1.Invasiveness assessment by CT quantitative and qualitative features of lung cancers manifesting ground-glass nodules in 555 patients: A retrospective cohort study
Yantao YANG ; Wei WANG ; Yichen YANG ; Biying WANG ; Huilian HU ; Ziqi JIANG ; Dezhong CAI ; Yaowu DUAN ; Jiezhi JIANG ; Jia LUO ; Guangqiang ZHAO ; Yunchao HUANG ; Lianhua YE
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(01):51-58
Objective To explore the correlation between the quantitative and qualitative features of CT images and the invasiveness of pulmonary ground-glass nodules, providing reference value for preoperative planning of patients with ground-glass nodules. Methods The patients with ground-glass nodules who underwent surgical treatment and were diagnosed with pulmonary adenocarcinoma from September 2020 to July 2022 at the Third Affiliated Hospital of Kunming Medical University were collected. Based on the pathological diagnosis results, they were divided into two groups: a non-invasive adenocarcinoma group with in situ and minimally invasive adenocarcinoma, and an invasive adenocarcinoma group. Imaging features were collected, and a univariate logistic regression analysis was conducted on the clinical and imaging data of the patients. Variables with statistical difference were selected for multivariate logistic regression analysis to establish a predictive model of invasive adenocarcinoma based on independent risk factors. Finally, the sensitivity and specificity were calculated based on the Youden index. Results A total of 555 patients were collected. The were 310 patients in the non-invasive adenocarcinoma group, including 235 females and 75 males, with a meadian age of 49 (43, 58) years, and 245 patients in the invasive adenocarcinoma group, including 163 females and 82 males, with a meadian age of 53 (46, 61) years. The binary logistic regression analysis showed that the maximum diameter (OR=4.707, 95%CI 2.060 to 10.758), consolidation/tumor ratio (CTR, OR=1.027, 95%CI 1.011 to 1.043), maximum CT value (OR=1.025, 95%CI 1.004 to 1.047), mean CT value (OR=1.035, 95%CI 1.008 to 1.063), spiculation sign (OR=2.055, 95%CI 1.148 to 3.679), and vascular convergence sign (OR=2.508, 95%CI 1.345 to 4.676) were independent risk factors for the occurrence of invasive adenocarcinoma (P<0.05). Based on the independent predictive factors, a predictive model of invasive adenocarcinoma was constructed. The formula for the model prediction was: Logit(P)=–1.293+1.549×maximum diameter of lesion+0.026×CTR+0.025×maximum CT value+0.034×mean CT value+0.72×spiculation sign+0.919×vascular convergence sign. The area under the receiver operating characteristic curve of the model was 0.910 (95%CI 0.885 to 0.934), indicating that the model had good discrimination ability. The calibration curve showed that the predictive model had good calibration, and the decision analysis curve showed that the model had good clinical utility. Conclusion The predictive model combining quantitative and qualitative features of CT has a good predictive ability for the invasiveness of ground-glass nodules. Its predictive performance is higher than any single indicator.
2.Preparation of anti-PD-L1 nanobodies fused with C3Fab and their effect on plasma half-life
Zhanxiong WANG ; Meng LEI ; Yichen DENG ; Chu LOU ; Tianning YANG ; Qianqian HU ; Jiangwei LI
International Journal of Biomedical Engineering 2024;47(1):53-59
Objective:To prepare the anti-programmed death-ligand 1 (PD-L1) nanoantibody P3C8-C3Fab by ligating with C3Fab and to investigate its role in plasma half-life.Methods:The C3Fab peptide derived from protein G was molecularly fused with the nanobody P3C8 by DNA recombination technology. The nanoantibody P3C8-C3Fab was inducibly expressed and purified in the E. coli BL21 strain, and the binding of it to PD-L1 protein, mouse IgG, and PD-L1-expressing tumor cells was detected by enzyme-linked immunosorbent assay (ELISA). The residual P3C8-C3Fab was detected in mouse serum at different times using double-antibody sandwich ELISA to assess the prolongation of the plasma half-life of PD-L1 nanobodies by C3Fab. Results:The nanoantibody P3C8-C3Fab was successfully constructed, and it could efficiently express itself in soluble form in BL21. The purified NbP3C8-C3Fab protein was obtained with a mass fraction of about 90% at a yield of 7.18 mg/L. The affinity of P3C8-C3Fab for PD-L1 protein and mouse IgG gradually increased with increasing mass concentration and showed a concentration correlation. The binding of P3C8-C3Fab to lung cancer A549 cells showed a concentration correlation. The concentration standard curve of P3C8-C3Fab in mouse serum showed a typical S-shape with a concentration correlation. The plasma half-life of P3C8 was only 0.44 h, while the plasma half-life of P3C8-C3Fab was 21.27-fold higher, up to 9.36 h.Conclusions:The linkage of C3Fab to the nanobodies of P3C8 can significantly prolong the plasma half-life of P3C8, which is valuable for the improvement of in vivo nanobody effects.
