CircORC2 promoted proliferation and inhibited the sensitivity of osteosarcoma cell lines to cisplatin by regulating the miR-485-3p/TRIM2 axis.

Resistance to chemotherapy leads to poor prognosis for osteosarcoma (OS) patients. However, due to the high metastasis of tumor and the decrease in sensitivity of tumor cells to cisplatin (DDP), the 5-year survival rate of OS patients is still unsatisfactory. This study explored a mechanism for improving the sensitivity of OS cells to DDP. A DDP-resistant OS cell model was established, and we have found that circORC2 and TRIM2 were upregulated in DDP-resistant OS cells, but miR-485-3p was downregulated. The cell viability and proliferation of the OS cells decreased gradually with the increase of DDP dose, but a gradual increase in apoptosis was noted. CircORC2 promoted OS cell proliferation and DDP resistance and upregulated TRIM2 expression by targeting miR-485-3p. Functionally, circORC2 downregulated miR-485-3p to promote OS cell proliferation and inhibit DDP sensitivity. Additionally, it promoted cell proliferation and inhibited the sensitivity of DDP by regulating the miR-485-3p/TRIM2 axis. In conclusion, circORC2 promoted cell proliferation and inhibited the DDP sensitivity in OS cells via the miR-485-3p/TRIM2 axis. These findings indicated the role of circORC2 in regulating the sensitivity of OS cells to DDP.

Candidate Marker Genes for Diagnosis of Osteoarthritis and Prediction of Their Regulatory Mechanisms.

We have screened candidate marker genes for the diagnosis of osteoarthritis and predicted their regulatory mechanisms. Six expression chips of tissue samples and one expression chip of peripheral blood mononuclear cell (PMBC) samples were obtained from the GEO database. Differential analysis, GSEA, and WGCNA were performed on the integra-ted tissue sample data with batch correction. Can-didate genes were obtained from the intersection of the genes significantly related to osteoarthritis in the WGCNA and the differentially expressed genes. ROC analysis was performed on the candidate genes in the tissue and PMBC samples. Genes with AUC values greater than 0.6 were retained as final candidates, and their upstream regulatory miRNAs were predicted. A total of 106 genes with differential expression were found in osteoarthritis tissue samples, which were mainly enriched in cell cycle and p53 signalling pathways. WGCNA selected a gene module significantly correlated with the occurrence of osteoarthritis. Fourteen candidate genes were obtained from the intersection of the genes in the module and the differentially expressed genes. ROC analysis showed that among these 14 candidate genes, only ADM, CX3CR1 and GADD45A had AUC values greater than 0.6 in both tissue and PMBC samples. The AUC values of the gene set of these three genes were greater than 0.7. Multiple miRNAs were predicted to be regulators of these three genes. ADM, CX3CR1 and GADD45A have potential as diagnostic marker genes for osteoarthritis and may be regulated by multiple miRNAs.

Development of submicron precision three-dimensional low cross-interference air-floating motion stage.

To meet the high requirements for positioning accuracy and multiple dimensions of positioning systems in the fields of precision measurement and precision machining, a new submicron-precision three-dimensional (3D) low cross-interference positioning system is designed and fabricated in this paper. The 3D motion stage mainly includes a mechanical structure, a support and guide system, and a driving system. The Abbe offset error is eliminated by adopting a coplanar structure in the X and Y directions, thus minimizing the mutual cross-interference of the motion stage. The X and Y motion stages are driven by a ball screw pair and an alternating current servo motor, which are supported and guided by an air-floating rail and slider. Moreover, the X and Y air-floating stages adopt a lateral structure and double rails, respectively. The Z-motion stage is directly driven by a high-precision piezoelectric motor. In addition, the system achieves high-precision motion by using the dual-loop control technology of secondary feedback combined with the high-resolution control characteristics of the servo motor. The performance of the positioning system is evaluated through a series of verification experiments. Results show that the stroke of the positioning system of the 3D air-floating motion stage can reach 100 × 100 × 100 mm3, and the repeated positioning accuracy is better than 0.41 µm (k = 2, k is defined by the International Organization for Standardization as the coverage factor). The maximum cross-interference of the X-stage is 180 nm, and the Y-stage reaches 320 nm when running with a full stroke of 100 mm in the Z-direction, demonstrating good repeatability, stable running, and high straightness. The submicron-precision 3D air-floating motion stage developed in this paper can be used as a suitable solution for coordinate measuring machines, microlithography, and micromachining applications when combined with an additional nanoprecision microstage.

