Objective To explore the potential cuproptosis-related genes(CRGs)in patients with multiple myeloma(MM)and develop a prognostic model for improving prognosis and revealing features of the MM immune microenvironment.Methods ① Transcriptome sequencing data and clinical information were retrieved from the GSE4581 dataset in the Gene Expression Omnibus(GEO)database and the Cancer Genome Atlas-Multiple Myeloma Research Foundation(TCGA-MMRF)database.The 859 patients from the TCGA-MMRF database were assigned into a training set,and the other 414 ones from the GSE4581 dataset into a validation set.LASSO-Cox and multivariate Cox regression analyses were used to construct prognostic models and calculate risk scores.Based on the median risk score,they were categorized into high-and low-risk cohorts.Time-dependent receiver operating characteristic(ROC)and calibration curves were plotted to assess the predictive performance and accuracy of the model.The differences between the high-and low-risk cohorts were explored using Kaplan-Meier survival curve analysis and immune microenvironment correlation analysis.② RT-qPCR and Western blotting were used to verify the expression of prognostic model genes in MM cell lines and normal bone marrow single-nucleated cells,and CCK-8 assay,flow cytometry,and Western blotting were applied to verify the biological function of UBE2D1 in MM cells.Results ① LASSO-Cox and multivariate Cox regression analyses revealed that the model consisted of 4 genes,CDKN2A[HR=1.60(95%CI:1.24～2.05),P=2.5e-4],PDE3B[HR=1.33(95%CI:1.09～1.62),P=4.2e-3],UBE2D1[HR=1.65(95%CI:1.20～2.26),P=2.1e-3]and COA6[HR=1.35(95%CI:1.07～1.71),P=0.01].In the training set,the time-dependent ROC curves predicted that the area under curve(AUC)value of 1-,3-,and 5-year survival rate was 0.63,0.71,and 0.78,respectively,and in the validation set,the AUC value was 0.656,0.657,and 0.797,respectively.Calibration curve analysis showed excellent agreement in predicting 1-,3-,and 5-year prognosis.In the training set,Kaplan-Meier curves showed that patients in the high-risk cohort had a significantly shorter overall survival(OS)than the low-risk cohort[HR=2.18(95%CI:1.58～3.02),P<0.001],and in the validation set,the high-risk cohort still had a shorter OS than the low-risk cohort[HR=2.45(95%CI:1.49～4.05),P<0.001].Immune correlation analysis revealed that the ratios of immune cells,such as plasma cells and CD4+T cells were significantly lower in the high-risk cohort(P<0.05),and the risk scores were positively correlated with the expression of immune checkpoint CTLA-4,tumor-targeted therapeutic sites TNFSF4 and ENTPD1,and microenvironmental chemokines CXCL16,CCL8,and CCL16(P<0.05).② Remarkable differences were observed in the expression of all 4 prognostic model genes between the MM cell lines and normal bone marrow single-nucleated cells(P<0.05),and knockdown of UBE2D1 notably inhibited the proliferation of MM cells(P<0.05).Conclusion Our prognostic models based on CDKN2A,PDE3B,UBE2D1,and COA6 genes can predict the prognosis of MM patients.The risk scores of the genes are significantly correlated with immune infiltration in the tumor microenvironment,which providing new molecular markers for individualized therapy.

OBJECTIVE: To verify the clinical effect of acupoint embedding therapy on post-stroke constipation. METHODS: The multi-central randomized controlled trial was adopted. 210 patients of post-stroke constipation were divided into an acupoint embedding group (105 cases, 4 cases dropped off) and a sham-embedding group (105 cases, 6 cases dropped off). In the acupoint embedding group, the acupoint embedding therapy was used at Tianshu (ST 25), Daheng (SP 15), Xiawan (CV 10), Zhongwan (CV 12), Qihai (CV 6), Guanyuan (CV 4) and Daju (ST 27). In the sham-embedding group, the sham-embedding therapy was given, in which, the acupoint selection, needle devices and manipulation were the same as the acupoint embedding group. But, no absorbable surgical suture was used in the needle tube. The treatment was given once every two weeks and 4 treatments were required in either group. It was to compare the weekly average complete spontaneous bowel movements (CSBMs) during treatment (from the 3rd to the 8th week) between the two groups, the weekly average spontaneous bowel movements (SBMs), Bristol stool form score (BSFS), the score of the patient assessment of constipation quality of life questionnaire (PAC-QOL) and the score of defecation difficulty before and after treatment. RESULTS: The percentage of the cases with weekly average CSBMs ≥ 3 times in the patients of the acupoint embedding group was higher markedly than the sham-embedding group [91.1% (92/101) vs 43.4% (43/99), <0.01]. Compared with the values before treatment, the weekly average SBMs and BSFS scores after treatment were all increased obviously in the two groups (<0.01), and PAC-QOL score and the score of defecation difficulty were reduced remarkably (<0.01). After treatment, the increase range of SBMs and BSFS scores, as well as the decrease range of PAC-QOL score and the defecation difficulty score in the acupoint embedding group were all higher than the sham-embedding group respectively (<0.05). CONCLUSION The acupoint embedding therapy remarkably increases the spontaneous bowel movements, improves in feces form and defecation difficulty and strengthens the quality of life in the patients of post-stroke constipation.
Acupuncture Points ; Acupuncture Therapy ; Constipation ; etiology ; therapy ; Humans ; Quality of Life ; Stroke ; complications ; Treatment Outcome

OBJECTIVE: To study the effect of hesperidin and rutin on oxidative modification of high density lipoprotein (HDL) in vitro. METHODS: HDL was isolated from healthy human plasma by sequential ultracentrifugation, and was oxidized by copper ions. The inhibitory effects of hesperidin and rutin on HDL oxidative modification were valued by the formation of malondialdehyde (MDA). RESULTS: Hesperidin and rutin significantly inhibited copper-induced oxidation of HDL in a dose-dependent manner. CONCLUSION: Both hesperidin and rutin can prevent HDL from copper-induced oxidative modification in vitro. This result suggests that they might have antiatherogenic effect.

Objective To study the effects of monocyte chemotactic protein-1(MCP-1) on the growth of human umbilical vein endothelial cells (hUVEC). Methods hUVEC were cultured in vitro and identified. hUVEC that grew vigorously were stimulated for 24 h or 48 h respectively with MCP-1(0.1, 1.0, 10, and 100 ?g/L). The survival rate of hUVEC was first detected by MTT assay. The cell cycle and DNA content were detected and analyzed by flow cytometry. Results hUVEC were isolated from human umbilical veins and cultured, and then identified by immunofluorescence and immunohistochemistry with factor Ⅷ and KDR. MCP-1 induced the apoptosis of hUVEC in a dose-dependentmanner and a time-dependentmanner (P