1.Mammalian pluripotent stem cells:effects on creating disease models,pathogenesis,drug discovery and personalized treatment
Wenqiang XU ; Haolin CHEN ; Chang YAN ; Tao XU ; Yabin XIE ; Xueling LI
Chinese Journal of Tissue Engineering Research 2025;29(1):136-146
BACKGROUND:The self-renewal and multi-directional differentiation of pluripotent stem cells possess the potential to revolutionize people's understanding of biology,medicine,development,and disease.Stem cells play an important role in the early stage of embryonic development,and the study of them could be beneficial to understanding of the basic principles of biological development and tissue or organ formation,exploring the potential mechanisms of various diseases,studying the repair and regeneration of damaged tissues or organs,and promoting drug discovery and personalized treatment. OBJECTIVE:To review the research progress of pluripotent stem cells,summarize and categorize the fundamental types of pluripotent stem cells,and elucidate the lineage situations of various types of pluripotent stem cells in common mammals. METHODS:PubMed,Web of Science,CNKI,and WanFang databases were searched systematically,with the keywords"pluripotent stem cells;embryonic stem cells;induced pluripotent stem cells;expanded potential stem cells;livestock pluripotent stem cells"in English and Chinese.The 99 articles related to mammalian pluripotent stem cells were systematically screened according to inclusion and exclusion criteria,and then reviewed. RESULTS AND CONCLUSION:(1)According to classical theory in mouse embryonic stem cell research,the pluripotent state of stem cells is divided into two forms:na?ve and primed.Na?ve state corresponds to the inner cell mass of pre-implantation embryos before attachment to the uterine wall,while primed state corresponds to the epiblast after implantation.These two states exhibit significant differences in epigenetic features,transcriptional activity,external signal dependency,and metabolic phenotype.It is later discovered that there is an intermediate state between na?ve and primed called formative pluripotency.Therefore,the pluripotency of pluripotent stem cells is a continuous developmental process rather than a unique cell state.(2)In addition to obtaining pluripotent stem cells from the inner cell mass,there are various methods and lineages for acquiring pluripotent stem cells,including embryonic germ cells established using primitive germ cells from mouse embryos,induced pluripotent stem cells created by the dedifferentiation of adult mouse and human fibroblasts with four factors—Oct3/4,Sox2,c-Myc,and Klf4;embryonic stem cell-like cell lines cultured from somatic cell nuclear transfer,parthenogenesis,neonatal or adult testicular or ovarian tissue,very small embryonic-like stem cells derived from various adult tissues and expanded pluripotent stem cells derived from pre-implantation stages.These pluripotent stem cells all share the common characteristics of continuous self-renewal,expressing core pluripotency factors and possessing the ability to differentiate into the three primary germ layers.(3)Currently,pluripotent stem cells are being used for disease modeling to study the mechanisms of various diseases and develop new drugs.Simultaneously,scientists are attempting to use pluripotent stem cells to cultivate various tissues and organs,offering new possibilities for regenerative medicine and transplantation.However,the clinical application of pluripotent stem cells faces safety challenges,including issues of cell mutations and immune rejection.Continual improvement in the methods of generating pluripotent stem cells will make them safer and more efficient for clinical applications.(4)Based on the methods of obtaining and lineage establishment of pluripotent stem cells in mice and humans,various types of pluripotent stem cells have been established in livestock,including embryonic stem cells,induced pluripotent stem cells,germ lineages of pluripotent stem cells,and expanded potential stem cells.Research on livestock pluripotent stem cells opens up new avenues for animal reproduction,breeding,genetic engineering,disease modeling,drug screening,and the conservation of endangered wildlife.
