Palladium-platinum bimetallic nanomaterials and their application in Staphylococcus aureus detection on paper-based devices.

In this study, we demonstrate how palladium@platinum nanoparticles (Pd@Pt NPs) can be used as a nanozyme for the detection of Staphylococcus aureus (S. aureus) on a paper-based analytical device. Pt was doped with Pd to form bimetallic NPs that serve as a peroxidase mimetic, which can enhance the reaction area with a substrate (3, 3', 5, 5'-tetramethylbenzidine, TMB). After material characterization, we show the peroxidase-like activity of the Pd@Pt NPs featured a 13-times higher binding affinity value (Km) for TMB compared to horseradish peroxidase, which is currently widely used in immunoassays. By incorporating the Pd@Pt NPs in a paper-based immunoassay, we can detect protein A, the biomarker of S. aureus, within 30 min with a detection limit of 9.56 ng/mL. We have also successfully validated this nanozyme-immobilized paper-based analytical device (nPAD) for the detection of human immunoglobulin G to demonstrate the capability of the Pd@Pt NPs for different target analytes. This highly sensitive, rapid, and portable nPAD design has the potential for personalized medicine and point-of-care testing, which could expand on-site prognoses in resource-limited settings.

Activation of Angiogenesis and Wound Healing in Diabetic Mice Using NO-Delivery Dinitrosyl Iron Complexes.

In diabetes, abnormal angiogenesis due to hyperglycemia and endothelial dysfunction impairs wound healing and results in high risks of diabetic foot ulcers and mortality. Alternative therapeutic methods were attempted to prevent diabetic complications through the activation of endothelial nitric oxide synthase. In this study, direct application of nitric oxide using dinitrosyl iron complexes (DNICs) to promote angiogenesis and wound healing under physiological conditions and in diabetic mice is investigated. Based on in vitro and in vivo studies, DNIC [Fe2(µ-SCH2CH2OH)2(NO)4] (DNIC-1) with a sustainable NO-release reactivity (t1/2 = 27.4 ± 0.5 h at 25 °C and 16.8 ± 1.8 h at 37 °C) activates the NO-sGC-cGMP pathway and displays the best pro-angiogenesis activity overwhelming other NO donors and the vascular endothelial growth factor. Moreover, this pro-angiogenesis effect of DNIC-1 restores the impaired angiogenesis in the ischemic hind limb and accelerates the recovery rate of wound closure in diabetic mice. This study translates synthetic DNIC-1 into a novel therapeutic agent for the treatment of diabetes and highlights its sustainable •NO-release reactivity on the activation of angiogenesis and wound healing.

Extension of C. elegans lifespan using the ·NO-delivery dinitrosyl iron complexes.

The ubiquitous and emerging physiology function of endogenous nitric oxide in vascular, myocardial, immune, and neuronal systems prompts chemists to develop a prodrug for the controlled delivery of ·NO in vivo and for the translational biomedical application. Inspired by the discovery of natural [Fe(NO)2] motif, herein, we develop the synthetic dinitrosyl iron complexes (DNICs) [Fe2(µ-SR)2(NO)4] (1) as a universal platform for the O2-triggered release of ·NO, for the regulation of ·NO-release kinetics (half-life = 0.6-27.4 h), and for the activation of physiological function of ·NO. Using C. elegans as a model organism, the ·NO-delivery DNIC 1 regulates IIS signaling pathway, AMPK signaling pathway, and mitochondrial function pathway to extend the lifespan and to delay the aging process based on the lifespan analysis, SA-ßgal activity assay, and next-generation RNA sequencing analysis. This study unveils the anti-aging effect of ·NO and develops DNICs as a chemical biology probe for the continued discovery of unprecedented NO physiology.

Modified Bunnell suture expands the surgical indication of the treatment of Haglund's syndrome heel pain with endoscope.

