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The interaction between microbes and the human immune system has long been a focus in biomedical research. Next-generation sequencing has revealed that in addition to gut microbiota， the respiratory tract also harbors microbial communities， forming an interconnected network with the gut microbiota through immune cells and active factors. This review aims to explore how the gut and lung microbiota regulate immune responses， including their roles in local and systemic immune modulation. It also delineates the immunological connections along the gut-lung axis. Further elucidating the influence of microbes on the immune system holds important clinical significance for understanding diseases and exploring novel diagnostic and therapeutic strategies.
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The main characteristics of neurodegenerative diseases represented by Alzheimer’s disease (AD) and Parkinson’s disease (PD) is the progressive irreversible loss of neurons, leading to varying degrees of pathological changes and loss of cognitive function. There is still no effective treatment. With the acceleration of global aging society, the incidence of neurodegenerative diseases is rapidly increasing, becoming a serious global public health concern that urgently requires the development of effective therapeutic strategies. The Hippo signaling pathway, a highly evolutionarily conserved pathway, consists of the core components MST1/2, LATS1/2, and downstream effectors, transcriptional co-activators YAP and TAZ. It plays a crucial role in the regulation of various biological processes such as cell proliferation, differentiation, development, and apoptosis. Dysregulation of the Hippo pathway contributes to the development of many diseases, including cancer, cardiovascular diseases, immune disorders, etc. Therefore, targeting the dysregulated components of the Hippo pathway may be an effective strategy for treating various diseases. Increasing evidence indicates that the Hippo pathway is excessively activated in the development of neurodegenerative diseases, manifested by increased expression of MST1 and downregulation of YAP. Stabilizing the Hippo pathway levels has shown improvements in AD and PD. However, most studies on the Hippo pathway in AD and PD focus on changes in the expression levels of Hippo pathway components, and research in other neurodegenerative diseases is still lacking. Therefore, further investigation is needed to fully understand the mechanistic role of the Hippo pathway in neurodegenerative diseases. Meanwhile, miRNA, similarly dysregulated in neurodegenerative diseases and serving as biomarkers, is a primary target for miRNA therapy in neurodegenerative diseases, including AD and PD. Activating or inhibiting dysregulated miRNAs is the main strategy of miRNA therapy during the neurodegenerative disease development. Evidence suggests that the interaction between the Hippo pathway and miRNA can result in widespread biological effects and crosstalk in the occurrence of different types of diseases. However, studies on the interplay between the Hippo pathway and miRNA in neurodegenerative diseases are relatively scarce. In this paper, we predicted the miRNAs related to Hippo pathway through bioinformatics database, and further screened the miRNAs with crosstalk relationship with Hippo signaling pathway through experiments in combination with PubMed. Then, the mechanism of action of Hippo signaling pathway related miRNAs in AD and PD is further elucidated. It is reported that the Hippo pathway and its related miRNA may exert neuroprotective effects by reducing oxidative stress, improving neuroinflammation, stabilizing autophagy levels, maintaining neuronal mitochondrial function, and ameliorating blood-brain barrier dysfunction, thereby delaying the progression of AD and PD. However, research on miRNA directly regulating the Hippo pathway to improve AD and PD is limited, and observations of the Hippo pathway and its related miRNA in other neurodegenerative diseases are scarce. However, considering the regulatory relationship between the Hippo pathway and miRNA in multiple diseases and their respective roles in key mechanisms of neurodegenerative diseases, such as oxidative stress and neuroinflammation, the crosstalk between miRNA and the Hippo pathway holds a crucial regulatory role in the development of neurodegenerative diseases. Thus, the interaction pathways of the Hippo pathway and its related miRNA may be a pivotal avenue for exploring effective therapeutic strategies for neurodegenerative diseases in the future.
