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Background. Osteosarcoma (OS) is a rare form of malignant bone cancer that is usually detected in young adults and adolescents. This disease shows a poor prognosis owing to its metastatic status and resistance to chemotherapy. Hence, it is necessary to design a risk model that can successfully forecast the OS prognosis in patients. Methods. The researchers retrieved the RNA sequencing data and follow-up clinical data related to OS patients from the TARGET and GEO databases, respectively. The coxph function in R software was used for carrying out the Univariate Cox regression analysis for deriving the aging-based genes related sto the OS prognosis. The researchers conducted consistency clustering using the ConcensusClusterPlus R package. The R software package ESTIMATE, MCPcounter, and GSVA packages were used for assessing the immune scores of various subtypes using the ssGSEA technique, respectively. The Univariate Cox and Lasso regression analyses were used for screening and developing a risk model. The ROC curves were constructed, using the pROC package. The performance of their developed risk model and designed survival curve was conducted, with the help of the Survminer package. Results. The OS patients were classified into 2 categories, as per the aging-related genes. The results revealed that the Cluster 1 patients showed a better prognosis than the Cluster 2 patients. Both clusters showed different immune microenvironments. Additional screening of the prognosis-associated genes revealed the presence of 5 genes, i.e., ERCC4, GPX4, EPS8, TERT, and STAT5A, and these data were used for developing the risk model. This risk model categorized the training set samples into the high- and low-risk groups. The patients classified into the high-risk group showed a poor OS prognosis compared to the low-risk patients. The researchers verified the reliability and robustness of the designed 5-gene signature using the internal and external datasets. This risk model was able to effectively predict the prognosis even in the samples having differing clinical features. Compared with other models, the 5- gene model performs better in predicting the risk of osteosarcoma. Conclusion. The 5-gene signature developed by the researchers in this study could be effectively used for forecasting the OS prognosis in patients.

Rheumatoid arthritis (RA) is a great concern across the globe. It is characterized as an autoimmune disease, where the body's immune system mistakenly attacks bone joints causing them to erode which leads to deformity in structure. Thus, the present study was conducted to elucidate the effect of Lidang Tang (LDT) decoction, a traditional Chinese medicine against rheumatoid arthritis. The rheumatoid arthritis was induced in Sprague-Dawley albino rats by intradermal injection of bovine collagen II type at the tail. Results suggested that LDT reduces paw swelling and arthritic scores in rats. The protective effect of LDT against RA was further substantiated by histopathological analysis of synovial tissue of rats, where LDT improves the architecture of the tissues as compared to CIA rats. It also reduces oxidative stress and inflammation in CIA rats as compared to the disease model group. The serum level of anti-collagen II-specific immunoglobulins (IgG1 and IgG2a) was reduced significantly in LDT treated group. In a western blot analysis, LDT treated group showed a significant reduction in the expression of NF-ĸB and COX-2 as compared to CIA rats. Collectively, our study for the first time demonstrated the protective effect of Lidang Tang decoction against rheumatoid arthritis.

It is known that the circular RNA (circRNA) molecule circRIMS is overexpressed in gastric cancer and plays an oncogenic role. However, its role in other cancers is unknown. In this study, we analyzed its role in endometrial cancer (EC). EC and paired non-tumor tissue samples were collected from a total of 63 EC patients and subjected to total RNA isolations and reverse transcription quantitative polymerase chain reaction (RT-qPCR) to analyze the differential expression of circRIMS and miR-505. Overexpression of circRIMS and miR-505 was reached in EC cells and their interaction was analyzed using RT-qPCRs. The role of circRIMS in regulating miR-505 methylation was analyzed by methylation-specific RT-qPCR. Bromodeoxyuridine (BrdU) assay was performed to analyze the roles of circRIMS and miR-505 in regulating cell proliferation. circRIMS was upregulated in EC, while miR-505 was downregulated in EC. circRIMS and miR-505 were inversely correlated across both EC and non-tumor tissues. In EC cells, circRIMS overexpression decreased miR-505 expression and increased miR-505 gene methylation. BrdU assay showed that circRIMS overexpression increased cell proliferation and reduced the inhibitory effects of miR-505 overexpression on cell proliferation. circRIMS may downregulate miR-505 through methylation to increase cell proliferation.