The aim of the present study was to develop a method which can solve the problem of partial tearing of the Achilles tendon insertion caused by the debridement for Haglund's syndrome using endoscopy-assisted percutaneous repair. Seven patients with Haglund's syndrome were prospectively recruited. All 7 patients (3 female, 4 male) had intratendinous calcifications. Preoperative diagnosis was made according to the clinical symptoms and diagnosis, medical examination results, plain film radiographs, and magnetic resonance imaging. The patients whose average age was 35.2 years, had experienced symptoms and were treated by conservative methods for 12-24 months (average 17.1 months). All 7 cases were treated with debridement of Achilles tendon insertion site with a standard 4.0 mm bur and underwent repair treatment with a modified Bunnell suture method under direct visualization using arthroscopy. The American Orthopaedic Foot and Ankle Society (AOFAS) score and the changes of the patient's parallel pitch lines were used to evaluate and assess the results. The follow-up period averaged 22 months. The lateral X-ray film after operation of all the heels of the patients showed that sufficient osseous planning of all the patients was completed. None of the patients converted to conventional open surgery. The average AOFAS scores of the 7 cases were improved significantly at final follow-up compared to pretherapy (P<0.005). The results of 5 of the 7 cases were excellent, 2, were good, and 0 was fair or poor. None of the cases had permanent nerve injuries, wound infections or Achilles tendon avulsion. Our study is a supplement of endoscopic repairing and strengthening of the Achilles tendon. The advantages and clinical significance of endoscopy during the treatment of Haglunds syndrome under the premise of strict control of operation indications were further verified.

Three-dimensional virtual planning in precise chimeric fibula free flap for metacarpal defects: A case report.

RATIONALE: Metacarpal and phalanx defects with soft tissue loss were suggested to be reconstructed by vascularized bone flap. The fibular osteocutaneous flap is a preferred method. Three-dimensional virtual planning has successfully applied in mandibular reconstruction with fibular free flap. We applied three-dimensional virtual planning in precise fibula flap harvest to maintain the continuity of the fibula and to achieve accurate metacarpal and phalanx reconstruction. PATIENT CONCERNS: A 35-year-old male presented with extensive soft tissue defects and first metacarpal defect involving the first metacarpophalangeal joint. DIAGNOSES: There were 4 cm of first metacarpal defect involving the first metacarpophalangeal joint and soft tissue defects of 5cm × 3cm + 3cm × 2cm. INTERVENTIONS: By combining three-dimensional virtual planning, we harvested a chimeric fibular flap. The precise fibula partial osteotomies were performed with cutting guides designed in virtual planning. OUTCOMES: All the chimeric flaps survived and no significant donor-site morbidity was noted. Michigan Hand Outcome Questionnaire scores indicated acceptable functional results. LESSONS: Our preliminary experience with the approach of three-dimensional virtual planning in precise chimeric fibula free flap is practical and efficient. Although more cases and follow-up are needed to evaluate it, this approach is expected to benefit patients.

In vitro and in vivo imaging of peroxynitrite by a ratiometric boronate-based fluorescent probe.

Peroxynitrite (ONOO-) is an important species involved in many physiopathological processes. Progresses have been made in developing novel fluorescent probes to detect peroxynitrite with relatively high sensitivity and specificity. Herein, we report the synthesis, characterization and biological applications of a new boronate-based fluorescent probe, 4-MB. The studies showed that 4-MB exhibits a dual ratiometric and calorimetric response toward peroxynitrite due to ONOO--triggered oxidative reaction. A possible mechanism of the oxidation reaction was proposed and the reaction product was isolated and characterized using different spectroscopic methods. We have thoroughly demonstrated the utility of 4-MB for intracellular peroxynitrite imaging. Further, we showed that 4-MB can be potentially employed to visualize exogenous and endogenous peroxynitrite in RAW264.7 macrophages, EAhy926 cells, zebrafish and in live tissues from a high-fat diet-induced obese mouse model.

Water-Soluble Dinitrosyl Iron Complex (DNIC): a Nitric Oxide Vehicle Triggering Cancer Cell Death via Apoptosis.

Nitric oxide (NO) is an important cellular signaling molecule that modulates various physiological activities. Angiogenesis-promoting activities of NO-donor drugs have been explored in both experimental and clinical studies. In this study, a structurally well characterized and water-soluble neutral {Fe(NO)2}(9) DNIC [(S(CH2)2OH)(S(CH2)2NH3)Fe(NO)2] (DNIC 2) was synthesized to serve as a NO-donor species. The antitumor activity of DNIC 2 was determined by MTT assay, confocal imaging, and Annexin-V/PI staining. The IC50 values of DNIC 2 were 18.8, 42.9, and 38.6 µM for PC-3, SKBR-3, and CRL5866 tumor cells, respectively. Moreover, DNIC 2 promoted apoptotic cell death via activation of apoptosis-associated proteins and inhibition of survival associated proteins. In particular, DNIC 2 treatment suppressed PC-3 tumor growth by 2.34- and 19.3-fold at 7 and 21 days, in comparison with the control group. These results indicate that water-soluble DNIC 2 may serve as a promising drug for cancer therapy.

