[A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020]. / 2019­2020å¹´160ä¾‹å„¿ç«¥è‚ºç‚Žé“¾çƒèŒè„‘è†œç‚Žä¸´åºŠæµè¡Œç— å­¦å¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To investigate the clinical characteristics and prognosis of pneumococcal meningitis (PM), and drug sensitivity of Streptococcus pneumoniae (SP) isolates in Chinese children. METHODS: A retrospective analysis was conducted on clinical information, laboratory data, and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country. RESULTS: Among the 160 children with PM, there were 103 males and 57 females. The age ranged from 15 days to 15 years, with 109 cases (68.1%) aged 3 months to under 3 years. SP strains were isolated from 95 cases (59.4%) in cerebrospinal fluid cultures and from 57 cases (35.6%) in blood cultures. The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87) and 27% (21/78), respectively. Fifty-five cases (34.4%) had one or more risk factors for purulent meningitis, 113 cases (70.6%) had one or more extra-cranial infectious foci, and 18 cases (11.3%) had underlying diseases. The most common clinical symptoms were fever (147 cases, 91.9%), followed by lethargy (98 cases, 61.3%) and vomiting (61 cases, 38.1%). Sixty-nine cases (43.1%) experienced intracranial complications during hospitalization, with subdural effusion and/or empyema being the most common complication [43 cases (26.9%)], followed by hydrocephalus in 24 cases (15.0%), brain abscess in 23 cases (14.4%), and cerebral hemorrhage in 8 cases (5.0%). Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old, with rates of 91% (39/43) and 83% (20/24), respectively. SP strains exhibited complete sensitivity to vancomycin (100%, 75/75), linezolid (100%, 56/56), and meropenem (100%, 6/6). High sensitivity rates were also observed for levofloxacin (81%, 22/27), moxifloxacin (82%, 14/17), rifampicin (96%, 25/26), and chloramphenicol (91%, 21/23). However, low sensitivity rates were found for penicillin (16%, 11/68) and clindamycin (6%, 1/17), and SP strains were completely resistant to erythromycin (100%, 31/31). The rates of discharge with cure and improvement were 22.5% (36/160) and 66.2% (106/160), respectively, while 18 cases (11.3%) had adverse outcomes. CONCLUSIONS: Pediatric PM is more common in children aged 3 months to under 3 years. Intracranial complications are more frequently observed in children under 1 year old. Fever is the most common clinical manifestation of PM, and subdural effusion/emphysema and hydrocephalus are the most frequent complications. Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates. Adverse outcomes can be noted in more than 10% of PM cases. SP strains are high sensitivity to vancomycin, linezolid, meropenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.

Association between gestational exposure and risk of orofacial clefts: a systematic review and meta-analysis.

BACKGROUND: The occurrence of orofacial Clefts (OFCs) is a congenital disease caused by many factors. According to recent studies, air pollution has a strong correlation with the occurrence of OFCs. However, there are still some controversies about the current research results, and there is no relevant research to review the latest results in recent years. OBJECTIVE: In this paper, the authors conducted a systematic review and meta-analysis to explore the correlation between ambient air pollution and the occurrence of neonatal OFCs deformity. METHODS: We searched Pubmed, Web of science, and Embase databases from the establishment of the database to May 2023. We included observational studies on the relationship between prenatal exposure to fine particulate matter 2.5 (PM2.5), fine particulate matter 10 (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), carbon monoxide (CO) and the risk of cleft lip (CL), cleft palate (CP), cleft lip with or without palate (CL/P). the Newcastle-Ottawa quality assessment scale (NOS) was used to evaluate the quality of the literature. Funnel plot and Egger's regression were used to verify the publication bias. Random effect model or fixed effect model was used to estimate the combined relative risk (RR) and 95% confidence interval (95%CI). RESULTS: A total of eleven studies were included in this study, including four cohort studies and seven case-control studies, including 22,453 cases of OFCs. Ten studies had low risk of bias and only one study had high risk of bias. Three studies reported that PM2.5 was positively correlated with CL and CP, with a combined RR and 95%CI of 1.287(1.174,1.411) and 1.267 (1.105,1.454). Two studies reported a positive correlation between O3 and CL, with a combined RR and 95%CI of 1.132(1.047,1.225). Two studies reported a positive correlation between PM10 and CL, with a combined RR and 95%CI of 1.108 (1.017,1.206). No association was found between SO2, CO, NO2 exposure during pregnancy and the risk of OFCs. CONCLUSION: The results of this study showed that there was a significant statistical correlation between exposure to PM10, PM2.5, O3 and the risk of OFCs in the second month of pregnancy. Exposure assessment, research methods and mechanisms need to be further explored.

