Sarcopenia is a progressive and systemic skeletal muscle disease and an important extrapulmo-nary complication of chronic obstructive pulmonary disease(COPD).Multiple studies have confirmed that COPD patients with sarcopenia have more severe airflow obstruction and emphysema,higher dyspnea index scores,reduced quality of life and exercise capacity,frequent acute exacerbations,and increased mortality.Although sarcopenia has been mentioned as a complication of COPD for many years,current clinical practice has received insufficient attention and insufficient intervention.The main reason is that its pathogenesis is unknown and drug treatment regi-mens are ineffective.As more and more research has been done on COPD combined with sarcopenia in recent years,this article reviews the current research progress to pay attention to further research and early intervention,including new mechanisms,diagnostic criteria,and drug treatment progress.

Since COVID-19 infection,many infected patients have developed multiple systemic symptoms that persist long after 3 months of infection,which is called Long COVID.Numerous studies have shown that fatigue is the most common symptom among the many symptoms of Long COVID that has severely impacted the quality of their life.Therefore,it is particularly important to understand the mechanisms by which Long COVID causes fatigue symptoms.This article summarizes the possible mechanisms of Long COVID fatigue,including immune response,oxidative stress,and affecting the central nervous system,by combing through the relevant literature,aiming to increase clinical awareness of fatigue induced by Long COVID and to provide certain ideas for its treatment.

Objective To Investigate the effect of copper ions on the radiosensitivity of nasopharyngeal carcinoma(NPC)and identify potential targets to improve the efficacy of NPC radiation therapy.Methods The content of copper ions in normal nasopharyngeal epithelial cell line NP69 and a variety of NPC cell lines was detected by a copper microplate assay.After adding 0,5,10,20,50,100,200 μmol/L copper ion solution and 0,0.05,0.1,0.2,0.5,1.0,2.0 mmol/L TEPA solution,CCK-8 assay was used to determine the effect of intracellular copper ion content on the survival rate of NPC cells before and after irradiation.And determine the drug concentration to be used in subsequent experiments.CCK-8 assay was used to determine the effect of intracellular copper ion content on the survival rate of NPC cells before and after irradiation,and to determine the drug concentration used in the copper ion group and TEPA group in the subsequent experiments.CCK-8 assay and clone formation assay were used to detect the changes in radiosensitivity of NPC cells after drug treatment.The DNA damage and MAPK-ERK signaling pathway-related protein expression of NPC cells in each group before and after irradiation were detected by Western blot.Results The content of copper ions in NPC cells was significantly higher than that in normal naso-pharyngeal epithelial cells(P＜0.05).When the concentration of copper ion solution was lower than 50 μmol/L,the radiation resistance of CNE1 cells was improved,and the radiation sensitivity of SUNE1 cells was increased by 0.1～0.2 mmol/L TEPA(P＜0.05).Compared with the control group,the NPC cell radiotherapy resistance of copper ion group was enhanced,and the NPC cell radiotherapy sensitivity of copper ion group was enhanced(P＜0.05).Compared with the control group,the activation degree of MAPK-ERK pathway in copper ion group was up-regulated(P＜0.05).MAPK-ERK pathway inhibitor SCH772984 effectively reversed copper-mediated NPC radiotherapy resistance(P＜0.05).Conclusion The increased copper ion content in NPC cells promoted the radiotherapy resistance of NPC cells by activating the MAPK-ERK signaling pathway.

Objective To study the influence of ANGPTL8 in lipopolysaccharide(LPS)-induced hepatic lipid deposition.Methods Male wild-type(WT)and ANGPTL8 knockout mice at 6-8 weeks were used to induce sepsis models by intrabitoneal injection of LPS(10 mg/kg).qPCR and immunofluorescence were used to detected the mRNA and protein expression of ANGPTL8 in liver tissue and HepG2 cells respectively;The contents of alanine aminotransferase(ALT),aspartate aminotransferase(AST)in serum and the triglyceride(TG)and malondialdehyde(MDA)in liver homogenate were detected by kits;the histopathological changes of liver tissue were analyzed through HE staining.Lipids accumulation in liver were detected by oil red O staining.The apoptosis of liver was determinated by TUNEL staining.RNA-seq was used to analyzing the differentially expressed genes in the liver tissue of WT and ANGPTL8 KO mice,and the qPCR and Western Blot were used to verify the differential expressed genes.Results The expression of ANGPTL8 in the liver was significantly upregulated at 48 hours after LPS stimulation.Compared with WT mice,the hepatic lipid deposition,steatosis,and apoptosis were significantly alleviated in liver of ANGPTL8 KO mice,the ALT and AST levels in serum and the TG and MDA content in liver homogenate of ANGPTL8 KO mice were also reduced significantly.The expression of caveolin-1(CAV1)in liver of ANGPTL8 KO mice was significantly higher than that of WT mice.Conclusions LPS promoted the expression and secretion of ANGPTL8 in liver tissue,and ANGPTL8 increased hepatic lipid deposition and peroxidation by inhibiting the expression of CAV1.