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Objective To evaluate the efficacy and safety of polyene phosphatidylcholine injection in the treatment of liver disease.Methods Pubmed,Embase,The Cochrane Library,ClinicalTrial.gov,CNKI,SinoMed,VIP,and WanFang Data were electronically searched to collect randomized controlled trials(RCTs)of polyene phosphatidylcholine injection in the treatment of liver disease from inception to December 31st,2022.Two researchers independently screened literature,extracted data and assessed the risk of bias of the included studies.The Meta-analysis was performed using Stata 17.0 software.Results A total of 10 RCTs were included,including 809 patients.Meta-analysis showed that the effective rate in the polyene phosphatidylcholine injection group was higher than that in the control group(RR=1.12,95％CI 1.04 to 1.20,P=0.003 8).Compared with the control group,polyene phosphatidylcholine injection could decrease ALT level(MD=-18.92 U/L,95％CI-27.75 to-10.09,P＜0.001),AST level(MD=-31.19 U/L,95％CI-46.27 to-16.11,P=0.000 1),TBiL level(MD=-7.31 μmol/L,95％CI-10.75 to-3.88,P＜0.001),and GGT levels(MD=-48.93 U/L,95％CI-54.64 to-43.21,P＜0.001).Only one study reported mild adverse events,and six studies reported no severe adverse events in patients.Conclusion Current evidence shows that polyene phosphatidylcholine injection in the treatment of alcoholic liver disease can increase the effective rate,improve the levels of liver function indicators(ALT,AST,TBiL,and GGT),and has less adverse events.Due to the limited number and quality of included studies,the above conclusions need to be verified by more high-quality studies.
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Objective To observe the value of laparoscopic ultrasound(LUS)combined with CT three-dimensional reconstruction for guiding laparoscopic hepatectomy(LH).Methods Data of 78 hepatocellular carcinoma(HCC)patients who underwent LH were retrospectively analyzed.The patients were divided into observation group(n=46)or control group(n=32)based on whether underwent preoperative CT three-dimensional reconstruction and LUS.Clinical data,perioperative data and prognosis were compared between groups.Results No significant difference of clinical data was found(all P＞0.05),whereas significant differences of tumor body mainly location,resection method,tumor resection margin,surgical operation time,intraoperative blood loss,postoperative hospital stay,postoperative complication grading and incidence were found between groups(all P＜0.05).During follow-up period,15 patients died in observation group and 14 died in control group.Significant difference of disease-free survival rate was detected between groups(x2=4.210,P=0.040).Conclusion LUS combined with CT three-dimensional reconstruction for guiding LH could reduce intraoperative injury and complication incidence,improving disease-free survival rate of HCC patients.
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Objective To observe the value of transesophageal echocardiography(TEE)for guiding left atrial appendage closure(LAAC)with LAmbre occluder.Methods Data of 40 non-valvular atrial fibrillation(NVAF)patients who underwent LA AC with LAmbre occluder were retrospectively analyzed.CT angiography(CTA)before treatment,TEE and digital subtraction angiography(DSA)findings during LAAC were comparatively observed,and the correlations of the anchor area diameter and left atrial appendage opening diameter measured with the above three as well as occluder size were analyzed,and TEE and DSA for evaluating peri-device leak(PDL)were compared.Results LAAC were successfully performed with LAmbre occlude in all 40 cases.The diameter of the fixed umbrella was positively correlated with anchor area diameter measured with CTA,TEE and DSA(r=0.79,0.82,0.91,all P＜0.01),of occlusion umbrella was positively correlated with left atrial appendage opening diameter measured with CTA,TEE and DSA(r=0.56,0.89,0.86,all P＜0.01).Immediately after the release of occluder in LAAC,PDL occurred in 16 cases and were detected with both TEE and DSA,while in the rest 24 cases no PDL was found with neither TEE nor DSA.Conclusion TEE had comparable value to DSA for guiding LAAC using LAmbre occluder.
