Adipose-derived stromal vascular fraction injection following core decompression and biochemistry artificial bone graft implantation in osteonecrosis of the femoral head.

PURPOSE: To determine how adipose-derived stromal vascular fraction (SVF) injection following core decompression (CD) and biochemistry artificial bone graft implantation affects outcomes in patients with osteonecrosis of the femoral head (ONFH). METHODS: A total of 19 patients (28 hips) with stage I-IIIA ONFH received adipose-derived SVF injection and combined core decompression and biochemistry artificial bone graft implantation, followed up for a minimum of two years. Disease progression was evaluated according to the Association Research Circulation Osseous (ARCO) staging system, and the change of the ratio of the necrotic volume to femoral head volume was calculated with MRI before and after operation. RESULTS: At the last follow-up, 15 hips remained stable, and 13 hips had a progression, according to the ARCO staging system. A total of eight hips (5 with ARCO stage II and 3 with staged IIIA at baseline) progressed to post-collapse stage (stage IIIB-IV). In total, seven of eight hips with post-collapse stage and one with IIIA stage at follow-up converted to THAs in an average of 17.5 months (range, 11-68 months) postoperatively. The mean ratio of the necrotic lesion volume to the femoral head significantly decreased in hips with ARCO stage I (17.9 ± 3.0% to 9.8 ± 1.3%, p = 0.012, Δ necrosis ratio = 8.1 ± 4.2%) and stage II (22.7 ± 6.3% to 17.1 ± 9.4%, p = 0.001, Δ necrosis ratio = 5.7 ± 6.6%) at baseline. For the eight hips that progressed to post-collapse stage, the mean necrosis ratio increased from 27.4 ± 5.4% to 31.1 ± 4.0% (p = 0.146), Δ necrosis ratio = - 3.7 ± 3.9%. For the other 20 hips radiological survived, the mean necrosis ratio improved from 19.9 ± 4.4% to 11.8 ± 3.3% (p < 0.001), with Δ necrosis ratio = 8.1 ± 4.9%. CONCLUSION: Adipose-derived SVF injection following core decompression and biochemistry artificial bone graft implantation is safe and could effectively repair the necrosis lesion and delay disease progression in patients with early-stage ONFH.

An unusual sternalis with variation of the contralateral sternocleidomastoid muscle: a case report.

PURPOSE: To report a previously undocumented variant of sternalis. METHODS: An unusual muscle was observed during routine dissection. RESULTS: The sternalis muscle located in the right thoracic region originated from the superior portion of the rectus abdominis sheath and 5-6th costal cartilages, crossed the midline and attached at the sternum. The muscle fibers then ascended with the left sternocleidomastoid muscle as an additional fasciculus, of which the superior ends were finally terminated at the left mastoid process. The sternalis muscle of the thoracic region was innervated by the anterior cutaneous branches of right intercostal nerve, while the additional fasciculus ascended with the left sternocleidomastoid muscle was innervated by the branches of left accessory nerve. CONCLUSIONS: This study presents a unilateral sternalis muscle with the contralateral sternocleidomastoid variation. It will enhance the exhaustive classification of sternalis, and provide significant information to radiologists, angiologists and surgeons for better interpretation of images and safer interventions.

The effects of MEX3A knockdown on proliferation, apoptosis and migration of osteosarcoma cells.

BACKGROUND: Osteosarcoma is an aggressive malignant tumor which has attracted worldwide attention. MEX3A may be associated with tumors while has not yet seen its coverage on osteosarcoma. Herein, this study was to investigate the correlation between MEX3A and the progression of osteosarcoma. METHODS: Firstly, we determined that expression of MEX3A was significantly higher in osteosarcoma tissues than that in marginal bone by immunohistochemical staining. Additionally, MEX3A expression was downregulated by the RNAi-mediated knockdown. The functions of MEX3A knockdown on proliferation, apoptosis, cell cycle, migration was assessed by MTT assay, flow cytometry, wound-healing assay and Transwell assay, respectively. Knockdown of MEX3A resulted in suppressing cell proliferation, increasing cell apoptosis, inducing the G2 phase cell cycle arrest, and attenuating cellular migration. Furthermore, mouse xenograft model confirmed inhibitory effects of MEX3A knockdown on osteosarcoma formation. RESULTS: The preliminary exploration on the molecular mechanism of MEX3A in osteosarcoma cells showed that the induction of apoptosis needs the participation of a series of apoptosis- associated factors, such as upregulation of Caspase 3, Caspase 8 and HSP60, downregulation of HSP27 and XIAP. CONCLUSIONS: In summary, these findings predicated that therapy directed at decreasing MEX3A expression is a potential osteosarcoma treatment.

