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This paper focuses on the incorporation of kinematic constraints with the learning of 3D skeleton reconstruction without suffering from corrupted pose estimations. Specifically, we devote to exploring a kinematic constrained learning architecture that incorporates the forward kinematics constraint into building a learning model for predicting skeletal key points from observed radar data in the form of range-Doppler spectrum, which contributes to eliminating the corruption of skeleton reconstruction in the scenarios when the radar signals suffer from incomplete sensing process or insufficient granularity due to the bandwidth limitation of radar sensors. In developing our learning paradigm, we define two loss functions, namely the distance loss and the angle loss with respect to the parent-child nodes of skeleton joints, to guide the learning of the deep kinematic network, which is essential to facilitate the skeleton reconstruction without corruption. In addition, the proposed learning architecture involves a refined network module to compensate the estimation offset due to error accumulation of the kinematic model in an iterative fashion. The experimental results are presented to validate the proposed method.

Background Pancreaticopleural fistula (PPF) is a rare disease, especially in children. Conservative treatment and surgery are traditional therapies, but surgery is invasive. The emergence of endoscopic retrograde cholangiopancreatography (ERCP) has provided a new noninvasive treatment for PPF and may become the first choice for children with PPF. Aim To explore the treatment response to ERCP for PPF in children. Methods Seven children with PPF were hospitalized in the Gastroenterology Department of Beijing Children's Hospital from December 2007 to May 2019. Data on these seven patients' clinical characteristics, diagnosis, treatments, and outcomes were analyzed, and their treatment responses following surgery and ERCP were compared. The correlation between the length of hospital stay and conservative treatment was analyzed. Peer-reviewed articles written in English and Chinese published from January 2009 to December 2019 were obtained from various open data sources and reviewed. Results The seven patients comprised three boys and four girls with a mean age of 6.57 ± 3.26 years. The main symptoms were chest tightness and pain (n = 4), intermittent fever (n = 3), dyspnea (n = 3), and abdominal pain (n = 1), and all patients had bloody pleural effusion. All seven patients were diagnosed with PPF by magnetic resonance cholangiopancreatography, and all were initially treated conservatively for a mean of 34.67 ± 22.03 d with a poor response. Among five patients who underwent ERCP, one required surgery because of intubation failure; thus, the success rate of ERCP was 80%. Two patients were successfully treated with surgery (100%). The postoperative hospital stay of the two patients treated by surgery was 20 and 30 d, respectively (mean of 25 d), and that of the four patients treated by ERCP ranged from 12 to 30 d (mean of 19.25 ± 8.85 d). The recovery time after ERCP was short [time to oral feeding, 4-6 d (mean, 5.33 ± 1.15 d); duration of closed thoracic drainage, 2-22 d (mean, 13.3 d)]. Analysis of previous cases of PPF published worldwide during the past decade showed that the treatment success rate of ERCP is not lower than that of surgery. There was no significant difference in the postoperative hospital stay between surgery (16 ± 10.95 d) and ERCP (18.7 ± 6.88 d, P > 0.05). A positive linear correlation was found between the overall hospital stay and ERCP intervention time (R 2 = 0.9992). Conclusion ERCP is recommended as the first-choice treatment for PPF in children. ERCP should be performed as early as possible if conditions permit.

In order to realize the storage of the residual coal in the goaf on the flue gas of the power plant, the adsorption characteristics of nitrogen dioxide in the flue gas of the power plant were studied. The Gaussian09 was used to study the adsorption process of NO2 molecules on coal at the density functional (DFT) B3LYP/6-311G level, and the model of NO2 adsorption by coal was established. Different quantities were obtained using orbital energy changes and molecular bond length changes. According to the principle of molecular adsorption, the adsorption of NO2 by coal is considered to be physical adsorption with endothermic heat. On the basis of simulation, using self-organized experimental devices, the single-component NO2 gas and the simulated coal-fired power plant flue gas were introduced into anthracite, bituminous coal and lignite. In single-component adsorption, the adsorption of NO2 by lignite increases with time. The time to reach equilibrium is related to the properties of the coal itself. In the process of simulated flue gas adsorption, the order of the adsorption amount of coal to flue gas is CO2 > NO2 > N2 > O2. In the simulated flue gas, coal is easy to absorb NO2 and CO2, and the competition between gases reduces the frequency of contact between NO2 and the coal surface. Simulation and experimental results show that coal has obvious adsorption characteristics for NO2, and it is feasible for the residual coal in the goaf to adsorb NO2 in the flue gas of power plants.

With the change in environment and lifestyle, the number of diabetic patients is increasing rapidly. Diabetes has become one of the most important chronic diseases affecting the health of the Chinese people, and complications, disability, death and treatment costs caused by diabetes have placed a heavy burden on families and society. If the high-risk population of diabetes can be identified and the adverse lifestyle can be changed as soon as possible, the incidence of diabetes can be reduced or the onset of diabetes can be slowed down. Risk prediction model can accurately predict the risk of disease and has been widely used in the field of health management and medical care. This study was based on the special occupational group of steel workers, the risk prediction model of type 2 diabetes was established by using convolutional neural network, and the feasibility of the model was discussed. The results showed that the prediction accuracy of the established model in the training set, verification set, and test set is relatively high, which is 94.5%, 91.0%, and 89.0%, respectively. The area under the ROC curve was 0.950 (95 CI 0.938–0.962), 0.916 (95 CI 0.888–0.945), and 0.899 (95 CI 0.899–0.939), respectively, indicating that the model can accurately predict the risk of type 2 diabetes among steel workers, provide a basis for self-health management of steel workers, facilitate the rational allocation of medical and health resources and the development of health services, and provide a basis for government departments to make decisions.

Objective: The aim of this study was to explore the diagnostic value of gastroscopy under local anesthesia for congenital pyriform sinus fistula (CPSF).Methods: This research was a diagnostic study. Patients received gastroscopy under local anesthesia to diagnose CPSF, and suspension laryngoscopy under general anesthesia was performed 2 days after gastroscopy. Various conditions of the internal opening of CPSF were then recorded. Patients were grouped according to lesion sides, age, time after the inflammation subsided, and history of previous surgery. The sensitivity, specificity, area under the receiver operating characteristic curve (AUC), accuracy, and positive and negative predictive values of gastroscopy were compared between the groups.Results: A total of 48 patients were recruited in this study, and no patients had severe gastroscopy-related complications. The diagnostic values of gastroscopy in 41 cases (85.4%) were consistent with suspension laryngoscopy. The sensitivity of gastroscopy was 86.4%, the specificity was 75%, the AUC was 0.807, the positive prediction rate was 97.4%, the negative prediction rate was 33.3%, the accuracy rate was 85.4%, and the diagnostic odds ratio (DOR) was 2.1. The kappa consistency test results had statistical significance (P = 0.0026, kappa = 0.3913). The diagnostic value of gastroscopy was better for the patients with inflammation subsiding for more than 4 weeks (P < 0.0001).Conclusion: Gastroscopy under local anesthesia is a safe, effective, reliable and novel diagnostic method for CPSF, and it is especially recommended as a diagnostic method for the patients with inflammation subsiding for more than 4 weeks.

