1.Application of stem cells in endothelialization of small-diameter blood vessel prosthesis
Ankai ZHENG ; Ruiming LIU ; Qiuling XIANG
Chinese Journal of Tissue Engineering Research 2025;29(1):120-127
BACKGROUND:The small-diameter blood vessel prosthesis faces the problem of lumen stenosis or even occlusion due to thrombogenesis and intimal hyperplasia after transplantation.The application of stem cells as seed cells to achieve endothelialization of blood vessel prosthesis helps to improve the long-term patency rate after vascular graft transplantation. OBJECTIVE:To summarize the research progress of the application of stem cells in the endothelialization of small-diameter blood vessel prosthesis. METHODS:The relevant articles published on PubMed and WanFang databases from 2013 to 2023 were retrieved by the first author.Chinese and English search terms included"vascular graft,tissue-engineered blood vessel/vascular tissue engineering,endothelialization,stem cells,endothelial progenitor cells,mesenchymal stem cells,induced pluripotent stem cells,embryonic stem cells."The relative articles in the domestic and overseas about the application of stem cells in the endothelialization of small-diameter blood vessel prosthesis in the past 10 years were retrieved.A total of 552 articles were initially found and we finally selected 81 articles to review according to inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)The low long-term patency rate restricts the application of small-diameter blood vessel prosthesis in clinic.The main causes of low long-term patency rate are thrombogenesis and intimal hyperplasia.The endothelium of native vessels has the function of anti-thrombogenesis and intimal hyperplasia.Endothelialization can simulate the function of native vessels,which is an effective way to improve long-term patency rate.(2)The small-diameter blood vessel prosthesis will undergo in vivo endothelialization after being implanted,but it is difficult to form complete endothelium.Stem cells have the potential to differentiate into endothelial cells.Recruiting stem cells in vivo or seeding them on the inner surface of blood vessel prosthesis in vitro is research strategy to achieve endothelialization.(3)The long-term patency rate of small-diameter blood vessel prosthesis has been improved to a certain extent through seeding endothelial progenitor cells,mesenchymal stem cells,induced pluripotent stem cells,and embryonic stem cells.Each has its own advantages.Endothelial progenitor cells are easy to obtain and can be directly used for seeding.Mesenchymal stem cells come from a wide range of sources and have the function of paracrine and immunological regulation.Induced pluripotent stem cells are rich in sources and the immunogenicity can be eliminated.Embryonic stem cells have a strong proliferative ability and can differentiate into many cells.(4)The application of stem cells in blood vessel prosthesis has not yet been transformed into clinic.Further researches are needed to promote clinical translation.
2.Dual activation of GCGR/GLP1R signaling ameliorates intestinal fibrosis via metabolic regulation of histone H3K9 lactylation in epithelial cells.
Han LIU ; Yujie HONG ; Hui CHEN ; Xianggui WANG ; Jiale DONG ; Xiaoqian LI ; Zihan SHI ; Qian ZHAO ; Longyuan ZHOU ; JiaXin WANG ; Qiuling ZENG ; Qinglin TANG ; Qi LIU ; Florian RIEDER ; Baili CHEN ; Minhu CHEN ; Rui WANG ; Yao ZHANG ; Ren MAO ; Xianxing JIANG
Acta Pharmaceutica Sinica B 2025;15(1):278-295
Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.
3.Cost-utility Analysis of PD-1/PD-L1 Inhibitor Combination Therapies as First-line Treatment for Advanced Non-small-cell Lung Cancer
HE Yimin ; NIAN Zilin ; LIU Wenbin ; YANG Lin ; DONG Liangliang ; ZHAO Qiuling
Chinese Journal of Modern Applied Pharmacy 2024;41(13):1820-1829
OBJECTIVE
To compare the cost-utility of eight programmed death 1(PD-1)/programmed cell death-ligand 1(PD-L1) inhibitor combination regimens for first-line treatment of advanced non-small cell lung cancer(NSCLC) from the perspective of Chinese healthcare system.
METHODS
Relevant data were derived from a published network meta-analysis and randomized controlled trails, a three-state Markov model was established to analyze the cost-utility of eight immunotherapy combinations. The robustness of results were validated through sensitivity analyses and a series of scenario analyses was also conducted.
RESULTS
The incremental cost-utility ratio(ICUR) of the sintilizumab plus chemotherapy group and the tislelizumab plus chemotherapy group were ¥125143.88/quality adjusted life year(QALY) and ¥189609.64/QALY, respectively, which were less than the willingness-to-pay(WTP) threshold of ¥257094/QALY, and all the ICURs of other PD-1/PD-L1 inhibitor combination regimens exceeded the WTP threshold and were not economical. Scenario analyses found that even if the medical insurance reimbursement ratio reached 80%, the different combinations of pembrolizumab, nivolumab and atezolizumab were not economical.
