1.Predictive Value of miRNAs Markers for Advanced Lung Squamous Cell Carcinoma.
Anna WANG ; Jingjing CONG ; Yingjia WANG ; Xin'ge LI ; Junjian PI ; Kaijing LIU ; Hongjie ZHANG ; Xiaoyan YAN ; Hongmei LI
Chinese Journal of Lung Cancer 2025;28(5):325-333
BACKGROUND:
Lung cancer is one of the leading causes of cancer-related mortality worldwide, with above 80% of cases be non-small cell lung cancer (NSCLC), among which lung squamous cell carcinoma (LUSC) occupies a significant proportion. Although comprehensive cancer therapies have considerably improved the overall survival of patients, patients with advanced LUSC have a poorer prognosis. Therefore, there is a need for a biomarker to predict the progress of advanced LUSC in order to improve prognosis through early diagnosis. Previous studies have shown that miRNAs are differentially expressed in lung cancer tissues and play roles as potential oncogenes or tumor suppressors. The aim of this study is to identify differentially expressed miRNAs between early-stage and advanced-stage LUSC, and to establish a set of miRNAs that can predict the progress of advanced LUSC.
METHODS:
Clinical data and miRNA-related data of LUSC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Bioinformatic methods were applied to analyze the data. Receiver operating characteristic (ROC) curves were plotted, and various online tools were used to predict target genes, with subsequent analysis of the potential biological mechanisms of these genes.
RESULTS:
A total of 58 differentially expressed miRNAs were identified between the experiment group and the control group. Seven miRNAs were selected for potential construction of a miRNA biomarker through LASSO regression, and based on the area under the curve (AUC) values of each miRNA, four of these miRNAs (miR-377-3p, miR-4779, miR-6803-5p, miR-3960) were ultimately chosen as biomarkers for predicting advanced LUSC. The AUC under the ROC curve for the combined four miRNAs was 0.865. Enrichment analysis showed that these target genes were involved in several pathways, including cancer-related pathways, mitogen-activated protein kinase (MAPK) signaling pathway, serine/threonine kinase, and tyrosine kinase signaling pathways.
CONCLUSIONS
The combined use of miR-377-3p, miR-4779, miR-6803-5p and miR-3960 provides a good predictive ability for the progress of advanced LUSC patients, with an AUC of 0.865.
Humans
;
MicroRNAs/metabolism*
;
Lung Neoplasms/metabolism*
;
Biomarkers, Tumor/metabolism*
;
Carcinoma, Squamous Cell/pathology*
;
Gene Expression Regulation, Neoplastic
;
Male
;
Female
;
Prognosis
;
ROC Curve
;
Middle Aged
2.Action mechanism of gluteus medius width ratio in progression of non-traumatic femoral head necrosis by finite element analysis
Yingjia YUAN ; Yulai JIANG ; Jin LI ; Ke WANG ; Yu WANG ; Tianye LIN ; Qingwen ZHANG ; Wei HE ; Qiushi WEI
Chinese Journal of Tissue Engineering Research 2024;33(33):5276-5282
BACKGROUND:The gluteus medius not only abducts the hip joint,but also plays an important role in limiting the external movement of the femoral head.At present,there is a lack of research on the correlation between gluteus medius status and non-traumatic femoral head necrosis. OBJECTIVE:To investigate the relationship between the gluteus medius width ratio and the medial space ratio of the hip joint and the progression of non-traumatic femoral head necrosis,and to explore the effect of gluteus medius atrophy on the surface and necrotic zone stress of the femoral head necrosis through finite element analysis. METHODS:Retrospective analysis of unilateral non-traumatic femoral head necrosis patients admitted to Third Affiliated Hospital of Guangzhou University of Chinese Medicine was performed.All patients were followed up for an average of more than 2 years.They were divided into a collapsed