Discovery of 1,2,4-Triazole-3-thione Derivatives as Potent and Selective DCN1 Inhibitors for Pathological Cardiac Fibrosis and Remodeling.

DCN1, a critical co-E3 ligase during the neddylation process, is overactivated in many diseases, such as cancers, heart failure as well as fibrotic diseases, and has been regarded as a new target for drug development. Herein, we designed and synthesized a new class of 1,2,4-triazole-3-thione-based DCN1 inhibitors based the hit HD1 identified from high-throughput screening and optimized through numerous structure-activity-relationship (SAR) explorations. HD2 (IC50= 2.96 nM) was finally identified and represented a highly potent and selective DCN1 inhibitor with favorable PK properties and low toxicity. Amazingly, HD2 effectively relieved Ang II/TGFß-induced cardiac fibroblast activation in vitro, and reduced ISO-induced cardiac fibrosis as well as remodeling in vivo, which was linked to the inhibition of cullin 3 neddylation and its substrate Nrf2 accumulation. Our findings unveil a novel 1,2,4-triazole-3-thione-based derivative HD2, which can be recognized as a promising lead compound targeting DCN1 for cardiac fibrosis and remodeling.

Genotype and phenotype in patients with ACAN gene variants: Three cases and literature review.

OBJECTIVE: To characterize the phenotype spectrum, diagnosis, and response to growth-promoting therapy in patients with ACAN variants causing familial short stature. METHODS: Three families with ACAN variants causing short stature were reported. Similar cases in the literature were summarized, and the genotype and phenotype were analyzed. RESULTS: Three novel heterozygous variants, c.757+1G>A, (splicing), c.6229delG, p.(Asp2078Tfs*1), and c.6679C>T, p.(Gln2227*) in the ACAN gene were identified. A total of 314 individuals with heterozygous variants from 105 families and 8 individuals with homozygous variants from 4 families were confirmed to have ACAN variants from literature and our 3 cases. Including our 3 cases, the variants reported comprised 33 frameshift, 39 missense, 23 nonsense, 5 splicing, 4 deletion, and 1 translocation variants. Variation points are scattered throughout the gene, while exons 12, 15, and 10 were most common (25/105, 11/105, and 10/105, respectively). Some identical variants existing in different families could be hot variants, c.532A>T, p.(Asn178Tyr), c.1411C>T, p.(Gln471*), c.1608C>A, p.(Tyr536*), c.2026+1G>A, (splicing), and c.7276G>T, p.(Glu2426*). Short stature, early-onset osteoarthritis, brachydactyly, midfacial hypoplasia, and early growth cessation were the common phenotypic features. The 48 children who received rhGH (and GnRHa) treatment had a significant height improvement compared with before (-2.18 ± 1.06 SD vs. -2.69 ± 0.95 SD, p < 0.001). The heights of children who received rhGH (and GnRHa) treatment were significantly improved compared with those of untreated adults (-2.20 ± 1.10 SD vs. -3.24 ± 1.14 SD, p < 0.001). CONCLUSION: Our study achieves a new understanding of the phenotypic spectrum, diagnosis, and management of individuals with ACAN variants. No clear genotype-phenotype relationship of patients with ACAN variants was found. Gene sequencing is necessary to diagnose ACAN variants that cause short stature. In general, appropriate rhGH and/or GnRHa therapy can improve the adult height of affected pediatric patients caused by ACAN variants.

Continuous age- and sex-specific reference ranges of liver enzymes in Chinese children and application in pediatric non-alcoholic fatty liver disease.