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Purpose To construct a benign and malignant prediction model of thyroid nodules based on ultrasound image features and clinical features,and to evaluate its diagnostic efficacy.Materials and Methods The data of 121 patients diagnosed with thyroid nodules admitted to the General Hospital of Northern Theater Command from September 2020 to March 2022 were retrospectively analyzed.Taken surgical pathology as the gold standard,there were 70 benign nodules and 51 malignant nodules.Logistic regression was used to analyze the ultrasound image characteristics and clinical data of thyroid nodules,and the characteristic indexes with statistical differences were obtained and a comprehensive prediction model was established.Results There were significant differences in the maximum diameter,morphology,calcification,capsule continuity,blood flow grade,elastography score and contrast-enhanced ultrasound characteristics between benign and malignant thyroid nodules(χ2=11.709,17.707,6.901,12.785,16.984,57.095,98.854,all P<0.05).There were significant differences in age,free thyroxine/free thyroxine ratio,and free thyroxine between the two groups(χ2/t=5.944,2.519,-2.468,all P<0.05).The sensitivity,specificity and accuracy of the clinical model,ultrasonic characteristic model and ultrasonic-clinical combined model were 55.7%,98.6%and 97.0%;72.5%,94.1%and 96.1%;and 61.9%,95.1%and 95.9%,respectively.The area under the curve of the three models were 0.619,0.991 and 0.994,respectively.The diagnostic efficiency of the ultrasonic characteristic model and the combined model was superior to the clinical model,and the difference was statistically significant(Z=-1.75,-2.25,P=0.039,0.012).The area under the curve of the combined model was greater than that of the multi-modal ultrasound model,however,the difference was not statistically significant(Z=-1.60,P=0.054).Conclusion Both the multimodal ultrasound model and the clinical model have certain diagnostic value in predicting benign and malignant thyroid nodules.The diagnostic efficiency of the multimodal ultrasound model is higher than that of the clinical model,and the combined prediction model of the two can improve the diagnostic value.
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Aim To investigate the role of metabolites of eicosapentaenoic acid (EPA) in promoting the transdifferentiation of pancreatic α cells to β cells. Methods Male C57BL/6J mice were injected intraperitoneally with 60 mg/kg streptozocin (STZ) for five consecutive days to establish a type 1 diabetes (T1DM) mouse model. After two weeks, they were randomly divided into model groups and 97% EPA diet intervention group, 75% fish oil (50% EPA +25% DHA) diet intervention group, and random blood glucose was detected every week; after the model expired, the regeneration of pancreatic β cells in mouse pancreas was observed by immunofluorescence staining. The islets of mice (obtained by crossing GCG
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Objective:To investigate associations between cardiac biomarkers with stroke severity and short-term outcome in patients with acute ischemic stroke (AIS).Methods:Patients with AIS admitted to the Affiliated Hospital of Qingdao University from June 2018 to February 2024 whose etiological classification was large artery atherosclerosis (LAA), small vessel occlusion (SVO) or cardioembolism (CE) were included retrospectively. According to the National Institutes of Health Stroke Scale score at admission, patients were divided into mild stroke group (≤8) and moderate to severe stroke group (>8). According to the modified Rankin Scale score at discharge, patients were divided into good outcome group (≤2) and poor outcome group (>2). Multivariate logistic regression analysis was used to determine the independent correlation between cardiac biomarkers and short-term outcome. The predictive value of cardiac biomarkers for poor outcome in patients with AIS and different stroke etiology subtypes were evaluated using receiver operating characteristic (ROC) curves. Results:A total of 2 151 patients with AIS were enrolled, including 1 256 males (58.4%), aged 67.40±11.34 years. 1 079 patents were LAA type (50.2%), 679 were SVO type (31.6%), and 393 were CE type (18.3%); 1 223 were mild stroke (56.86%) and 928 (43.14%) were moderate to severe stroke; 1 357 patients (63.09%) had good short-term outcome, and 794 (36.91%) had poor short-term outcome. Multivariate logistic regression analysis showed that N-terminal pro-B type natriuretic peptide (NT-proBNP), NT-proBNP/creatine kinase (CK) isoenzyme MB (CK-MB) ratio, and CK-MB/CK ratio were independent risk factors for poor short-term outcome. ROC curve analysis shows that the CK-MB/CK ratio had a higher predictive value for short-term poor outcome in patients with AIS (the area under the curve, 0.859, 95% confidence interval 0.839-0.879). Various cardiac biomarkers had a higher predictive value for short-term outcome of CE type and LAA type, but the predictive value for short-term outcome of SVO type was lower. Conclusions:Cardiac biomarkers are associated with the severity and poor outcome of AIS. NT-proBNP/CK-MB and CK-MB/CK ratios have higher predictive value for short-term poor outcome of AIS, especially in patients with CE type.
