1.Effect and mechanism of reactive oxygen species-responsive nanoparticles on the regulation of human gingival fibroblast function and inflammation induced by lipopolysaccharide
QIU Xinyi ; SONG Lutong ; REN Shuangshuang ; MIAO Leiying
Journal of Prevention and Treatment for Stomatological Diseases 2024;32(4):257-265
		                        		
		                        			Objective:
		                        			To investigate the effects of PssL-NAC reactive oxygen species (ROS)-responsive nanoparticles on intracellular ROS production, inflammatory factor levels, collagen production, cell function and Toll-like receptor 4 (TLR4), NF-κB nuclear factor-κB (p65) pathway protein expression in human gingival fibroblasts (HGFs) induced by Porphyromonas gingivalis-lipopolysaccharide (P.g-LPS).
		                        		
		                        			Methods:
		                        			This study was reviewed and approved by the ethics committee. PssL-NAC microspheres containing oil soluble antioxidant N-acetylcysteine (NAC) were obtained by connecting the hydrophobic end of polycaprolactone (PCL) and the hydrophilic end of polyethylene glycol (PEG) via thioketal (TK) bonds in response to ROS, and self loading in the aqueous and oil phases. After preparation of the PssL-NAC microspheres and aqueous NAC solution, successful synthesis of the nanoparticles was verified by transmission electron microscopy. Then, HGFs were exposed to P.g-LPS (0, 5, or 10 μg/mL), P.g-LPS (0, 5, or 10 μg/mL)+NAC, and P.g-LPS (0, 5, or 10 μg/mL)+PssL-NAC, and the ROS levels in the different groups were observed under confocal microscopy to determine the concentration of P.g-LPS for use in subsequent experiments. The groups were as follows: control group (no treatment), P.g-LPS group (HGFs treated with P.g-LPS), NAC group (HGFs treated with P.g-LPS and NAC), and PssL-NAC group (HGFs treated with P.g-LPS and PssL-NAC). Cell counting kit-8 (CCK-8) assays verified the biosafety of PssL-NAC. The ROS levels in the different groups were detected by DCFH-DA probes and observed via confocal microscopy. Real-time qPCR (RT-qPCR) was used to monitor the gene expression levels of the intracellular inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), collagen 1 (COL1) and collagen 3 (COL3). The effect of PssL-NAC on the migration of HGFs was observed via the scratch test. The protein expression of TLR4-NF-κB, and phosphorylated p65 (p-p65) in the TLR4-NF-κB pathway was evaluated by Western blot.
		                        		
		                        			Results:
		                        			PssL-NAC had no significant effect on HGF proliferation (P>0.05). At elevated P.g-LPS concentrations, PssL-NAC maintained intracellular ROS levels approximately twice those in the control group (P<0.001). PssL-NAC significantly decreased P.g-LPS-induced IL-6 (P<0.001) and TNF-α (P<0.001) gene expression and increased COL1 gene expression (P<0.001). After P.g-LPS stimulation, PssL-NAC restored cell migration to the control level (P>0.05) and decreased the protein expression of TLR4 (P<0.001), p65 (P = 0.006), and p-p65 (P = 0.017) in the TLR4-NF-κB pathway.
		                        		
		                        			Conclusion
		                        			PssL-NAC maintains the appropriate intracellular ROS concentration, alleviates P.g-LPS-induced inflammation in HGFs through the TLR4-NF-κB pathway, and restores the cell functions of collagen production and migration in an inflammatory environment.
		                        		
		                        		
		                        		
		                        	
2.Efficacy of modified electroconvulsive therapy combined with medication in inpatient schizophrenia patients and urban-rural differences
Hongcheng XIE ; Shuangshuang FENG ; Tingting WANG ; Junfan LIANG ; Jiajun REN ; Hongli ZHANG ; Ziyuan LIN ; Siru WANG ; Bo XIANG ; Kezhi LIU
Sichuan Mental Health 2024;37(6):497-501
		                        		