BACKGROUND: Alanine aminotransferase (ALT) is widely used to screen patients with hepatic diseases. However, the current reference ranges (< 50 U/L) were developed by laboratories and have not been validated in populations with a large number of healthy individuals. METHODS: This study collected venous blood and anthropometric data from a total of 13,287 healthy children aged 3 months to 18 years who underwent routine physical examinations in the Department of Pediatric Healthcare. We applied the least mean square algorithm to establish age- and sex-related reference percentiles of serum levels of transaminases. For validation, we recruited 4276 children and adolescents with obesity/overweight who underwent evaluation and metabolic tests in the hospital. Using receiver operating characteristic curves, we determined age- and sex-specific upper limit percentiles of liver enzymes for fatty liver diseases. RESULTS: This study revealed a significant correlation between serum transaminase levels and age and sex (P < 0.01). These transaminase levels exhibited age- and sex-specific patterns. Among individuals in the non-alcoholic fatty liver disease (NAFLD) cohort, elevated ALT levels displayed a positive association with clinical markers of disease severity, including homeostatic model assessment of insulin resistance, waist-hip ratio, and serum uric acid levels (P < 0.01). According to the receiver operating characteristic curves, ALT levels at the 92.58th percentile for boys and the 92.07th percentile for girls yielded the highest accuracy and specificity. CONCLUSIONS: This study provides age- and sex-specific reference ranges for ALT, aspartate aminotransferase, and γ-glutamyltransferase in Chinese children and adolescents, making it the largest population study to date. Furthermore, the study establishes a precise upper limit for ALT levels, facilitating their use in NAFLD screening. Video Abstract.

Lanostane triterpenoids from the fruiting bodies of Ganoderma amboinense.

Lanostane-type triterpenoids are the main characteristic constituents in Ganoderma mushrooms. Phytochemical analysis on the ethanol extract of the fruiting bodies of Ganoderma amboinense led to isolation and identification of twelve previously undescribed lanostane triterpenoids (1-12). Their chemical structures were determined by HR-ESI-MS, IR, and NMR spectroscopic analysis, NMR calculation, as well as X-ray crystallography. All isolates were evaluated for the α-glucosidase inhibitory and anti-inflammatory activities. Compounds 1, 5, 6, and 11 showed significant α-glucosidase inhibitory activity with IC50 values ranging from 33.5 µM to 96.0 µM. Moreover, compound 12 showed anti-inflammatory activity with IC50 value of 21.7 ± 2.1 µM.

Development and validation of a novel non-invasive test for diagnosing nonalcoholic fatty liver disease in Chinese children.

BACKGROUND: With the exploding prevalence of obesity, many children are at risk of developing nonalcoholic fatty liver disease. Using anthropometric and laboratory parameters, our study aimed to develop a model to quantitatively evaluate liver fat content (LFC) in children with obesity. METHODS: A well-characterized cohort of 181 children between 5 and 16 years of age were recruited to the study in the Endocrinology Department as the derivation cohort. The external validation cohort comprised 77 children. The assessment of liver fat content was performed using proton magnetic resonance spectroscopy. Anthropometry and laboratory metrics were measured in all subjects. B-ultrasound examination was carried out in the external validation cohort. The Kruskal-Wallis test, Spearman bivariate correlation analyses, univariable linear regressions and multivariable linear regression were used to build the optimal predictive model. RESULTS: The model was based on indicators including alanine aminotransferase, homeostasis model assessment of insulin resistance, triglycerides, waist circumference and Tanner stage. The adjusted R2 of the model was 0.589, which presented high sensitivity and specificity both in internal [sensitivity of 0.824, specificity of 0.900, area under curve (AUC) of 0.900 with a 95% confidence interval: 0.783-1.000] and external validation (sensitivity of 0.918 and specificity of 0.821, AUC of 0.901 with a 95% confidence interval: 0.818-0.984). CONCLUSIONS: Our model based on five clinical indicators was simple, non-invasive, and inexpensive; it had high sensitivity and specificity in predicting LFC in children. Thus, it may be useful for identifying children with obesity who are at risk for developing nonalcoholic fatty liver disease.

Knockdown of the long non­coding RNA MALAT1 ameliorates TNF­α­mediated endothelial cell pyroptosis via the miR­30c­5p/Cx43 axis.