3.Comparison of Direct and Extraction Immunoassay Methods With Liquid Chromatography-Tandem Mass Spectrometry Measurement of Urinary Free Cortisol for the Diagnosis of Cushing’s Syndrome
Danni MU ; Jiadan FANG ; Songlin YU ; Yichen MA ; Jin CHENG ; Yingying HU ; Ailing SONG ; Fang ZHAO ; Qi ZHANG ; Zhihong QI ; Kui ZHANG ; Liangyu XIA ; Ling QIU ; Huijuan ZHU ; Xinqi CHENG
Annals of Laboratory Medicine 2024;44(1):29-37
Background:
Twenty-four-hour urinary free cortisol (UFC) measurement is the initial diagnostic test for Cushing’s syndrome (CS). We compared UFC determination by both direct and extraction immunoassays using Abbott Architect, Siemens Atellica Solution, and Beckman DxI800 with liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, we evaluated the value of 24-hr UFC measured by six methods for diagnosing CS.
Methods:
Residual 24-hr urine samples of 94 CS and 246 non-CS patients were collected.A laboratory-developed LC-MS/MS method was used as reference. UFC was measured by direct assays (D) using Abbott, Siemens, and Beckman platforms and by extraction assays (E) using Siemens and Beckman platforms. Method was compared using Passing–Bablok regression and Bland–Altman plot analyses. Cut-off values for the six assays and corresponding sensitivities and specificities were calculated by ROC analysis.
Results:
Abbott-D, Beckman-E, Siemens-E, and Siemens-D showed strong correlations with LC-MS/MS (Spearman coefficient r = 0.965, 0.922, 0.922, and 0.897, respectively), while Beckman-D showed weaker correlation (r = 0.755). All immunoassays showed proportionally positive bias. The areas under the curve were 0.975 for Abbott-D, 0.972 for LCMS/MS, 0.966 for Siemens-E, 0.948 for Siemens-D, 0.955 for Beckman-E, and 0.877 for Beckman-D. The cut-off values varied significantly (154.8–1,321.5 nmol/24 hrs). Assay sensitivity and specificity ranged from 76.1% to 93.2% and from 93.0% to 97.1%, respectively.
Conclusions
Commercially available immunoassays for measuring UFC show different levels of analytical consistency compared to LC-MS/MS. Abbott-D, Siemens-E, and Beckman-E have high diagnostic accuracy for CS.
4.Influence of gestational weight gain and preconception body mass index on overweight and obesity of school-age children
Caixia HU ; Tianfeng WU ; Hua CHEN ; Sen WANG ; Yichen CHEN ; Jiayi SHENG ; Lianghong SUN ; Xiaobin QU ; Yi ZHOU ; Pinqing BAI
Chinese Journal of Child Health Care 2024;32(3):248-254
【Objective】 To understand the prevalence of overweight/obesity among school-age children in Pudong New Area of Shanghai, and to explore the influence of gestational weight gain and pre-pregnancy body mass index (BMI) on weight status of school-age children. 【Methods】 From November to December 2020,a stratified cluster sampling method was adopted to select first-grade students from 13 primary schools in Pudong New Area of Shanghai.After matching with the birth monitoring database, 755 students with complete birth information were selected as the study subjects.The relevant information of mothers before and during pregnancy was retrospectively collected, and the effects of pregnancy weight gain combined with pre-pregnancy BMI on overweight/obesity in school-age children were analyzed. 【Results】 1) The prevalence rates of overweight and obesity of first-grade children were 15.89% and 18.41%, respectively.2) Maternal excessive weight gain during pregnancy (OR=1.678) and overweight/obesity before pregnancy (OR=2.315,2.412) were risk factors for overweight/obesity of the offspring at school age(P<0.05).3) For mothers who were underweight before pregnancy, excessive weight gain during pregnancy was associated with overweight/obesity in school-age children in their offspring (OR=7.436, 95%CI: 1.489 - 37.143,P<0.05).4) Excessive weight gain during pregnancy combined with overweight/obesity before pregnancy significantly increased the risk of overweight/obesity in offspring (OR=3.606, 95%CI: 2.030 - 6.405, P<0.05). Mothers who gained a moderate amount of weight during pregnancy and were emaciated before pregnancy had a significantly lower risk of overweight/obesity in their school-age children (OR=0.217, 95%CI: 0.049 - 0.967, P<0.05). 【Conclusion】 Excessive weight gain during pregnancy increases the risk of overweight/obesity in school-age children in their offspring, strengthening pregnancy health education and perinatal care to help pregnant women maintain appropriate weight gain during pregnancy may be an important and novel strategy to prevent childhood obesity.
