1.Intra-and peri-tumoral radiomics model for predicting the response to concurrent chemoradiotherapy in cervical squamous cell carcinoma based on dynamic contrast-enhanced MRI
Yaying SU ; Dan ZHAO ; Zhiying PANG ; Fei YANG ; Shujun CUI
Journal of Practical Radiology 2024;40(3):411-416
Objective To investigate the correlation between intra-and peri-tumoral radiomics features and the response to con-current chemoradiotherapy(CCRT)in cervical squamous cell carcinoma,and to explore the difference of predictive performance between 2D and 3D radiomics models.Methods The imaging data of 132 patients were analyzed retrospectively and randomly divided into training set(n=92)and validation set(n=40).Radiomics features were extracted based on the dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI),the correlation analysis and least absolute shrinkage and selection operator(LASSO)algorithm were used for dimensionality reduction and screening,then the radiomics score was calculated and the logistic model was constructed.The receiver operating characteristic(ROC)curve,internal validation of Bootstrap and Brier score were used to evaluate the discrimina-tion and calibration of the model,and the improvement in predictive performance of 3D model compared with 2D model was evaluated by the integrated discrimination improvement(IDI).Results In the training set,the ROC curve showed that the area under the curve(AUC)of the models(2D-intratumoral,3D-intratumoral,3D-peritumoral,3D-combined)ranged from 0.774 to 0.893.The internal validation of Bootstrap showed the AUC were 0.772,0.860,0.847 and 0.888,respectively,while in the validation set,the AUC were 0.757,0.849,0.824 and 0.887,respectively.The Brier scores indicated that the models were well calibrated.In the training set and the validation set,the IDI values were 0.155 and 0.179,respectively,and the differences were statistically significant(P<0.05).Conclusion The radiomics analysis based on the tumor volume can fully explore the tumor heterogeneity.The intra-and peri-tumoral radiomics combined model shows the best predictive performance,which is important to assist clinicians in developing individualized therapies.
2.Effect of Baicalein on Osteogenic Differentiation of MC3T3-E1 Cells and Its Bacteriostasis against Common Oral Bacteria
Yue WANG ; Fangchen LIN ; Qi SU ; Xia HUANG ; Zhiying ZHOU
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(4):602-612
[Objective]To investigate the impact of varying concentrations of baicalein on the proliferation and biological responses of MC3T3-E1 cells,as well as the antibacterial efficacy of baicalein against prevalent oral bacteria,and to elucidate the underlying mechanisms.[Methods]MC3T3-E1 cells were exposed to different concentrations of baicalein(0,6,12,18,and 24 μmol/L)and cell viability was determined by using the CCK-8 assay.Alkaline phosphatase(ALP)activity of MC3T3-E1 cells following osteogenic induction was assessed.RT-PCR was used to examine the expression of RunX2,BMP2,and Osterix.After 24 hours of treatment,the antibacterial potential of baicalein against Escherichia coli,Staphylococcus Aureus and Streptococcus Sanguis was evaluated by using the K-B paper disk method.[Results]Baicalein exhibited a modest reduction in proliferation of MC3T3-E1 cells but without affecting their sustained proliferation.Baicalein at a concentration of 18 μmol/L enhanced ALP activity of MC3T3-E1 cells,upregulated BMP2 and Osterix expression,downregulated RunX2 expression,significantly inhibited the proliferation of Staphylococcus Aureus and Streptococcus Sanguis(P<0.05).[Conclusions]Baicalein at an optimal concentration(18 μmol/L)demonstrated a promotional effect on the osteogenic differentiation of MC3T3-E1 cells and effectively suppressed the proliferation of common oral bacteria,including Staphylococcus Aureus and Streptococcus Sanguis.