		                        			
		                        			BackgroundCombination of antipsychotic drugs and modified electroconvulsive therapy (MECT) is currently a commonly used method for treating schizophrenia, but its efficacy varies among different patient groups. ObjectiveTo explore the therapeutic effects of MECT on schizophrenia patients living in different urban versus rural environments, so as to provide references for the selection of treatment plans based on patients' residence. MethodsA total of 587 patients hospitalized at Luzhou Mental Health Center, Zigong Mental Health Center and Yibin Fourth People's Hospital from May 2018 to August 2022, who met the diagnostic criteria for schizophrenia in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) ,were included in the study. Patients were divided into two groups: medication-only group (n=106) and MECT combined with medication group (n=481). In MECT combined with medication group, 24 rural patients residing in urban areas were excluded, leaving the remaining patients divided into urban group (n=103) and rural group (n=354) based on their place of residence. Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of symptoms. Clinical efficacy was evaluated using PANSS score reduction rate, and covariance analysis was used to compare the therapeutic effects of different patients. ResultsThe differences of reduction rate of PANSS total score, positive symptom scale score and negative symptom scale score as well as treatment effectiveness rate between MECT combined with medication group and medication-only group were statistically significant (F=11.149, 12.111, 31.725, χ2=14.010, P<0.01). Statistically significant differences were also observed in reduction rate of PANSS total score and positive symptom subscale score as well as treatment effectiveness rate between urban and rural patients in MECT combined with medication group (F=3.946, 4.523, χ2=4.033, P<0.05). ConclusionThe efficacy of MECT combined with medication may be superior to medication alone in the treatment of schizophrenia, and the combined therapy may be more effective in urban patients than that in rural patients, with potentially more pronounced improvements in positive symptoms. 
		                        		
		                        		
		                        		
		                        	
3.Expression of genes associated with homologous recombinant repair defects in endometrial cancer and its relationship with clinicopathologic features and immune infiltration
Jinyun WANG ; Shen ZHANG ; Shuangshuang REN ; Xianping SHANG
Chinese Journal of Postgraduates of Medicine 2024;47(7):617-623
		                        		
		                        			
		                        			Objective:To explore the expression of homologous recombination repair (HRR) deficiency related genes in endometrial cancer and their relationship with clinical pathological features and immune infiltration.Methods:A total of 53 patients with endometrial cancer (endometrial cancer group) who underwent surgical treatment at the Affiliated People′s Hospital of Shandong First Medical University from June 2018 to June 2020 were selected as the study subjects. Clinical data of the patients were retrospectively analyzed, and 50 healthy women who underwent physical examinations were selected as the control group. Clinical and pathological characteristics of 53 patients with endometrial cancer were collected, and real-time fluorescence quantitative polymerase chain reaction (RT-PCR) was performed Methods The mRNA expressions of human breast cancer susceptibility gene 1 (BRCA1), tumor suppressor gene homologous loss phosphatase tensin gene (PTEN) on chromosome 10 in the peripheral blood of the subjects were detected, and the proportions of CD 4+ T cell subsets in peripheral blood monocytes were detected by flow cytometry; Pearson analysis of the correlation between peripheral blood BRCA1, PTEN mRNA expression and various subsets of CD 4+ T cell; Analysis of prognostic factors for endometrial cancer using COX risk regression model. Results:The peripheral blood BRCA1 and PTEN mRNA expression levels in patients with endometrial cancer were higher than those in the healthy control group: 2.87 ± 0.65 vs. 1.02 ± 0.13, 3.25 ± 0.74 vs. 1.01 ± 0.20, and the differences were statistically significant ( P<0.01). The proportion of peripheral blood helper T cell-2 (Th2), helper T cell-17 (Th17), regulatory T cell (Treg) and helper T cell-22 (Th22) in patients with endometrial cancer was significantly higher than that in the healthy control group: (10.72 ± 1.33)% vs. (5.43 ± 0.80)%, (9.78 ± 0.80)% vs. (3.31 ± 0.62)%, (10.81 ± 1.29)% vs. (5.74 ± 0.69)%, (6.09 ± 0.70)% vs. (3.09 ± 0.73)%, and the proportion of helper T cell-1 (Th1) was significantly lower than that in the healthy control group: (5.54 ± 0.90)% vs. (13.07 ± 2.55)%, the difference was statistically significant ( P<0.01). The peripheral blood BRCA1 and PTEN mRNA expression levels were significantly higher in patients with muscle infiltration depth ≥1/2, histological grade G 2 to G 3, lymph node metastasis, and International Federation of Obstetrics and Gynecology (FIGO) stage Ⅲ to Ⅳ than in patients with muscle infiltration depth<1/2, histological grade G 1, no lymph node metastasis, and FIGO stage Ⅰ to Ⅱ, with statistical significance ( P<0.01 or<0.05). Peripheral blood BRCA1 and PTEN mRNA were significantly positively correlated with Th2, Th17, Treg and Th22 ratios ( P<0.01), and negatively correlated with Th1 ratios ( P<0.01). COX risk regression analysis showed that histological grading, FIGO staging, depth of muscle infiltration, peripheral blood BRCA1 and PTEN mRNA expression with lymph node metastasis were all independent prognostic factors for endometrial cancer ( P<0.01 or<0.05). Conclusions:HRR deficiency related genes BRCA1 and PTEN mRNA exhibit high levels in patients with endometrial cancer, and are closely related to muscle infiltration depth, histological grading, lymph node metastasis, and FIGO staging. They can also affect the immune microenvironment of endometrial cancer patients, thereby affecting disease progression and prognosis.
		                        		