CONCLUSION
Compared with other PD-1/PD-L1 inhibitor combination regimens, sintilizumab plus chemotherapy and tislelizumab plus chemotherapy have cost-utility advantages in the first-line treatment of advanced NSCLC, which can provide a certain reference for selecting a reasonable treatment plan for NSCLC patients.
4.Construction and evaluation of hyperkalemia risk prediction model in patients with chronic kidney disease
Chinese Journal of Nephrology 2024;40(11):894-900
This study retrospectively analyzed the risk factors of hyperkalemia in patients with chronic kidney disease (CKD), established a risk assessment model, and validated it. It was a retrospective study. Data from 505 CKD patients who visited the Department of Nephrology at Linping First People's Hospital from June 2022 to January 2024 were retrospectively collected. Patients were divided into a modeling set ( n=354) and a validation set ( n=151) in a 7∶3 ratio. The independent risk factors for hyperkalemia in CKD patients were screened using least absolute shrinkage and selection operator (Lasso) regression, and a risk prediction model was constructed using multivariate Logistic regression. Hosmer-Lemeshow test was used to judge the fit degree of the prediction model, and the nomogram, the receiver operating characteristic curve, the calibration curve and clinical decision curve were drawn. The results showed that 155 out of 505 CKD patients developed hyperkalemia, with an incidence rate of 30.69%. Lasso regression and multivariate logistic regression analysis showed that serum albumin, blood sodium, blood phosphorus, parathyroid hormone, and risk score X (the value was based on the CKD hyperkalemia risk prediction model established in China in 2020) were the independent factors associated with hyperkalemia in CKD patients (all P<0.05). The analysis of the receiver operating characteristic curve of the subjects showed that the area under the modeling set curve was 0.840 (95% CI 0.796-0.884), and the area under the validation set curve was 0.849 (95% CI 0.784-0.915). The calibration curve suggested good consistency between the predicted and actual results of the model, and the decision curve analysis suggested that the model could increase patient benefits. Finally, the authors drew a visual nomogram of the model. The authors believe that the column chart prediction model for hyperkalemia in CKD patients constructed based on the predictive variables selected by Lasso regression ha good predictive ability and is helpful for clinical medical personnel to detect and manage hyperkalemia early in CKD patients.
5.Non-enterotoxin-producing Bacteroides fragilis inhibits TNF-α-induced inflammatory response in colonic epithelial cells by down-regulating the NF-κB signaling pathway
Qiuyue HE ; Qiuling HUANG ; Jian MAO ; Yongshi ZHAO ; Yingxuan CHEN ; Yan ZHANG ; Yan DU
Chinese Journal of Microbiology and Immunology 2024;44(10):829-837
Objective:To investigate the mechanism by which non-enterotoxin-producing Bacteroides fragilis (NTBF) inhibits TNF-α-induced inflammatory responses in human normal colonic epithelial cells hcoEPIC, and explore new probiotic therapies for the prevention and treatment of colitis. Methods:The co-culture system of NTBF and hcoEPIC cells was established, and the adhesion and invasion ability of NTBF were detected, respectively. TNF-α was added to induce cellular inflammation after 4 h of co-culture of NTBF and hcoEPIC cells, and cell survival and apoptosis were detected by the CCK-8 assay and the AnnexinⅤ-FITC/PI assay respectively after 24 h. Key proteins of the NF-κB signalling pathway in hcoEPIC cells in different treatment groups were detected by Western blot and RT-qPCR, and the expression of downstream cytokines of this pathway incluing IL-1β, TNF-α and IL-10 were detected by ELISA. The effect of NTBF intervention on dextran sodium sulfate(DSS)-induced colitis mice was assessed by in vivo animal experiments. Results:NTBF adhered to hcoEPIC cells, and was non-toxic to the cells. Compared with control group, NTBF treatment alone did not affect cell survival and apoptosis of hcoEPIC cells ( P>0.05), but significantly reduced cell damage and apoptosis induced by TNF-α ( P<0.05); Compared with the TNF-α treatment alone group, the expression levels of p-NF-κB p65 and p-IκBα protein as well as NF-κB and IκBα mRNA were significantly reduced ( P<0.05); the production of IL-1β and TNF-α in the cell supernatant was reduced and the release of IL-10 was increased ( P<0.05). Animal experiments demonstrated that NTBF was indeed effective in alleviating DSS-induced colitis in ulcerative colitis model mice, which was mainly manifested by inhibiting weight loss, lowering DAI scores, improving colonic shortening, and attenuating colonic pathological damage in colitis-induced mice. Conclusions:NTBF may inhibit TNF-α-induced inflammatory responses in colonic epithelial cells by down-regulating the NF-κB pathway.
