Development and validation of an HPLC-MS/MS method for the simultaneous analysis of volatile organic compound metabolites, hydroxylated polycyclic aromatic hydrocarbons, and 8-hydroxy-2'-deoxyguanosine in human urine.

Humans are widely and concurrently exposed to volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs). However, few studies have reported the internal co-exposure levels of these chemicals in occupational and general populations. Specifically, the associations revealed between the urinary levels of metabolites of VOCs (mVOCs), hydroxylated PAHs (OH-PAHs), and oxidative stress biomarkers for humans remain limited. In this study, a method based on solid-phase extraction (SPE) and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was developed for the simultaneous analysis of 22 mVOCs, 12 OH-PAHs, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in human urine samples. The method was validated with all target analyte accuracies and precisions in the range of 76 %-120 % and 1 %-14 % at three levels of spiked urine samples, respectively. The limit of detection (LOD) and limit of quantification (LOQ) of the target analytes were 0.01-0.34 ng/mL and 0.01-7.57 ng/mL, respectively. And the method was applied to measure urinary levels of target analytes from 38 petrochemical workers in Guangzhou, South China. Except for 3-hydroxy-benzo[a]pyrene, all target analytes were detected in the urine samples. The average levels were 0.05-12.6 ng/mL for individual OH-PAHs, 0.20-73620 ng/mL for individual mVOCs, and 1.00 ng/mL for 8-OHdG. Additionally, 3-hydroxy-phenanthrene, 1-hydroxy-pyrene, 6-hydroxy-chrysene, N-acetyl-S-(trichlorovinyl)-L-cysteine, 2-methylhippuric acid, thiodiacetic acid, trans, trans-Muconic acid, and N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine had statistically significant positive effects on 8-OHdG levels, while 1-hydroxy-naphthalene, 1,2-dihydroxybenzene, and hippuric acid showed a negative effect on 8-OHdG, indicating these metabolites could lead to synergistic or antagonistic oxidative DNA damage. This study provides a robust analytical method that permits a comprehensive assessment of co-exposure to PAHs and VOCs and their potential adverse health effects.

Guidelines for management of pediatric acute hyperextension spinal cord injury.

Pediatric acute hyperextension spinal cord injury (SCI) named as PAHSCI by us, is a special type of thoracolumbar SCI without radiographic abnormality and highly related to back-bend in dance training, which has been increasingly reported. At present, it has become the leading cause of SCI in children, and brings a heavy social and economic burden. Both domestic and foreign academic institutions and dance education organizations lack a correct understanding of PAHSCI and relevant standards, specifications or guidelines. In order to provide standardized guidance, the expert team formulated this guideline based on the principles of science and practicability, starting from the diagnosis, differential diagnosis, etiology, admission evaluation, treatment, complications and prevention. This guideline puts forward 23 recommendations for 14 related issues.

Ultrasound-assisted closed reduction and percutaneous pinning for displaced and rotated lateral condylar humeral fractures in children.

BACKGROUND: It is difficult for surgeons to successfully perform closed reduction and percutaneous pinning on displaced and rotated lateral condylar humeral fractures in children. This study aimed to introduce an ultrasound-assisted closed reduction and percutaneous pinning technique and determine its usefulness in the treatment of displaced and rotated lateral condylar humeral fractures in children. METHODS: Between 2013 and 2018, 42 of 44 displaced and rotated pediatric lateral humeral condylar fractures were successfully treated with ultrasound-assisted closed reduction and percutaneous pinning. All surgical procedures were performed by 1 senior surgeon. Demographic and clinical data including age, sex, affected side, time from injury to reduction, operative time, and number of intraoperative radiographs (without fluoroscopy) were analyzed. Postoperative data were evaluated in terms of Kirschner wire in situ duration, follow-up duration, range of motion, carrying angle, cosmetic result, and complications. RESULTS: The average operative time was 67 minutes from 2013 to 2015 and 51 minutes from 2016 to 2018. All 42 patients who successfully underwent ultrasound-assisted closed reduction were followed up for >3 months, and 31 of 42 patients were followed up for >1 year. Among these 31 patients, the range-of-motion outcomes were excellent in 25 and good in 6. The carrying angle outcomes were excellent in 28 patients and good in 3. Two instances of wire infection, 9 instances of granulation tissue hyperplasia, and 23 instances of lateral spur formation occurred. No nonunion, avascular necrosis, or postoperative nerve issues were identified. CONCLUSIONS: The surgical technique of ultrasound-assisted closed reduction and percutaneous pinning presented in this study can effectively help surgeons reduce displaced and rotated lateral condylar humeral fractures in children to avoid some open reductions and achieve satisfactory outcomes.

