Correlation between the gut microbiome and neurodegenerative diseases:a review of metagenomics evidence

A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain axis.As a contributing factor,microbiota dysbiosis always occurs in pathological changes of neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis.High-throughput sequencing technology has helped to reveal that the bidirectional communication between the central nervous system and the enteric nervous system is facilitated by the microbiota’s diverse microorganisms,and for both neuroimmune and neuroendocrine systems.Here,we summarize the bioinformatics analysis and wet-biology validation for the gut metagenomics in neurodegenerative diseases,with an emphasis on multi-omics studies and the gut virome.The pathogen-associated signaling biomarkers for identifying brain disorders and potential therapeutic targets are also elucidated.Finally,we discuss the role of diet,prebiotics,probiotics,postbiotics and exercise interventions in remodeling the microbiome and reducing the symptoms of neurodegenerative diseases.

The pivotal role of microglia in injury and the prognosis of subarachnoid hemorrhage

Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter injury.Microglia,which are the key immune cells in the central nervous system,maintain homeostasis in the neural environment,support neurons,mediate apoptosis,participate in immune regulation,and have neuroprotective effects.Increasing evidence has shown that microglia play a pivotal role in the pathogenesis of subarachnoid hemorrhage and affect the process of injury and the prognosis of subarachnoid hemorrhage.Moreover,microglia play certain neuroprotective roles in the recovery phase of subarachnoid hemorrhage.Several approaches aimed at modulating microglia function are believed to attenuate subarachnoid hemorrhage injury.This provides new targets and ideas for the treatment of subarachnoid hemorrhage.However,an in-depth and comprehensive summary of the role of microglia after subarachnoid hemorrhage is still lacking.This review describes the activation of microglia after subarachnoid hemorrhage and their roles in the pathological processes of vasospasm,neuroinflammation,neuronal apoptosis,blood–brain barrier disruption,cerebral edema,and cerebral white matter lesions.It also discusses the neuroprotective roles of microglia during recovery from subarachnoid hemorrhage and therapeutic advances aimed at modulating microglial function after subarachnoid hemorrhage.Currently,microglia in subarachnoid hemorrhage are targeted with TLR inhibitors,nuclear factor-κB and STAT3 pathway inhibitors,glycine/tyrosine kinases,NLRP3 signaling pathway inhibitors,Gasdermin D inhibitors,vincristine receptorαreceptor agonists,ferroptosis inhibitors,genetic modification techniques,stem cell therapies,and traditional Chinese medicine.However,most of these are still being evaluated at the laboratory stage.More clinical studies and data on subarachnoid hemorrhage are required to improve the treatment of subarachnoid hemorrhage.

Network pharmacology-based analysis of heat clearing and detoxifying drug JC724 on the treatment of colorectal cancer

BACKGROUND Heat-clearing and detoxifying drugs has protective effect on colorectal cancer(CRC).Given the complicated features of Traditional Chinese medicine formulas,network pharmacology is an effective approach for studying the multiple interactions between drugs and diseases.AIM To systematically explore the anticancer mechanism of heat-clearing and detoxifying drug JC724.METHODS This study obtained the active compounds and their targets in JC724 from Traditional Chinese Medicine System Pharmacology Database.In addition,the CRC targets were obtained from Drugbank,TTD,DisGeNET and GeneCards databases.We performed transcriptome analysis of differentially expressed genes in CRC treated with JC724.Venn diagram was used to screen the JC724-CRC intersection targets as candidate targets.Core targets were selected by proteinprotein interaction network and herb ingredient-target-disease network analysis.The functional and pathway of core targets were analysed by enrichment analysis.RESULTS We found 174 active ingredients and 283 compound targets from JC724.940 CRC-related targets were reserved from the four databases and 304 CRC differentially expressed genes were obtained by transcriptome analysis.We constructed the network and found that the five core ingredients were quercetin,βBeta sitosterol,wogonin,kaempferol and baicalein.The core JC724-CRC targets were CYP1A1,HMOX1,CXCL8,NQO1 and FOSL1.JC724 acts on multiple signaling pathways associated with CRC,including the Nrf2 signaling pathway,oxidative stress,and the IL-17 signaling pathway.CONCLUSION In this study,we systematically analyzed the active ingredients,core targets and main mechanisms of JC724 in the treatment of CRC.This study could bring a new perspective to the heat-clearing and detoxifying therapy of CRC.