Spinal cord injury (SCI) is a common disease in spinal surgery. SCI affects the metabolism of patients and changes their lifestyle. Nutritional problems may occur, which may be manifested as insufficient or overnutrition. Nutrition status is related to many complications and final outcome after SCI. In this paper, the nutritional status of patients with SCI and the progress of nutritional intervention were reviewed by comprehensive domestic and foreign literature. Medical staff should routinely screen and evaluate the nutrition of patients after SCI operation, and provide comprehensive nutritional intervention such as diet, exercise and dietary supplement.

Objective: To observe therapeutic effect of sodium aescinate Tablets on knee osteoarthritis complicated with synovitis. Methods: 86 patients with knee osteoarthritis combined with synovitis treated in the Honghui Hospital Affiliated to Xi’an Jiaotong University from January 2018 to December 2019 were randomly divided into control group and intervention group, with 43 cases in each group. The control group was given routine treatment, and the intervention group was given sodium aescinate Tablets orally on the basis of routine treatment, twice a day, 2 tablets each time. The curative effect was evaluated after 2 weeks of treatment. The knee pain and joint function of the two groups were evaluated by Visual Analogue Scale (VAS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC), and the clinical effects of the two groups were compared. Results: Before treatment, there was no significant difference in general information, VAS and WOMAC scores between the two groups (P > 0.05). After treatment, the VAS and WOMAC scores of the two groups were both lower than those before treatment, and the difference was statistically significant (P < 0.05). The vas and WOMAC scores of the intervention group were lower than those of the control group (VAS, 1.87 ± 0.79 vs 3.38 ± 0.81. In this study, sodium aescinate tablets were applied to the treatment of KOA combined with synovitis. The results showed that the intervention group was better than the control group in alleviating knee pain, improving joint function and improving clinical efficacy, and the difference was statistically significant. The total effective rate of the intervention group was higher than that of the control group (100% vs 86.05%), and the difference was statistically significant (P < 0.05). Conclusion: Sodium aescinate tablet in the treatment of knee osteoarthritis combined with synovitis can effectively alleviate knee pain, improve joint function and improve clinical efficacy.

Rheumatoid arthritis (RA) is categorized as an autoimmune disease that leads to bone or joint deformity due to altered immune response. Studies have concluded the role of inflammation and oxidative stress in the progression of RA and agents inhibiting these processes showed benificial effect against the disease. Xuebijing (XBJ) injection is an intravenous patent preparation made from five-traditional Chinese medicines. Previous studies showed its excellent pharmacological activities, such as against sepsis, inflammation, and oxidative stress which has encouraged us to investigate the protective effect of XBJ against rheumatoid arthritis cell line (MH7A). For this purpose, the effect of XBJ was quantified on several parameters on the human synovial MH7A cell line activated with tumor necrosis factor-α (TNF-α). The results of the study showed that the level of tested interleukines (IL- 1β, IL- 6, IL- 8) and collagenases 1, and 13, and matrix metallo-proteinases 1, and 13 (MMP-1, and MMP-13) were found significantly reduced in XBJ treated group as compared to TNF-α treated MH7A cells. The XBJ treated group showed reduction in mRNA protein expression of COX-2 and iNOS in RT-qPCR assay. The rate of cellular apoptosis was found increased in XBJ treated group with reduction of cell viability of MH7A cells. The XBJ also showed attenuation of the expression of p-MEK/1/2 and p-p65 in MH7A cells in a western blot analysis. Our results demonstrated that XBJ significantly inhibits the inflammatory response, prevents cell viability, and induces apoptosis in human RA synovial cells by preventing the activation of the MEK/NF-κB pathway.