2.Characteristics of coagulation function and immune function in children with severe adenovirus pneumonia and their clinical significance
Jia LIU ; Yabin YU ; Lan WANG ; Ying LI ; Xin YU ; Yongyan CAI ; Na MA ; Zhixin YAN
Journal of Clinical Medicine in Practice 2025;29(5):122-126
Objective To explore the characteristics of coagulation and immune function and their clinical significance in children with severe adenovirus pneumonia(SAP).Methods A total of 122 children with SAP and 120 children with non-severe adenovirus pneumonia(NSAP)were enrolled and assigned to severe group and non-severe group.The severe group was further subdivided into good prognosis subgroup(n=105)and poor prognosis subgroup(n=17)according to prognosis.Addition-ally,120 healthy children undergoing physical examination during the same period were included as control group.Coagulation function indicators,including prothrombin time(PT),activated partial thromboplastin time(APTT),fibrinogen(FIB),and thrombin time(TT)were measured.Levels of immunoglobulin A(IgA),immunoglobulin G(IgG),and immunoglobulin M(IgM)were determined using the nephelometric immunoassay.Multivariate Cox regression analysis was conducted to explore the influencing factors of poor prognosis.Results Compared with the control group,children in both the non-severe and severe groups exhibited increased levels of white blood cells(WBC),neutrophils(N),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),interleukin-6(IL-6),procalci-tonin(PCT),FIB,and IgG,as well as decreased levels of B lymphocytes,natural killer(NK)cells,PT,APTT,IgA,and IgM(P<0.05).Compared with the non-severe group,children in the severe group showed increased levels of WBC,N,CRP,ESR,IL-6,PCT,FIB,and IgG,as well as decreased levels of B lymphocytes,NK cells,PT,APTT,IgA,and IgM(P<0.05).Compared with the good prognosis subgroup,the poor prognosis subgroup exhibited increased levels of CRP,IL-6,PCT,and IgG,as well as decreased levels of APTT,IgM,and IgA(P<0.05).The results of multivariate Cox regression analysis showed that PCT,APTT,and IgM were influencing factors of poor prognosis in children with SAP(P<0.05).Conclusion Children with SAP have decreased levels of PT,APTT,IgA,and IgM,as well as increased levels of FIB and IgG.Coagulation and im-mune function indicators are correlated with the prognosis of SAP.
3.Association between quantitative CT-measured body composition and metabolic syndrome components in obese patients before bariatric surgery
Wei HONG ; Xiaojun HAO ; Chao TAO ; Pengzhan YIN ; Yabin XIA ; Yan JIN ; Yunfeng ZHOU
Chinese Journal of Health Management 2024;18(2):127-134
Objective:To investigate the association between quantified CT (QCT)-measured body composition and metabolic syndrome (MS) components in obese populations before bariatric surgery.Methods:A cross-sectional study. A retrospective analysis was conducted on a cohort of 97 obese patients scheduled for weight-loss surgery at the First Affiliated Hospital of Wannan Medical College from January 2021 to March 2023. The patients′ body mass index (BMI), biochemical parameters and body composition measurements obtained by QCT were recorded. The patients were stratified into groups based on gender, obesity severity and the number of MS components. Differences in body composition among the groups were compared. Additionally, the correlations between each body composition parameter and metabolic indicators were analyzed. The diagnostic efficacy of each body composition parameter for identifying obese individuals with different MS components was assessed using receiver operating characteristic (ROC) curve analysis.Results:There were 75 females (77.3%). Male obese patients had higher total abdominal fat area [(693.23±148.90) vs (574.99±114.89) cm 2, t=-3.958, P<0.001], visceral fat area [(289.65±57.67) vs (195.60±57.37) cm 2, t=-6.753, P<0.001], fat content of pancreatic head [27.45%(21.65%, 45.48%) vs 21.60%(17.6%, 26.9%), Z=-2.675, P=0.007], and skeletal muscle index [73.36(68.74, 81.26) vs 61.52(55.74, 66.41) cm 2/m 2, Z=-5.246, P<0.001]. With the increase of obesity, abdominal fat mainly increases in subcutaneous fat. With the increase of MS components (MS2 group, MS3 group, MS4 group, MS5 group), the abdominal fat area, abdominal fat/subcutaneous fat, liver fat content, pancreatic head fat content, and skeletal muscle index of patients all increased accordingly. In diagnosing the presence of two components of MS, area under the curve of visceral fat area was the largest (AUC=0.706, 95% CI=0.577-0.834). For diagnosing the presence of three, four and five components of MS, area under curve of liver fat content were all the largest (MS3=0.712, 95% CI=0.605-0.818; MS4=0.652, 95% CI=0.537-0.766; MS5=0.706, 95% CI=0.576-0.836). Conclusion:There are differences in QCT body composition among obese patients with different MS components, and there is a correlation between each body composition and MS component. Among them, intra-abdominal fat area and liver fat content are of great value in evaluating obese patients with different MS components.