The routine cutoff displacement of 2 mm may not reliably reflect the stability of paediatric lateral humeral condyle fractures.

INTRODUCTION: Lateral humeral condyle fracture is one of the most common fractures in children. However, the prediction of the stability of the fracture with a cutoff displacement of 2 mm remains controversial. The aim of this study was to evaluate the reliability of the routine cutoff displacement of 2 mm in predicting the stability of paediatric lateral humeral condyle fractures. METHODS: A cohort of 79 children with imaging results for lateral humeral condyle fractures from 2013 to 2019 was evaluated. The displacement on the radiographs was measured by three surgeons at different levels, and ultrasound images were obtained by two senior surgeons. The interobserver and intraobserver reliability was assessed by the intraclass correlation coefficient (ICC). A binary logistic regression model and receiver operating characteristic (ROC) curves were used to evaluate the association between the measurement and the integrity of cartilage hinges. RESULTS: The ICC for the interobserver reliability was 0.85, and the intraobserver reliability was 0.93. For each additional millimetre of displacement, the odds of cartilage hinge disruption increased by 70%. The ROC curve determined that the Youden index was only 0.07 (sensitivity, 97.8%; specificity, 8.8%) with a cutoff displacement of 2 mm. CONCLUSIONS: The routine cutoff displacement of 2 mm may not reliably reflect the stability of paediatric lateral humeral condyle fractures. The cutoff value is sensitive but not specific for predicting whether the cartilage hinge is intact.

Impact of Transverse Ultrasound Images on the Classification and Treatment of Pediatric Lateral Humeral Condyle Fractures.

BACKGROUND: Pediatric lateral humeral condyle fractures (LHCFs) are sometimes misdiagnosed and inappropriately treated on the basis of x-ray radiographs because cartilage cannot be seen on radiographs. However, as a useful technique, transverse ultrasonography can accurately and readily determine the integrity of the cartilage hinge in pediatric LHCFs. The purpose of this study was to assess the reliability of the Jakob classification, the treatment plan, and the necessity for further examination of pediatric LHCFs with the use of x-ray with and without transverse ultrasound images. METHODS: Five pediatric orthopaedic surgeons with different levels of experience evaluated 62 cases on the basis of the use of x-ray alone and x-ray combined with transverse ultrasound images. These 2 types of evaluations were repeated after an interval of 4 to 6 weeks. At the time of each evaluation, all observers were asked to classify the fractures according to the Jakob classification, to formulate treatment plans, and to determine whether further examinations were required. RESULTS: After the training of transverse ultrasound image interpretation, the interobserver reliability of the Jakob classification significantly improved from fair (a kappa of 0.54) to moderate (a kappa of 0.71) with the addition of transverse ultrasound images. The treatment plan was changed from conservative treatment to surgical treatment in 7% of the ratings but from surgical treatment to conservative treatment in 15% of the ratings after reviewing the ultrasound images, and the difference was statistically significant (P=0.003). CONCLUSIONS: The use of the Jakob classification and a treatment plan for pediatric LHCFs can be optimized by the addition of transverse ultrasound images, especially after training for transverse ultrasound image interpretation. LEVEL OF EVIDENCE: Level III-diagnostic study.

