1.The clinical value of artificial intelligence quantitative parameters in distinguishing pathological grades of stage Ⅰ invasive pulmonary adenocarcinoma
Yun LIANG ; Mengmeng REN ; Delong HUANG ; Jingyan DIAO ; Xuri MU ; Guowei ZHANG ; Shuliang LIU ; Xiuqu FEI ; Dongmei DI ; Ning XIE
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(05):598-607
Objective To explore the clinical value of artificial intelligence (AI) quantitative parameters in distinguishing pathological grades of stageⅠ invasive adenocarcinoma (IAC). Methods Clinical data of patients with clinical stageⅠ IAC admitted to Yantaishan Hospital Affiliated to Binzhou Medical University from October 2018 to May 2023 were retrospectively analyzed. Based on the 2021 WHO pathological grading criteria for lung adenocarcinoma, IAC was divided into gradeⅠ, grade Ⅱ, and grade Ⅲ. The differences in parameters among the groups were compared, and logistic regression analysis was used to evaluate the predictive efficacy of AI quantitative parameters for grade Ⅲ IAC patients. Parameters were screened using least absolute shrinkage and selection operator (LASSO) regression analysis. Three machine learning models were constructed based on these parameters to predict grade Ⅲ IAC and were internally validated to assess their efficacy. Nomograms were used for visualization. Results A total of 261 IAC patients were included, including 101 males and 160 females, with an average age of 27-88 (61.96±9.17) years. Six patients had dual primary lesions, and different lesions from the same patient were analyzed as independent samples. There were 48 patients of gradeⅠ IAC, 89 patients of grade Ⅱ IAC, and 130 patients of grade Ⅲ IAC. There were statitical differences in the AI quantitive parameters such as consolidation/tumor ratio (CTR), ect among the three goups. (P<0.05). Univariate analysis showed that the differences in all variables except age were statistically significant (P<0.05) between the group gradeⅠ+grade Ⅱand the group grade Ⅲ . Multivariate analysis suggested that CTR and CT standard deviation were independent risk factors for identifying grade Ⅲ IAC, and the two were negatively correlated. Grade Ⅲ IAC exhibited advanced TNM staging, more pathological high-risk factors, higher lymph node metastasis rate, and higher proportion of advanced structure. CTR was positively correlated with the proportion of advanced structures in all patients. This correlation was also observed in grade Ⅲ but not in gradeⅠand grade ⅡIAC. CTR and CT median value were selected by using LASSO regression. Logistic regression, random forest, and XGBoost models were constructed and validated, among which, the XGBoost model demonstrated the best predictive performance. Conclusion Cautious consideration should be given to grade Ⅲ IAC when CTR is higher than 39.48% and CT standard deviation is less than 122.75 HU. The XGBoost model based on combined CTR and CT median value has good predictive efficacy for grade Ⅲ IAC, aiding clinicians in making personalized clinical decisions.
2.Preliminary study on delaying aging induced thymus degeneration in SAMP6 mice with Bazi Bushen capsule
Zhao-Dong LI ; Yin-Xiao CHEN ; Bo-Yang GONG ; Zhe XU ; Zhi-Xian YU ; Yue-Xuan SHI ; Yan-Fei PENG ; Yu-Hong BIAN ; Yun-Long HOU ; Xiang-Ling WANG ; Shu-Wu ZHAO
Chinese Pharmacological Bulletin 2024;40(6):1186-1192
Aim To explore the improvement effect of Bazi Bushen capsule on thymic degeneration in SAMP6 mice and the possible mechanism.Methods Twenty 12 week old male SAMP6 mice were randomly divided into the model group(SAMP6)and the Bazi Busheng capsule treatment group(SAMP6+BZBS).Ten SAMR1 mice were assigned to a homologous control group(SAMR1).The SAMP6+BZBS group was oral-ly administered Bazi Bushen capsule suspension(2.8 g·kg-1)daily,while the other two groups were orally administered an equal amount of distilled water.After nine weeks of administration,the morphology of the thymus in each group was observed and the thymus in-dex was calculated;HE staining was used to observe the structural changes of thymus tissue;SA-β-gal stai-ning was used to detect thymic aging;flow cytometry was used to detect the proportion of thymic CD3+T cells in each group;Western blot was used to detect the levels of p16,Bax,Bcl-2,and cleaved caspase-3 proteins in thymus;immunofluorescence was applied to detect the proportion of cortical thymic epithelial cells in each group;ELISA was employed to detect IL-7 lev-els in thymus.Results Compared with the SAMP6 group,the thymic index of the SAMP6+BZBS group significantly increased(P<0.05);the disordered thy-mic structure was significantly improved;the positive proportion of SA-β-gal staining significantly decreased(P<0.01);the proportion of CD3+T cells apparently increased(P<0.05);the level of p16 protein signifi-cantly decreased(P<0.05);the level of Bcl-2 pro-tein significantly increased(P<0.05),while the lev-el of cleaved caspase-3 protein markedly decreased(P<0.05);the proportion of cortical thymic epithelial cells evidently increased;the level of IL-7 significantly increased(P<0.01).Conclusions Bazi Bushen capsule can delay thymic degeneration,inhibit cell ap-optosis in thymus and promote thymic cell development in SAMP6 mice,which may be related to increasing the proportion of cortical thymic epithelial cells and promoting IL-7 secretion.