Rapid and Simple Analysis of the Human Pepsin Secondary Structure Using a Portable Raman Spectrometer.

Human pepsin is a digestive protease that plays an important role in the human digestive system. The secondary structure of human pepsin determines its bioactivity. Therefore, an in-depth understanding of human pepsin secondary structure changes is particularly important for the further improvement of the efficiency of human pepsin biological function. However, the complexity and diversity of the human pepsin secondary structure make its analysis difficult. Herein, a convenient method has been developed to quickly detect the secondary structure of human pepsin using a portable Raman spectrometer. According to the change of surface-enhanced Raman spectroscopy (SERS) signal intensity and activity of human pepsin at different pH values, we analyze the change of the human pepsin secondary structure. The results show that the content of the ß-sheet gradually increased with the increase in the pH in the active range, which is in good agreement with circular dichroism (CD) measurements. The change of the secondary structure improves the sensitivity of human pepsin SERS detection. Meanwhile, human pepsin is a commonly used disease marker for the noninvasive diagnosis of gastroesophageal reflux disease (GERD); the detection limit of human pepsin we obtained is 2 µg/mL by the abovementioned method. The real clinical detection scenario is also simulated by spiking pepsin solution in saliva, and the standard recovery rate is 80.7-92.3%. These results show the great prospect of our method in studying the protein secondary structure and furthermore promote the application of SERS in clinical diagnosis.

Dual molecular diagnosis of tricho-rhino-phalangeal syndrome type I and Okur-Chung neurodevelopmental syndrome in one Chinese patient: a case report.

BACKGROUND: Okur-Chung neurodevelopmental syndrome (OCNDS) and tricho-rhino-phalangeal syndrome type I (TRPSI) are rare Mendelian diseases. OCNDS is caused by CSNK2A1 gene variants and TRPSI is caused by the TRPS1gene. However, to have two Mendelian diseases in one patient is even rarer. CASE PRESENTATION: A 6-year-10-month-old boy characterized by special facial features, short stature and mental retardation was referred to our pediatric endocrinology department. Whole-exome sequencing (WES) was done to detect the molecular basis of his disease. This patient was confirmed to carry two variants in the CSNK2A1 gene and one in the TRPS1 gene. The variant in the CSNK2A1 gene was vertically transmitted from his father, and the variant in TRPS1 gene from his mother. These two variants are classified as pathogenic and the causes of the presentation in this child. This patient's father and mother have subsequently been diagnosed as having OCNDS and TRPSI respectively. CONCLUSION: This is the first reported case of a dual molecular diagnosis of tricho-rhino-phalangeal syndrome type I and Okur-Chung neurodevelopmental syndrome in the same patient. This patient is the first published example of vertical transmission of this recurrent CSN2A1 variant from parent to child. A novel variant in the TRPS1 gene that is pathogenic was also identified. In conclusion, identification of the variants in this patient expands the phenotypes and molecular basis of dual Mendelian diseases.

IRF4 and STAT3 activities are associated with the imbalanced differentiation of T-cells in responses to inhalable particulate matters.