Paeonol accelerates skin wound healing by regulating macrophage polarization and inflammation in diabetic rats.

Diabetic ulcer is usually seen in people with uncontrolled blood sugar. Reportedly, many factors such as impaired glucose metabolism, and macrovascular and microvascular diseases caused angiogenesis disorders and delayed the healing of diabetic ulcers, thus affecting the body's metabolism, nutrition, and immune function. This study aimed to explore the effect of paeonol on skin wound healing in diabetic rats and the related mechanism. A rat model of diabetic ulcer was established. High glucose-treated mouse skin fibroblasts were co-cultured with M1 or M2-polarized macrophages treated with or without paeonol. H&E and Masson staining were used to reveal inflammatory cell infiltration and collagen deposition, respectively. Immunohistochemistry visualized the expression of Ki67, CD31, and vascular endothelial growth factor (VEGF). Western blot was used to detect interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-4, IL-10, CD31, VEGFA, and collagen I/III. The expression of iNOS and arginase 1 was revealed by immunofluorescence staining. Paeonol treatment augmented collagen deposition and the expression of Ki67, CD31, VEGF, and macrophage M2 polarization markers (IL-4 and IL-10) and reduced wound area, inflammatory cell infiltration, and macrophage M1 polarization markers (IL-1ß and TNF-α) in the ulcerated area. In vitro, paeonol treatment promoted M2-polarization and repressed M1-polarization in macrophages, thereby improving the repair of cell damage induced by high glucose. Paeonol accelerates the healing of diabetic ulcers by promoting M2 macrophage polarization and inhibiting M1 macrophage polarization.

EGCG Restores Keratinocyte Autophagy to Promote Diabetic Wound Healing through the AMPK/ULK1 Pathway.

BACKGROUND: Delayed wound healing, a common problem in patients with diabetes mellitus (DM), is associated with impaired keratinocyte autophagy. Epigallocatechin gallate (EGCG), a catechin, has been proven to promote diabetic wound healing. This study aims to explore the therapeutic mechanism of EGCG on diabetic wound healing. METHODS: High glucose (HG)-induced keratinocytes and streptozotocin (STZ)-induced DM rats were prepared and intervened with EGCG to examine its therapeutic effects in in vivo and in vitro settings. The AMPK inhibitor, Compound C, was utilized to determine whether EGCG exerted its therapeutic effects through the AMPK/ULK1 pathway. RESULTS: In vitro, EGCG improved HG-induced autophagy impairment in keratinocytes by increasing LC3II/LC3I, Becline1, and ATG5 levels and decreasing p62 level. Mechanically, EGCG activated the AMPK/ULK1 pathway, thereby promoting keratinocyte autophagy through the phosphorylation of AMPK and ULK1. Notably, EGCG promoted the proliferation, migration, synthesis and release of C-C motif chemokine ligand 2 (CCL2) in HG-treated keratinocytes. Furthermore, EGCG indirectly promoted the activation of fibroblasts, as evidenced by increased alpha-smooth muscle actin (α-SMA) and Collagen I levels. In vivo, EGCG promoted wound healing in DM rats, primarily by reducing inflammatory infiltration and increasing granulation tissue to promote wound epithelialization. Besides, EGCG promoted ATG5, KRT10, KRT14, TGF-ß1, Collagen I, and α-SMA expressions in the neonatal epithelial tissues of DM rats. However, the use of Compound C reversed the effects of EGCG. CONCLUSIONS: These findings indicated that EGCG restored keratinocyte autophagy to promote diabetic wound healing through the AMPK/ULK1 pathway.

Health utility measurement for people living with HIV/AIDS under combined antiretroviral therapy: A comparison of EQ-5D-5L and SF-6D.