		                        		
		                        		
		                        	
4.Surgical treatment and current advances of persistent fetal vasculature syndrome
Jianing REN ; Jie PENG ; Shuangshuang CHEN ; Yihua ZOU ; Peiquan ZHAO
Chinese Journal of Ocular Fundus Diseases 2022;38(2):163-167
		                        		
		                        			
		                        			Persistent fetal vasculature syndrome (PFVS) is a rare congenital vitreous dysplasia, which is classified as anterior, posterior and combined types according to the location of the vascular abnormalities. The clinical manifestations of PFVS are diverse, and early surgical intervention is very important. The main objective of surgical treatment is to remove the anterior and posterior traction between fibrovascular membranes and retina as well as lens, and to reconstruct clear visual axis. Surgical treatments include pupilloplasty, lensectomy with or without intraocular lens implantation and vitrectomy via limbal or scleral approach. For new technologies, the applications of ophthalmic viscosurgical device and femtosecond lasers have desirable results . In addition to focusing on improving the success rate of surgery, it is also necessary to systematically and comprehensively assess the overall preoperative condition and postoperative visual function of the patients. PFVS eyes have limited improvement in postoperative vision, which is related to the extent of lesion involvement and the occurrence of complications. Eyes with macular dysplasia and tractional retinal detachment, as well as elongated ciliary process, have a poor prognosis of vision after surgery. How to improve postoperative vision in the eye affecting the posterior segment of the eye with PFVS from the microscopic anatomical relationship between the fibrous vascular pedicle and the retina is worth further study. On the other hand, reducing surgical trauma and optimizing surgical procedures in order to improve postoperative visual acuity and reduce postoperative complications are also the key research directions of future PFVS treatments.
		                        		
		                        		
		                        		
		                        	
5.Applying artificial intelligence for cancer immunotherapy.
Zhijie XU ; Xiang WANG ; Shuangshuang ZENG ; Xinxin REN ; Yuanliang YAN ; Zhicheng GONG
Acta Pharmaceutica Sinica B 2021;11(11):3393-3405
		                        		
		                        			
		                        			Artificial intelligence (AI) is a general term that refers to the use of a machine to imitate intelligent behavior for performing complex tasks with minimal human intervention, such as machine learning; this technology is revolutionizing and reshaping medicine. AI has considerable potential to perfect health-care systems in areas such as diagnostics, risk analysis, health information administration, lifestyle supervision, and virtual health assistance. In terms of immunotherapy, AI has been applied to the prediction of immunotherapy responses based on immune signatures, medical imaging and histological analysis. These features could also be highly useful in the management of cancer immunotherapy given their ever-increasing performance in improving diagnostic accuracy, optimizing treatment planning, predicting outcomes of care and reducing human resource costs. In this review, we present the details of AI and the current progression and state of the art in employing AI for cancer immunotherapy. Furthermore, we discuss the challenges, opportunities and corresponding strategies in applying the technology for widespread clinical deployment. Finally, we summarize the impact of AI on cancer immunotherapy and provide our perspectives about underlying applications of AI in the future.
		                        		
		                        		
		                        		
		                        	
6.Recent advances in foveal development after treatment for retinopathy of prematurity
Shuangshuang CHEN ; Qi ZHANG ; Jianing REN ; Jie PENG ; Peiquan ZHAO
Chinese Journal of Ocular Fundus Diseases 2021;37(5):394-398
		                        		
		                        			
		                        			Retinopathy of prematurity (ROP) is a proliferative vascular retinal disease. Cryotherapy, laser photocoagulation, intravitreal injection of anti-vascular endothelial growth factor, scleral buckling surgery and vitrectomy are the main treatments. Treated with cryotherapy or laser photocoagulation or intravitreal injection of anti-vascular endothelial growth factor, patients with a history of ROP have thicker foveas, and the morphology of the fovea and the development of the retinal vessels in the macular area are affected, resulting in abnormal vision development. However, the specific mechanisms by which different treatments of ROP affecting the development of the macula are not yet clear. It still need further study with large samples to verify and explore, whether changes in the levels of intraocular vascular endothelial growth factor changing the process of normal macular development and how the abnormal development of the macula affects visual function.
		                        		