BACKGROUND: Particulate Matter (PM) is known to cause inflammatory responses in human. Although prior studies verified the immunogenicity of PM in cell lines and animal models, the effectors of PM exposure in the respiratory system and the regulators of the immunogenicity of PM is not fully elucidated. METHODS: To identify the potential effector of PM exposure in human respiratory system and to better understand the biology of the immunogenicity of PM, We performed gene-expression profiling of peripheral blood mononuclear cells from 171 heathy subjects in northern China to identify co-expressed gene modules associated with PM exposure. We inferred transcription factors regulating the co-expression and validated the association to T-cell differentiation in both primary T-cells and mice treated with PM. RESULTS: We report two transcription factors, IRF4 and STAT3, as regulators of the gene expression in response to PM exposure in human. We confirmed that the activation of IRF4 and STAT3 by PM is strongly associated with imbalanced differentiation of T-cells in the respiratory tracts in a time-sensitive manner in mouse. We also verified the consequential inflammatory responses of the PM exposure. Moreover, we show that the protein levels of phosphorylated IRF4 and STAT3 increase with PM exposure. CONCLUSIONS: Our study suggests the regulatory activities of IRF4 and STAT3 are associated with the Th17-mediated inflammatory responses to PM exposure in the respiratory tracts, which informs the biological background of the immunogenicity of particulate matters.

Intelligent diagnosis with Chinese electronic medical records based on convolutional neural networks.

BACKGROUND: Benefiting from big data, powerful computation and new algorithmic techniques, we have been witnessing the renaissance of deep learning, particularly the combination of natural language processing (NLP) and deep neural networks. The advent of electronic medical records (EMRs) has not only changed the format of medical records but also helped users to obtain information faster. However, there are many challenges regarding researching directly using Chinese EMRs, such as low quality, huge quantity, imbalance, semi-structure and non-structure, particularly the high density of the Chinese language compared with English. Therefore, effective word segmentation, word representation and model architecture are the core technologies in the literature on Chinese EMRs. RESULTS: In this paper, we propose a deep learning framework to study intelligent diagnosis using Chinese EMR data, which incorporates a convolutional neural network (CNN) into an EMR classification application. The novelty of this paper is reflected in the following: (1) We construct a pediatric medical dictionary based on Chinese EMRs. (2) Word2vec adopted in word embedding is used to achieve the semantic description of the content of Chinese EMRs. (3) A fine-tuning CNN model is constructed to feed the pediatric diagnosis with Chinese EMR data. Our results on real-world pediatric Chinese EMRs demonstrate that the average accuracy and F1-score of the CNN models are up to 81%, which indicates the effectiveness of the CNN model for the classification of EMRs. Particularly, a fine-tuning one-layer CNN performs best among all CNNs, recurrent neural network (RNN) (long short-term memory, gated recurrent unit) and CNN-RNN models, and the average accuracy and F1-score are both up to 83%. CONCLUSION: The CNN framework that includes word segmentation, word embedding and model training can serve as an intelligent auxiliary diagnosis tool for pediatricians. Particularly, a fine-tuning one-layer CNN performs well, which indicates that word order does not appear to have a useful effect on our Chinese EMRs.

Effects of particulate matter (PM) on childhood asthma exacerbation and control in Xiamen, China.

BACKGROUND: The short-term effects of particulate matter (PM) exposure on childhood asthma exacerbation and disease control rate is not thoroughly assessed in Chinese population yet. The previous toxic effects of PM exposure are either based on long-term survey or experimental data from cell lines or mouse models, which also needs to be validated by real-world evidences. METHODS: We evaluated the short-term effects of PM exposure on asthma exacerbation in a Chinese population of 3106 pediatric outpatientsand disease control rate (DCR) in a population of 3344 children using case-crossover design. All the subjects enrolled are non-hospitalized outpatients. All data for this study were collected from the electronic health record (EHR) in the period between January 1, 2016 and June 30, 2018 in Xiamen, China. RESULTS: We found that exposure to PM2.5 and PM10 within the past two weeks was significantly associated with elevated risk of exacerbation (OR = 1.049, p < 0.001 for PM2.5and OR = 1.027, p < 0.001 for PM10). In addition, exposure to PM10 was associated with decreased DCR (OR = 0.976 for PM10, p < 0.001). CONCLUSIONS: Our results suggest that exposure to both PM10 and PM2.5 has significant short-term effects on childhood asthma exacerbation and DCR, which serves as useful epidemiological parameters for clinical management of asthma risk in the sensitive population.

