Smartphone-assisted ratiometric fluorescent sensor to quantitatively detect curcumin in traditional Chinese medicine based on Förster resonance energy transfer.

A ratiometric fluorescence sensor (Fe-MIL-88-NH2/curcumin) based on luminescent metal-organic frameworks (LMOFs) for the determination of curcumin was constructed. Upon the addition of curcumin, the 535-nm emission of curcumin was enhanced, while the fluorescence emission at 438 nm was quenched, under 367-nm excitation. This sensor demonstrated a broad linear range from 1.5 to 40 µM, a low detection limit of 35 nM, and a fast response time of at most 30 s. We verified the Förster resonance energy transfer (FRET) mechanism between donor (Fe-MIL-88-NH2) and acceptor (curcumin), which further proved the selectivity of the approach. The sensing system enabled the detection of curcumin in the traditional Chinese medicine (TCM) Turmeric. A smartphone-assisted sensing platform was prepared to visually detect curcumin in a portable manner. This study represents the first attempt to fabricate LMOFs for ratiometric fluorescence detection of curcumin, which has promising potential for application in TCM.

Environmental fate and toxicity of androgens: A critical review.

Androgens are released by humans and livestock into the environment and which cause potent endocrine disruptions even at nanogram per liter levels. In this article, we reviewed updated research results on the structure, source, distribution characteristics and the fate of androgens in ecological systems; and emphasized the potential risk of androgens in aquatic organism. Androgens have moderately solubility in water (23.6-58.4 mg/L) and moderately hydrophobic (log Kow 2.75-4.40). The concentration of androgens in surface waters were mostly in ng/L ranges. The removal efficiencies of main wastewater treatment processes were about 70-100%, except oxidation ditch and stabilization ponds. Sludge adsorption and microbial degradation play important role in the androgens remove. The conjugated androgens were transformed into free androgens in environmental matrices. Global efforts to provide more toxicity data and establish standard monitoring methods need a revisit. Of the day available, there is an urgent need for comprehensive consideration of the impact of androgens on the environment and ecology.

Adipose tissue macrophage-derived exosomal miR-29a regulates obesity-associated insulin resistance.

Obesity-associated insulin resistance is a forerunner of type 2 diabetes. Macrophages reside within adipose tissue (ATMs) have been reported to regulate insulin sensitivity through secreting miRNAs containing exosomes. Here, we show that miR-29a is increased in obese ATMs derived exosomes (ATMs-Exos) and can be transferred into adipocytes, myocytes and hepatocytes causing insulin resistance in vitro and in vivo. Administration of obese ATMs-Exos impairs insulin sensitivity of lean mice. While knockdown miR-29a level in obese ATM-Exos blunts this effect. PPAR-δ is identified to function as downstream target of miR-29a in regulating insulin resistance. PPAR-δ agonist GW501516 partially rescued the insulin resistance induced by miR-29a. Taken together, these findings suggest that ATMs derived exosomal miR-29a could regulate obesity-associated insulin resistance, which may serve as a potential therapeutic target for obesity-associated type 2 diabetes.

Codelivery of dihydroartemisinin and doxorubicin in mannosylated liposomes for drug-resistant colon cancer therapy.

Multidrug resistance (MDR) is a major hurdle in cancer chemotherapy and makes the treatment benefits unsustainable. Combination therapy is a commonly used method for overcoming MDR. In this study we investigated the anti-MDR effect of dihydroartemisinin (DHA), a derivative of artemisinin, in combination with doxorubicin (Dox) in drug-resistant human colon tumor HCT8/ADR cells. We developed a tumor-targeting codelivery system, in which the two drugs were co-encapsulated into the mannosylated liposomes (Man-liposomes). The Man-liposomes had a mean diameter of 158.8 nm and zeta potential of -15.8 mV. In the HCT8/ADR cells that overexpress the mannose receptors, the Man-liposomes altered the intracellular distribution of Dox, resulting in a high accumulation of Dox in the nuclei and thus displaying the highest cytotoxicity (IC50=0.073 µg/mL) among all the groups. In a subcutaneous HCT8/ADR tumor xenograft model, administration of the Man-liposomes resulted in a tumor inhibition rate of 88.59%, compared to that of 47.46% or 70.54%, respectively, for the treatment with free Dox or free Dox+DHA. The mechanisms underlying the anti-MDR effect of the Man-liposomes involved preferential nuclear accumulation of the therapeutic agents, enhanced cancer cell apoptosis, downregulation of Bcl-xl, and the induction of autophagy.

