1.Osteopontin activates the PI3K/AKT pathway by upregulating LGALS3BP in promotion of hepatoma cell migration
Linlin DENG ; Riwen AN ; Fangxin ZHAO ; Ting LIN ; Cuihua LIU ; Mei HONG ; Jianqiang WU ; Xuan ZHANG
Chinese Journal of Comparative Medicine 2024;34(2):9-15
		                        		
		                        			
		                        			Objective To investigate the effect and mechanism of osteopontin(OPN)in hepatoma cell migration through galectin-3 binding protein(LGALS3BP).Methods Human hepatoma cell lines SMMC-7721,SMMC-P(stably transfected with empty eukaryotic expression vectors),and SMMC-OPN(stably transfected with the OPN gene)were cultured.mRNA expression levels of OPN and LGALS3BP were measured by RT-qPCR.Western blot assays were used to analyze the relative protein expression of OPN and LGALS3BP and PI3K/AKT pathway.Wound healing assays were performed to explore the cell migration ability.After transfection with LGALS3BP-targeting small interfering RNA(si-LGALS3BP)or negative control small RNA(si-NC)into SMMC-OPN cells,cell migration and relative expression of PI3K/AKT pathway-related proteins were assessed.Results Compared with SMMC-7721 and SMMC-P,the migratory ability of SMMC-OPN cells was significantly reinforced,and expression of LGALS3BP was obviously upregulated at both mRNA and protein levels.Moreover,relative expression of p-PI3K/PI3K and p-AKT/AKT proteins was significantly increased.Wound healing assays showed that the si-LGALS3BP obviously suppressed the migratory ability of SMMC-OPN cells.Furthermore,relative expression of p-PI3K/PI3K and p-AKT/AKT proteins in SMMC-OPN cells was significantly decreased after transfection of si-LGALS3BP.Conclusions OPN activates the PI3K/AKT pathway by upregulating LGALS3BP expression to promote hepatoma cell migration.
		                        		
		                        		
		                        		
		                        	
2.Relationship between the serum CCL28 and SDF-1 levels and the condition and prognosis of chronic obstructive pulmonary disease complicated with pulmonary hypertension
Mei YAN ; Jian LIU ; Linlin LIU
Journal of Chinese Physician 2024;26(10):1535-1539
		                        		
		                        			
		                        			Objective:To investigate the relationship between the expression levels of CC chemokine ligand 28 (CCL28) and stromal cell derived factor-1 (SDF-1) in serum and the condition and therapeutic effect of chronic obstructive pulmonary disease (COPD) complicated with pulmonary hypertension.Methods:A total of 98 COPD patients with pulmonary hypertension admitted to the Affiliated Hospital of Jining Medical College from January 2019 to June 2023 were selected as case group A, 100 COPD patients without pulmonary hypertension were selected as case group B, and 100 healthy volunteers were selected as control group. The serum levels of CCL28 and SDF-1 in the three groups were compared, and the correlation between the serum levels of CCL28 and SDF-1 in patients with COPD combined with pulmonary hypertension and pulmonary artery pressure parameters and pulmonary function indexes was analyzed, and the changes of various indexes in patients with COPD combined with pulmonary hypertension were compared before and after treatment.Results:The levels of CCL28 and SDF-1 in the case group A were significantly higher than those in the case group B and the control group, with statistical significance (all P<0.05). The levels of CCL28 and SDF-1 in the case group B were significantly higher than those in the control group, and the differences were statistically significant (all P<0.05). The mean pulmonary artery pressure (mPAP), pulmonary artery wedge pressure, pulmonary vascular resistance, arterial partial pressure of carbon dioxide (PaCO 2) and percentage of residual total gas volume (RV/TLC) in the case group A were higher than those in the case group B. The partial pressure of arterial blood oxygen (PaO 2), the percentage of forced expiratory volume in the first second to the predicted value (FEV 1 pred%), and the pulmonary carbon monoxide dispersion (DLCO) were lower than those of case group B, and the differences were statistically significant (all P<0.05). Serum CCL28 and SDF-1 levels in the case group A were positively correlated with mPAP and pulmonary wedge pressure (all P<0.05), but not with FEV 1 pred%, RV/TLC and DLCO (all P>0.05). After treatment, the serum levels of CCL28 and SDF-1, mPAP, pulmonary wedge pressure, pulmonary vascular resistance, PaCO 2 and RV/TLC in case group A were significantly decreased compared with before treatment, while PaO 2, FEV 1 pred% and DLCO were significantly increased compared with before treatment, with statistical significance (all P<0.05). Conclusions:The serum levels of CCL28 and SDF-1 in patients with COPD combined with pulmonary hypertension are significantly increased, and are closely related to the severity of pulmonary hypertension. After active treatment, the serum levels of CCL28 and SDF-1 in patients will be significantly reduced.
		                        		