Identification of IL2RG and CYBB mutations in two Chinese primary immunodeficiency patients by whole-exome sequencing.

BACKGROUND: Primary immunodeficiency diseases are a group of genetic disorders that lead to increased propensity to a variety of infections, sometimes with fatal outcomes. METHOD: In this study, whole-exome sequencing (WES) was used to identify mutations in two patients suspected of having primary immunodeficiency. Sanger sequencing was used to confirm the results in the patients and their family. RESULT: One patient was diagnosed as X-linked severe combined immunodeficiency (X-SCID) and another patient as X-linked chronic granulomatous disease (X-CGD) by WES. Sequencing analysis of IL2RG gene revealed a novel mutation (c.794T>A, p.I265N) and CYBB gene revealed a missense mutation (c.935T>A, p.M312K). DISCUSSION AND CONCLUSION: This study identifies one novel mutation in the IL2RG gene and another, previously described mutation in the CYBB genes. It is the first report establishing a diagnosis of X-SCID and X-CGD using WES in Chinese patients.

Fragment-wise design of inhibitors to 3C proteinase from enterovirus 71.

BACKGROUND: Enterovirus 71 (EV71) is a causative agent of hand, foot and mouth disease (HFMD), which can spread its infection to central nervous and other systems with severe consequence. A key factor in the replication of EV71 is its 3C proteinase (3C(pro)), a significant drug target. Peptidomimetics were employed as inhibitors of this enzyme for developing antivirals. However, the peptide bonds in these peptidomimetics are a source of low bioavailability due to their susceptibility to protease digestion. To produce non-peptidomimetic inhibitors by replacing these peptide bonds, it would be important to gain better understanding on the contribution of each component to the interaction and potency. METHODS: A series of compounds of different lengths targeting 3C(pro) and having an α,ß-unsaturated ester as the warhead were synthesized and their interactions with the enzyme were evaluated by complex structure analyses and potency assays for a better understanding on the relationship between potency and evolution of interaction. RESULTS: The P2 moiety of the compound would need to be oriented to interact in the S2 site in the substrate binding cleft and the P3-P4 moieties were required to generate sufficient potency. A hydrophobic terminal group will benefit the cellular uptake and improve the activity in vivo. CONCLUSIONS AND GENERAL SIGNIFICANCE: The data presented here provide a basis for designing a new generation of non-peptidomimetics to target EV71 3C(pro).

Association between air pollutants and birth defects in Xiamen, China.

Objective: To explore the relationship between common air pollution and common birth defects, and to provide reference for the prevention of birth defects. Methods: We conducted a case-control study in Xiamen, a city in southeastern China from 2019 to 2020. Logistics regression was used to analyze the relationship between sulfur dioxide(SO2), fine particulate matter 2.5(PM2.5), nitrogen dioxide(NO2), ozone(O3), carbon monoxide(CO) and the occurrence of common birth defects such as congenital heart disease, facial cleft, and finger deformity. Results: SO2 significantly increased the risk of birth defects such as congenital heart disease, cleft lip and/or cleft palate, and ear deformity in the first and second months of pregnancy. Conclusion: Exposure to common air pollutants increases the risk of birth defects, and SO2 significantly affects the occurrence of birth defects in the first two months of pregnancy.