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Mental disorders are characterized by disturbances in behavior,volition,emotion,and cognition and are considered emotional diseases in traditional Chinese medicine.Acupuncture is one of the most widely used complementary alternative therapies for the treatment of mental disorders.Recently,there has been growing interest in the use of the Tong Du Tiao Shen(Dredging Du meridian to regulate the spirit)as a primary treatment.However,a comprehensive summary of the establishment and related acupuncture methods of Tong Du Tiao Shen is lacking.This paper aims to address this gap by exploring the origin and development of Tong Du Tiao Shen,its application in treating mental disorders,and the modern biological mechanisms involved.Ultimately,this paper seeks to expand the clinical application of Tong Du Tiao Shen acupuncture and provide a scientific basis for future research in this field.
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Objective To study the serum levels of adisintegrin and metalloproteases 17(ADAM17)and C-X-C chemokine ligand 16(CXCL16)in patients with chronic atrophic gastritis(CAG)and their clinical value.Methods A total of 174 patients admitted to Xidian Group Hospital Affiliated to Shaanxi University of Traditional Chinese Medicine from January 2018 to January 2020 due to abdominal discomfort and other symptoms were selected.Based on pathological biopsy results,they were divided into CAG group(n=94)and non CAG group(n=80).The CAG group was divided into mild group(n=27),moderate group(n=30),and severe group(n=37)based on the severity.Meanwhile,50 healthy examinees were used as the control group.Enzyme-linked immunosorbent assay was used to detect serum ADAM17 and CXCL16 levels.Multivariate logistic regression analysis was used to investigate the influencing factors of CAG occurrence,and the diagnostic values of serum ADAM17 and CXCL16 for CAG were analyzed using receiver operating characteristic curves.Results The serum levels of ADAM17(79.25±9.34ng/L)and CXCL16(4.66±0.58μg/L)in CAG group were higher than those in non-CAG group(73.94±8.26ng/L,4.03±0.55μg/L)and control group(53.04±7.20ng/L,1.02±0.35μg/L),and the differences were statistically significant(t=5.794,24.854;11.053,55.497,all P＜0.05).The serum levels of ADAM17(87.17±9.30ng/L)and CXCL16(5.14±0.51μg/L)in severe CAG patients were higher than those in mild CAG group(79.12±9.52ng/L,4.65±0.57μg/L)and moderate groups(68.54±7.89ng/L,4.02±0.63μg/L),and the differences were statistically significant(t=11.574,5.152;11.065,4.987,all P＜0.05).Serum ADAM17(OR=1.851,95%CI:1.350～2.522)and CXCL16(OR=1.682,95%CI:1.233～2.296)were independent risk factors for CAG.The area under the curve of serum ADAM17 and CXCL16 combined diagnosis of CAG was 0.912(95%CI:0.858～0.949),which was larger than the single indicator of 0.843(95%CI:0.801～0.907)and 0.785(95%CI:0.722～0.834),and the differences were statistically significant(Z= 9.357,12.894,all P＜0.05).Conclusion The serum levels of ADAM17 and CXCL16 were increased in CAG patients,indicating they may be related to the severity of CAG.The combined detection of ADAM17 and CXCL16 has a high predictive value for CAG.
