BACKGROUND:Adult stem cell therapy is one of the research hotspots in the field of peripheral nerve injury repair and regeneration.With excellent properties of mesenchymal stem cells such as high acquisition rate,wide source,and rapid proliferation,mesoderm have been regarded as the ideal source of adult stem cells,while ectoderm-derived adult stem cells,especially neural crest stem cells,have certain neurogenic properties and attract more and more attention from researchers. OBJECTIVE:To mainly review the role and mechanism of multifunctional adult stem cells from ectoderm and mesoderm in peripheral nerve injury repair and regeneration,so as to explore the research progress and application prospect of adult stem cells from different sources and discuss the potential application value of adult stem cell therapy and the problems to be solved in connection with clinical studies. METHODS:The first author searched the relevant articles published from December 2001 to February 2024 in PubMed and SinoMed by computer in February 2024.The Chinese and English search terms were"ectodermal stem cells,mesenchymal stem cells,peripheral nerve injury,repair,regeneration."Finally,69 articles were included and analyzed. RESULTS AND CONCLUSION:(1)Ectodermal adult stem cells have excellent differentiation and regeneration potential,especially epidermal neural crest stems cells,olfactory stem cells,and dental ectomesenchymal stem cells,which have certain neurogenic properties and can express neural specific markers in vitro.However,relevant clinical research needs to be accumulated.(2)There are many types of adult stem cells derived from mesoderm,which are easy to obtain and purify.Among them,the efficacy and safety of bone marrow mesenchymal stem cells and umbilical cord mesenchymal stem cells in the repair of peripheral nerve injury are supported by clinical trials;that is,they can improve sensory and motor nerve conduction and there are no complications and obvious adverse reactions in follow-up.The acquisition of bone marrow mesenchymal stem cells needs invasive surgery and requires the patient to match the donor bone marrow type,which limit the application to some extent.Although umbilical cord mesenchymal stem cells do not require invasive harvesting,their isolation is difficult and phenotypically unstable.(3)Adult stem cells derived from endoderm often fail to grow in vitro,so the possibility of clinical application is low.(4)In conclusion,bone marrow mesenchymal stem cells are still the first choice for adult stem cell therapy in the treatment of peripheral nerve injury,which is suitable for cases without surgical contraindications and meeting the matching requirements,followed by umbilical cord mesenchymal stem cells supplemented by improved isolation methods and advanced phenotypic stability strategies.(5)Dental ectomesenchymal stem cells and adipose-derived mesenchymal stem cells have high application potential and need to be further tested in clinical trials.Other adult stem cells derived from ectodermal and mesodermal layers have significant advantages in animal and cell experimental studies due to their excellent properties.

OBJECTIVE: To compare the biomechanical properties of personalized Y-shaped plates with horizontal plates, vertical plates, and traditional Y-shaped plates in the treatment of distal humeral intra-articular fractures through finite element analysis, and to evaluate their potential for clinical application. METHODS: The study selected a 38-year-old male volunteer and obtained a three-dimensional model of the humerus by scanning his upper limbs using a 64-slice spiral CT. Four types of fracture-internal fixation models were constructed using Mimics 19.0, Geomagic Wrap 2017, Creo 6.0, and other software: horizontal plates, vertical plates, traditional Y-shaped plate, and personalized Y-shaped plate. The models were then meshed using Hypermesh 14.0 software, and material properties and boundary conditions were defined in Abaqus 6.14 software. AnyBody 7.3 software was used to simulate elbow flexion and extension movements, calculate muscle strength, joint forces, and load torques, and compare the peak stress and maximum displacement of the four fixation methods at different motion angles (10°, 30°, 50°, 70°, 90°, 110°, 130°, 150°) during elbow flexion and extension. RESULTS: Under dynamic loading during elbow flexion and extension, the personalized Y-shaped plate exhibits significant biomechanical advantages. During elbow flexion, the peak internal fixation stress of the personalized Y-shaped plate was (28.8±0.9) MPa, which was significantly lower than that of the horizontal plates, vertical plates, and traditional Y-shaped plate ( P<0.05). During elbow extension, the peak internal fixation stress of the personalized Y-shaped plate was (18.1±1.6) MPa, which was lower than those of the other three models, with significant differences when compared with horizontal plates and vertical plates ( P<0.05). Regarding the peak humeral stress, the personalized Y-shaped plate model showed mean values of (10.9±0.8) and (13.1±1.4) MPa during elbow flexion and extension, respectively, which were significantly lower than those of the other three models ( P<0.05). Displacement analysis showed that the maximum displacement of the humerus with the personalized Y-shaped plate during elbow flexion was (2.03±0.08) mm, slightly higher than that of the horizontal plates, but significantly lower than that of the vertical plates, showing significant differences ( P<0.05). During elbow extension, the maximum displacement of the humerus with the personalized Y-shaped plate was (1.93±0.13) mm, which was lower than that of the other three models, with significant differences when compared with vertical plates and traditional Y-shaped plates ( P<0.05). Stress contour analysis showed that the stress of the personalized Y-shaped plate was primarily concentrated at the bifurcation of the Y-shaped structure. Displacement contour analysis showed that the personalized Y-shaped plate effectively controlled the displacement of the distal humerus during both flexion and extension, demonstrating excellent stability. CONCLUSION The personalized Y-shaped plate demonstrates excellent biomechanical performance in the treatment of distal humeral intra-articular fractures, with lower stress and displacement, providing more stable fixation effects.
Humans ; Male ; Adult ; Healthy Volunteers ; Finite Element Analysis ; Tomography, Spiral Computed ; Models, Anatomic ; Biomechanical Phenomena ; Humeral Fractures, Distal/surgery* ; Fracture Fixation, Internal/instrumentation* ; Bone Plates ; Computer Simulation ; Precision Medicine/methods* ; Elbow Joint/surgery* ; Elbow/surgery* ; Humerus/surgery* ; Torque ; Stress, Mechanical ; Intra-Articular Fractures/surgery* ; Prosthesis Design/methods* ; Imaging, Three-Dimensional ; Range of Motion, Articular