Objective The present study aimed to explore the effects of CC-chemokine receptor 5 antagonism on tumor growth and immune microenvironment.Methods Cell Counting Kit-8 was used to detect in vitro anti-proliferation activity of maraviroc,a selective CC-chemokine receptor 5 inhibitor,on Lewis cells,a mouse lung adenocarcinoma cell strain.Flow cytometry and real-time quantitative PCR were respectively used to detect cell apop-tosis and Caspase 8 gene expression.In a congenic mouse lung cancer model,the mice were intraperitoneally admin-istered with maraviroc or vehicle.Tumor sizes were measured and tumor infiltrating CD4+,CD8+ and Foxp3+ cells were determined by immunofluorescent staining.Results Our results showed that maraviroc could inhibit the growth of Lewis cancer cells not only in vitro but also in vivo.This in-vitro inhibition was presumably attributable to apoptosis induction by the enhancement of Caspase 8 gene expression after maraviroc blockade.Additionally,more CD4+ and CD8+ cells but less Foxp3+ cells were detected in tumor mass from the mice administered with maraviroc.Conclusions Taken together,it can be speculated that CCR5 blockade may inhibit the growth of Lewis cells by inducing cell apoptosis and impairing the immunosuppressive tumor microenvironment.It is worthy of further investi-gation as a candidate for cancer therapy.

Objective To investigate the effect of human pulp stem cells(hDPSC)-derived exosomes(Exo)modified by circRNA(circRNA)signal-induced proliferation-associated protein-like 1(SIPA1L1)on the angiogenesis of human umbilical vein endothelial cells(HUVEC).Methods hDPSC was isolated and cultured from pulp tissue,the circSIPA1L1 overexpression plasmid was transfected into hDPSC,and Exo was isolated and identified.HUVEC was divided into control group,hDPSC Exo group and circSIPA1L1-hDPSC Exo group.After culture for 48 h,the vasculoformation ability was detected by Matrigel matrix gel vasculoformation test,the expres-sion levels of vascular endothelial growth factor(VEGF),vascular endothelial growth factor receptor 2(VEGFR2)and placental growth factor(PGF)were determined by qRT-PCR and Western blot.Results The Exo was success-fully isolated from the untransfected hDPSC and the hDPSC transfected with circSIPA1L1,and compared with the HDPSC-derived Exo,the relative expression of circSIPA1L1 in the hDPSC Exo transfected with circSIPA1L1 was significantly up-regulated(P＜0.05).Compared with hDPSC Exo group,the number of HUVEC tubular structures in circSIPA1L1-hDPSC Exo group was significantly increased(P＜0.05),and the mRNA and protein relative expressions of VEGF,VEGFR2 and PGF were also significantly up-regulated(P＜0.05).Conclusions Modification of hDPSC-derived Exo by circRNA SIPA1L1 can promote angiogenesis,and the mechanism may be related to up-regulation of VEGF,VEGFR2 and PGF expression levels.

Objective We systematically analyze the changes in the count and function of platelet at the early sepsis based on clinical study and single cell sequencing.Methods Clinical data of sepsis patients at the early stage were collected and had been compared between different prognostic groups in the prospective case-control study.The independent risk factors of death were analyzed by logistic regression,and the predictive efficacy of clini-cal indicators was evaluated by receiver operating characteristic(ROC)curve.The healthy volunteers and sepsis patients were recruited.Clinical researchers collected peripheral venous blood samples for sorting cell samples to carry out single-cell RNA sequencing(sc-RNA seq).Through bioinformatics techniques,we analyzed the changes in platelet count,the significantly differential-expressed genes and its enriched functional signaling pathways in the early stages of sepsis.Results(1)A total of 224 patients were enrolled,with a 90 day survival rate of 70.5%.Compared with the survival group,the count of platelet and MAP in the death group at the early stage of sepsis were significantly lower,but the plasma lactate content and SOFA score were significantly higher.(2)Based on single cell sequencing technology,cells are annotated as six groups.The proportion of innate immune cells(neutrophils,monocytes,and dendritic cells)was significantly increased in the early stage of sepsis compared to the healthy volun-teers(2.15∶1),while platelets significantly decreased(0.31∶1).(3)Through bioinformatics technology,CD41/CD42a/CD61 was identified as platelet specific molecules,with significantly increased expression levels in sepsis.Three molecules can distinguish platelets together.(4)771 genes were significantly upregulated and 1101 genes were significantly downregulated in platelets of patients with sepsis,including core molecules involved in physiological functions such as cell adhesion,chemotaxis,and immune response.Functional analysis suggests that differentially expressed genes are enriched in coagulation,immune functions and cell death,participating in oxidative phosphory-lation,leukocyte chemotaxis,iron death,and NOD like receptor signaling pathways.Conclusion Reduced platelet count is associated with poor prognosis in the early stage of sepsis.The specific high expression molecules CD41/CD42a/CD61 that are significantly upregulated in platelets can serve as biomarkers for platelets.Platelets not only mediate cell adhesion and coagulation cascade,but also participate in functional changes such as immune cell chemotaxis,inflammatory response,and the pathological death of inflammatory cells.