Fibroma of tendon sheath in planta.

PURPOSE: Fibroma of tendon sheath in planta is comparatively rare, and its differentiate diagnose, tumour features, treatment and complications were lack of retrospective study in clinics. METHODS: This was a retrospective study of 13 patients (seven women, six men) operated between July 2001 and May 2013 for FTS in planta. The average age at the time of the procedure was 49.8 ± 8.3 years old (range 31-64). The female-to-male ratio was 9:4. Before the surgery, anteroposterior, lateral and oblique position of foot X-rays were performed in all patients. Ultrasonography (n = 11) and magnetic resonance imaging (n = 11) were performed selectively. The tumor located on the metatarsal par (n = 6), the central part of plantar (n = 4), the lateral part (n = 2) and the medial part (n = 1). Eight patients presented with painless mass (62 % of cases), while five patients presented with pain mass (38 % of cases). No patient had bony erosion. This paper studies the different features of FTS and classifies them into two types-superficial type that tumour grows at planter fascia; deep type that breaks through the planter fascia growing around tendon and joint capsule. Eight and five patients were diagnosed as superficial type and deep type respectively. RESULTS: In all cases, the tumor was excised, pathological results was FTS. The mean follow-up period was 3.2 ± 1.1 years (range 2-7) years. Five patients had neurovascular bundle involvement (38 % of cases). Two patients had a recurrence (15 % of cases), they undergone another operation. Four patients had a pain (31 % of cases), two patients had numbness (15 % of cases), and one patient had pain and numbness (8 % of cases). They recovered after conservative treatment. CONCLUSION: For the FTS that grows in the plantar, we should select differential diagnosis and the corresponding therapy according to the features of two types, also the prognosis is different. LEVEL OF EVIDENCE: IV.

Surgically treated solitary giant gluteal and retroperitoneal neurofibroma: a case report.

BACKGROUND: Giant neurofibromas in patients with neurofibromatosis type 1 involve multiple regions and are often difficult to surgically extirpate. However, surgical intervention is the most effective means for improving quality of life. The case reported herein is unique in that it involves a giant neurofibroma, involving the patient's peritoneal and pelvic cavities, retroperitoneal space, and buttock, which was causing compressive displacement of abdominal and pelvic organs. A challenging surgical intervention was required to accomplish near-total resection to relieve organ compression while preserving visceral and genitoanal function. CASE PRESENTATION: The case reported is of a patient presenting with a solitary giant retroperitoneal neurofibroma that threatened to obliterate both peritoneal and pelvic cavities and protruded conspicuously into the right gluteal region. The enormous dumbbell-shaped mass was surgically removed in three parts. Postoperative pathology studies confirmed a diagnosis of neurofibroma. Follow-up computed tomography images taken three months postoperatively revealed residual tumor in the perianal region. The patient's quality of life had measurably improved on follow-up at eight months. CONCLUSIONS: Surgical intervention in such extraordinary circumstances of a giant neurofibroma causing compressive displacement of critical organs reduces tumor burden, restores appearance and function of patient's body and internal organs, and improves the patient's quality of life.

Endoscope-assisted medial sural artery perforator flap for head and neck reconstruction.

BACKGROUND: Head and neck defect reconstructions with various free perforator flaps have been widely reported. We recommend a technique of using endoscopy to confirm the location of the medial sural artery perforator (MSAP). Further, we use a free MSAP flap for the reconstruction of head and neck defects. PATIENTS AND METHODS: Since 2010, we have carried out 18 transfers of the free MSAP flap in various anatomical locations of the head and neck. The free flap was designed based on endoscopy confirmation and contained perforator vessels. The donor site was directly sutured or skin grafted. RESULTS: Twenty perforators (35.7%) detected by Doppler were confirmed by endoscopy. The number of sizable perforators ranged from one to three (mean, 1.4). The size of the flaps ranged from 22 to 88 cm(2) (mean, 41 cm(2)). The length of vascular pedicle ranged from 5 to 14 cm (mean, 8.3 cm). All 18 flaps survived with good quality and aesthetic contours. CONCLUSIONS: The MSAP flap is an ideal flap for head and neck reconstruction. It has generally thin and pliable skin, a long and reliable vascular pedicle, straightforward intramuscular dissection, the possibility of chimeric flap design, and minimal donor-site morbidity. The reliability and safety of harvesting an MSAP flap may be increased by endoscopic confirmation of the perforators.

