Randomized， Open， Parallel Controlled， Multi-center Study for Efficacy and Safety of Lianhua Qingke Tablets in Treatment of Acute Bronchitis in Children with Syndrome of Phlegm-heat Obstructing Lung / 中国实验方剂学杂志

ObjectiveTo evaluate the efficacy and safety of Lianhua Qingke tablets in the treatment of acute bronchitis in children with the syndrome of phlegm-heat obstructing lung. MethodA randomized， open， parallel controlled， and multi-center clinical study was conduted. Children with acute bronchitis （syndrome of phlegm-heat obstructing lung） were randomly assigned to an observation group and a control group. The control group received routine basic treatment， and the observation group was treated with Lianhua Qingke Tablets on the basis of routine basic treatment. After 7 days of treatment， the clinical efficacy， TCM efficacy， time to symptom disappearance， time to cough disappearance， and clinical safety were compared between the two groups. ResultA total of 248 children were included （124 in the observation group and 124 in the control group）. After 7 days of treatment， the total response rate in terms of clinical efficacy in the observation group was 96.8% （120/124）， which was higher than that （90.3%， 112/124） in the control group （Z=-5.034， P<0.01）. The total response rate in terms of TCM syndrome in the observation group was 97.6% （121/124）， which was higher than that （93.5%， 116/124） in the control group （χ2=-5.326， P<0.01）. The scores of physical signs and TCM symptoms in the observation group were lower than those in the control group at the time of taking medicine for 3 days and 7 days （P<0.01）. The time to symptom disappearance and the time to cough disappearance in the observation group were shorter than those in the control group （P<0.01）. Drug-related adverse reactions occurred in neither group. ConclusionLianhua Qingke tablets demonstrate a definite effect on acute bronchitis in children with the syndrome of phlegm-heat blocking lung. The tablets can significantly shorten the course of disease and relieve cough and TCM symptoms， with high safety， which is worthy of clinical application and promotion.

Echinacoside promotes mitochondrial biosynthesis and inhibition of myocardial apoptosis by up-regulating the PGC-1/NFR signaling pathway / 西安交通大学学报(医学版)

【Objective】 To investigate the effects of echinacoside （ECH） on mitochondrial biosynthesis and cardiomyocytes’ apoptosis in heart failure （HF） and to explore its related mechanisms. 【Methods】 The experimental animals were divided into three groups： the rat model of HF （HF） was induced by intraperitoneal injection of ISO， and pre-treated with ECH by intraperitoneal injection （ECH） and nomal control （ctrl group）. Cardiac function was detected by echocardiography after 2 weeks of treatment. The ultrastructure of myocardium was observed by transmission electron microscopy and the mitochondrial density and vacuolation rate were analyzed. The expressions of apoptosis-associated proteins were evaluated by Western blotting， and genes related to mitochondrial biosynthesis were examined by Real-time PCR. 【Results】 ECH increased 1eft ventricular ejection fraction （LVEF） and 1eft ventricular fraction shortening （LVFS）， but decreased 1eft ventricular end-systolic diameter （LVEDs） and 1eft ventrieular end-diastolic diameter （LVEDd） when compared to HF group （P<0.01） and improved cardiac function. The myocardial ultrastructure was significantly improved by ECH， the density of regular shapes of mitochondria was increased， and the percentage of vacuolated rate was reduced by ECH （P<0.01）. The expression of anti-apoptotic protein Bcl-2 was upregulated and that of pro-apoptotic protein Bax was downregulated in ECH group. The mRNA of mitochondrial biosynthesis related genes PGC-1， NFR-1， NFR-2 and TFAM was significantly upregulated in ECH group. 【Conclusion】 ECH promotes mitochondrial biosynthesis and inhibits cardiomyocytes’ apoptosis by up-regulating PGC-1/NFR signaling pathway， thus improving cardiac function.

Expression analysis of myocardial strain index after repair of abnormal origin of left coronary artery of pulmonary artery in children / 中华胸心血管外科杂志

