1.Application of Recombinant Collagen in Biomedicine
Huan HU ; Hong ZHANG ; Jian WANG ; Li-Wen WANG ; Qian LIU ; Ning-Wen CHENG ; Xin-Yue ZHANG ; Yun-Lan LI
Progress in Biochemistry and Biophysics 2025;52(2):395-416
Collagen is a major structural protein in the matrix of animal cells and the most widely distributed and abundant functional protein in mammals. Collagen’s good biocompatibility, biodegradability and biological activity make it a very valuable biomaterial. According to the source of collagen, it can be broadly categorized into two types: one is animal collagen; the other is recombinant collagen. Animal collagen is mainly extracted and purified from animal connective tissues by chemical methods, such as acid, alkali and enzyme methods, etc. Recombinant collagen refers to collagen produced by gene splicing technology, where the amino acid sequence is first designed and improved according to one’s own needs, and the gene sequence of improved recombinant collagen is highly consistent with that of human beings, and then the designed gene sequence is cloned into the appropriate vector, and then transferred to the appropriate expression vector. The designed gene sequence is cloned into a suitable vector, and then transferred to a suitable expression system for full expression, and finally the target protein is obtained by extraction and purification technology. Recombinant collagen has excellent histocompatibility and water solubility, can be directly absorbed by the human body and participate in the construction of collagen, remodeling of the extracellular matrix, cell growth, wound healing and site filling, etc., which has demonstrated significant effects, and has become the focus of the development of modern biomedical materials. This paper firstly elaborates the structure, type, and tissue distribution of human collagen, as well as the associated genetic diseases of different types of collagen, then introduces the specific process of producing animal source collagen and recombinant collagen, explains the advantages of recombinant collagen production method, and then introduces the various systems of expressing recombinant collagen, as well as their advantages and disadvantages, and finally briefly introduces the application of animal collagen, focusing on the use of animal collagen in the development of biopharmaceutical materials. In terms of application, it focuses on the use of animal disease models exploring the application effects of recombinant collagen in wound hemostasis, wound repair, corneal therapy, female pelvic floor dysfunction (FPFD), vaginal atrophy (VA) and vaginal dryness, thin endometritis (TE), chronic endometritis (CE), bone tissue regeneration in vivo, cardiovascular diseases, breast cancer (BC) and anti-aging. The mechanism of action of recombinant collagen in the treatment of FPFD and CE was introduced, and the clinical application and curative effect of recombinant collagen in skin burn, skin wound, dermatitis, acne and menopausal urogenital syndrome (GSM) were summarized. From the exploratory studies and clinical applications, it is evident that recombinant collagen has demonstrated surprising effects in the treatment of all types of diseases, such as reducing inflammation, promoting cell proliferation, migration and adhesion, increasing collagen deposition, and remodeling the extracellular matrix. At the end of the review, the challenges faced by recombinant collagen are summarized: to develop new recombinant collagen types and dosage forms, to explore the mechanism of action of recombinant collagen, and to provide an outlook for the future development and application of recombinant collagen.
2.Radiomics-semantic models based on multicenter MRI to predict the treatment resistance of brain gliomas to chemoradiotherapy
Zhaotao ZHANG ; Yun PENG ; Youming ZHANG ; Di WU ; Binyan QIAN ; Lan LIU ; Yawen XIAO ; Jiman SHAO ; Xinlan XIAO
Journal of Practical Radiology 2025;41(9):1432-1436,1466
Objective To construct radiomics-semantic models to predict the treatment resistance of chemoradiotherapy in brain gliomas based on MRI and clinical data of multicenter patients.Methods Among 2 108 brain gliomas patients from five medical institutions,132 patients had residual gliomas after surgery.The clinical risk factors and multimodal MRI were collected.All patients were divided into training set(n=95)and validation set(n=37).The treatment response of gliomas after standardized chemoradiotherapy were divided into resistant and non-resistant types.The semantic features of MRI were evaluated by two radiologists.Three different segmentation regions of interest(ROI)were delineated to extract radiomics features.And that three groups of radiomics models were con-structed based on different sequence MRIs.The radiomics model with the best predictive efficacy in each group was selected and combined with MRI semantic features,three radiomics-semantic models(combined models)were established.Finally,a MRI semantic model,three groups of radiomics models and three combined models were developed.Results Comparisons between the different models showed that the radiomics-semantic model based on pre-operative T2-fluid attenuated inversion recovery(FLAIR)sequence,had the best predictive efficacy,the area under the curve(AUC)in the training and validation sets were 0.866[95%confidence interval(CI)0.790-0.942]and 0.810(95%CI 0.667-0.952),respectively.The radiomics-semantic model based on postoperative T1 WI sequence performed the second best,with the AUC of the training and validation sets being 0.812(95%CI 0.726-0.898)and 0.711(95%CI 0.541-0.881),respectively.Conclusion The combined models based on MRI radiomics and semantic features are able to predict the treatment resistance of chemoradiotherapy in brain gliomas patients,and may be used as an important basis for optimizing treatment.