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Objective To evaluate the potential clinical value of T2 mapping and mDixon Quant in the diagnosis of early interver-tebral disc degeneration.Methods A total of 79 volunteers who underwent lumbar MRI examination were enrolled.All subjects were examined for 3.0T MR with T2WI,T2 mapping,and mDixon Quant while recording the condition of low back pain.The differ-ences between T2 mapping(map)value and fat fraction(FF)values of the vertebral(V)and nucleus pulposus(NP)within the Pfir-rmann Ⅰ and Pfirrmann Ⅱ intervertebral disc(grade Ⅰ 76,grade Ⅱ 87)were statistically analyzed.Receiver operating characteristic(ROC)curve analyses were performed for meaningful parameters.Results V-FF showed a mild positive correlation with degenera-tive intervertebral disc lesions,and NP-FF and NP-map values showed a mild negative correlation with lesions.There were statistically significant differences between the two groups in V-FF(P＜0.001),NP-FF(P=0.005),and NP-map(P＜0.001).Some measure-ments had statistically significant differences when different intervertebral disc segments were compared.Conclusion V-FF,NP-FF,and NP-map are associated with intervertebral disc degeneration.T2 mapping and mDixon Quant are potentially valuable as diagnostic tools to quantitatively assess early intervertebral disc degeneration and help diagnose.
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Objective:To explore the current situation of binary coping in patients with perimenopausal syndrome and analyze its influencing factors, in order to provide a basis for improving the level of binary coping.Methods:Using convenience sampling method, a total of 210 patients with perimenopausal syndrome and their spouses from the First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine were cross-sectional surveyed by a general data questionnaire, the Binary Coping Scale, and the Modified Kupperman Score Scale. The influencing factors of binary coping level in patients with perimenopausal syndrome were explored by univariate analysis and variance decomposition model analysis.Results:A total of 200 valid questionnaires were retrieved.The patients aged (50.52 ± 2.89) years old. The binary coping score was (79.64 ± 22.74) points. The variance decomposition model analysis showed that marriage age, type of medical insurance, number of children, education level, family monthly income, spouse′s education level, presence of major comorbidities in spouse, modified Kupperman score, presence of generalized anxiety in spouse were the main influencing factors of binary coping in patients with perimenopausal syndrome (all P<0.05). Conclusions:The binary coping scores of patients with perimenopausal syndrome are lower than normal, and considering the influence and involvement of patients' spouses, nursing staff should pay special attention to patients who are married relatively early, have more children, have lower education levels, and have lower family monthly incomes. Additionally, attention should be given to spouses who experience widespread anxiety, have a lower level of education, and suffer from major chronic diseases. By developing and implementing comprehensive intervention measures aimed at improving the Kupperman score and the level of binary coping, both parties can be encouraged to support each other more effectively, thereby improving the marital relationships of patients during the perimenopausal period.
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Exosomes are extracellular vesicles commonly detected in numerous body fluids and contain a variety of components such as proteins,nucleic acids,lipids,and metabolites.These components enable exosomes to mediate intercellular communication and impact diverse cellular processes.Recently,research has highlighted that exosomes have a significant regulatory role in numerous aspects of hepatocellular carcinoma(HCC)occur-rence,development,and drug resistance.Non-coding RANs,a crucial component of exosomes,can regulate the HCC tumour microenvironment with a direct impact on biological behaviours such as tumour growth,metastasis,angiogenesis,and immunomodulation.To this end,exosomes present an interesting avenue for further research in the field of HCC therapy.It is anticipated to become a novel diagnostic,prognostic marker,or therapeutic target for hepatocellular carcinoma(HCC).Our review of the role played by exosomal components in HCC progression over the last five years aims to furnish references and innovative perspectives for early diagnosis,prognosis,and treatment of HCC.
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Objective To investigate the effect of berberine hydrochloride tablets combined with compound glutamine in treating ulcerative colitis(UC).Methods One hundred and two patients with UC admitted to our hospital were collected and grouped into two groups according to the random number table.Fifty-one patients in the control group were given conventional treatment+compound glutamine,and 51 patients in the experimental group were given berberine hydrochloride tablets based on the control group.Both groups were treated for 8 weeks.The efficacy,modified Mayo score,intestinal mucosal barrier function,soluble late glycation end product receptor(sRAGE),interleukin-17(IL-17),IL-6 and incidence of untoward reactions were compared between the two groups.Results The total effective rate of the experimental group was higher than that of the control group(92.2%vs.76.5%,P＜0.05).After treatment,scores of defecation frequency,blood in stool,endoscopic findings,physician's overall evaluation,diamine oxidase(DAO),D-lactic acid,endotoxin,sRAGE,IL-17 and IL-6 were lower in both groups than those before treatment(P＜0.05),and the research group was lower than the control group(P＜0.05).There was no significant difference in the total incidence of untoward reactions between the experimental group and the control group(P＞0.05).Conclusion Berberine hydrochloride tablets combined with compound glutamine are effective in treating UC,which can reduce the activity of UC,improve the intestinal mucosal barrier function,regulate serum sRAGE,IL-17 and IL-6 levels,without increasing adverse reactions.
