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Objective: To explore the effects of sodium hyaluronate combined with Jintiange on knee joint function after arthroscopic debridement. Methods: Totally 122 knee osteoarthritis patients underwent arthroscopic debridement were randomized into control and experimental groups. The interleukin-1β, interleukin-6 and tumor necrosis factor-α serum levels were tested via Elisa before and after treatment. The Lysholm knee joint function score, effective rate of treatment, interleukin-1β, interleukin-6 and tumor necrosis factor-α expression, visual analogue scale of pain, incidence of adverse reactions and patient satisfaction were compared. Results: Compared with the control group, the effective rate of treatment and the score of Lysholm knee joint function in the other were higher (both P β, interleukin-6, tumor necrosis factor-α expression and visual analogue scale score were lower (all P P >0.05), but the satisfaction scores of the experimental group were higher (P Conclusion: sodium hyaluronate combined with Jintiange is helpful for knee joint function recovery after arthroscopic knee osteoarthritis, which effectively decreases the level of inflammatory factors and increase patients’ satisfaction.

Even with the in-depth implementation of forestry ecological projects, such as restoring farmland to forest (grass) in the loess area of northern Shaanxi, the characteristics of soil macrofauna communities and their coupling relationship with environmental factors after vegetation restoration in the study area are yet obscure. However, the soil macrofauna community characteristics are of great significance for evaluating the effectiveness of vegetation restoration in the study area. Therefore, the study aims to reveal the characteristics of the soil macrofauna community and their coupling relationships with the environment in the loess area of northern Shaanxi. In this study, all organisms of the five typical vegetation types in the study area were collected by manual sorting (Armeniaca sibirica and Populus simonii mixed forest (M), Robinia pseudoacacia (P), Populus simonii (S), Populus hopeiensis (H) and Hippophae rhamnoides (R)), and the adjacent abandoned grassland (G) was used as a control group. The group number and the individual number of soil macrofauna of different vegetation types in the study area and their coupling relationships with environmental factors are studied, and the following conclusions were drawn. (1) The study shows that there are certain differences in the environmental factors of different vegetation types in the study area, which include the significant differences in the alkaline nitrogen content of various vegetation types (p < 0.05). (2) The effects of different vegetation on soil macrofauna community were different. There were no significant differences in the soil macrofauna community structure between Armeniaca sibirica and Populus simonii mixed forest, Robinia pseudoacacia, Populus simonii and Populus hopeiensis, but there was a large difference from that of the abandoned grasslands. The community density of soil macrofauna in Armeniaca sibirica and Populus simonii mixed forest and Populus simonii were significantly higher than that in the abandoned grassland (p < 0.05), but the other indexes showed no significant differences. The Shannon–Wiener index of Robinia pseudoacacia and Populus hopeiensis were much lower than that of the abandoned grassland (p < 0.05). (3) The diversity of soil macrofauna communities was mainly affected by pH, alkaline nitrogen, potassium available, vegetation coverage and litter production. (4) Different groups of soil macrofauna were closely related and reacted differently to environmental factors, and vegetation coverage, litter production and alkaline nitrogen content were the key factors affecting the composition of soil macrofauna communities.

Background Osteoarthritis (OA) is a common joint disease, which is characterized by degradation of articular cartilage. Evidence indicated that miR-23b-3p was upregulated in cartilage tissues of a patient with OA. However, the mechanism by which miR-23b-3p regulates the occurrence and development of OA remains unclear. Thus, this study aimed to investigate the role of miR-23b-3p in the progression of OA. Methods In this study, qRT-PCR was used to measure the expression of miR-23b-3p in OA tissue samples and normal controls, respectively. Western blotting assay was performed to detect the levels of collagen II, aggrecan, Bax and active caspase 3 in CHON-001 cells. In addition, the dual-luciferase reporter system assay was used to detect the interaction between miR-23b-3p and COL11A2 in OA. Results The levels of miR-23b-3p were upregulated, while the expressions of collagen II and aggrecan were decreased in OA tissues and in IL-1β-treated CHON-001 cells. In addition, IL-1β significantly induced apoptosis of CHON-001 cells via increasing the levels of Bax and active caspase 3. However, downregulation of miR-23b-3p markedly inhibited IL-1β-induced apoptosis in CHON-001 cells via increasing the collagen II and aggrecan levels and decreasing Bax and active caspase 3 expressions. Meanwhile, dual-luciferase assay showed that COL11A2 was the direct target of miR-23b-3p in CHON-001 cells. Overexpression of miR-23b-3p markedly decreased the level of COL11A2 in cells. Moreover, downregulation of miR-23b-3p alleviated synovitis/cartilage destruction and reduced Osteoarthritis Research Society International scores and subchondral bone thickness in vivo. Conclusion Downregulation of miR-23b-3p could alleviate the progression of OA through upregulating COL11A2 in vivo and in vitro. Therefore, downregulation of miR-23b-3p might be a potential therapeutic strategy for the treatment of OA.