4.Application of optical surface monitoring system guided volumetric modulated arc therapy in total body irradiation
Zhuangling LI ; Heli ZHONG ; Yan GAO ; Longxing LI ; Yabin SHI ; Xiaonian DENG ; Xin FU ; Ding ZHANG ; Fang ZHENG ; Hongtao CHEN ; Weisi CHEN
Chinese Journal of Medical Physics 2024;41(9):1070-1077
Objective To establish a novel clinical application process of the optical surface monitoring system(OSMS)guided volumetric modulated arc therapy(VMAT)for total body irradiation(TBI),and to assess the accuracy and effectiveness of OSMS in inter-fractional auxiliary positioning before radiotherapy and real-time monitoring of intra-fractional motion during radiotherapy.Methods A retrospective analysis was conducted on 15 leukemia patients who underwent OSMS-guided VMAT-TBI before hematopoietic stem cell transplantation.CT simulation positioning was performed,and the whole-body image data which were collected in head-first supine position(HFS)and feet-first supine position(FFS)were transmitted to the treatment planning system for image registration,multicenter VMAT planning and dose verification.The prescription dose was 800 cGy in 4 fractions twice daily.OSMS was used to assist positioning before delivery,and CBCT was used for position verification.During treatment,OSMS was used for monitoring.The intra-fractional error monitored by OSMS in real time was obtained by analyzing the offline log files.Results The mean dose and coverage of the target area in HFS plan were(905.4±19.0)cGy and 93.0%±2.8%.The mean doses to lung and kidney were(603.7±55.7)cGy and(600.4±49.6)cGy,respectively,and the maximum dose to the lens was(393.9±58.9)cGy.The mean dose and coverage of the target area in FFS plan were(888.5±58.9)cGy and 94.0%±3.2%;and the maximum dose at the junction was(1148.9±72.9)cGy.Fractional treatment delivery time was(75.1±15.1)min.OSMS-assisted positioning was carried out before delivery,and the total deviations of CBCT three-dimensional vector in translational and rotation directions were(2.71±1.96)mm and 0.91°±0.90°,respectively.The three-dimensional vector deviation of the intra-fractional motion amplitude in translational direction monitored by OSMS during the treatment was(1.95±1.88)mm,of which the deviation within 1 mm accounted for 57.5%,79.7%and 62.1%in longitudinal,lateral and vertical directions,respectively.The three-dimensional vector deviation in rotation direction was 0.76°±0.72°,of which the deviation within 1°accounted for 93.1%,85.7%and 94.3%in rotation,pitch and roll directions,respectively.Conclusion VMAT simplifies TBI process,while improving target coverage and organs-at-risk sparing.The use of OSMS can reduce positioning errors,especially rotation errors.In order to ensure the accurate implementation of TBI and the safety of patients,it is necessary to use OSMS for auxiliary positioning and intra-fractional position monitoring.