A novel transverse ultrasonography technique for minimally displaced lateral humeral condyle fractures in children.

INTRODUCTION: Management of minimally displaced lateral humeral condyle fractures in pediatric patients is controversial. This is primarily because with current imaging modalities it is difficult to accurately and conveniently determine the stability of the fractures by detecting the integrity of the cartilage hinge. Nevertheless, transverse ultrasonography has not been intensively reported in previous studies. HYPOTHESIS: Transverse ultrasonography can determine the integrity of the cartilage hinge in minimally displaced lateral condyle fractures. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 39 pediatric patients with minimally displaced fractures of the lateral humeral condyle who underwent transverse ultrasonography between 2014 and 2017. Conservative treatment was given to pediatric patients with intact cartilage hinges that had been confirmed by transverse ultrasound images. Surgical treatment was recommended for pediatric patients with disrupted cartilage hinges. Data regarding healing of the lateral humeral condyle fractures were recorded and analyzed. RESULTS: According to transverse ultrasonography, there were 14 children with intact cartilage hinges and 25 children with disrupted cartilage hinges. Fourteen children with intact cartilage hinges of the fracture were treated conservatively, and none of them showed secondary displacement. There were 16 children in whom there was surgical intervention, and 9 other children decided to have conservative treatment among the 25 children with disruption of the cartilage hinge. Five of these 9 children who underwent conservative treatment were found to have further displacement during an average of 12.6 days after the fracture event, and no other patient was found to have further displacement. CONCLUSION: Transverse ultrasonography can simply and accurately determine the stability of minimally displaced lateral condyle fractures without sedation, ionizing radiation or invasive techniques. We recommend routine use of transverse ultrasonography to detect stability of the fractures, which can effectively avoid inadequate treatment and unnecessary surgery in pediatric patients with minimally displaced fractures of the lateral humeral condyle. LEVEL OF EVIDENCE: IV, retrospective cohort study.

Traction does not decrease failure of reduction and femoral head avascular necrosis in patients aged 6-24 months with developmental dysplasia of the hip treated by closed reduction: a review of 385 patients and meta-analysis.

This study aimed to investigate the effects of preliminary traction on the rate of failure of reduction and the incidence of femoral head avascular necrosis (AVN) in patients with late-detected developmental dysplasia of the hip treated by closed reduction. A total of 385 patients (440 hips) treated by closed reduction satisfied the inclusion criteria. Patients were divided in two groups according to treatment modality: a traction group (276 patients) and a no-traction group (109 patients). Tönnis grade, rate of failure reduction, AVN rate, acetabular index, center-edge angle of Wiberg, and Severin's radiographic grade were assessed on plain radiographs, and the results were compared between the two groups of patients. In addition, a meta-analysis was performed based on the existing comparative studies to further evaluate the effect of traction on the incidence of AVN. Tönnis grade in the traction group was significantly higher than in the no-traction group (P = 0.021). The overall rate of failure reduction was 8.2%; no significant difference was found between the traction (9.2%) and no-traction groups (5.6%) (P = 0.203). The rates of failure reduction were similar in all Tönnis grades, regardless of treatment modality (P > 0.05). The rate of AVN in the traction group (14%) was similar to that of the no-traction group (14.5%; P = 0.881). Moreover, the rates of AVN were similar in all Tönnis grades, regardless of treatment modality (P > 0.05). The meta-analysis did not identify any significant difference in the AVN rate whether preliminary traction was used or not (odds ratio = 0.76, P = 0.32). At the last follow-up visit, the two groups of patients had comparable acetabular indices, center-edge angles, and Severin's radiographic grades (P > 0.05). In conclusion, preliminary traction does not decrease the failure of reduction and the incidence of AVN in developmental dysplasia of the hip treated by closed reduction between 6 and 24 months of age.

Carbon nanotubes-based drug delivery to cancer and brain.

