1.Erythropoietin-overexpressed umbilical cord mesenchymal stem cells inhibit neuroapoptosis in ischemic-hypoxic SH-SY5Y and its mechanism
Ruibo LI ; Ning KONG ; Lei SUN ; Baodong MA ; Ranran JIN ; Wenjin ZHANG ; Han YUE ; Hui ZHANG
Chinese Journal of Tissue Engineering Research 2024;28(31):4937-4944
BACKGROUND:Previous studies have successfully constructed erythropoietin-overexpressed umbilical cord mesenchymal stem cells.It was found that the apoptosis of ischemic and hypoxic human neuroblastoma cell line(SH-SY5Y)was significantly reduced by erythropoietin-overexpressed umbilical cord mesenchymal stem cells. OBJECTIVE:To explore the possible neuroprotective mechanisms of erythropoietin-overexpressed umbilical cord mesenchymal stem cells against ischemic-hypoxic SH-SY5Y and their associated epigenetic mechanisms. METHODS:Oxygen-glucose deprivation was applied to ischemia-hypoxia-induced SH-SY5Y cell injury,and multifactorial assays were applied to detect the expression levels of inflammatory factors in the cells before and after hypoxia and co-culture,respectively,with mesenchymal stem cells,as well as lentiviral-transfected null-loaded plasmids of the negative control mesenchymal stem cells and erythropoietin-overexpressed umbilical cord mesenchymal stem cells.The expression levels of supernatant inflammatory factors were detected by multifactor assay after co-culture.Proteomics was used to detect the differentially expressed proteins of negative control mesenchymal stem cells and erythropoietin-overexpressed umbilical cord mesenchymal stem cells.Cleavage under targets and tagmentation sequencing was applied to detect genomic H3K4me2 modification,and joint analysis was conducted with RNA-sequencing.Lentiviral vector infection was applied to construct the stable knockdown of REST in SH-SY5Y cells.qRT-PCR and western blot assay were performed to detect the expression level of REST.The apoptosis was detected by flow cytometry after co-culture of oxygen-glucose deprivation treatment with erythropoietin-overexpressed umbilical cord mesenchymal stem cells.The expression difference of H3K36me3 group proteins was detected by western blot assay,and transcriptome sequencing was performed to analyze the differentially expressed genes. RESULTS AND CONCLUSION:(1)Compared with the control group,monocyte chemotactic protein 1,interleukin-6,interleukin-18,and interleukin-1 beta,interferon α2,and interleukin-23 levels significantly increased in the cerebrospinal fluid supernatant of patients with ischemic-hypoxic encephalopathy(P<0.01).(2)After co-culturing SH-SY5Y cells with erythropoietin-overexpressed umbilical cord mesenchymal stem cells under ischemia and hypoxia,the expression levels of monocyte chemotactic protein 1 and interleukin-6 were significantly reduced.(3)Analysis of protein network interactions revealed significant downregulation of monocyte chemotactic protein 1,interleukin-6 related regulatory proteins CXCL1 and BGN.(4)Transcriptome sequencing analysis found that pro-inflammatory genes were down-regulated,and functional enrichment of histone modifications,and the expression of transcription factors REST and TET3 significantly up-regulated in the erythropoietin-overexpressed umbilical cord mesenchymal stem cell group compared with the negative control mesenchymal stem cell group.(5)Combined analysis of transcriptome sequencing and cleavage under targets and tagmentation revealed changes in epigenetic levels as well as significant activation of the promoter regions of transcription factors REST and TET3.(6)Stable knockdown REST in SH-SY5Y cells was successfully constructed;the transcript levels of REST mRNA and protein expression were both decreased.(7)After the REST knockdown SH-SY5Y cells were co-cultured with erythropoietin-overexpressed umbilical cord mesenchymal stem cells,apoptosis was significantly increased and H3K36me3 expression was significantly decreased.Transcriptome sequencing results showed that the expression of inflammation-related genes Aldh1l2 and Cth,as well as apoptosis-suppressor genes Mapk8ip1 and Sod2 was reduced at mRNA transcription level(P<0.01).(8)It is concluded that erythropoietin-overexpressed umbilical cord mesenchymal stem cells activated the expression of REST and TET3 by altering the kurtosis of H3K4me2 and upregulated the modification level of H3K36me3,which in turn regulated the expression of inflammation-related genes Aldh1l2 and Cth,as well as apoptosis-suppressor genes Mapk8ip1 and Sod2,and facilitated neuronal survival.
