Utilidad del complejo posterior para el diagnóstico prenatal de sintelencefalia

Introducción y objetivo: Demostrar el valor del plano axial del complejo posterior, como apoyo a la detección antenatal de sintelencefalia, variante de holoprosencefalia. Método: Se incluyeron todas las pacientes con diagnóstico de sintelencefalia evaluadas desde el año 2008. En todos los casos se consignaron los datos clínicos, de neurosonografía (NSG), de resonancia magnética (RM) y genética. Resultados: Cuatro casos fueron diagnosticados en el segundo trimestre y en todos se realizó estudio genético y RM. Tres tuvieron en su evolución anomalías extra-SNC y dos de ellos alteraciones cromosómicas, una de ellas incompatible con la vida extrauterina. Lo hallazgos descritos en neuroimagen para esta afección fueron detectados en la NSG, con una excelente correlación con RM, ya fuera esta última realizada en periodo fetal o posnatal. Conclusión: El diagnóstico prenatal de variantes de holoprosencefalia es difícil, considerando la existencia de una fusión medial más acotada que en las formas clásicas. El presente estudio demuestra la utilidad del plano del complejo posterior para la sospecha diagnóstica de sintelencefalia.

Introduction and objective: To demonstrate the value of the axial plane of the posterior complex, as a clue for the antenatal detection of synthelencephaly, a variant of holoprosencephaly. Method: All patients diagnosed with syntelencephaly evaluated since 2008 were included. In all cases, clinical, neurosonography (NSG), magnetic resonance imaging (MRI) and genetic data were recorded. Results: Four cases were diagnosed in the second trimester and in all of them a genetic study and MRI were performed. Three had extra-CNS anomalies in their evolution and two of them chromosomal anomalies, one of them incompatible with extrauterine life. Neuroimaging findings described for this condition were detected by NSG, with an excellent correlation with MRI, whether the latter was performed in the fetal or postnatal period. Conclusion: The prenatal diagnosis of holoprosencephaly variants is difficult, considering the existence of a more limited medial fusion than in the classical forms. The present study demonstrates the usefulness of the posterior complex plane for the diagnostic suspicion of synthelencephaly.

Regulation of Immune Balance by Traditional Chinese Medicine in Treatment of Cough Variant Asthma： A Review / 中国实验方剂学杂志

Cough variant asthma （CVA） is a chronic respiratory disease with cough as its main symptom. The occurrence of CVA is closely related to non-specific airway inflammation， and its pathogenesis involves environmental， genetic， immune， and other factors. In recent years， the advantages of traditional Chinese medicine （TCM） in the treatment of CVA have attracted the attention of experts and scholars in China and abroad， especially its prominent role in regulating immune balance， relieving cough symptoms in CVA patients， and reducing recurrence. T Helper cells 1 （Th1）， T helper cells 2 （Th2）， T helper cells 17 （Th17）， and regulatory T cells （Treg） are derived from CD4+ T cells. Immune imbalance of Th1/Th2 and Th17/Treg is a new hotspot in the pathogenesis of CVA and a potential key target in the treatment of CVA by TCM. Th cell subsets are in dynamic balance under physiological conditions， maintaining respiratory immune homeostasis in which pro-inflammatory cytokines and anti-inflammatory cytokines are balanced. Immature helper T cells （Th0） can be differentiated into Th1， Th2， Th17， Treg， and other cell subsets due to cytokine types in the microenvironment in the stage of CVA maturation. The proliferation of Th2 cells leads to eosinophilic airway inflammation. Excessive differentiation of Th17 cells induces neutrophil airway inflammation. Th1/Th2 and Th17/Treg cells are mutually restricted in number and function， and the immune imbalance of Th1/Th2 and Th17/Treg is easy to aggravate the generation of inflammatory response. Restoring immune balance is particularly important for the airway anti-inflammatory therapy of CVA. In this paper， the imbalance of Th1/Th2 and Th17/Treg and the pathogenesis of CVA were systematically expounded. Meanwhile， the latest research on the regulation of immune imbalance by TCM compound， single TCM， and its effective ingredients in the treatment of CVA was reviewed. It provides ideas and references for revealing the scientific connotation of TCM regulating immune balance therapy of CVA， as well as the development of clinical treatment and basic research of CVA.

