
		                        	
9.Effect of bronchoalveolar lavage with fiberoptic bronchoscopy combined with vibration sputum drainage on mechanically ventilated patients with severe pneumonia: a prospective randomized controlled trial in 286 patients
Zeya SHI ; Yuelan QIN ; Yimin ZHU ; Xiaoji PAN ; Xu ZHOU ; Yuting TAN ; Yanhui LIU
Chinese Critical Care Medicine 2017;29(1):66-70
		                        		
		                        			
		                        			Objective To investigate the curative effect of bronchoalveolar lavage with fiberoptic bronchoscopy combined with vibration sputum drainage in the treatment of severe pneumonia patients undergoing mechanical ventilation (MV).Methods A prospective randomized controlled trial was conducted. 286 severe pneumonia patients undergoing MV admitted to intensive care unit (ICU) of Hunan People's Hospital from January 2014 to July 2016 were enrolled, and they were divided into control group and observation group according to random number table, with 143 patients in each group. Patients in both groups received sensitive antibiotics for anti-infection, etiological treatment, and calefacient and humidifying treatment. The patients in the control group received bronchoalveolar lavage with fiberoptic bronchoscopy, and those in the observation group received bronchoalveolar lavage combined with vibration sputum drainage. The parameters of respiratory function and inflammation before and after treatment, curative effect, and prognosis were compared between the two groups.Results ① There were no significant differences in respiratory function parameters between the two groups before treatment, 2 hours after treatment, the parameters were improved in both groups. Moreover, oxygenation index (PaO2/FiO2) in observation group was significantly higher than that of control group [mmHg (1 mmHg = 0.133 kPa): 379.1±20.2 vs. 351.8±24.7], and arterial partial pressure of carbon dioxide (PaCO2) and airway resistance (Raw) were significantly lower than those of the control group[PaCO2 (mmHg): 36.5±5.8 vs. 45.3±6.9, Raw (cmH2O, 1 cmH2O = 0.098 kPa): 12.9±0.6 vs. 13.1±0.8, allP < 0.01]. ② There were no significant differences in inflammation parameters between the two groups before treatment, 24 hours after intervention, which were significantly decreased in both groups. Moreover, white blood cell count (WBC), procalcitonin (PCT) and C-reactive protein (CRP) in the observation group were significantly lower than those of the control group [WBC (×109/L): 8.2±1.7 vs. 12.8±3.7, PCT (μg/L): 15.4±2.4 vs. 21.8±3.1, CRP (mg/L): 37.1±6.1 vs. 67.2±7.2, allP < 0.01]. ③ Compared with the control group, the treatment efficiency of observation group was improved [95.1% (136/143) vs. 87.4% (125/143)], the quantity of sputum excretion was increased (mL: 49.2±12.5 vs. 36.9±11.0), duration of MV and length of ICU stay were significantly shortened (days: 6.4±3.6 vs. 9.4±2.1, 8.6±5.7 vs. 12.4±4.6, bothP < 0.01), however, there was no significantly statistical difference in 28-day mortality between control group and observation group [2.8% (4/143) vs. 2.1% (3/143),P > 0.05].Conclusion Compared with bronchoalveolar lavage with fiberoptic bronchoscopy alone, the treatment of bronchoalveolar lavage combined with vibration sputum drainage is more effective in sputum excretion for severe pneumonia patients undergoing MV, which could improve the respiratory function, reduce infection, shorten the duration of MV and the length of ICU stay, and improve the recovery.
		                        		
		                        		
		                        		
		                        	
10.Clinical and etiological characteristics of secondary nosocomial bacterial infections associated with infectious mononucleosis in children
Tao WANG ; Yimin HUA ; Kaiyu ZHOU ; Xiaoqin WANG ; Xiaoqing SHI ; Qiuhong LUO ; Lina QIAO
Chinese Journal of Applied Clinical Pediatrics 2017;32(22):1717-1720
		                        		
		                        			
		                        			Objective To investigate the clinical manifestations and pathogenic characteristics of nosocomial bacterial infection in children with infectious mononucleosis (IM).Methods A retrospective analysis was performed for IM children from January to December 2015 in West China Second University Hospital.According to whether there was the process of secondary bacterial infection,the patients were divided into the secondary infection group and the non-infection group.The clinical manifestations and pathogenic bacteria were analyzed.Results Two hundred and sixteen children with IM were enrolled,of whom,177 cases (81.9%) were in the non-infection group,and 39 cases (18.1%) were in the secondary infection group.The patients in non-infection group were (4.7 ± 3.2) years old,and the patients in secondary infection group were (7.0 ± 3.8) years old,and the difference was statistically significant (t =3.066,P < 0.05).The secondary infection group included bacterial tonsillitis in 17 cases,bronchial pneumonia in 11 cases,otitis media in 5 cases,cervical bacterial lymphadenitis in 3 cases,periorbital cellulitis in 2 cases,and sepsis in 1 case.Meanwhile,3 cases of concomitant thrush were observed in the secondary infection group.The rate of nosocomial bacterial infection in IM children [18.1% (39/216 cases)] was significantly higher than the incidence of nosocomial infection [1.53% (644/41 992 cases)] in the same period,and the difference was statistically significant (x2 =368.474,P < 0.01).The patients with secondary bacterial infection were treated with antibiotics,and the pathogenic bacteria were mainly gram-negative bacteria,which was consistent with pharyngeal tonsil colonization bacteria on admission.In 212 cases (98.1%) with IM,variant lymphocytes increased,and there was no significant difference between 2 groups in the variation of lymphocyte composition (x2 =2.087,P > 0.05).C-reactive protein (CRP) level of IM children on admission was (11.3 ± 17.4) mg/L,while the secondary infection group was (10.2 ±9.7) mg/L and the non-infection group was (11.5 ± 18.1) mg/L,and there was no significant difference between the 2 groups (t =1.309,P > 0.05).CD3 +,CD4+,CD8 + lymphocytes in the secondary infection group were 0.877 6 ± 0.031 8,0.079 0 ± 0.032 5 and 0.682 1 ± 0.053 5,compared with the non-infection group,while CD3 + lymphocytes (t =12.652,P < 0.01) and CD8 + lymphocytes (t =-9.723,P < 0.01) increased significantly,but the proportion of CD4+ lymphocytes decreased significantly (t =18.341,P <0.01).Conclusions The IM children are susceptible to nosocomial bacterial infection,which is more obvious in school-age children.Secondary respiratory tract infections are the most common type,and pathogenic bacteria may be caused by the dissemination of colonization bacteria in the pharyngeal tonsils.The CRP and variant lymphocytes on admission could not be used as the marker for predicting noscoomial bacterial infection in IM.
		                        		
		                        		
		                        		
		                        	
            
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