Background The prevalence of metabolic syndrome continues to rise sharply worldwide, seriously threatening people’s health. The optimal model can be used to identify people at high risk of metabolic syndrome as early as possible, to predict their risk, and to persuade them to change their adverse lifestyle so as to slow down and reduce the incidence of metabolic syndrome. Methods Design existing circumstances research. A total of 1468 workers from an oil company who participated in occupational health physical examination from April 2017 to October 2018 were included in this study. We established the Logistic regression model, the random forest model and the convolutional neural network model, and compared the prediction performance of the models according to the F1 score, sensitivity, accuracy and other indicators of the three models. Results The results showed that the accuracy of the three models was 82.49,95.98 and 92.03%, the sensitivity was 87.94,95.52 and 90.59%, the specificity was 74.54, 96.65 and 94.14%, the F1 score was 0.86,0.97 and 0.93, and the area under ROC curve was 0.88,0.96 and 0.92, respectively. The Brier score of the three models was 0.15, 0.08 and 0.12, Observed-expected ratio was 0.83, 0.97 and 1.13, and the Integrated Calibration Index was 0.075,0.073 and 0.074, respectively, and explained how the random forest model was used for individual disease risk score. Conclusions The study showed that the prediction performance of random forest model is better than other models, and the model has higher application value, which can better predict the risk of metabolic syndrome in oil workers, and provide corresponding theoretical basis for the health management of oil workers.

Pathological examination is of great significance for the diagnosis and treatment of prostate cancer, but artificial pathological examination is time-consuming, laborious and error prone. Automatic pathological examination can assist doctors in diagnosis and treatment. In this paper, a deep learning convolution network based on group equivariant convolution and conditional random field is proposed, which solves the problem of inconsistent features of data after random rotation in the learning process and enhances the robustness of the network. On the other hand, the conditional random field method is used to produce the same result on the slice image, which makes the segmentation edge of the probability image clearer.

Background : Infantile-onset inflammatory bowel disease (IO-IBD) patients with interleukin-10/interleukin-10 receptor (IL-10/IL-10R) mutations suffer from more severe and intractable disease. We aimed to investigate the clinical phenotypes and genotypic characteristics of IO-IBD patients with IL-10RA gene mutations. Methods : Data on 22 patients with IO-IBD with IL-10RA gene mutations were retrospectively analyzed, and high-throughput sequencing was used to identify the IL-10RA gene mutations. Results : In 22 patients with IO-IBD with IL-10RA mutations, c.C301T (p.R101W) (86.4%, 19/22) and c.G537A (p.T179T) (36.4%, 8/22) were the most common ones, and one novel mutation was identified (c.635G>C (p.R212P)). Patients had extremely early onset of symptoms, with 81.8% (18/22) having disease onset within 1 month after birth, and median onset time was 8.5 (interquartile range: 3.0–24.0) days. In addition, 77.3% (17/22) of patients had recurrent perianal lesions. Oral ulcers and skin rashes were common extra-intestinal manifestations, accounting for 72.7% (16/22) and 63.6% (14/22), respectively. In this study, three patients underwent enterostomy and one experienced intestinal perforation repair. Thalidomide was used in five patients in this study: one achieved clinical remission, three were clinical improvement and one still had disease activity. Two patients underwent umbilical cord blood transplantation (UCBT) and remained stable. Follow-up showed that the mortality rate was as high as 45% (9/20). Conclusions : In 22 IO-IBD patients with IL-10RA mutations, the most common mutations were c.C301T (p.R101W) and c.G537A (p.T179T). Patient characteristics included extremely early onset of symptoms and extra-intestinal manifestations such as recurrent perianal lesions, oral ulcers, and skin rashes, which were common. UCBT and thalidomide might be effective treatments, although the mortality rate was high in this study.

Backgroud: Very-early-onset inflammatory bowel disease (VEO-IBD) with onset in infancy may be caused by genetic mutation. We collected the VEO-IBD patients with interleukin-10 receptor A (IL-10RA) gene mutations to investigate the clinical phenotype and genetic characteristics.Methods: The data of 22 patients with VEO-IBD with IL-10RA gene mutations were retrospectively analyzed, and high-throughput sequencing was used to identify IL-10RA gene mutations.Results: All 22 patients in this study had IL-10RA gene mutations, including 4 (18.2%) homozygous mutations and 18 (81.8%) compound heterozygous mutations. Among these mutations, 10 mutations had been previously described and 1 novel mutation was identified. In these patients, c.C301T (p.R101W) (86.4%, 19/22) and c.G537A (p.T179T) (36.4%, 8/22) mutations were the most common mutations. This study showed that the patients had extremely early onset of symptoms, about 81.8% (18/22) of the patients had onset within 1 month after birth, and the onset time was 8.5 (IQR: 3.0–24.0) days. In addition, 77.3% (17/22) of patients had recurrent perianal lesions. Oral ulcers and skin rash were common extra-intestinal manifestations, accounting for 72.7% (16/22) and 63.6% (14/22), respectively. In this study, 3 patients underwent enterostomy and 1 patient experienced intestinal perforation repair. Umbilical cord blood transplantation (UCBT) and thalidomide proved efficacious. Follow-up showed the mortality rate was as high as 45% (9/20).Conclusions: We should consider the genetic defects in the IL-10 signaling pathway in VEO-IBD patients, particularly when they had early onset of symptoms, perianal lesions and severe colitis.

Background. The prevalence of metabolic syndrome continues to rise sharply worldwide, seriously threatening people's health.In this paper, three kinds of risk prediction models applicable to the metabolic syndrome of oil workers were established, and the optimal models were found through comparison. The optimal model can be used to identify people at high risk of metabolic syndrome as early as possible, to predict their risk, and to persuade them to change their adverse lifestyle so as to slow down and reduce the incidence of metabolic syndrome.Methods. A total of 1,468 workers from an oil company who participated in occupational health physical examination from April 2017 to October 2018 were included in this study. We established the Logistic regression model, the random forest model and the convolutional neural network model, and compared the prediction performance of the models according to the F1 score, sensitivity, accuracy and other indicators of the three models.Results. The results showed that the accuracy of the three models in the training set was 83.45%, 94.21% and 86.34%, the sensitivity was 78.47%, 94.62% and 81.30%, the F1 score was 0.79, 0.93 and 0.83, and the area under the ROC curve was 0.894, 0.987 and 0.935, respectively. In the test set, the accuracy was 76.72%, 80.66% and 78.69%, the sensitivity was 70.00%, 77.50% and 68.33%, the F1 score was 0.70, 0.76 and 0.71, and the area under the ROC curve was 0.797, 0.861 and 0.855, respectively.Conclusions. The study showed that the prediction performance of random forest model is better than other models, and the model has higher application value, which can better predict the risk of metabolic syndrome in oil workers, and provide corresponding theoretical basis for the health management of oil workers.

