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.Influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis
Danqing XU ; Huan MU ; Yingyuan ZHANG ; Lixian CHANG ; Yuanzhen WANG ; Weikun LI ; Zhijian DONG ; Lihua ZHANG ; Yijing CHENG ; Li LIU
Journal of Clinical Hepatology 2025;41(2):269-276
ObjectiveTo investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis, and to establish a predictive model. MethodsA total of 217 patients who were diagnosed with decompensated hepatitis C cirrhosis and were admitted to The Third People’s Hospital of Kunming l from January, 2019 to December, 2022 were enrolled, among whom 63 patients who were readmitted within at least 1 year and had no portal hypertension-related complications were enrolled as recompensation group, and 154 patients without recompensation were enrolled as control group. Related clinical data were collected, and univariate and multivariate analyses were performed for the factors that may affect the occurrence of recompensation. The independent-samples t test was used for comparison of normally distributed measurement data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed measurement data between two groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A binary Logistic regression analysis was used to investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis, and the receiver operating characteristic (ROC) curve was used to assess the predictive performance of the model. ResultsAmong the 217 patients with decompensated hepatitis C cirrhosis, 63 (29.03%) had recompensation. There were significant differences between the recompensation group and the control group in HIV history (χ2=4.566, P=0.034), history of partial splenic embolism (χ2=6.687, P=0.014), Child-Pugh classification (χ2=11.978, P=0.003), grade of ascites (χ2=14.229, P<0.001), albumin (t=4.063, P<0.001), prealbumin (Z=-3.077, P=0.002), high-density lipoprotein (t=2.854, P=0.011), high-sensitivity C-reactive protein (Z=-2.447, P=0.014), prothrombin time (Z=-2.441, P=0.015), carcinoembryonic antigen (Z=-2.113, P=0.035), alpha-fetoprotein (AFP) (Z=-2.063, P=0.039), CA125 (Z=-2.270, P=0.023), TT3 (Z=-3.304, P<0.001), TT4 (Z=-2.221, P=0.026), CD45+ (Z=-2.278, P=0.023), interleukin-5 (Z=-2.845, P=0.004), tumor necrosis factor-α (Z=-2.176, P=0.030), and portal vein width (Z=-5.283, P=0.005). The multivariate analysis showed that history of partial splenic embolism (odds ratio [OR]=3.064, P=0.049), HIV history (OR=0.195, P=0.027), a small amount of ascites (OR=3.390, P=0.017), AFP (OR=1.003, P=0.004), and portal vein width (OR=0.600, P<0.001) were independent influencing factors for the occurrence of recompensation in patients with decompensated hepatitis C cirrhosis. The ROC curve analysis showed that HIV history, grade of ascites, history of partial splenic embolism, AFP, portal vein width, and the combined predictive model of these indices had an area under the ROC curve of 0.556, 0.641, 0.560, 0.589, 0.745, and 0.817, respectively. ConclusionFor patients with decompensated hepatitis C cirrhosis, those with a history of partial splenic embolism, a small amount of ascites, and an increase in AFP level are more likely to experience recompensation, while those with a history of HIV and an increase in portal vein width are less likely to experience recompensation.