3.Development of a droplet digital polymerase chain reaction assay for the sensitive detection of total and integrated HIV-1 DNA
Lin YUAN ; Zhiying LIU ; Xin ZHANG ; Feili WEI ; Shan GUO ; Na GUO ; Lifeng LIU ; Zhenglai MA ; Yunxia JI ; Rui WANG ; Xiaofan LU ; Zhen LI ; Wei XIA ; Hao WU ; Tong ZHANG ; Bin SU
Chinese Medical Journal 2024;137(6):729-736
Background::Total human immunodeficiency virus (HIV) DNA and integrated HIV DNA are widely used markers of HIV persistence. Droplet digital polymerase chain reaction (ddPCR) can be used for absolute quantification without needing a standard curve. Here, we developed duplex ddPCR assays to detect and quantify total HIV DNA and integrated HIV DNA.Methods::The limit of detection, dynamic ranges, sensitivity, and reproducibility were evaluated by plasmid constructs containing both the HIV long terminal repeat (LTR) and human CD3 gene (for total HIV DNA) and ACH-2 cells (for integrated HIV DNA). Forty-two cases on stable suppressive antiretroviral therapy (ART) were assayed in total HIV DNA and integrated HIV DNA. Correlation coefficient analysis was performed on the data related to DNA copies and cluster of differentiation 4 positive (CD4 +) T-cell counts, CD8 + T-cell counts and CD4/CD8 T-cell ratio, respectively. The assay linear dynamic range and lower limit of detection (LLOD) were also assessed. Results::The assay could detect the presence of HIV-1 copies 100% at concentrations of 6.3 copies/reaction, and the estimated LLOD of the ddPCR assay was 4.4 HIV DNA copies/reaction (95% confidence intervals [CI]: 3.6-6.5 copies/reaction) with linearity over a 5-log 10-unit range in total HIV DNA assay. For the integrated HIV DNA assay, the LLOD was 8.0 copies/reaction (95% CI: 5.8-16.6 copies/reaction) with linearity over a 3-log 10-unit range. Total HIV DNA in CD4 + T cells was positively associated with integrated HIV DNA ( r = 0.76, P <0.0001). Meanwhile, both total HIV DNA and integrated HIV DNA in CD4 + T cells were inversely correlated with the ratio of CD4/CD8 but positively correlated with the CD8 + T-cell counts. Conclusions::This ddPCR assay can quantify total HIV DNA and integrated HIV DNA efficiently with robustness and sensitivity. It can be readily adapted for measuring HIV DNA with non-B clades, and it could be beneficial for testing in clinical trials.
4.Changing roles of CD3 +CD8 low T cells in combating HIV-1 infection
Xin ZHANG ; Xiuwen WANG ; Ling QIN ; Xiaofan LU ; Zhiying LIU ; Zhen LI ; Lin YUAN ; Rui WANG ; Junyan JIN ; Zhenglai MA ; Hao WU ; Yonghong ZHANG ; Tong ZHANG ; Bin SU
Chinese Medical Journal 2023;136(4):433-445
Background::Cluster of differentiation 8 (CD8 T) cells play critical roles in eradicating human immunodeficiency virus (HIV)-1 infection, but little is known about the effects of T cells expressing CD8 at low levels (CD8 low) or high levels (CD8 high) on HIV-1 replication inhibition after HIV-1 invasion into individual. Methods::Nineteen patients who had been acutely infected with HIV-1 (AHI) and 20 patients with chronic infection (CHI) for ≥2 years were enrolled in this study to investigate the dynamics of the quantity, activation, and immune responses of CD3 +CD8 low T cells and their counterpart CD3 +CD8 high T cells at different stages of HIV-1 infection. Results::Compared with healthy donors, CD3 +CD8 low T cells expanded in HIV-1-infected individuals at different stages of infection. As HIV-1 infection progressed, CD3 +CD8 low T cells gradually decreased. Simultaneously, CD3 +CD8 high T cells was significantly reduced in the first month of AHI and then increased gradually as HIV-1 infection progressed. The classical activation of CD3 +CD8 low T cells was highest in the first month of AHI and then reduced as HIV-1 infection progressed and entered the chronic stage. Meanwhile, activated CD38 -HLA-DR +CD8 low T cells did not increase in the first month of AHI, and the number of these cells was inversely associated with viral load ( r = -0.664, P = 0.004) but positively associated with the CD4 T-cell count ( r = 0.586, P = 0.014). Increased programmed cell death protein 1 (PD-1) abundance on CD3 +CD8 low T cells was observed from the 1st month of AHI but did not continue to be enhanced, while a significant T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif (ITIM) domains (TIGIT) abundance increase was observed in the 12th month of infection. Furthermore, increased PD-1 and TIGIT abundance on CD3 +CD8 low T cells was associated with a low CD4 T-cell count (PD-1: r = -0.456, P = 0.043; TIGIT: r = -0.488, P = 0.029) in CHI. Nonetheless, the nonincrease in PD-1 expression on classically activated CD3 +CD8 low T cells was inversely associated with HIV-1 viremia in the first month of AHI ( r = -0.578, P = 0.015). Notably, in the first month of AHI, few CD3 +CD8 low T cells, but comparable amounts of CD3 +CD8 high T cells, responded to Gag peptides. Then, weaker HIV-1-specific T-cell responses were induced in CD3 +CD8 low T cells than CD3 +CD8 high T cells at the 3rd and 12th months of AHI and in CHI. Conclusions::Our findings suggest that CD3 +CD8 low T cells play an anti-HIV role in the first month of infection due to their abundance but induce a weak HIV-1-specific immune response. Subsequently, CD3 +CD8 low T-cell number decreased gradually as infection persisted, and their anti-HIV functions were inferior to those of CD3 +CD8 high T cells.
