1.Stem cell therapy for amyotrophic lateral sclerosis:cell source,number,modification,and administration route
Wen ZHAO ; Yulin BI ; Xuyang FU ; Hongmei DUAN ; Zhaoyang YANG ; Xiaoguang LI
Chinese Journal of Tissue Engineering Research 2025;29(19):4083-4090
BACKGROUND:With the continuous advancement of medical technology,stem cell therapy has been used to treat a variety of diseases,including amyotrophic lateral sclerosis. OBJECTIVE:To review the research progress of stem cell therapy for amyotrophic lateral sclerosis,and prospect the development trend of this field. METHODS:PubMed,China National Knowledge Infrastructure(CNKI),and WanFang Data were searched for articles published from 1995 to 2024 using the key words"amyotrophic lateral sclerosis,mesenchymal stem cells,neural stem/progenitor cells,pluripotent stem cells."A total of more than 1 700 articles were retrieved,and 58 articles were finally included in this review. RESULTS AND CONCLUSION:Amyotrophic lateral sclerosis is a neurodegenerative disease that affects lower motor neurons in the brainstem and spinal cord and upper motor neurons in the motor cortex.The related research of stem cells in the treatment of amyotrophic lateral sclerosis has become a research hotspot.In this review,we summarize the application of different types of stem cells in amyotrophic lateral sclerosis research,including mesenchymal stem cells,neural stem progenitor cells,and induced pluripotent stem cells,and evaluate the key points of preclinical research such as stem cell source,cell volume,stem cell modification methods,and drug delivery routes,which lays the foundation for the future application of stem cell therapy.
2.Cardiomyocyte pyroptosis inhibited by dental pulp-derived mesenchymal stem cells via the miR-19a-3p/IRF-8/MAPK pathway in ischemia-reperfusion.
Yi LI ; Xiang WANG ; Sixian WENG ; Chenxi XIA ; Xuyang MENG ; Chenguang YANG ; Ying GUO ; Zuowei PEI ; Haiyang GAO ; Fang WANG
Chinese Medical Journal 2025;138(18):2336-2346
BACKGROUND:
The protective effect of mesenchymal stem cells (MSCs) on cardiac ischemia-reperfusion (I/R) injury has been widely reported. Dental pulp-derived mesenchymal stem cells (DP-MSCs) have therapeutic effects on various diseases, including diabetes and cirrhosis. This study aimed to determine the therapeutic effects of DP-MSCs on I/R injury and elucidate the underlying mechanism.
METHODS:
Myocardial I/R injury model mice were treated with DP-MSCs or a miR-19a-3p mimic. The infarct volume, fibrotic area, pyroptosis, inflammation level, and cardiac function were measured. Cardiomyocytes exposed to hypoxia-reoxygenation were transfected with the miR-19a-3p mimic, miR-19a-3p inhibitor, or negative control. Pyroptosis and protein expression in the interferon regulatory factor 8/mitogen-activated protein kinase (IRF-8/MAPK) pathway were measured.
RESULTS:
DP-MSCs protected cardiac function in cardiac I/R-injured mice and inhibited cardiomyocyte pyroptosis. The upregulation of miR-19a-3p protected cardiac function, inhibited cardiomyocyte pyroptosis, and inhibited IRF-8/MAPK signaling in cardiac I/R-injured mice. DP-MSCs inhibited cardiomyocyte pyroptosis and the IRF-8/MAPK signaling by upregulating the miR-19a-3p levels in cardiomyocytes injured by I/R.
CONCLUSION
DP-MSCs protected cardiac function by inhibiting cardiomyocyte pyroptosis through miR-19a-3p under I/R conditions.