BACKGROUND:Osteoporosis is a disease in which bone density and structure are destroyed and fractures are caused by increased bone fragility,leading to high clinical disability and mortality rates. OBJECTIVE:To review the research progress in the role of bone immunity in physiological and pathological processes related to bone metabolism,providing ideas for the research and clinical application of bone immunity in bone diseases. METHODS:The first author searched PubMed and CNKI databases in November 2022 for relevant literature using the keywords of"osteoimmunology,immuno-skeletal interface,bone metabolism,skeletal metabolism,lymphocyte,immune factor"in English and Chinese,respectively.The time range of retrieval was mainly from January 2010 to November 2022,and a small number of classical long-term literatures were included.After reading the topic and abstract for preliminary screening and excluding repetitive studies,low-quality journals and unrelated literature,81 documents were finally included for review. RESULTS AND CONCLUSION:Osteoimmunology refers to that bone and immune cells share the same microenvironment and interact with each other to jointly perform the"bone immune system,"which includes all cells in the bone marrow.Immuno-skeletal interface has protective effects on bone under physiological conditions,but it may lead to bone destruction under pathological conditions.Osteoprotegerin is mainly derived from B cells and can inhibit osteoclast metabolism.However,when the body is in an inflammatory state,T cells and B cells work together to promote bone resorption.In addition,interleukin-1,interleukin-6 and tumor necrosis factor-α regulate the expression of receptor activator of nuclear factor-κB ligand in vivo and affect bone metabolism.In most clinical diseases(such as rheumatoid arthritis,estrogen deficiency,HIV infection,and hyperparathyroidism),the immuno-skeletal interface interacts with the bone immune system,resulting in the regulation of bone metabolism.In terms of clinical prospect,the interaction between bone immunity and bone metabolism should be studied in order to propose new strategies for therapeutic intervention to reduce the risk of fracture.

Objective To explore the risk signals of adverse events(ADE)in the use of exenatide microspheres by the FDA adverse event reporting system(FAERS),and provide reference for clinical rational drug use and drug safety.Methods With exenatide microspheres as the target drug,the search keywords were Exenatide Microspheres for Injection,LY05006,AC 2 993 LAR and Bydureon.SAS software was used to extract the ADE report data from January 2,2012 to March 31,2023 in the FAERS database and the duplicates were removed.Data mining of exenatide microspheres-related ADE reports was performed by the reporting odds ratio method and the comprehensive standard method.Results A total of 27 248 exenatide microspheres-related ADE reports were retrieved,involving 27 SOCs,of which 4 719 were severe ADE reports.The reporting personnel were mainly consumers(18 435 cases,67.66%),the United States was the mainly reporting country(26 295 cases,96.50%).A total of 163 ADE risk signals were obtained by reporting odds ratio method and comprehensive standard method,including new adverse reactions such as abnormal blood cholesterol,elevated lipase and mixed hyperlipidemia.Conclusion Based on the FAERS database,the post-marketing ADE of exenatide microspheres was mined and analyzed,which could provide reference for clinical medication safety and improvement of patients'medication compliance.

