Clinical and genetic characteristics of Chinese pediatric patients with chronic granulomatous disease.

BACKGROUND: Chronic granulomatous disease (CGD) is a rare disease in China, and very little large-scale studies have been conducted to date. We aimed to investigate the clinical and genetic features of CGD in Chinese pediatric patients. METHODS: Pediatric patients with CGD from Beijing Children's Hospital, Capital Medical University, China, were enrolled from January 2006 to December 2016. RESULTS: A total of 159 pediatric patients with CGD were enrolled. The median age of clinical onset was 1.4 months, and 73% (116/159) had clinical onset symptoms before the 1 year of age. The most common site of invasion was the lungs. The lymph nodes, liver, and skin were more frequently invaded in X-linked (XL) CGD patients than in autosomal recessive (AR) CGD patients (P < 0.05). Approximately 64% (92/144) of the pediatric patients suffered from abnormal response to BCG vaccination. The most frequent pathogens were Aspergillus and Mycobacterium tuberculosis. Gene analysis indicated that 132 cases (89%, 132/147) harbored CYBB pathogenic variants, 7 (5%, 7/147) carried CYBA pathogenic variants, 4 (3%, 4/147) had NCF1 pathogenic variants, and 4 (3%, 4/147) had NCF2 pathogenic variants. The overall mortality rate in this study was 43%, particularly the patients were males, with CYBB mutant and did not receive HSCT treatment. CONCLUSIONS: Chronic granulomatous disease is a rare disease affecting Chinese children; however, it is often diagnosed at a later age, and thus, the mortality rate is relatively high. The prevalence and the severity of disease in XL-CGD are higher than AR-CGD.

TFA-Mediated DMSO-Participant Sequential Oxidation/1,3-Dipolar Cycloaddition Cascade of Pyridinium Ylides for the Assembly of Indolizines.

A trifluoroacetic acid (TFA)-mediated cascade oxidation/1,3-dipolar cycloaddition reaction of stabilized pyridinium salts with dimethyl sulfoxide (DMSO) has been developed in the presence of K2S2O8 and trimethylethylenediamine (TMEDA). In this transition-metal-free reaction, DMSO acts as a one-carbon source, thus providing a convenient method for the efficient and direct synthesis of various indolizine derivatives.

A cascade oxidation/[4 + 1] annulation of sulfonium salts for synthesis of polyfunctional furans: DMSO as one carbon source.

A novel DMSO-involved cascade reaction of stabilized sulfonium salts has been established for direct construction of polyfunctional furans. This one-pot sequential reaction involving in situ generated α-methylene sulfonium salts was followed by [4 + 1] annulation with sulfur ylides. Notably, DMSO plays a very important role in this transformation, not only as a solvent but also as one carbon source.

The epidemiology of paediatric Mycoplasma pneumoniae pneumonia in North China: 2006 to 2016.

Paediatric Mycoplasma pneumoniae pneumonia (MPP) is a major cause of community-acquired pneumonia in China. Data on epidemiology of paediatric MPP from China are little known. This study retrospectively collected data from June 2006 to June 2016 in Beijing Children's Hospital, Capital Medical University of North China and aims to explore the epidemiological features of paediatric MPP and severe MPP (SMPP) in North China during the past 10 years. A total of 27 498 paediatric patients with pneumonia were enrolled. Among them, 37.5% of paediatric patients had MPP. In this area, an epidemic took place every 2-3 years at the peak, and the positive rate of MPP increased during these peak years over time. The peak age of MPP was between the ages of 6 and 10 years, accounting for 75.2%, significantly more compared with other age groups (χ2 = 1384.1, P < 0.0001). The epidemics peaked in September, October and November (χ2 = 904.9, P < 0.0001). Additionally, 13.0% of MPP paediatric patients were SMPP, but over time, the rate of SMPP increased, reaching 42.6% in 2016. The mean age of paediatric patients with SMPP (6.7 ± 3.0 years old) was younger than that of patients with non-SMPP (7.4 ± 3.2 years old) (t = 3.60, P = 0.0001). The prevalence of MPP and SMPP is common in China, especially in children from 6 to 10 years old. Paediatric patients with SMPP tend to be younger than those with non-SMPP. MPP outbreaks occur every 2-3 years in North China. September, October and November are the peak months, unlike in South China. Understanding the epidemiological characteristics of paediatric MPP can contribute to timely treatment and diagnosis, and may improve the prognosis of children with SMPP.