Long noncoding RNAs (lncRNAs) are related to the development of atherosclerosis (AS). However, the role of lncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in tumor necrosis factor­α (TNF­α)­induced rat aortic endothelial cell (RAOEC) pyroptosis, as well as the underlying mechanisms, remain unclear. RAOEC morphology was assessed using an inverted microscope. The mRNA and/or protein expression levels of MALAT1, microRNA(miR)­30c­5p and connexin 43 (Cx43) were assessed using reverse transcription­quantitative PCR (RT­qPCR) and/or western blotting, respectively. The relationships among these molecules were validated by dual­luciferase reporter assays. Biological functions, such as LDH release, pyroptosis­associated protein levels and the proportion of PI­positive cells, were evaluated using a LDH assay kit, western blotting and Hoechst 33342/PI staining, respectively. The present study demonstrated that compared with the control group, the mRNA expression levels of MALAT1 and protein expression levels of Cx43 were significantly up­regulated, whereas miR­30c­5p mRNA expressions levels were significantly decreased in TNF­α­treated RAOEC pyroptosis. Knockdown of MALAT1 or Cx43 significantly attenuated the increase in LDH release, pyroptosis­associated protein expression and PI­positive cell numbers among RAOEC treated using TNF­α, whereas an miR­30c­5p mimic exerted the opposite effect. Furthermore, miR­30c­5p was demonstrated to be a negative regulator of MALAT1 and could also target Cx43. Finally, co­transfection with siMALAT1 and miR­30c­5p inhibitor could attenuate the protective effect of MALAT1 knockdown against TNF­α­mediated RAOEC pyroptosis by upregulation of Cx43 expression. In conclusion, MALAT1 might serve an important role in TNF­α­mediated RAOEC pyroptosis by regulating the miR­30c­5p/Cx43 axis, which would provide a potential novel diagnostic and therapeutic target for AS.

Corrigendum: Case report: Potential predictive value of MMR/MSI status and PD-1 expression in immunotherapy for urothelial carcinoma.

[This corrects the article DOI: 10.3389/pore.2022.1610638.].

Case Report: Potential Predictive Value of MMR/MSI Status and PD-1 Expression in Immunotherapy for Urothelial Carcinoma.

Immune checkpoint inhibitors (ICIs) have shown encouraging outcomes against Lynch syndrome (LS)-associated colorectal cancer (CRC) and endometrial cancer with mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H). However, there is as yet no clarity on the safety and efficacy of immunotherapy combined with chemotherapy in LS-associated urothelial carcinoma (UC). Here, we report a patient with recurrent and metastatic LS-associated UC who achieved sustained response to programmed death protein 1 (PD-1) inhibitor combined with chemotherapy over 31 months, during which the side effects of immunotherapy could be controlled and managed. Our findings indicate that the dMMR/MSI status and PD-1 expression in UC may have potential predictive value for the response to PD-1-targeted immunotherapy. Our case supports the inclusion of such combination and/or monotherapy for UC in clinical studies and using dMMR/MSI status and PD-1 expression as potential predictive biomarkers for assessment of the therapeutic response.

Critical Roles of Polycomb Repressive Complexes in Transcription and Cancer.

Polycomp group (PcG) proteins are members of highly conserved multiprotein complexes, recognized as gene transcriptional repressors during development and shown to play a role in various physiological and pathological processes. PcG proteins consist of two Polycomb repressive complexes (PRCs) with different enzymatic activities: Polycomb repressive complexes 1 (PRC1), a ubiquitin ligase, and Polycomb repressive complexes 2 (PRC2), a histone methyltransferase. Traditionally, PRCs have been described to be associated with transcriptional repression of homeotic genes, as well as gene transcription activating effects. Particularly in cancer, PRCs have been found to misregulate gene expression, not only depending on the function of the whole PRCs, but also through their separate subunits. In this review, we focused especially on the recent findings in the transcriptional regulation of PRCs, the oncogenic and tumor-suppressive roles of PcG proteins, and the research progress of inhibitors targeting PRCs.

Clinical Incidence and Characteristics of Newly Diagnosed Type 1 Diabetes in Chinese Children and Adolescents: A Nationwide Registry Study of 34 Medical Centers.