Background Osteoarthritis (OA) is a common joint disease, which is characterized by degradation of articular cartilage. Evidence indicated that miR-23b-3p was upregulated in cartilage tissues of a patient with OA. However, the mechanism by which miR-23b-3p regulates the occurrence and development of OA remains unclear. Thus, this study aimed to investigate the role of miR-23b-3p in the progression of OA. Methods In this study, qRT-PCR was used to measure the expression of miR-23b-3p in OA tissue samples and normal controls, respectively. Western blotting assay was performed to detect the levels of collagen II, aggrecan, Bax and active caspase 3 in CHON-001 cells. In addition, the dual-luciferase reporter system assay was used to detect the interaction between miR-23b-3p and COL11A2 in OA. Results The levels of miR-23b-3p were upregulated, while the expressions of collagen II and aggrecan were decreased in OA tissues and in IL-1β-treated CHON-001 cells. In addition, IL-1β significantly induced apoptosis of CHON-001 cells via increasing the levels of Bax and active caspase 3. However, downregulation of miR-23b-3p markedly inhibited IL-1β-induced apoptosis in CHON-001 cells via increasing the collagen II and aggrecan levels and decreasing Bax and active caspase 3 expressions. Meanwhile, dual-luciferase assay showed that COL11A2 was the direct target of miR-23b-3p in CHON-001 cells. Overexpression of miR-23b-3p markedly decreased the level of COL11A2 in cells. Moreover, downregulation of miR-23b-3p alleviated synovitis/cartilage destruction and reduced Osteoarthritis Research Society International scores and subchondral bone thickness in vivo. Conclusion Downregulation of miR-23b-3p could alleviate the progression of OA through upregulating COL11A2 in vivo and in vitro. Therefore, downregulation of miR-23b-3p might be a potential therapeutic strategy for the treatment of OA.

Osteoarthritis (OA) is the most common degenerative joint disease and results from progressive loss and destruction of articular cartilage and the underlying bone. The disease affects millions of people worldwide with an associated risk of mobility disability. However, the molecular basis underlying OA initiation and progression is not well understood and, currently, there is no effective intervention available to decelerate disease progression or restore degraded cartilage. We have found that lncRNA long intergenic nonprotein coding RNA 341 (LINC00341) is aberrantly downregulated in OA patient tissues and cultured OA chondrocytes. This is likely responsible for the increased apoptosis of chondrocytes and pathological destruction of cartilage. Further investigation has revealed that LINC00341 interacts with miR-141 to suppress its functional binding to the 3'-untranslated region of YY1-associated factor 2 (YAF2) messenger RNA. Aberrant downregulation of LINC00341 thus may ultimately lead to inhibition of the YAF2 protein, which has been implicated to be an antiapoptotic factor. Our study has revealed a new noncoding RNA-mediated regulatory network that highly likely protects chondrocytes by preventing apoptosis under normal conditions. The results will help further explore the molecular details pertaining to the progression of OA and stimulate efforts to develop effective therapies.