		                        		
		                        		
		                        	
3.Immune Thrombocytopenia Induced by Sintilimab in Lung Cancer: A Case Report and Literature Review.
Jingjing CAI ; Guangxia YANG ; Xuemei ZHANG ; Linlin LIU ; Mei YAN
Chinese Journal of Lung Cancer 2023;26(9):717-720
		                        		
		                        			
		                        			Immune checkpoint inhibitors (ICIs) show unique advantages in the treatment of lung cancer, making the treatment of lung cancer enter the era of immunotherapy, but ICIs will also have adverse reactions, and the incidence of immune-induced hematological toxicity is not very high. Immunotherapy-induced thrombocytopenia is a rare adverse event.We report one case of thrombocytopenia induced by ICIs and review the literature on thrombocytopenia associated with ICIs and discuss the clinical features, possible mechanisms, and optimal treatment. 
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		                        			Humans
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		                        			Purpura, Thrombocytopenic, Idiopathic/drug therapy*
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		                        			Lung Neoplasms/drug therapy*
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		                        			Thrombocytopenia/chemically induced*
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		                        			Antibodies, Monoclonal, Humanized/adverse effects*
		                        			
		                        		
		                        	
4.Serum Anti-Fumarate Hydratase Autoantibody as a Biomarker for Predicting Prognosis of Acute-on-Chronic Liver Failure
Linlin WEI ; Ting WANG ; Sisi CHEN ; Yeying LIU ; Xueying HUANG ; Sujun ZHENG ; Bin XU ; Feng REN ; Mei LIU
Gut and Liver 2023;17(5):795-805
		                        		
		                        			 Background/Aims:
		                        			To investigate the autoantibody against fumarate hydratase (FH), which is a specific liver failure-associated antigen (LFAA) and determine whether it can be used as a biomarker to evaluate the prognosis of acute-on-chronic liver failure (ACLF). 
		                        		
		                        			Methods:
		                        			An immunoproteomic approach was applied to screen specific LFAAs related to differential prognosis of ACLF (n=60). Enzyme-linked immunosorbent assay (ELISA) technology was employed for the validation of the frequency and titer of autoantibodies against FH in ACLF patients with different prognoses (n=82). Moreover, we clarified the expression of autoantibodies against FH in patients with chronic hepatitis B (n=60) and hepatitis B virus-related liver cirrhosis (n=60). The dynamic changes in the titers of autoantibodies against FH were analyzed by sample collection at multiple time points during the clinical course of eight ACLF patients with different prognoses. 
		                        		
		                        			Results:
		                        			Ultimately, 15 LFAAs were screened and identified by the immunoproteomic approach.Based on ELISA-based verification, anti-FH/Fumarate hydratase protein autoantibody was chosen to verify its expression in ACLF patients. ACLF patients had a much higher anti-FH autoantibody frequency (76.8%) than patients with liver cirrhosis (10%, p=0.000), patients with chronic hepatitis B (6.7%, p=0.022), and normal humans (0%, p=0.000). More importantly, the frequency and titer of anti-FH protein autoantibodies in the serum of ACLF patients with a good prognosis were much higher than that of patients with a poor prognosis (83.9% vs 61.5%, p=0.019; 1.41±0.85 vs 0.94±0.56, p=0.017, respectively). The titer of anti-FH autoantibodies showed dynamic changes in the clinical course of ACLF. 
		                        		
		                        			Conclusions
		                        			The anti-FH autoantibody in serum may be a potential biomarker for predicting the prognosis of ACLF. 
		                        		
