1.Evaluation of A Liver Yin Deficiency Mouse Model Based on Untargeted Metabolomics
Xuening HUANG ; Xia ZHAO ; Mengyu HOU ; Zhiyu GUO ; Yaohui YE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):118-125
ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS), to evaluate the establishment of a mouse model of liver Yin deficiency by thyroid tablet suspension combined with 10% carbon tetrachloride(CCl4) from the perspective of non-targeted metabolomics, in order to lay the foundation for the establishment of a traditional Chinese medicine(TCM) syndrome model. MethodA total of 24 mice were randomly divided into blank group and model group. The model group was given thyroid tablet suspension(0.003 2 g·kg-1) by gavage for 14 consecutive days, and 10% CCl4(5 mL·kg-1) was intraperitoneally injected once a week to establish a liver Yin deficiency model, while the blank group was injected with an equal amount of olive oil intraperitoneally and gavaged with an equal amount of distilled water, and was fed with normal feed. After the modeling was completed, 6 mice in each group were randomly selected, the levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), cyclic adenosine monophosphate(cAMP), cyclic guanosine monophosphate(cGMP), interleukin(IL)-6, IL-10, tumor necrosis factor-α(TNF-α)were measured in the mice serum, and malondialdehyde(MDA), superoxide dismutase(SOD), total protein(TP), hydroxyproline(HYP) and other indicators were measured in the mice liver. Liver tissue sections were taken for hematoxylin-eosin(HE) staining and observing pathological changes. The remaining 6 mice in each group were subjected to UPLC-Q-TOF-MS combined with principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to screen differential metabolites in the liver Yin deficiency mouse model, Kyoto Encyclopedia of Genes and Genomes(KEGG) database was used to analyze the corresponding metabolic pathways of differential metabolites. ResultCompared with the blank group, mice in the model group showed liver Yin deficiency manifestations such as reduced body weight, fatigue and sleepiness, disheveled and lusterless hair, irritability. The levels of ALT, cAMP/cGMP, IL-6, AST, MDA, cAMP, TNF-α significantly increased(P<0.05, P<0.01), while the levels of SOD, IL-10 and cGMP significantly decreased(P<0.05, P<0.01), and the changes of HYP and TP were not statistically significant. Hepatic steatosis and distortion of the radial arrangement of the liver plate cells were seen in the section images of the model group, endogenous substances were clearly separated, and 252 differential metabolites were identified in the serum samples, which were mainly involved in the metabolic pathways of purine metabolism, steroid hormone biosynthesis and pyrimidine metabolism. A total of 229 differential metabolites were identified in the liver samples, mainly involving nucleotide metabolism, purine metabolism, steroid hormone biosynthesis, pyrimidine metabolism, antifolate resistance, insulin resistance, primary bile acid biosynthesis, prostate cancer, sulfur relay system, arachidonic acid metabolism and other metabolic pathways. ConclusionThe successful establishment of liver Yin deficiency model in mice by CCl4 combined with thyroid hormone is evaluated through the investigation of serum and liver metabolomics, combined with biochemical indicators, which provides a biological basis and experimental foundation for the Yin deficiency syndrome model of TCM.