3.Spatial transcriptome changes in striatum brain region of model mice subjected to chronic social defeat stress
Wenxin YUN ; Zhen HE ; Fanxing XU ; Fei LI ; Ning WU
Chinese Journal of Pharmacology and Toxicology 2024;38(8):575-586
OBJECTIVE To investigate the transcriptomal charactersistics of the striatum in the chronic social defeat stress(CSDS)model mice by using spatial transcriptome analysis and to address the underlying mechanism of the striatum in regulating depressive states.METHODS The CSDS para-digm was employed to establish a depression-like mouse model.The depressive indicators of behavioral despair,anhedonia,and social disorders were assessed through a battery of tests,including the tail suspension test,forced swim test,sucrose preference test,and social interaction experiments.The control mice and the mice exhibiting CSDS-sensitive depression-like behaviors were selected for spatial tran-scriptome sequencing of the striatal region.This sequencing aimed to identify highly expressed genes,followed by KEGG and GO enrichment analyses using the DAVID database.RESULTS The CSDS mouse model effectively induced behavioral despair,anhedonia and social avoidance(P<0.05,P<0.01).Spatial transcriptome analysis revealed 193 differentially expressed genes in the striatum of normal mice.KEGG and GO analyses indicated that these genes were primarily associated with striatal devel-opment,locomotor behaviors,and drug addiction.They were strongly implicated in signaling pathways such as cyclic adenosine monophosphate,cyclic guanosine monophosphate-protein kinase G,calcium signaling,Ras-related protein 1,and mitogen-activated protein kinase,and synaptic linked to GABAergic and dopaminergic neurons.In contrast,CSDS modeling mice led to the identification of 298 differentially expressed genes in the striatum compared with the normal control mice.These genes were significantly enriched in pathways related to neurodegenerative diseases,including Huntington disease,Alzheimer disease,and Parkinson disease.CONCLUSION Depressive states induced by CSDS are associated with the pathological processes underlying neurodegenerative diseases in the striatum.