3.Pituitary radiomics combined with MRI features for predicting growth hormone status in pediatric short stature
Fukun SHI ; Lan ZHANG ; Yu GAO ; Xiaoyang ZHAI ; Qian XU ; Jiaxu LIANG ; Shengli SHI ; Ling WU
Chinese Journal of Medical Imaging Technology 2025;41(7):1073-1078
Objective To observe the value of pituitary radiomics and MRI features combined model for predicting growth hormone(GH)status in pediatric short stature.Methods Totally 300 children with short stature were enrolled as training set,while other 73 cases were taken as external validation set.Based on growth hormone stimulation test,the children were divided into GH deficiency(GHD)group(n=228)and non-GHD group(n=145).The training set included 196 cases in GHD subgroup and 104 cases in non-GHD subgroup,while the validation set included 32 cases in GHD subgroup and 41 cases in non-GHD subgroup.Radiomics features of pituitary were extracted from T1WI.The key features were selected using least absolute shrinkage and selection operator(LASSO)regression,and machine learning models were subsequently constructed using support vector machine(SVM),logistic regression(LR),naive Bayes(NB)and K-nearest neighbor(KNN),respectively.Then combined models were constructed combining with MRI features,and the efficacy of each model was evaluated.Results The area under the curve(AUC)of SVM,LR,NB,and KNN radiomics model for predicting GH status in pediatric short stature was 0.860,0.831,0.838 and 0.901 in training set,0.788,0.829,0.823 and 0.770 in validation set,while of the relative combined SVM,LR,NB and KNN model was 0.924,0.903,0.859 and 0.920 in training set,and 0.827,0.881,0.836 and 0.718 in validation set.LRcombined model had the best overall performance,with sensitivity of 84.94%,specificity of 80.56%and accuracy of 83.61%in training set,and 80.95%,72.22%and 80.00%in validation set,respectively.Conclusion Pituitary radiomics and MRI features combined model could effectively predict GH status in pediatric short stature.
4.Interaction between influenza A virus nucleoprotein and TRIM25 protein
Xin-yan HU ; Qian-yun LIU ; Le-le AN ; Qiu-ju LAN ; Xiao-xia MA
Chinese Journal of Zoonoses 2025;41(3):219-226
This study was aimed at exploring the interaction between the nucleoprotein(NP)of influenza A virus(IAV)and TRIM25.The physicochemical properties and protein structure of IAV NP protein were analyzed through bioinformatics methods.The interaction between IAV NP and TRIM25 proteins was simulated with molecular docking techniques,and the in-teraction sites were predicted.With the cDNA of the A/Puerto Rico/8/1934(H1N1)PR8 strain as the template,the NP pro-tein was cloned into the eukaryotic expression vector pCMV-C-Flag through PCR amplification,the eukaryotic expression re-combinant plasmid pCMV-Flag-NP was constructed,and the expression was further verified.The protein expression levels of pCMV-Flag-NP and pCMV-HA-TRIM25 were detected at various time periods.The interaction between NP protein and TRIM25 protein was verified by co-immunoprecipitation.The co-localization of NP protein and TRIM25 protein in cells was ob-served with laser confocal microscopy.Bioinformatics analysis revealed that the NP protein consists of 498 amino acids and 20 amino acids,and is an unstable hydrophilic protein.The NP protein has multiple phosphorylation sites,as well as N-glycosyla-tion and O-glycosylation sites,but no transmembrane domain or signal peptide domain.Additionally,the NP protein's second-ary structure consists of a high proportion of alpha-helices and random coils.The molecular docking prediction results indicated that IAV NP interacts with TRIM25 protein and has multiple potential interaction sites,including the 233rd alanine,234th ala-nine,236th lysine,and 440th alanine of the NP protein.After successfully constructing and expressing the IAV NP protein,we verified the interaction between IAV NP and TRIM25 protein by immunoprecipitation and laser confocal microscopy obser-vations.Our results together suggested that the structure of the IAV NP protein is closely related to its function,and its im-portance to the virus is clear.In addition,the interaction between IAV NP and TRIM25 protein may be associated with TRIM25's anti-influenza virus mechanism.Further in-depth research may provide new ideas for anti-influenza virus strategies.