5.Expression of alcohol dehydrogenase 1 A and vascular endothelial growth factor-A in hepatocellular carcinoma
Lele XUE ; Yuying JING ; Kaige YANG ; Liwen QI ; Tong WU ; Yilin REN ; Yichen ZANG ; Lianghai WANG ; Haijun ZHANG ; Weihua LIANG ; Jianming HU
Acta Universitatis Medicinalis Anhui 2024;59(3):499-505
Objective To investigate the expression,synergistic relationship and clinical significance of alcohol de-hydrogenase(ADH1A)and vascular endothelial growth factor-A(VEGFA)in hepatocellular carcinoma(HCC).Methods The expression and correlation of ADH1A and VEGFA in HCC and adjacent normal tissues were ana-lyzed by GEPIA.TCGA and GSEA were used to analyze the pathway of ADH1A in HCC.The clinical and patho-logical data of 84 patients with HCC were collected,and 54 patients with paracancer normal tissue samples were se-lected as controls to analyze the correlation between ADH1A and VEGFA and clinicopathological parameters of HCC.Immunohistochemistry was used to detect the protein expression of ADH1A and VEGFA in cases and con-trols,and the correlation between the expression of ADH1A and VEGFA and the clinical progression and prognosis of patients with HCC was analyzed based on clinical pathological parameters and Kaplan-Meier.Results Bioinfor-matics analysis found that ADH1A was low-expressed in HCC and VEGFA was highly expressed in HCC,and there was a negative correlation between the two(P<0.001);immunohistochemical detection results showed that the expression of ADH1A in HCC tissue was lower than that in normal tissue adjacent to cancer(P<0.01)while the expression rate of VEGFA in HCC tissue was significantly higher than that of normal tissue adjacent to cancer(P<0.01);The recurrence rate of vascular thrombus and HCC patients in HCC group with high expression of ADH1A was lower(P<0.05).The proportion of tumor diameter>5 cm,high TNM stage,microsatellite and G2-G3 dif-ferentiation in HCC tissues in VEGFA high expression group was higher(P<0.05).Kaplan-Meier survival analy-sis showed that patients with high ADH1A expression and low VEGFA expression had a higher five-year survival rate.Conclusion Low expression of ADH1A and high expression of VEGFA in tumor tissues of patients with HCC indicate tumor progression and can be used as one of the prognostic evaluation indicators for patients with HCC.
6.Analysis of Thrombophilia Gene Screening Results in Blood Samples of 582 16-year-old Adolescents in Xi'an Area
Yichen ZHANG ; Ning AN ; Yaozhen CHEN ; Xingbin HU
Journal of Modern Laboratory Medicine 2024;39(6):201-205
Objective To analyze the mutation rates of thrombolytic genes antiphospholipid antibody(APOH),thrombo-regulatory protein(THBD)and PC anticoagulant protein(PROC),providing a theoretical basis for the prevention and treatment of thrombolytic diseases in adolescents.Methods A total of 582 cases 16-year-old adolescents who underwent routine physical examination from May to December 2019 were selected as the study objects.The gene loci such as PROC c.574_576del,THBD c.-151G>T and APOHc.461G>A were detected by PCR-RFLP genotyping detection and gene sequencing technology,and statistical analysis was performed on mutation rates.Results PCR-RFLP genotyping detecting of 582 samples showed that the mutation rate of PROC c.574_576del was about 0.69%(4/582),which was lower than the overall mutation rate in the Chinese population(2.4%),while the mutation rates of THBD c.-151G>T and APOHc.461G>A were about 2.92%(17/582)and 12.71%(74/582),which were higher than the overall mutation rates in Chinese population(0.97%,10.27%).Sequencing analysis showed that APOHc.461G>A mutation was linked with APOHc.422T>C and APOHc.1004G>C mutation.Conclusion The mutation rate of thrombolytic gene in adolescents is different from that of the whole population.The mutation rates of APOHc.461G>A and THBD c.-151G>T are higher than those of the whole Chinese population,indicating that timely detection should be used in the diagnosis and treatment of thrombolytic diseases in adolescents.