		                        		
		                        		
		                        	
7.Diagnostic value of Gd-EOB-DTPA enhanced MRI compared with contrast-enhanced ultrasound for small hepatocellular carcinoma
Tao REN ; Shuangshuang XIE ; Lixiang HUANG ; Chao CHAI ; Wen SHEN
Journal of Practical Radiology 2018;34(5):690-693
		                        		
		                        			
		                        			Objective To compare the diagnostic value of Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced MRI and contrast-enhanced ultrasound (CEUS) in detection of small hepatocellular carcinoma (sHCC).Methods A total of 22 patients with 29 lesions who underwent Gd-EOB-DTPA enhanced MRI and CEUS scan,and confirmed as sHCCs by pathology were included in this study.Gd EOB DTPA enhanced MRI pattern for the conclusive diagnosis of sHCC were lesions showed iso or low signal on T1 WI,showed slightly high signal or high signal on T2 WI,showed high signal on DWI and obviously enhanced in the arterial phase and/or clearance in the hepatobiliary phase;CEUS pattern for the conclusive diagnosis of sHCC were rapidly increasing in the arterial phase and showing low echo in the delay phase.Results The diagnostic sensitivity of detecting sHCC by Gd EOB-DTPA enhanced MRI and CEUS were 82.76% and 65.52% respectively,and there was no statistical difference (x2 =2.248,P=0.134),the diagnosis specificity were both 100 %.Conclusion Both of the diagnostic sensitivity and specificity for detecting sHCC by Gd EOB DTPA enhanced MRI and CEUS showed no difference,the value of diagnostic sensitivity of the former is higher.
		                        		
		                        		
		                        		
		                        	
8.Correlation research of renal perfusion and diffusion function using MRI in renal allograft early after renal transplantation
Lihua CHEN ; Tao REN ; Chenglong WEN ; Fan MAO ; Shuangshuang XIE ; Lixiang HUANG ; Zhen WANG ; Yingxin FU ; Panli ZUO ; Shuang XIA ; Wen SHEN
Chinese Journal of Radiology 2017;51(9):689-694
		                        		
		                        			
		                        			Objective To explore the correlationships between microperfusion diffusion indexes derived from intravoxel incoherent motion(IVIM)and perfusion values measured by arterial spin labeling (ASL)in renal allograft. Methods A total of 76 renal allograft recipients and 26 age-matched volunteers (group 0)were included in this prospective study. All subjects were underwent conventional MRI, IVIM and ASL MRI which were performed in the oblique-sagittal plane. Seventy-six recipients were divided into two groups based on the estimated glomerular filtration rate(eGFR):recipients with good allograft function(group 1, eGFR≥ 60 ml · min-1 · 1.73m-2,n=44)and recipients with impaired allograft function(group 2, eGFR<60 ml · min-1 · 1.73m-2,n=32). Three IVIM indexes values, including true diffusion coefficient(ADCslow), pseudo-diffusion coef fi cient(ADCfast), perfusion fraction(PF), and one ASL index value of renal cortex(renal blood flow, RBF)were measured. One-way analysis of variance and the least significant difference were used to compare the different of each cortical index values among three groups. Correlations between the ADCslow, ADCfast, PF, RBF and eGFR as well as the correlation among the indexes were evaluated using Pearson correlation coefficients. Results For cortical ADCslow, ADCfast, PF and RBF values, allografts with good function and impaired function showed significantly differences compared healthy controls(all P<0.01). In allografts with good function, cortical ADCslow,ADCfast,PF showed no significantly differences compared with controls(all P>0.05), but RBF value was significantly lower(P<0.05). The ADCslow, ADCfast, PF and RBF values of renal cortex were significantly lower in allografts with impaired function compared to allografts with good function(all P<0.01). In renal allografts, there were significant positive correlations between cortical ADCslow, ADCfast, PF, RBF value and eGFR(r values were 0.604, 0.552, 0.579 and 0.673, all P<0.01). Cortical ADCfast and PF value exhibited a significant correlation with RBF for recipients(r values were 0.501 and 0.423, all P<0.01). Conclusion Cortical ADCfast and PF values derived from IVIM and RBF measured by ASL show a significant positive correlation in renal allografts.
		                        		