Detection of biogenic amines in C57BL/6 mice brain by capillary electrophoresis electrokinetic supercharging.

Ischemic stroke is caused when blood flow to the brain is stopped and is a major cause of death and long term disability across the globe. Excessive release of neurotransmitters is triggered in the brain by ischemia that mediates neuronal damage and causes ischemic injury. In this study, a simple, sensitive, and on-line preconcentration capillary electrophoresis method based on electrokinetic supercharging (EKS) was developed for the determination of the biogenic amines including dopamine (DA), epinephrine (E), and norepinephrine (NE) in C57BL/6 mice brain. Under the optimized conditions, the analytes were concentrated and detected within 10 min. The detection limits for the analytes ranged from 0.42 to 0.57 ng mL(-1) for a mice brain matrix. With the proposed method, the analyses of three neurochemical amines in C57BL/6 mice brain tissue during cerebral ischemic/reperfusion had been performed successfully.

Perfluorinated carboxylic and sulphonic acids in surface water media from the regions of Tibetan Plateau: Indirect evidence on photochemical degradation?

Perfluorinated surfactants and repellents are synthetic substances that have found numerous industrial and customer applications. Due to their persistence, at least two groups of these substances-perfluorinated carboxylic acids (PFCAs) and perfluorinated sulfonic acids (PFSAs)-are diffused widely in the environment. It is hypothesized that the Tibetan Plateau, is one of few unique places on the Earth, due to its topography, specifically the vast space and high elevation above sea level, geographic location, climate, high solar radiation, lack of industry, little urbanization and general lack of significant direct sources of pollution. There it is believed possible to gain an insight into atmospheric fate (possible photochemical degradation of higher molecular mass and formation of lower molecular mass PFCAs and PFSAs) of PFASs under un-disturbed environmental conditions. Ultratrace analytical method for PFCAs and PFSAs and use of transportation and field blanks, laboratory blanks and isotopically labelled surrogates for recovery control has allowed the determination of nine perfluorinated carboxylic acids and six perfluorinated sulfonic acids at ultra-trace levels in water based samples from the alpine dimension regions of the Tibetan Plateau, the eastern slope of Minya Konka peak at the eastern edge of the Tibetan Plateau, and also from the city of Chengdu from the lowland of the Sichuan Province in China. The specific compositional pattern of PFCAs and PFSAs and low levels of pollution with those compounds were observed in the central region of the Tibetan Plateau and in the region adjacent to the peaks of Minya Konka in the Eastern Tibetan Plateau. The fingerprint of the compositional pattern of PFCAs and PFSAs in water samples in the central region of the Tibetan Plateau and in the alpine region adjacent to the peaks of Minya Konka in the Eastern Tibetan Plateau may be explained by the result of photochemical degradation with dealkylation of longer chain compounds and formation of shorter chain compounds, which are more resistant to photochemical degradation.

Determination of enantiomers by FESI-sweeping with an acid-labile sweeper in nonaqueous capillary electrophoresis.

In this work, a facile and highly efficient on-line concentration strategy based on a coupling of field enhanced sample injection (FESI) and sweeping was developed for the determination of trace enantiomers (propranolol, PL) by nonaqueous capillary electrophoresis (NACE). In this FESI-sweeping method, the use of a sample of high acidity and low conductivity (pH* = 2.5, 4.0 µS cm(-1)) allowed for a large amount of analyte injection. Then, the concentration of the analytes was carried out by sweeping based on the interaction of an acid-labile anionic selector, di-n-butyl L-tartrate-boric acid complex acid, and cationic analytes. Simultaneously, the concentrated analytes were released and focused at the boundary of the acid sample solution and separation buffer due to the decomposition of the selector in the acid sample solution. Under the optimum conditions, a 21,000-fold sensitivity enhancement upon normal capillary zone electrophoresis (CZE) was achieved for PL enantiomers. The detection limits of R-propranolol and S-propranolol were 0.26 ng mL(-1) and 0.31 ng mL(-1), respectively. Eventually, the FESI-sweeping method was applied to detect PL enantiomers in plasma, saliva, and urine.