Development and verification of cation exchange high performance liquid chromatography for detection of charge variants of pembrolizumab / 中国生物制品学杂志

@#Objective To develop and verify a cation exchange high performance liquid chromatography(CEX-HPLC)method for the detection of charge variants of pembrolizumab.Methods Pembrolizumab was bound to the exchange column matrix by using MabPac SCX-10 column,and the variants with different charges were eluted by gradually increasing the salt concentration of the mobile phase.The specificity,precision,linear range,accuracy and durability of the method were verified,and the charge variants of three batches of pembrolizumab finished products were detected by using the developed method.Results The resolution of the last acidic isomer peak and the first basic isomer peak of pembrolizumab from the main peak were 1.28 and 1.42,respectively.The mobile phase A and preparation buffer had no obvious interference peaks at the peak of the sample;The RSD values of the precision verification were all less than 2.0%;The total peak area,main peak area,acidic isomer peak area and basic isomer peak area of the standard all exhibited good linear relationship with the theoretical dilution concentration with each R~2 of 1.00;The recovery rates of the total peak area and main peak area of the standard at three concentrations were between 96.81% and 106.07%;When pH value of the mobile phase was within the range of 6.30±0.10,the RSD values of the total peak area and main peak area percentage of the standard were1.5% and 1.9%,and when the column temperature was within the range of(35±4) ℃,the RSD values of the total peak area and main peak area percentage of the standard were 0.4% and 0.3%,respectively.The RSD value of the main peak retention time of the three batches of finished products was 0.Conclusion The developed CEX-HPLC method can effectively separate the acidic isomers,main peaks and basic isomers of pembrolizumab with good specificity,precision and accuracy,which can be used for the follow-up research and development of pembrolizumab,the process verification of expanding production and the stability research.

Clinical follow-up study of SARS-CoV-2 Omicron infection / 上海预防医学

ObjectiveTo observe the clinical course and explore the risk factors for SARS-CoV-2 RNA negative conversion duration （NCD） in asymptomatic and mild-symptomatic patients infected with the SARS-CoV-2 Omicron variant. MethodsClinical data were collected from 244 confirmed cases of corona virus disease （COVID-19） with Omicron variant infection admitted to a temporal makeshift hospital in Shanghai from April 9， 2022 to May 20， 2022. Demographic and clinical data were analyzed， with a primary focus on the time of COVID-19 nucleic acid conversion. Univariate and multivariate Cox regression analysis were used to determine identify risk factors associated with NCD. ResultsThe median duration of negative RNA conversion was 9 days （ranged 7‒12 days）. The percentage of patients with positive nucleic acid results on the 5th， 7th， 10th， and 14th days after confirmed infection was 68.4%， 47.1%， 20.1%， and 5.7%， respectively. Kaplan-Meier curves indicated a median nucleic acid conversion time of 12 days （ranged 10‒14 days） for patients with hypertension， 9 days （ranged 7‒11 days） in patients without hypertension， and 11 days （ranged 9‒13 days） for patients aged ≥60 years， and 9 days （ranged 7‒11 days） for patients aged <60 years. Multivariate Cox regression analysis showed that only hypertension was an independent risk factor of NCD （RR=1.60； 95% CI： 1.03‒2.49， P=0.036）. ConclusionIn asymptomatic or mildly symptomatic patients infected with the Omicron variant， 20.1% patients continue to exhibit positive viral nucleic acid on the 10th days of infection. The independent risk factor associated with the conversion of SARS-CoV-2 nucleic acid to negative is hypertension.