2.Correlation between disease perception and partner support in erectile dysfunction patients
Zhiqin CAO ; Li ZHANG ; Zhiping WU ; Yao FU ; Xingfeng CHEN ; Wenjin ZHANG
Journal of Modern Urology 2024;29(2):175-178
【Objective】 To investigate the status quo of disease perception and partner support of erectile dysfunction (ED) patients, and to analyze their correlation. 【Methods】 With convenient sampling method, 220 ED patients in a first-class hospital in Taiyuan were surveyed with the short version of disease perception questionnaire (BIPQ) and partner support coping questionnaire (DCI). 【Results】 The BIPQ score was (41.90±7.33), and the DCI score was (116.79±20.37). Pearson correlation analysis showed that except life influence, treatment control and emotional influence, the mutual support dimension of partner support of ED patients was correlated with all dimensions of disease perception (r=-0.173, 0.151, -0.182, 0.163, 0.188,P<0.05).Except cognitive comprehension, the negative support dimension of partner support of ED patients was correlated with the dimensions and total score of disease perception (r=0.399, 0.185, -0.167, -0.306, 0.269, 0.445, 0.320, 0.357,P<0.05). 【Conclusion】 ED patients have negative disease perception, and their partners have better coping strategies. Medical staff may pay more attention to partner support so as to reduce patients’ negative perception of disease and promote recovery.
3.Relation between self-perceived burden and quality of life in liver transplant recipients:the effecting path of anxiety and depression
Yun GUO ; Lina ZHOU ; Feng ZHANG ; Yumei CHEN ; Zonghui BU ; Wenjin WAN ; Yu WANG
Sichuan Mental Health 2024;37(5):444-450
Background Self-perceived burden,anxiety and depression are among the most important factors affecting quality of life.At present,there is a lack of understanding on the research status and influencing factors of self-perceived burden in liver transplant recipients.Previous studies have shown that self-perceived burden,anxiety,depression and quality of life are correlated in pairs,but the effecting path among the three are not yet clear.Objective To explore the correlation of self-perceived burden and anxiety/depression with quality of life in liver transplant recipients,so as to provide guidance for psychological nursing intervention in clinical patients.Methods A total of 200 patients liver transplant recipients were enrolled from the liver transplantation inpatient and outpatient clinics of Jiangsu Province Hospital and Qinhuai Medical Area,General Hosptial of Eastern Theater Command of People's Liberation Army of China from March 2022 to February 2023.Patients were evaluated using Self-perceived Burden Scale(SPBS),Hospital Anxiety and Depression Scale(HADS)and the Chinese version of Post Liver Transplant Quality of Life Questionnaire(pLTQ).Spearman correlation analysis was used to examine the correlation among the scales.A structural equation model using Mplus 8.3 was utilized to testify the relationship among self-perceived burden,anxiety/depression and quality of life in liver transplant recipients.Bootstrap method was used to test the effecting pathway.Results There were statistically significant differences in SPBS scores of liver transplant recipients with different levels of education and fannual family income(H=9.656,18.796,P<0.05).There were statistically significant differences in HADS scores of liver transplant recipients with different numbers of somatic symptoms(H=9.859,P<0.05).There were statistically significant differences in the Chinese version of pLTQ scores of liver transplant recipients with different levels of education,postoperative survival time and numbers of somatic symptoms(H=6.892,8.023,16.099,P<0.05).The total and each dimension scores in SPBS of liver transplant recipients were positively correlated with the total score and anxiety/depression dimension scores in HADS(r=0.464~0.586,0.460~0.593,0.286~0.408,0.464~0.583,P<0.01)and negatively correlated with the total score and each dimension scores in the Chinese version of pLTQ(r=-0.572~-0.416,-0.599~-0.441,-0.365~-0.213,-0.559~-0.428,P<0.01).Structural equation model denoted that self-perceived burden negatively affected quality of life(β=-0.186,P<0.01).Anxiety/depression also negatively affected quality of life(β=-0.679,P<0.01).The self-perceived burden indirectly affected the quality of life of liver transplant recipients through anxiety and depression,with an effect value of-0.429,accounting for 69.76%of the total effect.Conclusion The quality of life in liver transplant recipients may be related to their self-perceived burden and anxiety/depression.Self-perceived burden may affect the quality of life of liver transplant patients through anxiety and depression.