Fast and visual detection of nucleic acids using a one-step RPA-CRISPR detection (ORCD) system unrestricted by the PAM.

CRISPR-Cas12a (Cpf1) is widely used for pathogen detection. However, most Cas12a nucleic acid detection methods are limited by a PAM sequence requirement. Moreover, preamplification and Cas12a cleavage are separate. Here, we developed a one-step RPA-CRISPR detection (ORCD) system unrestricted by the PAM sequence with high sensitivity and specificity that offers one-tube, rapid, and visually observable detection of nucleic acids. In this system, Cas12a detection and RPA amplification are performed simultaneously, without separate preamplification and product transfer steps, and 0.2 copies/µL of DNA and 0.4 copies/µL of RNA can be detected. In the ORCD system, the activity of Cas12a is the key to the nucleic acid detection; specifically, reducing Cas12a activity increases the sensitivity of ORCD assay detection of the PAM target. Furthermore, by combining this detection technique with a nucleic acid extraction-free method, our ORCD system can be used to extract, amplify and detect samples within 30 min, as verified with tests of 82 Bordetella pertussis clinical samples with a sensitivity and specificity of 97.30% and 100% compared with PCR. We also tested 13 SARS-CoV-2 samples with RT-ORCD, and the results were consistent with RT-PCR.

Long-term Pegylated GH for Children With GH Deficiency: A Large, Prospective, Real-world Study.

CONTEXT: The evidence of long-term polyethylene glycol recombinant human GH (PEG-rhGH) in pediatric GH deficiency (GHD) is limited. OBJECTIVE: This study aimed to examine the effectiveness and safety of long-term PEG-rhGH in children with GHD in the real world, as well as to examine the effects of dose on patient outcomes. DESIGN: A prospective, observational, posttrial study (NCT03290235). SETTING, PARTICIPANTS AND INTERVENTION: Children with GHD were enrolled from 81 centers in China in 4 individual clinical trials and received weekly 0.2 mg/kg/wk (high-dose) or 0.1 to <0.2 mg/kg/wk (low-dose) PEG-rhGH for 30 months. MAIN OUTCOMES MEASURES: Height SD score (Ht SDS) at 12, 24, and 36 months. RESULTS: A total of 1170 children were enrolled in this posttrial study, with 642 patients in the high-dose subgroup and 528 in the low-dose subgroup. The Ht SDS improved significantly after treatment in the total population (P < 0.0001), with a mean change of 0.53 ± 0.30, 0.89 ± 0.48, 1.35 ± 0.63, 1.63 ± 0.75 at 6 months, 12 months, 24 months, and 36 months, respectively. In addition, the changes in Ht SDS from baseline were significantly improved in the high-dose subgroup compared with the low-dose subgroup at 6, 12, 24, and 36 months after treatment (all P < 0.05). A total of 12 (1.03%) patients developed serious adverse events. There was no serious adverse event related to the treatment, and no AEs leading to treatment discontinuation or death occurred. CONCLUSIONS: PEG-rhGH showed long-term effectiveness and safety in treating children with GHD. Both dose subgroups showed promising outcomes, whereas PEG-rhGH 0.2 mg/kg/wk might show additional benefit.

Ozone Exposure and Asthma Attack in Children.

Background: Increasing evidence indicated that ozone (O3) exposure could trigger asthma attacks in children. However, the effect of O3 at low concentrations is uncertain. Purpose: This study aimed to explore the effects of O3 exposure at low concentrations on asthma attacks in children. Methods: A total of 3,475 children with asthma attacks from the First Affiliated Hospital of Xiamen University were available for the analyses. Air pollution data and meteorological data in Xiamen during 2016-2019 were also collected. A case-crossover design and conditional logistic regression models were conducted to evaluate the association between asthma attacks and outdoor air pollution with lag structures (from lag 0 to lag 6) in both single and multi-pollutant models. Furthermore, we estimated the influence of various levels of O3 exposure on an asthma attack in three groups categorized by maximum daily 8-h sliding average ozone (O3-8 h) (O3-8 h ≥ 100 µg/m3, O3-8 h: 80-99 µg/m3, O3-8 h < 80 µg/m3). Results: For both single-pollutant models and multi-pollutant models, when O3-8 h was higher than 80 µg/m3, O3 exposure was increased the risk of acute asthma attacks on each day of lag. The effect of O3 on children with asthma was significant when O3 concentration was higher than 100 µg/m3. Conclusion: O3 concentration above 80 µg/m3 contributed to an increased risk of asthma attacks in children.