4.Clinical manifestation and imaging diagnostic analysis of fat embolism syndrome
Qian DAN ; Hai-Yan WU ; Yun-Jie HUANG ; Fei LUO ; Xu-Xue LI
China Journal of Orthopaedics and Traumatology 2024;37(3):306-310
Objective To explore characteristics of clinical and imaging findings in patients with fat embolism syndrome.Methods From January 2021 to October 2022,clinical manifestations of 13 patients with fat embolism due to fracture or or-thopaedic surgery were retrospectively analyzed,including 11 males and 2 females,aged from 17 to 60 years old.Mental and respiratory abnormalities and changes in vital signs occurred after admission or after surgery,and patient's chest and brain imaging results were abnormal.The patient's mental and respiratory abnormalities,vital signs,chest and brain imaging results were continuously monitored.Results The main clinical manifestations of fat embolism syndrome were abnormal pulmonary respiration in 13 patients,abnormal central nervous function in 7 patients,and spotted rash in 2 patients.Chest CT showed dif-fuse distribution of ground glass shadows in 13 patients,and severe symptoms were"snowstorm".Nine patients with ground glass fusion consolidation,5 patients with multiple nodules and 4 patients accompanied by bilateral pleural effusion.Head CT findings of 5 patients were negative,and head MRI findings of 1 patient showed multiple T1WI low signal,T2WI high signal shadow,DWI high signal shadow,and"starry sky sign"in basal ganglia,radiative crown,hemioval center,thalamus,frontal parietal cortex and subcortex.Conclusion Fat embolism syndrome has a high mortality rate.Clinical manifestations of respira-tory system and nervous system are not specific,and the skin spot rash has a characteristic manifestation.The"blizzard"sign is the specific manifestation of chest X-ray and CT examination of fat embolism,and the"starry sky"sign is the typical manifesta-tion of diffusion-weighted sequence of brain MRI examination of fat embolism.
5.Antibiotic bone cement covered reconstruction plate for infected anterior pelvic ring fractures
Meng LI ; Ke-Jing WANG ; Zhen-Yang GAO ; Yun-Fei XIE ; Tao GUO
China Journal of Orthopaedics and Traumatology 2024;37(5):451-457
Objective To explore the clinical efficacy of antibiotic bone cement covered reconstruction steel plate in the treatment of infected anterior pelvic ring fracture.Methods From January 2017 to March 2022,11 patients with infected ante-rior pelvic ring fracture were treated with antibiotic bone cement covered reconstruction steel plate including 7 males and 4 fe-males and the age ranged from 27 to 49 years old.The pelvic fractures were classified according to the Tile typology:4 cases of Cl type,4 cases of C2 type,and 3 cases of C3 type.Among them,2 cases of infected anterior ring were infected after internal fixation of anterior ring,and 9 patients were infected with infected anterior ring due to incomplete early debridement,which was classified as infected according to the injury severity score(ISS)for 24 to 38 scores.The anterior ring was internally fixed by extended debridement,irrigation,and antibiotic bone cement covered reconstruction plate,and the posterior ring fractures were all closed reduction and internally fixed with sacroiliac screws.Results All 11 cases obtained follow-up from 13 to 20 months.A-mong them,2 patients had recurrence of postoperative infection,1 case was re-dissected and replaced with antibiotic bone cement-coated internal fixation,and 1 case had a milder infection without accumulation of the medullary cavity,and the infection was controlled by retaining the plate and replacing the antibiotic bone cement only after dissecting.Two cases developed incisional oozing,which healed after removal of the internal fixation three months postoperatively.All patients did not show pelvic fracture redisplacement or reinfection during the follow-up period.All 11 cases eventually healed bony.At the final follow-up,according to the Matta score,the fracture reduction was excellent in 6 cases,good in 4,and possible in 1.According to the Majeed functional score,it was excellent in 6,good in 3,and possible in 2.Conclusion Antibiotic bone cement covered reconstruction plate is ef-fective in the treatment of infected anterior pelvic ring fracture,with high intraoperative safety and low recurrence rate of infec-tion,which is conducive to the early postoperative rehabilitation and significantly shortens the course of the disease.
6.Research status of risk prediction model of post-endoscopic retrograde cholangiopancreatography pancreatitis
Zhe-Yu ZHU ; Yi-Yu HU ; Peng CHEN ; Fei-Fan WU ; Si-Yu WANG ; Wei-Min WANG ; Chun-Mu MIAO ; Yun-Bing WANG ; Xiong DING
Journal of Regional Anatomy and Operative Surgery 2024;33(12):1105-1109
Post-endoscopic retrograde cholangiopancreatography pancreatitis(PEP)is one of the most common complications after endoscopic retrograde cholangiopancreatography(ERCP).Numerous PEP prediction models have been established based on different statistical methods at home and abroad.The PEP prediction model,as a tool for evaluating and screening high-risk populations,can provide a basis for medical staff to find high-risk PEP patients early and take effective preventive measures.In recent years,new PEP prediction models have appeared one after another,but there is still a lack of recognized reliable prediction models in clinic.This article reviews the research status of PEP risk prediction models,aim to provide a direction for establishing a more reliable,accurate,and practical PEP risk prediction model in the later period.