[Study on the Effects of Ginsenoside Rb1 on DPPC Bilayers by Using Thermo-Raman Spectrum and DSC].

The research on the interactions between Ginsenosides and biomembranes plays a crucial role in thorough understanding the pharmacological activity and biologyical effect of Chinese medicine Panax ginseng. With the bilayer structure, DPPC often serves as an simulation model of the cell membrane to study the role of drug molecules and cell membranes. Ginsenoside Rb1, one of the most important components of Panaxginseng, playing the significant roles of pharmacological effects and biological properties. Raman and differential scanning calorimetry (DSC) are respectively a powerful tool for discussing the molecular interaction, and a kind of general technology by which researching the bilayer monomer structures and its interactions with drug molecules. However, rarely research reports on the interactions between drug molecules and biomembranes by means of both technologies above. In this paper, the influence of ginsenoside monomer Rb1 on DPPC membrane bilayers was investigated by thermo-Raman and DSC. In Raman spectra, the changes of DPPC molecule have been observed before and after interacted with ginsenoside Rb1, the data analysis indicates three aspects: the O-C-C-N+ polar head group skeleton, C-C stretching vibration area, and the C-H bond stretching vibrarion in terminated methyl group of alkyl chains. The results showed that ginsenoside Rb1 molecule with certain concentration has not changed the gauche conformation of the polar head backbone group in DPPC bilayers, the order of the internal molecular chain and the lateral chain-chain packing have been decreased as the temperature increased, the lateral disposed disorder has been increased. The changes of some thermodynamic constants obtained by DSC experiment such as phase transition temperature (Tm), the temperature at which the transition is half completed (ΔT1/2), and the transition enthalpy normalized per mol of DPPC (AH) have been showed further results of the thermo Raman experiments, with increasing the concentration of ginsenoside Rb1, the pre-transition temperature of DPPC bilayers dropped immediately with small amount of the Rb1 drug when the containtion was only 5 mol% and the whole system has been destructed at the same time, the main phase transition peak showed as a new little shoulder seam, however, both pre- and main transition peak disappeared completely until the drug concentration increased to 20 mol%, the phase transition temperature of DPPC has been reduced significantly, and the fluidity of bilayers has been increased. Both experiments indicated that the strong effects of ginsenoside Rb1 on DPPC.

[Raman and DSC spectroscopic studies on the interaction between ginsenosides and DMPC bilayer membranes].

Study the effect of drugs and biological membranes is of prime importance on understanding drugs' curative effects and improving their biological properties. In this article, Raman spectrum has been combined with differential thermal scanning technology to discuss the relationship between five categories of ginsenoside molecules and DMPC bilayer films. Raman results indicated that the saponin molecules have not altered the polarity conformation of O-C-C-N+ backbone in DMPC bilayers, and the polarity head still paralleled to the membrane surface. The order of the internal molecular chain and the lateral chain-chain packing have been decreased as the panaxadiol saponins Rb1 and Rh2 increased, and to the opposite, the panaxatriol saponins Re, Rf and Rg1 have showed weak effects on DMPC bilayers. The DSC showed further results that the strong effects of ginsenoside Rb1 and Rh2 on DMPC, which both have obviously reduced the DMPC molecular phase transition temperature, thus increasing the fluidity of bilayers. In addition, panaxatriol saponin Rf has displayed stronger disturbance effect on DMPC than Re and Rg1.

TiO2 nanofilms for surface-enhanced Raman scattering analysis of urea.

In this study, titanium dioxide (TiO2) nanofilms with nanoparticle structure were grown in situ on metallic aluminum (Al) sheets using a simple sol-hydrothermal method. Al sheets were chosen because they can form Schottky junctions with TiO2 during the calcination process, thus achieving a tight bonding between the nanoparticles and the solid substrate, which cannot be achieved with conventional glass substrates. The substrates synthesized with different contents of titanium butoxide [Ti(OBu)4] were investigated using 4-mercaptobenzoic acid as a probe molecule, and the results showed that the substrate with 9 % of the total volume of Ti(OBu)4 had the highest surface-enhanced Raman scattering (SERS) performance. As a low-cost SERS substrate that is simple to synthesize, it has excellent signal reproducibility, with a relative standard deviation of 4.51 % for the same substrate and 6.43 % for different batches of synthesized substrates. Meanwhile, the same batch of substrate can be stored at room temperature for at least 20 weeks and still maintain stable SERS signals. In addition, the synthetic substrate was used to quantitatively detect urea with a detection limit of 4.23 × 10-3 mol/L, which is comparable to the application of noble metal substrates. The feasibility of this method was verified in human urine, and the results were consistent with the clinical results, indicating that this method has great potential for clinical application.