Objective: To investigate the clinical incidence and characteristics of type 1 diabetes mellitus (T1DM) of children and adolescents at the time of initial diagnosis in China. Methods: Data on all pediatric patients with newly diagnosed T1DM were retrospectively collected from 34 medical centers in 25 major cities in China from January 2015 to January 2020. Patients were classified into three age groups: <5 years, 5 to <10 years, and ≥10 years of age. The same patient population was also categorized into diabetic ketoacidosis (DKA) and non-DKA groups based on clinical criteria. Results: The mean annual clinical incidence of T1DM was 3.16/100,000 from the years 2015 to 2019. A total of 6,544 patients with newly diagnosed T1DM aged 0-16 years (median 7.84 ± 3.8) were studied [ages <5 years (29.3%), 5 to <10 years (38.7%), and ≥10 years (32%)], 52.4% of them were women. In total, 90.5% of the cases were occurred in individuals without a family history. Patients had lower C-peptide (CP) and body mass index (BMI) z scores when compared with healthy children, 41.8% of them had measurable T1DM-related antibodies and 52.7% had DKA. Among all three age groups, the <5 years group had the lowest BMI z score, CP, and glycated hemoglobin (HbA1c) on average, while it had the highest incidence rate of DKA (56.9%). Compared to the non-DKA group, the DKA group was significantly younger, with a lower BMI z score and CP, higher antibody positive rate, HbA1c, and the rate of insulin pump therapy. Conclusion: The clinical incidence of T1DM in children and adolescents in China was 3.16/100,000. Patients with DKA at the first diagnosis of T1DM have a worse ß-cell function. Public health measures for the prevention and treatment of T1DM should focus on preschoolers (aged <5 years) in particular, considering the severity and the highest frequency of DKA in this age group. More efforts should be dedicated to early screening and diagnosis of the T1DM.

The contribution of type 2 diabetes mellitus to hypothalamic inflammation and depressive disorders in young patients with obesity.

Background: To explore the contribution of type 2 diabetes mellitus (T2DM) to hypothalamic inflammation and depressive disorders in young patients with obesity. Methods: According to the diagnostic criteria for T2DM, all of patients with obesity were divided into the diabetic and the non-diabetic groups. The severity of depressive disorders was assessed by self-rating depression scale (SDS). The signal intensity (SI) ratio of the T2-weighted phase of the superior hypothalamus/amygdala (H/A) was measured using a quantitative magnetic resonance imaging (MRI) technique to evaluate hypothalamic inflammation. Univariate and multivariate logistic regression analysis was used to find the influencing factors of depressive disorder. The prediction equation's sensitivity and specificity for the depressive disorder were calculated based on the receiver operating characteristic (ROC) curve. Results: In young patients with obesity and diabetes, the incidence of depression is 79.49%, which was much higher than that in patients without diabetes (P<0.001). The SI of the left H/A in young patients with obesity and diabetes is significantly higher than that in non-diabetic patients (P<0.001). The relative risks of depression are fasting blood glucose (FBG) (OR 1.60; CI: 1.26-2.05), HbA1c (OR 1.94; CI: 1.40-2.68) and triglycerides (OR 1.40; CI: 1.03-1.90). Only FBG enters the predictive equation for depressive disorder, with a 52.8% sensitivity and 84.5% specificity. Conclusions: In young diabetic patients with obesity, the incidence of depressive disorder is high, a mechanism possibly related to the left hypothalamus inflammation. Elevated FBG can be an independent predictor of depressive disorder in young patients with obesity.

A clinical analysis of bronchiectasis in 78 children / 中国小儿急救医学

Objective:To analyze the clinical features of bronchiectasis, in order to improve the diagnosis, treatment, and prognosis.Methods:The clinical data of 78 children with bronchiectasis at Qingdao Women and Children′s Hospital of Qingdao University from January 2010 to January 2020 were analyzed, including age, regional distribution, etiology, clinical manifestations, lung function characteristics, results of lung high-resolution CT, results of fiberbronchoscopy examination, treatment, and prognosis.Results:Among 78 children with bronchiectasis, there were 35 males(44.9%)and 43 females(55.1%), with a median age of 8.7(6.1, 9.0)years.There were 51 children in rural areas(65.4%)and 27 children in urban areas(34.6%). The incidence of children in rural areas was higher than that in urban areas.The top three causes of bronchiectasis were 40 (51.3%)cases after infection, nine cases(11.5%)of primary immunodeficiency and seven cases(9.0%)of inhalation.The main clinical manifestations were wet cough, expectoration, wheezing and repeated respiratory infection.High-resolution CT of the lungs showed 36(46.2%)cases with diffuse bronchiectasis and 37 (47.4%) cases with localized bronchiectasis.Forty-nine(62.8%) cases had abnormal pulmonary ventilation function.Sixty-one(78.2%)cases were treated with fiberoptic bronchoscopy, of which 49(80.3%)cases had "fishbone" changes.After anti-infection, fiberbronchoscopy examination, expectorant and physical therapy, 67 cases were discharged and followed up for more than one year.Among them, 55 cases had symptoms improved, 12 patients had recurrent respiratory tract infection, and three patients died.Conclusion:The clinical manifestations of bronchiectasis in children have no obvious specificity.Early diagnosis, identification of the cause and comprehensive management are critical to prognosis of bronchiectasis.