Brain-derived neurotrophic factor (BDNF) is the potential link between depression and cardiovascular disease and estrogen receptor α (ERα), an estrogen-mediated major regulator, plays an important role in protecting against depression and cardiovascular disease. However, the relationship between BDNF and ERα remains obscure. Herein, quercetin (QUE), a kind of plant flavonoids and existed in many vegetables and fruits, was found to simultaneously reverse ERα-/--induced depression-like and cardiac dysfunction by reducing immobility time in the tail suspension test (TST) and forced swimming test (FST), and decreasing systolic blood pressure and activating the apoptosis-related proteins, BDNF, tropomyosin-related kinase B (TrkB), protein kinase B (AKT), and extracellular regulatory protein kinase (ERK1/2) in the hippocampal and cardiac tissues of female mice. These findings suggested that ERα might be involved in the regulation of BDNF activity, thereby regulating depression-like and cardiovascular responses in female mice, and QUE exerted significant antidepressant and cardioprotective effects, at least in part, through BDNF-TrkB-AKT/ERK1/2 to effectively inhibit ERα-/--induced hippocampal and cardiac dysfunction.

Bacterial canker caused by Pseudomonas syringae pv. actinidiae (Psa) has led to considerable losses in all major kiwifruit-growing areas. There are no commercial products in the market to effectively control this disease. Therefore, the defense resistance of host plants is a prospective option. In our previous study, sulfur could improve the resistance of kiwifruit to Psa infection. However, the mechanisms of inducing resistance remain largely unclear. In this study, disease severity and protection efficiency were tested after applying sulfur, with different concentrations in the field. The results indicated that sulfur could reduce the disease index by 30.26 and 31.6 and recorded high protection efficiency of 76.67% and 77.00% after one and two years, respectively, when the concentration of induction treatments was 2.0 kg/m3. Ultrastructural changes in kiwifruit stems after induction were demonstrated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and the activities of phenylalanine ammonia-lyase (PAL), peroxidase (POD) and polyphenol oxidase (PPO), and the accumulation of lignin were determined by biochemical analyses. Our results showed that the morphological characteristics of trichomes and lenticels of kiwifruit stem were in the best defensive state respectively when the sulfur concentration was 3.0 kg/m3 and 1.5 kg/m3. Meanwhile, in the range of 0.5 to 2.0 kg/m3, the sulfur could promote the chloroplast and mitochondria of kiwifruit stems infected with Psa to gradually return to health status, increasing the thickness of the cell wall. In addition, sulfur increased the activities of PAL, POD and PPO, and promoted the accumulation of lignin in kiwifruit stems. Moreover, the sulfur protection efficiency was positively correlated with PPO activity (p &lt, 0.05) and lignin content (p &lt, 0.01), which revealed that the synergistic effect of protective enzyme activity and the phenolic metabolism pathway was the physiological effect of sulfur-induced kiwifruit resistance to Psa. This evidence highlights the importance of lignin content in kiwifruit stems as a defense mechanism in sulfur-induced resistance. These results suggest that sulfur enhances kiwifruit canker resistance via an increase in phenolic components and morphology structure modification in the kiwifruit stems. Therefore, this study could provide insights into sulfur to control kiwifruit canker caused by Psa.

Current non-invasive prenatal screening is targeted toward the detection of chromosomal abnormalities in the fetus1,2. However, screening for many dominant monogenic disorders associated with de novo mutations is not available, despite their relatively high incidence3. Here we report on the development and validation of, and early clinical experience with, a new approach for non-invasive prenatal sequencing for a panel of causative genes for frequent dominant monogenic diseases. Cell-free DNA (cfDNA) extracted from maternal plasma was barcoded, enriched, and then analyzed by next-generation sequencing (NGS) for targeted regions. Low-level fetal variants were identified by a statistical analysis adjusted for NGS read count and fetal fraction. Pathogenic or likely pathogenic variants were confirmed by a secondary amplicon-based test on cfDNA. Clinical tests were performed on 422 pregnancies with or without abnormal ultrasound findings or family history. Follow-up studies on cases with available outcome results confirmed 20 true-positive, 127 true-negative, zero false-positive, and zero-false negative results. The initial clinical study demonstrated that this non-invasive test can provide valuable molecular information for the detection of a wide spectrum of dominant monogenic diseases, complementing current screening for aneuploidies or carrier screening for recessive disorders.

Zinc finger E‑box binding homeobox 2 (ZEB2) is a member of the Zfh1 family of two‑handed zinc finger/homeodomain proteins. To date, the role of ZEB2 in human laryngeal carcinoma has not been clearly defined. In the present study, the level of ZEB2 expression in laryngeal squamous cell carcinoma (LSCC) tissues and adjacent normal tissues was evaluated using reverse transcription‑quantitative polymerase chain reaction. The effects of ZEB2 on the growth, migration, invasion, cell cycle distribution and apoptosis of laryngeal cancer cells were also explored using MTT, Transwell and flow cytometry assays. It was identified that ZEB2 was upregulated in LSCC tissues compared with normal tissues. Silencing of ZEB2 inhibited the viability, migration and invasion of LSCC cells. It was also observed that ZEB2 silencing induced cell cycle arrest and apoptosis in LSCC cells. Furthermore, ZEB2 silencing inhibited the process of epithelial‑mesenchymal transition. Overall, the results indicated that ZEB2 promotes the progression of LSCC and that it may be a potential target for the treatment of this type of cancer.

Background Geosocial networking smartphone applications (apps) are popular tools for seeking sexual partners among men who have sex with men (MSM). We evaluated app use and risk of sexually transmitted infections (STIs) in app-using MSM (app-users) by a systematic review and meta-analysis. Methods A literature search for relevant studies was performed. We extracted date of STIs (ever being diagnosed with human immunodeficiency virus [HIV], syphilis, gonorrhea and chlamydia) and sexual behavior (e.g., number of app-met partners, unprotected anal/oral sex, HIV testing) from the eligible studies. Pooled proportions and odds ratios (ORs) with 95% confidence intervals (95% CIs) were estimated. Results Twenty-five studies were included. The self-reported prevalence of prior diagnosis of HIV among app-users ranged from 2.2 to 37.7%, and the pooled prevalence of HIV infection was 6% (95% CI, 4–11%). Compared with non-users, app-users were more likely to have gonorrhea (OR = 2.36; 95% CI, 2.07–2.70) and chlamydia (OR = 2.22; 95% CI, 1.92–2.56). The two groups were similar in terms of diagnoses of HIV (OR = 0.89, 95% CI, 0.68–1.16) and syphilis (OR = 1.92; 95% CI, 0.91–4.03). However, when one study that caused substantial heterogeneity was omitted, the pooled OR for app-users to contract syphilis became 3.00 (95% CI, 1.84–4.91) . Conclusions MSM who seek sexual partners using apps may be more likely to have STIs as than are non-users. Electronic supplementary material The online version of this article (10.1186/s12889-018-6092-3) contains supplementary material, which is available to authorized users.

