Ultra-high performance liquid chromatography-tandem mass spectrometry assay for simultaneous determination of 22 marker compounds in traditional herbal medicine Ojeoksan.

Traditional herbal medicines (THMs) have long been in use worldwide and are considered safe for use as tonics or complementary treatments for many diseases. Advanced quality control methods for THMs are required in the regulatory framework of modern medicines. In this study, an ultra-high performance liquid chromatography-tandem mass spectrometry assay was established for the simultaneous determination of 22 marker compounds in Ojeoksan (OJS), which is composed of 15 herbal substances. All marker compounds were analyzed within 20 min and successfully identified via scheduled multiple reaction monitoring. The method validation revealed excellent performance characteristics of the method such as specificity, linearity, sensitivity, precision, and accuracy, demonstrating its suitability for intended use. The developed method was applied to samples of commercial OJS tablet and soft-extract dosage forms. The 14 marker compounds corresponding to 12 component herbal substances were determined in the samples; ephedirine, albiflorin, paeoniflorin, ferulic acid, hesperidine, neohesperidin, cinnamic acid, platycodin D, 6-gingerol, atractylenolide III, glycyrrhizin, honokiol, decursin, and magnolol. A fast and easy assay method with sufficient discrimination power was established. As a novel assay, this method can contribute to the quality control of OJS products.

The Korean hip fracture registry study.

BACKGROUND: The purpose of the Korean Hip Fracture Registry (KHFR) Study is to establish a nationwide, hospital-based prospective cohort study of adults with hip fracture to explore the incidence and risk factors of second osteoporotic fractures for a Fracture Liaison Service (FLS) model. METHODS: The KHFR, a prospective multicenter longitudinal study, was launched in 2014. Sixteen centers recruited participants who were treated for hip fracture. The inclusion criteria were patients, who were treated for proximal femur fracture due to low-energy trauma and aged 50 or more at the time of injury. Until 2018, 5,841 patients were enrolled in this study. Follow-up surveys were conducted annually to determine occurrence of second osteoporotic fracture, and 4,803 participants completed at least one follow-up survey. DISCUSSION: KHFR is a unique resource of individual level on osteoporotic hip fracture with radiological, medical, and laboratory information including DXA (dual energy x-ray absorptiometry), bone turnover marker, body composition, and hand grip strength for future analyses for FLS model. Modifiable factors for mortality after hip surgery is planned to be identified with nutritional assessment and multi-disciplinary interventions from hospitalization to follow-ups. The proportions of femoral neck, intertrochanteric, and subtrochanteric fractures were 517 (42.0%), 730 (53.6%), and 60 (4.4%), respectively, from 2014 to 2016, which was similar in other studies. Radiologic definition of atypical subtrochanteric fracture was adopted and 17 (1.2%) fractures among 1,361 proximal femoral fractures were identified. Internal fixation showed higher reoperation rate compared to arthroplasty in unstable intertrochanteric fractures (6.1% vs. 2.4%, p = 0.046) with no significant difference in mortality. The KHFR plans to identify outcomes and risk factors associated with second fracture by conducting a 10-year cohort study, with a follow-up every year, using 5,841 baseline participants. TRIAL REGISTRATION: Present study was registered on Internet-based Clinical Research and Trial management system (iCReaT) as multicenter prospective observational cohort study (Project number: C160022, Date of registration: 22th, Apr, 2016).

Surgical strategy of the treatment of atypical femoral fractures.

The atypical femoral fracture (AFF) has been attracting significant attention because of its increasing incidence; additionally, its treatment is challenging from biological and mechanical aspects. Although surgery is often required to manage complete AFFs, clear guidelines for the surgical treatment of AFFs are currently sparse. We reviewed and described the surgical treatment of AFFs and the surveillance of the contralateral femur. For complete AFFs, cephalomedullary intramedullary nailing spanning the entire length of the femur can be used. Various surgical techniques to overcome the femoral bowing common in AFFs include a lateral entry point, external rotation of the nail, and the use of a nail with a small radius of curvature, or a contralateral nail. In the case of a narrow medullary canal, severe femoral bowing, or pre-existing implants, plate fixation may be considered as an alternative. For incomplete AFFs, prophylactic fixation depends on several risk factors, such as a subtrochanteric location, presence of a radiolucent line, functional pain, and condition of the contralateral femur; the same surgical principles as those in complete AFFs can be applied. Finally, once AFF is diagnosed, clinicians should recognize the increased risk of contralateral AFFs, and close surveillance of the contralateral femur is recommended.