A Novel Retrograde AAV Variant for Functional Manipulation of Cortical Projection Neurons in Mice and Monkeys / 神经科学通报·英文版

Retrograde adeno-associated viruses (AAVs) are capable of infecting the axons of projection neurons and serve as a powerful tool for the anatomical and functional characterization of neural networks. However, few retrograde AAV capsids have been shown to offer access to cortical projection neurons across different species and enable the manipulation of neural function in non-human primates (NHPs). Here, we report the development of a novel retrograde AAV capsid, AAV-DJ8R, which efficiently labeled cortical projection neurons after local administration into the striatum of mice and macaques. In addition, intrastriatally injected AAV-DJ8R mediated opsin expression in the mouse motor cortex and induced robust behavioral alterations. Moreover, AAV-DJ8R markedly increased motor cortical neuron firing upon optogenetic light stimulation after viral delivery into the macaque putamen. These data demonstrate the usefulness of AAV-DJ8R as an efficient retrograde tracer for cortical projection neurons in rodents and NHPs and indicate its suitability for use in conducting functional interrogations.

Relato de caso: aorta dorsal dupla persistente / Case report: persistent double dorsal aorta

Resumo A aorta dorsal dupla persistente é uma anomalia congênita extremamente rara, com apenas 13 casos publicados até o presente momento. Este estudo tem como objetivo apresentar a variação embriológica observada em aorta abdominal do paciente. A descrição anatômica foi realizada a partir da revisão de prontuário eletrônico e exames de imagem. Desta forma, o presente caso refere-se a um paciente idoso de 79 anos admitido em atendimento hospitalar por queixa de dor em membro inferior esquerdo ao repouso. Foi solicitada a internação do mesmo, assim como exames laboratoriais e de imagem. Obtida como um achado de imagem a partir de angiotomografia, a variação consiste na completa separação em duas porções: uma ventral e outra dorsal, de calibres diferentes, da aorta abdominal, ao nível da terceira vértebra lombar. Isso ocorre em conjunto com a origem anômala da artéria mesentérica inferior.

Abstract Persistent double dorsal aorta is an extremely rare congenital anomaly, with only 13 cases published to date. The objective of this study is to present this embryological variant as observed in the abdominal aorta of a patient. The anatomical description was written up on the basis of a review of electronic medical records and imaging exams. The patient in this case was an elderly 79-year-old man who presented at emergency with pain at rest in the left lower limb. He was admitted and laboratory tests and imaging exams were ordered. The variation was an imaging finding observed on angiotomography, consisting of complete separation of the abdominal aorta into two portions - a ventral and a dorsal, with different calibers - at the level of the third lumbar vertebra. There was also an anomalous origin of the inferior mesenteric artery.

Insulin-like growth factor binding protein 3 promoter variant (rs2854744) is associated with nonalcoholic fatty liver disease

ABSTRACT Objective: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease and a growing global epidemic. In NAFLD, liver fat surpasses 5% of hepatocytes without the secondary causes of lipid accumulation or excessive alcohol consumption. Given the link between NAFLD and insulin resistance, the possible association between the rs2854744 (−202 G>T) promoter polymorphism of insulin-like growth factor binding protein 3 (IGFBP3) gene and NAFLD was investigated in this study. Materials and methods: In this genetic case-control association study, the IGFBP3 rs2854744 genotypes of 315 unrelated individuals, including 156 patients with biopsy-proven NAFLD and 159 controls, were determined using polymerase chain reaction/restriction fragment length polymorphism analyses. Results: The "GT+TT" genotype of the IGFBP3 rs2854744 polymorphism, compared with the "GG" genotype, was associated with a 2.7-fold increased risk of NAFLD after adjustment for confounding factors (P = 0.009; odds ratio [OR] = 2.71; 95% confidence interval [CI] = 1.19-3.18). Additionally, the IGFBP3 rs2854744 "T" allele, in comparison with the "G" allele, was significantly overrepresented in NAFLD patients than the controls (P = 0.008; OR = 1.85; 95%CI = 1.23-2.94). Conclusion: Our findings first indicated that the IGFBP3 rs2854744 "GT+TT" genotype is a marker of increased NAFLD susceptibility; however, it needs to be supported by further investigations in other populations.