2.A CT-based radiomics nomogram for predicting local tumor progression of colorectal cancer lung metastases treated with radiofrequency ablation
Haozhe HUANG ; Hong CHEN ; Dezhong ZHENG ; Chao CHEN ; Ying WANG ; Lichao XU ; Yaohui WANG ; Xinhong HE ; Yuanyuan YANG ; Wentao LI
China Oncology 2024;34(9):857-872
Background and Purpose:The early prediction of local tumor progression-free survival(LTPFS)after radiofrequency ablation(RFA)for colorectal cancer(CRC)lung metastases has significant clinical importance.The application of radiomics in the prediction of tumor prognosis has been explored.This study aimed to construct a radiomics-based nomogram for predicting LTPFS after RFA in CRC patients with lung metastases.Methods:This study retrospectively analyzed 172 CRC patients with 401 lung metastases admitted to Department of Interventional Radiology,Fudan University Shanghai Cancer Center from August 2016 to January 2019.This study was reviewed by the medical ethics committee of Fudan University Shanghai Cancer Center(ethics number:2402291-24).After augmentation of pre-ablation and immediate post-ablation computed tomography(CT)images,the target metastases and ablation regions were segmented manually to extract the radiomic features.Maximum relevance and minimum redundancy algorithm(MRMRA)and least absolute shrinkage and selection operator(LASSO)regression models were applied for feature selection.The clinical model,the radiomics model,and the fusion model were constructed based on the selected radiomic features and clinical variables screened by the multivariate analysis.The Harrell concordance index(C-index)and area under receiver operating characteristic(ROC)curves(AUC)were calculated to evaluate the prediction performance.Finally,the corresponding nomogram of the best model was drawn.Results:Among all the lung metastases,102(25.4%)had final recurrence,and 299(74.6%)had complete response(CR).The median follow-up time was 21 months(95%CI:19.466-22.534),and the LTPFS rates at 1,2,and 3 years after RFA were 76.5%(95%CI:72.0-80.4),72.1%(95%CI:66.6-76.9)and 69.9%(95%CI:64.0-75.1).In both the training and test dataset,the fusion model based on the final 12 radiomic features through the LASSO regression and 4 clinical variables screened by multivariate analysis achieved the highest AUC values for LTPFS,with C-index values of 0.890(95%CI:0.854-0.927)and 0.843(95%CI:0.768-0.916),respectively.Conclusion:The fusion model based on radiomic features and clinical variables is feasible for predicting LTPFS after RFA of CRC patients with lung metastases,whose performance is superior to the single radiomic and clinical model.At the same time,the nomogram of the fusion model can intuitively predict the prognosis of CRC patients with lung metastases after RFA,thus assisting clinicians in developing individualized follow-up review plans for patients and adjusting treatment strategies flexibly.
3.Immunosuppressive tumor microenvironment contributes to tumor progression in diffuse large B-cell lymphoma upon anti-CD19 chimeric antigen receptor T therapy.
Zixun YAN ; Li LI ; Di FU ; Wen WU ; Niu QIAO ; Yaohui HUANG ; Lu JIANG ; Depei WU ; Yu HU ; Huilai ZHANG ; Pengpeng XU ; Shu CHENG ; Li WANG ; Sahin LACIN ; Muharrem MUFTUOGLU ; Weili ZHAO
Frontiers of Medicine 2023;17(4):699-713
Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has achieved 40%-50% long-term complete response in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) patients. However, the underlying mechanism of alterations in the tumor microenvironments resulting in CAR-T cell therapy failure needs further investigation. A multi-center phase I/II trial of anti-CD19 CD28z CAR-T (FKC876, ChiCTR1800019661) was conducted. Among 22 evaluable DLBCL patients, seven achieved complete remission, 10 experienced partial remissions, while four had stable disease by day 29. Single-cell RNA sequencing results were obtained from core needle biopsy tumor samples collected from long-term complete remission and early-progressed patients, and compared at different stages of treatment. M2-subtype macrophages were significantly involved in both in vivo and in vitro anti-tumor functions of CAR-T cells, leading to CAR-T cell therapy failure and disease progression in DLBCL. Immunosuppressive tumor microenvironments persisted before CAR-T cell therapy, during both cell expansion and disease progression, which could not be altered by infiltrating CAR-T cells. Aberrant metabolism profile of M2-subtype macrophages and those of dysfunctional T cells also contributed to the immunosuppressive tumor microenvironments. Thus, our findings provided a clinical rationale for targeting tumor microenvironments and reprogramming immune cell metabolism as effective therapeutic strategies to prevent lymphoma relapse in future designs of CAR-T cell therapy.