Inetetamab combined with S-1 and oxaliplatin as first-line treatment for human epidermal growth factor receptor 2-positive gastric cancer

BACKGROUND Patients with human epidermal growth factor receptor 2(HER2)-positive advanced gastric cancer have poor outcomes.Trastuzumab combined with chemotherapy is the first-line standard treatment for HER2-positive advanced gastric cancer.Inetetamab is a novel anti-HER2 drug,and its efficacy and safety in gastric cancer have not yet been reported.AIM To evaluate the efficacy and safety of the S-1 plus oxaliplatin(SOX)regimen combined with inetetamab as a first-line treatment for HER2-positive advanced gastric cancer.METHODS Thirty-eight patients with HER2-positive advanced gastric cancer or gastroeso-phageal junction adenocarcinoma were randomly divided into two groups:One group received inetetamab combined with the SOX regimen,and the other group received trastuzumab combined with the SOX regimen.After 4-6 cycles,patients with stable disease received maintenance therapy.The primary endpoints were progression-free survival(PFS)and overall survival(OS),and the secondary endpoints were the objective response rate,disease control rate,and adverse events(AEs).RESULTS Thirty-seven patients completed the trial,with 18 patients in the inetetamab group and 19 patients in the trastuzumab group.In the inetetamab group,the median PFS was 8.5 months,whereas it was 7.3 months in the trastuzumab group(P=0.046);this difference was significant.The median OS in the inetetamab group vs the trastuzumab group was 15.4 months vs 14.3 months(P=0.33),and the objective response rate was 50%vs 42%(P=0.63),respectively;these differences were not significant.Common AEs included leukopenia,thrombocytopenia,nausea,and vomiting.The incidence rates of grade≥3 AEs were 56%in the inetetamab group and 47%in the trastuzumab group(P=0.63),with no significant difference.CONCLUSION In the first-line treatment of HER2-positive advanced gastric cancer,inetetamab and trastuzumab showed comparable efficacy.The inetetamab group showed superior PFS,and both groups had good safety.

Inetetamab combined with tegafur as second-line treatment for human epidermal growth factor receptor-2-positive gastric cancer: A case report

BACKGROUND Human epidermal growth factor receptor-2(HER-2)plays a vital role in tumor cell proliferation and metastasis.However,the prognosis of HER2-positive gastric cancer is poor.Inetetamab,a novel anti-HER2 targeting drug independently developed in China,exhibits more potent antibody-dependent cell-mediated cytotoxicity than trastuzumab,which is administered as the first-line treatment for HER2-positive gastric cancer in combination with chemotherapy.In this case,the efficacy and safety of inetetamab combined with tegafur was investigated as a second-line treatment for HER2-positive gastric cancer.CASE SUMMARY A 52-year-old male patient with HER2-positive gastric cancer presented with abdominal distension,poor appetite,and fatigue two years after receiving six cycles of oxaliplatin combined with tegafur as first-line treatment after surgery,followed by tegafur monotherapy for six months.The patient was diagnosed with postoperative recurrence of gastric adenocarcinoma.He received 17 cycles of a combination of inetetamab,an innovative domestically developed anti-HER2 monoclonal antibody,and tegafur chemotherapy as the second-line treatment(inetetamab 200 mg on day 1,every 3 wk combined with tegafur twice daily on days 1–14,every 3 wk).Evaluation of the efficacy of the second-line treatment revealed that the patient achieved a stable condition and progression-free survival of 17 months.He tolerated the treatment well without exhibiting any grade 3-4 adverse events.CONCLUSION Inetetamab combined with chemotherapy for the treatment of metastatic HER2-positive gastric cancer demonstrates significant survival benefits and acceptable safety.

Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment

Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of SUMOylation.We used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other cancers.We demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by nutlin-3.This underscores the intricate relationship between natural compounds such as nutlin-3 and immune regulation.Using comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma progression.We also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic simulation.Nutlin-3a inhibited glioma cell proliferation and activated the p53 pathway.Its efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or exercise.Experiments using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway regulation.Notably,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing cells.These results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma management.Our research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.

CRABP2 regulates infiltration of cancer-associated fibroblasts and immune response in melanoma

Finding biomarkers for immunotherapy is an urgent issue in cancer treatment.Cellular retinoic acid-binding protein 2(CRABP2)is a controversial factor in the occurrence and development of human tumors.However,there is limited research on the relationship between CRABP2 and immunotherapy response.This study found that negative correlations of CRABP2 and immune checkpoint markers(PD-1,PD-L1,and CTLA-4)were observed in breast invasive carcinoma(BRCA),skin cutaneous melanoma(SKCM),stomach adenocarcinoma(STAD)and testicular germ cell tumors(TGCT).In particular,in SKCM patients who were treated with PD-1 inhibitors,high levels of CRABP2 predicted poor prognosis.Additionally,CRABP2 expression was elevated in cancer-associated fibroblasts(CAFs)at the single-cell level.The expression of CRABP2 was positively correlated with markers of CAFs,such as MFAP5,PDPN,ITGA11,PDGFRα/βand THY1 in SKCM.To validate the tumor-promoting effect of CRABP2 in vivo,SKCM xenograft mice models with CRABP2 overexpression have been constructed.These models showed an increase in tumor weight and volume.Enrichment analysis indicated that CRABP2 may be involved in immunerelated pathways of SKCM,such as extracellular matrix(ECM)receptor interaction and epithelial-mesenchymal transition(EMT).The study suggests that CRABP2 may regulate immunotherapy in SKCM patients by influencing infiltration of CAFs.In conclusion,this study provides new insights into the role of CRABP2 in immunotherapy response.The findings suggest that CRABP2 may be a promising biomarker for PD-1 inhibitors in SKCM patients.Further research is needed to confirm these findings and to explore the clinical implications of CRABP2 in immunotherapy.

Effect of alprostadil in the treatment of intensive care unit patients with acute renal injury

BACKGROUND Acute kidney injury(AKI)is a sudden or rapid decline in the filtration function of the kidneys which is marked by increased serum creatinine or blood urea nitrogen.AIM To examine the value of alprostadil-assisted continuous venous-venous hemofiltration(CVVH)in the treatment of severe AKI in severely ill patients.METHODS This was a retrospective study and the inclusion criteria were as follows:(1)Age of patients(≥18 years);(2)Admission to intensive care unit due to non-renal primary disease,APACHE II score(≥18 points);(3)The diagnostic criteria of AKI guidelines were formulated with reference to the Global Organization for the Improvement of Prognosis in Kidney Diseases,with AKI grades of II-III;(4)All patients were treated with CVVH;and(5)Complete basic data were obtained for all patients.RESULTS The clinical effect of alprostadil administered in the treatment group was better than that observed in the control group(P<0.05).The urine output of patients in the alprostadil group returned to normal time(9.1±2.0 d)and was lower than that in the control group(10.6±2.5 d),the difference was statistically significant(P<0.05);adverse reactions occurred in the alprostadil group compared with the control group,but the difference was not statistically significant(P>0.05).CONCLUSION Alprostadil-assisted CVVH in the treatment of severely ill patients with AKI can effectively improve the renal resistance index and partial pressure of urine oxygen,and has a positive effect on improving renal function.

Association between Hypertension with Hyperhomocysteinemia and Cognitive Impairment in the Kailuan Community of China:A Cross-sectional Study

Cognitive impairment,especially dementia,is common in elderly individuals and seriously affects life quality.Dementia is the most severe expression of cognitive impairment characterized by a progressive functional decline in one or more cognitive domains.The prevalence of dementia has increased dramatically,and the number of patients with dementia will reach 130 million in 2050.The worldwide prevalence of dementia among elderly individuals is approximately 5.0%.In China,more than 220 million people aged over 60 years in 2016.