Identification of DNA hydroxymethylation associated genes in osteoarthritis by combined analysis of hydroxymethylation and gene expression.

BACKGROUND: Our study aimed to explore more mechanistic insights into the epigenetic regulation of osteoarthritis (OA). METHODS: The expression profiles (accession number: GSE64393 and GSE64394) were downloaded from the Gene Expression Omnibus database. The differentially hydroxymethylated regions (DhMRs) and differentially expressed genes (DEGs) between OA and control groups were identified. The distribution of DhMRs in the whole genome and the correlation between DhMRs and DEGs were analyzed. Functional module mining for the DEGs and DhMRs was conducted, followed by protein-protein interaction (PPI) analysis. The transcriptional factor (TF) was predicted. RESULTS: Total 52,282 DhMRs were obtained, among which 31,452 ones were annotated to 9726 genes. Additionally, 1806 DEGs were selected. Hydroxymethylation mainly occurred in gene body region. Correlation analysis revealed that more than 70% of DhMRs were uncorrelated with DEGs expression. Functional module mining for the DEGs and DhMRs identified 2 functional modules, which were involved in pathways of regulation of actin cytoskeleton, and TGF-ß signaling pathway. A PPI network was constructed, and ITGB3 had the highest degree. Furthermore, 7 TFs were predicted, which regulated 12 candidate genes, such as HES1-PTEN. CONCLUSIONS: The onset and progression of OA may be associated with the upregulated hydroxymethylation in gene body region of PTEN. HES1 may be important TF in the pathogenesis of OA. Additionally, pathways of regulation of actin cytoskeleton, and TGF-beta signaling pathway may also play important roles in OA progression.

Anti-Inflammatory Effects of a Cordyceps sinensis Mycelium Culture Extract (Cs-4) on Rodent Models of Allergic Rhinitis and Asthma.

Allergic rhinitis and asthma are common chronic allergic diseases of the respiratory tract, which are accompanied by immunoglobulin E (IgE)-mediated inflammation and the involvement of type 2 T helper cells, mast cells, and eosinophils. Cordyceps sinensis (Berk.) Sacc is a fungal parasite on the larva of Lepidoptera. It has been considered to be a health-promoting food and, also, one of the best-known herbal remedies for the treatment of airway diseases, such as asthma and lung inflammation. In the present study, we demonstrated the antiallergic rhinitis effect of Cs-4, a water extract prepared from the mycelium culture of Cordyceps sinensis (Berk) Sacc, on ovalbumin (OVA)-induced allergic rhinitis in mice and the anti-asthmatic effect of Cs-4 in a rat model of asthma. Treatment with Cs-4 suppressed the nasal symptoms induced in OVA-sensitized and challenged mice. The inhibition was associated with a reduction in IgE/OVA-IgE and interleukin (IL)-4/IL-13 levels in the nasal fluid. Cs-4 treatment also decreased airway responsiveness and ameliorated the scratching behavior in capsaicin-challenged rats. It also reduced plasma IgE levels, as well as IgE and eosinophil peroxidase levels, in the bronchoalveolar fluid. Cs-4 treatment completely suppressed the increases in IL-4, IL-5, and IL-13 levels in rat lung tissue. In conclusion, our results suggest that Cs-4 has the potential to alleviate immune hypersensitivity reactions in allergic rhinitis and asthma.

Arthroscopic treatment of popliteal cyst using a figure-of-four position and double posteromedial portals.

PURPOSE: The purpose of this study was to introduce a modified arthroscopic treatment technique for popliteal cyst and hypothesize that this modified technique would provide good clinical efficacy and low recurrence rate. METHODS: From January 2013 to January 2017, 34 patients with symptomatic popliteal cysts were treated with our technique. A figure-of-four position and double posteromedial portals were used to achieve adequate enlargement of the posteromedial valvular opening between the cyst and the joint cavity and complete excision of the cyst wall. MRI was used to detect the recurrence of the popliteal cyst, and the Rauschning and Lindgren score was recorded to evaluate the clinical outcome. RESULTS: All patients were followed up with a mean period of 14.8 months (range, 12 to 36 months). Associated intra-articular lesions were found and treated in all cases. Degenerative cartilage damage was the most common pathology, which affected 23 (67.6%) of the cases. The Rauschning and Lindgren score improved significantly after surgery, and no evidence of recurrence was found from MRI in any case. CONCLUSIONS: Our modified arthroscopic treatment technique, using a figure-of-four position and double posteromedial portals, is effective and safe for treating popliteal cyst.