Predictive value of SYNTAX-Ⅱ score on prognosis of patients with chronic total occlusion undergoing percutaneous coronary intervention / 中华心血管病杂志

Objective: To investigate the predictive value of SYNTAX-Ⅱ score on long term prognosis of patients diagnosed with chronic total occlusion (CTO) and received percutaneous coronary intervention (PCI). Methods: Patients undergoing CTO-PCI in Fuwai hospital from January 2010 to December 2013 were enrolled in this retrospective analysis. The SYNTAX-Ⅱ score of the patients was calculated. According to SYNTAX-Ⅱ score tertiles, patients were stratified as follows: SYNTAX-Ⅱ≤20, 20<SYNTAX-Ⅱ≤27, SYNTAX-Ⅱ>27. Primary endpoint was major adverse cardiac events (MACCE), including all-cause death, myocardial infarction, stroke and any revascularization. Secondary endpoints included stent thrombosis, heart failure and target lesion failure (TLF). Patients were followed up by outpatient visit or telephone call at 1 month, 6 months and 1 year after PCI, and annually up to 5 years. Multivariate Cox regression model was used to analyze the independent risk factors of all-cause death in patients undergoing CTO-PCI. The predictive value of SYNTAX score with SYNTAX-Ⅱ score for all-cause death was evaluated by the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Results: A total of 2 391 patients with CTO and received PCI were enrolled in this study. The mean age was (57.0±10.5) years, 1 994 (83.40%) patients were male. There were 802 patients in lower tertile group (SYNTAX-Ⅱ≤20), 798 patients in intermediate group (20<SYNTAX-Ⅱ≤27) and 791 patients in upper tertile group (SYNTAX-Ⅱ>27). At the end of 5-year follow-up, the loss to follow-up rate of the three groups was 9.10%(73/802), 10.78%(86/798)and 8.85%(70/791), respectively. The rate of all-cause mortality (1.78% (13/729) vs. 3.65% (26/712) vs. 9.02% (65/721), P<0.001), cardiac death (1.37% (10/729) vs. 2.11% (15/712) vs. 4.85% (35/721), P<0.001), target vessel myocardial infarctions (4.25% (31/729) vs. 4.49% (32/712) vs. 7.07% (51/721), P=0.03), probable stent thrombosis (1.51% (11/729) vs. 2.81% (20/712) vs. 3.61% (26/721), P=0.04) and heart failure (1.78% (13/729) vs. 1.97% (14/712) vs. 5.41% (39/721), P<0.001) increased in proportion to increasing SYNTAX-Ⅱ score (all P<0.05). Multivariable Cox regression analysis indicated that female (HR=2.05, 95%CI 1.12-3.73, P=0.01), left ventricular ejection fraction (HR=0.97, 95%CI 0.95-1.00, P=0.05) and SYNTAX-Ⅱ score (HR=1.07, 95%CI 1.02-1.11,P=0.01) were independent predictors for all-cause mortality in patients undergoing CTO-PCI. The predicted value of the SYNTAX-Ⅱ score for all-cause death was significantly higher than the SYNTAX score (AUC 0.71 vs. 0.60, P=0.003). Conclusion: For CTO patients who underwent percutaneous coronary intervention, SYNTAX-Ⅱ score is an independent predictor for 5-year all-cause death, and SYNTAX-Ⅱ serves as an important predictor for all-cause death in these patients.

Discovery of Potent and Selective 2-(Benzylthio)pyrimidine-based DCN1-UBC12 Inhibitors for Anticardiac Fibrotic Effects.