5.Study on the association between temperature and relative humidity with fall risk in Hubei Province
Miaoyan SHEN ; Keqing LIANG ; Lan ZHANG ; Shuzhen ZHU ; Wenjun MA ; Fen LUO ; Yonghong WANG ; Xiuli LIU ; Yi FU ; Qian LI
Chinese Journal of Epidemiology 2025;46(4):596-604
Objective:To explore the associations of temperature, relative humidity, and their interaction effect with fall risk.Methods:Data on fall cases were collected using the national injury surveillance system from May to September, in 2006-2022 in Hubei Province. Combined with the meteorological and air pollution data, we conducted a time-stratified case-crossover design and used conditional logistic regression models and distributed lag nonlinear models to examine the exposure-response relationships between temperature, humidity, and fall risk. We further divided the low and the high temperature groups and the low and the high relative humidity groups and analyzed the excess risk ( ER) of falls attributed to dry-hot or wet-hot events. Finally, we calculated the additive interactions of temperature and humidity on fall risk. Results:A total of 55 401 fall cases were included. With the increase in temperature and relative humidity decrease, the exposure-response curves of fall showed nonlinear upward trends among all populations. Gender and age differences were found in temperature-fall and relative humidity-fall risk relationships. Compared with wet-non-hot (normal temperature and high relative humidity) events, the ER of fall in dry-hot (high temperature and low relative humidity) events was 14.80% (95% CI: 9.69%- 20.15%), and the ER of wet-hot (high temperature and high relative humidity) events was 9.59% (95% CI: 2.52%-17.13%). However, there was no statistically significant difference between dry-hot and wet-hot events in the fall, and no statistically significant difference between different genders, ages, occupations, and fall occurred place (all P>0.05). No significant synergistic additive interaction was found between temperature and relative humidity on fall risk (relative excess risk due to interaction=-0.08, 95% CI: -0.19-0.02). Conclusions:Higher temperatures and lower relative humidity were associated with increased fall risk. Both dry-hot and wet-hot events had a higher risk of fall, while high temperature and low humidity have no synergistic effect on fall risk.
6.Role and mechanism of TDO2 mediated apoptosis of renal tubular epithelial cells in Cis-AKI
Qian-qian LIN ; Xue-mei ZONG ; Yue-lan CHEN ; Wen-li WANG ; Yue-ye WANG ; Shang-xue YAN ; Wei WEI ; Yan CHANG
Chinese Pharmacological Bulletin 2025;41(3):475-482
Aim To investigate the role of tryptophan 2,3-dioxygenase(TDO2)in cisplatin-acute kidney in-jury(Cis-AKI)and to explore the mechanism of TDO2 in relation to apoptosis in tubular epithelial cells(TECs)to investigate the mechanism of TDO2 associ-ated with apoptosis.Methods An AKI model was es-tablished by intraperitoneal injection of cisplatin(Cis).Colorimetric assay was used to detect CRE and BUN levels,and PAS staining was employed to observe renal injury in mice.Immunohistochemistry was used to detect TDO2 protein expression and distribution and macrophage(F4/80+)infiltration;immunofluores-cence was used to detect the co-localization of TDO2 with the tubular marker LTL;TUNEL staining was used to detect apoptosis in mouse kidney;flow cytome-try was used to detect overexpression of human renal cortical proximal tubular epithelial cells(HK2)and apoptosis after administration of the TDO2 inhibitor 680C91;Western blot was used to detect TDO2 and NF-κB pathway protein levels in HK2 cells after over-expression and inhibition of TDO2.Results In the o-verall animal experiments,Cis-AKI mice showed signif-icantly higher levels of CRE and BUN and obvious tu-bular damage compared with the control group;at the same time,the renal tissues of Cis-AKI mice showed increased expression of F4/80,and the proportion of apoptotic cells in kidney cells was increased.Immuno-histochemistry and immunofluorescence showed that the expression of TDO2 increased,mainly localized in TECs.In cellular experiments,HK2 cells overexpress-ing TDO2 increased the proportion of apoptosis,and the expression of TDO2,p-IKBα,and p-p65 proteins was elevated,and p-IKBα/IκBα and p-p65/p65 were ele-vated;furthermore,the proportion of apoptosis was re-duced by the administration of 680C91,and the expres-sion of p-IκBα,and p-p65 proteins decreased,and the expression of p-IKBα/IKBα,and p-p65/p65 de-creased.Conclusions Elevated TDO2 in TECs is in-volved in the pathological mechanism of Cis-AKI,which may be related to its induction of apoptosis in TECs and activation of the NF-κB signaling pathway and consequently renal injury.