Yam protein ameliorates cyclophosphamide-induced intestinal immunosuppression by regulating gut microbiota and its metabolites.

Yam is a dual-purpose crop used in both medicine and food that is commonly used as a dietary supplement in food processing. Since yam proteins are often lost during the production of yam starch, elucidating the functionally active value of yam proteins is an important guideline for fully utilizing yam in industrial production processes. This study aimed to explore the potential protective effect of yam protein (YP) on cyclophosphamide (CTX)-induced immunosuppression in mice. The results showed that YP can reduce immune damage caused by CTX by reversing immunoglobulins (IgA, IgG and IgM), cytokines (TNF-α, IL-6, etc.) in the intestines of mice. Moreover, YPs were found to prevent CTX-induced microbiota dysbiosis by enhancing the levels of beneficial bacteria within the microbiome, such as Lactobacillus, and lowering those of Desulfovibrio_R and Helicobacter_A. Metabolomics analyses showed that YP significantly altered differential metabolites (tryptophan, etc.) and metabolic pathways (ABC transporter protein, etc.) associated with immune responses in the gut. Furthermore, important connections were noted between particular microbiomes and metabolites, shedding light on the immunoprotective effects of YPs by regulating gut flora and metabolism. These findings deepen our understanding of the functional properties of YPs and lay a solid foundation for the utilization of yam.

Clonidine suppresses the induction of long-term potentiation by inhibiting HCN channels at the Schaffer collateral-CA1 synapse in anesthetized adult rats.

Activation of alpha2-adrenoceptors inhibits long-term potentiation and long-term depression in many brain regions. However, effectiveness and mechanism of alpha2-adrenoceptors for synaptic plasticity at the Schaffer collateral-CA1 synapses in rat in vivo is unclear. In the present study, we investigated the effects of alpha2-adrenoceptors agonist clonidine on high-frequency stimulation (HFS)-induced long-term potentiation (LTP) and paired-pulse facilitation (PPF) at the Schaffer collateral-CA1 synapse of rat hippocampus in vivo. Clonidine (0.05, 0.1 mg/kg, ip) inhibited synaptic plasticity in a dose-dependent manner, accompanying with the decreasing of aortic pressure and heart rate (HR) in anesthetized rats. Clonidine (1.25, 2.5 µg/kg, icv, 10 min before HFS) also dose-dependently inhibited synaptic plasticity, which had no remarkable effect on HR and aortic pressure. But, 20 min after HFS, administration of clonidine (2.5 µg/kg) had no effect on LTP. The inhibitory effect of clonidine (2.5 µg/kg) on LTP was completely reversed by yohimbine (18 µg/kg, icv) and ZD7288 (5 µg/kg, icv). Moreover, the inhibition was accompanied by a significant increase of the normalized PPF ratio. Furthermore, clonidine at 1 and 10 µM significantly decreased glutamate (Glu) content in the culture supernatants of hippocampal neurons, and yohimbine at 1 and 10 µM had no effect on Glu release, while it could reverse the inhibition of clonidine (1 and 10 µM) on Glu release. In conclusion, clonidine can suppress the induction of LTP at the Schaffer collateral-CA1 synapse, and the possible mechanism is that activation of presynaptic alpha2-adrenoceptors reduces the Glu release by inhibiting HCN channels.

[Trans-splicing of Cys mutated coagulation factor VIII].