Intra-articular injection of autologous adipose-derived stromal vascular fractions for knee osteoarthritis: a double-blind randomized self-controlled trial.

OBJECTIVE: The purpose of this study was to compare the clinical and radiological efficacy of autologous adipose-derived stromal vascular fraction (SVF) versus hyaluronic acid in patients with bilateral knee osteoarthritis. METHODS: Sixteen patients with bilateral symptomatic knee osteoarthritis (K-L grade II to III; initial pain evaluated at four or greater on a ten-point VAS score) were enrolled in this study, which were randomized into two groups. Each patient received 4-ml autologous adipose-derived SVF treatment (group test, n = 16) in one side of knee joints and a single dose of 4-ml hyaluronic acid treatment (group control, n = 16) in the other side. The clinical evaluations were performed pre-operatively and post-operatively at one month, three months, six months, and 12-months follow-up visit, using the ten-point visual analog scale (VAS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the knee range of motion (ROM). The whole-organ assessment of the knees was performed with whole-organ magnetic resonance imaging score (WORMS) based on MRI at baseline, six months and 12-months follow-up. The articular repair tissue was assessed quantitatively and qualitatively by magnetic resonance observation of cartilage repair tissue (MOCART) score based on follow-up MRI at six months and 12 months. RESULTS: No significant baseline differences were found between two groups. Safety was confirmed with no severe adverse events observed during 12-months follow-up. The SVF-treated knees showed significantly improvement in the mean VAS, WOMAC scores, and ROM at 12-months follow-up visit compared with the baseline. In contrast, the mean VAS, WOMAC scores, and ROM of the control group became even worse but not significant from baseline to the last follow-up visit. WORMS and MOCART measurements revealed a significant improvement of articular cartilage repair in SVF-treated knees compared with hyaluronic acid-treated knees. CONCLUSION: The results of this study suggest that autologous adipose-derived SVF treatment is safe and can effectively relief pain, improve function, and repair cartilage defects in patients with knee osteoarthritis.

Ursolic Acid-enriched herba cynomorii extract induces mitochondrial uncoupling and glutathione redox cycling through mitochondrial reactive oxygen species generation: protection against menadione cytotoxicity in h9c2 cells.

Herba Cynomorii (Cynomorium songaricum Rupr., Cynomoriaceae) is one of the most commonly used 'Yang-invigorating' tonic herbs in Traditional Chinese Medicine (TCM). An earlier study in our laboratory has demonstrated that HCY2, an ursolic acid-enriched fraction derived from Herba Cynomorii, increased mitochondrial ATP generation capacity (ATP-GC) and induced mitochondrial uncoupling as well as a cellular glutathione response, thereby protecting against oxidant injury in H9c2 cells. In this study, we demonstrated that pre-incubation of H9c2 cells with HCY2 increased mitochondrial reactive oxygen species (ROS) generation in these cells, which is likely an event secondary to the stimulation of the mitochondrial electron transport chain. The suppression of mitochondrial ROS by the antioxidant dimethylthiourea abrogated the HCY2-induced enhancement of mitochondrial uncoupling and glutathione reductase (GR)-mediated glutathione redox cycling, and also protected against menadione-induced cytotoxicity. Studies using specific inhibitors of uncoupling protein and GR suggested that the HCY2-induced mitochondrial uncoupling and glutathione redox cycling play a determining role in the cytoprotection against menadione-induced oxidant injury in H9c2 cells. Experimental evidence obtained thus far supports the causal role of HCY2-induced mitochondrial ROS production in eliciting mitochondrial uncoupling and glutathione antioxidant responses, which offer cytoprotection against oxidant injury in H9c2 cells.

ß-sitosterol protects against carbon tetrachloride hepatotoxicity but not gentamicin nephrotoxicity in rats via the induction of mitochondrial glutathione redox cycling.

