Objective To understand the current status of social support among the elderly,aged ≥60 years,as well as to identify influencing factors and to provide a reference for relevant health care services.Methods Publications about social support of the elderly were collected by searching the database of CNKI,VIP,Wanfang Data,Pubmed,and Web of Science.A random effects model was employed according to the results of heterogeneity (I2＞50％) to pool the extracted data.Results Thirty-two articles were included,with a total sample of 21 763 articles.Total scores of social support and three dimensions were low,with social support of 34.047 (95％CI:32.532-35.563),subjective support of 19.218 (95％CI:17.589-20.846),objective support of 7.787 (95％CI:7.483-8.091),and support utilization of 7.075 (95％CI:6.884-7.266).Scores of elderly with character of high age (aged 80:30.907,95％CI:28.378-33.436),female (32.512,95％CI:30.723-34.300),low education (illiteracy:32.088,95％CI:30.944-33.231;primary school:32.709,95％CI:30.069-35.349),country side (33.780,95％CI:31.523-36.038),empty nest (32.301,95％CI:27.061-37.542) and incomplete marriage (discoverture:27.044,95％CI:24.652-29.437;divorced:29.159,95％CI:24.520-33.791) was lower than the others.Conclusions The current status of social support is not optimistic.Scores of social support and its dimensions were relatively low,and a significant difference was found between elderly of different character,indicating that health interventions should be implemented based on character.

Objective·To explore the regulatory mechanism of folate cycle metabolism in the immunosuppressive effect of myeloid derived suppressor cells(MDSCs).Methods·Bone marrow cells were isolated from C57BL/6 mice and cultured in RPMI 1640 medium supplemented with GM-CSF,G-CSF,and IL-6 to induce MDSCs in vitro.PD-L1 expression level and ROS production level of induced MDSCs were detected by flow cytometry.CD8+T cells were enriched from the spleen by MACS with anti-CD8a-conjugated microbeads,labeled with Celltrace violet,and then co-cultured with MDSCs.After 72 h,proliferation was assessed by flow cytometry.Folate cycle-related metabolic enzymes in MDSCs were detected by real-time quantitative PCR.MDSCs were treated with folate cycle metabolic enzyme MTHFD2 inhibitor DS18561882(DS18)and folic acid antagonist Pemetrexed.ROS and mitoROS production in MDSCs were assessed by flow cytometry.CD8+T cells were enriched from the spleen by MACS with anti-CD8a-conjugated microbeads,labeled with Celltrace violet,and then co-cultured with Pemetrexed or DS18-treated MDSCs.After 72 h,proliferation was assessed by flow cytometry.Transcript levels of folate cycle-related metabolic enzymes in pemetrexed or DS18-treated MDSCs were detected by RNAseq.A subcutaneous tumor mouse model of colon cancer was established.From the tenth day post-implantation,tumor-bearing mice were intraperitoneally injected with Pemetrexed(200 mg/kg)and tumor size was recorded for tumor growth curve.On the fourteenth day,mice were sacrificed,and tumors were harvested.MC38 tumor-bearing mice were treated with isotype antibody,anti-CD8 monoclonal antibody(1 mg/kg,deplete CD8+T cells),Pemetrexed(200 mg/kg),and combination of Pemetrexed with anti-CD8 antibody.MC38 tumor-bearing mice were treated with isotype antibody,anti-Gr1 monoclonal antibody(1.25 mg/kg,clearing MDSCs),combination of Pemetrexed with anti-Gr1 antibody.On the tenth day after implantation,tumor-bearing mice were treated with Pemetrexed(50 mg/kg),anti-PD-1 monoclonal antibody(250 μg/kg),Pemetrexed,and combination of Pemetrexed with anti-PD-1 antibody.Results·Flow cytometry data showed that PD-L1 level and ROS production were increased in induced MDSCs,and CD8+T cell proliferation was also suppressed significantly.qPCR data revealed the expression of folate cycle-related metabolic enzymes MTHFD2 and others was increased in MDSCs.The accumulation of MDSCs was affected by DS18 or Pemetrexed,ROS production in MDSCs was reduced,and the immunosuppression of CD8+T cells was relieved.RNA-seq results showed that genes related to MDSCs differentiation,such as S100 calc-binding protein A8,and genes related to MDSCs inhibition,such as cytochrome b-245β chain,which is related to ROS production,were also down-regulated after treatment with two folic acid cycling inhibitors.Tumor growth was suppressed by Pemetrexed.Tumor progression was promoted by combination of Pemetrexed with anti-CD8 antibody,compared with Pemetrexed monotherapy.However,tumor growth delay was inhibited by combination of Pemetrexed and anti-CD8,compared with anti-CD8 monotherapy.Tumor growth delay was caused by MDSCs depletion.But tumor growth was promoted by combination of pemetrexed and anti-Gr1,compared with pemetrexed monotherapy.Tumor growth was restricted by combination of pemetrexed and anti-PD-1 antibody,compared with anti-PD-1 monotherapy.Conclusion·Pemetrexed relies on CD8+T cells for anti-tumor effects and further retards tumor growth by reprogramming MDSCs to an anti-tumor phenotype.Modulating MDSCs by targeting folate cycle could impair their immunosuppressive ability and enhance the efficacy of immune checkpoint blockade in cancer treatment.