5.Optimization of immobilization and positioning methods in hypofractionated stereotactic radiotherapy for brain metastases
Longxing LI ; Yan GAO ; Hongtao CHEN ; Zihuang LI ; Yabin SHI
Chinese Journal of Radiological Medicine and Protection 2024;44(7):587-593
Objective:To compare translational and rotational setup errors between immobilization with open masks combined with positioning with the optical surface monitoring system (OSMS) and immobilization with full masks combined with positioning with laser lights and mask markers, find the advantages of open masks combined with OSMS in hypofractionated stereotactic radiotherapy (HSRT) for brain metastases, and calculate planning target volume (PTV) expansions with different immobilization and positioning method for patients with brain metastases.Methods:The setup data of 55 patients with brain metastases who received HSRT were analyzed retrospectively. According to immobilization and positioning method, the patients were divided into group A (OSMS + open masks), group B1 (full head-neck-shoulders masks + polyurethane foam cushions), and group B2 (full head-neck-shoulders masks + standard headrests). Positioning was directed by automatic couch motion in OSMS in group A and by laser lights and mask markers in groups B1 and B2. Cone beam computed tomography (CBCT) scans were registered using the bone registration method to obtain setup errors in six directions ( x, y, z, roll, pitch, yaw). PTV expansions were calculated according to the van Herk formula. Results:A total of 288 sets of CBCT registration data were acquired. Among three groups, group A showed the smallest mean setup errors and 3D vector error, which were (0.47±0.33) mm, (0.49±0.31) mm, (0.44±0.31) mm, (0.42±0.32)°, (0.48±0.31)°, (0.42±0.22)°, and (0.90±0.39) mm, respectively. Group A differed significantly from group B1 and group B2 in the errors at all directions ( P < 0.05) except for the yaw direction compared with group B1 ( P > 0.05). Group A had no setup error ≥2 mm in translational directions or ≥2° in rotational directions. Group B1 showed significantly smaller setup errors in the y, z, and yaw directions and 3D vector error than group B2 ( P < 0.05). In group A, PTV expansions in three directions ( x, y, and z) were 1.32, 1.19, and 1.22 mm, respectively, which were smaller than those of the other two groups. Conclusions:In HSRT for patient with brain metastases, compared with full head-neck-shoulders masks combined with laser lights and mask markers, open masks combined with OSMS can significantly improve setup precision in six directions and reduce repeated setup and PTV expansions, which shows promise for clinical application.
6.The non-invasive methods in the diagnosis of pancreatic fibrosis:a review
Yabin HU ; Xiangran JIA ; Hui DING ; Jing SONG ; Fengxian WANG ; Yan LI ; He REN
Tumor 2024;44(12):1216-1224
Pancreatic fibrosis is an important pathological feature of pancreatic cancer and chronic pancreatitis,and plays an important role in the progression of pancreatic cancer and chronic pancreatitis.Pancreatic fibrosis blocks the chemotherapy drugs from reaching the cancer cells to do their job and also affects the stiffness of the pancreatic tissue.Therefore,it is important to assess the degree of pancreatic fibrosis as an adjunct to surgical and chemotherapeutic treatments for pancreatic cancer and chronic pancreatitis.In recent years,there have been new research advances and technological breakthroughs in non-invasive diagnostic methods for pancreatic fibrosis.The fields of CT,ultrasound elastography and magnetic resonance imaging have extended new imaging techniques,yielded new imaging indices to assess the degree of pancreatic fibrosis.In this paper,we have collected relevant literatures since 2018 to describe the research progress related to non-invasive diagnostic methods for pancreatic fibrosis.