Previous findings have demonstrated that ß-sitosterol (BSS), an active component of Cistanches Herba, protected against oxidant injury in H9c2 cardiomyocytes and in rat hearts by enhancing mitochondrial glutathione redox cycling, possibly through the intermediacy of mitochondrial reactive oxygen species production. We therefore hypothesized that BSS pretreatment can also confer tissue protection against oxidant injury in other vital organs such as liver and kidney of rats. In this study, the effects of BSS pretreatment on rat models of carbon tetrachloride (CCl4) hepatotoxicity and gentamicin nephrotoxicity were investigated. The findings showed that BSS pretreatment protected against CCl4-induced hepatotoxicity, but not gentamicin nephrotoxicity in rats. The hepatoprotection afforded by BSS was associated with the improvement in mitochondrial glutathione redox status, presumably through the glutathione reductase-mediated enhancement in mitochondrial glutathione redox cycling. The hepatoprotection afforded by BSS was also accompanied by the improved mitochondrial functional ability in rat livers. The inability of BSS to protect against gentamicin nephrotoxicity was likely due to the relatively low bioavailability of BSS in rat kidneys. BSS may serve as potential mitohormetic agent for the prevention of oxidative stress-induced injury in livers.

Cynomorium songaricum: UHPLC/ESI-LTQ-Orbitrap-MS analysis and mechanistic study on insulin sensitivity of a flavonoid-enriched fraction.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by elevated blood glucose levels, posing a significant global health concern due to its increasing prevalence. Insulin resistance (IR) plays a major role in the development of T2DM and is often linked to factors such as obesity, physical inactivity, and a sedentary lifestyle. Recently, there has been growing interest in exploring the potential of natural products for improving insulin sensitivity and glucose metabolism. Among these, Cynomorium songaricum Rupr., an edible parasitic plant, has shown promising antidiabetic effects. However, research on its beneficial effects on IR is still nascent. Therefore, this study aims to investigate the application of a Cynomorium songaricum flavonoid-enriched fraction (CSF) in the treatment of IR in T2DM, along with elucidating the chemical and biochemical mechanisms involved. METHOD: First, UHPLC/ESI-LTQ-Orbitrap-MS was utilized to perform a chemical profiling of CSF. Subsequently, glycogen synthesis, gluconeogenesis and glucose consumption assays were conducted on HepG2 cells with a high glucose high insulin-induced IR model to illustrate the favorable impacts of CSF on IR. Then, an innovative network pharmacology analysis was executed to predict the potential chemical components and hub genes contributing to CSF's protective effect against IR. To further elucidate molecular interactions, molecular docking studies were performed, focusing on the binding interactions between active constituents of CSF and crucial targets. Additionally, an RNA-sequencing assay was employed to uncover the underlying biochemical signaling pathway responsible for CSF's beneficial effects. To validate these findings, western blot and qPCR assays were employed to verify the pathways related to IR and the potential signaling cascades leading to the amelioration of IR. RESULTS: The UHPLC/ESI-LTQ-Orbitrap-MS analysis successfully identified a total of thirty-six flavonoids derived from CSF. Moreover, CSF was shown to significantly improve glycogen synthesis and glucose consumption as well as inhibit gluconeogenesis in HepG2 cells of IR. An innovative network pharmacology analysis unveiled key hub genes-AKT1 and PI3K-integral to metabolic syndrome-related signaling pathways, which contributed to the favorable impact of CSF against IR. Noteworthy active ingredients including quercetin, ellagic acid and naringenin were identified as potential contributors to these effects. The results of western blot and qPCR assays provided compelling evidence that CSF improved insulin sensitivity by modulating the PI3K-Akt signaling pathway. Subsequent RNA-sequencing analysis, in tandem with western blot assays, delved deeper into the potential mechanisms underlying CSF's advantageous effects against IR, potentially associated with the enhancement of endoplasmic reticulum (ER) proteostasis. CONCLUSION: CSF exhibited a remarkable ability to enhance insulin sensitivity in the IR model of HepG2 cells. This was evident through enhancements in glycogen synthesis and glucose consumption, along with its inhibitory impact on gluconeogenesis. Furthermore, CSF demonstrated an improvement in the insulin-mediated PI3K-Akt signaling pathway. The potential active constituents were identified as quercetin, ellagic acid and naringenin. The underlying biochemical mechanisms responsible for CSF's beneficial effects against IR were closely linked to its capacity to mitigate ER stress, thereby offering a comprehensive understanding of its protective action.