Sonographic Findings in Superficial Angiomyxoma of the Vulva in a Perimenopausal Female.

Superficial angiomyxoma (SAM) is an extremely rare soft tissue tumor. It is especially rare in the vulva, with only a few such cases reported in the medical literature. Here, we report a case of SAM of the vulva that was initially suspected to be a Bartholin gland cyst. The patient underwent local excision of the vulvar cyst under lumbar anesthesia. Clinical manifestations and B-scan ultrasonographic features are similar between SAM and cysts. Echoes in the mass are uneven and exhibit low echoes and punctate hyperechoic floating. Thus, increasing sonographers' awareness of the high-frequency ultrasonography findings associated with this rare tumor could broaden their knowledge base.

Sequential σ-Bond Insertion/Benzannulation Involving Arynes: Selective Synthesis of Polysubstituted Naphthalenes.

An interesting σ-bond insertion/benzannulation reaction for the synthesis of polysubstituted naphthalene derivatives has been developed from readily accessible ketones, arynes, and alkynoates. This practical and transition-metal-free method provides a novel route to diverse naphthalenes through a substrate-controlled rearrangement reaction with the cleavage of C-C bonds.

Targeted Gene Sanger Sequencing Should Remain the First-Tier Genetic Test for Children Suspected to Have the Five Common X-Linked Inborn Errors of Immunity.

To address inborn errors of immunity (IEI) which were underdiagnosed in resource-limited regions, our centre developed and offered free genetic testing for the most common IEI by Sanger sequencing (SS) since 2001. With the establishment of The Asian Primary Immunodeficiency (APID) Network in 2009, the awareness and definitive diagnosis of IEI were further improved with collaboration among centres caring for IEI patients from East and Southeast Asia. We also started to use whole exome sequencing (WES) for undiagnosed cases and further extended our collaboration with centres from South Asia and Africa. With the increased use of Next Generation Sequencing (NGS), we have shifted our diagnostic practice from SS to WES. However, SS was still one of the key diagnostic tools for IEI for the past two decades. Our centre has performed 2,024 IEI SS genetic tests, with in-house protocol designed specifically for 84 genes, in 1,376 patients with 744 identified to have disease-causing mutations (54.1%). The high diagnostic rate after just one round of targeted gene SS for each of the 5 common IEI (X-linked agammaglobulinemia (XLA) 77.4%, Wiskott-Aldrich syndrome (WAS) 69.2%, X-linked chronic granulomatous disease (XCGD) 59.5%, X-linked severe combined immunodeficiency (XSCID) 51.1%, and X-linked hyper-IgM syndrome (HIGM1) 58.1%) demonstrated targeted gene SS should remain the first-tier genetic test for the 5 common X-linked IEI.

[The clinical application of the emergency remedial transthoracic cardiac pacing used by a steel wire loop electrode].

OBJECTIVE: To explore an effective method of emergency remedial cardiac pacing and evaluate its clinical application. METHODS: The transthoracic cardiac pacing was used by a steel wire loop electrode to 18 patients with cardiac arrest or serious bradycardia, after a routine cardiac pacing was failed by way of jugular or subclavian vein. RESULTS: It is a simple procedure used by steel wire loop. All the pacing had been successfully captured the hearts except 5 cases without capturing. There were 3 cases of cardiac arrest, 2 cases of cardiac arrest after electric defibrillation, 1 case of cardiac arrest after electric shock because of ventricular running and all the 5 cases of severe cardiac bradycardia due to serious atrioventricular block caused by high blood potassium were survived. Eight cases of cardiac arrest were successful capture, that was due to the short period of time from cardiac arrest to ventricle puncture than that of 5 cases of ventricular pacing which was not successful [(17.6+/-4.6) minutes vs. (26.4+/-5.4) minutes, P<0.05]. CONCLUSION: The steel wire loop electrode is a safe and reliable emergency cardiac pacing method, which contribute to the rapid establishment of an effective emergency cardiac pacing. When the conventional intravenous cardiac pacing was not successful, the method of emergency transthoracic cardiac pacing used by steel wire loop electrode should be bold and use to improve the successful rate of resuscitation.

[Preventive and therapeutic effects of Yiqi Huayu Recipe on degeneration of articular cartilage in rats with osteoarthritis].