		                        		
		                        		
		                        	
5.Investigation on the status and influencing factors of caregivers′ empowerment after gastrointestinal tumor surgery
Jing LI ; Huaxia LIU ; Yingying YUAN ; Xiuhong XING ; Mei LI ; Linlin WANG ; Jianli CUI
Chinese Journal of Practical Nursing 2022;38(9):687-694
		                        		
		                        			
		                        			Objective:To describe the status and influencing factors of the empowerment of caregivers after gastrointestinal tumor.Methods:From March 2019 to October 2019, using convenience sampling method, 124 pairs of gastrointestinal tumor patients and caregivers who were hospitalized in the general surgery and anorectal surgery of the department of Shandong Tai′an City Central Hospital and the Second Affiliated Hospital of Shandong First Medical University were selected as the subjects. A general information questionnaire, Main Caregivers′Empowerment Measurement were used as research tools. To investigate the empowerment ability of caregivers of patients with gastrointestinal tumors after operation.Results:The total caregiver′s empowerment score was 168.81 ± 19.49. The scores of each dimension ranged from high to low: relationship with caregivers (3.83 ± 0.43), expectation of care outcomes (3.80 ± 0.43), awareness of caregiving roles (3.70 ± 0.51), caregivers′ subjectivity (3.37 ± 0.60), caregiving beliefs (3.34 ± 0.67), caregiving knowledge and skills (3.27 ± 0.73), personal resources (2.94 ± 0.65), goodwill caregiving (2.85 ± 0.65) , the scruples around (2.75 ± 0.88). Multiple linear regression results showed that, patient gender, whether the disease is first attack, whether the patient is aware of the disease, the caregiver marriage, and the caregiver working status were the influencing factors of the caregiver′s empowerment ability after gastrointestinal tumor operation ( t values were -8.15-8.72, R2=0.62, all P<0.05). Conclusions:There is room for further improvement in the empowerment of caregivers after gastrointestinal tumor surgery, especially in personal resources, goodwill care and scruples around. The results suggest that medical staff should guide caregivers to emancipate their minds, enhance the breadth of empowerment, and promote self care and fast rehabilitation of patients.
		                        		
		                        		
		                        		
		                        	
6.Monomorphic epithelial intestinal T-cell lymphoma: a clinicopathological characteristic analysis
Mei TANG ; Linlin HUANG ; Jing ZHU ; Hong CHEN ; Jing LI ; Wenbo ZHOU ; Liqun YANG
Journal of Leukemia & Lymphoma 2021;30(12):739-743
		                        		
		                        			
		                        			Objective:To investigate the histopathological morphology, immunophenotype, molecular pathological features, clinical prognosis and treatment of monomorphic epithelial intestinal T-cell lymphoma (MEITL).Methods:The clinicopathological data of 5 patients with MEITL in Sichuan Jinyu Medical Laboratory Center Co., Ltd from March 2019 to February 2021 were retrospectively analyzed, and literatures were reviewed. All cases were tested by using histopathology, immunohistochemistry, in situ hybridization of Epstein-Barr virus (EBV) and T-cell clonability assessment, and 1 case had second-generation sequencing (NGS) test. Clinical follow-up was performed in 2 patients.Results:All 5 MEITL cases were middle-aged and old men. The histopathology showed that intestinal wall was diffuse with tumor cells infiltrating, and the cells were obviously epitheliophilic. All the tumor cells CD3, CD8, CD56, GrB were positively expressed, and expressions of other T-cell markers were different, among which 1 case had CD30 positive and 1 case had CD20 positive. All 5 cases were negative for EBV by in situ hybridization. Monoclonal rearrangement of T-cell receptor gene was detected in all 5 cases. Mutations of BCOR, JAK3, STAT5B and ATM were detected in 1 case by using NGS. Among 2 cases followed-up, 1 patient relapsed 7 months after he had the initial onset and underwent the first operation, and then he had another operation. This patient finally died of extensive metastasis in the lung, liver and abdominal cavity as well as ascites 13 months later; another patient died 1 month after emergency surgery for perforation.Conclusions:MEITL is a rare primary T-cell lymphoma of the digestive tract. The oncogenic event in the pathogenesis of MEITL mainly involves mutations in the tumor suppressor gene SETD2 and mutations in one or more genes of the JAK/STAT pathway. Currently, there is no standard treatment for MEITL. Most treatment options include surgical resection and anthracycline-based chemotherapy.
		                        		