7.Species identification of hard ticks and molecular survey of Ana plasma in partial areas of Anhui Province
Xue ZHAO ; Khakhane LERATO ; Wan-Qing LU ; Xin-Yun WU ; Fang-Fei SONG ; Yu XIN ; Ying-Ying ZHANG ; Chen XING ; Ke-Han XU ; Mao-Zhang HE ; Yan LIU
Chinese Journal of Zoonoses 2024;40(4):302-307
The distribution of Ixodes and Ana plasma carried by Ixodes ticks in Anhui Province was clarified as reference for prevention and control of anaplasmosis.In total,630 hard ticks were collected from Jinzhai County,Hanshan County,Jing-de County and Chaohu City in Anhui Province from April to August 2023.Ticks were identified by morphological analysis and 16S rRNA sequencing.Nested PCR with Anaplasma species-specific primers were used to detect 16S rRNA of Anaplasma spe-cies carried by ticks.A phylogenetic tree was constructed using MEGA11.0 software.Of the identified ticks,18.8%(18/96)were Rhipicephalus microplus and 81.2%(78/96)were Haemaphysalis longicorni in Jinzhai County of Anhui Province,all were H.longicorni in Hanshan County and Chaohu City,while the main species in Jingde County was R.microplus.The posi-tive rate of Anaplasma carried by H.longicornis was 30.9%(102/330),which included A.bovis at 1.8%(6/330),A.phagocytophilum at 21.8%(72/330)and uncultured Anaplasma species at 7.3%(24/330).R.microplus was positively cor-related to A.bovis(13.6%,18/132).The uncultured Anaplasma species was mainly detected in host-free ticks.A.phagocy-tophilum was detected in 24.4%of parasitic ticks and 15.8%of host-free ticks.The positive rates of host-free and parasitic ticks were 19.9%and 17.8%,respectively.These results show that H.longicornis and R.microplus were the dominant ticks in several counties of Anhui Province.H.longicornis and R.microplus as well as free and parasitic ticks all carried Anaplas-ma.
8.Evaluation and optimization of metagenomic sequencing platforms for bloodstream infection samples
Xin PENG ; Hang FAN ; Meng-Nan CUI ; Lei LIN ; Guang-Qian PEI ; Yun-Fei WANG ; Xiu-Juan ZUO ; Xiao-Feng FANG ; Yan GUO ; Yu-Jun CUI
Chinese Journal of Zoonoses 2024;40(10):928-934
This study was aimed at comparing performance differences among three metagenomic sequencing platforms,MGISEQ-2000,Illumina NextSeq 2000,and Ion GeneStudio S5 Plus,to optimize the sequencing process for trace samples.The three sequencing platforms were used to perform high-throughput sequencing on DNA standards and simulated samples.Through analysis of the quality of raw data and microbial detection capabilities,systematic differences among platforms were compared.The sequencing results were optimized for trace samples by incorporation of exogenous nucleic acids during the li-brary preparation process.In terms of data output per batch and base quality,MGISEQ-2000 surpassed the other two plat-forms.Illumina NextSeq 2000 had the lowest proportion of duplicate reads,whereas Ion GeneStudio S5 Plus had the highest proportion,and significant differences were observed across platforms(P<0.001).In sequencing uniformity,MGISEQ-2000 and Illumina NextSeq 2000 were superior to Ion GeneStudio S5 Plus.MGISEQ-2000 provided a substantial advantage in microbial detection capability(P<0.001),but the advantage diminished with decreasing bacterial fluid concentration.Ion GeneStudio S5 Plus had the shortest duration for single-batch sequencing.Moreo-ver,for trace samples with DNA content ≤0.05 ng,the experi-mental group(with added exogenous nucleic acids)achieved a higher number of reads than the control group(without exogenous nucleic acids),with a 11.09±8.03 fold increase.In conclu-sion,the different sequencing platforms each had advantages and disadvantages,thus allowing researchers to choose the appro-priate platform according to specific needs.Furthermore,the addition of exogenous nucleic acids improved the microorganism detection efficiency,and provided better support for subsequent diagnosis and evaluation of results.