Characterization of macrophage activation after treatment with polysaccharides from ginseng according to heat processing.

The worldwide persistence of infectious diseases is a significant public health issue. Consequently, studying immunomodulatory ingredients present in natural products, such as ginseng, is important for developing new treatment options. Here, we extracted three different types of polysaccharides from white (P-WG), red (P-RG), and heat-processed (P-HPG) ginseng and analyzed their chemical properties and immunostimulatory activity against RAW 264.7 murine macrophages. Carbohydrates were the main components of all three polysaccharide types, while uronic acid and protein levels were relatively low. Chemical analysis indicated that the content of carbohydrates (total sugar) increased with processing temperature, while that of uronic acid decreased. Treatment with P-WG, P-RG or P-HPG stimulated nitric oxide (NO) production and increased tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6 levels in RAW 264.7 macrophages, with P-WG showing the highest activity among the three polysaccharides. The expression of inducible NO synthase, which affects NO secretion, was highest in the macrophages treated with P-WG. Analysis of intracellular signaling pathways showed that mitogen-activated protein kinases (ERK, JNK, and p38) and NF-kB p65 were strongly phosphorylated by P-WG in macrophages but were only moderately phosphorylated by P-RG and P-HPG. Collectively, these results suggest that the polysaccharides isolated from ginseng undergo different changes in response to heat processing and display different chemical compositions and immune-enhancing activities.

Passivation of precipitation-hardened UNS N07718 in a shallow sour aqueous solution.

Passivation of precipitation-hardened UNS N07718 in 5 wt% NaCl + 0.5 wt% CH3COOH was investigated. Cyclic potentiodynamic polarisation revealed that the alloy surface was passivated without active-passive transition behaviour. The alloy surface was in a stable passive state during potentiostatic polarisation at 0.5 VSSE for 12 h. Bode and Mott-Schottky plots showed that the passive film became electrically resistive and less defective with n-type semiconductive properties during the polarisation. X-ray photoelectron spectra revealed that Cr- and Fe-enriched hydro/oxide layers were formed on the outer and inner layers of the passive film, respectively. The thickness of the film was almost constant with the increase of the polarisation time. The outer Cr-hydroxide layer changed into a Cr-oxide layer during the polarisation, resulting in a decreased donor density in the passive film. The film's composition change during the polarisation should be related to the corrosion resistance of the alloy in the shallow sour conditions.

Coiled-coil structure mediated inhibition of the cytotoxic huntingtin amyloid fibrils by an IP3 receptor fragment.

Disruption of cellular homeostasis by the aggregation of polyglutamine (polyQ) in the huntingtin protein (Htt) leads Huntington's disease (HD). Effective drugs for treating HD have not been developed, as the molecular mechanism underlying HD pathogenesis remains unclear. To develop strategies for inhibiting HD pathogenesis, the intermolecular interaction of Htt with IP3 receptor 1 (IP3R1) was investigated. Peptide (termed ICT60) corresponding to a coiled-coil motif in the C-terminus of IP3R1 was designed. Several biophysical approaches revealed the strong and specific binding of ICT60 to the N-terminal part of HttEx1. ICT60 inhibited not only amyloid formation by HttEx1, but also the cytotoxicity and cell-penetration ability of the amyloid fibrils of HttEx1. The importance of coiled-coil structure was verified by charge-manipulated variants. The coiled-coil structures of ICT60-KK and -EE were partially and largely disrupted, respectively. ICT60 wild-type and -KK inhibited amyloid formation by HttEx1-46Q, whereas ICT60-EE did not block amyloidogenesis. Similarly, the cytotoxicity and cell-penetration ability of the amyloid fibrils of HttEx1-46Q were efficiently inhibited by ICT60 wild-type and ICT60-KK, but not by ICT60-EE. We propose a mechanical model explaining how an IP3 receptor-inspired molecule can modulate cytotoxic amyloid formation by Htt, providing a molecular basis for developing therapeutics to treat HD.

Discharge transitional care programme for older adults after hip fracture surgery: a quasi-experimental study.