group and a non-collapsed group based on whether there was collapse of the femoral head during the follow-up.Medial space ratio,gluteus medius width ratio,Sharp angle,gluteus medius length ratio,and gluteus medius activation angle were measured and calculated.The differences in these indicators were compared between the two groups.At the first visit and follow-up at 3,6,12,and 24 months,the medial space ratio and gluteus medius width ratio were measured and calculated to explore the changes of these two indicators in the course of non-traumatic femoral head necrosis.In addition,using three-dimensional finite element analysis,a Japanese Investigation Committee classification C1 type femoral head necrosis model was constructed based on CT data.At the same time,based on MRI data,a model of the gluteus medius muscle was constructed and divided into a gluteus medius muscle atrophy group(gluteus medius width ratio:74%-76%)and a gluteus medius muscle normal group(gluteus medius width ratio:94%-96%).Each group constructed 10 models,with 6 degrees of freedom of the distal femur constrained to zero.600 N pressures were applied along the Z-axis to the upper surface of the sacrum.The stress distribution,maximum stress values on the surface and necrotic area of the femoral head,and the maximum displacement of the necrotic area were compared between two groups of models. RESULTS AND CONCLUSION:(1)A total of 153 patients(67 males and 86 females)with 153 hips were included in this study.(2)At the 24-hour follow-up,the medial space ratio of the collapsed group was significantly higher than that of the non-collapsed group(P<0.05).The gluteus medius width ratio of the collapsed group was significantly lower than that of the non-collapsed group(P<0.05).There was no statistically significant difference in Sharp angle,gluteus medius activation angle,and gluteus medius length ratio between the two groups(P>0.05).(3)Since the follow-up time exceeded 3 months,the gluteus medius width ratio of the collapsed group was lower than that of the non-collapsed group(P<0.05).Since the follow-up time exceeded 12 months,the medial space ratio of the collapsed group was higher than that of the non-collapsed group(P<0.05).(4)Pearson correlation analysis showed a significant positive correlation between follow-up time and medial space ratio in the collapsed group(P<0.05),and a significant negative correlation between follow-up time and gluteus medius width ratio(P<0.05).The regression coefficient of gluteus medius width ratio was larger than that of medial space ratio.(5)The group with middle gluteal muscle atrophy showed significant stress concentration on the surface of the femoral head,and the stress zone was significantly located on the outside.The maximum stress on the surface of the femoral head in the group with middle gluteal muscle atrophy was significantly greater than that in the group with normal middle gluteal muscle(P<0.05).There was significant stress concentration in the necrotic area of the middle gluteal muscle atrophy group,and the maximum stress was located at the edge of the necrotic area.The maximum stress and maximum displacement in the necrotic area of the middle gluteal muscle atrophy group were significantly greater than those of the normal group(P<0.05).(6)It is indicated that gluteus medius width ratio is an effective indicator for evaluating changes in gluteal muscle atrophy.In the progression of non-traumatic femoral head necrosis,atrophy of the gluteus medius muscle first occurs,followed by widening of the medial hip joint space.The mechanical mechanism may be that the atrophy of the gluteus medius muscle affects the stability of the hip joint,leading to external displacement of the femoral head,and increasing stress and displacement on the surface and necrotic area of the femoral head.
