This article reported a case of pyruvate dehydrogenase E1-α deficiency suggested by abnormal brain development during prenatal ultrasound imaging. Prenatal ultrasound revealed a mild enlargement of bilateral cerebral ventricles and the possibility of intracranial hemorrhage in the fetus at 25 +1 weeks of gestation. MRI showed the fetus with absent corpus callosum, enlarged bilateral cerebral ventricles and paraventricular cysts. After genetic counseling and careful consideration, the couple opted for pregnancy termination. To clarify the cause of the disease, whole-exome sequencing was performed on the fetal skin to detect possible variants, and which revealed a frameshift mutation c.924_930dup(p.R311Gfs*5) in exon 10 of the PDHA1 gene. Sanger sequencing confirmed the mutation was a de novo pathogenic variant, indicating that the fetus was affected by pyruvate dehydrogenase E1-α deficiency.

Objective:To understand the spectrum of pathogens and epidemic characteristics of respiratory infectious diseases in influenza virus-negative influenza-like cases in Yantai, and provide reference for disease prevention and control and clinical diagnosis and treatment.Methods:From March 2020 to February 2021, nasopharyngeal swab samples of 233 influenza virus-negative influenza like cases were collected in all sentinel hospitals monitored by Yantai National Influenza Network Laboratory, and 22 respiratory pathogens were detected by multiple fluorescence quantitative polymerase chain reaction to analyze epidemiological characteristics.Results:The total pathogen detection rate of 233 samples was 69.96% (163/233). A total of 17 respiratory pathogens were detected. The top three pathogens were human coronavirus (HCoV, 32.62%), rhinovirus/enterovirus (RhV/EV, 17.17%) and Legionella pneumophila (LP, 16.74%). The detection rates in different age groups were 80.28% (57/71) in the 0-15 years old group, 62.65% (52/83) in the 16-30 years old group, 68.18% (30/44) in the 31-45 years old group, 64.28% (9/14) in the 46-60 years old group, and 71.43% (15/21) in the >60 years old group. There was no significant difference among the groups. Respiratory pathogens were detected throughout the year, mainly in a single pathogen carrying mode (44.21%), and there was no significant difference in the physical examination rate of respiratory pathogens in different seasons. The seasonal prevalence of various pathogens was different, and the detection rate of HCoV 229E was the highest in spring (68.75%); the detection rate of rhinovirus/enterovirus was higher in autumn (26.98%) and winter (23.08%); the detection rate of LP was high in spring (19.05%) and summer (27.27%); the detection rate of human parainfluenza virus (HPIV) in spring (22.22%) was significantly higher than that in summer (3.64%). The number of HPIV and Bordetella pertussis (Bp) detected in the 0-15 year old group was the highest, and the detection rate was statistically significant among different age groups. Conclusions:The continuous monitoring of respiratory pathogens such as HCoV, RhV, EV, LP, HPIV should be strengthened to understand their epidemiologic characteristics and the standardization of pathogenicity, which provides data support and reference for epidemiological investigation of outbreaks that may be caused by other pathogens.

Objective:To assess the clinical value of metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid in pathogenic diagnosis of neurological infectious disease.Methods:Patients who were clinically diagnosed with infectious encephalitis and meningitis and treated in Department of Neurology, Affiliated Hospital of Chifeng University from March 2018 to September 2019 were retrospectively analyzed, including the clinical characteristics and data of mNGS and traditional laboratory test of pathogens.Results:Totally 104 patients with infectious encephalitis and meningitis were eligible for enrollment, and mNGS detected 22 bacterial species(22/104,21.15%), 24 viral species (24/104,23.08%), one fungal species (1/104,0.96%), one parasitic species (1/104,0.96%) and one mycoplasma species (1/104,0.96%).The three leading positive detections were varicella-zoster virus ( n=19), streptococcus ( n=7) and Mycobacterium tuberculosis ( n=4). Combined with traditional pathogen detection methods, clinical manifestations, final diagnosis and treatment results, the number of cases diagnosed by mNGS was 49 cases. The positive rate of the mNGS was 47.12% (49/104).False positives occurred in 21 (20.19%) patients. False negatives occurred in 34 (32.69%) patients. Conclusions:mNGS is more sensitive in evaluating the pathogens causing the infectious encephalitis and meningitis. It has advantages in accurate diagnosis of infectious encephalitis and meningitis.