Background: Hip fractures require extended periods of recovery and rehabilitation, subjecting older adults to discontinuous care. Discharge transition is a critical point of heightened vulnerability for older adults. Aims: This study aimed to evaluate the effectiveness of a transitional care programme on the physical functions and quality of life (QOL) of older adults after hip fracture surgery. Methods: Seventy-five older adults were assessed from pre-discharge to 6 weeks after hip surgery, and their physical functions, including walking status and activities of daily living, were measured. The QOL was measured using the European Quality of life-5 Dimensions-5 Levels (EQ 5D 5L). Results: There was a significant strong effect of time (B = 10.565; 95% CI = 2.584-18.547; p = 0.009) on the EuroQol Visual Analog Scale (EQ-VAS) for the experimental group. However, there were no significant effects of time on physical functions and EQ-5D-5L scores. Conclusions: The discharge transitional care programme improved the EQ-VAS of older adults following hip fracture surgery 6 weeks post-surgery. However, there were no significant differences in physical functions and EQ-5D between the groups.

Pyruvate dehydrogenase kinase 4 promotes ubiquitin-proteasome system-dependent muscle atrophy.

BACKGROUND: Muscle atrophy, leading to muscular dysfunction and weakness, is an adverse outcome of sustained period of glucocorticoids usage. However, the molecular mechanism underlying this detrimental condition is currently unclear. Pyruvate dehydrogenase kinase 4 (PDK4), a central regulator of cellular energy metabolism, is highly expressed in skeletal muscle and has been implicated in the pathogenesis of several diseases. The current study was designed to investigated and delineate the role of PDK4 in the context of muscle atrophy, which could be identified as a potential therapeutic avenue to protect against dexamethasone-induced muscle wasting. METHODS: The dexamethasone-induced muscle atrophy in C2C12 myotubes was evaluated at the molecular level by expression of key genes and proteins involved in myogenesis, using immunoblotting and qPCR analyses. Muscle dysfunction was studied in vivo in wild-type and PDK4 knockout mice treated with dexamethasone (25 mg/kg body weight, i.p., 10 days). Body weight, grip strength, muscle weight and muscle histology were assessed. The expression of myogenesis markers were analysed using qPCR, immunoblotting and immunoprecipitation. The study was extended to in vitro human skeletal muscle atrophy analysis. RESULTS: Knockdown of PDK4 was found to prevent glucocorticoid-induced muscle atrophy and dysfunction in C2C12 myotubes, which was indicated by induction of myogenin (0.3271 ± 0.102 vs 2.163 ± 0.192, ****P < 0.0001) and myosin heavy chain (0.3901 ± 0.047 vs. 0.7222 ± 0.082, **P < 0.01) protein levels and reduction of muscle atrophy F-box (10.77 ± 2.674 vs. 1.518 ± 0.172, **P < 0.01) expression. In dexamethasone-induced muscle atrophy model, mice with genetic ablation of PDK4 revealed increased muscle strength (162.1 ± 22.75 vs. 200.1 ± 37.09 g, ***P < 0.001) and muscle fibres (54.20 ± 11.85% vs. 84.07 ± 28.41%, ****P < 0.0001). To explore the mechanism, we performed coimmunoprecipitation and liquid chromatography-mass spectrometry analysis and found that myogenin is novel substrate of PDK4. PDK4 phosphorylates myogenin at S43/T57 amino acid residues, which facilitates the recruitment of muscle atrophy F-box to myogenin and leads to its subsequent ubiquitination and degradation. Finally, overexpression of non-phosphorylatable myogenin mutant using intramuscular injection prevented dexamethasone-induced muscle atrophy and preserved muscle fibres. CONCLUSIONS: We have demonstrated that PDK4 mediates dexamethasone-induced skeletal muscle atrophy. Mechanistically, PDK4 phosphorylates and degrades myogenin via recruitment of E3 ubiquitin ligase, muscle atrophy F-box. Rescue of muscle regeneration by genetic ablation of PDK4 or overexpression of non-phosphorylatable myogenin mutant indicates PDK4 as an amenable therapeutic target in muscle atrophy.

Average 22-Year Results of Total Hip Arthroplasty Using Harris-Galante Prosthesis in Patients under 50 Years.