Systemic lupus erythematosus (SLE) is a severe autoimmune disorder, the pathogenesis of which remains largely unknown. The present study aimed to investigate the role and mechanism of circular RNAs in the etiopathogenesis of SLE. CD4+ T cells in patients with SLE expressed higher levels of hsa_circ_0010957 compared with healthy individuals and was a good differentiator of the active from inactive SLE disease. It was also determined that hsa_circ_0010957 mediated microRNA (miR)‑125b/STAT3 signaling and subsequent secretion of inflammatory cytokines interleukin (IL)‑18, IL‑6 and IL‑17, which are important factors in the process of SLE. Hsa_circ_0010957 abrogated the proinflammatory effect of IL‑6 via the blockade of STAT3 signaling. In conclusion, increased hsa_circ_0010957 may be involved in SLE pathogenesis via miR‑125b/STAT3 signaling. Hsa_circ_0010957 promises to be a potential biomarker and therapeutic target for SLE.

Forkhead box O1 (FOXO1) is a key regulator of osteogenesis. The aim of this study was to identify the mechanisms of microRNAs (miRNAs) targeting FOXO1 in osteogenic differentiation of human bone marrow mesenchymal stem cells (hMSCs). Three miRNA target prediction programs were used to search for potential miRNAs that target FOXO1. Quantitative real-time polymerase chain reaction was conducted to detect the expression of miR-1271-5p and FOXO1 during osteogenic differentiation. Target gene prediction and screening, luciferase reporter assay was used to verify the downstream target gene of miR-1271-5p. The expression levels of FOXO1 and Runx2 were detected by RT-qPCR and Western blot analysis. Alkaline phosphatase (ALP) activity and matrix mineralization were detected by biochemical methods. The expression levels of Runx2, ALP, and osteocalcin were detected by RT-qPCR. Our results showed that miR-1271-5p was downregulated during osteogenic induction. And the expression levels of miR-1271-5p were higher in osteoporotic tissues than that in adjacent nonosteoporotic tissues. The expression levels of FOXO1 were lower in osteoporotic tissues than that in adjacent nonosteoporotic tissues. And a negative correlation was found between miR-1271-5p and FOXO1 in osteoporotic tissues. Overexpression of miR-1271-5p downregulated FOXO1 and inhibited osteogenic differentiation in hMSCs. Overexpression of miR-1271-5p downregulated the expression of osteogenic markers and reduced ALP activity. In addition, ectopic expression of FOXO1 reversed the effect of miR-1271-5p on osteogenic differentiation. In conclusion, miR-1271-5p functioned as a therapeutic target of osteogenic differentiation in hMSCs by inhibiting FOXO1, which provides valuable insights into the use of miR-1271-5p as a target in the treatment of osteoporosis and other bone metabolic diseases.

Reasoning machine reading comprehension (R-MRC) aims to answer complex questions that require discrete reasoning based on text. To support discrete reasoning, evidence, typically the concise textual fragments that describe question-related facts, including topic entities and attribute values, are crucial clues from question to answer. However, previous end-to-end methods that achieve state-of-the-art performance rarely solve the problem by paying enough emphasis on the modeling of evidence, missing the opportunity to further improve the model’s reasoning ability for R-MRC. To alleviate the above issue, in this paper, we propose an Evidence-emphasized Discrete Reasoning approach (EviDR), in which sentence and clause level evidence is first detected based on distant supervision, and then used to drive a reasoning module implemented with a relational heterogeneous graph convolutional network to derive answers. Extensive experiments are conducted on DROP (discrete reasoning over paragraphs) dataset, and the results demonstrate the effectiveness of our proposed approach. In addition, qualitative analysis verifies the capability of the proposed evidence-emphasized discrete reasoning for R-MRC (Code is released at https://github.com/JD-AI-Research-NLP/EviDR).