OBJECTIVE: To study the efficacy and possible mechanism of Yiqi Huayu Recipe (YQHYR), a compound traditional Chinese herbal medicine, in preventing and treating degeneration of the articular cartilage in rats with osteoarthritis (OA). METHODS: A total of 90 one-month-old SD rats were randomly divided into normal control group, untreated group and YQHYR group, with 30 rats in each group. The osteoarthritis was induced by shoulder disarticulation plus upright posture in rats. The rats in YQHYR group were treated with YQHYR at 5-, 7- and 9-month old (4, 6 and 8 months after the surgery) for one month. Ten rats in each subgroup were sacrificed at 6-, 8- and 10-month old (5, 7 and 9 months after the surgery) respectively and the knee joint samples were harvested for detection. Safranin-O/fast green staining was performed to examine the morphology of articular cartilage. The expressions of type II collagen (Col2A1), aggrecan-1 (Agc1), matrix metalloproteinase-13 (MMP-13) and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNAs were evaluated by real-time fluorescent quantitation polymerase chain reaction. RESULTS: Histological analysis showed that the structure of articular cartilage was seriously destroyed in rats in the untreated group. On the contrary, the degenerative changes of the articular cartilage in the YQHYR group were dropped off. Real-time fluorescent quantitation polymerase chain reaction showed that expressions of Agc1, TIMP-1 and Col2A1 mRNAs were up-regulated in 6- and 10-month-old rats in the YQHYR group as compared with those in the untreated group (P<0.01, P<0.05), but there was no significant difference in expression of MMP-13 mRNA between the YQHYR group and the untreated group. The expression of Agc1 mRNA was up-regulated and the expression of MMP-13 mRNA was down-regulated in the 8-month-old rats in YQHYR group as compared with those in the untreated group (P<0.01). CONCLUSION: YQHYR can promote the synthesizing of aggrecan and type II collagen in chondrocytes and delay articular cartilage degradation in OA rats.

[Clinical features of coronary artery spasm patients with or without myocardial bridge].

OBJECTIVE: To investigate the clinical features of coronary artery spasm patients with or without myocardial bridge and explore the roles of endothelial dysfunction in these patients. METHODS: One hundred eighteen patients undergone acetylcholine provoking test were divided into myocardial bridge (MB) group (n = 26) and non-myocardial bridge (NMB) group (n = 92). The results of acetylcholine test, treadmill exercise electrocardiography, stress myocardial perfusion scintigraphy, plasma level of endothelin-1 and nitric oxide were compared between MB group and NMB group. RESULTS: Coronary artery spasm was induced in 21 patients in MB group (81%) and 52 patients in NMB group (57%, P < 0.05). Positive treadmill electrocardiography was obtained in 19 patients in MB group (73%) and 7 patients in NMB group (8%, P < 0.001). Ischemic perfusion defect in 20 (77%) and 9 patients (10%, P < 0.001) and reverse redistribution in 23 (88%) and 68 patients (74%, P > 0.05). Patients showed different clinical features in MB group and NMB group (more short-duration exertional angina and could not be readily released by nitroglycerine in MB group while more patients experienced long-lasting variant angina and symptoms could be readily released by nitroglycerine). Plasma endothelin-1 level was significantly higher [(132.1 +/- 6.5) ng/L vs. (108.5 +/- 8.2) ng/L, P < 0.01] while nitric oxide was significant lower [(84.7 +/- 17.5) ng/L vs. (99.8 +/- 18.2) ng/L, P < 0.05] in MB group compared to NMB group. CONCLUSION: MB patients were prone to coronary artery spasm partly due to endothelial dysfunction. Patients with MB and coronary artery spasm also showed classic clinical symptoms and positive stress tests for ischemia.

[Clinical features of 17 cases of X-linked agammaglobulinemia].

OBJECTIVE: To investigate clinical features of X-linked agammaglobulinemia (XLA) in children. METHODS: The medical records of 17 children with XLA between January 2001 and April 2007 were reviewed. RESULTS: The age at first diagnosis in 88.2% of patients was more than 6 years, with a mean of 7.7 years. Twelve patients (70.6%) presented first symptoms over 2 years old, with a mean of 4.2 years. Respiratory infections as first symptoms and complaints occurred in 64.7% of the patients and 35.3% of the patients presented with polyarthritis. Skin and soft tissue infections were rarely seen in less than 1 year old group children. Abrupt sepsis and abscess in deep tissues were seen in the older children. CD4+ T cells decreased and CD8+ T cells increased in 9 patients and an inversed ratio of CD4+/ CD8+ was observed in 11 patients. CONCLUSIONS: Both the age presenting first symptoms and the age at first diagnosis in children with XLA in this study were later than the reported data. Respiratory infection was the most common manifestation. High prevalence of polyarthritis was observed. Abnormal T cell phenotypes occurred in more than one half of patients.