Short-term efficacy and safety of a lower dose of polyethylene glycol recombinant human growth hormone in children with growth hormone deficiency: A randomized, dose-comparison study.

Objective: Polyethylene glycol recombinant human growth hormone (PEG-rhGH, Jintrolong®) is the first long-acting rhGH preparation that is approved to treat children with growth hormone deficiency (GHD) in China. Clinical experience with dose selections of PEG-rhGH is scarce. The present study compared the efficacy and safety of a lower dose to increase dosing regimens of PEG-rhGH treatment. Methods: A multicenter, randomized, open-label, dose-comparison clinical study was conducted to compare the improvements in the height standard deviation score (Ht SDS), height velocity (HV), insulin-like growth factor-1 (IGF-1) SDS, and safety profiles of children with GHD who are treated with 0.2 mg/kg/week of PEG-rhGH dose or 0.14 mg/kg/week for 26 weeks. Results: Ht SDS, HV, and IGF-1 SDS increased significantly after PEG-rhGH treatment in the two dose groups (p < 0.05). The improvements of Ht SDS, HV, and IGF-1 SDS were more significant in the high-dose group than in the low-dose group (p < 0.05). Ht SDS improvement in low-dose group was not non-inferiority to that in the high-dose group (p = 0.2987). The incidences of adverse events were comparable between the two groups. Conclusion: The improvements of Ht SDS, HV, and IGF-1 SDS were more significant in the high-dose group than in the low-dose group (p < 0.05). PEG-rhGH at the dose of 0.14 mg/kg/week was effective and safe for children with GHD. Clinical Trial Registration: clinicaltrials.gov, identifier NCT02908958.

Environmental and sensitization variations among asthma and/or rhinitis patients between 2008 and 2018 in China.

BACKGROUND: Little is known about the changes in allergen sensitization in China secondary to the environmental variations over the past decade. We aimed at investigating the variations in sensitization among asthma and/or rhinitis patients in China between 2008 and 2018. METHODS: This study analyzed cross-sectional data from national surveys conducted in China in 2008 and 2018. After finishing the questionnaire, participants underwent serum specific IgE measurements. A total of 2322 and 2798 patients were enrolled in 2008 and 2018, respectively. The significance of differences in sensitization rates among four regions of China were assessed. Correlation analysis was used to identify the associations of sensitization with climate change and planting of Artemisia desertorum between the two surveys. RESULTS: Compared with 2008, the general sensitization rate to mites significantly increased in 2018, which ranked highest among all tested allergens. Sensitization to pollens, especially Artemisia vulgaris, showed the greatest increase in the north. The annual mean temperature, rainfall and relative humidity in all four regions, and the Artemisia desertorum coverage in the northeastern area, increased significantly in 2018 as compared with 2008. From 2008 to 2018, an increase in Dermatophagoides pteronyssinus sensitization was significantly associated with an increase in relative humidity (r = 0.54, p = 0.037). The increase in A. vulgaris sensitization was significantly associated with the increase in the A. desertorum planting area (r = 0.67, p = 0.006) and with a decrease in rainfall (r = -0.59, p = 0.021). CONCLUSIONS: House dust mites remain the most important allergen in Chinese individuals with asthma and/or rhinitis. Pollen sensitization dramatically increased in northern China. Increases in sensitization to dust mites and Artemisia were related to the increases in humidity and planting area of A. desertorum.