3.Yulin Hukun Decoction Ameliorates Diminished Ovarian Reserve via PI3K/Akt/mTOR-Mediated Autophagy
Ruixia WANG ; Huan CHENG ; Yaxing FAN ; Tingyun CAI ; Meifang LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):77-85
ObjectiveTo observe the effect of Yulin Hukun decoction on autophagy mediated by phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway in the mouse model of cyclophosphamide-induced diminished ovarian reserve and explore the follicular development-improving mechanism of this decoction. MethodsSixty female ICR mice with normal estrous cycle were assigned into a blank group (n=10) and a modeling group (n=50). The model was established by intraperitoneal injection of cyclophosphamide (60 mg·kg-1) for 5 days. The successfully modeled mice were randomly grouped as follows: model, estradiol (0.26 mg·kg-1), and high-, medium-, and low-dose (56.42, 28.21, 14.105 g·kg-1, respectively) Yulin Hukun decoction, with 10 mice in each group. The blank group and the model group received normal saline (10 mL·kg-1). The intervention was performed once a day for 21 days. The general conditions, estrous cycle, body weight, and ovary index were observed and recorded for each group. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Müllerian hormone (AMH) were measured by enzyme-linked immunosorbent assay. Histopathological changes in the ovarian tissue were observed by hematoxylin-eosin staining. Western blot was employed to determine the protein levels of PI3K, Akt, mTOR, autophagy-related protein 7 (Atg7), beclin1, microtubule-associated protein 1 light chain 3Ⅱ (LC3Ⅱ), ubiquitin-binding adaptor protein (p62), forkhead box protein O1 (FoxO1), and acetylated forkhead box protein O1 (Ac-FoxO1) in mouse ovaries. Real-time PCR was adopted to determine the mRNA levels of PI3K, Akt, mTOR, Atg7, beclin1, and LC3Ⅱ in the mouse ovarian tissue. ResultsCompared with the blank group, the model group had disturbed estrous cycle, decreased body weight (P<0.05), loose ovarian structure with increased atretic follicles, increased serum FSH level (P<0.05), and decreased AMH and estradiol levels (P<0.05). Compared with the model group, the treatment groups showed recovered estrous cycles and body weight. The estradiol group and high- and medium-dose Yulin Hukun decoction groups showed declined FSH level (P<0.05) and elevated AMH levels (P<0.05). In addition, the treatment groups showed downregulated protein levels of Atg7, LC3Ⅱ, beclin1, FoxO1, and Ac-FoxO1 (P<0.01), upregulated protein levels of PI3K, Akt, mTOR, and p62 (P<0.01) in the ovarian tissue, gradual repair of the ovarian structure, with more intact and numerous follicles of various stages. ConclusionYulin Hukun decoction can inhibit autophagy in ovarian granulosa cells by activating the PI3K/Akt/mTOR signaling pathway and inhibiting the expression of autophagy-related proteins and transcription factors, thereby improving follicular development and ovarian reserve.
4.Efficacy and safety of remimazolam tosylate for general anesthesia in morbidly obese patients
Gong CHEN ; Yan-Xi LU ; Jin LI ; Fan ZHANG ; Can-Can CHENG ; Xin-Lin YIN ; Sai-Ying WANG ; Huan CHANG
Chinese Pharmacological Bulletin 2024;40(5):859-864
Aim To evaluate the effectiveness and safety of remimazolam tosylate for administering general anesthesia in morbidly obese patients.Methods This clinical trial was conducted at a single center from De-cember 2021 to October 2023.It assessed 108 morbid-ly obese patients(body mass index,BMI≥40)who underwent laparoscopic sleeve gastrectomy.Patients were randomly assigned to either the remimazaolam group(Group R)or the propofol group(Group P)for general anesthesia induction and maintenance.The primary outcome was to compare the incidence of ad-verse events and postoperative recovery characteristics between the two groups.Results During induction pe-riod,the incidence of adverse events was higher in group P,including hypotension(P<0.01),hypox-emia(P<0.05),bradycardia(P<0.01),and in-creased vasopressor requirement(P<0.05).The time to loss of consciousness and BIS falling to 60 was shor-ter in group P than in group R(P<0.01).There were no statistically significant differences between the two groups in terms of postoperative quality of recovery(QoR-40 score),24-hour postoperative pain visual an-alogue scale(VAS)scores and morphine consump-tion.In conclusion,remimazolam tosylate,utilized for anesthesia induction in morbidly obese patients,signif-icantly reduced hypotension and hypoxemia compared to propofol,while it could also maintain similar postop-erative recovery quality.Conclusions Remimazolam is effective in reducing the incidence of hypotension and hypoxaemia during the induction period of general anaesthesia in morbidly obese patients and it is compa-rable to propofol in terms of quality of postoperative re-covery.