Objectives:To assess the effectiveness and safety of ivabradine for the treatment of chronic heart failure in the context of the new quadruple combination. Methods:Clinical data of 656 chronic heart failure patients hospitalized in Nanjing Drum Tower Hospital from March 2021 to June 2022 were retrospectively collected,and the patients were divided into control group(n=361)and observation group(n=295)according to ivabradine use,and both groups were treated with the new quadruple drug therapy.Propensity score matching was performed,268 patients in the observation group and 268 patients in the control group were successfully matched.The effectiveness(primary endpoint was the composite endpoint of cardiovascular death and rehospitalisation for worsening heart failure within 1 year of discharge;secondary endpoints were rehospitalisation for worsening heart failure,all-cause rehospitalisation,cardiovascular death,and all-cause death)and safety outcome measures(including bradycardia,atrial fibrillation,blurred vision,renal impairment,and hypertension)were compared between the two groups at 1 year after treatment. Results:After matching,there were no statistically significant differences at baseline characteristics between the two groups.Kaplan-Meier survival curve showed that the occurrence rates of primary endpoints(P=0.031),readmission for worsening heart failure(P=0.020),and all-cause readmission(P=0.036)were lower in the observation group than in the control group.Multivariate Cox proportional hazard regression analysis showed that the occurrence rates of primary endpoint events(P=0.045)and readmission for heart failure worsening(P=0.028)were lower in the observation group than in the control group. Conclusions:The ivabradine use on top of the new quadruple therapy regimen in patients with chronic heart failure is beneficial to improve one-year prognosis with favorable safety profile.

Objective:To evaluate the correlation between vascular hyperintensity of magnetic resonance fluid-attenuated inversion recovery (FLAIR) sequence(FVH) and related parameters of magnetic resonance perfusion weighted imaging (MR-PWI) in patients with middle cerebral artery stenosis cerebral infarction, and to explore the hemodynamic factors related to FVH and the effect of FVH on the short-term clinical prognosis of patients.Methods:A total of 116 patients with middle cerebral artery stenosis cerebral infarction in the Department of Neurology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University from January 2020 to December 2022 were collected.According to the diagnostic criteria of FVH, they were divided into FVH (+ ) group (78 cases) and FVH(-) group (38 cases). All patients underwent magnetic resonance(MR) and MR-PWI scans.Demographic and cerebrovascular risk factors were collected, clinical neurological function of patients was assessed by national institate of health stroke scale(NIHSS) upon admission and discharge, and cognitive function of patients was assessed by mini-mental state examination (MMSE). Short-term clinical outcome was assessed using modified Rankin scale(mRS) at the 90th day after discharge.The degree of middle cerebral artery stenosis, positive or negative FVH, FVH score, hypoperfusion volume and MR-PWI related parameters, including peak time (Tmax), mean transit time (MTT), cerebral blood volume (CBV) and cerebral blood flow (CBF), were evaluated in relation to clinical symptoms.SPSS 22.0 statistical software was used for t test, Chi-square test and Pearson correlation analysis. Results:There were significant differences in hypoperfusion volume, Tmax, MTT and CBF between FVH (+ ) group and FVH(-) group( t=1.989, 3.830, 5.223, 3.911, all P<0.05). In terms of short-term clinical outcome, the improvement rate of neurological function ((8.25±6.39)%, (12.22±6.08)%) and MMSE score(25.48±1.59), (26.31±1.26) in FVH (+ ) group were significantly lower than those in FVH(-) group, and the number of patients with progressive stroke during hospitalization in FVH(+ ) group was more than that of FVH(-) group(22(28.21%), 4(10.53%)) (all P<0.05). Pearson correlation analysis showed that FVH score was positively correlated with hypoperfusion volume ( r=0.786, P<0.01) and MTT ( r=0.692, P<0.01), and negatively correlated with CBF ( r=-0.568, P<0.01), but no significant correlation with the degree of arterial stenosis ( r=0.363, P>0.05). Conclusion:FVH is closely related to the Tmax, MTT and CBF values shown in MR-PWI, and the incidence of stroke in progression and short-term adverse prognosis are more likely in FVH(+ ) group, suggesting that FVH can be used as a convenient imaging indicator to reflect the hypoperfusion status of patients with middle cerebral artery stenosis cerebral infarction, and can provide an objective basis for further individualized treatment.