Comparative analysis of SARS-CoV-2 variants Alpha (B.1.1.7), Gamma (P.1), Zeta (P.2) and Delta (B.1.617.2) in Vero-E6 cells: ultrastructural characterization of cytopathology and replication kinetics

Abstract This study compares the effects of virus-cell interactions among SARS-CoV-2 variants of concern (VOCs) isolated in Brazil in 2021, hypothesizing a correlation between cellular alterations and mortality and between viral load and transmissibility. For this purpose, reference isolates of Alpha, Gamma, Zeta, and Delta variants were inoculated into monolayers of Vero-E6 cells. Viral RNA was quantified in cell supernatants by RT‒PCR, and infected cells were analyzed by Transmission Electron Microscopy (TEM) for qualitative and quantitative evaluation of cellular changes 24, 48, and 72 hours postinfection (hpi). Ultrastructural analyses showed that all variants of SARS-CoV-2 altered the structure and function of mitochondria, nucleus, and rough endoplasmic reticulum of cells. Monolayers infected with the Delta variant showed the highest number of modified cells and the greatest statistically significant differences compared to those of other variants. Viral particles were observed in the cytosol and the cell membrane in 100 % of the cells at 48 hpi. Alpha showed the highest mean particle diameter (79 nm), and Gamma and Delta were the smallest (75 nm). Alpha and Gamma had the highest particle frequency per field at 48 hpi, while the same was observed for Zeta and Delta at 72 hpi and 24 hpi, respectively. The cycle threshold of viral RNA varied among the target protein, VOC, and time of infection. The findings presented here demonstrate that all four VOCs evaluated caused ultrastructural changes in Vero-E6 cells, which were more prominent when infection occured with the Delta variant.

La genética de la epilepsia en la práctica clínica / The genetics of epilepsy in the clinical practice

Resumen La epilepsia es un trastorno neurológico caracterizado por crisis epilépticas recurrentes no provocadas, en el cual la genética tiene un factor etiológico importante. Durante las últimas décadas se ha logrado encontrar genes específicos involucrados en la patogénesis de esta condición. Actualmente existen múltiples exámenes disponibles en la práctica clínica para el diagnóstico genético, siendo los más útiles los paneles multi-genes y la secuenciación del exoma completo por medio de next generation sequencing (NGS). El tener un diagnósti co genético puede mejorar la calidad de vida de cada paciente y su familia, al mismo tiempo que nos ayuda a individualizar el tratamiento haciéndolo más eficaz. Algunos ejemplos en los que el diagnóstico genético puede modificar la conducta terapéutica incluyen el gen SCN1A en que se recomienda no utilizar medicamentos bloqueadores de canales de sodio y el gen SLC2A1 en el que se recomienda el inicio de la dieta cetogénica. El futuro de la investigación en medicina de precisión en epilepsia es muy prometedor, con el objetivo de que cada paciente reciba un tratamiento acorde a su etio logía genética.

Abstract Epilepsy is a neurological disorder characterized by recurrent unprovoked seizures. It is known that genetics play an important etiology roll. During the last decades it has been possible to find specific genes involved in the pathogenesis of this condition. There are currently multiple studies available in clinical practice for genetic diagnosis, the most useful being the next generation se quencing (NGS) techniques with multi-gene panels and whole exome sequencing. Having a genetic diagnosis can help improve the quality of life of each patient and their family, while it helps us to individualize the treatment, making it more effective. Some examples in which ge netic diagnosis can modify therapeutic conduct include the SCN1A gene, in which it is recommended not to use drugs that block Sodium channels, and the SLC2A1 gene, in which starting ketogenic diet is recommended. The future of precision medicine research in epilepsy is very promising, with the goal that each patient receives treatment according to their genetic etiology.