Objective:To study the expression characteristics of myocardial strain index after the abnormal origin of the left coronary artery of the pulmonary artery in children was repaired.Methods:The data of 30 children (study group) with abnormal origin of pulmonary artery left coronary artery repair from August 2017 to August 2021 were analyzed. In addition, healthy children during the same period were selected as the control group, and the study group was compared before and after treatment and the control group. Circumferential and radial peak myocardial strain index, post-contraction strain index.Results:The longitudinal, circumferential, and radial overall peak strain indexes of the study group before and after treatment were significantly lower than those of the control group, and the longitudinal, circumferential, and radial overall peak strain indexes of the study group after treatment were significantly higher than those before treatment ( P<0.05); The longitudinal, circumferential, and radial peak strain indexes of the study group before treatment were significantly lower than those of the control group. After treatment in the study group, the middle section of the longitudinal inferior wall, the middle section of the anterior wall, the basal section of the anterior wall, the apex, and the circumferential direction were significantly lower The peak strain index of the basal segment of the inferior wall and the middle segment of the inferior wall was significantly lower than that of the control group; and the longitudinal, circumferential, and radial peak strain indexes of the study group after treatment were significantly higher than those before treatment ( P<0.05); the study group children before treatment Longitudinal, circumferential, and radial PSI indexes were significantly lower than those of the control group. After treatment, the study group was treated in the longitudinal inferior wall, septal apical segment, circumferential inferior wall basal segment, inferior wall middle segment, and radial PSI anterior wall basal segment, apex. The part was significantly higher than that of the control group; and the longitudinal, circumferential, and radial PSI of the study group after treatment were significantly lower than before treatment ( P<0.05). Conclusion:After ALCAPA repair, the overall and regional strain and overall synchronization are improved, indicating that the resting myocardium has recovered, but the strain of certain segments supplied by the abnormal left coronary artery fails to normalize after ALCAPA repair. Persistent myocardial injury is consistent, which can provide some guidance for the prognosis assessment of children with ALCAPA.

Transcriptome Analysis and Expression Profiling of Molecular Responses to Cd Toxicity in Morchella spongiola.

Morchella is a genus of fungi with the ability to concentrate Cd both in the fruit-body and mycelium. However, the molecular mechanisms conferring resistance to Cd stress in Morchella are unknown. Here, RNA-based transcriptomic sequencing was used to identify the genes and pathways involved in Cd tolerance in Morchella spongiola. 7444 differentially expressed genes (DEGs) were identified by cultivating M. spongiola in media containing 0.15, 0.90, or 1.50 mg/L Cd2+. The DEGs were divided into six sub-clusters based on their global expression profiles. GO enrichment analysis indicated that numerous DEGs were associated with catalytic activity, cell cycle control, and the ribosome. KEGG enrichment analysis showed that the main pathways under Cd stress were MAPK signaling, oxidative phosphorylation, pyruvate metabolism, and propanoate metabolism. In addition, several DEGs encoding ion transporters, enzymatic/non-enzymatic antioxidants, and transcription factors were identified. Based on these results, a preliminary gene regulatory network was firstly proposed to illustrate the molecular mechanisms of Cd detoxification in M. spongiola. These results provide valuable insights into the Cd tolerance mechanism of M. spongiola and constitute a robust foundation for further studies on detoxification mechanisms in macrofungi that could potentially lead to the development of new and improved fungal bioremediation strategies.

Potent in vitro Neutralization of SARS-CoV-2 by Hetero-bivalent Alpaca Nanobodies Targeting the Spike Receptor-Binding Domain

Cell entry by SARS-CoV-2 requires the binding between the receptor-binding domain (RBD) of the viral Spike protein and the cellular angiotensin-converting enzyme 2 (ACE2). As such, RBD has become the major target for vaccine development, while RBD-specific antibodies are pursued as therapeutics. Here, we report the development and characterization of SARS-CoV-2 RBD-specific VHH/nanobody (Nb) from immunized alpacas. Seven RBD-specific Nbs with high stability were identified using phage display. They bind to SARS-CoV-2 RBD with affinity KD ranging from 2.6 to 113 nM, and six of them can block RBD-ACE2 interaction. The fusion of the Nbs with IgG1 Fc resulted in homodimers with greatly improved RBD-binding affinities (KD ranging from 72.7 pM to 4.5 nM) and nanomolar RBD-ACE2 blocking abilities. Furthermore, fusion of two Nbs with non-overlapping epitopes resulted in hetero-bivalent Nbs, namely aRBD-2-5 and aRBD-2-7, with significantly higher RBD binding affinities (KD of 59.2 pM and 0.25 nM) and greatly enhanced SARS-CoV-2 neutralizing potency. The 50% neutralization dose (ND50) of aRBD-2-5 and aRBD-2-7 was 1.22 ng/mL ([~]0.043 nM) and 3.18 ng/mL ([~]0.111 nM), respectively. These high-affinity SARS-CoV-2 blocking Nbs could be further developed into therapeutics as well as diagnosis reagents for COVID-19. ImportanceTo date, SARS-CoV-2 has caused tremendous loss of human life and economic output worldwide. Although a few COVID-19 vaccines have been approved in several countries, the development of effective therapeutics including SARS-CoV-2 targeting antibodies remains critical. Due to their small size (13-15 kDa), highly solubility and stability, Nbs are particularly well suited for pulmonary delivery and more amenable to engineer into multi-valent formats, compared to the conventional antibody. Here, we report a serial of new anti-SARS-CoV-2 Nbs isolated from immunized alpaca and two engineered hetero-bivalent Nbs. These potent neutralizing Nbs showed promise as potential therapeutics against COVID-19.

