Application of Next Generation Sequencing in Laboratory Medicine

The rapid development of next-generation sequencing (NGS) technology, including advances in sequencing chemistry, sequencing technologies, bioinformatics, and data interpretation, has facilitated its wide clinical application in precision medicine. This review describes current sequencing technologies, including short- and long-read sequencing technologies, and highlights the clinical application of NGS in inherited diseases, oncology, and infectious diseases. We review NGS approaches and clinical diagnosis for constitutional disorders; summarize the application of U.S. Food and Drug Administration-approved NGS panels, cancer biomarkers, minimal residual disease, and liquid biopsy in clinical oncology; and consider epidemiological surveillance, identification of pathogens, and the importance of host microbiome in infectious diseases. Finally, we discuss the challenges and future perspectives of clinical NGS tests.

Environmental behavior of pahs in dianchi lake distributions, sources and risk assessment of poly cyclic aromatic hydrocarbons in surface sediments from Dianchi Lake,China

Polycyclic aromatic hydrocarbons [PAHs] in the priority controlling list of US EPA were systematically evaluated in surface sediments in Dianchi Lake and its estuaries. Total PAH concentrations [IPAHs] varied from 210 to 11,070 ng/gdry weight [d.w] in Dianchi Lake, and from 230 to 12,271 microg/g d.w. in the estuaries. IPAHs in sediments from Caohai section were higher than those from Waihai section. The occurrences of PAHs in the Lake were closely related to the distributions of rivers, indicating that the river runoff was an important pathway of PAHs into the Lake. Compared with the US Sediment Quality Guidelines [SQGs], IPAHs in most area were below the effect range low [ERL], which implied that the adverse biological effects would occur rarely. The toxic equivalent concentrations of potentially carcinogenic PAHs [TEQ[carc]] varied from 19to967ngTEQ/gd.w., and the higher values were found in northern Caohai area. The proportions of the toxic equivalent quantity [TEQ[carc]] to the total TEQs in sediments were all above 96%, suggesting that the carcinogenicity of PAHs could be occurred. Significantly positive correlations between total organic carbon [TOC] and less molecular weight PAHs [2, 3-ring] [LPAHs] were observed in the Lake. Diagnostic ratios showed that the primary source of PAHs in Dianchi Lake and most estuaries is biomass combustion, but is petroleum combustion or petrogenic origin in several other estuaries

Copper and nickel recovery from electroplating sludge by the process of acid-leaching and electro-depositing

In this work, we developed a method which combined the processes of acid-leaching, ammonium jarosite precipitating and electro-depositing to recover copper and nickel from electroplating sludge. Residual sludge from an electroplating plant located in Qingdao was used for acid-leaching, and more than 95% of copper, nickel, zinc, chromium and iron were extracted from the sludge. After acid-leaching, the extracted solution was put into an electrolytic cell for copper recovery by electro-depositing process, and about 95% of copper was recovered under the optimized operation parameters such as cell voltage, pH and electrode material. After copper recovery, the extracted solution was treated with ammonium jarosite precipitating process. About 99% of chromium and iron could be deposited as chromium ferrite in this process. Finally, the left solution was treated with electro-depositing process again for nickel recovery, and about 57% of nickel could be recovered in this process under the condition of pH 5.5 and voltage 5.5 V

Multiple Chromatographic and Chemometric Methods for Quality Standardisation of Chinese Herbal Medicines / 世界科学技术-中医药现代化