		                        		
		                        		
		                        	
9.Aterial Spin Labeling Evaluation of Residual Renal Function After Partial Nephrectomy on Renal Cell Carcinoma
Chenglong WEN ; Tao REN ; Lihua CHEN ; Lixiang HUANG ; Shuangshuang XIE ; Chao CHAI ; Qian LIU ; Wen SHEN
Chinese Journal of Medical Imaging 2017;25(7):555-558
		                        		
		                        			
		                        			Purpose To investigate the value of arterial spin labeling (ASL) in evaluating renal function in patients with renal cell carcinoma (RCC) after laparoscopic partial nephrectomy.Materials and Methods Fifteen patients with RCC undergoing laparoscopic partial nephrectomy were studied prospectively.The patients were performed ASL scan one week before and three months after operation.The correlation between renal blood flow (RBF) value measured by ASL and the glomerular filtration rate (GFR) measured by radionuclide method in the renal cortex of healthy side was analyzed.The RBF values in the kidney of affected side or healthy side were measured,the difference of which between before operation and three months after operation was compared.Results The RBF value and GFR data in the renal cortex of healthy side had positive correlation (r=0.638,P<0.05).In the affected side of kidney,the RBF value of remaining renal tissue [(291.5 ± 37.3) ml/(100g·min)] compared with that of preoperative renal tissue [(237.8 ± 46.2) ml/(100g·min)]increased about 53.7 ml/(100g · min) (P<0.05).In the healthy side of kidney,the RBF value of renal tissue [(241.1 ± 50.3) ml/(100 g · min)] compared with that of preoperative renal tissue [(290.4 ± 51.8) ml/(100 g·min)] decreased about 49.3 ml/(100 g·min) (P<0.05).Conclusion ASL can be used to evaluate renal function,and it is valuable to evaluate renal perfusion function after laparoscopic partial nephrectomy of RCC.
		                        		
		                        		
		                        		
		                        	
10.The value of arterial spin labeling MRI for evaluating early renal allograft function
Tao REN ; Chenglong WEN ; Lihua CHEN ; Shuangshuang XIE ; Lixiang HUANG ; Zhen WANG ; Jianzhong YIN ; Wen SHEN
Chinese Journal of Radiology 2016;50(3):165-169
		                        		
		                        			
		                        			Objective To assess the value of arterial spin labeling(ASL) MRI in the staging of early renal allograft function. Methods Sixty two renal allograft recipients (2 to 4 weeks after kidney transplantation) and 20 age match volunteers were included in this study. All subjects underwent conventional MRI and ASL MRI which was performed in the oblique-sagittal plane. Recipients were divided into two groups according to the estimated glomerular filtration rate (eGFR), recipients with good allograft function (eGFR≥60 ml · min-1 · 1.73 m-2,n=37) and recipients with impaired allograft function (eGFR<60 ml · min - 1 · 1.73 m - 2,n=25). Renal blood flow (RBF) was measured and an intra-class correlation coefficient (ICC) was calculated to confirm the reproducibility of the measured results from two doctors. One-way analysis of variance (ANOVA) and Bonferroni were used to compare the different cortical RBF among three groups. Correlation of RBF with eGFR was evaluated using Pearson correlation coefficients. The receiver operating characteristic (ROC) curve was performed to assess the diagnostic efficacy of using cortical RBF to discriminate allografts with impaired function from good function. Results RBF values showed good reproducibility between doctors with an ICC larger than 0.90 in different group. Mean cortical RBF were (390 ± 61),(290 ± 69),(201 ± 86) ml · 100 g-1 · min-1 for healthy controls, recipients with good and impaired allograft function, respectively(F=37.313,P<0.01). RBF exhibited a significant correlation with renal function as determined by eGFR for recipients (r=0.60,P<0.01). Mean cortical RBF showed a high area under the ROC curve (0.773) to discriminate renal allografts with different function, with a sensitivity of 56.0% (14/25) and a specificity of 89.2% (33/37). Conclusion ASL MRI can assess the early renal allografts perfusion, and provide valuable information in the staging of renal function. It could be a useful method for evaluating renal function noninvasively.
		                        		
		                        		
		                        		
		                        	
            

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