DCN1, a co-E3 ligase, interacts with UBC12 and activates cullin-RING ligases (CRLs) by catalyzing cullin neddylation. Although DCN1 has been recognized as an important therapeutic target for human diseases, its role in the cardiovascular area remains unknown. Here, we first found that DCN1 was upregulated in isolated cardiac fibroblasts (CFs) treated by angiotensin (Ang) II and in mouse hearts after pressure overload. Then, structure-based optimizations for DCN1-UBC12 inhibitors were performed based on our previous work, yielding compound DN-2. DN-2 specifically targeted DCN1 at molecular and cellular levels as shown by molecular modeling studies, HTRF, cellular thermal shift and co-immunoprecipitation assays. Importantly, DN-2 effectively reversed Ang II-induced cardiac fibroblast activation, which was associated with the inhibition of cullin 3 neddylation. Our findings indicate a potentially unrecognized role of DCN1 inhibition for anticardiac fibrotic effects. DN-2 may be used as a lead compound for further development.

Kinship Verification Based on Cross-Generation Feature Interaction Learning.

Kinship verification from facial images has been recognized as an emerging yet challenging technique in many potential computer vision applications. In this paper, we propose a novel cross-generation feature interaction learning (CFIL) framework for robust kinship verification. Particularly, an effective collaborative weighting strategy is constructed to explore the characteristics of cross-generation relations by corporately extracting features of both parents and children image pairs. Specifically, we take parents and children as a whole to extract the expressive local and non-local features. Different from the traditional works measuring similarity by distance, we interpolate the similarity calculations as the interior auxiliary weights into the deep CNN architecture to learn the whole and natural features. These similarity weights not only involve corresponding single points but also excavate the multiple relationships cross points, where local and non-local features are calculated by using these two kinds of distance measurements. Importantly, instead of separately conducting similarity computation and feature extraction, we integrate similarity learning and feature extraction into one unified learning process. The integrated representations deduced from local and non-local features can comprehensively express the informative semantics embedded in images and preserve abundant correlation knowledge from image pairs. Extensive experiments demonstrate the efficiency and superiority of the proposed model compared to some state-of-the-art kinship verification methods.

Using quantitative imaging to determine the correlation between hypothalamic inflammation and anxiety and depression in young patients with obesity.

BACKGROUND: To investigate the incidence of anxiety and depressive disorders in young adults with obesity and the correlation between the severity of these disorders and hypothalamic inflammation. METHODS: The severity of anxiety and depressive disorders was assessed using the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS), respectively. Hypothalamic inflammation was evaluated by measuring the hypothalamus/amygdala (H/A) signal intensity (SI) ratio in T2-weighted phase quantitative magnetic resonance imaging (MRI). RESULTS: The incidence of depressive disorders in young (18-45 years) patients with obesity (n=66) was higher than that in the control group (n=44); anxiety disorder incidence did not differ significantly between groups. The bilateral H/A SI ratio in the obesity group was significantly higher than that in the control group. In the obesity group, there was no significant correlation between bilateral H/A SI ratio and body mass index (BMI) (right: r=-0.145, P=0.721; left: r=0.102, P=0.415) or SAS scores (right: r=-0.118, P=0.444; left: r=-0.295, P=0.052); SDS scores were significantly correlated with left H/A SI ratio (r=-0.353, P=0.019), but not right H/A SI ratio (r=-0.031, P=0.843). CONCLUSIONS: Patients with obesity had a higher incidence of depressive disorders. Left hypothalamus inflammation may be one of the links between obesity and depressive disorders.

Surrogate markers and predictors of endogenous insulin secretion in children and adolescents with type 1 diabetes.