To investigate the improving effect of inter-chain disulfide formation on protein trans-splicing, we introduce a Cys point mutation at Tyr(664) in heavy chain and at Thr(1826) in light chain of B-domain-deleted FVIII (BDD-FVIII). By co-transfection of COS-7 cell with the two Cys mutated chain genes, the intracellular protein splicing, inter-chain disulfide formation, secreted BDD-FVIII and bioactivity in culture supernatant were observed. The data showed that a strengthened spliced BDD-FVIII with an inter-chain disulfide detected by Western blotting and an elevated secretion of spliced BDD-FVIII (128 +/- 24 ng mL(-1)) compared to control (89 +/- 15 ng mL(-1)), assayed by a sandwich ELISA. A Coatest was performed to assay the secretion of bioactivity in culture supernatant and shown a much higher value (0.94 +/- 0.08 u mL(-1)) compared to that of control (0.62 +/- 0.15 u mL(-1)). It suggests that inter-chain disulfide formation could improve protein trans-splicing based dual-vector delivery of BDD-FVIII gene providing experimental evidence for ongoing in vivo study.

[Leucine zippers improves protein splicing-mediated coagulation factor VIII gene delivery by dual-vector system].

In our recent study by exploring an intein-based dual-vector to deliver a B-domain-deleted FVIII (BDD-FVIII) gene, it showed that covalently ligated intact BDD-FVIII molecules with a specific coagulant activity could be produced from expressed heavy and light chains by protein trans-splicing. Here, we assessed the hypothesis that the efficiency of trans-splicing may be increased by adding to the intein sequences a pair of leucine zippers that are known to bring about specific and strong protein binding. The intein-fused heavy and light chain genes were co-transferred into cultured COS-7 cells using a dual-vector system. After transient expression, the intracellular BDD-FVIII splicing was observed and the spliced BDD-FVIII and bioactivity secreted to culture media were quantitatively analyzed. An enhanced splicing of BDD-FVIII with decreased protein precursors from gene co-transfected cells was observed by Western blotting. The amount of spliced BDD-FVIII and bioactivity secreted to the culture media were 106 +/- 12 ng x mL(-1) and 0.89 +/- 0.11 U x mL(-1) analyzed by ELISA and Coatest method respectively, which was greater than leucine zipper free intein-fused heavy and light chain genes co-transfected cells (72 +/- 10 ng x mL(-1) and 0.62 +/- 0.07 U x mL(-1)). The activity of cellular mechanism-independent protein splicing was also improved, as showed by the increasing of spliced BDD-FVIII and bioactivity in culture media from combined cells separately transfected with heavy and light chain genes which was 36 +/- 11 ng x mL(-1) and 0.28 +/- 0.09 U x mL(-1). It demonstrated that the leucine zippers could be used to increase the efficiency of protein trans-splicing to improve the efficacy of a dual-vector mediated BDD-FVIII gene delivery by strengthening the interaction between the two intein-pieces fused to heavy and light chains. It provided evidence for further study in animal model using a dual-adeno-associated virus vector to deliver FVIII gene in vivo.

Development of ecological risk assessment for Diisobutyl phthalate and di-n-octyl phthalate in surface water of China based on species sensitivity distribution model.

Phthalic acid esters (PAEs) are commonly used as plasticizer and are emerging concern worldwide for potent adverse effects of aquatic organisms. Certain PAEs were often detected in different environmental matrices but related toxicity data were still lacking to support their risk assessment. The study investigated the acute toxicity of Diisobutyl phthalate (DiBP) and Di-n-octyl phthalate (DnOP) using 6 Chinese resident aquatic organisms from 3 phyla and 6 species and constructed the species sensitivity distribution (SSD) models for ecological risk assessment. Lethal concentration 50% (LC50) ranges of DiBP and DnOP were 4.89-21.45 mg/L and 1.45-1200 mg/L, respectively. The derived acute and chronic predicted no-effect concentrations (PNECs) based on log-normal model of water were 0.54 and 0.04 mg/L for DiBP and 0.23 and 0.05 mg/L for DnOP, respectively. The ERA for DiBP and DnOP in the surface water and sediment of China was conducted. Water samples of Haihe Rive (RQ = 0.41) and Hun River (RQ = 0.16) of DiBP showed medium risk. And sediment samples of Yellow River (RQ = 0.71) and Chao Hu Lake (RQ = 0.42) of DiBP showed medium risk. Meanwhile, the above water and sediment samples (RQ＜0.1) of DnOP showed low risk.

Enhanced Glioblastoma Selectivity of Harmine via the Albumin Carrier.