7.Minimally Invasive Transthoracic Intramyocardial Cellular Transplantation Under Echocardiographic Guidance for Myocardial Impairment
Sulei LI ; Bo TAO ; Junsong LIU ; Dongyue LIU ; Yujia WANG ; Jibin ZHANG ; Lei TIAN ; Baixuan XU ; Yan FANG ; Yabin WANG ; Xin LOU ; Jinming ZHANG ; Feng LAN ; Feng CAO
Cardiology Discovery 2024;04(4):260-273
Objective::To explore the approach of minimally invasive transthoracic intramyocardial cellular transplantation under echocardiographic guidance to promote ischemic myocardial repair in a preclinical big-animal study.Methods::Female Guangxi Bama miniature pigs (weight: 25–30 kg) were randomly allocated into the sham group, untreated myocardial infarction (MI) group (MI group), the MI and surgical intramyocardial injection (SIM) group (MI-SIM group), and the MI and transthoracic echocardiography-guided percutaneous intramyocardial injection (TTEPIM) group (MI-TTEPIM group) ( n = 4 each) using a lottery method. A swine MI model was established in the 3 groups excluding the sham group, and human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) labeled with the herpes simplex virus type-1 thymidine kinase reporter gene (hiPS-CM TK+) were transplanted by SIM in MI-SIM group and TTEPIM in MI-TTEPIM group. The operation time, postoperative recovery time of animals and volume of blood loss were collected for comparison between MI-SIM group and MI-TTEPIM group. 9-(4-[ 18F] fluoro-3-(hydroxymethyl) butyl) guanine positron emission tomography/computed tomography imaging was performed to track the hiPS-CM TK+in vivo. Cardiac function and morphology were evaluated by echocardiography. Results::The operation time and postoperative recovery time of MI-TTEPIM group were significantly shorter than those of MI-SIM group ((28.3 ± 3.6) min vs. (97.0 ± 6.7) min, P < 0.001; (1.3 ± 0.3) d vs. (7.5 ± 0.9) d, P < 0.001). MI-TTEPIM also showed significantly lesser volume of blood loss during cell transplantation than MI-SIM group ((4.3 ± 0.8) mL vs. (47.0 ± 4.1) mL, P < 0.001). The transplanted cells could be traced more accurately in vivo in MI-TTEPIM than in MI-SIM. The circumferential strain of intervention region in the MI-TTEPIM group (–25.07% ± 0.27%) was significantly higher than that of the MI-SIM (–20.39% ± 0.67%) and MI groups (–19.68% ± 0.67%), respectively ( P < 0.01). Conclusion::A minimally invasive TTEPIM protocol with stem cells for treating the ischemic myocardium was established in this study. Transplantation of hiPS-CM TK+ with this method could promote the recovery of the circumferential strain of the ischemic myocardium. The findings of this study lay a foundation for the clinical transformation of this auxiliary means of treatment in the future.
8.Minimally Invasive Transthoracic Intramyocardial Cellular Transplantation Under Echocardiographic Guidance for Myocardial Impairment
Sulei LI ; Bo TAO ; Junsong LIU ; Dongyue LIU ; Yujia WANG ; Jibin ZHANG ; Lei TIAN ; Baixuan XU ; Yan FANG ; Yabin WANG ; Xin LOU ; Jinming ZHANG ; Feng LAN ; Feng CAO
Cardiology Discovery 2024;04(4):260-273
Objective::To explore the approach of minimally invasive transthoracic intramyocardial cellular transplantation under echocardiographic guidance to promote ischemic myocardial repair in a preclinical big-animal study.Methods::Female Guangxi Bama miniature pigs (weight: 25–30 kg) were randomly allocated into the sham group, untreated myocardial infarction (MI) group (MI group), the MI and surgical intramyocardial injection (SIM) group (MI-SIM group), and the MI and transthoracic echocardiography-guided percutaneous intramyocardial injection (TTEPIM) group (MI-TTEPIM group) ( n = 4 each) using a lottery method. A swine MI model was established in the 3 groups excluding the sham group, and human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) labeled with the herpes simplex virus type-1 thymidine kinase reporter gene (hiPS-CM TK+) were transplanted by SIM in MI-SIM group and TTEPIM in MI-TTEPIM group. The operation time, postoperative recovery time of animals and volume of blood loss were collected for comparison between MI-SIM group and MI-TTEPIM group. 9-(4-[ 18F] fluoro-3-(hydroxymethyl) butyl) guanine positron emission tomography/computed tomography imaging was performed to track the hiPS-CM TK+in vivo. Cardiac function and morphology were evaluated by echocardiography. Results::The operation time and postoperative recovery time of MI-TTEPIM group were significantly shorter than those of MI-SIM group ((28.3 ± 3.6) min vs. (97.0 ± 6.7) min, P < 0.001; (1.3 ± 0.3) d vs. (7.5 ± 0.9) d, P < 0.001). MI-TTEPIM also showed significantly lesser volume of blood loss during cell transplantation than MI-SIM group ((4.3 ± 0.8) mL vs. (47.0 ± 4.1) mL, P < 0.001). The transplanted cells could be traced more accurately in vivo in MI-TTEPIM than in MI-SIM. The circumferential strain of intervention region in the MI-TTEPIM group (–25.07% ± 0.27%) was significantly higher than that of the MI-SIM (–20.39% ± 0.67%) and MI groups (–19.68% ± 0.67%), respectively ( P < 0.01). Conclusion::A minimally invasive TTEPIM protocol with stem cells for treating the ischemic myocardium was established in this study. Transplantation of hiPS-CM TK+ with this method could promote the recovery of the circumferential strain of the ischemic myocardium. The findings of this study lay a foundation for the clinical transformation of this auxiliary means of treatment in the future.