Application of multidisciplinary collaborative nursing with family care for enhanced recovery after surgery in children with inguinal hernia

BACKGROUND Perioperative nursing can reduce the stress reaction and improve the prognosis of children.AIM To elucidate the influence of multidisciplinary collaborative nursing for enhanced recovery after surgery(ERAS)with family care in perioperative nursing children with an inguinal hernia and its impact on the prognosis.METHODS The data of 100 children with inguinal hernia were retrospectively analyzed.The participants were divided into three groups according to different nursing methods:Groups A(n=38),B(n=32),and C(n=30).Group A received multidisciplinary collaborative ERAS nursing combined with family care nursing;Group B received multidisciplinary collaborative nursing for ERAS;and Group C received routine nursing.The postoperative recovery results of the three groups were compared,including intraoperative blood loss and postoperative feeding time,time of getting out of bed,hospitalization time,and defecation time.Furthermore,the incidence of common complications was also compared between the three groups.RESULTS There was less intraoperative blood loss in Groups A and B than in Group C(P<0.05),and the time of getting out of bed and postoperative hospitalization and defecation times were also decreased in Group C(P<0.05).There was no significant difference in postoperative feeding time among the three groups(P>0.05).Each index had no statistical significance between Groups A and B(P>0.05).The incidence of urinary retention,infection,hematoma,and hernia recurrence in Group A was less than that in Group C(P<0.05).No significant difference was observed in the overall complication rate between Groups A and B and between Groups B and C(P>0.05).CONCLUSION The application of multidisciplinary collaborative nursing combined with family care in the perioperative care of children with an inguinal hernia for ERAS may promote postoperative rehabilitation for children and reduce the incidence of complications.

Ferroptosis mechanism and Alzheimer's disease

Regulated cell death is a genetically determined form of programmed cell death that commonly occurs during the development of living organisms.This process plays a crucial role in modulating homeostasis and is evolutionarily conserved across a diverse range of living organisms.Ferroptosis is a classic regulatory mode of cell death.Extensive studies of regulatory cell death in Alzheimer’s disease have yielded increasing evidence that fe rroptosis is closely related to the occurrence,development,and prognosis of Alzheimer’s disease.This review summarizes the molecular mechanisms of ferroptosis and recent research advances in the role of ferro ptosis in Alzheimer’s disease.Our findings are expected to serve as a theoretical and experimental foundation for clinical research and targeted therapy for Alzheimer’s disease.

Exploration of Teaching and Education: Integration of Sports and Medicine in Physical Education in Colleges and Universities

Based on the concept and definition of“integration of sports and medicine,”this paper analyzes the current situation of the integration,where it lacks innovative physical education curriculum content and physical education teachers with conventional medical professional knowledge;in addition,physical education disciplines with medical characteristics are not highlighted.Therefore,relevant measures are put forward for reference and discussion.

Relationship between multi-slice computed tomography features and pathological risk stratification assessment in gastric gastrointestinal stromal tumors