		                        		
		                        		
		                        	
7.Correlation of insulin-like growth factor-1 and its receptor in ovarian cancer with clinicopathological features
Linlin MEI ; Xiaona TIAN ; Xujing YAN
Chinese Journal of Endocrine Surgery 2020;14(1):67-71
		                        		
		                        			
		                        			Objective:To study the correlation between insulin-like growth factor-1 (IGF-1) and its receptor IGF-1R expression in ovarian cancer and clinicopathological features, surgical prognosis.Methods:The positive expression rates of IGF-1 and IGF-1R in ovarian cancer, borderline ovarian tumors and benign ovarian tumors were detected by immunohistochemistry. The correlation of IGF-1 and IGF-1R with clinicopathological features, surgical prognosis was analyzed.Results:The positive expression rate of IGF-1 and IGF-1R in ovarian cancer was 65.63%, 70.31%, significantly higher than 22.22%, 16.67% in borderline ovarian tumors, 5.00%, 10.00% in benign ovarian tumors ( χ2/ P=27.548/0.000, 31.335/0.000) . The mRNA and protein expression of IGF-1 and IGF-1R were also significantly higher than borderline ovarian tumors and benign ovarian tumors ( F/P=31.922/0.000, 26.865/0.000, 34.567/0.000, 27.667/0.000) . The positive expression rates of IGF-1 and IGF-1R in ovarian cancer with FIGOIII-IV stage, tissue differentiation G2-G3 stage, CA125>35 U/mL, Ki-67 positive expression were significantly higher than those in ovarian cancer with FIGOI-II stage, tissue differentiation G1 stage, CA125<35 U/mL, Ki-67 negative expression (IGF-1: χ2/ P=8.505/0.004, 4.980/0.026, 7.481/0.006, 10.907/0.001, IGF-1R: χ2/ P=9.785/0.002, 4.950/0.026, 7.211/0.007, 6.471/0.011) . The total survival time of ovarian cancer patients with positive IGF-1 and IGF-1R was shorter than those of patients with negative IGF-1 and IGF-1R. Conclusion:IGF-1 and IGF-1R are highly expressed in ovarian cancer and are associated with the deterioration of pathological features and surgical prognosis.
		                        		
		                        		
		                        		
		                        	
8.Analysis of blood free carnitine levels in preterm infants with respiratory distress syndrome
Wenxin WEI ; Hua MEI ; Linlin LI ; Chunli LIU ; Yanan HU ; Yaqin ZHOU ; Yanbo ZHANG
Chinese Pediatric Emergency Medicine 2020;27(10):726-729
		                        		
		                        			
		                        			Objective:The blood free carnitine levels of preterm infants with neonatal respiratory distress syndrome (NRDS) were detected within 7 days after birth, and the correlation between blood free carnitine levels and NRDS in preterm infants was explored.Methods:Seventy premature infants with gestational ages from 28 to 36 weeks who were admitted to the NICU of the Affiliated Hospital of Inner Mongolia Medical University from January 1, 2017 to December 31, 2019 were selected as the participants.Among them, 35 cases were in the NRDS group, while 35 cases of premature infants without NRDS were chosen as the control group.Heel blood samples were collected from all subjects within 6 hours, 3 days and 7 days after birth, and the levels of blood free carnitine were detected by tandem mass spectrometry.Results:Within 7 days after birth, the levels of free carnitine in blood of premature infants in the two groups gradually decreased with time, but the decreasing trend was not similar( F=4.096, P=0.021). Compared with 6 hours after birth, the blood free carnitine level in NRDS group decreased significantly with 3 days after birth[(35.24±9.58) μmol/L vs.(23.96±7.12) μmol/L, P<0.05]. The levels of blood free carnitine in NRDS group at 6 hours and 3 days after birth were significantly lower than those in control group[(35.24±9.58) μmol/L vs.(40.85±11.39) μmol/L; (23.96±7.12) μmol/L vs.(29.60±8.05) μmol/L, P<0.05]. There was no significant difference in blood free carnitine levels between the two groups at 7 days after birth ( P>0.05). Conclusion:The blood free carnitine levels of premature infants decreased within 7 days after birth.The decrease of carnitine level in premature infants with NRDS may be related to the occurrence and development of NRDS.
		                        		
		                        		
		                        		
		                        	
9.Analysis of the relationship between antimicrobial resistance and integrons of Escherichia coli isolated from community patients with urinary tract infections
Mei CAO ; Muzhen SUN ; Long ZHANG ; Xiaotong WANG ; Nana KONG ; Linlin XIAO ; Quhao WEI
Chinese Journal of Laboratory Medicine 2020;43(4):457-462
		                        		