Mechanism of Sophorae Flavescentis Radix (Kushen) in treating NSCLC: Insights from miRNA-mRNA network analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophorae Flavescentis Radix (Kushen) is the primary herb component of Compound Kushen Injection (CKI), an approved clinical treatment for tumors. Despite CKI's widespread use, the underlying mechanisms of Kushen regarding microRNA-target and pathway remain unclear in non-small cell lung cancer (NSCLC). AIM OF THE STUDY: This study aimed to elucidate the crucial miRNAs-targets and pathways responsible for the Kushen's impact on NSCLC. MATERIALS AND METHODS: CCK8, colony formation, and apoptosis assays were performed to assess the effects of Kushen on NSCLC cells. Subsequently, we treated the A549 cell line with varying concentrations of Kushen to obtain mRNA and miRNA expression profiles. A DE (differentially expressed) miRNAs-DEGs network was then constructed to identify the critical miRNA-mRNA interaction influenced by Kushen. Furthermore, we performed clinical significance and prognosis analyses of hub genes to narrow down key genes and their corresponding miRNAs. Finally, the effects of Kushen on critical miRNA-mRNA interaction and related pathway were verified by in vitro and in vivo experiments. RESULTS: In this study, we initially demonstrated that Kushen significantly inhibited cell proliferation, suppressed colony formation, and induced apoptosis in the A549 cells, PC9 cells, and the A549 zebrafish xenograft model. Through expression profile analysis, a DE miRs-DEGs network was constructed with 16 DE miRs and 68 DEGs. Through the network analysis and expression validation, we found Kushen could significantly down-regulate miR-183-5p expression and up-regulate EGR1 expression. Additionally, Kushen affected the PTEN/Akt pathway, increasing PTEN expression and decreasing pAkt expression. Finally, matrine, the essential active compound of Kushen, also inhibited cell growth, induced apoptosis, and regulated miR-183-5p/EGR1 and PTEN/AKT pathway. CONCLUSIONS: Altogether, these findings supported the critical role of miR-183-5p/EGR1 and the PTEN/AKT pathway in the beneficial effects of Kushen on NSCLC, highlighting the therapeutic potential of Kushen in NSCLC treatment.

Chemical characterization and metabolic profiling of Xiao-Er-An-Shen Decoction by UPLC-QTOF/MS.

Background: Xiao-Er-An-Shen decoction (XEASD), a TCM formula composed of sixteen Chinese medicinal herbs, has been used to alleviate tic disorders (TD) in clinical practice for many years. However, the chemical basis underlying the therapeutic effects of XEASD in the treatment of TD remains unknown. Purpose: The present study aimed to determine the major chemical components of XEASD and its prototype compounds and metabolites in mice biological samples. Methods: The chemical constituents in XEASD were identified using ultra-high Performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Following this, XEASD was orally administered to mice, and samples of plasma, urine, feces, bile, and tissue were collected in order to identify effective compounds for the prevention or treatment of TD. Result: Of the total 184 compounds identified to be discriminated in the XEASD, comprising 44 flavonoids, 26 phenylpropanoids, 16 coumarins, 16 triterpenoids, 14 amino acids, 13 organic acids, 13 alkaloids, 13 ketones, 10 cyclic enol ether terpenes, 7 citrullines, 3 steroids, and 5 anthraquinones, and others. Furthermore, we summarized 54 prototype components and 78 metabolic products of XEASD, measured with biological samples, by estimating metabolic principal components, with four prototype compounds detected in plasma, 58 prototypes discriminated in urine, and 40 prototypes identified in feces. These results indicate that the Oroxylin A glucuronide from Citri reticulatae pericarpium (CRP) is a major compound with potential therapeutic effects identified in brain, while operating positive effect in inhibiting oxidative stress in vitro. Conclusion: In summary, our work delineates the chemical basis underlying the complexity of XEASD, providing insights into the therapeutic and metabolic pathways for TD. Various types of chemicals were explored in XEASD, including flavonoids, phenylpropanoids, coumarins, organic acids, triterpenoid saponins, and so on. This study can promote the further pharmacokinetic and pharmacological evaluation of XEASD.

Exploring the possible mechanism(s) underlying the nephroprotective effect of Zhenwu Decoction in diabetic kidney disease: An integrated analysis.