Association of HLA-DRB1, -DQB1, -DPB1 alleles and haplotype polymorphisms with acute myeloid leukemia (non-M3) in northern Han population / 中国输血杂志

【Objective】 To explore the association of HLAII(-DRB1, -DQB1, -DPB1) alleles and haplotypes polymorphisms with acute myeloid leukemia (AML) in northern Han population. 【Methods】 A total of 308 AML (non-M3) patients (patient group) and 824 unrelated healthy bone marrow donors (control group) were genotyped at a high-resolution level using polymerase chain reaction-sequence-based typing (PCR-SBT), next-generation sequencing (NGS) with Ion Torrent S5 platform and sequence specific oligonueleotide probes (SSO) with LABScan® 3D platform. Frequencies of HLA II alleles and haplotypes were calculated with Arlequin 3.5.2.2 software. The odds ratio (OR) of AML was also calculated for case-control study. 【Results】 By χ2 test and correction, an increased frequency of HLA-DRB1*07∶01(14.61% vs 9.53%, P<0.01), HLA-DQB1*02∶02(12.82% vs 8.31%, P<0.01), HLA-DQB1*06∶02(11.53% vs 8.74%, P<0.05) and HLA-DPB1*17∶01(5.84% vs 3.16%, P<0.01) among AML patients was discovered in significant comparison with the control group. After Bonferroni correction, the frequency of HLA-DRB1*07∶01(Pc<0.05), HLA-DQB1*02: 02(Pc<0.05) and HLA-DPB1*17∶01(Pc<0.05) in AML patients were still higher than those in the control group, which had a strong positive correlation with AML (OR=1.62 (95% CI=1.23~2.14), 1.62(95% CI=1.21~2.18) and 1.91(95% CI=1.23~2.94), respectively. The frequency of two loci haplotype HLA-DRB1*07∶01-DQB1*02∶02 in AML patients was still higher than that of the control group after Bonferroni correction (12.66% vs 8.19%, Pc<0.05). The frequency of the 3 loci haplotype HLA-DRB1*07∶01-DQB1*02∶02-DPB1*17∶01, as a susceptible haplotype of AML, was higher than that of the control group and was strongly correlated with AML. 【Conclusion】 The data on the association of HLA II (-DRB1, -DQB1, -DPB1) alleles and haplotype polymorphisms with AML in northern Han populations was obtained in this study. HLA-DRB1*07∶01, HLA-DQB1*02∶02, HLA-DPB1*17∶01 and the HLA-DRB1*07∶01-DQB1*02∶02-DPB1*17∶01 haplotype are the risk genes and susceptible extended haplotype for AML. The risk prediction based on HLA haplotype might be more accurate than that based on single allele.

Practice and experience of standardized management of radiation hygiene in medical institutions / 中国辐射卫生

More than 90% of artificial irradiation comes from medical irradiation. New radiation technologies are constantly emerging in the medical field, bringing benefits to patients. At the same time, the harm of medical irradiation has attracted more and more attention. There are many problems in the supervision and management of radiation health in medical institutions, such as many standards and specifications involved in radiation health in medical institutions, uneven professional ability of personnel in primary health supervision institutions, inadequate implementation of the main responsibility for the safety of radiation diagnosis and treatment in medical and health institutions, and non-standard service of radiation health technical service institutions, etc. In view of the above problems, the implementation plan of standardization of radiation health supervision, radiation diagnosis and treatment behavior, and radiation technical service behavior has been set. After the pilot operation, the effect is obvious.

Characterization of a rare HLA-C*08:84 allele and analysis of its 3-D molecular structure / 中华医学遗传学杂志

OBJECTIVE@#To verify a rare allele of human leukocyte antigen (HLA) and analyze its inheritance and 3D molecular structure.@*METHODS@#PCR-sequence-based typing, PCR-single strand oligonucleotide polymorphism and single allele-specific sequencing were carried out to characterize the rare HLA-C allele and its transmission in the family. Its protein structure was modeled by using SWISS-MODEL, Phyre2 and FATCAT software.@*RESULTS@#Analysis indicated that the rare allele (HLA-C*08:84) has transmitted from the proband's mother and has differed from HLA-C*08:01 by a single base (g.512G>C), resulting in substitution of an amino acid (p.Trp147Ser). Modeling of the 3D structure of the encoded protein indicated that the amino acid residue variation is located at the alpha 2 helix, which participates the formation of pocket F. Modeling of the structures of C*08:84, C*08:01, C*08:02, C*08:03 and C*08:22 has suggested significant variation in the peptide binding regions of the backbone, with root mean square errors being 1.70 nm, 1.79 nm, 0.71 nm and 1.70 nm, respectively.@*CONCLUSION@#A rare HLA-C*08:84 allele has been identified, and its clinical significance has been analyzed.