3.Combined ultrasound and clinical characteristics to predict the treatment time of 90Sr radioisotope applicator therapy for pathologic scars
Yanjing CHEN ; Yongshuai QI ; Zhouyue JIANG ; Yanyan ZHANG ; Ting LANG ; Yue LIN ; Min CHANG ; Yingjia LI
Chinese Journal of Ultrasonography 2024;33(7):603-608
Objective:To combine ultrasound and clinical characteristics for predicting the treatment time of strontium 90( 90Sr) radioisotope applicator therapy for pathological scars when the therapeutic effect meets the clinical effective criteria. Methods:From September 2022 to October 2023, 48 patients (90 lesions) with pathological scars who underwent 90Sr radioisotope applicator therapy at the Department of Nuclear Medicine, Nanfang Hospital, Southern Medical University were prospectively collected. The clinically effective criteria of 90Sr radioisotope applicator therapy for pathological scars were defined as a reduction of the superficial height of the scar higher than 50%. All lesions were divided into short period treatment group (2 months, 38 lesions) and long period treatment group (>2 months, 52 lesions) according to the duration of treatment when the therapeutic effect met the clinical criteria. Univariate comparative analyses of ultrasound and clinical characteristics between the two groups were performed. The statistically significant variates were used to build a multivariate logistic regression model for analyzing the independent predictors of the treatment time of 90Sr radioisotope applicator therapy for pathological scars. Results:Family history, blood flow signal, disease duration, age, and scar Young′s modulus were independent predictors of the effective treatment time of 90Sr radioisotope applicator therapy for pathological scars (all P<0.05). By using the selected variables, a predictive model was developed, area under the ROC curve (AUC) were 0.886 (95% CI=0.817-0.955, P<0.001), and the calibration curve showed that the model was well calibrated(χ 2=5.668, P=0.684). Conclusions:The multivariate logistic regression model with family history, blood flow signal, disease duration, age, and scar Young′s modulus could be used to predict the treatment time of 90Sr radioisotope applicator therapy for pathologic scars, which can help to guide the design of treatment plan, reduce unnecessary radiation damage, and improve patient compliance.
4.Visually amplification-free rapid detection of 2019-nCoV nucleic acid based on CRISPR/Cas13a
Nan ZHAO ; Yong QI ; Wei LI ; Yingqing MAO ; Wenjing LIU ; Yifang HAN ; Erxin ZHANG ; Yingjia XU ; Ruichen LYU ; Yuxin JIANG ; Yuzhen LAI ; Jiameng LI ; Wanpeng SHEN ; Yue SONG ; Yuexi LI
Chinese Journal of Laboratory Medicine 2024;47(6):658-666
Objective:Based on the specific cleavage and non-specific "trans-cleavage" activities of the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein(CRISPR/Cas13), we established a visually amplification-free rapid detection technique of 2019-nCoV nucleic acid. This technique is easily processed with a low detection limit and good specificity.Methods:According to the 2019-nCoV gene sequence, specific CRISPR RNAs were screened and designed by bioinformatics analysis, and then synthesized as universal signal-strained RNA transcription targets in vitro to establish and optimize the reaction system. Moreover, the 2019-nCoV pseudoviral nucleic acid was used as a standard substance to evaluate the detection limit. A total of 65 positive samples were collected from various 2019-nCoV variants, while 48 negative samples included other clinically common respiratory pathogens, such as influenza A virus, influenza B virus, human parainfluenza virus, Klebsiella pneumonia, etc. All samples were tested by quantitative PCR (qPCR), digital PCR, and the method established in this study. The sensitivity and specificity of the newly established method were analyzed and evaluated. Results:With the newly established technique, the detection time for 2019-nCoV nucleic acid could be minimized to 6 minutes. In addition, the detection limit was 14 copies/μl when assisted by the displaying instrument, whereas it increased to 28 copies/μl with the naked eye. This technique had a sensitivity and specificity of 98.5% (66/67) and 100% (46/46) respectively, showing no statistically significant difference compared to the gold standard qPCR( P=1). Conclusions:This study has successfully established a CRISPR/Cas13a-based visually rapid detection technique for 2019-nCoV nucleic acid. This technique offers the advantages of a simple process, convenient operation, low environmental operating requirements, a detection limit close to qPCR, and a strong potential for on-site testing applications.
5.Predictive Value of A miRNA Signature for Distant Metastasis in Lung Cancer.