4.Significance of echocardiography in distinguishing between two main subtypes of myocardial amyloidosis
Chong FAN ; Leilei PEI ; Chun YANG ; Tao ZHANG ; Wenjin ZHU ; Shun WANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(5):789-793
Objective To explore the application value of echocardiography in the differential diagnosis of transthyretin cardiac amyloidosis(ATTR-CA)and immunoglobulin light chain cardiac amyloidosis(AL-CA).Methods We conducted a retrospective analysis of echocardiographic parameters of 50 confirmed CA patients diagnosed between November 2021 and January 2024 at The First Affiliated Hospital of Xi'an Jiaotong University,including 6 cases of ATTR and 44 cases of AL.Parameters that could potentially distinguish between the two subtypes were selected using t-tests and x2 tests,and the diagnostic capabilities of these parameters for the two subtypes were analyzed using receiver operating characteristic(ROC)curves.Results There were no statistically significant differences in general characteristics,global longitudinal strain(GLS),ratio of apical to basal strain,ejection fraction to GLS ratio(EFSR),maximum thickness of left ventricular myocardium,relative thickness of left ventricular wall,presence of thickened atrioventricular valves,or presence of enlarged atria between ATTR and AL groups(P>0.05).The interventricular septal thickness was greater than in ATTR group than in AL group(P<0.05),and the E/e'ratio(ratio of spectral Doppler early diastolic peak velocity to tissue Doppler early diastolic peak velocity)was greater in ATTR group than in AL group(P<0.05).ROC curve analysis showed that the areas under the curve for distinguishing between the two subtypes based on interventricular septal thickness and E/e'ratio were 0.891(95%CI:0.792-0.991)and 0.826(95%CI:0.698-0.955),respectively,with a sensitivity of 100.00%and specificity of 95.24%for combined diagnosis.Conclusion Echocardiographic parameters,including E/e'ratio and interventricular septal thickness,may have clinical significance in distinguishing between the two main subtypes of CA in patients.
5.2024 Expert Consensus on Hospital Acquired Infection Control Principles in the Department of Critical Care Medicine
Wenzhao CHAI ; Jingjing LIU ; Xiaoting WANG ; Xiaojun MA ; Bo TANG ; Qing ZHANG ; Bin WANG ; Xiaomeng WANG ; Shihong ZHU ; Wenjin CHEN ; Zujun CHEN ; Quanhui YANG ; Rongli YANG ; Xin DING ; Hua ZHAO ; Wei CHENG ; Jun DUNA ; Jingli GAO ; Dawei LIU
Medical Journal of Peking Union Medical College Hospital 2024;15(3):522-531
Critically ill patients are at high risk for hospital acquired infections, which can significantly increase the mortality rate and treatment costs for these patients. Therefore, in the process of treating the primary disease, strict prevention and control of new hospital infections is an essential component of the treatment for critically ill patients. The treatment of critically ill patients involves multiple steps and requires a concerted effort from various aspects such as theory, management, education, standards, and supervision to achieve effective prevention and control of hospital infections. However, there is currently a lack of unified understanding and standards for hospital infection prevention and control. To address this, in March 2024, a group of experts in critical care medicine, infectious diseases, and hospital infection from China discussed the current situation and issues of hospital infection control in the intensive care unit together. Based on a review of the latest evidence-based medical evidence from both domestic and international sources,
6.Genomic characterization and cluster analysis of Carbapenem-resistant Klebsiella pneumoniae
Lijuan LI ; Ziyang YUAN ; Lu ZHANG ; Rentang DENG ; Lisha LAI ; Wencai HUANG ; Wenjin FU
Chinese Journal of Preventive Medicine 2024;58(9):1372-1378