We compared the discriminative validity, agreement and sensitivity of EQ-5D-5L and SF-6D utility scores in people living with HIV/AIDS (PLWHIV). We conducted a cross-sectional survey among PLWHIV aged more than 18 years old in 9 municipalities in Yunnan Province, China. A convenience sample was enrolled. We administered the SF-12 and EQ-5D-5L to measure health-related quality of life. The utility index of the SF-6D was derived from the SF-12. We calculate correlation coefficients to evaluate the relationship and agreement of 2 instruments. To evaluate the homogeneity of the EQ-5D-5L and SF-6D, intraclass correlation coefficients, scatter plots, and Bland-Altman plots were computed and drawn. We also used receiver operating characteristic curves to compare the discriminative properties and sensitivity of the econometric index. A total of 1797 respondents, with a mean age of 45.6 ±â€…11.7 years, was interviewed. The distribution of EQ-5D-5L scores skewed towards full health with a skewness of -3.316. The overall correlation between EQ-5D-5L and SF-6D index scores was 0.46 (P < .001). The association of the 2 scales appeared stronger at the upper end. An intraclass correlation coefficient of 0.59 between the EQ-5D-5L and SF-6D meant a moderate correlation and indicated general agreement. The Bland-Altman plot displayed the same results as the scatter plot. The receiver operating characteristic curve showed that the AUC for the SF-6D was 0.776 (95% CI: 0.757, 0.796) and that for the EQ-5D-5L was 0.732 (95% CI: 0.712, 0.752) by the PCS-12, and it was 0.782 (95% CI: 0.763, 0.802) for the SF-6D and 0.690 (95% CI: 0.669, 0.711) for the EQ-5D-5L by the MCS-12. Our study demonstrated evidence of the performance of EQ-5D-5L and SF-6D index scores to measure health utility in people living with HIV/AIDS. There were significant differences in their performance. We preferred to apply the SF-6D to measure the health utility of PLWHIV during the combined antiretroviral therapy period. Our study has demonstrated evidence for instrument choice and preference measurements in PLWHIV under combined antiretroviral therapy.

The role of personality, social economic and prevention strategy effects on health-related quality of life among people living with HIV/AIDS.

BACKGROUND: HIV/AIDS has transformed into a chronic controllable but not yet curable infectious disease as other chronic diseases to some extent. The additional of so called fourth 90% that included the improved health-related quality of life (HRQoL) for people living with HIV (PLWHIV) required solutions beyond antiretroviral therapy and viral load suppression. This study will explore the role of personality, social economic and prevention strategy effection on HRQoL among people living with HIV/AIDS. METHODS: A cross-sectional study was conducted among PLWHIV aged more than 16 years old in the 10 municipalities in Yunnan Province, China from October 2019 to May 2020, enrolling total 1997 participants. Individual-level HRQoL data were measured by 12-item Short Form Health Survey (SF-12) and EuroQol Five Dimensions Questionnaire (EQ-5D-5L). We assembled municipal-level data about social economic from Yunnan Statistical Yearbook in 2020 and strategy practice information from the self-evaluation system. We used the principal component analysis to build the social economic and strategy effect on each area respectively and one-way ANOVA was used to perform univariate analysis to identify the predictors with significant differences. Finally we used multi-level model (MLM) to explore the personality, social economic and strategy effects in health-related quality of life among PLWHIV. RESULTS: The global score for quality of life measured using EQ-5D-5L had an estimated mean score (standard deviation, SD) of 0.901 ± 0.146. The HRQoL score measured using PCS-12 had an estimated mean score (SD) of 46.62 ± 8.55. The mean MCS-12 score (SD) was estimated to be 47.80 ± 9.71. The area-level predictors explained a proportion of 13.6-17.2% for the between-area variation of the HRQoL scores, regardless of the total HRQoL, physical component and mental component. The impacts of stigma (P < 0.01), social support (P < 0.001), anxiety (P < 0.001), depression (P < 0.05) and social economic status (P < 0.05) on HRQoL at the individual-level were significantly different. The plots visualized the impact of individual-level factors on a respondent's HRQoL was modified by the area-level characteristics. CONCLUSIONS: The study identified the possible strategy determinant of individual HRQoL of PLWHIV and also the area effect on HRQoL. Stigma, social support, anxiety, depression and social economic status were the individual-level determinants on HRQoL. These could be a valuable resource for evaluating the overall health of the areas and help improve local decision making.

[Change trend of HIV/AIDS related risk factors and influencing factors among men who have sex with men in Yunnan, 2010-2013].