Study on HPLC Fingerprint of Bombyx mori from Different Producing Areas and Content Determination of Multi- component / 中国药房

OBJECTIVE：To establish the fingerprint of Bombyx mori and the method for the content determination of multi- components，and to provide reference for comprehensive quality evaluation of B. mori . METHODS ：Using 18 batches of B. mori from different producing areas as samples ，HPLC method was used. The column was Shiseido CAPCELL PAK C 18 AQ S 5 with mobile phase consisted of methanol- 0.05 mol/L potassium dihydrogen phosphate solution （gradient elution ）at the flow rate of 1.0 mL/min. The detection wavelength was 260 nm，and column temperature was set at 30 ℃. The sample size was 10 μL. HPLC fingerprint analysis and similarity evaluation were performed by using TCM Chromatogram Fingerprint Similarity Evaluation System（2012 edition），and the chromatographic peak was identified by comparing with the chromatogram of reference substance. The contents of 4 nucleosides as uracil ，guanine，xanthine，uridine were determined . RESULTS ：A total of 16 common peaks were identified in HPLC fingerprint for 18 batches of B. mori ，and peaks 3，6 ，7 and 8 were identified as uracil ，guanine，xanthine and uridine. The similarity of sample chromatogram with control fingerprint were 0.912-1.000. The linear range of uracil ，guanine， xanthine and uridine were 5.34-534，5.28-528，5.06-506，5.195-519.5 μg/mL（r≥0.999 8）. The limits of detection were 0.032 4， 0.032 0，0.030 7，0.031 2 μg/mL，and the limits of quantitation were 0.106 8，0.105 6，0.101 2，0.103 0 μg/mL. RSDs of precision，reproducibility and stability tests （24 h）were all lower than 1.00％（n＝6）. Average recoveries were 100.15％-102.95％， and RSD s were all lower than 2.00％（n＝9）. The content determination results showed that the content of uracil ，guanine， xanthine and uridine of B. mori from different producing areas were 0.41％-2.46％，0.37％-1.98％，0.72％-2.63％，0.94％-3.67％， respectively. CONCLUSIONS ：Established HPLC fingerprint and content determination method of 4 nucleosides were specific ， accurate and reliable ，which can be used for the quality evaluation and control of B. mori .

Analysis of the intestinal microbiota in COVID-19 patients and its correlation with the inflammatory factor IL-18 and SARS-CoV-2-specific IgA

The current global COVID-19 pandemic is caused by beta coronavirus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which already infected over 10 million and caused 500 thousand deaths by June 2020. Overproduction of cytokines triggered by COVID-19 infection, known as "cytokine storm", is a highly risk factor associated with disease severity. However, how COVID-19 infection induce cytokine storm is still largely unknown. Accumulating in vitro and in vivo evidence suggests that gut is also susceptible to COVID19 infection: Human intestinal organoids, an in vitro model which mimic the specific cell type and spatial structure of the intestine, were susceptible to SARS-CoV2 infection; A significant fraction of patients reported gut symptoms; Viral RNA may persist for more than 30 days and infectious virus could be isolated in fecal samples. The gastrointestinal tract is the primary site of interaction between the host immune system with symbiotic and pathogenic microorganisms. The bacteria resident in our gastrointestinal tract, known as gut microbiota, is important to maintain the homeostasis of our immune system. While imbalance of gut microbiota, or dysbiosis, is associated with multiple inflammation diseases5. It's possible that SARS-CoV-2 infection may lead to alternation of gut microbiota thus worsen the host symptom. IL-18 is a proinflammatory cytokine produced multiple enteric cells, including intestinal epithelial cells (IECs), immune cells as well as enteric nervous system, and was shown to increase in the serum of COVID-19 patients. Immunoglobin A (IgA) is mainly produced in the mucosal surfaces, in humans 40-60mg kg-1 day-1 than all other immunoglobulin isotypes combined, and at least 80% of all plasma cells are located in the intestinal lamina propria. Recent study showed that SARS-CoV-2 specific IgA in the serum is positively correlate with the disease severity in COVID-19 patients11. Here we investigated the alterations of microbiota in COVID-19 patients, and its correlation with inflammatory factor IL-18 and SARS-CoV2 specific IgA.