5.A case of emergency transcatheter aortic valve replacement treatment for aortic stenosis complicated with acute heart failure shock in primary hospital
Huan GUO ; Yu-Dong LI ; Nian-Guo DONG ; Xiao-Ke SHANG ; Yu-Cheng ZHONG ; Chang-Dong ZHANG ; Ling-Bo ZHANG
Chinese Journal of Interventional Cardiology 2024;32(5):291-294
Aortic valve stenosis,as a common heart valve disease,progresses rapidly and has a poor clinical prognosis.In the case of combined acute heart failure,the pumping function of the heart is severely impaired,which may lead to a significant decrease in cardiac output,resulting in a state of shock.Transcatheter aortic valve replacement(TAVR)has become a first-line treatment for elderly patients with aortic valve stenosis since its first successful case in 2002.In China,with the advancement of technology and the strengthening of physician training,the capacity of grassroots hospitals in TAVR treatment is increasing.This case reports a patient with severe aortic valve stenosis accompanied by acute heart failure and shock status who received emergency TAVR treatment at a grassroots hospital.Due to limitations in conditions,TAVR was urgently implemented without extracorporeal circulation and extracorporeal membrane oxygenation support.The patient's blood pressure immediately rose to 105/65 mmHg after valve dilation during surgery,and the postoperative symptoms were significantly relieved.Follow up color Doppler ultrasound showed that the stenosis was relieved and the heart function was significantly improved.The success of this surgery provides a reference for emergency TAVR treatment in patients with severe aortic valve stenosis and heart failure in grassroots hospitals.
6.Long-term therapeutic efficacy and prognosis analysis of complex high-risk coronary heart disease patients undergoing elective percutaneous coronary intervention with extracorporeal membrane oxygenation combined with intra-aortic balloon pump
Tian-Tong YU ; Shuai ZHAO ; Yan CHEN ; You-Hu CHEN ; Gen-Rui CHEN ; Huan WANG ; Bo-Hui ZHANG ; Xi ZHANG ; Bo-Da ZHU ; Peng HAN ; Hao-Kao GAO ; Kun LIAN ; Cheng-Xiang LI
Chinese Journal of Interventional Cardiology 2024;32(9):501-508
Objective We aimed to compare the efficacy and prognosis of percutaneous coronary intervention(PCI)in complex and high-risk patients with coronary heart disease(CHD)treated with extracorporeal membrane oxygenation(ECMO)combined with intra-aortic balloon pump(IABP)assistance,and explore the application value of combined use of mechanical circulatory support(MCS)devices in complex PCI.Methods A total of patients who met the inclusion criteria and underwent selective PCI supported by MCS at the Department of Cardiology,the First Affiliated Hospital of the Air Force Medical University from January 2018 to December 2022 were continuously enrolled.According to the mechanical circulatory support method,the patients were divided into ECMO+IABP group and IABP group.Clinical characteristics,angiographic features,in-hospital outcomes,and complications were collected.The intra-hospital outcomes and major adverse cardiovascular events(MACE)at one month and one year after the procedure were observed.The differences and independent risk factors between the two groups in the above indicators were analyzed.Results A total of 218 patients undergoing elective PCI were included,of which 66 patients were in the ECMO+IABP group and 152 patients were in the IABP group.The baseline characteristics of the two groups of patients were generally comparable,but the ECMO+IABP group had more complex lesion characteristics.The proportion of patients with atrial fibrillation(6.1%vs.0.7%,P=0.030),left main disease(43.9%vs.27.0%,P=0.018),triple vessel disease(90.9%vs.75.5%,P=0.009),and RCA chronic total occlusion disease(60.6%vs.35.5%,P<0.001)was higher in the ECMO+IABP group compared to the IABP group.The proportion of patients with previous PCI history was higher in the IABP group(32.9%vs.16.7%,P=0.014).There was no statistically significant difference in the incidence of in-hospital complications between the two groups(P=0.176),but the incidence of hypotension after PCI was higher in the ECMO+IABP group(19.7%vs.9.2%,P=0.031).The rates of 1-month MACE(4.5%vs.2.6%,P=0.435)and 1-year MACE(7.6%vs.7.9%,P=0.936)were comparable between the two groups.Multivariate analysis showed that in-hospital cardiac arrest(OR 7.17,95%CI 1.27-40.38,P=0.025)and after procedure hypotension(OR 3.60,95%CI 1.10-11.83,P=0.035)were independent risk factors for the occurrence of 1-year MACE.Conclusions Combination use of ECMO+IABP support can provide complex and high-risk coronary heart disease patients with an opportunity to achieve coronary artery revascularization through PCI,and achieve satisfactory long-term prognosis.