The rhabdoid variant of adrenocortical carcinoma-Report of three cases and literature review

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy. Extensive rhabdoid morphology in ACC has been described recently in very few cases. The proportion of rhabdoid morphology and the role of SMARCB1/ INI1 expression in these tumor cells to diagnose the specific variant is not described in the literature. We reviewed the clinicopathological features of nine cases of adrenocortical neoplasm. Out of which, three cases of ACC showed predominant rhabdoid morphology. Large discohesive cells with abundant cytoplasm containing eosinophilic inclusions, eccentric vesicular nucleus, and prominent nucleoli. INI1 immunostain was retained in all cases. We reported the rhabdoid variant of ACC, a novel entity, and its diagnostic approach from their histological mimickers. Identifying more cases of this entity will help to clearly understand the pathogenesis, biologic behaviour, and any specific molecular alterations in the future.

Identification of rare atypical BCR-ABL1 transcript: A case report

CML is characterized by the presence of a BCR-ABL1 fusion transcript. Several guidelines have been published for its detection and molecular monitoring. Here, a case is described of chronic myeloid leukemia presenting in the blast phase with a rare variant transcript, with a discussion on possible red flags in its detection and genetic testing and description of the patient's clinical characteristics. This case highlights the pitfalls of using real-time quantitative reverse-transcription polymerase chain reaction (RQ-PCR) for diagnosis of CML, especially when the clinical picture and the test results are discordant.

The B-cell non-Hodgkin’s lymphoma: An enigma to diagnose

Non-Hodgkin’s lymphoma is a heterogeneous group of malignancies characterized by an abnormal clonal proliferation of T-cells, B-cells, or both. Sometimes, tuberculosis and lymphoma presentation can share common symptoms and features. In this case report, we present the case of a 28-year-old female patient who came with a chief complaint of swelling on the right side of the face for the past 6 months. Initially, it was not associated with pain but gradually developed severe pain over the region and reduced salivary flow. The patient was planned for surgery with a differential diagnosis of salivary gland pathology. Post-operatively, the histopathological report showed atypical cells which were diffusely positive for cluster of differentiation (CD)20. Focally positive for CD45 and CD3 which was positive in reactive T lymphocytes. Immunohistochemistry pattern favors the diagnosis of B-cell type NHL. Through this case report, we want to share our experience in treating an aggressive tumor that mimics salivary gland pathology.

Ayudas diagnósticas y diagnóstico diferencial de la enfermedad de Pompe / Diagnostic aids and differential diagnosis of Pompe disease

Introducción: La enfermedad de Pompe (EP) o glucogenosis tipo II es una enfermedad autosómica recesiva causada por mutaciones en el gen GAA que codifica para la proteína alfa-1,4-glucosidasa. Su deficiencia lleva a un almacenamiento anormal de glucógeno en los lisosomas de varias células, a través de los diferentes tejidos, lo que causa un compromiso musculoesquelético predominante. Contenidos: Los fenotipos de la enfermedad dependen de las variantes genéticas y de los niveles de la actividad enzimática residual. La enfermedad se presenta como EP de inicio infantil, EP de inicio tardío y EP intermedio, por lo que es de suma importancia su diagnóstico temprano, por medio de estudios moleculares como la secuenciación de Sanger y la secuenciación de nueva generación. Conclusiones: Se ha demostrado, mediante diferentes estudios, que las variaciones genéticas pueden diferir entre etnias, y es importante su caracterización molecular para determinar el tratamiento más adecuado, de acuerdo con el estado del material inmunológico de reacción cruzada (CRIM).