BACKGROUND: Diabetic kidney disease (DKD) is one of the major chronic microvascular complications of diabetes and the main cause of end-stage renal failure. Zhenwu Decoction (ZWD), an ancient classic herbal formula in Chinese medicine, has been clinically used for the treatment of kidney disease in China for many years. However, there is currently limited research investigating the application of ZWD in the treatment of DKD and the underlying chemical and biochemical mechanisms involved. Therefore, in the present study, we aimed to identify active components in ZWD and unravel the possible mechanism(s) of action for ZWD in treating DKD. METHODS: The protective effect of ZWD against DKD was evaluated utilizing an in vitro model of diabetic renal proximal tubulopathy. The major chemical components from ZWD were identified by LC-MS/MS. Drug targets were predicted by submitting the SMILES (Simplified Molecular Input Line Entry System) of the compounds to SEA (Similarity Ensemble Approach) search server and SwissTargetPrediction. The differentially expressed genes (DEGs) of the disease were collected and integrated from GeneCards. The constructions of "Compounds-potential targets interaction" (CTI) network and Protein-Protein Interaction (PPI) network, as well as topology analysis were conducted by Cytoscape. Gene Ontology (GO) enrichment and Metacore pathway enrichment analysis were also performed. Lastly, molecular docking and experimental studies were adopted to validate the core target and identify an active component(s) of ZWD. RESULTS: We demonstrated that the ZWD extract could significantly rescue the palmitic acid (PA) and high glucose-induced apoptotic cell death in HK-2 cells, and the cytoprotection was accompanied by decreases in the extent of reactive oxygen species (ROS) production, mitochondrial membrane depolarization and ATP depletion. Fifty-seven compounds in the aqueous extract of ZWD were identified by LC-MS. The results of PPI analysis showed that top hub genes involved epidermal growth factor receptor (EGFR), Signal Transducer and Activator of Transcription 3 (STAT3), Serine/Threonine Kinase 1 (AKT1), Vascular Endothelial Growth Factor A (VEGFA) and Fibroblast Growth Factor 2 (FGF2). Pathway enrichment analysis revealed the involvement of S1P1 receptor signaling and EGFR pathways. The results of molecular docking analysis showed that albiflorin has a high binding affinity to EGFR. Albiflorin could also exert protective effects in an HK-2 cell model of DKD, which may be related to the inhibition of the high glucose/high lipid-induced EGFR and Akt phosphorylation. CONCLUSION: ZWD has been shown to be effective in ameliorating cell death in an experimental model of DKD. The beneficial effect of ZWD against DKD was associated with the interactions between the active ingredients and the hub genes, such as EGFR, STAT3, AKT1, and VEGF-A. Albiflorin may be one of the active components responsible for the nephroprotective effect in ZWD.

Panax notoginseng alleviates oxidative stress through miRNA regulations based on systems biology approach.

BACKGROUND: Herbal medicine Sanqi (SQ), the dried root or stem of Panax notoginseng (PNS), has been reported to have anti-diabetic and anti-obesity effects and is usually administered as a decoction for Chinese medicine. Alternative to utilizing PNS pure compound for treatment, we are motivated to propose an unconventional scheme to investigate the functions of PNS mixture. However, studies providing a detailed overview of the transcriptomics-based signaling network in response to PNS are seldom available. METHODS: To explore the reasoning of PNS in treating metabolic disorders such as insulin resistance, we implemented a systems biology-based approach with RNA sequencing (RNA-seq) and miRNA sequencing data to elucidate key pathways, genes and miRNAs involved. RESULTS: Functional enrichment analysis revealed PNS up-regulating oxidative stress-related pathways and down-regulating insulin and fatty acid metabolism. Superoxide dismutase 1 (SOD1), peroxiredoxin 1 (PRDX1), heme oxygenase-1 (Hmox1) and glutamate cysteine ligase (GCLc) mRNA and protein levels, as well as related miRNA levels, were measured in PNS treated rat pancreatic ß cells (INS-1). PNS treatment up-regulated Hmox1, SOD1 and GCLc expression while down-regulating miR-24-3p and miR-139-5p to suppress oxidative stress. Furthermore, we verified the novel interactions between miR-139-5p and miR-24-3p with GCLc and SOD1. CONCLUSION: This work has demonstrated the mechanism of how PNS regulates cellular molecules in metabolic disorders. Therefore, combining omics data with a systems biology strategy could be a practical means to explore the potential function and molecular mechanisms of Chinese herbal medicine in the treatment of metabolic disorders.

The Development Tendency of 3D-Printed Bioceramic Scaffolds for Applications Ranging From Bone Tissue Regeneration to Bone Tumor Therapy.