Endoscopic resection of nasopharyngeal angiofibroma is less traumatic, causes less bleeding, and provides a good curative effect. Using pre-operative embolization and controlled hypotension, reasonable surgical strategies and techniques lead to successful resection tumors of a maximum Andrews-Fisch classification stage of III.To investigate surgical indications, methods, surgical technique, and curative effects of transnasal endoscopic resection of nasopharyngeal angiofibroma, this study evaluated factors that improve diagnosis and treatment, prevent large intra-operative blood loss and residual tumor, and increase the cure rate.A retrospective analysis was performed of the clinical data and treatment programs of 23 patients with nasopharyngeal angiofibroma who underwent endoscopic resection with pre-operative embolization and controlled hypotension. The surgical method applied was based on the size of tumor and extent of invasion. Curative effects were observed.No intra-operative or perioperative complications were observed in 22 patients. Upon removal of nasal packing material 3-7 days post-operatively, one patient experienced heavy bleeding of the nasopharyngeal wound, which was treated compression hemostasis using post-nasal packing. Twenty-three patients were followed up for 6-60 months. Twenty-two patients experienced cure; one patient experienced recurrence 10 months post-operatively, and repeat nasal endoscopic surgery was performed and resulted in cure.

In the version of this article originally published, some cases that were presented in Fig. 3 should have been underlined but were not. The appropriate cases have now been underlined. The error has been corrected in the print, PDF and HTML versions of the article.

As a common chronic disease, sleep apnea syndrome (SAS) seriously threatens patients’ health, so it is imperative to find an effective way of apnea detection. In this paper, we present a new method that explores of using the high sensitivity characteristic of the micro-bending effect of the gradient multimode fiber to detect human breathing movement, and thereby collecting the respiratory signals. With characterizing central apnea, 8 different features in time-domain and frequency-domain are extracted from the respiratory signals, which are used to train the classifiers. In the feature modeling, we present a peak calculation method based on moving average curve (MAC) to increase the accuracy of estimating the respiratory frequency and amplitude. In our experimental studies, the forward sequence selection method (SFS) is employed to combine these features for training SVM classifier, and our approach can reach an accuracy rate of 94.6% in apnea discrimination.

SLIT2 is a candidate tumor suppressor gene and recent studies have shown that SLIT2 expression is suppressed or reduced by hypermethylation in the promoter region in various cancers. The aim of this study was to investigate the association between SLIT2 promoter methylation and nasopharyngeal carcinoma (NPC) and its relative diagnostic ability for NPC. Bisulfite pyrosequencing technology was performed to measure methylation levels of the SLIT2 promoter in tissue and plasma samples from 61 NPC patients and 38 normal volunteers. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the diagnostic ability of SLIT2 methylation for diagnosing NPC. Our results showed that methylation levels of the SLIT2 promoter were significantly higher in NPC patients compared with individuals, both in tissue samples (P=2.57E-10) and plasma samples (plasma: P=3.86E-13). In addition, the frequency of SLIT2 promoter methylation markedly increased in the advanced stage (tissue: P=3.50E-05; plasma: P=1.14E-04) and advanced T classified (tissue: P=9.00E-06; plasma: P=3.80E-05), as well as in lymph node metastasis patients (tissue: P=1.82E-03; plasma: P=2.22E-03). In addition, the AUCs according to tissue and plasma samples were 0.846 and 0.866, respectively. When these two sample-types were combined, the AUC increased slightly to 0.874. Our study revealed that elevated SLIT2 promoter methylation contributed to the risk of NPC, as well as being involved in its progression and metastasis. Therefore, the methylated SLIT2 promoter could serve as a potential biomarker for diagnosing NPC.

Cerebral creatine deficiency syndromes (CCDS) are a group of inborn errors of creatine metabolism that involve AGAT and GAMT for creatine biosynthesis disorders and SLC6A8 for creatine transporter (CT1) deficiency. Deficiencies in the three enzymes can be distinguished by intermediate metabolite levels, and a definitive diagnosis relies on the presence of deleterious mutations in the causative genes. Mutations and unclassified variants were identified in 41 unrelated patients, and 22 of these mutations were novel. Correlation of sequencing and biochemical data reveals that using plasma guanidinoacetate (GAA) as a biomarker has 100% specificity for both AGAT and GAMT deficiencies, but AGAT deficiency has decreased sensitivity in this assay. Furthermore, the urine creatine:creatinine ratio is an effective screening test with 100% specificity in males suspected of having creatine transporter deficiency. This test has a high false-positive rate due to dietary factors or dilute urine samples and lacks sensitivity in females. We conclude that biochemical screening for plasma GAA and measuring of the urine creatine:creatinine ratio should be performed for suspected CCDS patients prior to sequencing. Also, based on the results of this study, we feel that sequencing should only be considered if a patient has abnormal biochemical results on repeat testing.

The diagnosis of mitochondrial disorders is challenging because of the clinical variability and genetic heterogeneity. Conventional analysis of the mitochondrial genome often starts with a screening panel for common mitochondrial DNA (mtDNA) point mutations and large deletions (mtScreen). If negative, it has been traditionally followed by Sanger sequencing of the entire mitochondrial genome (mtWGS). The recently developed "Next-Generation Sequencing" (NGS) technology offers a robust high-throughput platform for comprehensive mtDNA analysis. Here, we summarize the results of the past 6 years of clinical practice using the mtScreen and mtWGS tests on 9,261 and 2,851 unrelated patients, respectively. A total of 344 patients (3.7%) had mutations identified by mtScreen and 99 (3.5%) had mtDNA mutations identified by mtWGS. The combinatorial analyses of mtDNA and POLG revealed a diagnostic yield of 6.7% in patients with suspected mitochondrial disorders but no recognizable syndromes. From the initial mtWGS-NGS cohort of 391 patients, 21 mutation-positive cases (5.4%) have been identified. The mtWGS-NGS provides a one-step approach to detect common and uncommon point mutations, as well as deletions. Additionally, NGS provides accurate, sensitive heteroplasmy measurement, and the ability to map deletion breakpoints. A new era of more efficient molecular diagnosis of mtDNA mutations has arrived.