Introduction: Pompe disease (PD) or Glycogenosis Type II is a rare autosomal recessive disease caused by mutations in the GAA gene that codes for the alpha-1,4-glucosidase protein. Its deficiency leads to abnormal glycogen storage in the lysosomes of various cells throughout the different tissues causing a predominant musculoskeletal compromise. Contents: The phenotypes of the disease depend on the genetic variants and the levels of residual enzyme activity, presenting as infantile-onset PD, late-onset PD, and intermediate PD; Therefore, early diagnosis of the disease through molecular studies such as Sanger sequencing and new generation sequencing is of utmost importance. Conclusions: It has been shown through different studies that genetic variations can vary between ethnic groups and the molecular characterization of the variants is important to determine the most appropriate treatment depending on the state of the cross-reactive immunological material (CRIM)

Huntington juvenil y fenocopia intrafamiliar a propósito de dos casos / Juvenile Huntington and intrafamily phenocopy, about two cases

RESUMEN La enfermedad de Huntington (EH) es una enfermedad neurodegenerativa hereditaria de progresión irremediablemente fatal. Existen otros trastornos con síntomas semejantes a los de esta enfermedad y que son llamados fenocopias. En nuestro reporte, se presentan los casos de dos hermanos con fenotipo compatible con EH, uno ellos con una fenocopia intrafamiliar, caracterizada por un síndrome coreico y cambios del comportamiento, con estudio genético negativo para EH. El caso índice cursa con una forma parkinsoniana de EH de inicio juvenil, con evolución lentamente progresiva que, además, presenta síntomas neuropsiquiátricos, con respuesta mínima a tratamiento sintomático con psicofármacos. El hermano mayor, caso de fenocopia intrafamiliar, cursó con movimientos discinéticos cervicofaciales y faciales severos, psicosis y cognición conservada. En conclusión, las fenocopias de EH pueden presentarse incluso dentro de una familia con EH genéticamente confirmada. Se recomienda una detallada evaluación neurológica y un estudio genético apropiado en todos los casos en que se tenga sospecha clínica de EH, incluso en familiares directos de pacientes diagnosticados con la enfermedad.

ABSTRACT Huntington's disease (HD) is an inherited neurodegenerative disorder with an always fatal outcome. Other disorders resemble the symptoms of this disease and are called phenocopies. The cases of two brothers in a family affected with a phenotype compatible with HD, are presented, one of them an intrafamilial phenocopy, characterized by choreic syndrome, abnormal behavior, and negative HD genetic testing. The index case evolves with a juvenile-onset slowly progressive parkinsonian form of HD that, in addition, presents neuropsychiatric symptoms with minimal response to symptomatic treatment with dopamine antagonists. The older brother, the intrafamilial phenocopy, experienced severe facial cervicofacial and cervical dyskinetic movements, psychosis, and preserved cognition. In conclusion, the HD phenocopies might occur even within a known, genetically confirmed HD family. It is recommended to perform a detailed neurological examination together with appropriate genetic testing in all cases with clinical suspicious of HD, including direct family members of HD affected individuals.

Introducción al filtrado, análisis y curación de variantes genéticas en pacientes con Discapacidad Intelectual / Introduction to filtering, analysis and curation of genetic variants in patients with Intellectual Disability

Resumen Actualmente la secuenciación del exoma completo (WES; Whole-exome sequencing) mediante la técnica NGS (Next-generation sequencing) es uno de los estudios genéticos más solicitados dentro del abordaje de pacientes con Discapacidad Intelectual con o sin otras anomalías. Al igual que con otros proce dimientos y estudios clínicos, es conveniente que los médicos prescriptores tengan una comprensión clara de los alcances y limitaciones del uso de WES, del proceso de análisis de las variantes genéticas identificadas, así como de aspectos a evaluar acerca de la calidad y estructura de los informes de los estudios de NGS, con el objetivo de que puedan interpretar mejor los resultados de un estudio y plantear de la mejor manera la correlación de los mismos con la clínica observada.

Abstract Currently, Whole exome sequencing (WES) using NGS (Next-generation sequencing) technology is one of the most requested genetic studies within the approach of patients with intellectual disability with or without other anomalies. As with other procedures and clinical studies, it is convenient for prescribing physicians to have a clear understanding of the scope and limitations of the use of WES, the analysis process of the genetic variants identified, as well as aspects to be evaluated regarding quality and structure of the reports of the NGS studies, with the aim that they can better interpret the results of a study, evaluate its quality, and propose in the best way the correlation of the same with the observed phenotype.