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Objective To investigate the mechanism of Gentianopsis paludosa xanthone(GPX)combined with probiotics in the intervention of colon inflammation-tumor transformation in rats by regulating TGF-β1/Smads pathway and inflammatory factors.Methods Ninety rats were divided into the normal group,the model group[drinking sodium dextran sulfate(DSS)for 3 days]and the intervention group by random number table method.The model group was subdivided into the inflammatory stage group,the pre-inflammatory cancer group(DMH injection for 4 weeks),the intermediate inflammatory cancer group(DMH injection for 13 weeks)and the advanced inflammatory cancer group(DMH injection for 21 weeks).The administration group was subdivided into the groups(after the first day of drinking DSS,drugs for each group were given by gavage once a day for 8 weeks)on the basis of the advanced inflammatory cancer group,including the GPX group(GPX 69.3 mg/kg),the probiotic group,the combined group(GPX+probiotics 400 mg/kg)and the thalidomide group(thalidomide 13.5 mg/kg).The disease activity index(DAI),colon length and wet mass index were compared between all groups.Characteristics of colon tumors were observed,and pathological changes of colon were observed by HE staining.The expression levels of transforming growth factor(TGF)-β1,Smad4,Smad7,interleukin(IL)-6 and tumor necrosis factor(TNF)-α were detected by Western blot assay and enzyme-linked immunosorbent assay,respectively.Results Compared with the advanced inflammatory cancer group,the administration groups showed an increase in colon length,the expression levels of TGF-β1 and Smad4 protein,a decrease in colon wall thickness,wet mass index,maximum tumor diameter,the levels of Smad7,IL-6,TNF-α,and DAI score decreased in the GPX group and the combined group(P＜0.05).The structure and morphology of intestinal mucosa were improved in the GPX group,the probiotic group and the combination group,and the structure of colonic crypt and goblet cell number were increased.Compared with the probiotic group and the GPX group,the colon wall thickness,colon wet mass index and tumor number were decreased,the protein expression levels of TGF-β1 and Smad4 were increased,and levels of IL-6 and TNF-α were decreased in the combination group(P＜0.05).Conclusion GPX combined with probiotics could inhibit the transformation of colon inflammation-tumor,and the mechanism may be related to the regulation of TGF-β1/Smads pathway and the inhibition of pro-inflammatory factors of IL-6 and TNF-α.
