Objective:To find the age-related indicators of human immune function in the blood, to explore the possibility to standardize the evaluation criterion of immune function in Chinese population.Methods:The peripheral blood samples from 478 healthy individuals with complete medical data collected at the Beijing Hospital from January 2019 to December 2019, were chosen and analyzed.The volunteers were divided into young(<40 years old)and elderly(≥70 years old)groups.The differences in RNA, cytokines and immune cell function(the proliferation of T cell as well as the ability of T cells and natural killer cells to lyse target cells)were compared between the young group versus the elderly group.Results:Real-time quantitative fluorescence RT-PCR detection method was used for detecting the following tumor immune-related genes in the peripheral blood of healthy people in young versus old groups: programmed death 1( PD1)gene, complement C3 gene( C3), complement C4 gene( C4), high sensitivity C-reactive protein gene( HsCRP), tumor necrosis factor alpha gene( TNFA), interferon gamma gene( INF- γ), interleukin-6 gene( IL-6), interleukin-8 gene( IL-8), cytotoxic T lymphocyte-associated antigen-4 gene( CTLA-4), nuclear transcription factor-κB gene( NF- κB), long intergenic noncoding RNA-erythroid pro-survival gene( lincRNA- EPS), long non-coding RNA-myeloid RNA regulator of Bim-induced death gene( lncRNA- Morrbid), lincRNA-cyclooxygenase 2 gene( lincRNA- Cox2), Lnc-Dendritic cells( Lnc- DC), and circRNA-7 gene( ciRS-7). The mRNA level of C4 was significantly lower in elderly people than in young controls[young group(1.01±0.18) vs.old group(0.64±0.13), P=0.047], while others showing a non-statistically significant difference( P>0.05). The protein levels of programmed death 1(PD1), complement C3(C3), complement C4(C4), high sensitivity C-reactive protein(HsCRP), tumor necrosis factor alpha(TNF-α), interferon gamma(INF-γ), interleukin-6(IL-6), interleukin-8(IL-8), cytotoxic T lymphocyte-associated antigen-4(CTLA-4)and nuclear transcription factor-κB(NF-κB)in plasma were detected by enzyme-linked immunosorbent assay(ELISA). The following protein levels were significantly higher in the elderly group than in the young group: IL-6 protein[young group(249.30±100.02)ng/L vs.old group(283.00±94.98)ng/L, P=0.021], HsCRP protein[young group(2543.00±1111.89)ng/L vs.old group(3056.00±1056.61)ng/L, P=0.002], INF-γ protein[young group(362.40±383.67)ng/L vs.old group(500.40±502.27)ng/L, P=0.047]and TNF-α protein[young group(20.74±29.47)ng/L vs.old group(33.09±48.91)ng/L, P=0.042]. While the level of C4 was significantly lower in the elderly group than in the young group[young group(449.50±51.17)ng/L vs.old group(407.10±59.78)ng/L, P<0.0001]. T-cell proliferation, quantified by flow cytometry-based fluorescent dye dilution, showed that the CD3 + T cells of elder people had proliferated through 4 generations, while the CD3 + T cells of young people had proliferated through 5 generations.As shown in the NK killing assays, the secretion of LDH in the target A549 tumor cells decreased significantly after treated with NK cells belonging to elder individuals.The result demonstrated that individuals over 70 years old have significantly lower levels of the killing activity of NK cells( P<0.05). However, there was not statistically significant in T lymphocyte killing activity between different ages( P>0.05). Conclusions:IL-6, HsCRP, INF-γ and TNF-α levels are increased with aging, while the level of C4 significantly is decreased.The proliferation ability of T cells and the ability of NK cells to kill tumor cells are weakened.

Objective: To investigate the prevalence of dyslipidemia among adults in the southern mountains of Ningxia Hui Aulonomous Region. Methods: A cross-sectional study was conducted among a representative sample of 10 639 adults in the southern mountains using a population proportionate-sampling method in 2014. Questionnaires were completed and physical and laboratory examinations were performed. A total of 10 172 subjects were included in the analysis after excluding those with missing data. Dyslipidemia was diagnosed according to "Chinese guidelines for the prevention and treatment of dyslipidemia in adults" (2007). Results: The prevalence of dyslipidemia, hypercholesterolemia, hypertriglyceridemia, decreased high-density lipoprotein cholesterol (HDL-C), and increased low-density lipoprotein cholesterol (LDL-C) was 33.90%, 0.30%, 12.52%, 28.53%, and 1.14%, and the age-specific prevalence was 32.42%, 0.29%, 10.97%, 27.70%, and 1.07%, respectively. Borderline high triglycerides and borderline increased LDL-C were found in 13.09% and 6.52% of the study population, respectively. The rates of hypertriglyceridemia, decreased HDL-C, and dyslipidemia were higher in males than in females (P<0.05). The prevalence of dyslipidemia was higher in the group characterized by the risk factors of obesity, hypertension, diabetes, hyperuricemia, smoking, and drinking, compared to those without these factors (P<0.05). Conclusion The prevalence of dyslipidemia was higher in men than in women, and the differences were statistically significant. Hypertriglyceridemia and decreased HDL-C were the two major types of dyslipidemia. Obesity, hypertension, diabetes, hyperuricemia, smoking, and drinking alcohol increased the risk of dyslipidemia.

Conjunctival melanoma (CM) is a rare and fatal malignant eye tumor. In this study, we deciphered a novel anti-CM mechanism of a natural tetracyclic compound named as cucurbitacin B (CuB). We found that CuB remarkably inhibited the proliferation of CM cells including CM-AS16, CRMM1, CRMM2 and CM2005.1, without toxicity to normal cells. CuB can also induce CM cells G2/M cell cycle arrest. RNA-seq screening identified KIF20A, a key downstream effector of FOXM1 pathway, was abolished by CuB treatment. Further target identification by activity-based protein profiling chemoproteomic approach revealed that GRP78 is a potential target of CuB. Several lines of evidence demonstrated that CuB interacted with GRP78 and bound with a K _d value of 0.11 μmol/L. Furthermore, ATPase activity evaluation showed that CuB suppressed GRP78 both in human recombinant GRP78 protein and cellular lysates. Knockdown of the GRP78 gene significantly induced the downregulation of FOXM1 and related pathway proteins including KIF20A, underlying an interesting therapeutic perspective. Finally, CuB significantly inhibited tumor progression in NCG mice without causing obvious side effects in vivo. Taken together, our current work proved that GRP78-FOXM1-KIF20A as a promising pathway for CM therapy, and the traditional medicine CuB as a candidate drug to hinder this pathway.