To investigate the genomic features and perform cluster analysis of Carbapenem-resistant Klebsiella pneumoniae (CRKP) to provide an experimental basis for guiding the prevention and treatment of CRKP infections.A retrospective case-cohort study was conducted on 19 non-redundant CRKP strains isolated from the Tenth Affiliated Hospital of Southern Medical University between January and June 2023. Whole genome sequencing (WGS) and multilocus sequence typing (MLST) were performed to compare genomic features and analyze the resistance genes and homology of the strains.The results showed that the 19 CRKP strains were isolated from 8 different clinical departments, mainly from respiratory specimens. The whole genome sequencing revealed that the genomic lengths of CRKP ranged from 4.90 to 5.85 Mbp, with contigs N50 values>20 kb for each genome. The median overall GC content was 57.0% (50.4%-57.1%). Comparative genomic analysis identified three regions with high genomic variability. WGS detected 32 resistance genes across 11 categories. All 19 strains carried carbapenem resistance genes ( blaKPC-2 and blaOXA-48), blaTEM-1B extended-spectrum β-lactamase resistance genes, qnrS1 quinolone resistance gene, and fosA fosfomycin resistance gene, with each strain carrying only one carbapenemase gene. The detection rate of blaKPC-2 was 94.7% (18/19). MLST identified three sequence types: ST11, ST437 and ST147, with ST11 being predominant (89.5%, 17/19). Clustering analysis based on acquired resistance genes revealed three clonal transmission patterns among strains 72 and 90, and strains 88, 84, 66 and 79.In conclusion, CRKP strains carry multiple resistance genes, and clustering analysis indicating that nosocomial clonal transmission is closely related to acquired resistance genes. The ST11- blaKPC-2 type strain is the predominant clone. Strengthened surveillance and effective control strategies are necessary to reduce nosocomial transmission of CRKP.
7.Analysis of sleep status and impact factor of patients in clinical trials of antineoplastic drugs
Lingjun LI ; Weiying ZHANG ; Wenjin WANG ; Xiuyue YANG ; Yuting HU ; Jing WANG ; Xinlu YAN
Chinese Journal of Practical Nursing 2024;40(29):2279-2284
Objective:To explore the sleep status and impact factor analysis of patients in clinical trials of antineoplastic drugs, and provide a basis for improving the sleep status and impact analysis of patients in clinical trials of antineoplastic drugs.Methods:From April to May 2023, 107 oncology patients in the Phase I Clinical Trial Ward of the Affiliated East Hospital of Tongji University were selected as the research objects by convenient sampling method. The general information questionnaire, Pittsburgh Sleep Quality Index Scale (PSQI), Numeric rating scale (NRS), Generalized Anxiety Disorder Scale (GAD-7) and Depression Self-Ration Tool Scale (PHQ-9). Multivariate Logistic regression analysis methods were used to carry out a cross-sectional investigation and the relevant factors affecting patients′sleep.Results:Totally 103 questionnaires were effectively collected. The 103 patients′ age ranged from 20 to 75 years old, including 61 males and 42 females. 47.57% (49/103) patients in clinical trials of antineoplastic drugs had abnormal sleep. The average score of patients (PSQI) (7.66 ± 3.93) was higher than the average score of the domestic norm (3.88 ± 2.52), and there was significant statistical difference ( t = 9.76, P<0.01). Logistic regression analysis showed that pain ( OR = 3.004, 95% CI 1.135-7.948, P<0.05) and trial cycle ( OR = 0.432, 95% CI 0.191-0.978, P<0.05) were significant risk factors for abnormal sleep quality. Conclusions:The incidence of abnormal sleep quality in patients of clinical trials of antineoplastic drugs is high, but the sleep quality is poor. The factors that affect the sleep quality of patients in clinical trials of antineoplastic drugs are mainly related to the patient′s trial cycle and cancer pain. According to these characteristics, individualized programs should be developed to improve the sleep quality of patients with advanced cancer, so as to improve the quality of life of patients with advanced cancer.