Biphasic squamoid alveolar renal cell carcinoma: A rare entity with an even rarer presentation as cutaneous metastases – A case report

Biphasic squamoid alveolar renal cell carcinoma (BSARCC) is a newly emerging distinct and rare morphologic variant of renal cell carcinoma (RCC). Morphological, immunohistochemical, and molecular data have shown that BSARCC is closely related to papillary RCC type 1. We report a case of Biphasic squamoid alveolar renal cell carcinoma with a rare presentation as cutaneous metastases. This variant tends to show an aggressive behavior. Hence, accurate histopathological diagnosis can help in effective treatment and for close follow-up of the patients.

A comparative computational approach on the most deleterious missense variant in Connexin 43 protein and its potent inhibitor analysis

Intercellular communication between the cell plays an essential role in cell growth and cell formation, including migration, metabolism, and cell differentiation. Cell function and tissue homeostasis are maintained through gap junction intercellular communication (GJIC), thus regulating connexin hemichannels. Mis regulation of such connexin, especially connexin (Cx) 43, affects a comprehensive process, including cell differentiation, inflammation, and cell death. Mis regulation may be due to the missense variant in Cx43. Thus, we screened the complete set of mutations from public mutational databases and obtained 219 missense variants, which were then classified based on their pathogenicity, functional impact, stability, conservation, and physiochemical properties. Variant L214P was scrutinized to have the most deleterious, which was then modelled using the I-TASSER server and performed molecular docking analysis to screen potent inhibitors. The compound Kanamycin, Ginsenoside, and Astragaloside IV have better interactions with Cx43 mutant with a maximum of 5 hydrogen bonds. Ginsenoside is a compound that follows a Lipinski rule of five. Thus, the result obtained from this study suggests that Ginsenoside would be a better potent inhibitor for native and mutant Cx43.

Clinical characteristics of family clustering pediatric and adult cases with severe acute respiratory syndrome coronavirus 2 Omicron variant infection / 中华传染病杂志

Objective:To investigate the clinical characteristics of family clustering pediatric and adult cases with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection in Shanghai City.Methods:A field investigation among the pediatric cases with Omicron variant infection and their household contacts from April 4 to April 30, 2022 in Children′s Hospital of Fudan University was conducted. The informations on case finding, clinical manifestations and SARS-CoV-2 vaccination status were collected. The epidemiological and clinical characteristics were compared between pediatric cases and adult cases. The independent sample t test or chi-square test was used for statistical analysis, and the relative risk ( RR) and 95% confidence interval (95% CI) were used to evaluate the protective effect of vaccination on the infection of Omicron variant. Results:There were 1 274 family members in 297 families including 370 children and 904 adults of whom 1 110(87.13%) were infected with Omicron variant, with 989(89.10%) symptomatic and 121(10.90%) asymptomatic. There were 355 children infected with Omicron variant, of whom 337(94.93%) were symptomatic, and the main manifestations were fever (96.74%(326/337)) and cough (40.36%(136/337)). Only one pediatric case with Rett syndrome developed critically severe pneumonia. A total of 194 pediatric cases had imaging examination, 64(32.99%) showed pulmonary inflammatory lesions. There were 755 adult cases infected with Omicron variant, of whom 652(86.26%) reported symptoms, and the main manifestations were fever (73.16%(477/652)) and cough (49.85%(325/652)). Among symptomatic cases, fever was more common in pediatric cases than in adult cases, while cough was more common in adult cases than in pediatric cases, and the differences were both statistically significant ( χ2=80.87 and 8.04, respectively, both P<0.01). The fever spike was higher in pediatric cases than in adult cases ((39.3±0.7) ℃ vs (38.6±0.6) ℃), and the difference was statistically significant ( t=9.85, P<0.001). The interval from the onset of symptoms to cycle threshold (Ct) value of the nucleic acid of Omicron variant≥35 was longer in pediatric cases than in adult cases ((13.0±3.1) d vs (10.9±3.6) d), and the difference had statistically significance ( t=2.97, P=0.004). Among 160 children aged 3 to 18 years, 54 (33.75%) received two-dose vaccination. Among the 904 adults, 388 (42.92%) received two-dose vaccination and 293 (32.41%) received a booster dose. In the adult cases, the risk of symptomatic infection was reduced by only 8% ( RR=0.92, 95% CI 0.86 to 0.98, P=0.014) following two-dose vaccination, and the risks of fever and cough following booster vaccination were reduced by 42%( RR=0.58, 95% CI 0.49 to 0.67, P=0.001) and 50% ( RR=0.50, 95% CI 0.34 to 0.78, P=0.001), respectively. Conclusions:Secondary attack rate and symptomatic rate of household infection are high in the context of the Omicron variant outbreak in Shanghai. Symptomatic infection is common in children and adults in household setting. Fever is the most common symptom and fever duration is short. Booster vaccination may provide certain protection against common symptoms caused by Omicron variant infection.