Jingjing CONG ; Anna WANG ; Yingjia WANG ; Xinge LI ; Junjian PI ; Kaijing LIU ; Hongjie ZHANG ; Xiaoyan YAN ; Hongmei LI
Chinese Journal of Lung Cancer 2024;27(12):919-930
BACKGROUND:
Lung cancer represents the main cause of cancer-related deaths worldwide, and non-small cell lung cancer (NSCLC) is the most main subtype. More than half of NSCLC patients have already developed distant metastasis (DM) at the time of diagnosis and have a poor prognosis. Therefore, it is necessary to find new biomarkers for predicting NSCLC DM in order to guide subsequent treatment and thus improve the prognosis of NSCLC patients. Numerous studies have shown that microRNAs (miRNAs) are abnormally expressed in lung cancer tissues and play an important role in tumorigenesis and progression. The aim of this study is to identify differentially expressed miRNAs in lung adenocarcinoma tissues with DM group compared to those with non-distant metastasis (NDM) group, and to construct a miRNA signature for predicting DM of lung adenocarcinoma.
METHODS:
We first obtained miRNA and clinical data for patients with lung adenocarcinoma from The Cancer Genome Atlas (TCGA) database. Subsequently, bioinformatics analysis, which included different R packages, Kaplan-Meier analysis, receiver operating characteristic (ROC) curve, and a range of online analysis tools, was performed to analyze the data.
RESULTS
A total of 12 differentially expressed miRNAs were identified between the DM and NDM groups, and 8 miRNAs (miR-377-5p, miR-381-5p, miR-490-5p, miR-519d-5p, miR-3136-5p, miR-320e, miR-2355-5p, miR-6784-5p) were screened for constructing a miRNA signature. The efficacy of this miRNA signature in predicting DM was good with an area under the curve (AUC) of 0.831. Logistic regression analysis showed that this miRNA signature was an independent risk factor for DM of lung adenocarcinoma. Next, target genes of the eight miRNAs were predicted, and enrichment analysis showed that these target genes were enriched in a variety of pathways, including pathways in cancer, herpes simplex virus I infection, PI3K-Akt pathway, MAPK pathway, Ras pathway, etc. CONCLUSIONS: This miRNA signature has good efficacy in predicting DM of lung adenocarcinoma and has the potential to be a predictor of DM of lung adenocarcinoma.
Humans
;
MicroRNAs/metabolism*
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Lung Neoplasms/diagnosis*
;
Male
;
Neoplasm Metastasis
;
Female
;
Gene Expression Regulation, Neoplastic
;
Middle Aged
;
Prognosis
;
Gene Expression Profiling
;
Aged
;
Biomarkers, Tumor/genetics*
6.Trajectories of glucose and lipid metabolism of schizophrenic patients in long-term hospitalization: a real-world study
Xiaoying YE ; Weiqun TAO ; Qingqing ZHANG ; Yingjia YANG ; Xinhui XIE ; Binrang YANG
Sichuan Mental Health 2023;36(2):111-117
ObjectiveTo picture the trajectory of changes in glucose and lipid metabolism among schizophrenic patients in long-term hospitalization. MethodsA total of 109 inpatients of Shenzhen Kangning Hospital from 2014 to 2022, who were diagnosed with schizophrenia based on the International Classification of Diseases, tenth edition (ICD-10) criteria, were recruited as subjects. Real-world follow-up data on longitudinal glucose metabolism (fasting blood glucose, glycosylated hemoglobin, C-peptide) and lipid metabolism (triglycerides, low density lipoprotein, high density lipoprotein, total cholesterol) were observed. The frequency of visit was once a year, with a total of 9 visits over 8 years. ResultsIn terms of glucose metabolism parameters, fasting blood glucose level decreased to 4.87 mmol/L at the 7th visit, lower than the baseline level (P<0.01). Glycated hemoglobin level was 6.08% at the 9th visit, higher than the baseline level (P<0.05). C-peptide level was 3.14 ng/mL at the 7th visit, higher than the baseline level (P<0.01). As for the trajectory of lipid metabolism parameters, high-density lipoprotein level were significantly lower than baseline level at the second visit (P<0.01) and stayed basically stable thereafter. Total cholesterol levels at the last three visits were 4.06, 4.07 and 3.95 mmol/L, respectively, all lower than the baseline level (P<0.01). ConclusionThe changes of glycolipid metabolism parameters in long-term inpatients with schizophrenia were generally smooth during the 8-year follow-up period.