7.Bioinformatics analysis based on effect of M2 macrophage-derived Siglec15 on malignant biological behaviour of esophageal squamous cell carcinoma cells and its experimental validation
Yilin REN ; Yichen ZANG ; Lele XUE ; Kaige YANG ; Sufang CHEN ; Weinan WANG ; Chenghua LUO ; Weihua LIANG ; Lianghai WANG ; Feng LI ; Jianming HU
Journal of Jilin University(Medicine Edition) 2024;50(4):881-890
Objective:To discuss the effect of sialic acid-binding immunoglobulin-like lectin-15(Siglec15)derived from M2 tumor-associated macrophages(M2-TAMs)on promoting the malignant biological behavior of the esophageal squamous cell carcinoma(ESCC)through bioinformatics analysis,and to validate the findings through cell experiment.Methods:The Tumor Immune Estimation Resource(TIMER)online Database was used to analyze the expression differences and immune infiltration of Siglec15 in pan-cancer and adjacent normal tissues.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of Siglec15 mRNA in M2-TAMs and ESCC EC109 and KYSE150 cells.Based on the non-contact co-culture of M2-TAMs and ESCC cells,the following groups were set up,such as EC109/KYSE150 group,EC109/KYSE150+si-NC group(transfected with si-NC sequence),and EC109/KYSE150+si-Siglec15 group(transfected with si-Siglec15#1 and si-Siglec15#2 sequences).CCK-8 method was used to detect the proliferation activities of the cells in various groups;wound healing assay was used to detect the wound healing rates of the cells in various groups;Transwell chamber assay was used to detect the numbers of migration and invasion cells in various groups;flow cytometry was used to detect the apoptotic rates of the cells in various groups.Results:The bioinformatics analysis results showed that compared with adjacent normal tissue,the expression levels of Siglec15 mRNA in pan-cancer tissues such as esophageal cancer,colon cancer,and head and neck squamous cell carcinoma tissues were increased(P<0.05 or P<0.01),and the expression level of Siglec15 mRNA in esophageal cancer tissue was significantly positively correlated with the infiltration of the macrophages(P<0.05).Compared with the EC109 cells and KYSE150 cells,the expression level of Siglec15 mRNA in M2-TAMs was significantly increased(P<0.01).There was no significant difference in the proliferation rate of the cells among EC109/KYSE150 group,EC109/KYSE150+si-NC group,and EC109/KYSE150+si-Siglec15 group(P>0.05).Compared with EC109/KYSE150 group,after treated for 24 and 48 h,the wound healing rate of the cells in EC109/KYSE150+si-NC group was increased(P<0.01),the numbers of migration and invasion cells were increased(P<0.05),and the apoptotic rate was decreased(P<0.01).Compared with EC109/KYSE150+si-NC group,the wound healing rates of the cells in EC109/KYSE150+si-Siglec15#1 group and EC109/KYSE150+si-Siglec15#2 group were decreased(P<0.05),the numbers of migration and invasion cells were decreased(P<0.05),and the apoptotic rates of the cells had no significant difference(P>0.05).Conclusion:Siglec15 derived from M2-TAMs may be a key factor in promoting the migration and invasion of the ESCC cells.
8.Recent advance in role of mitochondrial transfer in spinal cord injury
Sijia PENG ; Yichen MENG ; Miao HU ; Xuhui ZHOU
Chinese Journal of Neuromedicine 2024;23(6):613-617
Mitochondrial dysfunction after spinal cord injury (SCI) is recognized as a crucial pathological mechanism for secondary SCI. Studies have indicated that mitochondrial transfer plays a significant role in the process of neural regeneration following injury. After mitochondria migrating to injured neurons, they mainly function via enhancing the energy metabolism level of damaged neurons and reducing oxidative stress. In this article, we present an exhaustive overview on mechanism of mitochondrial transfer, and impact on neural regeneration after mitochondrial transfer so as to provide valuable insights for further exploring the role of mitochondrial transfer in SCI progression and offer innovative perspective on potential therapeutic strategies for SCI.