Background: The Harris-Galante (HG) prosthesis is a first-generation, cementless total hip arthroplasty (THA) prosthesis. Considering the recent increase in the demand for THA in young patients and their life expectancy, a study with a follow-up duration of longer than 20 years in a young population is needed. Therefore, we evaluated the long-term clinical and radiographic results after cementless THA using the HG prosthesis in patients younger than 50 years. Methods: A total of 61 THAs performed using the HG with a minimum follow-up of 10 years were included. There were 38 men and 11 women with an average age of 46 years and the mean follow-up duration was 22 years. Clinical evaluation included modified Harris Hip Score (HHS) and radiographic analysis consisted of cup inclination, anteversion angle, component stability, osteolysis, liner wear rate, wear-through, liner dissociation, and heterotopic ossification. Complications included recurrent dislocation, periprosthetic femoral fracture, and periprosthetic joint infection. Survivorship analysis included cup and stem revision for aseptic loosening, as well as any revision. Results: The HHS improved from 46.5 preoperatively to 81.8 postoperatively (p < 0.001). The average linear wear rate was 0.36 mm/yr. A total of 34 hips (56%) were revised: stem revision in 10 (16.4%), cup revision in 9 (14.8%), exchange limited to bearing surface in 8 (13.1%), and revision of all components in 7 (11.5%). Estimated survivorship at 34 years postoperatively was 90.9% for cup revision for aseptic loosening, 80.5% for stem revision for aseptic loosening, and 22.1% for any revision. Conclusions: THA using the HG prosthesis showed satisfactory estimated survivorship of the acetabular and femoral components at 34 years postoperatively with good clinical outcomes. Bearing-related problems, such as osteolysis and liner dissociation, accounted for 56% of revision operations and were concerns in patients younger than 50 years.

Determination of etomidate and etomidate acid in hair using liquid chromatography-tandem mass spectrometry.

Etomidate, with efficacy similar to that of propofol, has been used as a propofol substitute because propofol is a designated narcotic drug, and an increase in the frequency of illegal distribution and misuse has been reported in Korea. Previous analytical studies on etomidate used blood and urine. For long-term use and timing estimation, a method for etomidate analysis using hair should be developed. Therefore, in this study, an analytical method using LC-MS/MS was developed to determine etomidate and its major metabolite in hair. Human hair samples were segmented after washing to eliminate possible contaminants on the hair and stirred with methanol. The LC-MS/MS conditions were optimized, and the chromatographic separation time was 10 min. Selectivity, linearity, limit of detection, limit of quantification, precision, accuracy, recovery, process efficiency, matrix effect, and stability were evaluated to validate the analytical method. The calibration curves ranged from 0.25 to 50 pg/mg for etomidate and 2-250 pg/mg for etomidate acid; the coefficients of determination were higher than 0.997. The intra- and inter-assay precision results for all the compounds were <15% and satisfied at recovery, process efficiency, matrix effect, and stability. In addition, this method was applied to the hair of 4 rats which are administered with etomidate to evaluate. The etomidate concentrations in the rat hair ranged from 2.60 to 8.50 pg/mg, and the etomidate acid concentrations were 2.06-7.13 pg/mg. Thus, this method can be used as basic data for monitoring etomidate in hair.

Abnormal Lipid Profiles in Nontraumatic Osteonecrosis of the Femoral Head: A Comparison with Osteoarthritis Using Propensity Score Matching.

BACKGROUND: Abnormal lipid metabolism may play an important role in the development of nontraumatic osteonecrosis of the femoral head (ON). By comparing lipid biomarkers in patients with ON and osteoarthritis (OA) after propensity score matching, we sought to reveal (1) common lipid biomarkers that are abnormal in ON regardless of the etiology and (2) specific lipid biomarkers associated with ON according to the etiology. METHODS: Among 2,268 patients who underwent primary THA, 1,021 patients were eligible for this study. According to the Association Research Circulation Osseous criteria, ON was classified as either idiopathic (n = 230), alcohol-associated (n = 293), or glucocorticoid-associated ON (n = 132). Most common cause of OA was hip dysplasia in 106 patients (47%). We investigated patient lipid profiles by assessing total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), apolipoprotein (Apo) A1 and B, lipoprotein (a) levels and ApoB/A1 ratio. Since age and body mass index affect the lipid profile, we performed propensity score matching to select 304 patients for final analysis and compared lipid profiles between the ON and OA groups. We also compared biomarkers between the ON subgroups and the OA group. RESULTS: Overall, the ON group showed lower HDL-C (p < 0.001), higher TGs (p = 0.001) levels and higher ApoB/A1 ratio (p = 0.003). Idiopathic ON patients demonstrated lower HDL-C (p = 0.032), higher TGs (p = 0.016), ApoB (p = 0.024) levels and ApoB/A1 ratio (p = 0.008). The alcohol-associated ON subgroup showed lower HDL-C (p < 0.001), higher TGs (p = 0.010) levels and ApoB/A1 ratio (p = 0.030). Finally, the steroid-associated ON subgroup demonstrated lower HDL-C (p = 0.003), higher TGs (p = 0.039), lower TC (p = 0.022), LDL-C (p = 0.021), and ApoA1 (p = 0.004) levels. CONCLUSIONS: Higher TGs and lower HDL-C levels were associated with nontraumatic ON regardless of the etiology. Additionally, idiopathic ON was associated with higher ApoB levels and ApoB/A1 ratio. Alcohol-associated ON was related to higher ApoB/A1 ratio, and steroid-associated ON paired with decreased TC, LDL-C, and ApoA1 levels. Our findings may support future efforts for prevention and management of nontraumatic ON. LEVEL OF EVIDENCE: Diagnostic Level III.