		                        			
		                        			Objective:To explore the distribution of integrons in Escherichia coli isolated from community patients with urinary tract infections and their relationship with the phylogenetic groups and antimicrobial resistance. Methods:From November 2015 to December 2018, 152 isolates of E. coli that collected without repetition from the urine samples of outpatients in nephrology of Fengxian District Central Hospital in Shanghai, were studied retrospectively. Bacterial identification and antimicrobial susceptibility analysis was carried out by Phoenix 100 automatic microbiological analyzer. Class 1, 2 integron integrase genes, variable regions of integrons and the phylogenetic groups of isolated E.coli were screened by PCR. The type of promoters and gene cassette arrays of variable regions were determined by sequencing. The relationship of intergon with the phylogenetic groups and antimicrobial resistance was also analyzed. Results:The resistance rate of 152 E. coli to ampicillin was 70.39% (107/152), and the resistance rates to other antibacterial drugs were all less than 40.00%. Among the 152 E. coli isolates, class 1 integron integrase gene intI1 was detected in 65 isolates (42.76%), 8 gene cassette arrays and 14 antimicrobial resistance gene cassettes were detected in 68 class 1 integrons. The most popular gene cassette array was dfrA17-aadA5 (51.47%, 35/68), while the variable regions of class 1 integrons were failed to detected in 12 intI1-positive isolates. Five variable region promoters were detected in 68 class 1 integrons, with the relative weak promoter PcH1 to be the most popular type (77.94%, 53/68). The gene cassette array arr- 2-cmlA5-bla OXA-10-aadA1 was also detected in this study. 65 intI1-positive isolates were mainly belonged to group B2 and D. The class 2 integron integrase gene intI2 was detected in 4 isolates (2.63%,4/152), and their variable region gene cassette arrays were all dfrA1-sat2-aadA1. Conclusions:Class 1 integrons were closely related to antimicrobial resistance in E. coli isolated from community patients with urinary tract infection. Most of the variable region promoters of class 1 integrons were relatively weak promoters. The distribution of each phylogenetic group in the intI1-positive isolates was consistent with the distribution of the overall isolates. The gene cassette array arr-2-cmlA5-bla OXA-10-aadA1 was detected in E. coli.
		                        		
		                        		
		                        		
		                        	
10.Distribution of integrons and antimicrobial resistance in carbapenem-resistant Acinetobacter bauman-nii clinical strains
Chengchao XIAO ; Mei CAO ; Long ZHANG ; Nana KONG ; Xiaotong WANG ; Linlin XIAO ; Quhao WEI
Chinese Journal of Microbiology and Immunology 2019;39(4):277-282
		                        		
		                        			
		                        			Objective To investigate the distribution of integrons in clinical isolates of carbapen-em-resistant Acinetobacter baumannii and their relationships to bacterial resistance to antimicrobial agents.Methods A total of 115 carbapenem-resistant Acinetobacter baumannii strains were isolated from clinical samples of patients from January to October, 2017. Phoenix 100 automatic microbiological analyzer was used for antimicrobial sensitivity analysis. Classes 1 and 2 integrase genes and carbapenemase-encoding genes, bla IMP , blaVIM , blaKPC , blaNDM and blaOXA-23 , were screened by PCR. The variable regions of integrons were amplified by long fragment PCR. The types of promoters and gene cassette arrays of variable regions were de-termined by sequencing and overlap PCR. Relationships between integrons and antimicrobial resistance were analyzed. Results The 115 isolates of carbapenem-resistant Acinetobacter baumannii were resistant to most commonly used antimicrobial agents, but sensitive to polymyxin E. All of the isolates carried blaOXA-23 gene and none of them were positive for blaIMP , blaVIM , blaKPC or blaNDM gene. Class 1 integrase gene intI1 was de-tected in 40 isolates (34. 8% ), while class 2 integrase gene intI2 was not detected. Two gene cassette ar-rays of variable regions, aacA4-catB8-aadA1 (39 isolates) and aacC1-gacP-gacQ-aadA1a (23 isolates), were detected in intI1-positive isolates. Twenty-two isolates carried both aacA4-catB8-aadA1 and aacC1-gacP-gacQ-aadA1a. The upstream promoters of the variable regions were relatively strong promoters, PcH2 and PcS. The gene cassettes of the variable regions endowed bacteria with resistance to chloramphenicol and aminoglycoside antibiotics. The resistance rate of class 1 integron-positive isolates to compound sulfamethox-azole was higher than that of negative strains. However, their resistance rate to ampicillin/sulbactam was lower than that of negative strains. Conclusions Antimicrobial resistance in carbapenem-resistant Acineto-bacter baumannii was serious. Carbapenem resistance was associated with blaOXA-23 gene. The types of pro-moters of variable regions in class 1 integrons were all relatively strong promoters. Class 1 integrons were closely related to sulfonamides resistance.
		                        		
		                        		
		                        		
		                        	
            
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