Osteoarthritis (OA) is a common degenerative joint disease in the elderly. This study aimed to investigate the role and mechanism of lncRNA HOX transcript antisense RNA (HOTAIR) in lipopolysaccharide (LPS)-treated chondrocytes in OA. CHON-001 chondrocytes treated with LPS were used as a cell model of OA. The levels of HOTAIR, miR-1277-5p and small glutamine rich tetratricopeptide repeat containing beta (SGTB) were measured via quantitative real-time polymerase chain reaction or western blot. Cell viability and apoptosis were assessed using Cell Counting Kit-8 and flow cytometry. The levels of inflammation-related factors were examined via enzyme-linked immunosorbent assay (ELISA). Aggrecan and Collagen II protein levels were detected using western blot. The interaction among HOTAIR, miR-1277-5p and SGTB were validated by dual-luciferase reporter analysis. HOTAIR and SGTB were up-regulated, while miR-1277-5p was down-regulated in OA cartilages and LPS-stimulated CHON-001 chondrocytes. HOTAIR depletion inhibited LPS-induced apoptosis and inflammation in chondrocytes. Moreover, down-regulation of HOTAIR attenuated LPS-triggered chondrocyte apoptosis and inflammation via sponging miR-1277-5p. Also, miR-1277-5p repressed LPS-induced chondrocyte apoptosis and inflammation by targeting SGTB. Furthermore, HOTAIR enhanced SGTB expression by sponging miR-1277-5p. HOTAIR aggravated chondrocyte apoptosis and inflammation in OA via regulating miR-1277-5p/SGTB pathway.

Objective. This research aims to investigate and analyze the impact of alendronate sodium (ALN) plus elcatonin (EC) in treating postoperative bone pain (BP) in patients with osteoporotic fractures (OPFs). Methods. One hundred and thirty-eight cases of OPFs admitted between July 2018 and July 2021 were selected, of which 68 cases receiving ALN were set as the control group and 70 cases receiving ALN plus EC were set as the research group. Intercomparisons were performed in terms of BP, curative effect, complication rate, and serum bone metabolism indexes such as bone Gla protein (BGP), parathyroid hormone (PTH), and bone alkaline phosphatase (BALP). Results. Better postoperative BP relief, higher overall response rate, and lower complication rate were identified in the research group versus the control group. On the other hand, the research group presented with increased BGP and BALP after treatment, higher than those in the control group, while the posttreament PTH decreased obviously and was lower versus the control group.Conclusions. For OPF patients, ALN plus EC contributes to significantly reduced postoperative BP, improved clinical efficacy, higher treatment safety, and better bone metabolism, which has high clinical application value.

Aβ aggregation is one of the pathological biomarkers of Alzheimer's disease (AD). However, the possible mechanism related to Aβ-induced pathological signaling pathway is still unknown. In the present study, Aβ1-42-induced time-dependent memory impairment and its possible relationship to hypothalamic-pituitary-adrenal (HPA) axis hyperactivity were examined. Aβ1-42-treated mice significantly impaired acquisition activity in the learning curve at 10 days, 1 and 4 months in the Morris water-maze (MWM) task. This learning activity was back to normal at 8 months after Aβ1-42 treatment. In the probe trial test, Aβ1-42-treated mice needed longer latencies to touch the precious platform location and fewer numbers of crossing from 10 days to 4 months after microinjection. This Aβ1-42 induced memory loss was consistent with the results of the step-down passive avoidance test. The HPA axis related parameters, such as corticosterone (CORT) level in the serum, glucocorticoid receptor (GR) and corticotropin-releasing factor receptor (CRF-R) expression in the frontal cortex and hippocampus increased in Aβ1-42-treated mice from 10 days to 4 months. While the downstream molecules phosphorylation of cyclic AMP response element binding (pCREB) and brain-derived neurotrophic factor (BDNF) expression decreased during this time. These effects were back to normal 8 months after treatment with Aβ1-42. Altogether, our results suggested that Aβ1-42 induced significant learning and memory impairment, which is involved in HPA axis dysfunction.