Current treatments for cancer and the central nervous system diseases are limited, partly due to the difficulties posed by the insolubility, poor distribution of drugs among cells and lack of selectivity of drugs, the inability of drugs to cross cellular barriers and blood brain barrier (BBB). Carbon nanotubes (CNTs) possess many distinct properties including good electronic properties, remarkably penetrating capability on the cell membrane, high drug-loading and pH-dependent therapeutic unloading capacities, thermal properties, large surface area and easy modification with molecules, which render them as a suitable candidate to deliver drugs to cancer and brain. CNTs as a drug delivery could achieve a high efficacy, enhance specificity and diminish side effects. Whereas CNTs have been primarily employed in cancer treatment, a few studies have focused on the treatment and diagnosis of the central nervous system diseases using CNTs. Here, we review the current progress of in vitro and in vivo researches of CNTs-based drug delivery to cancer involving CNTs-based tumor-targeted drug delivery systems (DDS), photodynamic therapy (PDT) and photothermal therapy (PTT). Meanwhile, we also review the current progress of in vitro and in vivo researches of CNTs-based drug delivery to brain.

Carbon Nanotubes-based Drug Delivery to Cancer and Brain / 华中科技大学学报（医学）（英德文版）

Current treatments for cancer and the central nervous system diseases are limited,partly due to the difficulties posed by the insolubility,poor distribution of drugs among cells and lack of selectivity of drugs,the inability of drugs to cross cellular barriers and blood brain barrier (BBB).Carbon nanotubes (CNTs) possess many distinct properties including good electronic properiies,remarkably penetrating capability on the cell membrane,high drug-loading and pH-dependent therapeutic unloading capacities,thermal properties,large surface area and easy modification with molecules,which render them as a suitable candidate to deliver drugs to cancer and brain.CNTs as a drug delivery could achieve a high efficacy,enhance specificity and diminish side effects.Whereas CNTs have been primarily employed in cancer treatment,a few studies have focused on the treatment and diagnosis of the central nervous system diseases using CNTs.Here,we review the current progress of in vitro and in vivo researches of CNTs-based drug delivery to cancer involving CNTs-based tumor-targeted drug delivery systems (DDS),photodynamic therapy (PDT) and photothermal therapy (PTT).Meanwhile,we also review the current progress of in vitro and in vivo researches of CNTs-based drug delivery to brain.

Ultrasound assessment of the elbow joint in infants and toddlers and its clinical significance.

BACKGROUND: Ultrasound can be used for the diagnosis of elbow injuries in infants and toddlers. However, ultrasound is highly operator-dependent and accurate ultrasound examinations require a complete understanding of the complex anatomy of the elbow joint. PURPOSE: To report the normal ultrasound anatomy of the elbow, particularly of the humeroulnar joint, in infants and toddlers. MATERIAL AND METHOD: Thirty subjects aged <3 years with no history of elbow injuries underwent ultrasound examinations of the elbow joint from six directions: (i) lateral to the humeroradial joint; (ii) anterior to the humeroradial joint; (iii) posterior to the humeroradial joint; (iv) medial to the humeroulnar joint; (v) anterior to the humeroulnar joint; and (vi) posterior to the humeroulnar joint. RESULTS: The appearance of the humeroradial joint observed from three directions was similar and resembled a pair of double fists ("double-breast sign"). The appearance of the humeroulnar joint observed from three directions was different, which is related to the irregular morphology of the medial sides of the humerus and ulna. Anteroposteriorly, the coronoid and olecranon epiphyses and coronoid fossa appear anteriorly and the olecranon and trochlear epiphyses and olecranon fossa appear posteriorly, resembling a "check-mark sign". The medial epicondyle, cubital tunnel and distal humerus appear together ("double-hump sign"). The "anterior hump" is the medial epicondyle and is always higher than the "posterior hump", which is the bony protrusion on the articular surface of the distal humerus. The ultrasound signal of cortical bone in the metaphysis of the distal humerus is continuous with that of the epiphysis of the medial epicondyle. CONCLUSION: Ultrasound is useful for the diagnosis of elbow injuries in infants and toddlers.