5.Meta-analysis of the effect of information management on safe in-hospital transfer of patients in China
Ting ZHAO ; Xinyi SU ; Meiying GUO ; Jingjing MENG ; Honghong WANG ; Tao XIAO ; Sha WANG ; Zhiying SHEN ; Dun CAO
Chinese Journal of Modern Nursing 2023;29(26):3579-3587
Objective:To conduct a Meta-analysis on the application effect of information management on safe in-hospital transfer of patients in China.Methods:Using computers to search for randomized controlled trials and quasi experimental studies on the effect of information management on safe in-hospital transfer of patients in China from China National Knowledge Infrastructure, VIP, Wanfang Database, China Biomedical Mediline disc, PubMed, Embase, Web of Science, CINAHL and Cochrane Library. The search period was from establishment of databases to May 17, 2022. Literature screening, quality evaluation and data extraction were conducted independently by two trained researchers. Stata 15.1 software was used for Meta-analysis.Results:A total of 14 articles were included, involving a total of 130 670 patients. The results of Meta-analysis showed that the incidence of adverse event in in-hospital transfer of patients in the information management group was shorter than that in the control group ( OR=0.24, 95% CI: 0.17-0.35, P<0.01), duration of in-hospital tranfer was longer than that in the control group ( WMD=-5.76, 95% CI: -8.30-3.22, P<0.01), and patients' satisfaction ( OR=1.11, 95% CI: 1.05-1.17, P<0.01) and satisfaction of medical personnel responsible for transfer ( OR=1.37, 95% CI: 1.13-1.66, P<0.01) were higher than those of the control group. Conclusions:Information management can effectively control the incidence of adverse events in in-hospital transfer of patients in China, shorten the time required for hospital transfers and improve the satisfaction of patients and medical staff in hospital transfers.
6.miR-7/TGF-β2 axis sustains acidic tumor microenvironment-induced lung cancer metastasis.
Tao SU ; Suchao HUANG ; Yanmin ZHANG ; Yajuan GUO ; Shuwei ZHANG ; Jiaji GUAN ; Mingjing MENG ; Linxin LIU ; Caiyan WANG ; Dihua YU ; Hiu-Yee KWAN ; Zhiying HUANG ; Qiuju HUANG ; Elaine LAI-HAN LEUNG ; Ming HU ; Ying WANG ; Zhongqiu LIU ; Linlin LU
Acta Pharmaceutica Sinica B 2022;12(2):821-837
Acidosis, regardless of hypoxia involvement, is recognized as a chronic and harsh tumor microenvironment (TME) that educates malignant cells to thrive and metastasize. Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression, the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy. Here, chemical-induced and transgenic mouse models for colon, liver and lung cancer were established, respectively. miR-7 and TGF-β2 expressions were examined in clinical tissues (n = 184). RNA-seq, miRNA-seq, proteomics, biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis. Our data show that lung cancer is sensitive to the increased acidification of TME, and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5p. TGF-β2 is a direct target of miR-7-5p. The reduced expression of miR-7-5p subsequently increases the expression of TGF-β2 which enhances the metastatic potential of the lung cancer. Indeed, overexpression of miR-7-5p reduces the acidic pH-enhanced lung cancer metastasis. Furthermore, the human lung tumor samples also show a reduced miR-7-5p expression but an elevated level of activated TGF-β2; the expressions of both miR-7-5p and TGF-β2 are correlated with patients' survival. We are the first to identify the role of the miR-7/TGF-β2 axis in acidic pH-enhanced lung cancer metastasis. Our study not only delineates how acidification directly affects tumorigenesis, but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer (NSCLC) treatment. Our study opens an avenue to explore the pH-sensitive subcellular components as novel therapeutic targets for cancer treatment.