Aim Osteoarthritis (OA) is a chronic degenerative joint disease. Early studies have indicated that genetic and environmental factors contribute to the risk of OA. However, the etiology of OA remains unknown. Our study aimed to evaluate the association of DNMT3B gene with the risk of hip OA in Han Chinese individuals. Methods A total of 2070 subjects were recruited into the study, including 658 patients with hip OA and 1412 healthy controls. Twelve tag single nucleotide polymorphisms (SNPs) were selected and genotyped in our samples. Genetic associations between DNMT3B gene and the risk of hip OA were examined at both the single marker and haplotype levels. Cis-expression quantitative trait loci signals that achieve genome-wide significance of targeted SNPs from multiple types of human tissues were extracted from the GTEx database. Results Significant signals were identified for SNP rs2424905 in 4 genetic models. The T allele was significantly associated with an increased risk of hip OA (odds ratio = 1.53; 95% CI = 1.28-1.83). The T allele was also significantly associated with higher Kellgren-Lawrence grade in the patients with hip OA (χ2 = 32.70, P = 1.37 × 10-6 ). Moreover, SNP rs2424905 was significantly associated with the gene expression level of multiple genes, including DNMT3B, C20orf203, COMMD7, EFCAB8, MAPRE1, and RP5-1085F17.3, from several types of human tissues. Conclusion Our results indicated that rs2424905 of DNMT3B gene contributed to the risk of hip OA and its clinical severity in a Han Chinese population. These findings suggested that rs2424905 of DNMT3B could be a promising genetic marker to assess susceptibility to hip OA in Han Chinese populations.

In order to achieve the output of high-value patents, enterprises need to consider improving the technical level of the technical solution itself. At this point, it is necessary to compare the technical scheme with the existing patented technology to determine the advanced degree of the technical scheme. The ideal level is the ratio of the useful function to the harmful function in the technical solution, which can be used to describe the current technical level of the technical solution. In this study, idealization level is used to evaluate the gap between technology and existing patented technology. The patent information is different from the technical solution with complete information, and the existing technology described in the patent has a specific form of expression. Therefore, the main task is to evaluate the idealization level of the existing technology. It mainly includes three stages: shallow information analysis, deep information analysis and information reasoning and calculation. Automatic extraction of Chinese patent information is the basis for evaluating the technical advancement. This paper introduces in detail the automatic establishment process of component hierarchy model (CHM) and action and attribute model (AAM) of Chinese patent in the process of deep information analysis. The feasibility of the proposed method is verified by the analysis of shallow and deep information of electric toothbrush.

Alzheimer's disease (AD) is one of the neurodegenerative brain disorders inducing nearly half of dementia cases, and the diagnosis and treatment of AD are the primary issues clinically. However, there is a lack of effective biomarkers and drugs for AD diagnosis and therapeutics so far. In this study, bioinformatics analysis combined with an experimental verification strategy was used to identify the biomarkers and the quercetin targets for AD diagnosis and treatment. First, differentially expressed genes in the AD brain were identified by microarray data analysis. Second, quercetin, a predominant flavonoid, was used to screen the target genes. Third, the drug-disease network was determined, and the target genes of quercetin treatment were obtained in AD-related HT-22 cell-based assay. Six genes, including MAPT, PIK3R1, CASP8, DAPK1, MAPK1, and CYCS, were validated by the system pharmacology analysis in the hippocampus samples of AD patients. The results suggested that MAPT, PIK3R1, CASP8, and DAPK1 were significantly increased, but MAPK1 and CYCS were significantly decreased in HT-22 cells after Aβ1-42 treatment. Moreover, MAPK1 and CYCS were markedly increased, but MAPT, PIK3R1, CASP8, and DAPK1 were markedly decreased after quercetin treatment in these HT-22 cells. Altogether, MAPT, PIK3R1, CASP8, DAPK1, MAPK1, and CYCS are all the biomarkers for AD diagnosis and the targets of quercetin treatment, and our findings may provide valuable biomarkers for AD diagnosis and treatment.