6.Issue characteristics, evolutionary trends, and knowledge production in health insurance fund regulation policies
Ciran YANG ; Linqi XIAO ; Ruonan WU ; Rui WANG ; Qiuling ZHAO ; Fengran DUAN ; Yue WANG ; Zongfu MAO ; Dan CUI
Chinese Journal of Hospital Administration 2024;40(4):316-322
Health insurance fund regulation (HIFR) is a vital issue in the modernization of healthcare security governance, with its importance as a primary task of the healthcare security department continually reinforced in policy practice. This study focused on the 22 specialized policies issued by the National Healthcare Security Administration from its establishment in 2018 to March 2024, deeply analyzed their issue characteristics, and summarized the evolutionary trends of policy changes, as well as the knowledge production patterns that existed in the series of policy formulation, implementation, and feedback processes. Our analysis revealed that the diverse issue characteristics had led to heterogeneous directions in HIFR policies. The policy development process presented distinct composite evolutionary trends, mainly manifested in four aspects: the integration of regulatory system and content, the convergence of professional and societal forces, the parallelism of special governance and regular supervision, and the complementarity of conventional and emerging methods. Additionally, the study demonstrated that the knowledge production embedded in policy evolution encompassed four different dimensions: problem rectification, norm setting, pilot experience, and technical absorption. Together with issue characteristics and policy evolution, they formed an integrated, dynamic, and open system of knowledge production, continuously promoting the renewal and iteration of regulation policies.
7.Clinical value of serum IGF-1 and IGFBP-3 levelin predicting the risk of ARDS and prognosis in critical patients
Yanhuo XIA ; Yihua DONG ; Qiuling TONG ; Aiming ZHOU ; Songzhan QIAN
China Modern Doctor 2024;62(29):41-44,49
Objective To investigate the significance of plasma levels of insulin-like growth factor(IGF)-1 and insulin-like growth factor binding protein(IGFBP)-3 in predicting acute respiratory distress syndrome(ARDS)and prognosis in critical patients.Methods A totally of 131 critical patients in intensive care unit(ICU)of the First Affiliated Hospital of Wenzhou Medical University were reviewed.Plasma concentrations of IGF-1,IGFBP-3,blood biochemistry,procalcitonin(PCT),lactic acid(LAC)and blood albumin were measured in enrolled patients.The 60-day fatality of enrolled patients was calculated.The differences between ARDS group and control group,as well as 60-day dead group and survival group were compared.Results Plasma IGF-1 and IGFBP-3 in ARDS group were significantly lower than those in control group,while plasma PCT was higher than that in control group.Plasma levels of IGF-1 and IGFBP-3 in dead group were significantly lower than those in survival group.Multivariate Logistic regression analysis and receiver operating characteristic curve results showed that IGF-1 area under curve(AUC)was 0.770,sequential organ failure assessment(SOFA)(AUC=0.692)and PCT(AUC=0.710)were independent risk factors for ARDS in critical patients.IGF-1(AUC=0.807),IGFBP-3(AUC=0.759)and SOFA score(AUC=0.859)were independent risk factors for death in critical patients.Conclusion The plasma levels of IGF-1 and IGFBP-3 in critica patients are significantly decreased,which may be an important factor for ARDS risk and fatality in critical patients.
8.Progress of Research on Intestinal Flora and its Metabolites in Ulcerative Colitis
Qiuling HUANG ; Qiuyue HE ; Yan DU
Chinese Journal of Gastroenterology 2024;29(4):248-253
The incidence of ulcerative colitis(UC)is on the rise globally,but its pathogenesis has not yet been clarified.Existing studies suggest that UC is closely related to genetic susceptibility,impaired intestinal epithelial barrier,abnormal immune response,intestinal flora dysbiosis and environmental factors.Intestinal flora has the functions of substance metabolism,nutrient absorption,energy conversion,immune regulation and maintenance of intestinal mucosal barrier,and has been proved to play an important role in UC.This article reviewed the progress of research on intestinal flora and its metabolites in UC,thus providing theoretical basis and new ideas for the diagnosis and treatment of UC.