7.Discussion on Quality Assurance and Improvement Mode of Ethics Committee
Yao LI ; Zhiying SU ; Ying WU ; Xiaomin WANG
Chinese Medical Ethics 2022;35(12):1346-1351
With the continuous improvement of the ethics committee status and the rapid growth of ethical review projects, the ethics committee urgently needs to establish an evaluation mechanism for continuous improvement. In view of a series of problems faced by the ethics committee in its daily management and operation, this paper discussed the concept and measures of introducing quality assurance and quality improvement into the ethics committee. Through comparing the advantages and disadvantages of the three models of quality assurance and quality improvement, this paper summarized the practical experience, further determined the internal evaluation, improvement model and evaluation elements of ethics committee, constantly improve the internal evaluation system of the ethics committee, strengthen the education and training of the ethics committee, and implement the whole chain electronic review, so as to improve the operation efficiency and review ability of the ethics committee, and provide sufficient ethical protection for the protection of the rights and interests of subjects.
8.Combined resection of thoracic and abdominal organ clusters: a series of 50 cases
Silin LI ; Xuyong SUN ; Ke QIN ; Ning WEN ; Jixiang LIAO ; Liugen LAN ; Ying HUANG ; Zhiying LEI ; Qingdong SU ; Jihua WU
Chinese Journal of Surgery 2022;60(8):774-778
Objective:To examine the technique and effect of combined thoracic and abdominal organ clusters resection.Methods:From February 2019 to August 2021, totally 50 cases of combined thoracoabdominal organ cluster resection were completed at Transplant Medical Center, the Second Affiliated Hospital of Guangxi Medical University from donation after brain death donors. There were 47 males and 3 females, aging (34.8±12.3) years (range: 5 to 55 years). The length of hospital stay( M(IQR)) was 4(4) days (range: 2 to 43 days), the length of tube time was 4(2) days (range: 1 to 43 days). Through the midsternal incision and the abdominal grand cross incision, the cold perfusion was performing simultaneously when the perfusion lines of each target organ was established respectively. The combined resection was performed with the diaphragm as the boundary and the organ cluster as the unit. The heart and lung were separated on site and sent to the transplant hospital, and the abdominal organ cluster was directly preserved and returned to our hospital for further separation and repair. Results:Totaly 21 hearts, 47 pairs of lungs, 49 livers, 47 pairs of kidneys and 11 pancreas were harvested by this surgical treatment. The resection time was (32.6±6.5) minutes (range: 19 to 50 minutes), with no hot ischemia time. There was no accidental injury that affected organ quality and function. Heart transplantation was performed in 17 cases, combined heart-kidney transplantation in 2 cases, double lung transplantation in 43 cases, single lung transplantation in 6 cases, liver transplantation in 41 cases, combined liver-pancreas-duodenal cluster transplantation in 1 case, combined liver-kidney transplantation in 3 cases, combined pancreas-kidney transplantation in 9 cases, and kidney transplantation in 74 cases.Conclusion:Simultaneous perfusion and combined resection of thoracic and abdominal organ clusters for donation after brain death donors are feasible and effective.
9.Combined resection of thoracic and abdominal organ clusters: a series of 50 cases
Silin LI ; Xuyong SUN ; Ke QIN ; Ning WEN ; Jixiang LIAO ; Liugen LAN ; Ying HUANG ; Zhiying LEI ; Qingdong SU ; Jihua WU
Chinese Journal of Surgery 2022;60(8):774-778
Objective:To examine the technique and effect of combined thoracic and abdominal organ clusters resection.Methods:From February 2019 to August 2021, totally 50 cases of combined thoracoabdominal organ cluster resection were completed at Transplant Medical Center, the Second Affiliated Hospital of Guangxi Medical University from donation after brain death donors. There were 47 males and 3 females, aging (34.8±12.3) years (range: 5 to 55 years). The length of hospital stay( M(IQR)) was 4(4) days (range: 2 to 43 days), the length of tube time was 4(2) days (range: 1 to 43 days). Through the midsternal incision and the abdominal grand cross incision, the cold perfusion was performing simultaneously when the perfusion lines of each target organ was established respectively. The combined resection was performed with the diaphragm as the boundary and the organ cluster as the unit. The heart and lung were separated on site and sent to the transplant hospital, and the abdominal organ cluster was directly preserved and returned to our hospital for further separation and repair. Results:Totaly 21 hearts, 47 pairs of lungs, 49 livers, 47 pairs of kidneys and 11 pancreas were harvested by this surgical treatment. The resection time was (32.6±6.5) minutes (range: 19 to 50 minutes), with no hot ischemia time. There was no accidental injury that affected organ quality and function. Heart transplantation was performed in 17 cases, combined heart-kidney transplantation in 2 cases, double lung transplantation in 43 cases, single lung transplantation in 6 cases, liver transplantation in 41 cases, combined liver-pancreas-duodenal cluster transplantation in 1 case, combined liver-kidney transplantation in 3 cases, combined pancreas-kidney transplantation in 9 cases, and kidney transplantation in 74 cases.Conclusion:Simultaneous perfusion and combined resection of thoracic and abdominal organ clusters for donation after brain death donors are feasible and effective.