Background Most of the studies assessing the corrective posterior total hip arthroplasty (THA) mainly focused on the mini-incision approach. Studies exploring the short external rotator sparing approach are rare. Therefore, this study aimed to compare the effectiveness of standard posterior approach and short external rotator sparing approach. Methods This prospective observational study included 126 patients who underwent THA in June 2017–June 2018. Patients were assigned to standard (standard posterior approach) and corrective (short external rotator sparing approach) groups based on the surgical method. Surgical data were recorded postoperatively. Postoperative hip joint recovery was assessed using the times to ambulation and independent stair use, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Harris score, and Oxford hip score (OHS) at 2 and 8 postoperative weeks. The visual analog scale (VAS) was used for postoperative pain assessment. Results Postoperative changes of creatine kinase (CK), myoglobin, CRP, and prosthesis position were similar in both groups (P > 0.05). However, intraoperative blood loss (P < 0.001) and postoperative 6-h drainage volume (P = 0.03), hospital stay, blood transfusion rate, and times to ambulation and independent stair use were significantly reduced in the corrective group. Postoperatively, Oxford, and WOMAC scores significantly decreased in both groups. After surgery, the VAS score was more overtly decreased in the corrective group compared with the standard group. Conclusions This study concluded that the less invasive short external rotator sparing approach for THA caused less damage, reducing perioperative blood loss, shortening functional recovery time, maintaining prosthesis stability, and improving postoperative pain.

Systemic lupus erythematosus (SLE) is a severe autoimmune disorder, the pathogenesis of which remains largely unknown. The present study aimed to investigate the role and mechanism of circular RNAs in the etiopathogenesis of SLE. CD4+ T cells in patients with SLE expressed higher levels of hsa_circ_0010957 compared with healthy individuals and was a good differentiator of the active from inactive SLE disease. It was also determined that hsa_circ_0010957 mediated microRNA (miR)-125b/STAT3 signaling and subsequent secretion of inflammatory cytokines interleukin (IL)-18, IL-6 and IL-17, which are important factors in the process of SLE. Hsa_circ_0010957 abrogated the proinflammatory effect of IL-6 via the blockade of STAT3 signaling. In conclusion, increased hsa_circ_0010957 may be involved in SLE pathogenesis via miR-125b/STAT3 signaling. Hsa_circ_0010957 promises to be a potential biomarker and therapeutic target for SLE.

OBJECTIVE The aim of the study was to explore the mechanism of excessive apoptosis of nucleus pulposus cells induced by short hairpin RNA (shRNA) Piezo type mechanosensitive ion channel component 1 (Piezo1) under abnormal mechanical stretch stress. METHODS In vitro mechanical stretch stress model of nucleus pulposus cells in vitro was established, in which the expression of Piezo1 was interfered by transfection of shRNA-Piezo1 interfering vector. Both messenger RNA and protein level of Piezo1 were measured by reverse-transcription polymerase chain reaction and Western blot analysis, respectively. Cytoplasmic Ca2+ was detected by Fluo3-AM kit, and changes of mitochondrial membrane potential in cells were detected using Cell Meter Assay kit. Finally, the apoptosis was evaluated with annexin V-fluorescein isothiocyanate kit. RESULTS The highest transfection efficiency of lentivirus titer was 1 × 10 TU/mL and the nucleus pulposus cells were transfected with plural multiplicity of infection = 50. Homo-3201 sequence exhibited the most effective silencing effect and was used in subsequent experiments as the default sequence of shRNA-Piezo1. The calcium content in the cytoplasm of the tension stress group increased significantly compared with that in the blank control group ( q = 3.773; P

Low levels of inflammation-induced expression of matrix metalloproteinase (MMP) play a crucial role in articular cartilage matrix destruction in osteoarthritis (OA) patients. Interferon regulatory factor-8 (IRF-8), an important member in the IRF family, plays a key role in regulating the inflammation-related signaling pathway. The aim of this study is to investigate the physiological roles of IRF-8 in the pathological progression of OA. We found that IRF-8 was expressed in human primary chondrocytes. Interestingly, the expression of IRF-8 was upregulated in OA chondrocytes. In addition, IRF-8 was increased in response to interleukin-1β (IL-1β) treatment, mediated by the Janus kinase 2 (JAK2) pathway. Overexpression of IRF-8 in human chondrocytes by transduction with lentiviral-IRF-8 exacerbated IL-1β-induced expression of matrix metalloproteinase-13 (MMP-13) in human chondrocytes. In contrast, knockdown of IRF-8 inhibited IL-1β-induced expression of MMP-13. Importantly, IRF-8 could bind to the promoter of MMP-13 and stimulate its activity. Additionally, overexpression of IRF-8 exacerbated IL-1β-induced degradation of type II collagen. However, silencing IRF-8 abrogated the degradation of type II collagen. Taken together, our findings identified a novel function of IRF-8 in regulating articular cartilage matrix destruction by promoting the expression of MMP-13.