Tocilizumab treatment in severe COVID-19 patients attenuates the inflammatory storm incited by monocyte centric immune interactions revealed by single-cell analysis

ABSTRACTDespite the current devastation of the COVID-19 pandemic, several recent studies have suggested that the immunosuppressive drug Tocilizumab can powerfully treating inflammatory responses that occur in this disease. Here, by employing single-cell analysis of the immune cell composition of severe-stage COVID-19 patients and these same patients in post Tocilizumab-treatment remission, we have identified a monocyte subpopulation specific to severe disease that contributes to inflammatory storms in COVID-19 patients. Although Tocilizumab treatment attenuated the strong inflammatory immune response, we found that immune cells including plasma B cells and CD8+ T cells still exhibited an intense humoral and cell-mediated anti-virus immune response in COVID-19 patients after Tocilizumab treatment. Thus, in addition to providing a rich, very high-resolution data resource about the immune cell distribution at multiple stages of the COVID-19 disease, our work both helps explain Tocilizumab’s powerful therapeutic effects and defines a large number of potential new drug targets related to inflammatory storms.Competing Interest StatementJingwen Fang is the executive officer of HanGen BiotechView Full Text

COVID-19 diagnosis and study of serum SARS-CoV-2 specific IgA, IgM and IgG by a quantitative and sensitive immunoassay

BackgroundThe pandemic of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is causing great loss. Detecting viral RNAs is standard approach for SARS-CoV-2 diagnosis with variable success. Currently, studies describing the serological diagnostic methods are emerging, while most of them just involve the detection of SARS-CoV-2-specific IgM and IgG by ELISA or "flow immunoassay" with limited accuracy. MethodsDiagnostic approach depends on chemiluminescence immunoanalysis (CLIA) for detecting IgA, IgM and IgG specific to SARS-CoV-2 nucleocapsid protein (NP) and receptor-binding domain (RBD) was developed. The approach was tested with 216 sera from 87 COVID-19 patients and 483 sera from SARS-CoV-2 negative individuals. The diagnostic accuracy was evaluated by receiver operating characteristic (ROC) analysis. Concentration kinetics of RBD-specific serum antibodies were characterized. The relationship of serum RBD-specific antibodies and disease severity was analyzed. ResultsThe diagnostic accuracy based on RBD outperformed those based on NP. Adding IgA to a conventional serological test containing IgM and IgG improves sensitivity of SARS-CoV-2 diagnosis at early stage. CLIA for detecting RBD-specific IgA, IgM and IgG showed diagnostic sensitivities of 98.6%, 96.8% and 96.8%, and specificities of 98.1%, 92.3% and 99.8%, respectively. Median concentration of IgA and IgM peaked during 16-20 days after illness onset at 8.84 g/mL and 7.25 g/mL, respectively, while IgG peaked during 21-25 days after illness onset at 16.47 g/mL. Furthermore, the serum IgA level positively correlates with COVID-19 severity. ConclusionCLIA for detecting SARS-CoV-2 RBD-specific IgA, IgM and IgG in blood provides additional values for diagnosing and monitoring of COVID-19. SummaryChemiluminescence immunoanalysis of SARS-CoV-2 RBD-specific serum IgA as well as IgM and IgG improves accuracy of COVID-19 diagnosis. Concentration kinetics of serum RBD-specific IgA, IgM and IgG are revealed. Serum IgA levels positively correlate with COVID-19 severity.

Unraveling the genetic cause of juvenile neuronal ceroid-lipofuscinosis / 中华实验眼科杂志

Objective@#To analyze the clinical symptoms and hereditary information of suspicious juvenile neuronal ceroid-lipofuscinosis (JNCL) and determine the genotype in order to explore the diagnosis clues in the patients with ophthalmologic manifestations being initial symptom.@*Methods@#A case-control study was performed in this study.Two families were included in Eye Hospital of Wenzhou Medical in 2013 and 2017, respectively.Medical histories were collected and all participants underwent comprehensive ophthalmologic examinations, and the best corrected visual acuity (BCVA) was obtained.Fundus photography and optical coherence tomography (OCT) were used to image the retinal signs, and visual electrophysiology was recorded to evaluate the visual function.Genomic DNA of 3 patients who initially visited to ophthalmologists and 5 unaffected family members were extracted.Whole exome sequencing (WES), targeted exome sequencing (TES), Sanger sequencing and comprehensive analyses of pathogenicity were performed to determine the genetic cause of the patients.This study was approved by Ethics Committee of Eye Hospital of Wenzhou Medical University (KYK-2017-7), and written informed consent was obtained from each subject prior to any medical examination.@*Results@#All patients presented bull eye sign and disorder of pigment on the fundus photograph, and the retinas were thinning on the OCT image, indicating the diffuse retinal pigment epithelium atrophy of macula and loss of outer layer structure of retina.Three mutations in CLN3 gene were identified by WES, TES, Sanger validation and assessments of pathogenicity, including c. 154T>C(p.Y52H), c.982G>C(p.A328P) and c. 906+ 5G>A, among which p. A328P was a novel mutation.Patients of F1 family harbored the compound heterozygous mutations c. 154T>C (p.Y52H) and c. 982G>C(p.A328P), while proband of F2 family harbored the homozygous splice site mutation c. 906+ 5G>A, which was reported to be a pathogenic mutation of JNCL.Co-segregation and comprehensive pathogenicity analysis revealed that the compound heterozygous mutations in F1 family and the homozygous mutation in a splice site in F2 family were the genetic causes of their phenotypes.@*Conclusions@#A novel mutation in CLN3 gene for JNCL is identified, which expands the mutation spectrum of CLN3 gene.Considering the high clinical heterogeneity of inherited retinal diseases, especially syndromic cases, genetic test through next generation plays a vital role in diagnosis, guiding future treatment and prognostic evaluation.