10.Clinical characteristics of insulin resistance and its relationship with metabolic complications in obese children and adolescents
Li QING ; Luting PENG ; Qianqi LIU ; Zhiying JIANG ; Su WU ; Rong HUANG ; Mengying CHEN ; Rong LI ; Baoqing MO ; Xiaonan LI
Chinese Journal of Applied Clinical Pediatrics 2020;35(11):847-851
Objective:To study the clinical characteristics of growth development and metabolic disorders in obese children and adolescents with insulin resistance (IR).Methods:Normal weight or obese children and adolescents who hospitalized at the Department of Children′s Health Care of Children′s Hospital Affiliated to Nanjing Medical University from September 2015 to April 2018 were recruited.Children′s height, body weight and waist circumference were measured, and waist-to-height ratio (WHtR) and body mass index (BMI) were calculated.Puberty process was determined by Tanner stage.Blood glucose, blood lipid and insulin were measured in fasting state, and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated based on fasting blood glucose and insulin levels.IR was considered when HOMA-IR was over 2.69.Non-alcoholic fatty liver (NAFLD) was diagnosed by abdominal ultrasound.Results:(1) A total of 691 subjects were included, including 183 cases with the age of (9.73±2.38) years in the normal weight group/normal group, and 508 cases with the age of (10.24±2.05) years old in the obese group.The rate of IR was higher in obese group than that in normal group (55.71% vs. 10.38%), and the difference was statistically significant ( P<0.001). (2)HOMA-IR was positively correlated with age ( r=0.256, P<0.001), BMI ( r=0.426, P<0.001), waist circumference ( r=0.454, P<0.001), and WHtR ( r=0.321, P<0.001). After the adjustment for age, sex, and puberty stage, HOMA-IR was also positively correlated with BMI ( r=0.418, P<0.001), waist circumference ( r=0.419, P<0.001) and WHtR ( r=0.375, P<0.001). (3) During puberty, HOMA-IR in both of obese group and normal group was increased, and HOMA-IR in obese group was more particularly serious compared to normal group[TannerⅠ: 2.60(1.49, 3.94) vs.1.28(0.80, 1.90); Tanner Ⅱ: 3.07(1.75, 5.17) vs.1.80(1.16, 2.96); Tanner Ⅲ: 4.33(2.80, 6.57) vs.2.47(1.41, 3.68); Tanner Ⅳ-Ⅴ: 3.49(1.04, 5.78) vs.1.91(0.54, 2.60)], and the differences were all statistically significant(all P<0.05). (4)Compared with the obese objects without IR, obese children and adolescents with IR had higher systolic blood pressure[112(104, 124) mmHg vs.109(98, 121) mmHg, 1 mmHg=0.133 kPa], triglyceride level [1.27(0.95, 1.81) mmol/L vs.1.09(0.79, 1.61) mmol/L], fas-ting blood glucose level [4.80(4.46, 5.01) mmol/L vs.4.48(4.16, 4.76) mmol/L] and fasting insulin level [21.27(16.21, 28.56) mmol/L vs.7.62(4.43, 10.83) mmol/L], and the differences were all statistically significant(all P<0.05). IR was a risk factor for NAFLD in obese children( OR=1.536, 95% CI: 1.049-2.247, P<0.05). Conclusions:Serious and abdominal obesity in children and adolescents is a major risk factor for the development of IR.HOMA-IR of obese children and adolescents is particularly serious during puberty.The obese children with IR are more likely to have metabolic disorders in blood glucose, serum lipid and blood pressure, and have the risk of NAFLD development.

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