9.The non-invasive methods in the diagnosis of pancreatic fibrosis:a review
Yabin HU ; Xiangran JIA ; Hui DING ; Jing SONG ; Fengxian WANG ; Yan LI ; He REN
Tumor 2024;44(12):1216-1224
Pancreatic fibrosis is an important pathological feature of pancreatic cancer and chronic pancreatitis,and plays an important role in the progression of pancreatic cancer and chronic pancreatitis.Pancreatic fibrosis blocks the chemotherapy drugs from reaching the cancer cells to do their job and also affects the stiffness of the pancreatic tissue.Therefore,it is important to assess the degree of pancreatic fibrosis as an adjunct to surgical and chemotherapeutic treatments for pancreatic cancer and chronic pancreatitis.In recent years,there have been new research advances and technological breakthroughs in non-invasive diagnostic methods for pancreatic fibrosis.The fields of CT,ultrasound elastography and magnetic resonance imaging have extended new imaging techniques,yielded new imaging indices to assess the degree of pancreatic fibrosis.In this paper,we have collected relevant literatures since 2018 to describe the research progress related to non-invasive diagnostic methods for pancreatic fibrosis.
10.Short-term effect of robotic pancreaticoduodenectomy and laparoscopic pancreaticoduodenectomy: a meta-analysis
Yabin YU ; Quan JIN ; Yan SONG ; Jianbo XU ; Fuzhen QI
Chinese Journal of Hepatobiliary Surgery 2021;27(3):211-214
Objective:To evaluate the short-term effect of robotic pancreaticoduodenectomy (RPD) and laparoscopic pancreaticoduodenectomy (LPD) in the treatment of ampullary and periampullary tumor systematically.Methods:A systematic search of the PubMed, Embase and Cochrane library database using the key words "pancreaticoduodenectomy, duodenopanreatectpmy, whipple, laparoscopic, robotic, Da Vinci" . A systematic search of the Sinomed, Wangfang, VIP and CNKI databases including the key words "胰十二指肠切除" , "腹腔镜" , "机器人" , "达芬奇" . To investigate the differences of the conversion rate of laparotomy, incidence of postoperative complications, and the postoperative hospital stay between the RPD group and the LPD group. The software RevMan5.3 was used in this meta-analysis.Results:A total of 4 retrospective cohort studies and 1 001 patients were included in this meta-analysis, including 451 patients in the RPD group and 550 patients in the LPD group. The results of the meta-analysis showed that there were significant differences between RPD group and LPD group for the conversion rate laparotomy ( OR=0.35, 95% CI: 0.24-0.50, P<0.05). There were no significant differences between RPD group and LPD group for the incidence rate of overall complication( OR=1.23, 95% CI: 0.95-1.58, P>0.05), hemorrhage ( OR=0.71, 95% CI: 0.50-1.00, P>0.05), pancreatic fistula ( OR=1.09, 95% CI: 0.80-1.49, P>0.05), delayed gastric empty ( OR=0.81, 95%CI: 0.57-1.14, P>0.05) and hospital stay after surgery ( WMD=-2.87, 95% CI: -1.44-1.70, P>0.05). Conclusions:RPD is as safe as LPD, with the same complication rate. Therefor it is worthy for further application in medical institutions with relevant conditions.

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