Animals
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MicroRNAs/metabolism*
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Pyroptosis/genetics*
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Mesenchymal Stem Cells/metabolism*
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Myocytes, Cardiac/cytology*
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Mice
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Male
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Mice, Inbred C57BL
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Dental Pulp/cytology*
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Myocardial Reperfusion Injury/therapy*
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MAP Kinase Signaling System/physiology*
4.High-risk factors for significant liver histopathological damage in patients with indeterminate phase of chronic HBV infection
Wenchang WANG ; Xuyang LI ; Chunyan WANG ; Mengwen HE ; Yifan GUO ; Yiming FU ; Miao LIU ; Dong JI
Journal of Clinical Hepatology 2025;41(11):2258-2264
ObjectiveTo investigate the features of liver histopathological damage in patients with indeterminate phase of chronic HBV infection, as well as the timing for initiating antiviral therapy in such patients. MethodsA retrospective screening was performed for the patients with chronic HBV infection who were hospitalized in The Fifth Medical Center of Chinese PLA General Hospital and underwent liver biopsy from March 2018 to April 2022, among whom the patients who met the criteria for indeterminate phase defined in Chinese guidelines for chronic hepatitis B prevention and treatment (2022 edition) were enrolled, and their clinical data were collected. Liver histopathological stage was determined using the Scheuer scoring system, with stages 0 — 4 for inflammation grade (G) and stages 0 — 4 for fibrosis degree (S), and the patients were divided into groups based on the presence of significant necroinflammation (≥G2) and significant liver fibrosis (≥S2). The independent samples t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous 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 Spearman’s rank correlation analysis was used to investigate the correlation between liver histopathology and clinical factors, and the Logistic regression model was used to identify the independent influencing factors for significant necroinflammation and liver fibrosis. ResultsA total of 271 patients with indeterminate phase of chronic HBV infection were enrolled, among whom 61 (22.5%) had significant necroinflammation (≥G2) and 124 (45.8%) had significant liver fibrosis (≥S2). The Logistic regression analysis showed that alanine aminotransferase ≥30 U/L (for male patients) or ≥19 U/L (for female patients) (odds ratio [OR]=2.69, 95% confidence interval [CI]: 1.39 — 5.21, P=0.003), HBV DNA ≥2 000 IU/mL (OR=2.75, 95%CI: 1.38 — 5.48, P=0.004), and liver stiffness measurement (LSM) ≥6.0 kPa (OR=4.57, 95%CI: 2.17 — 9.62, P<0.001) were independent risk factors for significant inflammation. HBV DNA ≥2 000 IU/mL (OR=1.82, 95%CI: 1.01 — 3.32, P=0.049) and LSM ≥6.0 kPa (OR=2.06, 95%CI: 1.23 — 3.43, P=0.006) were independent influencing factors for significant liver fibrosis. ConclusionAmong the patients with indeterminate phase of chronic HBV infection, a substantial proportion of patients have significant liver histopathological damage. Antiviral therapy should be initiated in a timely manner for patients with high-risk factors.
5.Risk factors of abnormal urinary albumin/creatinine ratio in people with obesity
Zhe CAO ; Tongyue YANG ; Shiyu LIU ; Mengxing PAN ; Xuyang GONG ; Qianshuai LI ; Jiao WANG ; Lin ZHAO ; Guijun QIN ; Yanyan ZHAO
Chinese Journal of Endocrinology and Metabolism 2024;40(3):186-191
Objective:To explore the clinical characteristics and risk factors of abnormal urinary albumin/creatinine ratio(UACR) in obese population.Methods:Baseline data from 2011 to 2012 in Henan Sub-center of"Risk Evaluation of cAncers in Chinese diabeTic Individuals: A lONgitudinal(REACTION) study"were utilized and those of body mass index≥28 kg/m 2 were screened. The patients were divided into UACR normal group and UACR abnormal group(101 pairs) upon being matched on a 1∶1 basis by age and gender. Multivariate logistic regression analysis, receiver operating characteristic(ROC) curve, and restricted cubic spline(RCS)analysis were performed to explore the risk factors for abnormal UACR. Results:Compared with the normal UACR group, the UACR abnormal group had a higher number of alcohol consumers, a higher prevalence of hypertension, elevated systolic blood pressure, and triglyceride(all P<0.05). Multivariate logistic regression analysis showed that alcohol consumption( P=0.008), systolic blood pressure( P<0.001), triglyceride( P=0.049), and homeostasis model assessment for insulin resistance(HOMA-IR, P=0.033) were independent risk factors for abnormal UACR in obese people. The ROC curve analysis indicated that systolic blood pressure had the strongest diagnostic performance as a single factor(ROC curve area=0.801), and there was no significant difference in diagnostic performance compared to multiple factors combination. RCS analysis results showed that the probability of abnormal UACR increased monotonically with the increase of systolic blood pressure when the systolic blood pressure was between 130 and 158 mmHg(1 mmHg=0.133 kPa). When systolic blood pressure was not in the interval, the probability of abnormal UACR did not change significantly. The results of regression analysis of triglyceride subgroup showed that when triglyceride level was greater than or equal to 5.6 mmol/L, the risk of abnormal UACR level was significantly increased( P=0.029). Conclusion:Systolic blood pressure, triglyceride, HOMA-IR, and alcohol drinking history are independent risk factors for abnormal UACR in obese people. When systolic blood pressure is≥130 mmHg or triglyceride is≥5.6 mmol/L, the risk of abnormal UACR is significantly increased.