Structure and antiviral activity of a pectic polysaccharide from the root of Sanguisorba officinalis against enterovirus 71 in vitro/vivo.

The increasing prevalence and pandemic risk of viral diseases warrant the development of safe and effective treatments. In this study, we aimed to elucidate the structure and anti-enterovirus 71 (EV71) effects of polysaccharides isolated from the roots of Sanguisorba officinalis (SO), traditionally used for infectious diseases. The purified polysaccharide (S-a3) was a homogenous macromolecule (260.4 kDa) with a concave and porous surface. Linkage and NMR analyses confirmed that S-a3 is a polysaccharide interlinked with homogalacturonan, rhamnogalacturonan-I, 1,4-α-glucan, and arabinogalactan. S-a3 significantly inhibited cell death and viral gene expression in EV71-infected Vero cells, and alleviated EV71-induced body weight loss, death, and paralysis in the hSCARB2-transgenic mouse model. The effective dose of S-a3 was non-toxic to cells and mice. The antiviral mechanism of S-a3 was associated with the disruption of EV71 attachment to host cells. Our findings demonstrate that polysaccharides from SO can be a safe and effective treatment for EV71 infection.

Effect of carbon addition on the passivity of hypoeutectic high chromium cast irons.

The effect of adding C on the passivity of hypoeutectic high chromium cast iron (HCCI) was investigated in a pH 8.4 boric-borate buffer solution. The microstructure of HCCI is composed of austenite and carbide phases, whose fractions and chemical compositions are influenced by the amount of C added. Electrochemical and surface analyses revealed that the addition of C in the HCCI increased the defect densities in the n-type and p-type semiconductive oxide layers on the austenite and carbide phases, respectively.

Vital protocols for PolyWare™ measurement reliability and accuracy.

Background and objective: PolyWare™ software (PW) has been exclusively used in the majority of polyethylene wear studies of total hip arthroplasty (THA). PW measurements can be significantly inaccurate and unrepeatable, depending on imaging conditions or subjective manipulation choices. In this regard, this study aims to shed light on the conditions needed to achieve the best accuracy and reliability of PW measurements. Methods: The experiment looked at how PW fluctuated based on several measurement conditions. x-ray images of in-vitro THA prostheses were acquired under a clinical x-ray scanning condition. A linear wear rate of 6.67 mm was simulated in combination with an acetabular lateral inclination of 36.6° and anteversion of 9.0°. Results: Among all the imported x-ray images, those with a resolution of 1,076 × 1,076 exhibited the best standard deviation in wear measurements as small as 0.01 mm and the lowest frequencies of blurriness. The edge detection area specified as non-square and off the femoral head center exhibited the most blurriness. The x-ray image that scans a femoral head eccentrically placed by 15 cm superior to the x-ray beam center led to a maximum acetabular anteversion measurement error of 5.3°. Conclusion: Because PW has been the only polyethylene wear measurement tool used, identifying its sources of error and devising a countermeasure are of the utmost importance. The results call for PW users to observe the following measurement protocols: (1) the original x-ray image must be a 1,076 × 1,076 square; (2) the edge detection area must be specified as a square with edge lengths of 5 times the diameter of the femoral head, centered at the femoral head center; and (3) the femoral head center or acetabular center must be positioned as close to the center line of the x-ray beam as possible when scanning.