Three-dimensional (3D) printing concept has been successfully employed in regenerative medicine to achieve individualized therapy due to its benefit of a rapid, accurate, and predictable production process. Traditional biocomposites scaffolds (SCF) are primarily utilised for bone tissue engineering; nevertheless, over the last few years, there has already been a dramatic shift in the applications of bioceramic (BCR) SCF. As a direct consequence, this study focused on the structural, degeneration, permeation, and physiological activity of 3D-printed BCR (3DP-B) SCF with various conformations and work systems (macros, micros, and nanos ranges), as well as their impacts on the mechanical, degeneration, porosity, and physiological activities. In addition, 3DP-B SCF are highlighted in this study for potential uses applied from bone tissue engineering (BTE) to bone tumor treatment. The study focused on significant advances in practical 3DP-B SCF that can be utilized for tumor treatment as well as bone tissue regeneration (BTR). Given the difficulties in treating bone tumors, these operational BCR SCF offer a lot of promise in mending bone defects caused by surgery and killing any remaining tumor cells to accomplish bone tumor treatment. Furthermore, a quick assessment of future developments in this subject was presented. The study not only summarizes recent advances in BCR engineering, but it also proposes a new therapeutic strategy focused on the extension of conventional ceramics' multifunction to a particular diagnosis.

The Use of Chinese Yang/Qi-Invigorating Tonic Botanical Drugs/Herbal Formulations in Ameliorating Chronic Kidney Disease by Enhancing Mitochondrial Function.

Background: Chronic kidney disease (CKD) is a leading cause of morbidity and mortality. Mitochondrial dysfunction has been implicated as a key factor in the development of CKD. According to traditional Chinese medicine (TCM) theory, many Chinese Yang/Qi-invigorating botanical drugs/herbal formulations have been shown to produce promising outcomes in the clinical management of CKD. Experimental studies have indicated that the health-promoting action of Yang/Qi invigoration in TCM is related to the up-regulation of mitochondrial energy generation and antioxidant status. Objective: In this review, we aim to test whether Chinese Yang/Qi-invigorating tonic botanical drugs/herbal formulations can provide medical benefits in CKD and its complications. And we also explore the possible involvement of mitochondrial-associated signaling pathway underlying the beneficial effects of Yang/Qi invigoration in TCM. Methods: A systematic search of "PubMed", "China National Knowledge Infrastructure (CNKI)" and "Google Scholar" was carried out to collect all the available articles in English or Chinese related to Chinese Yang/Qi-invigorating tonic botanical drugs/herbal formulations and their effects on mitochondrial function and chronic kidney disease. Result and Discussion: The relationship between the progression of CKD and mitochondrial function is discussed. The effects of Chinese Yang/Qi-invigorating tonic botanical drugs/herbal formulations and their active ingredients, including phytosterols/triterpenes, flavonoids, and dibenzocyclooctadiene lignans, on CKD and related alterations in mitochondrial signaling pathways are also presented in this review. In the future, exploration of the possible beneficial effects and clinical studies of more Yang- and Qi-invigorating botanical drugs/herbal formulations in the prevention and/or/treatment of CKD and the molecular mechanisms relating to the enhancement of mitochondrial functions warrants further investigation. Conclusion: Given the critical role of mitochondrial function in safeguarding renal functional integrity, the enhancement of mitochondrial energy metabolism and antioxidant status in kidney tissue is likely involved in renal protection. Future studies on the biochemical and chemical basis underlying the effects of Chinese Yang/Qi-invigorating tonic botanical drugs/herbal formulations from a mitochondrial perspective will hopefully provide novel insights into the rational development of new drugs for the prevention and/or treatment of CKD.

Novel Mutations in Chinese Patients with Multiple Osteochondromas Identified Using Whole Exome Sequencing.

Background: Multiple osteochondromas (MO) are an autosomal-dominant disease characterized by the growth of multiple cartilage-capped prominences in the growth plate region of the metaphysis in long and flat bones. Materials and Methods: To detect genetic mutations related to MO, a three-generation Chinese family with MO was evaluated using whole exome sequencing for mutation screening. The candidate pathogenic mutation was validated by Sanger sequencing. Results: A novel frameshift (NM_000401.3:c.1321del:p.Leu441TrpfsTer28) in exon 8 of the exotosin 2 (EXT2) gene was identified in two affected individuals. Codons 441 and 468 in the EXT2 gene are highly conserved among vertebrates as demonstrated by multiple sequence alignment. The c.1321 del C resulted in an amino acid change at codon 441, which generated a premature stop codon at position 468, causing complete loss of the glycosyltransferase domain. Conclusions: A novel frameshift mutation c.1321delC detected in the EXT2 gene may help in prenatal genetic screening and early diagnosis of MO.