Resting Chest Pain, Negative Treadmill Exercise Electrocardiogram, and Reverse Redistribution in Dipyridamole Myocardial Perfusion Scintigraphy Might be the Features of Coronary Artery Spasm.

BACKGROUND: Coronary artery spasm usually attacks while at rest and the diagnosis depends on provoking tests which mostly are invasive, expensive and not practical. Previous investigations demonstrated that in most patients with coronary artery spasm, treadmill exercise electrocardiography (TEEC) did not induce any ischemic changes, and myocardial perfusion scintigraphy (MPS) showed reverse redistribution (RR). HYPOTHESIS: Combination of resting chest pain, negative TEEC and RR might be a rational noninvasive set to predict coronary artery spasm. METHODS: Patients with chest pain at rest, no significant coronary artery stenosis, and willing to undergo acetylcholine test were included. TEEC, dipyridamole and rest thallium-201 MPS were performed before or after coronary angiography. The patients were divided into spasm and nonspasm groups by acetylcholine test. The clinical features and results of TEEC and MPS were compared between the spasm and nonspasm groups. RESULTS: Acetylcholine test was performed in 92 patients and coronary artery spasm was successfully provoked in 68 patients. Positive TEEC was induced in only 4 patients in the spasm group. RR was present in totally 77 patients and 68 of them were from the spasm group. By a combination of resting chest pain, negative TEEC and RR to diagnose coronary artery spasm, the sensitivity and specificity were 94% and 96% respectively. CONCLUSION: Combination of resting chest pain, negative TEE and RR appears to be a rational noninvasive set to predict coronary artery spasm.

[The differential diagnostic value and significance of combined heart stress tests in patients with atypical chest pain].

OBJECTIVE: To investigate the value of stress electrocardiography (S-ECG) and stress myocardial perfusion scintigraphy (S-MPS) in the differential diagnosis of patients with atypical chest pain. METHODS: Patients with atypical chest pain were undergone S-ECG, S-MPS, coronary angiography and coronary artery spastic provocation with intracoronary acetylcholine test. The final diagnoses of those patients were coronary heart disease, coronary spasm, coronary artery muscular bridge, microvascular angina pectoris and chest pain with non-coronary heart disease. Those patients were grouped by final diagnoses to retrospectively compare the results of S-ECG and S-MPS between groups. RESULTS: Totally 186 patients with integrated data were included. The final diagnoses were coronary artery stenosis (above 50% stenosis in diameter) in 20%, coronary artery spasm in 27%, coronary artery muscular bridge in 14%, microvascular angina pectoris in 5%, and chest pain with non-coronary artery disease in 34%. The sensitivity and specificity to diagnose ischemic coronary artery disease (including coronary stenosis, coronary artery muscular bridge and syndrome X but not coronary artery spasm) were 92% and 65% in S-ECG, 62% and 79% in S-MPS, respectively. Combination of atypical chest pain, negative S-ECG and reversal redistribution of S-MPS was an accurate non-invasive method to diagnose coronary artery spasm with sensitivity of 94% and specificity of 96%. CONCLUSIONS: Most of patients with atypical chest pain have organic or functional ischemic coronary artery disease. Combination of heart stress tests are helpful to differentiate the etiology of atypical chest pain.

[Comparison of plasma low-density lipoprotein and oxidized low-density lipoprotein levels with coronary lesion severities in patients with coronary artery disease].

OBJECTIVE: To explore the relationship between plasma low-density lipoprotein (LDL) and oxidized low-density lipoprotein (ox-LDL) levels and the severity of coronary atherosclerosis. METHODS: Fasting plasma ox-LDL was measured by enzyme-linked immunosorbent assay and plasma LDL was measured by biochemical autoanalyser in 31 patients with coronary artery spasm (CAS group, chest pain with positive acetylcholine provocation test but without significant coronary artery stenosis), 35 patients with stable angina pectoris (SAP group) and 24 healthy persons (control group). RESULTS: Plasma LDL levels were similar between CAS and SAP groups but significantly higher than that in control group. Plasma ox-LDL levels significantly increased in proportion to coronary lesion severities [SAP (575 +/- 219 microg/L) > CAS (299 +/- 117 microg/L) > control (218 +/- 35 microg/L)]. In SAP group, plasma ox-LDL level was also significantly higher in multi-vessel disease group than that in single-vessel disease group (672 +/- 92 vs. 462 +/- 72 microg/L, P < 0.05). CONCLUSION: Plasma ox-LDL but not LDL level is significantly correlated to the severity of coronary atherosclerosis and should therefore be the focused therapy target in patients with coronary artery disease.