Objective:To investigate the pathogenic spectrum of enteroviruses associated with hand, foot and mouth disease (HFMD) in the Yantai region of Shandong province in 2016, and analyze the evolution of epidemic strains of coxsackie virus group A type 6 (CV-A6) in the pathogenic spectrum of HFMD enteroviruses and the variations of important amino acid sites in the VP1 region.Methods:A total of 738 samples were collected from the patients with HFMD in Yantai region in 2016 to conduct DNA and serotype tests of enterovirus (EV) by real-time RT-PCR and further count the number and proportion of each type of enterovirus positive specimens. Based on the predominant serotype of enteroviruses, eight serotypes of the CV-A6 strains were selected to carry out VP1 regions amplification for the determination and analysis of nucleotide sequencing and phylogenetic analysis.Results:A total of 460 enteroviruses strains were isolated from 738 samples, including pathogens strains: 258 CV-A16 (56.09%), 62 EV-A71 (13.48%), 49 CV-A10 (10.65%), 44 CV-A6 (9.57%) and 9 CV-A4 (1.96%). Eight CV-A6 positive specimens were isolated from the viruses and the nucleotide-sequence analysis of the whole VP1 region was conducted. The sequence analysis of eight CV-A6 strains demonstrated that the homologies of nucleotide and amino acid were 96.12% - 100% and 97.78% - 100% respectively. The phylogenetic analysis indicated that the eight CV-A6 strains were subdivided into the genotype D subtype D3. Compared with the reference strain, CVA6-Gdula-AY421764, amino acids of CV-A6 strains in Yantai city observed at sites 10, 14, 174, 194, 279, 283 and 305 in VP1 region appeared mutant.Conclusions:CV-A16, EV-A71, CV-A10 and CV-A6 were the main common pathogens of HFMD in Yantai region in 2016. All the CV-A6 strains isolated in this study belonged to subtype D3 in genotype D.

Pilot areas have achieved initial success in capitation reform. On the other hand, challenges remain unsolved in terms of practical pathways, change of national medical insurance management system, related measures, incentives and allocative mechanism for implement of the reform. With the concerning on progress, practice, effects and challenges of typical areas, this article established an institutional framework. On such basis, we propose to design and refine a scheme in terms of 5 aspects, namely strengthening the basic medical care packages′financing, setting contents and standard of the basic medical care packages rationally, establishing effective evaluation system and formulating supporting measures.

Objective To develop a diagnostic model based on deep neural network for intelligent discrimination of thyroid function. Methods A total of 1616 patients ( 283 males, 1333 females, average age:52 years) who underwent thyroid imaging between May 2016 and June 2018 were selected. According to the clinical diagnosis, the 1616 cases included 299 normal thyroid cases, 876 hyperthyroidism cases and 441 hypothyroidism cases. Feature extraction and learning training were performed on 1000 training set sam-ples by two deep neural network models ( AlexNet;deep convolution generative adversarial networks ( DCGAN) ) using deep learning algorithm. Performance verifications were implemented on 616 test set samples. The con-sistency between the verification results of the two models and the clinical diagnosis was analyzed by Kappa test. Meanwhile, the time advantage of the intelligent diagnosis models was analyzed. Results The average diagnostic time of AlexNet model was 1 s/case, and the classification accuracy for normal thyroid, hyperthy-roidism, hypothyroidism were 82.29％(79/96), 94.62％(369/390), 100％(130/130), respectively. The Kappa value between results of AlexNet model and clinical diagnosis was 0.886 ( P<0.05) . The average di-agnostic time of DCGAN model was 1 s/case, and the classification accuracy for normal thyroid, hyperthy-roidism, hypothyroidism were 85.42％(82/96), 95.64％(373/390), 99.23％(129/130), respectively. The Kappa value between results of DCGAN model and clinical diagnosis was 0.904 ( P<0.05) . Conclusion The deep neural network intelligent diagnosis model can quickly determine the functional status of thyroid gland in thyroid imaging, and it has a high recognition accuracy, thus providing a new method for thyroid image review.

In this study, the swabs were collected among patients with an influenza-like illness (ILI) admitted to 2 sentinel surveillance hospitals of Yantai from April 2014 to August 2017. All specimen were cultured and identified by hemagglutination inhibition assay. Complete sequences of Hemagglutinin (HA) of influenza A were amplified, sequenced and analyzed using molecular and phylogenetic methods. The potential vaccine efficacy were calculated using Pepitope model. The results showed that the antigenicity of A (H3N2) had changed greatly. 8 strains of influenza A (H1N1) pdm09 belonged to subclade 6B.1 and 14 strains clustered in 6B.2. 12 strains of influenza A (H3N2) fell into subgroup 3C.3a and 33 strains clustered in 3C.2a. Several residues at antigen sites and potential glycosylation sites had changed in influenza A strains. Vaccine efficacy of influenza A (H1N1) pdm09 in 2015/2016 and 2016/2017 seasons were 77.29% and 79.11% of that of a perfect match with vaccine strain, meanwhile vaccine efficacy of influenza A (H3N2) in 2014/2015, 2015/2016 and 2016/2017 were-5.18%, 16.97% and 42.05% separately. In conclusion, the influenza A virus circulated in Yantai from 2014 to 2017 presented continual genetic variation. The recommended vaccine strains still afforded protection against influenza A (H1N1) pdm09 strains and provided suboptimal protection against influenza A (H3N2) strains.