Clinical characteristics and genetic analysis of 6 cases of neonatal diabetes mellitus / 中国新生儿科杂志

Objective:To study the clinical features, genetic characteristics and prognosis of neonatal diabetes mellitus (NDM).Methods:From January 2015 to January 2022, neonates with NDM admitted to the Department of Neonatology of our hospital were retrospectively reviewed.Their clinical manifestations, biochemical data, genetic tests, treatments and outcomes were analyzed.Results:A total of 6 cases with NDM were included, with 3 males and 3 females. All 6 cases were full-term infants, 5 were low birth weight infants and 1 had family history of diabetes. High blood glucose were found on 1~11 d (average 4 d) after birth. 3 cases were diagnosed during blood glucose screening for low birth weight and 3 cases were diagnosed due to infection and/or diabetic ketoacidosis. Blood C-peptide levels were below normal range in all 6 cases. Blood insulin levels were decreased in 5 cases and remained at the lower limit of normal range in 1 case. All infants received genetic tests and 4 showed abnormal results, including 2 cases of ABCC8 gene mutation [c.2060C>T (p.T687M), not reported; c.674T>C (p.L225P), reported], 1 case of KCNJ11 gene mutation [c.602G>A (p.Arg201His), not reported] and 1 case of paternal uniparental disomy (UPD)6q24 (reported). All 6 cases were treated with insulin. Glibenclamide was experimented to replace insulin in 3 cases and 1 case was successful. During follow-up (at the age 4 months~5 years old), 4 cases were diagnosed with transient NDM, 1 case with permanent NDM and 1 case died at the age of 4 months without classification. 1 case showed psychomotor and language delay and the others had otherwise normal development.Conclusions:Most NDM infants are low birth weight infants with reduced blood insulin and C-peptide.Transient NDM are common. Proactive genetic testing may help treatment.

Diagnosis, treatment and prevention of severe acute respiratory syndrome coronavirus 2 infection in children: experts′ consensus statement (Fifth Edition)updated for the Omicron variant / 中华实用儿科临床杂志

China has classified the Corona Virus Disease 2019(COVID-19) as a statutory category B infectious disease and managed it according to Category B since January 8, 2023.In view that Omicron variant is currently the main epidemic strain in China, in order to guide the treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection in children with the times, refer to the Diagnosis and Treatment Protocol for Novel Coronavirus Infection (Trial 10 th Edition), Expert Consensus on Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fourth Edition) and the Diagnosis and Treatment Strategy for Pediatric Related Viral Infections.The Expert Consensus on the Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fifth Edition) has been formulated and updated accordingly on related etiology, epidemiology, pathogenic mechanism, clinical manifestations, auxiliary examination, diagnosis and treatment, and added key points for the treatment of COVID-19 related encephalopathy, fulminating myocarditis and other serious complications for clinical reference.