Glioblastoma, the most common tumor in the brain, has witnessed very little clinical progress over the last decades. Exploring and discovering new therapeutic strategies for glioblastoma has become a critical problem. Harmine (HM), belonging to the beta-carboline alkaloid, is a natural product and isolated from the seeds of Peganum harmala L., which own notable antitumor activity in vitro. However, the poor water solubility and less selectivity of HM severely limit its clinical use. For enhancing its selective ability to tumor cells, we fabricated a kind of protein nanoparticles (BSA-HM NPs), composed of the modified bovine serum albumin (BSA) and HM. It was substantiated through in vitro and in vivo experiment that BSA-HM NPs could predominantly accumulate in tumor tissues and exhibited remarkably enhanced antitumor efficacy. This study provides a promising strategy to improve the bioavailability and avoid side effects of HM as antitumor agents by choosing BSA as carriers.

[Enhancing effect of deoxynivalenol-mediated GRP78 down-regulation on heavy chain secretion and bioactivity of two-chain FVIII gene co-transfected cells].

Although two chain transfering separately could be used to overcome the volume limitation of adeno-associated virus vectors (AAV) in coagulation factor VIII (FVIII) gene delivery, it leads to chain imbalance for inefficient heavy chain secretion. In this study we aimed to improve the efficacy of two chain strategy in FVIII gene delivery through the degradation of glucose-regulated protein 78 (GRP78) known as a protein chaperone in endoplasmic reticulum (ER) by deoxynivalenol (DON) to decrease GRP78-bound FVIII heavy chain. By treating the two-chain gene transduced 293 cells with DON, the heavy chain (HC) secretion and FVIII bioactivity were observed. Data showed that 293 cells after three hours post-treatment with DON at a concentration of 500 ng mL(-1) resulted in obvious decrease the level of GRP78 but no effect on the cell proliferation. The HC secreted from DON-treated cells transfected with HC gene alone was 59 +/- 11 ng mL(-1), higher than that secreted by control cells (15 +/- 4 ng mL(-1)), and the HC secretion was further increasing to 146 +/- 34 ng mL(-1) in light chain (LC) gene co-transfected cells with an activity measured up to 0.66 +/- 0.15 U mL(-1), also greater than control cells (76 +/- 17 ng mL(-1) and 0.35 +/- 0.09 U mL(-1)). Taken together, these data suggest that DON-mediated GRP78 down-regulation could improve the efficacy of two-chain FVIII gene transfering by facilitating HC secretion, providing an experimental basis for in vivo dual-AAV application in FVIII gene delivery.

Long noncoding RNA H19 accelerates tenogenic differentiation by modulating miR-140-5p/VEGFA signaling.

Rotator cuff tear (RCT) is a common tendon injury, but the mechanisms of tendon healing remain incompletely understood. Elucidating the molecular mechanisms of tenogenic differentiation is essential to develop novel therapeutic strategies in clinical treatment of RCT. The long noncoding RNA H19 plays a regulatory role in tenogenic differentiation and tendon healing, but its detailed mechanism of action remains unknown. To elucidate the role of H19 in tenogenic differentiation and tendon healing, tendon-derived stem cells were harvested from the Achilles tendons of Sprague Dawley rats and a rat model of cuff tear was established for the exploration of the function of H19 in promoting tenogenic differentiation. The results showed that H19 overexpression promoted, while H19 silencing suppressed, tenogenic differentiation of tendon-derived stem cells (TDSCs). Furthermore, bioinformatic analyses and a luciferase reporter gene assay showed that H19 directly targeted and inhibited miR-140-5p to promote tenogenic differentiation. Further, inhibiting miR-140-5p directly increased VEGFA expression, revealing a novel regulatory axis between H19, miR-140-5p, and VEGFA in modulating tenogenic differentiation. In rats with RTC, implantation of H19-overexpressing TDSCs at the lesion promoted tendon healing and functional recovery. In general, the data suggest that H19 promotes tenogenic differentiation and tendon-bone healing by targeting miR-140-5p and increasing VEGFA levels. Modulation of the H19/miR-140-5p/VEGFA axis in TDSCs is a new potential strategy for clinical treatment of tendon injury.

Arthroscopic Hip Surgery versus Conservative Therapy on Femoroacetabular Impingement Syndrome: A Meta-Analysis of RCTs.