Bispecific Antibody Conjugated Manganese-Based Magnetic Engineered Iron Oxide for Imaging of HER2/neu- and EGFR-Expressing Tumors.

The overexpression of HER2/neu and EGFR receptors plays important roles in tumorigenesis and tumor progression. Targeting these two receptors simultaneously can have a more widespread application in early diagnosis of cancers. In this study, a new multifunctional nanoparticles (MnMEIO-CyTE777-(Bis)-mPEG NPs) comprising a manganese-doped iron oxide nanoparticle core (MnMEIO), a silane-amino functionalized poly(ethylene glycol) copolymer shell, a near infrared fluorescence dye (CyTE777), and a covalently conjugated anti-HER2/neu and anti-EGFR receptors bispecific antibody (Bis) were successfully developed. In vitro T2-weighted MR imaging studies in SKBR-3 and A431 tumor cells incubated with MnMEIO-CyTE777-(Bis)-mPEG NPs showed - 94.8 ± 3.8 and - 84.1 ± 2.8% negative contrast enhancement, respectively. Pharmacokinetics study showed that MnMEIO-CyTE777-(Bis)-mPEG NPs were eliminated from serum with the half-life of 21.3 mins. In vivo MR imaging showed that MnMEIO-CyTE777-(Bis)-mPEG NPs could specifically and effectively target to HER2/neu- and EGFR-expressing tumors in mice; the relative contrast enhancements were 11.8 (at 2 hrs post-injection) and 61.5 (at 24 hrs post-injection) fold higher in SKBR-3 tumors as compared to Colo-205 tumors. T2-weighted MR and optical imaging studies revealed that the new contrast agent (MnMEIO-CyTE777-(Bis)-mPEG NPs) could specifically and effectively target to HER2/neu- and/or EGFR-expressing tumors. Our results demonstrate that MnMEIO-CyTE777-(Bis)-mPEG NPs are able to recognize the tumors expressing both HER2/neu and/or EGFR, and may provide a novel molecular imaging tool for early diagnosis of cancers expressing HER2/neu and/or EGFR.

Identification of Id1 as a downstream effector for arsenic-promoted angiogenesis via PI3K/Akt, NF-κB and NOS signaling.

Exposure to arsenic is known to be a risk factor for various types of cancer. Apart from its carcinogenic activity, arsenic also shows promoting effects on angiogenesis, a crucial process for tumor growth. Yet, the mechanism underlying arsenic-induced angiogenesis is not fully understood. In this study, we aimed at investigating the involvement of inhibitor of DNA binding 1 (Id1) and the associated signal molecules in the arsenic-mediated angiogenesis. Our initial screening revealed that treatment with low concentrations of arsenic (0.5-1 µM) led to multiple cellular responses, including enhanced endothelial cell viability and angiogenic activity as well as increased protein expression of Id1. The arsenic-induced angiogenesis was suppressed in the Id1-knocked down cells compared to that in control cells. Furthermore, arsenic-induced Id1 expression and angiogenic activity were regulated by PI3K/Akt, NF-κB, and nitric oxide synthase (NOS) signaling. In summary, our current data demonstrate for the first time that Id1 mediates the arsenic-promoted angiogenesis, and Id1 may be regarded as an antiangiogenesis target for treatment of arsenic-associated cancer.

Three different methods for treating multiple enchondromatosis in one hand.