9.Status quo and influencing factors of pain crisis in advanced lung cancer patients
Liyuan DOU ; Qiuling JIANG ; Wenjia SHEN ; Xiaoping LI ; Xinxin QI
Chinese Journal of Nursing 2024;59(11):1353-1359
Objective To investigate the status quo of pain crisis in advanced lung cancer patients and analyze its influencing factors.Methods From August to November 2023,318 patients with advanced lung cancer were selected from 6 wards of respiratory department of a tertiary A hospital in Zhengzhou.The Numerical Rating Scale,Perceptive Social Support Scale,Self-rating Anxiety Scale and Self-rating Depression Scale were used to investigate the influencing factors of pain crisis in advanced lung cancer patients by Logistic regression.Results Among 318 patients with advanced lung cancer,102 patients had painful crisis,with the incidence rate of 32.08%.0lder age and high level of social support were protective factors for pain crisis,and bone metastasis,anxiety and mild to moderate depression were risk factors for pain crisis.Conclusion The incidence of pain crisis was high in advanced lung cancer patients.Medical staff should pay attention to those with younger age,bone metastasis,low level of social support,high level of anxiety and mild to moderate level of depression,and take timely intervention measures to reduce the occurrence of pain crisis.
10.Effects of periacetabular osteotomy with different approaches on traumatic stress,lower limb strength and prognosis of acetabular dysplasia
Shiqiang MA ; Donghui GUO ; Li XIAO ; Qiuling SHI ; Runbin SHEN
Journal of Clinical Surgery 2024;32(9):955-960
Objective To investigate the effects of different approaches of periacetabular osteotomy(PAO)on traumatic stress,lower limb strength and prognosis of acetabular dysplasia(DDH).Methods Ninety-seven patients with DDH in our hospital from January 2021 to January 2022 were randomly divided into two groups.Among them,48 patients in the control group received conventional ilioinguinal approach PAO treatment,while 49 patients in the study group received modified ilioinguinal approach PAO treatment.The surgical and postoperative rehabilitation indexes,Mckay clinical efficacy,lower limb line of force,complications,traumatic stress factors before and after surgery[adrenalin(NE),cortisol(COR),angiotensin Ⅱ(AngⅡ)],hip imaging indexes[anterior CE Angle(ACEA),lateral CE Angle(LCEA),acetabular index(AI)]and changes were compared between the two groups Good Harris hip function Score(mHHS),hip outcome score Daily Living Ability Scale(HOS-ADL).Results The operation time of the study group and the control group were(128.64±18.73)min and(141.80±21.59)min respectively,the intraoperative blood loss were(472.95±35.18)ml and(495.68±40.26)ml respectively,the postoperative drainage were(242.39±32.74)ml and(305.81±39.56)ml respectively,and the hospital stay were(11.57±2.29)D and(12.86±2.41)d respectively,with significant differences between the two groups(P<0.05);The excellent and good rate of McKay's clinical efficacy in the study group(95.92%)was higher than that in the control group(81.25%),and the differences were statistically significant(P<0.05);Serum NE in the study group and control group at 1 d,3 d,and7 d postoperatively were(73.16±8.07)ng/L and(81.33±8.52)ng/L,(65.81±7.29)ng/L and(72.24±7.65)ng/L,(45.98±6.31)ng/L and(50.37±7.02)ng/L,respectively,and COR were(164.84±19.35)ng/L and(178.62±21.46)ng/L,(142.69±17.81)ng/L and(157.36±19.22)ng/L,(88.79±16.13)ng/L and(97.62±17.50)ng/L,respectively,and AngⅡ was(138.74±20.51)mmol/L and(150.19±21.36)mmol/L,(128.35±17.69)mmol/L and(137.18±19.24)mmol/L,and(119.82±17.41)mmol/L and(128.73±18.50)mmol/L,respectively,and the differences between the two groups were all statistically significance(P<0.05);ACEA at 3,6,and 12 months postoperatively in the study and control groups were(29.71±4.81)° and(27.68±4.53)°,(29.80±4.75)° and(27.72±4.60)°,(29.64±4.79)° and(27.63±4.51)°,respectively,and LCEA was(33.79±6.12)° and(31.04±5.83)°,(33.82±6.10)° and(31.10±5.90)°,(33.75±6.08)° and(31.05±5.77)°,and AI was(6.15±1.86)° and(7.03±1.94)°,(6.08±1.82)° and(7.01±1.89)°,(6.12±1.84)° and(7.06±1.90)°,respectively.mHHS scores was(72.15±7.65)and(68.23±7.71),(76.51±7.52)and(72.19±7.94),(90.13±5.16)and(86.76±5.72),and HOS-ADL scores were(79.92±7.50)and(76.26±7.62)points,(80.85±7.42)and(77.13±7.66)points,(89.73±6.37)and(86.25±7.15)points,and the differences between the two groups were statistically significant(P<0.05);the comparison of lower limb force lines and complications between the two groups showed no statistically significant differences(P>0.05).Conclusion Modified ilioinguinal approach PAO in the treatment of DDH can optimize the operation,reduce traumatic stress factors,further improve the curative effect,improve the status of femoral head coverage and hip function,and improve the quality of life,with high safety.


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