7.Meta-analysis of the incidence and influencing factors of transient severe motion in the arterial phase of Gd-EOB-DTPA enhanced MRI
Fukun SHI ; Jiaxu LIANG ; Qian XU ; Junjie SHU ; Jiameng SI ; Yihao YAN ; Yong CHEN ; Suo YIN ; Lan ZHANG
Journal of Practical Radiology 2025;41(8):1392-1398
Objective To explore the incidence and its influencing factors of transient severe motion(TSM)in the arterial phase of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)enhanced MRI.Methods The databases of China National Knowledge Network(CNKI),VIP,Wanfang,PubMed,and Embase were searched for studies on the incidence and influencing factors of TSM,and the search time was from the establishment of the databases to October 2024.Meta-analysis was performed via Stata 17.0 software.Results A total of 30 papers(33 studies)were finally included,totaling 12 565 patients.Meta-analysis results showed that the incidence of TSM in the arterial phase of Gd-EOB-DTPA enhanced MRI was 13.0%.The risk factors for TSM included age[odds ratio(OR)=1.03;95%confidence interval(CI)1.02-1.05;P<0.001),chronic obstructive pulmonary disease(COPD)(OR=4.21;95%CI 1.76-10.09;P=0.001),and moderate-to-severe pleural effusion(OR=3.34;95%CI 1.69-6.63;P=0.001),while a previous usage history of Gd-EOB-DTPA(OR=0.56;95%CI 0.39-0.81;P=0.002)was a protective factor of TSM.Conclusion The incidence of TSM in the arterial phase of Gd-EOB-DTPA enhanced MRI is relatively high.Age,COPD,moderate-to-severe pleural effusion are risk factors for TSM,while the previous usage history of Gd-EOB-DTPA is a protective factor for TSM.
8.Risk Factors for Early Recurrence of Solitary Hepatocellular Carcinoma After Radiofrequency Ablation Based on Gd-EOB-DTPA-Enhanced MRI
Qian XU ; Lan ZHANG ; Tingting HUANG ; Yu GAO ; Xiaoyang ZHAI ; Jiacheng ZHANG ; Xu HE ; Fukun SHI
Chinese Journal of Medical Imaging 2025;33(3):238-244,259
Purpose To investigate the independent risk factors for early recurrence of solitary hepatocellular carcinoma after radiofrequency ablation based on gadoxetic acid disodium(Gd-EOB-DTPA)-enhanced MRI combined with clinical features.Materials and Methods Clinical and imaging data of hepatocellular carcinoma patients who underwent radiofrequency ablation at the First Affiliated Hospital of Henan University of Chinese Medicine from January 2019 to June 2022 were retrospectively collected.All patients underwent preoperative Gd-EOB-DTPA-enhanced MRI and were followed up for up to two years post-surgery.Univariate and multivariate Cox proportional hazards regression were performed to identify independent risk factors for recurrence after radiofrequency ablation.Results A total of 58 patients were finally included,including early recurrence group(n=22)and non-early recurrence group(n=36).Multivariate Cox regression analysis revealed that preoperative alpha-fetoprotein(AFP)levels(HR=1.103,95%CI 1.008-1.206,P=0.033),arterial-phase irregular margin enhancement(HR=4.647,95%CI 1.527-14.110,P=0.007),peritumoral arterial-phase enhancement(HR=11.575,95%CI 3.575-37.478,P=0.001)and peritumoral hepatobiliary phase hypointensity(HR=5.058,95%CI 1.129-22.668,P=0.034)were independent risk factors for early recurrence.The area under the curve for AFP combined with arterial-phase irregular margin enhancement,peritumoral arterial-phase enhancement and peritumoral hepatobiliary phase hypointensity were 0.896,0.842 and 0.860,with accuracy rates of 81.0%,84.5%and 82.8%,respectively.Conclusion Preoperative serum AFP levels,arterial-phase irregular margin enhancement,peritumoral arterial-phase enhancement and peritumoral hepatobiliary phase hypointensity are independent risk factors for early recurrence after radiofrequency ablation in hepatocellular carcinoma patients.The combination of AFP and any of these MRI features significantly improves predictive efficacy.