Quality standardization of complementary medicine is fundamental for industry and practice as it underpins the quality,safety and efficacy of Chinese herbal medicines.Current herbal standardizations are often based on the quantitative analysis of a single compound,which may not reflect the total characteristic,bioactive and toxic nature of the herbs or products.Therefore,there is a need to establish an internationally recognized methodology for quality standardization of Chinese herbal medicines.The analytical methods reviewed in this article are pharmacognosy,TLC,HPLC,LCMS,CE and chemo-metrics.This article also covers the developments and applications of these methods in quality standardization.Recent advances show that a combination of these methods creates an overall chemical profile of each herb.This iS supported by results reviewed in this article and obtained in our laboratory tests on medicinal herbs including Hypericum perforatum,Morinda officinalis and Centella asiatica.Significant variations in active components have been observed between herbal samples and products.It is proposed that the identification of active components,pharmacological activities and eventual clinical applications are required for a comprehensive quality standardization system.Our findings indicate that the combination of various chromatographic and chemometric methods will advance the methodology of quality standardization and enhance the overall confidence in herbal medicine for the health practitioner and the public.

Cerebral schistosomiasis caused by Schistosoma mansoni: a case report with clinical analysis

Central nervous system involvement arising from schistosomiasis is uncommon. It may be produced most frequently by Schistosoma japonicum infection, but reports of S. mansoni presenting as an intracerebral mass lesion are particularly rare. The authors describe the case of a 35-year-old woman with a 3-month history of partial epileptic seizures and headaches. She immigrated to Egypt 4 years ago and had worked in Iraq for 2 years after the immigration. The patient's general physical and neurological examinations were unremarkable. Magnetic resonance [MR] imaging revealed an enhancing lesion with surrounding edema and mild mass effect in the left frontal lobe. A stereotactic brain biopsy demonstrated intraparenchymal granulomas surrounding S. mansoni eggs. S. mansoni was identified by stool examination. Prednisone [1 mg/kg per day for 1 week, with gradual withdrawal during the following 3 weeks] and praziquantel [2 doses at 20 mg/kg per day] therapy was initiated. The patient's symptoms resolved following medical treatment and the follow-up MR imaging yielded normal findings. This case is the rare imported case of cerebral schistosomiasis in China and the neuroschistosomiasis should be considered as the patient lived in a region in which this disease is endemic

Inflammatory cytokines and childhood obstructive sleep apnoea

<p><b>OBJECTIVE</b>To evaluate serum cytokine concentrations in children with and without obstructive sleep apnoea (OSA) and to investigate the effects of OSA treatment on cytokines.</p><p><b>MATERIALS AND METHODS</b>Consecutive children with habitual snoring and symptoms suggestive of OSA were recruited. They completed a sleep apnoea symptom questionnaire, underwent physical examination and overnight polysomnography (PSG). OSA was diagnosed if obstructive apnoea index (OAI) >1. A blood sample was collected for analysis of IL-6, IL-8, and TNF-alpha after PSG.</p><p><b>RESULTS</b>One hundred forty-two children (97 males) with a median (IQR) age of 11.1 years (9.0-12.8) were recruited. The commonest presenting symptoms were nocturnal mouth breathing, prone sleeping position and poor attention at school. Forty-seven children were found to have OSA and they had higher serum IL-6 [0.1 (0.1-0.4) vs 0.1 (0.1-0.1) pg/mL, P = 0.001] and IL-8 [1.7 (1.0-2.3) vs 1.3 (0.9-1.7) pg/mL, P = 0.029] concentrations compared to their non-OSA counterparts. Multiple regression analysis indicated that OAI was significantly associated with both IL-6 (r = 0.351, P <0.001) and IL-8 (r = 0.266, P = 0.002). Sixteen children underwent treatment and there was significant reduction in mean (SD) serum IL-8 after intervention [pre vs post levels of 1.9 (1.0) vs 1.1 (0.6) pg/mL, P = 0.001] independent of weight loss.</p><p><b>CONCLUSION</b>Children with OSA had elevated levels of pro-inflammatory cytokines that normalised following treatment suggesting that the inflammatory response is potentially reversible. Early detection and intervention may be beneficial.</p>

9p subtelomere deletion: pathogenic mutation or normal variant? / 北京大学学报(医学版)

We report an apparently benign familial 9p subtelomere deletion identified using chromosome-arm-specific subtelomere probes in a patient with multiple congenital anomalies. Our experience demonstrated that the discovery of a subtelomeric deletion and/or duplication does not always guarantee the identification of the etiology for the patient's phenotype and a positive finding with subtelomere probes should always be followed by parental study with the same probe in order to distinguish a disease causing alteration from a benign familial polymorphism.