OBJECTIVE: To understand the change trend of the awareness rate of HIV/AIDS related knowledge, risk behaviors among men who have sex with men (MSM) in Yunnan and the factors influencing their condom use, and evaluate the effect of comprehensive intervention. METHODS: The data about the MSM's demographic information, HIV/AIDS related knowledge awareness, and sex behavior, condom use, drug use and intervention receiving were obtained from AIDS sentinel surveillance among MSM in Yunnan province during 2010-2013 to conduct change trend and influencing factor analysis. RESULTS: A total of 9 073 MSM were surveyed. The awareness rate of the HIV/AIDS related knowledge, homosexual behavior and condom use rate increased year by year (P < 0.01). The condom use rate was lower in heterosexual behavior, and the drug use rate and sexually transmitted disease prevalence declined with year (P < 0.01). Multivariate logistic regression analysis indicated that cohabiting, low awareness of HIV/AIDS related knowledge, being from other provinces, local residence for <1 year, low education level, receiving no intervention, frequent anal sex and receiving no HIV/AIDS detection were the risk factors influencing persistent condom use among MSM. CONCLUSION: The effect of HIV/AIDS comprehensive intervention was observed after 4 years implantation, but most of the index were at low level. More attention should be paid to the intervention among MSM with cohabiting habit, low education level, frequent anal sex, and heterosexual sex. It is necessary to expand intervention coverage, strengthen HIV test and promote condom use among MSM.

[An analysis of high risk behaviors among female sex workers in Yunnan province in 2013].

OBJECTIVE: To understand the high risk behaviors of female sex workers (FSWs) in Yunnan province in 2013. METHODS: A cross-sectional investigation was conducted during April to June, 2013 in Yunnan province, census was used to the investigation where the number of FSWs was close to 200, while probability sampling was used where the number of FSWs was obviously over 200. A total of 25 574 cases were investigated, and data on demography and risk behaviors were obtained by questionnaires one by one. RESULTS: A total of 25 574 cases were investigated, AIDS awareness among FSWs in high-level places, middle-level places and low-level place were 98.8% (92/7 401), 98.6% (150/10 995), and 96.0% (281/6 655). FSWs from low-level place had a lower rate than those from the other two types of places (P < 0.01). The rate of condom use each time when having sex with clients within the recent one month among FESs from high-level places, middle-level places and low-level place were 93.4% (6 307/6 755), 93.8% (10 109/10 782) and 90.4% (6 053/6 697), and the FSWs working in low-level place had a lower rate than those from the other two types of places(P < 0.01). Multi-factor logistic regression analysis showed that the following had a lower rate of condom use: the FSWs working in low-level place (OR = 1.56, 95% CI:1.36-1.79; OR = 1.36, 1.16-1.59), over 30 years old (OR = 0.77, 95%CI:0.69-0.85), Yunnan citizen (OR = 0.88, 95% CI:0.77-1.00), minority (OR = 1.32, 95% CI:1.16-1.50), under senior high school (OR = 0.61, 95%CI:0.49-0.75), married (OR = 0.81, 95% CI:0.71-0.92), living together (OR = 0.70, 95% CI:0.51-0.96), divorced or lost spouses (OR = 0.81, 95% CI:0.65-1.02), worked less than 6 months in local areas (OR = 1.74, 95% CI:1.34-2.27), drug users (OR = 1.65, 95% CI:1.11-2.46), had not accepted HIV interventions (OR = 2.91, 95% CI:2.36-3.58), had no knowledge about AIDS (OR = 4.50, 95% CI:3.48-5.82). The main reasons for not using condoms were the clients' unwilling to use, which accounted for 47.62% (270/567). The total rate of drug use was 1.0% (264/25 567) and the FSWs working in middle-level places had the highest rate of injecting drugs, which accounted for 0.6% (70/11 141). The FSWs working in low-level places had a higher rate than those who worked in high-level places and middle-level places in venereal diseases, which accounted for 1.2% (85/6 934) (P < 0.01). The rate of receiving effective interventions was 96.7% (24 717/25 574), the rate of accepting treatment and clean needles among drug users was 21.6% (57/264). CONCLUSION: High risk behaviors were serious among the FSWs who worked in low-level places, especially among the olders, the minorities, people who had lower educational level, the new-comer and drug users, which indicated that more attention needs to be paid among these populations.