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BACKGROUND:Platelet-rich plasma has been shown to enhance the viability and the pro-angiogenesis capacity of mesenchymal stem cells.Extracellular vesicles are one of the key mediators for mesenchymal stem cells to exert their effects,but currently,it is unclear whether platelet-rich plasma affects the functions of extracellular vesicles. OBJECTIVE:To investigate the effects of platelet-rich plasma on the function of extracellular vesicles from bone marrow mesenchymal stem cells,verify whether platelet-rich plasma can be used as an adjuvant to enhance the healing effects of bone marrow mesenchymal stem cells on repairing the peripheral nerve injury. METHODS:For in vitro study,bone marrow mesenchymal stem cells were cultured under normal conditions and with 1%platelet-rich plasma.The ultracentrifugation was used to extract the extracellular vesicles produced by bone marrow mesenchymal stem cells cultured under normal conditions(EVs-nor)or the condition supplemented with 1%platelet-rich plasma(EVs-prp).Extracellular vesicles were used to incubate with Schwann cells.The EdU assay,western blot assay,qPCR and light microscopy photography were performed to examine the effects of EVs-nor and EVs-prp on Schwann cell reprogramming,which was characterized by cell proliferation,c-Jun expression,reprogramming-associated gene expression and cell morphology.For in vivo study,the model of sciatic nerve injury in rats was established.Bone marrow mesenchymal stem cells were grafted with or without 1%platelet-rich plasma into the injured rat sciatic nerve using a chitin nerve conduit.Eight weeks after the surgery,the recovery was assessed by histological and functional indexes,including regenerated nerve fiber density,gastrocnemius wet weight ratio and sciatic function index. RESULTS AND CONCLUSION:(1)Compared with EVs-nor,EVs-prp was stronger in promoting Schwann cell proliferation.The gene expressions of c-Jun and GDNF were significantly upregulated in EVs-prp treated Schwann cells.The morphology of Schwann cells was significantly longer in EVs-prp group than that in EVs-nor group,indicating that EVs-prp had a stronger ability to stimulate Schwann cell reprogramming than EVs-nor.(2)Sciatic nerve injury animal experiment results revealed that grafting mesenchymal stem cells along with platelet-rich plasma into the injured sciatic nerve showed the best recovery compared with grafting mesenchymal stem cells or platelet-rich plasma alone,demonstrated by the significantly improved density of nerve fibers,gastrocnemius wet weight ratio,and sciatic function index.(3)These results suggested that platelet-rich plasma improved the function of bone marrow mesenchymal stem cell-derived extracellular vesicles and could be served as a practical and feasible preparation to synergize with bone marrow mesenchymal stem cells to improve peripheral nerve repair.
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Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.
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Objective To analyze the detection of helicobacter pylori(Hp)in different parts of gastric antrum,and to provide clinical guidance for finding the best biopsy site for Hp.Methods Patients who underwent 13C urea breath test and electronic gastroscopy from January 2020 to December 2022 were retrospectively analyzed and divided into 13C urea breath test positive group[delta over baseline(DOB)≥4]and 13C urea breath test negative group(DOB<4)according to DOB value.Gastroscopy reports and pathological data of patients were collected.According to different biopsy sites in gastric antrum,patients were divided into conventional biopsy site group,elevated erosive site group and flat erosive site group,and the detection rate of Hp in different biopsy sites was compared.13C urea breath test positive group was divided into group A(4<DOB≤16),group B(16<DOB≤35)and group C(DOB>35)according to DOB value,and the gastric antral biopsy and pathology of each group were classified and analyzed.Combined with endoscopic reports and pathological data,patients were divided into atrophic gastritis group and non-atrophic gastritis group.Results In the 13C urea breath test positive group,the detection rate of Hp in the elevated erosive site group(96.4%)was higher than that in the conventional biopsy site group(92.7%)and the flat erosive site group(93.9%),and the difference was statistically significant(P = 0.036).In DOB group A,the detection rate of Hp was the highest at the site of elevated erosive and the lowest at the site of conventional biopsy,and the detection rate of Hp at the three biopsy sites was compared,the difference was statistically significant(P = 0.016);There was no significant difference in the detection rate of Hp at three biopsy sites between group B and group C(P = 0.622;P = 0.721);the non-atrophic gastritis group,the detection rate of Hp at the elevated erosive site(96.5%)was higher than that at the conventional biopsy site(91.2%)and the flat erosive site(92.0%),and the difference was statistically significant(P = 0.043).There was no significant difference in the detection rate of Hp at three biopsy sites in the atrophic gastritis group(P = 0.614).13C urea breath test negative group:There was no significant difference in Hp detection rate among the three biopsy sites(P = 0.255).Conclusion For patients with positive 13C urea breath test but low DOB value,the positive rate of Hp in the elevated erosive site is higher.For non-atrophic gastritis patients,the detection rate of Hp was higher in the elevated erosive sites than in the conventional biopsy sites.But for patients with atrophic gastritis,there was little difference in the detection rate of Hp in different parts of antrum.For patients with negative 13C urea breath test,there was no significant difference in Hp detection rate among the three biopsy sites.In future clinical work,for similar patients,precise biopsy can be performed to improve the detection rate of Hp.