8.Percutaneous radiofrequency ablation of renal tumor under local anesthesia guided by ultrasound and CT
Wenjin YANG ; Xiaofeng WANG ; Haifeng HUANG ; Fan ZHANG ; Shengjie ZHANG ; Guangxiang LIU ; Changwei JI ; Hongqian GUO
Chinese Journal of Urology 2024;45(5):360-365
Objective:To explore the effectiveness and safety of percutaneous radiofrequency ablation for renal tumors, guided by both ultrasound and CT, under local anesthesia.Methods:A retrospective analysis was conducted on the clinical data of 40 patients with renal tumors admitted to Nanjing Drum Tower Hospital between January 2018 and December 2022. This treatment involved ultrasound/CT dual-guided radiofrequency ablation under local anesthesia. The cohort included 33 males and 7 females, with an average age of (61.5±11.9) years old and a body mass index (BMI) of (24.79±3.37) kg/m 2. The tumors were located in the left kidney in 20 cases and the right kidney in 16 cases, with 4 cases involving bilateral renal tumors. There were 44 tumors in 40 patients, with the maximum tumor diameter ranging from 1.0 to 4.0 cm [mean (2.3 ± 0.7) cm]. Distribution by kidney pole was as follows: 15 cases at the upper pole, 21 at the middle pole, and 8 at the lower pole. Of the tumors, 23 were exophytic, 5 were endophytic, and 16 exhibited mixed features. There were 2 patients with multiple metastases before surgery(including 1 patient with bilateral renal tumor). Preoperative serum creatinine level was 68.0(56.5, 87.5)μmol/L, and the estimated glomerular filtration rate (eGFR) was 114.2 (79.6, 132.4) ml/(min·1.73 m 2). All patients underwent renal biopsy before or during radiofrequency ablation. Percutaneous radiofrequency ablation surgery was performed using ultrasound and CT dual guidance on all patients, ensuring complete tumor destruction during the procedure as confirmed by dual positioning. Patients with bilateral tumors underwent two separate surgeries, spaced one month apart. Postoperatively, closely monitor the patient's vital signs and conduct long-term follow-ups to record any recurrence and metastasis. Results:In this series, all 40 procedures (involving 44 renal units) were successfully completed under local anesthesia without any need for blood transfusion, conversion to open surgery, or perioperative deaths. The average radiofrequency ablation time was (9.5 ± 3.6) min. Tumor characteristics included predominantly exophytic growths (23 cases, 52.3%), with 31 cases (70.5%) located more than 7 mm from the collecting system and 28 cases (63.6%) positioned posteriorly. Thirteen cases (29.5%) were entirely outside the polar line. The average R. E.N.A.L. nephrometry score was 6.1±0.2. Pathological examination revealed 34 cases of clear cell carcinoma, 2 of papillary renal cell carcinoma, 4 of unclassified renal cell carcinoma, and 4 benign renal tumors. In this cohort, two patients with bilateral renal tumors exhibited benign tumors on one side, while two other patients had malignant tumors in both kidneys. All 40 malignant tumors identified in 38 cases were classified at stage cT 1a.Postoperative serum creatinine level was 71.5 (59.0, 94.3) μmol/L, showing no statistically significant change from preoperative levels ( P > 0.05). Similarly, the eGFR post-operation was 107.4 (79.7, 132.2) ml/(min·1.73 m 2), which also did not differ significantly from preoperative values ( P > 0.05). There were no postoperative complications of Clavien-Dindo grade ≥Ⅱ, except for one case of severe pain (score 7-10). The follow-up period ranged from 15 to 70 months. Among the 38 cases, 36 patients did not have distant metastasis before surgery. There were 2 patients (5.5%) with local recurrence within 60 months after surgery. Among them, one case relapsed 6 months after radiofrequency ablation and was treated with partial nephrectomy. The patient was followed up for 60 months after the second treatment, and no local recurrence occurred. Another patient relapsed 41 months after surgery and was treated with radiofrequency ablation again. The patient was followed up for 12 months after the second treatment, and no local recurrence occurred. Two patients with distant metastasis before surgery were treated with targeted therapy plus immunotherapy for 12 months after surgery. One case had local recurrence 8 months after surgery and was treated with partial nephrectomy. The patient was followed up for 60 months after partial nephrectomy and no local recurrence occurred. Another patient with bilateral renal tumors developed left kidney recurrence 34 months after radiofrequency ablation, and underwent left partial nephrectomy. The right kidney recurred 42 months after radiofrequency ablation and underwent radiofrequency ablation again. After the second right renal radiofrequency ablation, no local recurrence occurred during 12 months of follow-up. Conclusions:Ultrasound/CT dual-guided percutaneous radiofrequency ablation, performed under local anesthesia for treating renal tumors, has minimal impact on the patient's renal function. The procedure boasts a low complication rate, with no postoperative severe complications. Additionally, the postoperative tumor control is effective, making it a safe and minimally invasive surgical option.