To determine the outcome and differences between arthroscopic hip surgery and conservative therapy in patients suffering from femoroacetabular impingement syndrome, we searched articles from PubMed, Embase, Cochrane, Web of Science and Clinicaltrials.gov using a Boolean search algorithm. Only randomized controlled trials comparing arthroscopic hip surgery and conservative therapy were included in this meta-analysis of femoroacetabular impingement syndrome management. Two authors determined eligibility, extracted the needed data and assessed the risk of bias of eligible studies independently. Then we meta-analyzed three articles to assess pooled estimate size (ES) and 95% confidence interval for Hip Outcome Score of activities of daily living (HOS ADL subscale), Hip Outcome Score sport (HOS sports subscale) and International Hip Outcome Tool (iHOT-33) analyses were performed by using STATA version 14.0 MP (STATA, College Station, TX, USA) with the principal summary measures are mean between group difference, sample size, and standard deviation. We collected 52 articles in total after removing duplicates and screened by titles and abstracts. A total of three RCTs were included finally. There was definite evidence of additional benefit of arthroscopic hip surgery against conservative therapy in the field of improving quality of life (three trials, 575 participants, ES = 2.109, 95% CI: 1.373 to 2.845, I2  = 42.8%, P = 0.000) and activity of daily living (two trials, 262 participants, ES = 9.220, 95% CI: 5.931 to 12.508, I2  = 16.5%, P = 0.000). However, no significant difference could be seen in sports function improvement (two trials, ES = 7.562, 95% CI: -2.957 to 18.082, I2  = 60.1%, P = 0.159). In conclusion, this meta-analysis suggests that arthroscopic hip surgery provided essential benefit compared with conservative therapy in improving activity of daily living and quality of life.

Diabetes mellitus accelerates the progression of osteoarthritis in streptozotocin-induced diabetic mice by deteriorating bone microarchitecture, bone mineral composition, and bone strength of subchondral bone.

BACKGROUND: The purpose of this study was to develop an optimal diabetes-osteoarthritis (DM-OA) mouse model to validate that diabetes aggravates osteoarthritis (OA) and to evaluate the microarchitecture, chemical composition, and biomechanical properties of subchondral bone (SB) as a consequence of the DM-OA-induced damage induced. METHODS: Mice were randomly divided into three groups: DM-OA group, OA group, and sham group. Blood glucose levels, body weight, and food intake of all animals were recorded. Serum calcium (Ca) and osteocalcin (OCN) levels were compared in the three groups. The messenger ribonucleic acid (mRNA) and protein expression of key regulators for bone metabolism were detected. A semi-quantitative grading system [Osteoarthritis Research Society International (OARSI)] was used to evaluate cartilage and SB degeneration. Microspectroscopy, microindentations, micro-computed tomography (CT) imaging, and fracture load of compression testing were also used to evaluate trabecular SB properties. RESULTS: Glycemic monitoring and pancreas pathological results indicated stable high blood glucose and massive destruction of pancreas and islet cells in the DM-OA group. Serum levels of bone specific alkaline phosphatase (ALP-B) and tartrate-resistant acid phosphatase 5b (TRACP-5b) in the DM-group were higher than those of the other two groups while levels of serum Ca and OCN were lower. Meanwhile, the protein and mRNA expression of osteoblast-specific biomarkers [osteoprotegerin/receptor activator of nuclear factor kappa-B ligand (OPG/RANKL) ratio, collagen type I (COL-I), Runt-related transcription factor 2 (RUNX-2), OCN] were suppressed, and osteoclast-specific biomarkers [sclerostin (SOST)] was elevated in the DM-OA group. The mineral-to-collagen ratio, microindentation elastic modulus, hardness, micro-architectural parameters, bone mineral density, and fracture load of SB trabecular bone of the DM-OA group joint were lower than those of the other two groups. On the other hand, The OARSI score, trabecular spacing, and structural model index of the DM-OA group joint were higher than those of the other two groups. CONCLUSIONS: The glycemic and pancreatic pathological results indicated that the DM-OA model was a simple and reliable model induced by streptozotocin (STZ) and surgery. The results revealed the mechanisms through which diabetes accelerates OA; that is, by damaging and deteriorating the functions of SB, including its microarchitecture, chemical composition, and biomechanical properties.