Influence of degree of specific allergic sensitivity on severity of rhinitis and asthma in Chinese allergic patients.

BACKGROUND: The association between sensitizations and severity of allergic diseases is controversial. OBJECTIVE: This study was to investigate the association between severity of asthma and rhinitis and degree of specific allergic sensitization in allergic patients in China. METHOD: A cross-sectional survey was performed in 6304 patients with asthma and/or rhinitis from 4 regions of China. Patients completed a standardized questionnaire documenting their respiratory and allergic symptoms, their impact on sleep, daily activities, school and work. They also underwent skin prick tests with 13 common aeroallergens. Among the recruited subjects, 2268 provided blood samples for serum measurement of specific IgE (sIgE) against 16 common aeroallergens. RESULTS: Significantly higher percentage of patients with moderate-severe intermittent rhinitis were sensitized to outdoor allergens while percentage of patients sensitized to indoor allergens was increased with increasing severity of asthma. Moderate-severe intermittent rhinitis was associated with the skin wheal size and the level of sIgE to Artemisia vulgaris and Ambrosia artemisifolia (p < 0.001). Moderate-severe asthma was associated with increasing wheal size and sIgE response to Dermatophagoides (D.) pteronyssinus and D. farinae (p < 0.001). Moderate-severe rhinitis and asthma were also associated with increase in number of positive skin prick test and sIgE. CONCLUSIONS: Artemisia vulgaris and Ambrosia artemisifolia sensitizations are associated with the severity of intermittent rhinitis and D. pteronyssinus and D. farinae sensitizations are associated with increasing severity of asthma in China. Increase in number of allergens the patients are sensitized to may also increase the severity of rhinitis and asthma.

Whole Exome Sequencing Identifies a Novel Mutation of TPK1 in a Chinese Family with Recurrent Ataxia.

TPK deficiency, also known as thiamine metabolism dysfunction syndrome 5, is a rare autosomal recessive disorder of inborn error of metabolism caused by TPK1 gene mutation. Its clinical manifestation is highly variable, ranging from spontaneous remission to fatal metabolic crisis. Here, we describe two affected siblings in a Chinese family presenting with recurrent episodes of acute ataxia. Whole exome sequencing identified a homozygous missense variant c.382C > T (p.Leu128Phe) in the TPK gene, which is located in the thiamine binding domain and affects a highly conserved amino acid. Besides, a review of the 18 previously reported patients provides a better understanding of the clinical and genetic features of this disorder. TPK deficiency may be an under-diagnosed cause of acute encephalopathy and ataxia. Given the potential benefit of early intervention, TPK deficiency should be considered in patients with episodic encephalopathy or ataxia, especially those associated with lactic acidosis and α-ketoglutaric aciduria. Significant decreased TPP in the blood is a strong hint of the disease. WES (whole exome sequencing) can help to further identify the molecular diagnosis.

Heme oxygenase-1 alleviates eosinophilic inflammation by inhibiting STAT3-SOCS3 signaling.