6.Placenta-derived mesenchymal stem cells in promoting acute skin wound healing in rats
Hongfei DONG ; Xi HUANG ; Xianhui LI ; Yanbiao ZHANG ; Xuyang WANG ; Bing WANG ; Hongyu SUN
Chinese Journal of Tissue Engineering Research 2024;28(13):2047-2053
BACKGROUND:Currently,a variety of mesenchymal stem cells have been confirmed to have the effect of promoting wound repair,but there is still a lack of relevant research on whether placenta-derived mesenchymal stem cells can promote acute skin wound healing. OBJECTIVE:To investigate the effect of placenta-derived mesenchymal stem cell transplantation on the healing of acute skin wound in rats. METHODS:Twenty SD rats were divided into PBS group and stem cell group by the random number table method,with 10 rats in each group.All rats were selected to establish a full-thickness skin defect model.In the PBS group and stem cell group,PBS buffer and placenta-derived mesenchymal stem cells were immediately injected on the wound surface and wound margin immediately and on day 8 after modeling.The wound healing was observed immediately and on days 2,4,6,8,10,12,and 14 after modeling.The skin tissue of the wound surface was taken on day 14 and treated with hematoxylin-eosin staining,Masson staining,immunohistochemical staining and immunofluorescence staining. RESULTS AND CONCLUSION:(1)The wound surface of the rats in each group decreased with the prolongation of treatment time.The wound healing rate and wound epithelization rate of the stem cell group at 14 days were higher than those of the PBS group(P<0.01),and the wound contracture rate was lower than that of the PBS group(P<0.01).(2)The results of hematoxylin-eosin staining showed that the skin wound healing of the stem cell group was better than that of the PBS group;the degree of wound epithelization was higher,and the morphology of collagen fibers was close to that of normal skin.(3)Masson staining results showed that compared with the PBS group,collagen fibers in the skin wound tissue of the stem cell group were significantly increased and thicker,and the content of collagen fibers in the new tissue was significantly higher than that of the PBS group(P<0.01).(4)Immunohistochemical staining showed that the number of new capillaries in the stem cell group was higher than that in the PBS group(P<0.01),while the expressions of tumor necrosis factor-α and interleukin-6 were lower than those in the PBS group(P<0.01).(5)Immunofluorescence staining showed that the number of M2 macrophages in the new wounds of the stem cell group was higher than that of the PBS group(P<0.01),while the number of M1 macrophages was less than that in the PBS group(P<0.01).These findings indicate that placenta-derived mesenchymal stem cells can accelerate skin wound healing,promote wound epithelization,and reduce wound contracture,which may be related to the promotion of capillary angiogenesis,regulation of collagen fiber production,inhibition of inflammation,and regulation of macrophage polarization to M2 type.