9.Genomic characterization and cluster analysis of Carbapenem-resistant Klebsiella pneumoniae
Lijuan LI ; Ziyang YUAN ; Lu ZHANG ; Rentang DENG ; Lisha LAI ; Wencai HUANG ; Wenjin FU
Chinese Journal of Preventive Medicine 2024;58(9):1372-1378
To investigate the genomic features and perform cluster analysis of Carbapenem-resistant Klebsiella pneumoniae (CRKP) to provide an experimental basis for guiding the prevention and treatment of CRKP infections.A retrospective case-cohort study was conducted on 19 non-redundant CRKP strains isolated from the Tenth Affiliated Hospital of Southern Medical University between January and June 2023. Whole genome sequencing (WGS) and multilocus sequence typing (MLST) were performed to compare genomic features and analyze the resistance genes and homology of the strains.The results showed that the 19 CRKP strains were isolated from 8 different clinical departments, mainly from respiratory specimens. The whole genome sequencing revealed that the genomic lengths of CRKP ranged from 4.90 to 5.85 Mbp, with contigs N50 values>20 kb for each genome. The median overall GC content was 57.0% (50.4%-57.1%). Comparative genomic analysis identified three regions with high genomic variability. WGS detected 32 resistance genes across 11 categories. All 19 strains carried carbapenem resistance genes ( blaKPC-2 and blaOXA-48), blaTEM-1B extended-spectrum β-lactamase resistance genes, qnrS1 quinolone resistance gene, and fosA fosfomycin resistance gene, with each strain carrying only one carbapenemase gene. The detection rate of blaKPC-2 was 94.7% (18/19). MLST identified three sequence types: ST11, ST437 and ST147, with ST11 being predominant (89.5%, 17/19). Clustering analysis based on acquired resistance genes revealed three clonal transmission patterns among strains 72 and 90, and strains 88, 84, 66 and 79.In conclusion, CRKP strains carry multiple resistance genes, and clustering analysis indicating that nosocomial clonal transmission is closely related to acquired resistance genes. The ST11- blaKPC-2 type strain is the predominant clone. Strengthened surveillance and effective control strategies are necessary to reduce nosocomial transmission of CRKP.
10.Single-cell transcriptomics reveals cell atlas and identifies cycling tumor cells responsible for recurrence in ameloblastoma
Xiong GAN ; Xie NAN ; Nie MIN ; Ling RONGSONG ; Yun BOKAI ; Xie JIAXIANG ; Ren LINLIN ; Huang YAQI ; Wang WENJIN ; Yi CHEN ; Zhang MING ; Xu XIUYUN ; Zhang CAIHUA ; Zou BIN ; Zhang LEITAO ; Liu XIQIANG ; Huang HONGZHANG ; Chen DEMENG ; Cao WEI ; Wang CHENG
International Journal of Oral Science 2024;16(2):251-264
Ameloblastoma is a benign tumor characterized by locally invasive phenotypes,leading to facial bone destruction and a high recurrence rate.However,the mechanisms governing tumor initiation and recurrence are poorly understood.Here,we uncovered cellular landscapes and mechanisms that underlie tumor recurrence in ameloblastoma at single-cell resolution.Our results revealed that ameloblastoma exhibits five tumor subpopulations varying with respect to immune response(IR),bone remodeling(BR),tooth development(TD),epithelial development(ED),and cell cycle(CC)signatures.Of note,we found that CC ameloblastoma cells were endowed with stemness and contributed to tumor recurrence,which was dominated by the EZH2-mediated program.Targeting EZH2 effectively eliminated CC ameloblastoma cells and inhibited tumor growth in ameloblastoma patient-derived organoids.These data described the tumor subpopulation and clarified the identity,function,and regulatory mechanism of CC ameloblastoma cells,providing a potential therapeutic target for ameloblastoma.

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