9.Evaluation of the Promoter Activity of the CHO Cell Expression System Based on Site-specific Integration
Chen LU ; Zi-Yu WANG ; Yan-Fei CAI ; Yong-Qiang DENG ; Jian JIN ; Xue-Feng DING ; Yun CHEN
Chinese Journal of Biochemistry and Molecular Biology 2024;40(10):1400-1408
In industrial production,the expression level of drug proteins in Chinese hamster ovary cells(CHO)is influenced by many factors:the regulatory elements on transcription and translation,the ge-nomic integration sites,and the expression system.Transcription,as the first step of gene expression,largely affects protein expression,and the promoter plays a crucial role in the initiation of transcription.Most of the promoters were screened through transient transfection or random integration,but the presence of unclear copy number or random integration sites makes it difficult to accurately evaluate the promoter activity.To some extent,site-specific integration can reduce the impact of positional effects on exogenous genes and may potentially increase the expression level of exogenous genes.In the early stage of our re-search,multiple sites that can stably express exogenous proteins were identified and verified in the CHO cell genome.In this study,one of these sites(2c6)was selected for the evaluation of promoter activity.The CRISPR/Cas9 gene editing technique was used to site-specifically integrate the reporter gene(EG-FP)regulated by the simian virus early promoter(SV40),mouse elongation factor-1α(mEF-1α),chicken β-actin(cACTB)promoter,and human phosphoglycerate kinase promoter(hPGK)into the 2c6 site,respectively.The mean fluorescence intensity of the cells was analyzed by flow cytometry,and the mRNA level of EGFP was detected by qPCR to comprehensively evaluate the activity of the promoter.The results showed that the activities of the mEF-1α and mACTB promoters were better than those of SV40 and hPGK.The results of the secondary flow cytometry sorting showed that site-specific integration can more accurately evaluate the activity of the promoter in the CHO cell expression system.
10.Influence of Methylenetetrahydrofolate Reductase C677T Polymorphism on High-Dose Methotrexate Toxicity in Pediatric Mature B-cell lymphoma Patients
Jia-Qian XU ; Juan WANG ; Su-Ying LU ; Yan-Peng WU ; Lan-Ying GUO ; Bo-Yun SHI ; Fei-Fei SUN ; Jun-Ting HUANG ; Jia ZHU ; Zi-Jun ZHEN ; Xiao-Fei SUN ; Yi-Zhuo ZHANG
Journal of Experimental Hematology 2024;32(6):1733-1737
Objective:To investigate the effect of genetic polymorphism of MTHFR C677T (rs1801133) on methotrexate (MTX) related toxicity in pediatric mature B-cell lymphoma patients. Methods:Fifty-eight intermediate and high risk patients under 18 years of age with mature B-cell lymphoma who received 5 g/m2 MTX (24 h intravenous infusion) in Sun Yat-sen University Cancer Center from August 2014 to December 2021 were included,and their toxicity of high-dose MTX (HD-MTX) were monitored and analyzed. Results:Among the 58 pediatric patients,the number of CC,CT,and TT genotypes for MTHFR C677T was 33,19 and 6,respectively. A total of 101 courses of HD-MTX therapy were counted,of which plasma MTX level>0.2 μmol/L at 48 h post-MTX infusion were observed in 35 courses,≤0.2 μmol/L in 66 courses. Inter-group comparison showed that plasma MTX level>0.2 μmol/L at 48 h post-MTX infusion increased the risk of developing oral mucositis (P<0.05). Compared with wild-type (CC genotype),patients in the mutant group (CT+TT genotype) were more likely to develop myelosuppression,manifested as anemia,leucopenia,neutropenia and thrombocytopenia. However,plasma MTX level at 48 h was not associated with MTHFR C677T gene polymorphism. Conclusion:The risk of developing oral mucositis in children with mature B-cell lymphoma is associated with plasma MTX concentration. Polymorphism of MTHFR C677T gene is not related to plasma MTX concentration in children with mature B-cell lymphoma,but is related to grade Ⅲ to Ⅳ hematological toxicity.

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