Background Major depressive disorder (MDD) is a severe mental disorder related to the deficiency of monoamine neurotransmitters, particularly to abnormalities of 5-HT (5-hydroxytryptamine, serotonin) and its receptors. Our previous study suggested that acute treatment with a novel curcumin derivative J147 exhibited antidepressant-like effects by increasing brain derived neurotrophic factor (BDNF) level in the hippocampus of mice. The present study expanded upon our previous findings and investigated the antidepressant-like effects of sub-acute treatment of J147 for 3 days in male ICR mice and its possible relevancy to 5-HT1A and 5-HT1B receptors and downstream cAMP-BDNF signaling. Methods J147 at doses of 1, 3, and 9 mg/kg (via gavage) was administered for 3 days, and the anti-immobility time in the forced swimming and tail suspension tests (FST and TST) was recorded. The radioligand binding assay was used to determine the affinity of J147 to 5-HT1A and 5-HT1B receptor. Moreover, 5-HT1A or 5-HT1B agonist or its antagonist was used to determine which 5-HT receptor subtype is involved in the antidepressant-like effects of J147. The downstream signaling molecules such as cAMP, PKA, pCREB, and BDNF were also measured to determine the mechanism of action. Results The results demonstrated that sub-acute treatment of J147 remarkably decreased the immobility time in both the FST and TST in a dose-dependent manner. J147 displayed high affinity in vitro to 5-HT1A receptor prepared from mice cortical tissue and was less potent at 5-HT1B receptor. These effects of J147 were blocked by pretreatment with a 5-HT1A antagonist NAD-299 and enhanced by a 5-HT1A agonist 8-OH-DPAT. However, 5-HT1B receptor antagonist NAS-181 did not appreciably alter the effects of J147 on depression-like behaviors. Moreover, pretreatment with NAD-299 blocked J147-induced increases in cAMP, PKA, pCREB, and BDNF expression in the hippocampus, while 8-OH-DPAT enhanced the effects of J147 on these proteins’ expression. Conclusion The results suggest that J147 induces rapid antidepressant-like effects during a 3-day treatment period without inducing drug tolerance. These effects might be mediated by 5-HT1A-dependent cAMP/PKA/pCREB/BDNF signaling.

To evaluate the effect and safety of Zuogui pill and Yougui pill, classic Yin and Yang tonic formula (CYYTF), in the treatment of osteoporosis and the underlying mechanism.Participants aged 55 to 75 with osteoporosis and Kidney deficiency in Traditional Chinese Medicine (TCM) will be included and randomly allocated into two groups: treatment group and control group. Participants in the treatment group were treated with Zuogui pill or Yougui pill TCM formula granule, while the control group received placebo. Primary outcomes are the lumbar spine on bone mineral density (BMD) (L1-4) and femoral BMD. Secondary outcomes include pain intensity, health-related quality of life (HRQoL), bone turnover markers and safety.Totally 200 patients were enrolled from December 2014 to April 2016 from four hospitals. There were no statistically significant differences between the two groups at baseline (P0.05) and it was good to comparability. Statistically significant differences between the two groups were observed for the lumbar BMD (L1-4), pain VAS scores and HRQoL at six months and twelve months and femoral BMD at twelve months (P0.05), but no significant differences for femoral BMD and bone turnover markers at six months (P0.05). Moreover, significant difference was observed at different time before and after treatment in terms of lumbar spine (L1-4) BMD, femoral BMD, pain VAS scores and health-related quality of life, and there was an crossover effect between the time and groups before and after treatment. In additional, in the treatment group, 8 patients lost to follow-up and 3 patients had adverse events (AEs) and in the control group, 10 patients lost to follow-up and 2 patients had AEs. No remarkable differences were observed between the two groups with regard to AEs, lost rate and safety (P0.05).Zuogui pill or Yougui pill could improve BMD, ease pain, relieve Kidney deficiency syndrome, improve the quality of life osteoporosis patients, inhibit bone conversion and regulate the coupling balance of bone formation and bone resorption, but long-term efficacy should be confirmed by a longer term follow-up and larger of samples clinical randomized controlled trials.

Radical innovations (RIs) bring dramatic progress of existing technologies. Although the QFD (Quality function deployment) and TRIZ (Theory of innovation problem solving) integration provides a framework of innovation activities, it is a challenge to effectively use this framework for RIs. QFD is extended into two phases including a product House of quality (HoQ) and a design HoQ in this research to support design decisions for RIs. Based on HoQs, TRIZ-based methods of the function decomposition and performance analysis are developed in product HoQ to identify performance features of RIs. TRIZ tools including 76 standard solutions and trimming strategies are applied in design HoQ to decide product specifications for a systematic approach of RIs. The proposed approach is applied in the design of a wind power system. The feasibility and effectiveness of the method are proved.