9.Compound Chaijin Jieyu formula modulates TLR4/NLRP3 signaling pathway to suppress central oxidative stress and ameliorate hippocampal synaptic plasticity impairment in depression
Lian-mei XUE ; De-guo LIU ; Qing-ping ZHANG ; Zi-rong LI ; Qian LIU ; Yi SHU ; Xiu-wen HUANG ; Li-dan LAN
Chinese Pharmacological Bulletin 2025;41(10):1972-1981
Aim To explore the mechanism by which the compound Chaijin Jieyu formula(CCJJY)regulates the TLR4/NLRP3 signaling pathway to inhibit central oxidative stress and improve hippocampal synaptic plasticity damage in depression.Methods SD rats were randomly divided into the control group,chronic unpredictable mild stress group,sleep deprivation group,chronic unpredictable mild stress combined with sleep deprivation group,positive drug group(venlafax-ine+melatonin),low-dose group of CCJJY,medium dose group of CCJJY,and high-dose group of CCJJY,with nine rats in each group.Except for the control group,a rat model of depression complicated with in-somnia was established using chronic unpredictable mild stress combined with sleep deprivation.Depres-sion-like and sleep behaviors in rats were evaluated through weight,food intake,water maze,and pento-barbital sodium tests.ELisa was used to detect ROS,AANAT,and HPLC-EC was used to detect 5-HT con-tent,while Western blot/RT-PCR was used to detect the expression of IL-1β,TLR4,NLRP3,PSD-95,and SYN related proteins and mRNA.HE and Golgic stai-ning were used to observe the pathological changes in the third ventricle,hippocampus,and neuronal synap-ses.Results Compared with the control group,the depression-like behaviors of the model group rats were significant.The expression of IL-1β,TLR4,and NL-RP3 in the hippocampus increased,while the expres-sion of PSD-95 and SYN decreased.Activation of NL-RP3 inflammasomes led to "sleeve like" pathological changes in the third ventricle,with hippocampal neu-rons undergoing apoptosis and significant damage to neuronal synaptic plasticity.Compared with the model group,after intervention with CCJJY,the expression of ROS,IL-1β,TLR4,and NLRP3 decreased,while the expression of AANAT,5-HT,PSD-95,and SYN in-creased.Pathological damage to the third ventricle and hippocampal neurons was repaired.Conclusion The CCJJY improves hippocampal synaptic plasticity dam-age in depression by regulating the TLR4/NLRP3 sig-naling pathway to inhibit central oxidative stress.
10.Interpretation of Imaging Diagnosis in the Multidisciplinary Experts Consensus on Diagnosis and Treatment of Precancerous Lesions of Hepatocellular Carcinoma
Fukun SHI ; Lan ZHANG ; Qian XU ; Jiameng SI ; Shengxiang RAO
Chinese Journal of Medical Imaging 2025;33(9):900-905
In recent years,the incidence and mortality rates of hepatocellular carcinoma in China have gradually become close to each other,reflecting persistent limitations in current diagnostic and therapeutic strategies.Given the close association between hepatocellular carcinoma development and the progression of precancerous lesions,the expert panel released the first edition of the Multidisciplinary Experts Consensus on Diagnosis and Treatment of Precancerous Lesions of Hepatocellular Carcinoma in 2020 and updated it in 2023,aiming to advance early-intervention strategies and improve overall patient survival rates.This article provides an in-depth interpretation of the key imaging diagnostic points outlined in the consensus,aiming to offer radiologists at all levels with a robust reference for early identification and diagnosis of hepatocellular carcinoma precancerous lesions,thereby facilitating critical support for timely patient intervention and treatment.

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