7.Scoping review of self-advocacy needs and behaviors of adult cancer patients
Yuanyuan LI ; Lin CHENG ; Yulu XU ; Bei PEI ; Huan LI ; Jinlong LIU ; Yan LOU
Chinese Journal of Modern Nursing 2024;30(21):2916-2923
Objective:To conduct a scoping review of research on the self-advocacy of adult cancer patients to identify their self-advocacy needs, behaviors, strengths and weaknesses, so as to provide guidance for future research in this field.Methods:Using the scoping review guidelines of Joanna Briggs Institute in Australia as a methodological framework, relevant literatures were searched in PubMed, Web of Science, Cochrane Library, Embase, Science Direct, CINAHL, Scopus, China National Knowledge Infrastructure, Wanfang, VIP and China Biology Medicine disc. The search period was from establishment of the databases to December 2023, and the results were summarized and analyzed.Results:A total of 14 articles were included, and self-advocacy needs included six types of needs, such as symptom management, communication, interpersonal support, disease information, decision-making and emotional management. Self-advocacy included four aspects, including seeking information, self-decision-making, strengthening contact with the outside world and effective communication.Conclusions:Adult cancer patients have diverse types of self-advocacy needs and certain self-advocacy behaviors. Future research should pay attention to self-advocacy needs assessment, develop corresponding tools, focus on self-advocacy behaviors, leverage the advantages of self-advocacy and explore strategies to achieve effective self-advocacy support.
8.Characterization of genomic islands and virulence factors of clinical isolates of Burkholderia pseudomallei in Hainan Province,China
Xiao-Ying FU ; Huan LI ; Sha LI ; Li-Cheng WANG ; Chong-Zhen WANG ; Yuan-Li LI ; Hai CHEN ; Xiong ZHU
Chinese Journal of Zoonoses 2024;40(4):359-368,390
The genomic island(GI)characteristics and virulence factor differences of clinical isolates of Burkholderia pseudomallei in Hainan Province,China were analyzed to provide a scientific basis for diagnosis and treatment of melioidosis.In total,52 B.pseudomallei isolates were collected for detection of virulence-related GIs by PCR.The whole genome sequence annotation format file was submitted on Islandviwer 4 platform,and the genomes of the same species and close relatives were added for comparison.Two algorithms,SIGI-HMM and IslandPath-DIMOB,were integrated to predict GIs and sequence a-lignments were conducted to identify specific GIs and differences in virulence factors.The genomes of 52 clinical strains could be divided into three branches based on evolutionary distance,with 82.69%(43/52)of strains concentrated in branch 1.In to-tal,828 GIs were identified among the 52 B.pseudomallei genomes,which formed 157 GI clusters based on sequence similari-ty.GIs accounted for 2.05%-6.38%of the genome content.While GI clusters 1 and 2 were present in all strains,a total of 84(53.50%)GI clusters only clustered within a single genome isolate.Of 10 GI likely specific clusters,five were from the same genus,two from another genus,and three with uncertain origins.Moreover,25 GI clusters were associated with virulence,which included eight shared by B.pseudomallei BP76 and BP169,which had the highest number of virulence-associated GIs among all isolates.O the 52 B.pseudomallei isolates,variations were identified in the virulence genes fhaB1,fhaB2,BPSL1661,cheY1,wzM,tssH-5/clpV,tssA-5,boaA,and boaB.Comparisons of these findings with clinical isolates from Thailand and Australia showed that B.pseudomallei isolates from Hainan had significant differences in the sequences of boaA,boaB,cheY1,and chbp.Additionally,fhaB1,fhaB3,and bimA displayed significant variations specifically within the Australian isolates.B.pseudomallei GI was conserved and specific to Hainan.The identification of specific GI and virulence factors was useful to clarify the source of horizontal gene transfer and differences in virulence at the molecular level.