Pluripotent stem cell (PSC) cultures form an integral part of biomedical and medical research due to their capacity to rapidly proliferate and differentiate into hundreds of highly specialized cell types. This makes them a highly useful tool in exploring human physiology and disease. Genomic editing of PSC cultures is an essential method of attaining answers to basic physiological functions, developing in vitro models of human disease, and exploring potential therapeutic strategies and the identification of drug targets. Achieving reliable and efficient genomic editing is an important aspect of using large-scale PSC cultures. The CRISPR/Cas9 genomic editing tool has facilitated highly efficient gene knockout, gene correction, or gene modifications through the design and use of single-guide RNAs which are delivered to the target DNA via Cas9. CRISPR/Cas9 modification of PSCs has furthered the understanding of basic physiology and has been utilized to develop in vitro disease models, to test therapeutic strategies, and to facilitate regenerative or tissue repair approaches. In this review, we discuss the benefits of the CRISPR/Cas9 system in large-scale PSC cultures.

Backgrounds Up-regulated HIF-2α (hypoxia induced factor 2) had been demonstrated to contribute to Osteoarthritis (OA) development via inducing the expression of matrix-degrading enzymes. However, the HIF-2α also could promote primary cilia loss through HIF-2α/AURKA (Aurora kinase A)/NEDD9 pathway. And the primary cilia dysfunction is another characteristic of the OA. Thus, we investigated here whether the HIF-2α also contributes the OA development through mediating the primary cilia loss. Methods The primary chondrocytes were isolated from the experimental OA mice induced by destabilization of the medial meniscus (DMM). Chondrocytes were cultured under normoxia (21% O2) or hypoxia (2% O2) conditions. The HIF-1α and HIF-2α expressions were assessed by western blot. The cilia formation was counted by immuno-staining the acetylated tubulin. The contribution of HIF-1α or HIF-2α to the primary cilia loss was assessed by knocking-down the HIF-1α or HIF-2α individually. The HIF-2α/AURKA/NEDD9 pathway was validated through over-expressing or knocking-down specific components of the pathway and then counting the primary cilia number. Finally, the pathway was further confirmed in the OA mice. Results Hypoxia could induce the expression of both HIF-1α and HIF-2α, and also reduce the number of primary cilia on the chondrocytes isolated from the experimental OA mice. Knocking-down or over-expressing HIF-1α or HIF-2α individually showed that the HIF-2α could induce the primary cilia reduction rather than the HIF-1α. Manipulating the HIF-2α expression could positively affect the AURKA and NEDD9 expression. Manipulating the AURKA and NEDD9 expressions could reverse the function of HIF-2α on primary cilia. In the mice, knocking-down both AURKA and NEDD9 could alleviate the OA development significantly. Conclusion Up-regulated HIF-2α contributes to the Osteoarthritis development through mediating the primary cilia loss, which might be developed as therapeutic targets for OA treatment.

A dual-channel supply chain system composed of one manufacturer and one retailer is considered in this paper, which existed uncertainty demands in both distribution channels and capital constraint on retailer. It set up the profit model of manufacturer dominated dual-channel supply chain system, studied to the optimal pricing and inventory strategies of decentralized and centralized supply chain, obtained the optimal pricing and inventory strategy of the two kinds of supply chain system. The analysis to the optimal solution indicated that the demand uncertainty of two distribution channels, deferred-payment rate etc, are all have certain influence relation on the pricing strategies of manufacturer and retailer. Numerical experiment has showed the effectiveness of the conclusions.