The development of the Industry 4.0 paradigm and the advancement of information technology have aroused new consumer requirements for smart products that are capable of context awareness and autonomous control. Nature holds huge potential for inspiring innovative design concepts that can meet the ever-growing need for smart products since biology perceive and interact with their living environment for survival. However, to date, very few studies have explored the application of natural wisdom in building innovative design concepts for smart products. This paper proposes a function-oriented design approach for smart products, by analogizing to biological prototypes. To do so, a unified functional representation, based on the Function–behavior–structure (FBS) ontology, is proposed to abstract biological prototypes, followed by a fuzzy triangular numbers-based algorithm designed to locate appropriate biological prototypes as analogical sources for smart product development. Moreover, functional innovative strategies and a hybrid design process are formulated to develop design concepts of smart products, by integrating several existing engineering design methods. Finally, an illustrative design case of a smart natural resource collecting system is used to demonstrate the workability of the proposed method.

Phosphodiesterase 2 is one of the phosphodiesterase (PDEs) family members that regulate cyclic nucleotide (namely cAMP and cGMP) concentrations. The present study determined whether PDE2 inhibition could rescue post-traumatic stress disorder (PTSD)-like symptoms. Mice were subjected to single prolonged stress (SPS) and treated with selective PDE2 inhibitor Bay 60–7550 (0.3, 1, or 3 mg/kg, i.p.). The behavioral tests such as forced swimming, sucrose preference test, open field, elevated plus maze, and contextual fear paradigm were conducted to determine the effects of Bay 60–7550 on SPS-induced depression- and anxiety-like behavior and fear memory deficits. The results suggested that Bay 60–7550 reversed SPS-induced depression- and anxiety-like behavior and fear memory deficits. Moreover, Bay 60–7550 prevented SPS-induced changes in the adrenal gland index, synaptic proteins synaptophysin and PSD95 expression, PKA, PKG, pCREB, and BDNF levels in the hippocampus and amygdala. These effects were completely prevented by PKG inhibitor KT5823. While PKA inhibitor H89 also prevented Bay 60-7550-induced pCREB and BDNF expression, but only partially prevented the effects on PSD95 expression in the hippocampus. These findings suggest that Bay 60–7550 protects mice against PTSD-like stress induced traumatic injury by activation of cGMP- or cAMP-related neuroprotective molecules, such as synaptic proteins, pCREB and BDNF.

Innovation activities are required for industry to develop competitive products in response to rapid changes of the market. Radical innovation (RI) enables products long-term technical advantages and market competitiveness. However, the existing RI research focuses on areas of the business and management. There is a lack of an effective method of RI for product development. This paper proposes a systematic effect solving method (ESM) for radical innovation of product design. The ESM includes the problem identification, function analysis, key problem determination, effect selection, structure mapping and scheme evaluation. The proposed method can not only improve the possibility of developing RI products, but also save time in design. The method is applied to develop a new type of wind turbines with a granted patent. Feasibility and effectiveness of the proposed method is proved.

Rationale: Owing to the unique structure and function of the heart, tumor metastasis in the heart is rare. Accordingly, no unique symptoms have yet been identified for cardiac metastasis. Patient and concerns: A patient presented with cardiac metastasis 3 years after surgical resection of alveolar soft tissue sarcomas in their late stage. Diagnosis: Ultrasonography showed a middle-high echo clump on the left surface of the mid-upper interventricular septum, which had an unclear boundary with the myocardium. Meanwhile, blood flow was found in the clump, with no blockage of blood flow having been observed. Lessons: Although cardiac metastasis in terminal cancer patients always carries a poor prognosis, there is still no effective treatment for cardiac metastasis. In the clinic, it is important to improve the patient's quality of life, reduce symptoms and signs, and extend the duration of survival.