Ollier's disease remains comparatively rare, and is a non-hereditary cartilage dysplasia of bone. It is usually associated with problems such as deformity and fracture. Three different methods were used in a one-hand of 15-year-old boy reporting his pain in the left hand and swellings. After the curettage of tumor, regarding as the differences of all parts of the bone structure reconstruction in the patient's hand, we chose three following methods for this boy, i.e. fixed by the locking plate with calcium phosphate cement, filled with allograft bone, curetted the tumor without any bone graft. After the surgery, the patient was able to perform full motion of the operated hand. No evidence of recurrence was noted four years after surgery. To choose the different ways with bone grafts or not that relies on the patients' conditions for bone structure reconstruction. However, patients with large osseous defects or pathological fracture, we demand full bone graft and reliable internal fixation. After surgery, early exercises can reach a desirable result and functional recovery.

Inflammatory myofibroblastic tumor of the hand: A case report.

The present study reports the case of a 58-year-old male patient who repeatedly presented with hand ulcers that were diagnosed as cellulitis. Upon histological analysis, however, an inflammatory myofibroblastic tumor (IMT) was diagnosed. IMTs rarely occur in the hands. The involved tissue was removed with the tumor, with the exception of the tendons and cutaneous nerve. The involved tendon sheath and epineurium were carefully resected. After 2 years of follow-up, the patient showed no signs of tumor recurrence and the hand function was good. IMTs in the hands are relatively rare, and are often easily misdiagnosed as infection. An early and correct diagnosis is the key to successful treatment. A biopsy is necessary following debridement of the infected lesion, particularly for recurrent infected lesions. The surgical approach should be conservative, in order to maintain maximum hand function.

A switch-on MRI contrast agent for noninvasive visualization of methylmercury.

This communication presents the first Gd(III)-based T1 MRI contrast agent, o-MeHgGad, for noninvasive visualization of CH3Hg(+). o-MeHgGad showed a relaxivity enhancement of 62% in the presence of 1 equiv. of CH3Hg(+). Moreover, a noticeable contrast enhancement was recorded in the liver, kidney, and intestine of mice exposed to CH3Hg(+). Thus, the newly designed contrast agent has the potential to be used for in vivo bio-imaging of CH3Hg(+) and could be useful for biomedical applications.

Reaction-based epoxide fluorescent probe for in vivo visualization of hydrogen sulfide.

Hydrogen sulfide (H2S) has emerged as the most important biosynthetic gasotransmitters along with nitric oxide (NO) and carbon monoxide (CO). In this study, we report the design and the synthesis of a new epoxide fluorescent probe 7-glycidyloxy-9-(2-glycidyloxycarbonylphenyl)-2-xanthone (FEPO) for use in in vivo visualization of hydrogen sulfide. The probe employs a fluorescein as a fluorophore, and is equipped with an operating epoxide unit. FEPO functions via epoxide ring opening upon nucleophilic attack of H2S. This ring opening strategy may open a new avenue for the development of various H2S fluorescent sensors. FEPO showed high selectivity and high sensitivity for H2S. FEPO's cytotoxicity was tested using MTT (2-(4,5-dimethyl-2-thiazolyl)-3,5-diphenyl-2H-tetrazolium bromide) assay. Furthermore, the use of confocal imaging of H2S and in vivo imaging in live zebra fish demonstrated FEPO's potential biological applications. We anticipate that, owing to their ideal properties, probes of this type will find great uses in exploring the role of H2S in biology.

Artificial finger joint replacement due to a giant cell tumor of the tendon sheath with bone destruction: A case report.

The current study presents the case of a 25-year-old male who developed tumor recurrence of the proximal phalange of the ring finger on the right hand 4 years after partial tumor resection surgery. An X-ray of the right hand showed that the distal bone of the proximal phalange on the ring finger was destroyed. An artificial finger joint replacement was performed using a silicone joint for this unusual tumor recurrence. The pathological findings were indicative of a giant cell tumor of the tendon sheath. As a result of surgery, the patient's proximal interphalangeal point motion recovered to the pre-operative level. The pre-operative and post-operative disabilities of the arm, at shoulder and hand and total activity measurement values were 1.67 and 3.33, and 255 and 243°, respectively. Complications such as tumor recurrence, joint dislocation and the requirement for prosthetic training were not observed during the 5-year follow-up period.

Tea consumption didn't modify the risk of fracture: a dose-response meta-analysis of observational studies.