9.Systematic biopsy combined with cognitive fusion targeted biopsy increases the detec-tion rate of clinically significant prostate cancer
Linjun HU ; Yonghai CHEN ; Yichen WANG ; Jianzhong SHOU
Chinese Journal of Clinical Oncology 2023;50(21):1081-1085
Objective:To investigate the ability of separate and combined biopsy methods to distinguish clinically significant prostate cancer(csPCa)from clinically insignificant prostate cancer(incsPCa),we assessed diagnostic positive rates for patients undergoing transperineal pro-state systematic biopsy(SB),cognitive fusion targeted biopsy(CF-TB),and combined biopsy(CB)(i.e.SB combined with CF-TB)under intra-venous anesthesia.Methods:We analyzed clinical data from 151 patients with prostate-specific antigen(PSA)≤50 ng/mL undergoing their first prostate biopsy in Cancer Hospital of Huanxing Chaoyang District Beijing and National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College from January 2019 to November 2021.The 3.0 Tesla standard prostate multi-parametric magnetic resonance imaging(mpMRI)examinations found 161 lesions with prostate ima-ging reporting and data system(PI-RADS)scores≥3.With patients under intravenous anesthesia and indwelling catheter,2-4 needle CF-TB biopsies were performed using transperineal ultrasound guidance,followed by 12 needle SB.Patients who underwent SB,CF-TB,and CB were each analyzed by stratification for their respective csPCa and incsPCa detection rates,age,PSA,CF-TB needle count,PI-RADS score,and digital rectal examination results.Results:The median PSA value for all patients was 11.50(0.52-49.37 ng/mL).In total,161 lesions with PI-RADS score≥3 points were found.All 151 patients received 12 needles of SB,while 47,52,and 52 patients received 2,3,and 4 needles of CF-TB,respectively.The respective positivity rates of SB,CF-TB and CB in diagnosing csPCa were 54.3%(82/151),53.0%(80/151)and 58.9%(89/151).Statistical results indicate that the difference in positivity rate between CB and SB is significant(P=0.016)as is the difference between CB and CF-TB positivity rates(P=0.004).The respective positivity rates of SB,CF-TB,and CB in diagnosing incsPCa were 7.9%(12/151)、9.3%(14/151),and 11.3%(17/151).The positivity rate of CB was not significantly different than that of SB or CF-TB(all P>0.05).Stratification plane analysis with age,PSA value,number of CF-TB needles,PI-RADS score,and digital rectal examination results showed that the 2-needle CF-TB scheme was inferior to CB in diagnosing csPCa(P=0.031).There was no significant difference in the csPCa positivity rates of 3-needle and 4-needle CF-TB relative to CB.Conclusions:CB achieves a higher csPCa diagnosis rate without increasing de-tection of incsPCa under transperineal ultrasound guidance.CF-TB with 3-needles per lesion was highly effective in diagnosing csPCa.
10.New insights into effects of Kaixin Powder on depression via lipid metabolism related adiponectin signaling pathway.
Wenshan YANG ; Hong YIN ; Yichen WANG ; Yuanbo WANG ; Xia LI ; Chaochen WANG ; Ping LIU ; Yuan HU
Chinese Herbal Medicines 2023;15(2):240-250
OBJECTIVE:
To clarify the anti-depressive potential mechanisms of Kaixin Powder (KP), a drug that helps to prevent and treat depression and other mentaldiseases, from genome-wide transcriptome profiling.
METHODS:
Transcriptome and KEGG pathway analysis were conducted on the hippocampus of depressed rats, then the differentially expressed genes were validated and serum concentration of lipid parameters were identified by enzymatic assays. Furthermore, high-fat diets induced depression-like behaviors in Syrian golden hamsters were conducted to verify the predicted molecular mechanisms acquired from the transcriptome analysis.
RESULTS:
Transcriptome results revealed that the 24 differentially expressed genes (DEGs) in chronic mild stress (CMS) rats could be reversed after two weeks of KP treatment. The mechanisms of KP in treating depression firstly involved the regulation of several pathology modules, including lipid metabolism, synapse function and inflammation. KP could regulate imbalances of lipid homeostasis in high-fat diet induced depressive symptoms. Furthermore, it was validated that cholesterol metabolism dysfunction can be ameliorated by KP, which was correlated with upregulation of the AdipoR1-BDNF (brain-derived neurotrophic factor) co-regulatory pathway.
CONCLUSION
Taken together, our results demonstrated that KP not only alleviates depression via traditional mental illness targets, but it may also simulates the cholesterol metabolism and adiponectin signaling with multi-target characteristics.


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