In this study, the swabs were collected among patients with an influenza?like illness (ILI) admitted to 2 sentinel surveillance hospitals of Yantai from April 2014 to August 2017. All specimen were cultured and identified by hemagglutination inhibition assay. Complete sequences of Hemagglutinin (HA) of influenza A were amplified, sequenced and analyzed using molecular and phylogenetic methods. The potential vaccine efficacy were calculated using Pepitope model. The results showed that the antigenicity of A (H3N2) had changed greatly. 8 strains of influenza A (H1N1) pdm09 belonged to subclade 6B.1 and 14 strains clustered in 6B.2. 12 strains of influenza A (H3N2) fell into subgroup 3C.3a and 33 strains clustered in 3C.2a. Several residues at antigen sites and potential glycosylation sites had changed in influenza A strains. Vaccine efficacy of influenza A (H1N1) pdm09 in 2015/2016 and 2016/2017 seasons were 77.29% and 79.11% of that of a perfect match with vaccine strain, meanwhile vaccine efficacy of influenza A (H3N2) in 2014/2015, 2015/2016 and 2016/2017 were-5.18%, 16.97% and 42.05% separately. In conclusion, the influenza A virus circulated in Yantai from 2014 to 2017 presented continual genetic variation. The recommended vaccine strains still afforded protection against influenza A (H1N1) pdm09 strains and provided suboptimal protection against influenza A (H3N2) strains.

In this study, the swabs were collected among patients with an influenza?like illness (ILI) admitted to 2 sentinel surveillance hospitals of Yantai from April 2014 to August 2017. All specimen were cultured and identified by hemagglutination inhibition assay. Complete sequences of Hemagglutinin (HA) of influenza A were amplified, sequenced and analyzed using molecular and phylogenetic methods. The potential vaccine efficacy were calculated using Pepitope model. The results showed that the antigenicity of A (H3N2) had changed greatly. 8 strains of influenza A (H1N1) pdm09 belonged to subclade 6B.1 and 14 strains clustered in 6B.2. 12 strains of influenza A (H3N2) fell into subgroup 3C.3a and 33 strains clustered in 3C.2a. Several residues at antigen sites and potential glycosylation sites had changed in influenza A strains. Vaccine efficacy of influenza A (H1N1) pdm09 in 2015/2016 and 2016/2017 seasons were 77.29% and 79.11% of that of a perfect match with vaccine strain, meanwhile vaccine efficacy of influenza A (H3N2) in 2014/2015, 2015/2016 and 2016/2017 were-5.18%, 16.97% and 42.05% separately. In conclusion, the influenza A virus circulated in Yantai from 2014 to 2017 presented continual genetic variation. The recommended vaccine strains still afforded protection against influenza A (H1N1) pdm09 strains and provided suboptimal protection against influenza A (H3N2) strains.

Objective To investigate the expressions of spleen tyrosine kinase (Syk), c-Jun amino terminal kinase (JNK) and nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in the heart tissue in SD rat model of diabetic cardiomyopathy, and to explore the relationship between Syk, JNK and NLRP3. Methods Clean male SD rats were randomly divided into the control (Ctrl) group and diabetic cardiomyopathy model (DCM) group. Rats of DCM group were treated with a single intraperitoneal injection of streptozotocin (STZ), while rats of Ctrl group were injected with the same dose of citrate buffer. The random blood glucose level and body weight were monitored every week until 20 weeks after STZ or citrate buffer injection, then all the rats were killed and their hearts were obtained. Rat H 9c2 cardiomyocytes were randomly divided into normal glucose treatment (NG) group, high glucose treatment (HG) group, Syk inhibitor control (BAY) group and Syk inhibitor high glucose (HG+BAY) group. The Syk and JNK phosphorylations and NLRP3 protein expression were detected by Western blot assay in the heart tissue of SD rats and H9c2 cardiomyocytes. The NLRP3, cysteine-containing aspartate specific protease 1(caspase-1) and interleukin (IL)-1β expressions at mRNA level were detected by reverse transcription-polymerase chain reaction (RT-PCR). Results The random blood glucose level was significantly increased (P<0.05) and the body weight was significantly decreased (P<0.05) in DCM group compared with those of Ctrl group. The expressions of cardiac p-Syk, p-JNK and NLRP3 at protein level were significantly increased in DCM group compared with those of Ctrl group (P<0.05). Furthermore, the mRNA levels of NLRP3, caspase-1 and IL-1β were significantly up-regulated (P < 0.05). BAY treatment significantly inhibited the high glucose-induced NLRP3, caspase-1 and IL-1β mRNA expressions and p-JNK, NLRP3 protein expressions in H9c2 cardiomyocytes (P < 0.05). Conclusion JNK phosphorylation and NLRP3 inflammasome activation induced by Syk play an important role in the pathogenesis of diabetic cardiomyopathy.