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Objective:To investigate the expression and clinical significance of microRNA-124(miR-124)and microRNA-1976(miR-1976)in the serum of patients with Parkinson's disease(PD).Methods:A total of 58 patients with PD were selected from September 2020 to June 2022 and categorized as the PD group.The Unified Parkinson's Disease Rating Scale(UPDRS)score was used to divide the PD patients into two groups: those with a UPDRS score≤60(25 patients)and those with a UPDRS score >60(33 patients). The Hoehn-Yahr grading scale was used to grade the PD patients.Additionally, 30 healthy individuals who had undergone a physical examination during the same period were selected as the control group.After collecting the subjects' serum, we performed real-time fluorescent quantitative PCR(qRT-PCR)to detect the expressions of miR-124 and miR-1976 in the serum.Logistic regression analysis was employed to analyze the influencing factors, and the diagnostic significance of serum miR-124 and miR-1976 in PD patients was evaluated using the receiver operating characteristic(ROC)curve.To predict the target genes of miR-1976, we utilized several software including TargetScan and Mirtarbase.Results:Compared to the control group, the PD group showed a significant down-regulation of serum miR-124 expression[(1.49±0.36) vs.(1.02±0.32)]( t=8.85, P<0.001), while miR-1976 expression was sharply up-regulated[(0.98±0.30) vs.(1.33±0.37)]( t=6.92, P<0.001). The low expression of serum miR-124 and the overexpression of miR-1976 were identified as independent risk factors for PD( OR>1, P<0.05). The Hoehn-Yahr rating of PD patients with a UPDRS score above 60 was higher than that of patients with a UPDRS score below 60[(3.42 ± 0.73) vs.(2.16 ± 0.42)]( t=3.05, P<0.05). However, there was no significant difference in serum miR-124 and miR-1976 expression between groups with different UPDRS scores[miR-124: (1.09±0.26) vs.(0.98±0.38)( t=0.89, P>0.05); miR-1976: (1.42±0.43) vs.(1.23±0.68)( t=0.62, P>0.05)]. The ROC analysis results demonstrated that miR-124 and miR-1976 had area under the curve(AUC)values of 0.832 and 0.797, respectively, in diagnosing PD.The corresponding cutoff values were 1.205 and 1.196, respectively.The sensitivity for miR-124 was 74.1%, while for miR-1976 it was 51.8%.The specificity for miR-124 was 77.8%, and for miR-1976 it was 90.1%.When both miR-124 and miR-1976 were combined in the diagnosis of PD, the AUC was 0.912, with a sensitivity of 76.4% and a specificity of 93.2%.Furthermore, it was found that miR-1976 targeted the PINK1 gene, suggesting its potential as a target gene in PD. Conclusions:The expression of miR-124 was found to be decreased in PD patients, while the expression of miR-1976 was increased.Both miR-124 and miR-1976 showed some reference value in PD diagnosis, and their combined diagnostic value was higher.This suggests that further study on their significance is warranted.However, it should be noted that the expressions of miR-124 and miR-1976 were not found to be correlated with the UPDRS score of PD patients.
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A 6-month primary care quality improvement (QI) project was conducted for 63 general practice residents at Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from November 2021 to April 2022. The effectiveness of the QI project on the post competency of general practice residents was comprehensively assessed by three dimensions: self-satisfaction, objective evaluation and teacher-evaluation. The overall satisfaction score of general practice residents was significantly increased after the implementation of QI project((3.83±0.67) vs. (3.41±0.63), t=3.35, P=0.009). The total score of objective assessment was increased from (73.48±8.04) before the project implementation to (78.14±5.24) after the implementation ( t=3.37, P=0.001). The total score of training effectiveness significantly increased from (57.57±11.84) before the project implementation to (79.27±8.40) after the implementation ( t=30.07, P<0.001). The results indicate that the primary care QI project can improve the post competency of general practice residents, and also improve the self-satisfaction of residents for active learning and participation in the training.