OBJECTIVE To evaluate the effects of ivabradine on vascular endothelial function in patients with coronary artery disease. METHODS PubMed， Embase， the Cochrane Library， Web of Science， CNKI， Wanfang Data， VIP and CBM databases were retrieved to collect randomized controlled trials （RCTs） about ivabradine （intervention group） versus placebo or β-blocker （control group） from the inception to Mar. 20th 2023. The meta-analysis was performed by using RevMan 5.4 software after literature screening， data extraction and quality evaluation. RESULTS A total of 12 RCTs were included， involving 1 206 patients. The results of meta-analysis showed that the levels of flow-mediated dilation （FMD） [MD＝1.71， 95%CI （0.96， 2.46）， P＜0.000 01] and nitric oxide （NO） [MD＝5.80， 95%CI （5.02， 6.59）， P＜0.000 01] in the intervention group were significantly higher than control group， while endothelin-1（ET-1） level was significantly lower than control group [MD＝－7.45， 95%CI （－8.42， －6.47）， P＜0.000 01]. There was no statistical significance in nitroglycerin-mediated dilation （NMD） level between 2 groups [MD＝0.13， 95%CI（－0.74， 1.00）， P＝0.77]. Subgroup analyses based on the different medications and intervention time in the control group showed better improvement in FMD level of patients receiving ivabradine， compared with placebo （P＜0.05）； compared with placebo and β-blocker， the level of NO in patients receiving ivabradine was improved significantly （P＜0.05）， while ET-1 level was decreased significantly （P＜0.05）. Regardless of the duration of the intervention， the levels of FMD， NO， and ET-1 in the intervention group were significantly improved compared to the control group （P＜0.01）， while the difference in NMD was not statistically significant （P＞0.05）. CONCLUSIONS Ivabradine can improve vascular endothelial function in patients with coronary artery disease.

Background::Liver cancer remains the sixth most commonly diagnosed cancer and the third leading cause of cancer-related deaths worldwide, causing a heavy burden globally. An updated assessment of the global epidemiology of the liver cancer burden that addresses geographical disparities is necessary to better understand and promote healthcare delivery.Methods::Data were extracted from the GLOBOCAN 2022 database, including the number, crude, and age-standardized rates of incidence and mortality at the global, country, continent, and human development index (HDI) regional levels. Age-standardized rates (incidence and mortality) per 100,000 person-years were adjusted based on the Segi-Doll World standard population. The mortality-to-incidence ratios (MIR) for each region and country were calculated. The HDI and gross national income (GNI) for 2022 were obtained, and a Pearson correlation analysis was conducted with the incidence, mortality, and MIR.Results::In 2022, approximately 866,136 new liver cancer cases and 758,725 related deaths were recorded worldwide, with a global MIR of 0.86. Males had a disproportionately higher burden than females across all levels, and the highest burden was observed in the elderly population. Geographically, the regions with the highest incidence rates included Micronesia, Eastern Asia, and Northern Africa, and the regions with the highest mortality rates included Northern Africa, Southeastern Asia, Eastern Asia, and Micronesia. Notably, Mongolia had a strikingly high burden compared to other countries. The highest MIR was observed in North America and the lowest in Africa. Negative associations of HDI and GNI with liver cancer mortality and MIR were identified, irrespective of sex.Conclusions::The current liver cancer burden underscores the presence of remarkable geographic heterogeneity, which is particularly evident across countries with varying HDI levels, highlighting the urgent need to prioritize health accessibility and availability to achieve health inequities.

Inhibitory cells derived from bone marrow are a kind of inhibitory cells derived from bone marrow.These cells are not only related to tumor growth,but also participate in the inflammatory immune process.Therefore,we established a rat model of chronic osteomyelitis,and used gemcitabine to inhibit the cell growth ratio of MDSCs.We detected the ratio of MDSCs in bone marrow and spleen of rats by flow cytometry and immunofluorescence,detected the changes of inflammatory factors in peripheral blood by ELISA,and analyzed the inflammatory factors(TNF-α,PCT,IL-4,IL-10,IL-11)in peripheral blood of normal rats,osteomyelitis rats and rats after gemcitabine inhibition.The results showed that the proportion of MDSCs cells in bone marrow and spleen of osteomyelitis model rats was increased,but it was significantly decreased in gemcitabine group(P<0.05).Levels of inflammatory factors(TNF-α,PCT,IL-4,IL-10,IL-17,IFN-γ,TGF-β)were positively correlated with the change of MDSCs cell proportion(P<0.05).From the results,it can be inferred that the change of the proportion of MDSCs cells in rat osteomyelitis is positively related to the inflammatory factors,and gemcitabine can reduce inflammatory factors by inhibiting MDSCs.