The effect of Lactobacillus pentosus strain S-PT84 (S-PT84) on postprandial hypertriacylglycerolemia was investigated in rats. S-PT84 dose-dependently inhibited the hydrolysis of triacylglycerols by pancreatic lipase in vitro. Intragastric administration of S-PT84 significantly reduced the lymphatic recovery of (3)H-trioleoylglycerol up to 8 h. The oral administration of a fat emulsion, with or without S-PT84, resulted in the concentration of plasma triacylglycerol 2 h and 3 h after administration being significantly lower in the S-PT84 group than in the group without S-PT84 (control group). These results suggest that S-PT84 alleviated postprandial hypertriacylglycerolemia by delaying triacylglycerol absorption in the intestine through the inhibition of pancreatic lipase.

The global robust exponential stability of interval complex-valued Cohen-Grossberg neural networks (CGNNs)with mixed delays and distributed delays are considered in this paper. Based on some mild assumptions, we prove the existence, uniqueness and exponential stability of the equilibrium point of the interval complex-valued CGNNs. We introduce two numerical examples in the end.

The avulsion fracture of the femoral attachment from the posterior cruciate ligament (PCL) is quite rare, particularly in adults. The patient we presented here was admitted to receive treatment in June 2017, whose knee injury resulted in avulsion fractures at three sites, the femoral attachment of the PCL, the tibial insertion of the anterior cruciate ligament (ACL), and the femoral attachment of the medial collateral ligament (MCL). We repaired PCL femoral attachment by arthroscopy and fixed MCL femoral insertion with cannulated screws.

By using an ELISA, increased levels of the soluble form (sgp130) of gp130, the IL-6 signal transducer, were detected in the sera of various HTLV-1-associated conditions (HC, ATL, HAM) as compared to normal healthy individuals. Sgp130 levels seemed to be correlated with disease severity. The 94 KD of sgp130 was specifically precipitated in the sera of HTLV-1-infected patients as revealed by Western blot analysis. A reverse transcriptase (RT)-polymerase chain reaction (PCR) method was used to detect the message for transmembrane (TM) lacking gp130 in mRNA isolated from peripheral blood mononuclear cells (PBMCs) of patients infected with or without HTLV-1 and those of various hematopoietic cell lines. Two PCR products, 648 and 507 bp were observed in the PBMCs from HTLV-1-infected patients. But the 507 by PCR product was not detected in the PBMCs from normal healthy individuals and HTLV-1-positive cell lines although the 648 bp product was equally expressed. A nucleotide sequence analysis of the 507 bp fragment showed deletion of the 141 bp at the region spanning from nucleotide 1702 (G) to 1842 (T) of the 648 bp product that matched completely with a conventional gp130 molecule. This deleted region was located upstream of the transmembrane (TM) domain, but not within the TM region itself. However, no frame shift was observed. These results indicate that the generation of sgp130 may not be due to an alternative splicing mechanism.

A polymerase chain reaction (PCR) method was used to detect the interleukin-2 receptor alpha-chain (IL-2R alpha) chain which lacks the conventional transmembrane (TM) domain in mRNA from human T-cell leukaemia virus type-I (HTLV-I)-infected cell lines or peripheral blood mononuclear cells (PBMC) isolated from adult T-cell leukaemia (ATL) patients. Primer pairs encompassing the TM domain were selected to generate a 357-base pair (bp) fragment. A 146-bp PCR product was observed consistently in addition to the target 357-bp PCR product in mRNA from HTLV-I-infected cell lines, such as MT-1, MT-2, MT-4 and in PBMC isolated from ATL patients. However, this 146-bp PCR product was undetectable in HTLV-I-negative cell lines. The product was also detected in PBMC from normal individuals if activated in vitro with phytohaemagglutinin but not without stimulation. DNA sequence analyses revealed that exons from 5 to 7, which define a 211-bp region containing the conventional TM domain, were deleted in the 146-bp PCR product. The C-terminal amino acid sequence starting from Gly174 of the 211-bp-deleted molecule was distinct from that of conventional IL-2R alpha as a result of an altered reading frame. We identified a 45000 MW peptide generated from IL-2R alpha mRNA through this exon skip in cell lysate of MT-1 and MT-2 by Western blot analyses using an antibody raised against the peptides specific to an altered IL-2R alpha. Our results indicate that an altered IL-2R alpha chain is expressed in HTLV-I-infected T lymphocytic cell lines and in ATL patients.