Family History of Early Infant Death Correlates with Earlier Age at Diagnosis But Not Shorter Time to Diagnosis for Severe Combined Immunodeficiency.

BACKGROUND: Severe combined immunodeficiency (SCID) is fatal unless treated with hematopoietic stem cell transplant. Delay in diagnosis is common without newborn screening. Family history of infant death due to infection or known SCID (FH) has been associated with earlier diagnosis. OBJECTIVE: The aim of this study was to identify the clinical features that affect age at diagnosis (AD) and time to the diagnosis of SCID. METHODS: From 2005 to 2016, 147 SCID patients were referred to the Asian Primary Immunodeficiency Network. Patients with genetic diagnosis, age at presentation (AP), and AD were selected for study. RESULTS: A total of 88 different SCID gene mutations were identified in 94 patients, including 49 IL2RG mutations, 12 RAG1 mutations, 8 RAG2 mutations, 7 JAK3 mutations, 4 DCLRE1C mutations, 4 IL7R mutations, 2 RFXANK mutations, and 2 ADA mutations. A total of 29 mutations were previously unreported. Eighty-three of the 94 patients fulfilled the selection criteria. Their median AD was 4 months, and the time to diagnosis was 2 months. The commonest SCID was X-linked (n = 57). A total of 29 patients had a positive FH. Candidiasis (n = 27) and bacillus Calmette-Guérin (BCG) vaccine infection (n = 19) were the commonest infections. The median age for candidiasis and BCG infection documented were 3 months and 4 months, respectively. The median absolute lymphocyte count (ALC) was 1.05 × 109/L with over 88% patients below 3 × 109/L. Positive FH was associated with earlier AP by 1 month (p = 0.002) and diagnosis by 2 months (p = 0.008), but not shorter time to diagnosis (p = 0.494). Candidiasis was associated with later AD by 2 months (p = 0.008) and longer time to diagnosis by 0.55 months (p = 0.003). BCG infections were not associated with age or time to diagnosis. CONCLUSION: FH was useful to aid earlier diagnosis but was overlooked by clinicians and not by parents. Similarly, typical clinical features of SCID were not recognized by clinicians to shorten the time to diagnosis. We suggest that lymphocyte subset should be performed for any infant with one or more of the following four clinical features: FH, candidiasis, BCG infections, and ALC below 3 × 109/L.

[Clinical features of patients with atypical coronary artery spasm].

OBJECTIVE: This study is aimed to compare the clinical characteristics of patients with typical and atypical coronary artery spasm. METHODS: Out of 64 patients with chest pain at rest and without significant coronary artery stenosis, coronary artery spasm was provoked by intracoronary injection of acetylcholine in 46 patients, including 12 with ST segment elevation (typical coronary artery spasm group) and 34 without ST segment elevation (atypical coronary artery spasm group). The demographic data, coronary angiographic findings, treadmill electrocardiogram, dipyridamole and rest thallium-201 myocardial perfusion computed tomography, and the follow-up clinical data of the two groups were compared. RESULTS: The patients with typical coronary artery spasm were younger (47 +/- 6 vs. 58 +/- 12, P < 0.05) than patients with atypical coronary artery spasm group. Hyperlipidemia were more common in atypical coronary artery spasm group (74% vs. 33%, P < 0.05) and myocardial bridging was more common in patients with typical coronary artery spasm group (67% vs. 32%, P < 0.01). Focal coronary spasm during acetylcholine provocation was seen in 92% patients with typical coronary spasm and in 32% patients with a atypical coronary artery spasm (P < 0.01) while diffuse coronary spasm was seen in 8% patients with typical coronary spasm and in 68% patients with a atypical coronary artery spasm (P < 0.01). All patients with coronary artery spasm were treated with aspirin, calcium channel blockers, long-acting nitroglycerine, with or without lipid-lowering drugs, 2 patients with typical coronary spasm and 4 patients with atypical coronary spasm were rehospitalized due to chest pain and rest of the patients remained free of chest pain during the median follow-up period of 18 +/- 14 months. CONCLUSION: Atypical coronary artery spasm is common in patients with rest angina and diffuse coronary microvascular spasm might be the cause of chest pain in these patients.