Sanger sequencing is a mainstay for the identification of gene mutations used in molecular diagnostic laboratories. However, in autosomal recessive disorders, failure of allele amplification can occur for a variety of reasons, leading heterozygous mutations to appear homozygous. We sought to investigate the frequency at which apparently homozygous mutations detected by Sanger sequencing in our laboratory appeared homozygous due to other molecular etiologies. A review of 12,406 cases from 40 different genetic tests that were submitted to the Medical Genetics Laboratories at Baylor College of Medicine for Sanger sequence analysis was performed. The molecular status of apparently homozygous cases was further investigated by testing parents using various methods. A total of 291 cases of apparent homozygosity were identified, ranging from 0 to 37% of the total per gene. One-third of the apparently homozygous cases were followed up by parental testing. Parental carrier status was confirmed in 88% of the cases. Of the cases in which parental carrier status could not be confirmed, deletions encompassing point mutations, allele dropout due to single-nucleotide polymorphisms at primer sites, and uniparental isodisomy were observed. For individuals with autosomal recessive disorders and apparently homozygous mutations, confirmation by parental testing can rule out other causes of apparent homozygosity, including allele dropout, copy number variations, and uniparental isodisomy. Genet Med 2012:14(10):877–882

The relationship among the lysyl oxidase (LOX) G473A single nucleotide polymorphism (SNP), cigarette smoking and lung, colorectal, colon and rectum cancer susceptibility was studied in 200 cases of lung cancer, 335 cases of colorectal cancer including 130 cases of colon cancer and 205 cases of rectum cancer, and 335 healthy people in Tangshan, China. Peripheral blood DNA samples were collected, DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) performed, followed by multivariate logistic regression analysis. In comparison to LOX473GG genotype carriers, individuals with LOX473AA exhibited a higher susceptibility to lung, colon-rectum, colon, and rectum cancers with OR values amounting to 3.84-, 2.74-, 2.75-, and 2.74-fold of the control, respectively. In the LOX 473AA-positive population, females were more susceptible than males to carcinogenesis with OR values (female vs. male): 5.25 vs. 3.23, 2.29 vs. 1.51, 2.27 vs. 1.45, and 2.25 vs. 1.53, respectively, for lung, colon-rectum combined, colon, and rectum cancers. LOX G473A polymorphism apparently elevated human sensitivity to cigarette smoking carcinogens for eliciting cancers in the lung and colon only. Thus, LOX G473A polymorphism positively correlates with carcinogenesis and it may be used as an ideal intrinsic biomarker for prediction or diagnosis of carcinogenesis in humans.

Background Danqi pill (DQP) is one of the most widely prescribed formulas and has been shown to have remarkable protective effect on coronary heart disease (CHD). However, its regulatory effects on lipid metabolism disorders haven’t been comprehensively studied so far. We aimed to explore the effects of DQP on Peroxisome Proliferator activated receptors α (PPARα), lipid uptake-transportation-metabolism pathway and arachidonic acid (AA)-mediated inflammation pathway in rats with CHD. Methods 80 Sprague-Dawley (SD) Rats were randomly divided into sham group, model group, positive control group and DQP group. Rat model of CHD was induced by ligation of left ventricle anterior descending artery and fed with high fat diet in all but the sham group. Rats in sham group only underwent thoracotomy. After surgery, rats in the positive control and DQP group received daily treatments of pravastatin and DQP respectively. At 28 days after surgery, rats were sacrificed and plasma lipids were evaluated by plasma biochemical detection. Western blot and PCR were applied to evaluate the expressions of PPARα, proteins involved in lipid metabolism and AA pathways. Results Twenty eight days after surgery, dyslipidemia developed in CHD model rats, as illustrated by elevated plasma lipid levels. Expressions of apolipoprotein A-I (ApoA-I), cluster of differentiation 36 (CD36) and fatty acid binding protein (FABP) in the heart tissues of model group were down-regulated compared with those in sham group. Expressions of carnitine palmitoyl transferase I (CPT-1A) and lipoproteinlipase (LPL) were also reduced significantly. In addition, levels of phospholipase A2 (PLA2) and cyclooxygenase 2 (COX-2) were up-regulated. Expressions of Nuclear factor-κB (NF- κB) and signal transducer and activator of transcription 3 (STAT3) also increased. Furthermore, Expression of PPARα decreased in the model group. DQP significantly up-regulated expressions of ApoA-I and FABP, as well as the expressions of CPT-1A and CD36. In addition, DQP down-regulated expressions of PLA2, COX-2 and NF-κB in inflammation pathway. Levels of STAT3 and LPL were not affected by DQP treatment. In particular, DQP up-regulated PPARα level significantly. Conclusions DQP could effectively regulate lipid uptake-transportation-metabolism process in CHD model rats, and the effect is achieved mainly by activating ApoA-I-CD36-CPT-1A molecules. Interestingly, DQP can up-regulate expression of PPARα significantly. The anti-inflammatory effect of DQP is partly exerted by inhibiting expressions of PLA2-COX2 -NF-κB pathway.

Next generation sequencing (NGS) based gene panel testing is increasingly available as a molecular diagnostic approach for inborn errors of metabolism. Over the past 40 years patients have been referred to the Vitamin B12 Clinical Research Laboratory at McGill University for diagnosis of inborn errors of cobalamin metabolism by functional studies in cultured fibroblasts. DNA samples from patients in which no diagnosis was made by these studies were tested by a NGS gene panel to determine whether any molecular diagnoses could be made. 131 DNA samples from patients with elevated methylmalonic acid and no diagnosis following functional studies of cobalamin metabolism were analyzed using the 24 gene extended cobalamin metabolism NGS based panel developed by Baylor Miraca Genetics Laboratories. Gene panel testing identified two or more variants in a single gene in 16/131 patients. Eight patients had pathogenic findings, one had a finding of uncertain significance, and seven had benign findings. Of the patients with pathogenic findings, five had mutations in ACSF3, two in SUCLG1 and one in TCN2. Thus, the NGS gene panel allowed for the presumptive diagnosis of 8 additional patients for which a diagnosis was not made by the functional assays.

Reduction of childhood mortality is a worldwide health priority. By investigating the most frequent causes of childhood death and analyzing the major causes of misdiagnosis, this study aims to quantify the value of autopsy and guide further research for improving health services. A total of 240 autopsied cases were recruited into the study. The major causes of death according to the system were respiratory diseases, followed by neoplasms and infectious diseases, while the top three causes of death according to diseases were lobular pneumonia, septicemia, and malignant histiocytosis. Agreement between pathologic and clinical diagnoses was shown in 169 autopsies (70.5%), and the other 71 cases (29.6%) had been misdiagnosed. This study demonstrated the value of the routine autopsy by documenting the high rate of disagreement between clinical and autopsy diagnoses. However, the role of routine autopsy for determining in-born errors of metabolism is limited.