BACKGROUND Computed tomography(CT)imaging features are associated with risk stratification of gastric gastrointestinal stromal tumors(GISTs).AIM To determine the multi-slice CT imaging features for predicting risk stratification in patients with primary gastric GISTs.METHODS The clinicopathological and CT imaging data for 147 patients with histologically confirmed primary gastric GISTs were retrospectively analyzed.All patients had received dynamic contrast-enhanced CT(CECT)followed by surgical resection.According to the modified National Institutes of Health criteria,147 lesions were classified into the low malignant potential group(very low and low risk;101 lesions)and high malignant potential group(medium and high-risk;46 lesions).The association between malignant potential and CT characteristic features(including tumor location,size,growth pattern,contour,ulceration,cystic degeneration or necrosis,calcification within the tumor,lymphadenopathy,enhancement patterns,unenhanced CT and CECT attenuation value,and enhancement degree)was analyzed using univariate analysis.Multivariate logistic regression analysis was performed to identify significant predictors of high malignant potential.The receiver operating curve(ROC)was used to evaluate the predictive value of tumor size and the multinomial logistic regression model for risk classification.RESULTS There were 46 patients with high malignant potential and 101 with low-malignant potential gastric GISTs.Univariate analysis showed no significant differences in age,gender,tumor location,calcification,unenhanced CT and CECT attenuation values,and enhancement degree between the two groups(P>0.05).However,a significant difference was observed in tumor size(3.14±0.94 vs 6.63±3.26 cm,P<0.001)between the low-grade and high-grade groups.The univariate analysis further revealed that CT imaging features,including tumor contours,lesion growth patterns,ulceration,cystic degeneration or necrosis,lymphadenopathy,and contrast enhancement patterns,were associated with risk stratification(P<0.05).According to binary logistic regression analysis,tumor size[P<0.001;odds ratio(OR)=26.448;95%confidence interval(CI):4.854-144.099)],contours(P=0.028;OR=7.750;95%CI:1.253-47.955),and mixed growth pattern(P=0.046;OR=4.740;95%CI:1.029-21.828)were independent predictors for risk stratification of gastric GISTs.ROC curve analysis for the multinomial logistic regression model and tumor size to differentiate high-malignant potential from low-malignant potential GISTs achieved a maximum area under the curve of 0.919(95%CI:0.863-0.975)and 0.940(95%CI:0.893-0.986),respectively.The tumor size cutoff value between the low and high malignant potential groups was 4.05 cm,and the sensitivity and specificity were 93.5%and 84.2%,respectively.CONCLUSION CT features,including tumor size,growth patterns,and lesion contours,were predictors of malignant potential for primary gastric GISTs.

血清免疫球蛋白GN-糖基的高通量分析——一种消化道癌症的非侵入性生物标志物

免疫球蛋白G(Immunoglobulin G,IgG)的N-糖基化在炎症性疾病的发展中起着重要作用。本研究旨在评价IgG N-糖基在消化道癌症亚型中的诊断效能。从中国医学科学院肿瘤医院招募749名消化道癌症患者,包括食管癌(esophageal cancer,EC)、胃癌(gastric cancer,GC)、结直肠癌(colorectal cancer,CRC)和胰腺癌(pancreatic cancer,PC)患者。采用亲水交互高效液相色谱-超高效液相色谱(hydrophilic interaction liquid chromatography using ultra-performance liquid chromatography,HILIC-UPLC)分析血浆中IgG的N-糖基构成。采用Bio-Plex悬液芯片系统检测方法(Bio-Rad)进行炎症因子检测。采用典型相关分析(canonical correlation analysis,CCA)探索糖基和炎症因子之间的相关性。采用LASSO回归和logistic回归模型,基于检测到的糖基谱建立可用于区分胃肠癌症患者和健康人群诊断模型。与健康对照组相比,EC、GC、CRC和PC患者的唾液酸化和半乳糖基化水平降低,而二等分乙酰葡萄糖胺基化水平在消化道癌症患者中升高。此外,只有胰腺癌患者具有低水平的岩藻糖基化。消化道癌症组的IL-1β、IL-31和sCD40L水平均高于对照组。IgG N-糖基的组成与炎症因子相关(r=0.556)。基于糖基的模型表现出良好的诊断效能,EC、GC、CRC和PC的受试者工作特征曲线下面积(AUC)分别为0.972、0.871、0.867和0.907。这些研究结果表明,IgG N-糖基在调节消化道肿瘤的发病机制中发挥了重要作用。血清IgG N-糖基可以作为潜在的非侵入性辅助消化道癌症临床诊断的方法。

Seroprevalence of influenza viruses in Shandong,Northern China during the COVID-19 pandemic