Objective Exploring the use of thromboelastography(TEG)to assess the risk of bleeding in patients with acute leukemia(AL)undergoing platelet transfusion refractoriness(PTR).Methods To investigate the differences in TEG parameters between the PTR group and the non-PTR group in adult AL patients,and compare the differences in PLT and TEG parameters between the bleeding group and the non-bleeding group in the PTR group.Results A total of 58 AL patients were positive for platelet-related antibodies,and the proportion of PTR was 48.28%.A total of 20 patients with PTR were transfused with large-dose immunoglobulin,the effective rate was 40%,and 26 patients with PTR were transfused with matching platelets,the effective rate was 42.62%.This study observed the difference of TEG parameters between the PTR group and the non-PTR group,and the results showed that there were no significant differences in PLT,R value,K value,α Angle and MA value before and after platelet transfusion in the PTR group.The PLT and MA values of the non-PTR group were significantly different before and after transfusion(P＜0.05),while the R value,K value and α Angle were not significantly different.The PLT and MA values of the non-PTR group were significantly higher than those in PTR group after transfusion(P＜0.05).Analysis and comparison of PLT and TEG parameters between the bleeding group and the non-bleeding group in patients with PTR showed that there was no significant difference in PLT value,R value,K value and α Angle of TEG,while MA value in the non-bleeding group was higher than that in the bleeding group,with significant difference(P＜0.05).Conclusions Platelet count alone cannot accurately reflect the risk of bleeding in AL patients with PTR.TEG can effectively predict and evaluate the bleeding risk in AL patients,among which the maximum amplitude index has the most significant clinical significance,which is of great significance for disease evaluation and treatment guidance.

Objective This study aims to develop a prognostic risk prediction model for gastric cancer based on m1A/m5C/m6A/m7G regulated genes and to investigate the relationship between this model and immunology.Methods The Cancer Genome Atlas(TCGA)gastric cancer dataset was utilized to identify m1A/m5C/m6A/m7G regulated genes with significant expression differences.A prognostic risk score(RS)model was constructed using univariate Cox regression analysis and the LASSO algorithm.The RS model was validated using the Kaplan-Meier(K-M)statistic and cell lines for RT-qPCR biological validation.A nomogram model was created using univariate and multivariate Cox regression analyses.The CIBERSORT algorithm and ESTIMATE package were employed to conduct immune correlation analysis.Results A prognostic RS model based on eight methylation regulated genes was developed to classify patients with gastric cancer as high-risk or low-risk.These eight genes showed significant expression in gastric cancer cell lines(P＜0.05).The TCGA-gastric cancer training set and GSE62254-validation set showed a substantial connection(P＜0.001)between overall survival rate(OS)and grouping status.The nomogram survival models accurately predicted 1-year(C-index = 0.703),3-year(C-index = 0.729),and 5-year(C-index = 0.734)survival rates.Immune correlation analysis showed that compared to the low-risk group,the high-risk group had higher immune scores and higher expression of immune checkpoint-related genes(P＜0.05).Conclusion We created a reliable prognostic RS model based on m1A/m5C/m6A/m7G regulated genes that can predict gastric cancer prognosis and guide individualized immunotherapy decisions.

Objective To explore the effect of the physician-nurse-social worker linkage rehabilitation model on the psychological status in patients receiving methadone maintenance treatment(MMT).Methods Ninety-four patients who received MMT were enrolled and randomly divided into experimental group(n = 48)and control group(n = 46).The experimental group received physician-nurse-social worker linkage rehabilitation model intervention,while the control group received conventional methadone treatment service.The anxiety,depression and quality of life of the two groups were evaluated before the intervention,3 months and 6 months after the intervention.Results After 6 months of physician-nurse-social worker linkage rehabilitation mode intervention,the depression status and the anxiety status of the experimental group subjects were significantly improved compared with those before intervention,and both BDI and BAI scores were significantly lower than those of the control group subjects(P＜0.05).Moreover,the proportion of"had depression"and"had anxiety"in the experimental group were significantly lower than those in the control group(P＜0.05).After 6 months of intervention,the QOL-DA score of the experimental group subjects(183.77±8.90)was significantly higher than that of the control group sub-jects(174.76±11.14)(P＜0.01).Conclusion The physician-nurse-social worker linkage rehabilitation model had certain advantages in improving the psychological state of MMT patients,which is worthy of promotion.