7.Three-dimensional digital model-assisted minimally invasive needle penetration and steel plate internal fixation in treatment of Sanders types Ⅱ and Ⅲ calcaneal fractures
Wendong LIU ; Hongle XIA ; Lin LIU ; Runbin SHEN ; Wei GUO ; Xuyang WANG ; Guoliang LI
Chinese Journal of Tissue Engineering Research 2024;28(18):2819-2824
BACKGROUND:At present,open reduction and internal fixation and minimally invasive needle aspiration are commonly used in patients with Sanders types Ⅱ and Ⅲ calcaneal fractures.However,there is little comparison between the clinical efficacy of the two methods and high-level clinical evidence is still available. OBJECTIVE:To compare the curative effect of Sanders types Ⅱ and Ⅲ calcaneal fractures treated by three-dimensional digital model-assisted minimally invasive needle penetration and tarsal sinus incision and manual reduction and internal fixation with steel plate. METHODS:From January 2021 to October 2022,80 patients with Sanders types Ⅱ and Ⅲ calcaneal fractures who were treated in the Department of Orthopedics,Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine in Hebei Province were randomly divided into control group(40 cases)and observation group(40 cases).The control group was treated with manual reduction and internal fixation with steel plate through the traditional tarsal sinus incision,while the observation group was treated with a three-dimensional digital model assisted with minimally invasive needle penetration fixation.The operation time,blood loss,hospitalization time and fracture healing time of the two groups were recorded.The changes in Maryland score,AO-FAS score,pain visual analog scale score,quality of life score(SF-36 score),and imaging parameters(B?hler angle,Gissane angle,calcaneal length,width and height)were observed before and 12 months after operation in the two groups.The complications during the follow-up were recorded. RESULTS AND CONCLUSION:(1)Operation time,blood loss,hospitalization time and fracture healing time in the observation group were lower than those in the control group(all P<0.05).(2)The Maryland score,AO-FAS score,SF-36 score,B?hler angle,Gissane angle,calcaneal length and height of the two groups after treatment were significantly higher than those before treatment(all P<0.05).Visual analog scale score and calcaneal width were significantly lower than those before treatment(all P<0.05).(3)After 12 months of follow-up,the incidence of complications in the observation group was lower than that in the control group(all P<0.05).(4)In conclusion,the treatment of Sanders types Ⅱ and Ⅲ calcaneal fractures with three-dimensional digital model-assisted minimally invasive needle penetration fixation can significantly improve the operation time,bleeding volume and other perioperative indicators,and can reduce the occurrence of multiple complications.The recovery of ankle function,relief of pain symptoms,and improvement of quality of life are equivalent to traditional therapy.
8.Clinical study of rhegmatogenous retinal detachment treatment with minimally invasive foldable capsular buckle scleral buckling
Xuyang SUN ; Taixiang CHEN ; Rui LI ; Wen SUN ; Fangtian DONG
International Eye Science 2024;24(2):277-283
AIM:To investigate the clinical efficacy of minimally invasive foldable capsular buckle(FCB)scleral buckling in treating rhegmatogenous retinal detachment(RRD).METHOD: This retrospective study enrolled 11 patients(11 eyes)with RRD treated with minimally invasive FCB scleral buckling at the Hainan Traditional Chinese Medicine Hospital from May to July 2023. The surgeries were performed without subconjunctival anesthesia, extraocular muscle pulling, intraocular positioning, retinal cryotherapy or drainage of subretinal fluid, or FCB suture fixation. Furthermore, the best corrected visual acuity(BCVA), intraocular pressure and complications were observed.RESULTS: Minimally invasive FCB scleral buckling was performed on 11 eyes, with successful retinal reattachment in 10 eyes(91%), and the remaining 1 eye(9%)had postoperative retinal re-detachment and underwent vitrectomy with silicone oil filling for multiple retinal tears. One-time successful surgery was in 4 eyes(40%), gas injection in vitreous body after the surgery was performed in 1 eye(10%), FCB position adjustment after the surgery was performed in 3 eyes(30%), gas injection in vitreous body and FCB position adjustment after the surgery were performed in 2 eyes(20%); and FCB was removed 4-12 wk after the surgery in 5 eyes(50%), without retinal redetachment. The average BCVA(LogMAR)of the 10 eyes improved from 1.30±1.10 before surgery to 0.37±0.39 at 4 wk after surgery(P<0.01); the average preoperative intraocular pressure was 11.51±3.37 mmHg and 13.72±2.57 mmHg at 4wk after surgery(P>0.05). No serious complications occurred.CONCLUSION:Minimally invasive FCB scleral buckling effectively treats RRD with minimal injury, simple operation, time-saving, and fewer complications.