To establish the model of hospitalization cost in patients with cerebral infarction based on neural network using artificial network mathematical model, and setting the appropriate parameters. LM, BR, OSS, SCG four algorithms were used respectively to model 3, 5,10,15, 20 neuron number in different hidden layers and comparisons between model fitting ability and its generalization ability were made. The model which involves a hidden layer, 8 input neurons, 15 neurons in output layer network is the optimal model by using OSS system.

Collected 2218 medical records of cerebral infarction patients from 2007 to 2008 in a third-class hospital in Tang Shan as sample. A statistical analysis was made of the hospitalization expenses and its influencing factors by BP nerve network model to identify the factors affecting hospitalization expense by using BP nerve network model. The results showed that the major factors impacting the hospitalization expense included age, hospitalization day, therapeutic result and emergency medical treatment. The sensitivity were: age is 0.91426, hospitalization day is 0.32131, therapeutic result is 0.19722, emergency medical treatment is 0.27564. BP nerve network model is a powerful analytical tool for hospitalization expenses and its influencing factors analysis.

The objective of the study was to explore the pathogenesis of mesial temporal lobe epilepsy (MTLE) and the mechanism of valproate administration in the early stage of MTLE development. We performed a global comparative analysis and function classification of differentially expressed proteins using proteomics. MTLE models of developmental rats were induced by lithium-pilocarpine. Proteins in the hippocampus were separated by 2-DE technology. PDQuest software was used to analyze 2-DE images, and MALDI-TOF-MS was used to identify the differentially expressed proteins. Western blot was used to determine the differential expression levels of synapse-related proteins synapsin-1, dynamin-1 and neurogranin in both MTLE rat and human hippocampus. A total of 48 differentially expressed proteins were identified between spontaneous and non-spontaneous MTLE rats, while 41 proteins between MTLE rats and post valproate-treatment rats were identified. All of the proteins can be categorized into several groups by biological functions: synaptic and neurotransmitter release, cytoskeletal structure and dynamics, cell junctions, energy metabolism and mitochondrial function, molecular chaperones, signal regulation and others. Western blot results were similar to the changes noted in 2-DE. The differentially expressed proteins, especially the proteins related to synaptic and neurotransmitter release function, such as synapsin-1, dynamin-1 and neurogranin, are probably involved in the mechanism of MTLE and the pharmacological effect of valproate. These findings may provide important clues to elucidate the mechanism of chronic MTLE and to identify an optimum medication intervention time and new biomarkers for the development of pharmacological therapies targeted at epilepsy.

Genotoxic stress triggers a rapid translocation of p53 to the mitochondria, contributing to apoptosis in a transcription-independent manner. Using immunopurification protocols and mass spectrometry, we previously identified the proapoptotic protein BAK as a mitochondrial p53-binding protein and showed that recombinant p53 directly binds to BAK and can induce its oligomerization, leading to cytochrome c release. In this work we describe a combination of molecular modeling, electrostatic analysis, and site-directed mutagenesis to define contact residues between BAK and p53. Our data indicate that three regions within the core DNA binding domain of p53 make contact with BAK; these are the conserved H2 α-helix and the L1 and L3 loop. Notably, point mutations in these regions markedly impair the ability of p53 to oligomerize BAK and to induce transcription-independent cell death. We present a model whereby positively charged residues within the H2 helix and L1 loop of p53 interact with an electronegative domain on the N-terminal α-helix of BAK; the latter is known to undergo conformational changes upon BAK activation. We show that mutation of acidic residues in the N-terminal helix impair the ability of BAK to bind to p53. Interestingly, many of the p53 contact residues predicted by our model are also direct DNA contact residues, suggesting that p53 interacts with BAK in a manner analogous to DNA. The combined data point to the H2 helix and L1 and L3 loops of p53 as novel functional domains contributing to transcription-independent apoptosis by this tumor suppressor protein.

Invasion and metastasis are the major characteristics of malignant tumors and are complex processes involving multiple genes. Gene regulation is a precise, large and complex biological control system, and its underlying mechanisms remain to be elucidated. Mesenchymal-specific genes are expressed primarily by mesenchymal cells, and the expression products of these genes are molecules with various structures and functions, including secreted proteins and extracellular matrix proteins. The periostin gene has been newly identified as a mesenchymal-specific gene and an extracellular-matrix secreted protein. Periostin is able to bind to various subtypes of integrin receptors on the surface of the cell membrane. This triggers relevant signal transduction pathways to alter the microenvironment of cancer cells in order to facilitate their survival, invasion, metastasis and angiogenesis as well as enhance the tolerance to hypoxia and chemicals. Therefore, periostin is associated with the grade of malignancy, level of invasion and prognosis of malignant tumors. The in-depth study of periostin may provide an effective marker for tumor diagnosis and prognosis, as well as a novel treatment target.

Possible roles of the Glu40-Ser48 loop connecting A domain and the first transmembrane helix (M1) in sarcoplasmic reticulum Ca(2+)-ATPase (SERCA1a) were explored by mutagenesis. Deletions of any single residues in this loop caused almost complete loss of Ca(2+)-ATPase activity, while their substitutions had no or only slight effects. Single deletions or substitutions in the adjacent N- and C-terminal regions of the loop (His32-Asn39 and Leu49-Ile54) had no or only slight effects except two specific substitutions of Asn39 found in SERCA2b in Darier's disease pedigrees. All the single deletion mutants for the Glu40-Ser48 loop and the specific Asn39 mutants formed phosphoenzyme intermediate (EP) from ATP, but their isomeric transition from ADP-sensitive EP (E1P) to ADP-insensitive EP (E2P) was almost completely or strongly inhibited. Hydrolysis of E2P formed from Pi was also dramatically slowed in these deletion mutants. On the other hand, the rates of the Ca(2+)-induced enzyme activation and subsequent E1P formation from ATP were not altered by the deletions and substitutions. The results indicate that the Glu40-Ser48 loop, with its appropriate length (but not with specific residues) and with its appropriate junction to A domain, is a critical element for the E1P to E2P transition and formation of the proper structure of E2P, therefore, most likely for the large rotational movement of A domain and resulting in its association with P and N domains. Results further suggest that the loop functions to coordinate this movement of A domain and the unique motion of M1 during the E1P to E2P transition.