Unraveling the genetic cause of juvenile neuronal ceroid-lipofuscinosis / 中华实验眼科杂志

Objective To analyze the clinical symptoms and hereditary information of suspicious juvenile neuronal ceroid-lipofuscinosis (JNCL) and determine the genotype in order to explore the diagnosis clues in the patients with ophthalmologic manifestations being initial symptom.Methods A case-control study was performed in this study.Two families were included in Eye Hospital of Wenzhou Medical in 2013 and 2017,respectively.Medical histories were collected and all participants underwent comprehensive ophthalmologic examinations,and the best corrected visual acuity (BCVA) was obtained.Fundus photography and optical coherence tomography (OCT) were used to image the retinal signs,and visual electrophysiology was recorded to evaluate the visual function.Genomic DNA of 3 patients who initially visited to ophthalmologists and 5 unaffected family members were extracted.Whole exome sequencing (WES),targeted exome sequencing (TES),Sanger sequencing and comprehensive analyses of pathogenicity were performed to determine the genetic cause of the patients.This study was approved by Ethics Committee of Eye Hospital of Wenzhou Medical University (KYK-2017-7),and written informed consent was obtained from each subject prior to any medical examination.Results All patients presented bull eye sign and disorder of pigment on the fundus photograph,and the retinas were thinning on the OCT image,indicating the diffuse retinal pigment epithelium atrophy of macula and loss of outer layer structure of retina.Three mutations in CLN3 gene were identified by WES,TES,Sanger validation and assessments of pathogenicity,including c.154T＞C (p.Y52H),c.982G＞C (p.A328P) and c.906+5G＞A,among which p.A328P was a novel mutation.Patients of F1 family harbored the compound heterozygous mutations c.154T＞C (p.Y52H) and c.982G＞C (p.A328P),while proband of F2 family harbored the homozygous splice site mutation c.906+5G＞A,which was reported to be a pathogenic mutation of JNCL.Co-segregation and comprehensive pathogenicity analysis revealed that the compound heterozygous mutations in F1 family and the homozygous mutation in a splice site in F2 family were the genetic causes of their phenotypes.Conclusions A novel mutation in CLN3 gene for JNCL is identified,which expands the mutation spectrum of CLN3 gene.Considering the high clinical heterogeneity of inherited retinal diseases,especially syndromic cases,genetic test through next generation plays a vital role in diagnosis,guiding future treatment and prognostic evaluation.

Diagnosis of dilated cardiomyopathy in children based on microRNA sequencing technology / 中华实用儿科临床杂志

Objective:To investigate the correlation between specific expression of serum micro ribonucleic acid (miRNA) and dilated cardiomyopathy (DCM) in children.Methods:Sixteen children diagnosed with DCM in Pediatric Heart Center of Beijing Anzhen Hospital from November 2013 to March 2016 were enrolled in the DCM group.Meanwhile, 12 age- and gender-matched healthy children who underwent medical examinations at the same time in the same hospital were selected as the healthy control group.Their serum was collected and miRNA sequencing was performed.The sample size was expanded at the later stage (the DCM group included 30 cases, and the healthy control group included 16 cases). The real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) verification experiment was conducted on 11 miRNAs with statistically significant sequencing results.Results:Serum miRNA sequencing showed that 172 miRNAs were up-regulated but no miRNAs were down-regulated in the DCM group, compared with the healthy control group (fold change>2, P<0.001). Top 11 significantly up-regulated miRNAs were verified by qRT-PCR, and it was found that 8 of the 11 miRNAs (let-7f, let-7g, miR142-5p, miR143-3p, miR26a, miR27a-3p, miR27b-3p, and miR126-3p) in the DCM group were significantly up-regulated (all P<0.05). In the receiver operating characteristic (ROC) curves of DCM patients, the area under the curves of serum miR142-5p, miR143-3p, miR27b-3p, and miR126-3p were 0.983, 0.992, 0.915 and 0.950, respectively, which were statistically significantly different from those of the healthy control group (all P<0.05). Conclusions:Four serum miRNAs (miR-142-5p, miR-126-3p, miR-143-3p and miR-27b-3p) can distinguish children with DCM from healthy children.Circulating miRNAs are effective in screening DCM children.