9.Clinical features and prognostic analysis of colorectal extranodal NK/T cell lymphoma
Xiangyu LI ; Jianning YAO ; Xuyang DONG ; Liangxing CHENG ; Xuexiu ZHANG ; Mengge SU ; Haining ZHOU ; Jinlin XIE ; Zhaoxiang SONG ; Fei HAN
Chinese Journal of Oncology 2024;46(8):782-793
Objective:To investigate the clinical manifestations, endoscopic characteristics, and prognostic factors of patients with colorectal extranodal NK/T cell lymphoma.Methods:The clinical data of 52 patients with colorectal extranodal NK/T cell lymphoma admitted to the First Affiliated Hospital of Zhengzhou University from January 2013 to January 2023 were retrospectively analyzed. Their clinical manifestations and endoscopic characteristics were summarized, and the prognostic factors were analyzed by Cox regression model.Results:Among the 52 patients with colorectal extranodal NK/T cell lymphoma, there were 35 males and 17 females, with a male-to-female ratio of 2.06∶1. Among the general symptoms, abdominal pain was the most common (39 cases), and B symptoms occurred in 47 patients, among which fever was the most common lymphoma B symptom (42 cases), and gastrointestinal perforation was the most common complication (18 cases). Forty-three patients underwent colonoscopy, and the main manifestations under endoscopy were the ulceration type (24 cases). The ulcers were irregular at the edges and often covered with moss at the bottom. The median survival time was 4.3 months. Multivariate Cox regression analysis showed that hemocytic syndrome ( HR=8.50,95% CI: 1.679-8.328, P=0.001), serum albumin ( HR=3.59,95% CI: 1.017-6.551, P=0.048), and with or without chemotherapy ( HR=0.31, 95% CI: 0.246-1.061, P=0.025) were independent factors influencing the overall survival of patients with colorectal extranodal NK/T cell lymphoma. Conclusions:Colorectal extranodal NK/T cell lymphoma is a rare disease with a very poor prognosis. When patients present with abdominal pain and lymphoma B symptoms, and when ulcers with irregular edges and moss covering the bottom are found under endoscopy, the disease should be considered, and endoscopic biopsy should be taken in time for pathological diagnosis. The prognosis of patients with hemophagocytic syndrome and hypoproteinemia is poor. This disease should be treated with chemotherapy and surgery, and on this basis, hemophagocytic syndrome and hypoproteinemia should be treated to improve the prognosis of patients.
10.Echocardiographic two-dimensional strain evaluation of right ventricular function in healthy adults
Yi LI ; Ying GUO ; Chenxi XIA ; Xuyang MENG ; Xiang WANG ; Tao XU ; You ZHONG ; Fang WANG
Chinese Journal of Cardiology 2024;52(1):58-63
Objective:To explore the feasibility of using two-dimensional speckle tracking echocardiography for measuring right ventricular strain and function in healthy adults, and to analyze the impact of age and gender.Methods:This study is a cross-sectional study. Healthy adults who underwent physical examination in the Physical Examination Center of Beijing Hospital from January 1, 2020 to January 1, 2021 were included. Two researchers independently measured various right ventricular longitudinal strain indices using the Echopac software, including (global longitudinal strain (GLS), apical longitudinal strain (ALS), midventricle longitudinal strain (MLS), basal longitudinal strain (BLS), free wall GLS (FWGLS), free wall ALS (FWALS), free wall MLS (FWMLS) and free wall BLS (FWBLS)) as well as tricuspid annular plane systolic excursion (TAPSE) and right ventricle-fraction of area change (RVFAC). The above indicators were taken as the average of two physicians. The consistency of the measurements by two physicians was evaluated by the within-group correlation coefficient ( ICC). Results:A total of 233 subjects were included, including 137 males, aged (58.5±14.2) years. ICC values was all above 0.8 with excellent agreement. The values of FWGLS and GLS in healthy adults were -26.63% and -21.89%, respectively. There was no statistically significant difference in TAPSE ((2.06±0.41)cm vs. (2.10±0.39)cm, P=0.510) and RVFAC ((51.17±9.91)% vs. (50.89±8.65)%, P=0.826) between males and females. The values of various right ventricular long axis strain indicators (GLS, ALS, MLS, BLS, FWGLS, FWMLS, FWMLS, FWBLS) in females aged 18 to 40 and 41 to 65 years were higher than those in males of the same age (all P<0.05), while there was no statistically significant difference in the values of various right ventricular long axis strain indicators between the sexes in subjects aged 65 years and above (all P>0.05). In females, the right ventricular GLS, ALS, MLS, FWGLS, FWALS, FWMLS, and FWBLS values in the groups aged 18 to 40 and 41 to 65 years were significantly higher than those in the group aged 65 years and above (all P<0.05). In contrast, no significant differences were found in these indices among different age groups in males (all P>0.05). Conclusions:Using two-dimensional speckle tracking technology in echocardiography to measure right ventricular strain indicators is feasible and highly reproducible. Gender and age have an impact on right ventricular strain indicators.

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