The blood–testis barrier (BTB) constituted by coexisting junction apparatus between Sertoli cells (SCs) plays an important role in spermatogenesis, which is a known target of various environmental toxicants. The commercial polychlorinated biphenyls mixture, Aroclor1254, has been shown to impair male reproduction by decreasing sperm count and affecting SC metabolism. This study was designed to investigate the effects of Aroclor1254 on the BTB integrity and elucidate the underlying mechanisms. We found that Aroclor1254 treatment in rats (1 or 3 mg/kg per day for 21 consecutive days) and in primary cultured SCs (5 or 10 μg/ml for 48 h) could induce BTB disruption via p38 MAPK pathway, concurrently with increments in junction proteins (JAM-A, N-cadherin, and β-catenin) endocytosis, and occludin ubiquitination. Either inhibition of caveolin-dependent membrane protein internalization by cholesterol oxidase or silencing E3 ubiquitine ligase Itch by small interfering RNA could partially counteract the effects of Aroclor1254 on the barrier function of cultured SCs. These results demonstrate that Aroclor1254 disrupts the BTB function by promoting the caveolin-dependent endocytosis and ubiquitine–proteasome degradation of junction proteins through the p38 MAPK pathway, which might be the potential reasons for its negative effects on spermatogenesis and male reproduction.

Our previous studies showed that the expressions of miR-148a, miR-152 and miR-148b are altered in gastric cancer (GC). The present study aimed to find relationship between individual single nucleotide polymorphisms (SNPs) or haplotypes of these miRNAs and susceptibility, clinicopathological parameters and prognosis of GC in a large sample of the Han population of Northern China. Twelve SNPs were genotyped using matrix- assisted laser desorption/ionisation time-of-flight mass spec- trometry in a case-control study of 571 Chinese GC patients and 571 cancer-free controls. The rs11170877 G allele (P = 0.027) and the rs12231393 C allele (P = 0.034) were associated with a decreased risk of GC. However, these associations were lost after Bonferroni correction. The rs4719839 G allele was asso- ciated with Borrmann type III-IV GC (P = 0.034), increased tumour size (P = 0.020), an increased rate of lymph node metas- tasis (P = 0.047) and advanced TNM stage (P = 0.009). These associations were also lost after Bonferroni correction. The hap- lotype of miR-148b was significantly correlated with GC risk. The haplotypes in miRNA-148a were different in Borrmann types. The haplotype of miR-152 distributed various in the positive lymphovascular invasion group compared to negative group. Polymorphisms of miR-148b rs11170877 and 12231393 and their haplotypes were predictive factors of susceptibility to GC. A functional genetic variant of miRNA rs4719839 and the corresponding haplotype were associated with clinicopathologi- cal features and prognosis of advanced GCs.

Mitochondrial energy metabolism disorder is one of the important reasons of leukodystrophy. Mutations of mitochondrial complex I genes have been implicated in more common neurological disorders such as Leigh syndrome. We describe a case of a child manifested as regression of mental and motor development, aggravated obviously after suffering infection. Physical and auxiliary examinations demonstrated that a series of changes including white matter lesions of magnetic resonance imaging, peripheral neuropathy with high muscle tension and hyperreflexia of limbs pointed to the diagnosis of leukodystrophy, with what can't explain the high levels of lactate and creatine kinase. Spontaneously, genetic analysis covered known leukodystrophy and mitochondrial genes were adapted for this child and his parents. Results showed the child was compound heterozygous mutation (c.278A G; c.247G A) within exon 2 in the NDUFAF1 gene, his parents carried a heterozygous mutation each. The authors report a case of leukodystrophy associated with mitochondrial complex I deficiency due to a novel mutation in the NDUFAF1 gene. This is the first report that NDUFAF1 mutations cause leukodystrophy.

Jingxu Sun,1,* Yongxi Song,1,* Zhenning Wang,1 Guoli Wang,2 Peng Gao,1 Xiaowan Chen,1 Zhaohua Gao,1 Huimian Xu1 1Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, People’s Republic of China *These authors contributed equally to this work Background: MicroRNAs are associated with tumor genesis and progression in various carcinomas. MicroRNA-148a (miR-148a) was reported to have low expression in gastrointestinal cancers, and might be regulated by promoter region DNA methylation. Methods: Bisulfite-modified sequencing was used to determine the promoter region DNA methylation status of human gastrointestinal cancer cell lines. Expression levels of miR-148a in cell lines treated with 5-aza-2′-deoxycytidine were determined by quantitative real-time polymerase chain reaction. Total DNA was extracted from the tissues of 64 patients with gastric cancer and 51 patients with colorectal cancer. Methylation status was determined by methylation-specific polymerase chain reaction. All statistical analyses were performed with SPSS 17.0 software. Results: The promoter regions of genes in human gastrointestinal cancer cell lines were all hypermethylated, except for HT-29, and the expression of miR-148a tended to be higher than in controls after treatment with 5-aza-2′-deoxycytidine. The methylation-specific polymerase chain reaction results showed that 56.25% of gastric cancer tissues and 19.61% of colorectal cancer tissues were hypermethylated. A strong correlation was found between the expression of miR-148a and the methylation status of promoter regions (P

Primary immunodeficiency diseases (PIDDs) are inherited disorders of the immune system. The most severe form, severe combined immunodeficiency (SCID), presents with profound deficiencies of T cells, B cells, or both at birth. If not treated promptly, affected patients usually do not live beyond infancy because of infections. Genetic heterogeneity of SCID frequently delays the diagnosis; a specific diagnosis is crucial for life-saving treatment and optimal management.We developed a next-generation sequencing (NGS)-based multigene-targeted panel for SCID and other severe PIDDs requiring rapid therapeutic actions in a clinical laboratory setting.The target gene capture/NGS assay provides an average read depth of approximately 1000×. The deep coverage facilitates simultaneous detection of single nucleotide variants and exonic copy number variants in one comprehensive assessment. Exons with insufficient coverage (20× read depth) or high sequence homology (pseudogenes) are complemented by amplicon-based sequencing with specific primers to ensure 100% coverage of all targeted regions.Analysis of 20 patient samples with low T-cell receptor excision circle numbers on newborn screening or a positive family history or clinical suspicion of SCID or other severe PIDD identified deleterious mutations in 14 of them. Identified pathogenic variants included both single nucleotide variants and exonic copy number variants, such as hemizygous nonsense, frameshift, and missense changes in IL2RG; compound heterozygous changes in ATM, RAG1, and CIITA; homozygous changes in DCLRE1C and IL7R; and a heterozygous nonsense mutation in CHD7.High-throughput deep sequencing analysis with complete clinical validation greatly increases the diagnostic yield of severe primary immunodeficiency. Establishing a molecular diagnosis enables early immune reconstitution through prompt therapeutic intervention and guides management for improved long-term quality of life.

This paper presents a handwriting movement analysis approach and its application in assistant diagnosis of the neuromuscular disorders rehabilitation by measuring the movement smoothness. The time-varying primitives extraction algorithm is developed to segment the handwriting strokes from natural handwriting data. Further seven smoothness metrics are proposed to evaluate the motor control abilities of neuromuscular disorders and normal people. In experimental studies, the real world handwriting data from five neuromuscular disorders' are acquired to verify the developed algorithm as well as the proposed smoothness criteria. Comparative analysis of the experimental results demonstrates that the presented approach can work well in assisting the rehabilitation diagnosis.