Dynamic assessment of high-resolution MRI with multi-planar reconstruction increases the yeld of lesion detection in patients with patial epilepsy

To investigate the presence and type of lesions associated with partial epilepsies by routine high resolution MRI and multi-planar reconstruction (MPR) and correlate the MRI abnormalities with semiology and EEG findings. We studied 100 consecutive patients followed in the epilepsy clinic of our Hospital with partial epilepsy who underwent MRI investigation. THE MRI protocol included 6 mm sagittal T1-weighted, 3-4 mm axial T1 and T2-weighted, 3 mm coronal T1 inversion recovery and T2-weighted images that were printed on a radiographic film for routine analysis. The clinical and EEG findings were tabulated independently, and results were comapred using Chi-square of Fisher exact test when appropriate. The patients were divided into 10 groups according to their etiological classification (structural lesions) establihed by MRI. Mesial temporal sclerosis (MTS) was the largest group (40 per cent). There were 65 women and 35 men. Mean age was 23.9 (+- 5.7) years and mean age of onset of recurrent seizures was 9.9 (+-0.8) years. The most frequent risk factors were family history of seizures (23 per cent), head trauma (10 per cent), peri-natal anoxia (5 per cent) and infection (9 per cent). High resolution MRI including thin coronal slices, in addition to a "dynamic" analysis in a workstation with MPR, allowed a significant improvement in lesion detection compared to the traditional analysis with radiographic films (94 per cent versus 80 per cent) (p<0.05). The lesions previously undetected were focal cortical dysplasia and subtle MTS. There was a good concordance between MRI lesions and clinical and EEG findings. High resolution MRI including thin coronal slices, in addition to a "dynamic" analysis in a workstation with MPR allowed a significative improvement in lesion detection compared to the traditional analysis with radiographic films 94 per cent versus 80 per cent). Patients with partial epilepsy and "normal" MRI need to to investigated further with thin slices and post-processing techniques using volume acquisitions tha allow adequate multi-planar re-slicing

Advanced molecular and cytogenetic technologies in birth defect diagnosis and prevention / 北京大学学报(医学版)

SUMMARY Fluorescence in situ hybridization (FISH) has become an important diagnostic tool as an adjunct to classical cytogenetics. FISH utilizes DNA probes comprised of specific nucleic acid sequences tagged with fluorescent molecules to identify the number and location of specific DNA sequences in human cells. These probes can be used to determine various numerical and structural chromosomal aberrations, in many cases, gene dosage and/or structure alterations. Chromosomal abnormalities are responsible for a considerable number of birth defects, and more than 50% of spontaneous abortions. These numbers have been significantly higher since the advent of FISH technology that allows the detection of submicroscopic chromosome alterations. The clinic application of FISH technology in postnatal, prenatal, and preimplantation diagnoses has been playing an important role in the diagnosis and prevention of birth defects. As new technologies evolve, more and more new FISH techniques - such as subtelomeric FISH, multicolor FISH (M-FISH), comparative genomic hybridization (CGH), and microarray - are used in clinical diagnoses, the role of FISH technology in both research and clinical aspects of birth defects will surely continue to expand.

Allergic skin rash with lamotrigine and concomitant valproate therapy

Cutaneous rash is one of the commonest adverse events associated with lamotrigine. We assessed whether the risk is increased in patients receiving concomitant valproate therapy in a population of 103 adult patients with intractable epilepsy, who had lamotrigine added to their treatment. Of the 33 patients taking valproate, 10 (30 per cent) developed a rash, whilst of the 70 not taking valproate, only 6 (8 per cent) developed a rash. This suggests a significantly higher risk of cutaneous rash when starting lamotrigine in patients already taking valproate (p