7.Effect of single locked-plate internal fixation combined with autogenous iliac bone graft in the treatment of Rorabeck type II periprosthetic distal femoral fracture after total knee arthroplasty
Shenghu ZHOU ; Yingjia ZHOU ; Jinsuo LI ; Yonggang CHENG ; Yongjie QIAO ; Yanfeng CHANG ; Shuo YE ; Ping ZHEN ; Haoqiang ZHANG
Chinese Journal of Trauma 2022;38(10):909-915
Objective:To investigate the efficacy of single locked-plate internal fixation combined with autologous iliac bone graft in the treatment of Rorabeck type II periprosthetic distal femural fracture (PDFF) after total knee arthroplasty (TKA).Methods:A retrospective case series study was made on 13 patients suffering from Rorabeck type II PDFF after primary TKA together with severe osteoporosis (T value≤ -2.5 SD) admitted to 940th Hospital of Joint Logistics Support Force of PLA from January 2016 to December 2020, including 4 males and 9 females, aged 65-85 years [(75.2±6.5)years]. All patients were treated with single locked-plate internal fixation combined with autologous iliac bone graft. Anti-osteoporosis and early standardized joint function rehabilitation were undertaken postoperatively. The operation time and intraoperative blood loss were recorded. The range of motion of knee joint was compared before operation, at postoperative 3, 6 and 12 months and at the last follow-up. The Hospital for Special Surgery (HSS) knee score was assessed at postoperative 3, 6 and 12 months and at the last follow-up to evaluate the recovery of knee joint function. The bone mineral density was reexamined at postoperative 6 months and 12 months to evaluate the therapeutic effect of anti-osteoporosis. Complications were detected as well.Results:All patients were followed up for 12-72 months [(43.2±19.9)months]. The operation time was 90-135 minutes [(103.8±12.6)minutes], with the intraoperative blood loss of 100-250 ml [(150.0±45.6)ml]. The range of motion of knee joint was (114.6±7.8)°, (90.4±8.0)°, (97.3±4.8)° and (98.1±6.3)° before operation and at postoperative 3, 6 and 12 months (all P<0.05). The HSS knee score was (80.2±2.2)points, (84.6±2.9)points and (87.3±3.3)points at postoperative 3, 6 and 12 months (all P<0.05). The knee joint function was excellent in 10 patients and good in 3 at postoperative12 months, and the excellent and good rate was 100%. The T value of bone mineral density was (-3.8±0.6)SD, (-3.4±0.6)SD and (-2.9±0.6)SD preoperatively and at postoperative 6 months and 12 months (all P<0.05). One patient experienced nonunion and was cured after secondary autologous iliac bone grafting combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) bone grafting. Three patients developed venous thrombosis of lower limbs and were cured with oral administration of rivaroxaban. One patient had mild knee flexion and extension limitation and was improved after manual release under femoral nerve block anesthesia and subsequent functional rehabilitation. Conclusion:For patients with Rorabeck type II PDFF after TKA, single locked-plate internal fixation combined with autologous iliac bone graft has advantages of short operation time, few intraoperative bleeding, satisfactory knee range of motion and functional recovery as well as significant improvement of bone mineral density.