4.Feasibility of using bedside ultrasound to evaluate residual gastric volume in critical ill patients with enteral nutrition support
Chenglin XIANG ; Ren FENG ; Yuanyuan MI ; Haiyan HUANG ; Jia WAN ; Enhua HU ; Zhiqiang PANG ; Yaohui MING
Chinese Journal of Practical Nursing 2020;36(19):1446-1451
Objective:To study the feasibility of using bedside ultrasound in evaluating gastric residual volume in critical ill patients with enteral nutrition support.Methods:From May 2019 to August 2019, 60 patients were selected to receive enteral nutrition via gastric tube in ICU of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. Patients were divided into the experimental group and the control group according to the odd and even number of beds, 30 patients in the experimental group with odd number of beds and 30 patients in the control group with even number of beds. Gastric residual volume was evaluated at 0, 4, 8, 12, 16, 20, 24 h of enteral nutrition. In the experimental group, the gastric residual volume was evaluated by bedside ultrasound and syringe suction at each time point. In the control group, only bedside ultrasound was used to evaluate gastric residual volume. The results of operation time, monitoring results at different time points, diarrhea and the utilization rate of gastrointestinal motility drugs target feeding time, vomiting, were compared between the two groups.Results:There was no statistical difference between the gastric residual amount monitored by ultrasound and the gastric residual amount monitored by suction ( P>0.05). The operating time of bedside ultrasound monitoring was (62.40 ± 4.00) s, the operating time of suction monitoring was (78.39 ± 12.15) s, and the operating time of bedside ultrasound monitoring was less than that of suction ( t value was 6.633, P<0.01). There was no significant difference in the rate of vomiting, diarrhea and gastrointestinal motility drugs between the two groups( P>0.05). The time to reach the target feeding amount in the control group was (3.04 ± 0.31) d, and the time to reach the target feeding amount in the experimental group was (4.19 ± 0.33) d. The time to reach the target feeding amount in the control group was less than that in the experimental group ( t value was 13.42, P<0.01). Conclusions:Bedside ultrasound can be used to evaluate the residual gastric volume of enteral nutrition support patients, guide the implementation of enteral nutrition, shorten the operation time, reduce the workload of nurses, and avoid the contamination of enteral nutrition preparation.
5.Diagnostic value of serum PG,G-17 combined with CA72-4 and 13C UBT in early gastric cancer
Xishun HUANG ; Lixin DENG ; Yaohui QIU ; Junkai SU
Chongqing Medicine 2017;46(10):1346-1348
Objective To investigate the change situation of serum pepsinogen (PG) and gastrin-17(G-17) levels change in gastric cancer,and on this basis diagnostic significance of combined detection of carbohydrate antigen 72-4 (CA72-4) and 13C urea breath test (13C UBT) detection in early gastric cancer.Methods The enzyme-linked immunosorbent (ELISA) method was used to detect serum PG Ⅰ,PG Ⅱ and G-17 levels in healthy people,atrophic gastritis group and gastric cancer group.Firstly the changes of above three indicators were compared;then according to PG Ⅰ and G-17,the carcinoma group was divided into the group A,B,C and D,these four groups were detected the helicobacter pylori infection status by 13C UBT.Finally the CA72-4 levels were performed the statistics by using the tumor markers detection results.Results Serum PG Ⅰ level and PG Ⅰ/PG Ⅱ ratio in the control group,atrophic gastritis group and gastric cancer group was gradually declined,the difference was statistically significant (P<0.05);serum G-17 level in the control group,atrophic gastritis group and gastric cancer group was gradually increased,the difference among 3 groups was statistically significant (P<0.05);in early gastric cancer rate ratio among 4 groups,which in the group B was highest,the difference was statistically significant (P<0.05);in the comparison of positive rates of 13 C UBT and CA72-4 level in early gastric cancer among 4 group,the 13 C UBT positive rate and CA72-4 level in the group B were higher than those in the group A,C and D,the differences were statistically significant (P<0.05).Moreover the CA72-4 level in the group B had significant difference between early gastric cancer and advanced gastric cancer (P<0.01).Conclusion Serum PG Ⅰ reduce and G-17 increase combined with CA72-4 high level and 13C UBT positive have an important forewarning value for the diagnosis of gastric cancer.
6.Cashmere goat bacterial artificial chromosome recombination and cell transfection system.
Tian HUANG ; Zhongyang CAO ; Yaohui YANG ; Gengsheng CAO
Chinese Journal of Biotechnology 2016;32(3):317-328
The Cashmere goat is mainly used to produce cashmere, which is very popular for its delicate fiber, luscious softness and natural excellent warm property. Keratin associated protein (KAP) and bone morphogenetic protein (BMP) of the Cashmere goat play an important role in the proliferation and development of cashmere fiber follicle cells. Bacterial artificial chromosome containing kap6.3, kap8.1 and bmp4 genes were used to increase the production and quality of Cashmere. First, we constructed bacterial artificial chromosomes by homology recombination. Then Tol2 transposon was inserted into bacterial artificial chromosomes that were then transfected into Cashmere goat fibroblasts by Amaxa Nucleofector technology according to the manufacture's instructions. We successfully constructed the BAC-Tol2 vectors containing target genes. Each vector contained egfp report gene with UBC promoter, Neomycin resistant gene for cell screening and two loxp elements for resistance removing after transfected into cells. The bacterial artificial chromosome-Tol2 vectors showed a high efficiency of transfection that can reach 1% to 6% with a highest efficiency of 10%. We also obtained Cashmere goat fibroblasts integrated exogenous genes (kap6.3, kap8.1 and bmp4) preparing for the clone of Cashmere goat in the future. Our research demonstrates that the insertion of Tol2 transposons into bacterial artificial chromosomes improves the transfection efficiency and accuracy of bacterial artificial chromosome error-free recombination.