[Studies on the flavonoidls from the herb of Striga asiatica].

OBJECTIVE: To study the chemical constituents of the herb of Striga asiatica. METHODS: The constituents were isolated by column chromatography and their structrues were elucidated through spectroscopic analysis. RESULTS: Eleven compounds were obtained and six flavonoiels were identified as apigenin-7-galacturonide( I ), apigenin-7-O-beta-D-glucopyranuronide (II), quercitrin (III), acacetin-7-O-beta-D-glucuronide (IV), apigenin (V), chrysoreiol (VI). CONCLUSION: Compounds I - IV are obtained from this plant for the first time.

Arthroscopic Suture Fixation With Autograft Augmentation Reconstruction for Delayed Tibial Avulsion Fractures of the Posterior Cruciate Ligament.

BACKGROUND: The optimal surgical treatment of delayed avulsion fractures of the posterior cruciate ligament (PCL) is still controversial. PURPOSE: To evaluate the clinical results of arthroscopic suture fixation of tibial avulsion fractures of the PCL with autograft augmentation reconstruction. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: From January 2013 to February 2017, we treated 15 patients with delayed tibial avulsion fractures of the PCL arthroscopically through posteromedial and posterolateral portals. The PCL and avulsion bone fragment were fixed with No. 2 nonabsorbable FiberWire sutures that were pulled out through a single tibial bone tunnel and fixed on a small Endobutton. Concomitantly, anatomic PCL augmentation reconstruction was performed, and the graft was pulled out through the same tunnel and fixed with an interference screw. Knee stability was assessed using the posterior drawer test, and the side-to-side difference was determined using a KT-1000 arthrometer with 134 N of posterior force at 30° of knee flexion. The International Knee Documentation Committee (IKDC) 2000 subjective form and Lysholm scale were used to evaluate clinical outcomes at follow-up. Overall, 12 patients were enrolled for analysis. The mean follow-up period was 34.4 months (range, 26-49 months). RESULTS: At the final follow-up, 2 patients encountered 10° terminal flexion limitations. All patients had negative posterior drawer test results. The KT-1000 arthrometer side-to-side difference was significantly decreased from 8.25 ± 1.96 mm preoperatively to 1.08 ± 0.86 mm at the last follow-up (P < .001). The mean IKDC and Lysholm scores, respectively, increased from 54.67 ± 7.13 and 53.50 ± 7.90 preoperatively to 91.13 ± 3.78 and 94.25 ± 3.32 at the final follow-up (P < .001 for both). CONCLUSION: Arthroscopic suture fixation with autograft augmentation reconstruction for delayed tibial avulsion fractures of the PCL showed good clinical stability and function in this study.

48Biochemical mechanisms of the anti-obesity effect of a triterpenoid-enriched extract of Cynomorium songaricum in mice with high-fat-diet-induced obesity.

BACKGROUND: HCY2, a triterpenoid-enriched extract of Cynomorii Herba, has been shown to reduce body weight and adiposity and attenuate manifestations of the associated metabolic syndrome in high-fat-diet (HFD)-fed mice. PURPOSE: The current study aimed to investigate the biochemical mechanism underlying the anti-obesity effect produced by HCY2. STUDY DESIGN: An HCY2-containing extract was examined for its effects on the regulation of adenosine monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma co-activator-1 (PGC1) pathways and the protein expression related to mitochondrial uncoupling and biogenesis in skeletal muscle using an HFD-induced obese mouse model. METHODS: The obese mouse model was produced by providing HFD (60% kcal from fat) ad libitum. The effects and signaling mechanisms of HCY2 were examined using analytical procedures which included enzyme-linked immunosorbent assay kits, Western blot analysis, and the use of a Clark-type oxygen electrode. RESULTS: The current study revealed that the weight reduction produced by HCY2 is associated with the activation of the AMPK signaling pathway, with resultant increases in mitochondrial biogenesis and expression of uncoupling protein 3 in skeletal muscle in vivo. The use of a recoupler, ketocholestanol, delineated the precise role of mitochondrial uncoupling in the anti-obesity effect afforded by HCY2 in obese mice. CONCLUSION: Our experimental findings offer a promising prospect for the use of HCY2 in the management of obesity through the regulation of AMPK/PGC1 pathways.