The application of massively parallel sequencing technology to the analysis of the mitochondrial genome has demonstrated great improvement in the molecular diagnosis of mitochondrial DNA–related disorders. The objective of this study was to investigate the performance characteristics and to gain new insights into the analysis of the mitochondrial genome. The entire mitochondrial genome was analyzed as a single amplicon using a long-range PCR–based enrichment approach coupled with massively parallel sequencing. The interference of the nuclear mitochondrial DNA homologs was distinguished from the actual mitochondrial DNA sequences by comparison with the results obtained from conventional PCR–based Sanger sequencing using multiple pairs of primers. Our results demonstrated the uniform coverage of the entire mitochondrial genome. Massively parallel sequencing of the single amplicon revealed the presence of single-nucleotide polymorphisms and nuclear homologs of mtDNA sequences that cause the erroneous and inaccurate variant calls when PCR/Sanger sequencing approach was used. This single amplicon massively parallel sequencing strategy provides an accurate quantification of mutation heteroplasmy as well as the detection and mapping of mitochondrial DNA deletions. The ability to quantitatively and qualitatively evaluate every single base of the entire mitochondrial genome is indispensible to the accurate molecular diagnosis and genetic counseling of mitochondrial DNA–related disorders. This new approach may be considered as first-line testing for comprehensive analysis of the mitochondrial genome. Genet Med 2013:15(5):388–394

Retrospective analysis of the data of hospitalized coal worker patients suffering from pneumoconiosis in the Tangshan money home since 2005. Using these data which provide seniority of exposure to dust, time of exposure to dust, age and the dust class as the influence factors of length of service, which build the model of the BP neural network, and forecast the length of service of coal worker’s pneumoconiosis. Making use of SPSS statistical software package, using matching t test comparison before and after the length of service of the forecast, prediction the D-value of the length of service before and after is 0.095 ± 2.399, t = 1.225, P = 0.221. The importance of each variable distribution result shows that the importance of the biggest is seniority of exposure in dust to forecast coal worker’s pneumoconiosis (0.632), followed is the dust class (0.247), time of exposure in dust (0.061), and age (0.060). BP neural network model has high forecasting accuracy to forecast the length of service of coal worker’s pneumoconiosis.

To control the irrational increase of medical costs, and improve the rational use of health resources. 2,218 medical records of cerebral infraction patients between 2007 and 2008 was collected from a tertiary hospital in Tangshan city, and univariate and multiple linear regression analysis was conducted for risk factors of hospital charges. The average hospital cost of cerebral patients was 8,371.22 yuan, univariate analysis results show that: gender, rescue, payment methods, hospital stay and treatment outcomes were important factors that has impact on hospital cost. Multiple linear regression results show that: hospital stay, rescue, payment methods, gender, treatment outcomes and admissions were the affect factors of hospital cost. It was found that hospital stay was a major factor of hospital cost, and comprehensive measures should be taken to shorten the hospital costs.

Carnitine-acylcarnitine translocase (CACT) deficiency is a rare autosomal recessive disease of fatty acid oxidation, mainly affecting long chain fatty acid utilization. The disease usually presents at neonatal period with severe hypoketotic hypoglycemia, hyperammonemia, cardiomyopathy and/or arrhythmia, hepatic dysfunction, skeletal muscle weakness, and encephalopathy. Definitive diagnosis of CACT deficiency by molecular analysis of the SLC25A20 gene has recently become clinically available. In contrast to biochemical analysis, sequence analysis is a more rapid and reliable method for diagnosis of CACT deficiency. In this study, we used Sanger sequencing and target array CGH to identify molecular defects in the SLC25A20 gene of patients with clinical features and an acylcarnitine profile consistent with CACT deficiency. Eight novel mutations, including a large 25.9 kb deletion encompassing exons 5 to 9 of SLC25A20 were found. Review of the published cases revealed that CACT deficiency is a pan-ethnic disorder with a broad mutation spectrum. Mutations are distributed along the entire gene without a hot spot. Two thirds of them are nonsense, frame-shift, or splice site mutations resulting in premature stop codons. This study underscores the importance of comprehensive molecular analysis, including sequencing and targeted array CGH of the SLC25A20 gene when CACT deficiency is suspected.

Based on the outpatient amount of one hospital in Tangshan from 2005 to 2009, we can make the forecast model of outpatient amount using GM(1,1) model in grey system theory. The result of testing the accuracy of the model shows that: the adapting accuracy of grey forecast model is high, the effect of the forecast is good. The GM (1,1) model have applicative value on predicating the outpatient amount and can be used in hospital.

Data on hospitalization expense for coronary heart disease from 2009 to 2010 in one tertiary hospital were taken as examples, so as to construct fitting models for hospitalization expense based on BP neural network. Sensitivity analysis of influence factors was executed to evaluate the effect degrees of influence factors on hospitalization expense. The purpose of this study was to evaluate application value of BP neural network used in hospitalization expense study, explore the analyze and evaluation method fitting for the construction and character of hospitalization expense, use medical costs rationally and control irrationally increase of hospitalization expense. The results showed that the main influence factors of hospitalization expense were hospitalization days, treatment outcome, times of rescuing and age, the comprehensive influences of which were 0.83101, 0.76113, 0.73227 and 0.44537 respectively.

To investigate the implementation of Grey Correlation Analysis in the research of the hospitalization fee, to analyze the influential factors of the hospitalization expenses, and to provide proof for medical expenses containing measurements.To analyzed the in patient hospital fee of the top ten diseases of internal medicine inpatient in a hospital by Grey correlation analysis The grey correlation analysis shows the correlative degree between each kind of expense and their rankings are as follows: pharmaceutical fee 0.938, bed fee 0.8411, laboratory test fee 0.8331, radiation diagnosis fee 0.7655, and examination fee 0.6108. It indicates that for the internal medical disease, the dominating factor in hospital expenditure is the pharmaceutical fee. It is the medicine expenses which should be cut mostly in order to control the excessive increase of hospital medical expenditure. In the study of hospital medical expenditure, the grey correlation analysis fully utilized information and data, and led to more reasonable conclusions.

Structures of 79 proteins involved in human diseases were predicted by sequence alignments with structural templates. The predicted structures for ALDP and CSA, proteins responsible for adrenoleukodystrophy and the Cockayne syndrome, respectively, were analyzed to elucidate the molecular basis of disease mutations. In particular we positioned residue P484 of ALDP in the homodimer interface. This positioning is consistent with a recent experimental finding that the mutation P484R significantly decreases the self-interaction of ALDP and suggests that the disease mechanism of this mutation lies in the impaired ALDP dimerization. We identified two new WD repeats in CSA and suggest that one of these forms part of the interaction surface with other proteins.