Nonpharmaceutical interventions(NPIs)have been commonly deployed to prevent and control the spread of the coronavirus disease 2019(COVID-19),resulting in a worldwide decline in influenza prevalence.However,the influenza risk in China warrants cautious assessment.We conducted a cross-sectional,seroepidemiological study in Shandong Province,Northern China in mid-2021.Hemagglutination inhibition was performed to test antibodies against four influenza vaccine strains.A combination of descriptive and meta-analyses was adopted to compare the seroprevalence of influenza antibodies before and during the COVID-19 pandemic.The overall seroprevalence values against A/H1N1pdm09,A/H3N2,B/Victoria,and B/Yamagata were 17.8%(95%CI 16.2%–19.5%),23.5%(95%CI 21.7%–25.4%),7.6%(95%CI 6.6%–8.7%),and 15.0(95%CI 13.5%–16.5%),respectively,in the study period.The overall vaccination rate was extremely low(2.6%).Our results revealed that antibody titers in vaccinated participants were significantly higher than those in unvaccinated individuals(P<0.001).Notably,the meta-analysis showed that antibodies against A/H1N1pdm09 and A/H3N2 were significantly low in adults after the COVID-19 pandemic(P<0.01).Increasing vaccination rates and maintaining NPIs are recommended to prevent an elevated influenza risk in China.

Hemophagocytic lymphohistiocytosis after autologous stem cell transplantation in angioimmunoblastic T-cell lymphoma:A case report

BACKGROUND Angioimmunoblastic T-cell lymphoma(AITL), a unique subtype of peripheral Tcell lymphoma, has relatively poor outcomes. High-dose chemotherapy with autologous stem cell transplantation(ASCT) can achieve complete remission and improve outcomes. Unfortunately, subsequent T-cell lymphoma-triggered hemophagocytic lymphohistiocytosis(HLH) has a worse prognosis than B-cell lymphoma-triggered HLH.CASE SUMMARY We here report a 50-year-old woman with AITL who achieved a favorable outcome after developing HLH 2 mo after receiving high-dose chemotherapy/ASCT. The patient was initially admitted to our hospital because of multiple enlarged lymph nodes. The final pathologic diagnosis, made on biopsy of a left axillary lymph node was AITL(Stage Ⅳ, Group A). Four cycles of the following chemotherapy regimen were administered: Cyclophosphamide 1.3 g, doxorubicin 86 mg, and vincristine 2 mg on day 1;prednisone 100 mg on days 1-5;and lenalidomide 25 mg on days 1-14. The interval between each cycle was 21 d. The patient received a conditioning regimen(busulfan, cyclophosphamide, and etoposide) followed by peripheral blood stem cell infusion. Unfortunately, she developed sustained fever and a low platelet count 17 d after ACST, leading to a diagnosis of HLH after ASCT. During treatment, she experienced thrombocytopenia and Pneumocystis carinii pneumonia. The patient was successfully treated with etoposide and glucocorticoids.CONCLUSION It is possible that development of HLH is related to immune reconstitution after ASCT.

A bare-metal stents treatment of arterial injuries at the joint levels

Reports indicate that peripheral arterial injuries are especially challenging as they are associated with a high risk of limb loss.Rapid diagnosis and intervention is required to provide limb salvage and can be lifesaving.As endovascular techniques and tools continue to evolve,open repair has been not the only option in the management of traumatic vascular injuries.Similarly,minimally invasive percutaneous endovascular therapies offer an attractive treatment alternative.Limb salvage in acute traumatic vascular lesions may be improved because of the endovascular therapies to perform diagnostic evaluation and therapeutic intervention nearly simultaneously.

Glomangiomatosis-immunohistochemical study:A case report

BACKGROUND Glomangiomatosis(also known as diffuse glomus tumor)is extremely rare,accounting for only 5%of glomus tumors.The prevalence of glomus tumors is only 2%of soft tissue tumors.Lesions can recur after resection.Although growth may be diffuse or infiltrating and invasive,definitive identifying standards for malignant glomus tumors are lacking.This article describes a case of glomangiomatosis with many nodular masses in the soft tissues of the right foot and calf.A review of the Chinese and English-language literature is included.CASE SUMMARY A case of glomangiomatosis in a 55-year-old Chinese woman who presented clinically with many nodular masses in the soft tissues of the right foot and calf.The tumor was examined histologically and immunostaining was performed.CONCLUSION Glomangiomatosis occurs most often in young people,in the distal extremities,but is rare.Multiple nodules are even rarer.Only 15 clinicopathological analyses of glomangiomatosis have been reported in the combined Chinese-and Englishlanguage literature.In the present case,microscopically,nested vascular globular cells were observed around the blood vessel wall.Immunohistochemistry revealed diffuse immunoreactivity for smooth muscle actin,vimentin,type Ⅳ collagen,and Bcl-2.Caldesmon,CD34,and calponin were weakly,partially,and slightly positive,respectively.There was no recurrence 1 year after resection.