Analysis on current situation and influencing factors of occupational stress among employees of disease control and prevention system in Beijing City / 中国职业医学

OBJECTIVE: To analyze the current situation and influencing factors of occupational stress among employees of disease control and prevention system in Beijing City. METHODS: A total of 903 employees from 7 centers for disease control and prevention(CDC) in Beijing City were selected as the research subjects using typical sampling method. The Job Demand-Control(JDC) Questionnaire and the Effort-Reward Imbalance(ERI) Questionnaire were used to evaluate and analyze the occupational stress and its influencing factors based on the JDC model and ERI model. RESULTS: The detection rate of high occupational stress in JDC model and ERI model were 54.5%(492/903) and 22.5%(203/903) respectively. The detection rate of high occupational stress in JDC model was higher than that in ERI model(P<0.01). Based on the JDC model, the multivariate logistic regression analysis showed that the lower the personal monthly income, the higher the risk of occupational stress of CDC employees(P<0.01). The risk of those in administrative position was higher than those in non-administrative position(P<0.01). The risk of employees with more than 10 years of service length was higher than those with less than 10 years of service length(P<0.01). The employees with longer weekly working hours had the higher risk(P<0.01). Based on the ERI model, the risk of occupational stress of CDC employees in the administrative position was higher than that of non-administrative position(P<0.05). The risk of professional technical post and work skill post were higher than that of management post(all P<0.05). The risk of employee with more than 10 years of service length was higher than that of less than 10 years(P<0.05). The longer weekly working hours had higher risk(P<0.01). CONCLUSION: The occupational stress of the JDC model is the main occupational stress model in Beijing CDC system. The main influencing factors include monthly income, position, service length and weekly working hours. The main factors of occupational stress in ERI model include position, post, service length and weekly working hours.

Value of 18F-FDG PET-CT imaging features in the prognosis evaluation of newly diagnosed patients with multiple myeloma / 白血病·淋巴瘤

Objective To explore the relevance between 18F-FDG PET-CT imaging features and laboratory parameters of multiple myeloma (MM) and its prognostic value. Methods The clinical data of 75 MM patients who received 18F-FDG PET-CT examination at the time of initial diagnosis in Tianjin Medical University Cancer Institute & Hospital from September 2008 to August 2016 were retrospectively analyzed, including their clinical features, survival time, PET-CT imaging and laboratory results. The correlation between imaging changes and laboratory results was analyzed. Kaplan-Meier method and log-rank test were used to make survival analysis. Results Of 75 patients, there were 48 patients (64.0%) who had lytic bone lesions everywhere of the bodies, especially in axial skeleton. Twenty-six patients (34.7%) had pathological fracture, which were either rib or spinal pathologic fracture. PET-CT at initial diagnosis showed that the osteolytic lesions were associated with anemia (χ2＝ 0.455, P ＝ 0.032), while pathological fractures were associated with C-reactive protein levels (χ 2 ＝ 0.976, P ＝ 0.007). The existence of pathologic fracture or lytic bone lesions showed no relevance to abnormal cytogenetics, extramedullary lesion, lactic dehydrogenase, albumin or β2-macroglobulin (β2-MG) levels as well as the survival time (all P＞0.05). Twenty-eight patients (37.3%) with

Effects of urate-lowering therapy on inflammatory responses, gout flares occurances, and the achieved target rate of serum uric acid in acute gout / 中华内分泌代谢杂志

Objective To observe the effects of urate-lowering therapy ( ULT) on indexes of inflammation, the frequency of gout flares, compliance of ULT, and the achieved rates of serum uric acid in patients at acute stage. Methods 151 patients with acute gout flares were randomly divided into observation group ( 60 cases with ULT in the acute phase) and control group (91 cases with ULT after 2 weeks of complete remission from acute flares). Visual analogue pain scores (VAS), joint swelling scores, white blood cell counts, erythrocyte sedimentation rates (ESR), as well as high sensitive-C reactive protein (hs-CRP) were measured respectively and compared between two groups. The observation group was treated with 40 mg/d of febuxostat for 12 weeks after effectively achieved inflammation ( VAS<3 points) , while the control group was treated with the same therapy after 2 weeks of symptoms complete remission from acute gout flares. Finally, these indexes were followed and recorded, including the number of gout flares, the compliance of ULT, the changes of liver and kidney function, and the proportion of patients with serum uric acid<360μmol/L. Results There was no statistical difference in the baseline condition, VAS pain scores, joint swelling scores, white blood cell counts, ESR, and hs-CRP between two groups after different ULTs ( all P>0.05) . There was no statistical difference in the frequency of gout flares between two groups during the ULT of 12 weeks ( P=0.658) . At the end of 12 weeks, the serum uric acid in the observation group was significantly lower compared with the control group [(318.38±95.16 vs 398.12±120.13)μmol/L,P<0.01]. The compliance rate of ULT and the rate of reaching the standard of serum uric acid<360μmol/L in the observation group were higher than those in the control group ( both P<0.01) . Conclusion The treatment of ULT with patients after effective achieved of acute gout inflammation has no detrimental effects on VAS pain, joint swelling score, the conversion of inflammation index, and the number of gout flares, while improving the compliance of ULT and the achieved rate of serum uric acid.