Multiple screw fixation versus cementless bipolar hemiarthroplasty for femur neck fracture using a nationwide hip fracture registry.

Cementless bipolar hemiarthroplasty (BHA) recently gained popularity as a treatment for femur neck fracture (FNF), but there have been few studies comparing this with multiple screw fixation (MSF) in the elderly population. The purpose of this study is to compare (1) surgery-related parameters, (2) reoperation rate as a local complication, (3) in-hospital systemic complication rate, and (4) mortality rate at 1 year after MSF and cementless BHA in patients with FNF using nationwide data. Six-hundred sixty-six hips (aged ≥ 50 years) extracted from nationwide Hip Fracture Registry were included in this study (133 MSF and 533 cementless BHA). One hundred fifty-six hips were divided into nondisplaced FNF (Group A) and 510 into displaced FNF (Group B). We evaluated (1) surgery-related parameters (anesthesia type, time to surgery, operation time, estimated blood loss and volume of postoperative transfusion), (2) the rate of and reasons for reoperation, (3) the rate and type of in-hospital systemic complications and (4) one-year mortality rate after surgery. In Group A, MSF showed shorter operation time (p = 0.004) and lower incidence of in-hospital systemic complications (p = 0.003). In Group B, cementless BHA demonstrated lower reoperation rate than MSF (p < 0.001). In both Group A and B, cementless BHA was associated with higher estimated blood loss than MSF (p < 0.001). Based on findings in our study, MSF might be a more favorable option for nondisplaced FNF, whereas cementless BHA might be a better one for displaced FNF in patients older than fifty. Nevertheless, our nationwide study also showed that numbers of cementless BHAs were being performed for nondisplaced FNF even in teaching hospitals.

Osteonecrosis of the Femoral Head: an Updated Review of ARCO on Pathogenesis, Staging and Treatment.

Non-traumatic osteonecrosis of the femoral head (ONFH) usually affects adults younger than 50 years and frequently leads to femoral head collapse and subsequent arthritis of the hip. It is becoming more prevalent along with increasing use of corticosteroids for the adjuvant therapy of leukemia and other myelogenous diseases as well as management of organ transplantation. This review updated knowledge on the pathogenesis, classification criteria, staging system, and treatment of ONFH.

Discharge transition experienced by older Korean women after hip fracture surgery: a qualitative study.

BACKGROUND: This study aimed to explore older Korean women's discharge transition experiences after hip fracture surgery. METHODS: This was a descriptive qualitative study. Face-to-face interviews following hip fracture surgery were conducted on 12 women aged 65-87 years. Data were collected 1 to 2 days before discharge and again 4 weeks after discharge following hip fracture surgery, and were analyzed using qualitative content analysis. RESULTS: Four main themes were identified: (1) challenge of discharge transition: unprepared discharge, transfer into other care settings, and eagerness for recovery; (2) physical and psychological distress against recovery: frail physical state and psychological difficulties; (3) dependent compliance: absolute trust in healthcare providers, indispensable support from the family, and passive participation in care; and (4) walking for things they took for granted: hope of walking and poor walking ability. CONCLUSIONS: After their hip fracture surgeries, older women hoped to be able to walk and perform simple daily chores they previously took for granted. Considering the physical and psychological frailty of older women undergoing hip surgery, systematic nursing interventions including collaboration and coordination with other healthcare professionals and settings are necessary to ensure the quality of continuous care during their post-surgery discharge transition. Encouraging partial weight bearing and initiating intervention to reduce fear of falling at the earliest possible time are essential to attain a stable discharge transition. Additionally, older women should be invited to participate in their care, and family involvement should be encouraged during the discharge transition period in South Korea.

Diagnosis and Treatment of Femoral Head Osteonecrosis: A Protocol for Development of Evidence-Based Clinical Practice Guidelines.