Objective To explore the effects of different phenotypes macrophages(Mφs)on the proliferation,mi-gration and osteogenic differentiation of periodontal ligament stem cells(PDLSCs).Methods PDLSCs were isola-ted and cultured by tissue block method.Tohoku Hospital Pediatrics-1(THP-1)cell line was stimulated to activate into unpolarized Mφs(M0),then induced to polarize into type Ⅰ Mφs(M1)and type Ⅱ Mφs(M2).Quantitative real-time PCR(qPCR)detected the inflammatory factors tumor necrosis factor α(TNF-α),interleukin(IL)-1 β,IL-6,IL-10 and transforming growth factor-β(TGF-β)mRNA expression level.After collecting culture superna-tants with different phenotypes,PDLSCs were stimulated,native control(NC)group did not receive the culture su-pernatant of Mφs.The effects of PDLSCs proliferation were assessed via Methylthiazolyldiphenyl-tetrazolium bro-mide(MTT)assay,while scratch assays were employed to evaluate their migration.Western blot was utilized to analyze the protein expression of Runt-related transcription factor 2(RUNX2)and alkaline phosphatase(ALP).Additionally,Alizarin Red staining was performed to investigate the deposition of calcified nodules in PDLSCs.Re-sults qPCR showed the relative expression of TNF-α,IL-1 β and IL-6 in M1 Mφs were higher than those in M0 and M2 Mφs(P＜0.05),and the relative expression of IL-10 and TGF-β in M2 Mφs were higher than those in M0 and M1 Mφs(P＜0.05);Western blot showed the expression of RUNX2 and ALP proteins in PDLSCs in M0 and M2 groups was higher than those in the NC group(P＜0.05),Alizarin Red staining showed increased calcified nodule deposition in PDLSCs in M0,M1 and M2 groups compared to the NC group;MTT assay showed the prolifer-ation of PDLSCs in the M0 and M1 groups was suppressed compared to the NC group(P＜0.05);and scratch ex-periment showed the migratory capacity of PDLSCs in the M1 and M2 groups was stronger than that in the NC group.Conclusion M0 and M1 Mφs inhibit PDLSCs proliferation,M1 and M2 Mφs promote PDLSCs migration,and all types of Mφs promote osteogenic differentiation of PDLSCs.

Targeting multiple immune mechanisms may overcome therapy resistance and further improve cancer immunotherapy for humans. Here, we describe the application of virus-like vesicles (VLV) for delivery of three immunomodulators alone and in combination, as a promising approach for cancer immunotherapy. VLV vectors were designed to deliver single chain interleukin (IL)-12, short-hairpin RNA (shRNA) targeting programmed death ligand 1 (PD-L1), and a dominant-negative form of IL-17 receptor A (dn-IL17RA) as a single payload or as a combination payload. Intralesional delivery of the VLV vector expressing IL-12 alone, as well as the trivalent vector (designated CARG-2020) eradicated large established tumors. However, only CARG-2020 prevented tumor recurrence and provided long-term survival benefit to the tumor-bearing mice, indicating a benefit of the combined immunomodulation. The abscopal effects of CARG-2020 on the non-injected contralateral tumors, as well as protection from the tumor cell re-challenge, suggest immune-mediated mechanism of protection and establishment of immunological memory. Mechanistically, CARG-2020 potently activates Th1 immune mechanisms and inhibits expression of genes related to T cell exhaustion and cancer-promoting inflammation. The ability of CARG-2020 to prevent tumor recurrence and to provide survival benefit makes it a promising candidate for its development for human cancer immunotherapy.