Comparative studies between humans and golden Syrian hamsters via thromboelastography

Background:Thromboelastography(TEG)is a widely utilized clinical testing method for real-time monitoring of platelet function and the thrombosis process.Lipid metab-olism disorders are crucial risk factors for thrombosis.The lipid metabolism charac-teristics of hamsters resemble those of humans more closely than mice and rats,and their relatively large blood volume makes them suitable for studying the mechanisms of thrombosis related to plasma lipid mechanisms.Whole blood samples from golden Syrian hamsters and healthy humans were obtained following standard clinical pro-cedures.TEG was employed to evaluate coagulation factor function,fibrinogen(Fib)function,platelet function,and the fibrinolytic system.Methods:The whole blood from hamster or healthy human was isolated following the clinical procedure,and TEG was employed to evaluate the coagulation factor func-tion,Fib function,platelet function,and fibrinolytic system.Coagulation analysis used ACLTOP750 automatic coagulation analysis pipeline.Blood routine testing used XN-2000 automatic blood analyzer.Results:TEG parameters revealed that hamsters exhibited stronger coagulation fac-tor function than humans(reaction time[R],p=0.0117),with stronger Fib function(alpha angle,p<0.0001;K-time[K],p<0.0001).Platelet function did not differ signifi-cantly(maximum amplitude[MA],p=0.077).Hamsters displayed higher coagulation status than humans(coagulation index[CI],p=0.0023),and the rate of blood clot dissolution in hamsters differed from that in humans(percentage lysis 30 min after MA,p=0.02).Coagulation analysis parameters indicated that prothrombin time(PT)and activated partial thromboplastin time(APTT)were faster in hamsters than in hu-mans(PT,p=0.0014;APTT,p=0.03),whereas the Fib content was significantly lower in hamsters than in humans(p<0.0001).No significant difference was observed in thrombin time(p=0.1949).Conclusions:In summary,TEG could be used to evaluate thrombosis and bleeding parameters in whole blood samples from hamsters.The platelet function of hamsters closely resembled that of humans,whereas their coagulation function was signifi-cantly stronger.

Human bone marrow mesenchymal stem cell-derived extracellular vesicles inhibit shoulder stiffness via let-7a/Tgfbr1 axis

Shoulder stiffness(SS)is a common shoulder disease characterized by increasing pain and limited range of motion.SS is considered to be an inflammatory and fibrotic disorder pathologically.However,there is no consensus on the most effective conservative treatment for fibrosis.Given that human Bone Marrow Mesen-chymal Stem Cell-derived extracellular vesicles(BMSC-EVs)displayed promising therapeutic effects for various tissues,we investigated the therapeutic effect of BMSC-EVs on fibrosis in a mice immobilization model and two cell models.By conducting a series of experiments,we found that BMSC-EVs can significantly inhibit the fibrogenic process both in vitro and in vivo.In detail,BMSC-EVs suppressed the aberrant proliferation,high collagen production capacity,and activation of fibrotic pathways in TGF-β-stimulated fibroblasts in vitro.Besides,in vivo,BMSC-EVs reduced cell infiltration,reduced fibrotic tissue in the shoulder capsule,and improved shoulder mobility.In addition,via exosomal small RNA sequencing and qPCR analysis,let-7a-5p was verified to be the highest expressed miRNA with predicted antifibrotic capability in BMSC-EVs.The antifibrotic capacity of BMSC-EVs was significantly impaired after the knockdown of let-7a-5p.Moreover,we discovered that the mRNA of TGFBR1(the membrane receptor of transforming growth factorβ)was the target of let-7a-5p.Together,these findings elucidated the antifibrotic role of BMSC-EVs in shoulder capsular fibrosis.This study clarifies a new approach using stem cell-derived EVs therapy as an alternative to cell therapy,which may clinically benefit patients with SS in the future.