BACKGROUND: Fractures are important causes of healthy damage and economic loss nowadays. The conclusions of observational studies on tea consumption and fracture risk are still inconsistent. The objective of this meta-analysis is to determine the effect of tea drinking on the risk of fractures. METHODS: A comprehensive literature search was conducted in PubMed, Embase and reference lists of the relevant articles. Observational studies that reported an estimate of the association between tea drinking and incidence of fractures were included. A meta-analysis was conducted by the STATA software. RESULTS: A total of 9 studies involving 147,950 individuals that examined the association between tea consumption and risk of fractures were included in this meta-analysis. The odds risks (ORs) with 95% confidence intervals (CIs) were pooled using a random-effects model. The pooled OR of 9 observational studies for the tea consumption on risk of fracture was 0.89 (95% CI, 0.78-1.04). In the subgroup analyses, no significant association was detected in neither cohort studies (n=3; OR, 0.97; 95% CI, 0.89-1.06) nor case-control studies (n=6; OR, 0.91; 95% CI, 0.70-1.19), respectively. No significant association was detected in the dose-response meta-analysis. CONCLUSIONS: Tea consumption might not be associated with the risk of fractures. The following large-sample and well-designed studies are required to confirm the existing conclusions. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5309904231178427.

Color Doppler imaging of an ulnar artery perforator forearm flap for resurfacing finger defects.

BACKGROUND: Fingertip defect reconstruction with various free perforator flaps has been widely reported. We recommend a technique of using color Doppler imaging to locate ulnar artery perforator. And we used a free mesioforearm flap based on ulnar artery perforator for the reconstruction of fingertip defect. PATIENTS AND METHODS: Since 2010, 7 fingertip defect cases have been repaired at our hospital using free mesioforearm flaps, based on the ulnar artery perforator. The free flap was designed according to Doppler detection. The flap contained perforator vessels and cutaneous nerves. The donor site was directly sutured or skin grafted. RESULTS: All 7 flaps survived with good quality and esthetic contours and grasp function of the hand was satisfactory. They were evaluated by 2-point discrimination, with 5 cases with neurorrhaphy of 6 to 8 mm and 2 cases without neurorrhaphy of 10 to 12 mm. CONCLUSIONS: Ultrasound is a suitable method for preoperatively locating the vascular pedicle. The free mesioforearm flap based on ulnar artery perforator is a good option to repair fingertip defect.

Peptide-based MRI contrast agent and near-infrared fluorescent probe for intratumoral legumain detection.

Recent studies suggest that intratumoral legumain promotes tumorigenesis. To monitor legumain activity in tumors, we developed a new MRI contrast agent ([Gd-NBCB-TTDA-Leg(L)]) and a NIR fluorescence probe (CyTE777-Leg(L)-CyTE807). The MRI contrast agent was prepared by introduction of cyclobutyl and benzyl group residues to TTDA (3,6,10-tri(carboxymethyl)-3,6,10-triaza-dodecanedioic acid), followed by the attachment of a legumain-specific substrate peptide (Leg(L)). The NIR fluorescence probe was designed by conjugating two NIR fluorochromes (CyTE777 and CyTE807) with Leg(L). Peptide cleavage of the MRI contrast agent by legumain can increase its hydrophobicity and promote rotational correlation time (τ(R)). Peptide cleavage of the NIR probes by the legumain relieves the self quench of the probe. Peptide cleavage of the MRI contrast agent and the NIR fluorescence probe by legumain were confirmed by T1 relaxometric studies and by fluorescence studies, respectively. In vivo MR images showed that [Gd-NBCB-TTDA-Leg(L)] attained 55.3 fold (254.2% versus 4.6%, at 2.0 h post-injection) higher imaging enhancement, as compared with control contrast agent bearing a noncleaveable peptide ([Gd-NBCB-TTDA-Leg(D)], in the CT-26 (legumain(+)) tumors. Similarly, optical imaging probe CyTE777-Leg(L)-CyTE807 attained 15.2 fold (3.34 × 10(9) photons/min versus 0.22 × 10(9) photons/min, at 24.0 h post-injection) higher imaging enhancement in the CT-26 (legumain(+)) tumors, compared to a NIR control probe (CyTE777-Leg(D)-CyTE807). These data indicate that the [Gd-NBCB-TTDA-Leg(L)] and the CyTE777-Leg(L)-CyTE807 probes may be promising tools to image the legumain-expressing cancers for diagnoses and targeted treatments.