BACKGROUND: No studies have examined endogenous insulin secretion in pediatric patients with type 1 diabetes in China using the gold-standard mixed-meal tolerance test. Because the latter is labor-intensive, we examined simpler surrogate markers of endogenous insulin secretion in Chinese youth, as previously reported for a European population. METHODS: Participants were 57 children and adolescents with type 1 diabetes aged 4.4-16.8 years (56% females). We performed 120-minute mixed-meal tolerance tests with serum C-peptide (CP) measurements every 30 minutes. Severe insulin deficiency (SID) was defined as CP peak < 0.2 nmol/L. Urine CP and creatinine levels were measured at 0 and 120 minutes. RESULTS: Twenty-five (44%) patients had SID. Fasting CP levels missed one case (96% sensitivity) with no false positives (100% specificity). While the 120-minute urine CP/creatinine had 100% sensitivity, it yielded markedly lower specificity (63%). Every 1-year increase in diabetes duration and 1-year decrease in age at diagnosis were associated with 37% (P < 0.001) and 20% (P = 0.005) reductions in serum CP area-under-the-curve, respectively. Thus, 86% of children aged < 5 years had SID compared to none among patients aged ≥ 11 years. CONCLUSIONS: Simple fasting CP measurements could be used to detect most SID cases in Chinese youth with type 1 diabetes. Fasting CP is a far more reliable measure of endogenous insulin secretion than the more commonly used insulin dose. Therefore, it could more precisely determine insulin secretory capacity to target those who could benefit, if treatments to preserve residual insulin secretion are developed.

A clinical analysis of protracted bacterial bronchitis in 102 children in Qingdao Area / 中国小儿急救医学

Objective:To summarize the clinical characteristics of 102 children with protracted bacterial bronchitis in Qingdao area.Methods:One hundred and two children with protracted bacterial bronchitis treated at respiratory clinic of Women and Children′s Hospital affiliated to Qingdao University from January 2016 to March 2021 were included in this study.The clinical data, age and seasonal distribution, etiology, clinical manifestations, high-resolution CT of the lungs, characteristics of lung function, bronchoscopy and treatment prognosis were retrospectively analized.Results:The top three pathogens of protracted bacterial bronchitis in 102 children (55 boys, 47 girls, median age: 1.7 (0.8, 4.2)years were Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, with frequency of 12.75%, 10.78%, and 6.86%, respectively.The onset season was mainly autumn and winter, with a total of 73 (71.57%) cases.The main clinical manifestations were wet cough and (or) wheezing, and the cough was not divided between day and night.CT of the lungs showed thickening of the bronchial wall in 16(15.69%) cases and uneven ventilation in 5(4.90%) cases.Twenty-three (22.55%) cases had abnormal lung function.Fifty-two (50.98%) cases underwent bronchoscopy, of which 33(32.35%) cases had multiple lung segmental purulent changes under the microscope.After standard anti-infection, bronchoscopy and alveolar lavage, expectorant and physical therapy, the prognosis was mostly good.Conclusion:The clinical manifestations of protracted bacterial bronchitis in children have no obvious specificity.Early diagnosis, identification of the cause and comprehensive management are critical to its prognosis.

The cause analysis of chronic wet cough in children in Qingdao area / 中国小儿急救医学

Objective:To explore the etiology and characteristics of chronic wet cough in children in Qingdao.Methods:Patients with chronic wet cough treated at respiratory clinic of the Women and Children′s Hospital Affiliated to Qingdao University from July 2018 to June 2019 were included in this study.After three-month follow-up, the etiological data was analyzed.Results:(1)A total of 213 children were included, ranging in age from 1 month to 14 years old, including 38 cases of 1 month~1 year old, 47 cases of 1~3 years old, 87 cases of 3~6 years old, and 41 cases of 6~14 years old.The median age was 4.7 years.The top four causes of chronic wet cough in children were upper airway cough syndrome(33.8%), protracted bacterial bronchitis(20.7%), asthma with upper airway cough syndrome(15.5%), and asthma with infection(10.8%). Other causes were postinfection cough, pertussis syndrome, bronchiectasis, gastroesophageal reflux, bronchial foreign body, abnormal airway development, cystic fibrosis and so on.(2)The first cause of chronic wet cough in different age groups: 1 month to 3 years old group was protracted bacterial bronchitis; 3 to 14 years old group was upper airway cough syndrome.(3)The causes of chronic wet cough showed seasonal differences.Upper airway cough syndrome and cough after infection had a more balanced incidence throughout the year; protracted bacterial bronchitis and pertussis syndrome were common in winter; asthma with upper airway cough syndrome and asthma with infection were common in spring and autumn.Conclusion:Upper airway cough syndrome, protracted bacterial bronchitis, asthma with upper airway cough syndrome, and asthma with infection are the 4 leading causes for children with chronic wet cough in Qingdao.The causes of chronic wet cough have age and seasonal differences.