Airway inflammation of eosinophilic asthma (EA) attributes to Th2 response, leaving the role of Th17 response unknown. Signal transducer and activator of transcription 3 (STAT3) induce both suppressors of cytokine signaling 3 (SOCS3) and retinoic acid receptor-related orphan nuclear receptor γ (RORγt) to initiate Th17 cell differentiation which is inhibited by SOCS3, a negative feedback regulator of STAT3. Heme oxygenase-1 (HO-1) is a stress-responsive, cytoprotective, and immunoregulatory molecular. Two other isoforms of the enzyme includes HO-2 and HO-3. Because HO-2 does not exhibit stress-related upregulation and distributes mainly in nervous system and HO-3 shows a low enzymatic activity, we tested a hypothesized anti-inflammatory role for HO-1 in EA by inhibiting STAT3-SOCS3 signaling. Animal model was established with Ovalbumin in wild type Balb/C mice. Hemin or SNPP was intraperitoneally (IP) injected ahead of the animal model to induce or inhibit HO-1 expression. Airway inflammation was evaluated by bronchoalveolar lavage, hematoxyline and eosin staining, enzyme-linked immunosorbent assay, and Western blot analysis. In vivo results showed that HO-1 induction inhibited phosphorylation of STAT3 and expression of SOCS3 and RORγt, decreased Th2 and Th17 immune responses, and alleviated airway inflammation. In vitro results revealed that HO-1 inhibited phosphorylation of STAT3 and expression of SOCS3 in naive CD4+ T cells. These findings identify HO-1 induction as a potential therapeutic strategy for EA treatment by reducing STAT3 phosphorylation, STAT3-SOCS3-mediated Th2/Th17 immune responses, and ultimate allergic airway inflammation.

Diagnosis and treatment of herpangina: Chinese expert consensus.

BACKGROUND: Herpangina is a common infectious disease in childhood caused by an enterovirus. This consensus is aiming to standardize and improve herpangina prevention and clinical diagnosis. METHODS: The Subspecialty Group of Infectious Diseases, the Society of Pediatric, Chinese Medical Association and Nation Medical Quality Control Center for Infectious Diseases gathered 20 experts to develop the consensus, who are specialized in diagnosis and treatment of herpangina. RESULTS: The main pathogenic serotypes of herpangina include Coxsackievirus-A, Enterovirus-A and Echovirus. Its diagnosis can be rendered on the basis of history of epidemiology, typical symptoms, characteristic pharyngeal damage and virological tests. The treatment is mainly symptomatic, and incorporates topical oral spray with antiviral drugs. The course of herpangina generally lasts 4-6 days with a good prognosis. CONCLUSION: The consensus could provide advices and references for the diagnosis, treatment and management of herpangina in children.

Fulminant Type 1 Diabetes Mellitus Caused by Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS): A Case Report and Review of the Literature.

Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS) is a rare, severe cutaneous adverse drug reaction characterized by fever, skin rashes, lymphadenopathy, leukocytosis with eosinophilia, and/or atypical lymphocytosis, and multiple visceral organ involvement. Moreover, patients with DRESS are at risk of developing autoimmune diseases including thyroiditis, diabetes mellitus (DM), and systemic lupus erythematosus (SLE), etc. several weeks or months after the initial resolution. We described a 9-month boy who was admitted to our hospital because of severe pneumonia and developed DRESS 3 weeks later. After the withdrawal of suspicious drug and administration of systemic corticosteroids, the patient's condition improved gradually. Nevertheless, hyperglycemia was detected 20 days after the initial onset of DRESS, and subsequent fulminant type 1 diabetes mellitus (F1DM) was diagnosed requiring continuous intravenous insulin infusion. After 13 months of follow-up, the blood glucose levels are now well-controlled. Literature research in PubMed for diabetes mellitus associated with DRESS showed 16 articles and 27 related case reports. Of 27 patients with DM related to DRESS, 11 were male, 16 were female. The mean age was 46 years. The duration from the onset of DRESS to the development of DM was 21 days on average. F1DM was diagnosed in 21 patients, T1DM was confirmed in 5 patients, and T2DM was only defined in 1 patient. Glutamic acid decarboxylase antibodies (GAD) were detected in 4 cases. Of 22 cases in which virus examination was carried out, evidence of virus reactivation was established in 16 cases (72.7%). Of patients with F1DM, 16 (88.9%) cases were evidenced by reactivation of herpes virus. A high frequency of HLA genotype and haplotype were found in 11 cases. DM was concomitant with acute pancreatitis in 3 patients and thyroiditis in 2 patients. No patients died from the disease. This work aims to raise awareness of long-term autoimmune sequelae in patients with DRESS.