Animals
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Bone Morphogenetic Proteins
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genetics
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Chromosomes, Artificial, Bacterial
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DNA Transposable Elements
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Fibroblasts
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Goats
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genetics
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Keratins
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genetics
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Transfection
7.Periodical quality control and testing of medical equipment
Wenna GAO ; Liyong HU ; Yaohui HUANG ; Xiangdong HUANG
Chinese Medical Equipment Journal 2015;(9):101-103
To realize dynamic and standardized periodical quality control of medical equipment. A set of auto reminder module for medical equipment quality control was established by using the user-defined flow of medical equipment operation maintenance system, and the continuous improvement was realized for medical equipment quality control in some hospital. Dynamic medical equipment quality control was formed from the static one, so that the efficiency of medical equipment quality control was enhanced greatly. References were provided for other hospitals in dynamic and informatzied medical equipment quality control and testing.
8.Giant benign symmetric lipomatosis of the neck: four case reports.
Rong ZHU ; Xinchun JIAN ; Yaohui CHEN ; Xieshan HUANG ; Deyu LIU
West China Journal of Stomatology 2015;33(4):439-443
Benign symmetric lipomatosis is a rare disease and may appear as a huge tumor in the neck. Four benign symmetric lipomatosis associated with gigantic painless mass or neck motion limitation were reported. Operative technique of one-time radical resection or stage resection was used to remove these tumors. One patient had a postoperative complication of incision effusion and infection, and three patients had no significant complication. At more than one-year follow-up, the motion and appearance of a patient's neck returned to normal, and no recurrence was observed. The etiology, clinical manifestations, diagnosis, and treatment of the disease were discussed.
Humans
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Lipomatosis, Multiple Symmetrical
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Neck
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Recurrence
9.Giant benign symmetric lipomatosis of the neck:four case reports
Rong ZHU ; Xinchun JIAN ; Yaohui CHEN ; Xieshan HUANG ; Deyu LIU
West China Journal of Stomatology 2015;(4):439-442
Benign?symmetric?lipomatosis?is?a?rare?disease?and?may?appear?as?a?huge?tumor?in?the?neck.?Four?benign?sym-metric?lipomatosis?associated?with?gigantic?painless?mass?or?neck?motion?limitation?were?reported.?Operative?technique?of?one-time?radical?resection?or?stage?resection?was?used?to?remove?these?tumors.?One?patient?had?a?postoperative?complication?of?incision?effusion?and?infection,?and?three?patients?had?no?significant?complication.?At?more?than?one-year?follow-up,?the?motion?and?appearance?of?a?patient’s?neck?returned?to?normal,?and?no?recurrence?was?observed.?The?etiology,?clinical?mani-festations,?diagnosis,?and?treatment?of?the?disease?were?discussed.
10.Relationship between methylenetetrahydrofolate reductase gene polymorphism and unstable angina pectoris disease
Hui YE ; Qiankun YE ; Gaixia DONG ; Xiangjing ZHOU ; Geng TIAN ; Ying LI ; Yaohui HUANG
Clinical Medicine of China 2009;25(5):480-482
Objective To explore the relationship between methylenetetra hydrofolate reduetase (MTHFR) C677T genotypo and unstable angina pectoris(UA) in Chinese population. Methods The study consisted of 90 UA cases (UA group), and an age- and sex- matched healthy control cases (control group, n = 90). PC R-RFLP was used to analyze polymorphism of the MTHFR C677T genotypo. The relationship between MTHFR C677T genotype and UA was observed. Results MTHFR 677C→T mutation was found in 30 of 90 patients with unstable angina pectoris (33.33%) and in 15 of 90 control subjects (16.67%). This difference was statistically significant (P<0.05). Conclusion MTHFR 677C→T mutation is closely related to the unstable angina poctoris.

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