Prenatal echocardiography in the diagnosis of fetal double aortic arch / 中华超声影像学杂志

To explore the way of prenatal echocardiography in the diagnosis of fetal double aortic arch . Methods T he data of fetuses diagnosed as double aortic arch in 6 prenatal centers in Hunan in echocardiograms performed at 20－36 weeks of gestation from 2013 to 2018 were reviewed . T he characteristics of echocardiographic with double aortic arch , and the associated malformations were observed ,the clinical outcome were analyzed . Results T he main echocardiographic features of the double aortic arch were three‐vessel‐tracheal view s ,which showed a bifurcation of the ascending aorta and a ring consisted of aortic right and left arch . From this retrospective analysis , 29 double aortic arches were identified ,which 8 cases ( 28% ) combined with cardiac defect and extracardiac abnormalities , 1 case with 22q11 deletion . Among them ,5 cases were confirmed by autopsy ,24 cases were diagnosed by computed tomography angiography ( 8 cases were confirmed by operation ) . Conclusions Systematic prenatal echocardiography in the diagnosis of fetal double aortic arch has significant clinical value in the cliagnose of double aortic arch ,w hether it is associated with other malformations and is important for assessing fetal prognosis .

Heat shock protein 22 reduces phenylephrine-induced cardiomyocytes hypertrophy / 中华急诊医学杂志

Objective To investigate the effect of Hsp22 on phenylephrine-induced cardiomyocytes hypertrophy.Methods Primary rat myocardial cells were isolated and cultured in Department of Cardiology,the First Affiliated Hospital of Zhengzhou University.Cells were divided into four groups randomly:Control group,model group,treatment group with 1 μg/mL Hsp22,and treatment group with 10 μg/mL Hsp22.Phenylephrine stimuli was used to induce cardiomyocytes hypertrophy model.Cell viability was measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.Cardiomyocytes surface area was evaluated by α-actin immunofluorescence staining.Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the transcription level of hypertrophic markers.Reactive oxygen species level was detected by 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe.Apoptosis was detected by TUNEL staining.Signal pathway protein expression was detected by Western blot.SPSS 13.0 was used for statistical analysis.Data were expressed as mean + standard deviation.All data were analyzed by one-way ANOVA between groups.Comparisons between two groups were performed using LSD-t test.A P＜0.05 was considered statistically significant.Results Different concentrations of Hsp22 had no effect on cardiomyocytes viability (F=6.622;P＞0.05).Phenylephrine stimulation significantly increased cardiomyocytes area (t=10.80;P＜0.05),increased the transcription level of hypertrophy markers atrial natriuretic peptide (t=37.72;P＜0.05),type B natriuretic peptide (t=16.85;P＜0.05),and myosin heavy chain beta (t=41.53;P＜0.05).Different concentrations of Hsp22 significantly reduced cardiomyocytes area (PE+ 1 μg/mL Hsp22 t=4.018;P＜0.05;PE+10 μg/mL Hsp22 t=10.80;P＜0.05),reduced the transcription level of hypertrophic markers atrial natriuretic peptide (PE+1 μg/mL Hsp22 t=27.12,P＜0.05;PE+10 μg/mL Hsp22 t=37.72,P＜0.05),type B natriuretic peptide (PE+1 μg/mL Hsp22 t=4.82,P＜0.05;PE+10 μg/mL Hsp22 t=12.74,P＜0.05),and myosin heavy chain beta (PE+1 μg/mL Hsp22 t=23.68,P＜0.05;PE+10 μg/mL Hsp22 t=30.54,P＜0.05).Westem blot showed that Hsp22 increased the activation of AMP-activated protein kinase α (PE+1 μg/mL Hsp22 t=5.89,P＜0.05;PE+10 μg/mL Hsp22 t=5.88,P＜0.05),reduced mTOR phosphorylation level (PE+1 μg/mL Hsp22 t=16.80,P＜0.05;PE+10.μg/mL Hsp22 t=20.46,P＜0.05).Conclusions Hsp22 inhibits cardiomyocytes hypertrophy by activating AMP-activated protein kinase α.Hsp22 may become a potential anti-hypertrophic drug.