8.A content analysis of the provincial laws and regulations for voluntary blood donation
Huiying HU ; Li CHEN ; Zijia ZHANG ; Ying CHANG ; Guiqi ZHAO ; Lifen LU ; Yan ZHANG ; Qingming WANG ; Yingjia JIANG ; Hai QI ; Ming ZHU
Chinese Journal of Blood Transfusion 2022;35(8):873-877
【Objective】 To perform quantitative analysis on the sample provincial laws and regulations for voluntary blood donation, and provide reference for further revision of laws and regulations. 【Methods】 31 study samples were current provincial laws and regulations for voluntary blood donation that can be collected from open sources. The issue date and the revision date of each sample were recorded. With "The Blood Donation Law of the People’s Republic of China" as reference, 5 categories were formed and additional clauses in samples were coded and rated following content analysis procedures. Sample provinces were divided into two groups based on donation rate and their differences in evaluation scores of categories were examined using rank sum test. 【Results】 Until December, 2021, 31 sample provinces had issued and implemented provincial laws and regulation for voluntary blood donation, and 14 of which had been revised. Many detailed clauses (total score 9.32±3.09) were added in sample provincial laws and regulations, more clauses were added in the categories of 'related government agencies and their responsibilities’, 'management of clinical blood use’ and 'rewards and punishment’. Sample provinces were divided into two groups according to the donation rate per 1 000 people recommended by World Health Organization(10‰). Compared to lower donation rate group, the total score and sub score in the categories of 'basic principles’, 'management of blood collection and supply’ were significantly higher in higher donation rate group. 【Conclusion】 In revision and improvement of provincial laws and regulations, 'basic principles’ and 'management of blood collection and supply’ could be considered. This assay mainly tries to provide a new research perspective and perform quantitative analysis on content of sample provincial laws and regulation for voluntary blood donation, the actual effect of the results in this study need longer time to be examined, and we will keep following its new advances.
9.Evaluation of conventional ultrasound in the detection of subclinical hemorrhage of hemophilia joint
Yaru ZHANG ; Hao LIU ; Fei MA ; Yang GAO ; Cong XU ; Mei YI ; Jing SUN ; Xiaoqin FENG ; Yingjia LI
Chinese Journal of Ultrasonography 2021;30(3):249-252
Objective:To explore the application value of conventional ultrasound(US) in detecting occult bleeding lesions in joints of patients with hemophilia.Methods:Twenty-seven children with severe hemophilia A who received factor Ⅷ prophylactic treatment from March 2017 to April 2018 in Nanfang Hospital, Southern Medical University were enrolled. Clinical data were collected from routine practice accompanied with US examination, hemophilia joint health score (HJHS) 2.1 assessment and the history of hemarthrosis of both ankles, elbows and knees at baseline and at 1 year follow-up.Results:A total of 157 joints of 27 patients were followed up for one year. During the treatments, 74 joints were found without history of hemarthrosis, among which the total US score of 14(14/74, 18.9%) joints increased, and HJHS 2.1 score of 11(11/74, 14.9%) joints developed. There was no significant change in the HJHS 2.1 score of 108 joints, among which 25 joints (25/108, 23.1%) had an increase in the total US score.However, there was no significant change in the total US score for 93 joints, of which 9(9/93, 9.7%) had an increase in HJHS 2.1 score.Conclusions:US examination can sensitively detect hemophilia arthropathy in joints without history of hemarthrosis and without obvious progression of arthropathy by HJHS 2.1 examination, and provide clinicians with more accurate joint information.
10.Tumor microenvironments self-activated nanoscale metal-organic frameworks for ferroptosis based cancer chemodynamic/photothermal/chemo therapy.
Yu LIANG ; Li ZHANG ; Chao PENG ; Shiyu ZHANG ; Siwen CHEN ; Xin QIAN ; Wanxian LUO ; Qing DAN ; Yongyan REN ; Yingjia LI ; Bingxia ZHAO
Acta Pharmaceutica Sinica B 2021;11(10):3231-3243
Ferroptosis, as a newly discovered cell death form, has become an attractive target for precision cancer therapy. Several ferroptosis therapy strategies based on nanotechnology have been reported by either increasing intracellular iron levels or by inhibition of glutathione (GSH)-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4). However, the strategy by simultaneous iron delivery and GPX4 inhibition has rarely been reported. Herein, novel tumor microenvironments (TME)-activated metal-organic frameworks involving Fe & Cu ions bridged by disulfide bonds with PEGylation (FCSP MOFs) were developed, which would be degraded specifically under the redox TME, simultaneously achieving GSH-depletion induced GPX4 inactivation and releasing Fe ions to produce ROS

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