INTRODUCTION: There are many treatment options for patients who have osteonecrosis of the femoral head (ONFH) and management strategies vary widely both among and within individual countries. Although many researchers have attempted to elucidate the optimal strategies for managing this disease, the lack of large-scale randomized control trials and the lack of agreement on disease staging have curtailed the development of clear-cut guidelines. MATERIALS AND METHODS: The Association Research Circulation Osseous (ARCO) group sought to address three questions for the management of patients who have ONFH: 1) What imaging studies are most sensitive and specific for the diagnostic evaluation of patients who have ONFH?; 2) What is the best treatment strategy for preventing disease progression in patients who have pre-collapse lesions?; and 3) What is the best treatment strategy for patients who have post-collapse disease? The Patient, Intervention, Comparison, and Outcome (PICO) format was used to formulate the search strategy for each research question. A systematic review will be performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. ARCO participants have been allocated to three groups, each representing one of the PICO questions. After qualitative and quantitative analysis of the data extracted from studies pertaining to each of the three research questions, a set of evidence-based clinical practice guidelines will be proposed for the management of patients who have ONFH. DISCUSSION: It is not always clear which treatment method is optimal for the management of ONFH. Thus, many surgeons have developed and performed various procedures based on patient-specific factors. As there is no consensus on the optimal treatment for various stages of disease, it was clear that developing evidence-based clinical practice guidelines would provide more structure and uniformity to management of these patients. Therefore, the results of this systematic review will lead to the development guidelines that may improve patient-care strategies and result in better outcomes for patients who have ONFH.

Synergistic Protection by Isoquercitrin and Quercetin against Glutamate-Induced Oxidative Cell Death in HT22 Cells via Activating Nrf2 and HO-1 Signaling Pathway: Neuroprotective Principles and Mechanisms of Dendropanax morbifera Leaves.

Dendropanax morbifera leaves (DML) have long been used as traditional medicine to treat diverse symptoms in Korea. Ethyl acetate-soluble extracts of DML (DMLE) rescued HT22 mouse hippocampal neuronal cells from glutamate (Glu)-induced oxidative cell death; however, the protective compounds and mechanisms remain unknown. Here, we aimed to identify the neuroprotective ingredients and mechanisms of DMLE in the Glu-HT22 cell model. Five antioxidant compounds were isolated from DMLE and characterized as chlorogenic acid, hyperoside, isoquercitrin, quercetin, and rutin by spectroscopic methods. Isoquercitrin and quercetin significantly inhibited Glu-induced oxidative cell death by restoring intracellular reactive oxygen species (ROS) levels and mitochondrial superoxide generation, Ca2+ dysregulation, mitochondrial dysfunction, and nuclear translocation of apoptosis-inducing factor. These two compounds significantly increased the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the presence or absence of Glu treatment. Combinatorial treatment of the five compounds based on the equivalent concentrations in DMLE showed that significant protection was found only in the cells cotreated with isoquercitrin and quercetin, both of whom showed prominent synergism, as assessed by drug-drug interaction analysis. These findings suggest that isoquercitrin and quercetin are the active principles representing the protective effects of DMLE, and these effects were mediated by the Nrf2/HO-1 pathway.

Facile synthesis of carbon dots from Tagetes erecta as a precursor for determination of chlorpyrifos via fluorescence turn-off and quinalphos via fluorescence turn-on mechanisms.

Convenient one-pot synthetic route for the fabrication of carbon dots (CDs) from Tagetes erecta flower (TEF), named as "TEF-CDs', through solvo(hydro)-thermal carbonization of the TEF was developed. The TEF-CDs revealed high selectivity towards chlorpyrifos and quinalphos, acting as a fluorescent probe. The CDs synthesized from T. erecta flower showed a strong blue color at 495 nm when excited at 420 nm, along with the exhibition of a strong quantum yield of 63.7%. The synthesized CDs revealed their richness in the surface-active organic group that synthesized CDs from T. erecta flower are mainly comprised of C, O, and N, which were crystalline in structure that was revealed by TEM image and XRD spectra. Furthermore, when the probe was exposed to different pH conditions, no major noticeable changes were recorded. Moreover, when the probe was exposed to chlorpyrifos and quinalphos, we have noticed that fluorescence spectra was turned off when the probe was exposed to chlorpyrifos and "turned on" after the exposure quinalphos. Moreover, fluorescence spectral changes showed a good linearity with chlorpyrifos and quinalphos concentrations in the range of 0.05-100.0 µM for chlorpyrifos and 0.01-50.0 µM for quinalphos. The limit of detection are 2.1 ng mL-1 and 1.7 ng mL-1 for chlorpyrifos and quinalphos, respectively. Finally, the TEF-CDs-based fluorescent nanoprobe was successfully applied to estimate chlorpyrifos and quinalphos with an effective accuracy in rice and fruit samples with rapid detection time.