9.Fluorescence Quantitative PCR Detection of ABL1 Kinase Region Mutations
Huan-Chen CHENG ; Si LI ; Dian-Zhi WANG ; Yu LIU ; Tie-Jun GONG ; Jun MA
Journal of Experimental Hematology 2024;32(5):1377-1380
Objective:To establish a highly sensitive and quantitative detection method for ABL1 kinase region mutations,provide strong support for the early diagnosis and treatment of chronic myeloid leukemia(CML).Methods:Sampele from 35 CML patients who were initially tested negative for ABL1 kinase region mutations by Sanger sequencing were collected.The ABL1 kinase region mutation was detected by the fluorescence quantitative detection kit of Shanghai Yuanqi Biopharmaceutical Technology Co.,Ltd.The mutation rate was analyzed byΔΔCt value method.The relative mutation rate of the final ABL1 kinase region was determined by dividing the mutation rate by the expression level of the fusion gene.Results:Among the 35 CML patients initially tested negative for ABL1 mutations by the Sanger sequencing method,7 cases of T315I mutation,2 cases of T315A mutation,2 cases of Y253H mutation,and 1 cases of E255K mutation after detection of the new method.The relative mutation rates range from 0.1%to 19.42%,which could not be detected by Sanger sequencing method.Subsequently,this method was used to detect the ABL1 mutation in 126 CML patients,and the positive rate exceeded that of the Sanger sequencing method.The BCR-ABL1 gene expression significantly reduced or negative after adjusting treatment strategy based on the mutation situation.Conclusion:Compared with Sanger sequencing,fluorescence quantitative PCR has higher sensitivity and can screen for low-frequency ABL1 kinase mutations in the early stage.Moreover,it can also perform relative quantitative analysis,so the method has good clinical application prospects for detecting ABL1 mutation.
10.Comparison of in vivo pharmacokinetics of six active constituents from Shaoyao Gancao Decoction in normal and gastric ulcer rats
He-Rong LI ; Yang JIN ; Huan ZHANG ; Tian-Tai WU ; Jian WEN ; Chao TANG ; Xue-Yi CHENG ; Wen LIU
Chinese Traditional Patent Medicine 2024;46(11):3572-3578
AIM To compare the in vivo pharmacokinetics of paeoniflorin,paeoniflorin,liquiritin,isoliquiritin,liquiritigenin and glycyrrhizic acid from Shaoyao Gancao Decoction in normal and gastric ulcer rats.METHODS Six rats were randomly assigned into two groups,after which the 75%ethanol-induced gastric ulcer model was established,the gastric tissues were collected.Twelve rats were randomly assigned into two groups and given intragastric administration(9.9 g/kg),after which blood collection was made at different time points,UPLC-MS/MS method was adopted in the determination of plasma concentrations,and main pharmacokinetic parameters were calculated.RESULTS Prolonged Tmax(P<0.05,P<0.01)of various active constituents,prolonged T1/2,MRT0-t(P<0.05,P<0.01),increased Cmax,AUC(P<0.05,P<0.01)and decreased Vd/F,CL/F(P<0.05,P<0.01)of paeoniflorin,increased Cmax,AUC(P<0.05,P<0.01)and decreased CL/F(P<0.05)of albiflorin,prolonged MRT(P<0.05),increased AUC(P<0.05)and decreased CL/F(P<0.01)of liquiritin,prolonged MRT(P<0.05,P<0.01)and decreased Vd/F(P<0.05)of isoliquiritin,no obviously changed pharmacokinetic parameters(except for Tmax)of liquiritigenin(P>0.05),and prolonged T1/2,MRT0-∞(P<0.05,P<0.01),increased Cmax,AUC(P<0.05,P<0.01)and decreased CL/F(P<0.01)of glycyrrhizic acid were observable in the model group as compared with those in the normal group.CONCLUSION Gastric ulcer exhibits certain influences on the velocities and degrees of in vivo absorption and metabolism of active constituents from Shaoyao Gancao Decoction.

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