Clinical analysis of Epstein-Barr virus-associated lymphoproliferative disease in children / 国际儿科学杂志

Objective:To investigate the clinical features of Epstein-Barr virus associated lymphoproliferative disease in children and to improve the understanding of this disease.Methods:This study included the children with Epstein-Barr virus associated lymphoproliferative disease admitted to the First Affiliated Hospital of College of Medicine of Zhejiang University from January 2014 to December 2018.Data of these children were collected, including age, clinical manifestations, laboratory results, treatment and outcome.The clinical features and therapeutic effects were analyzed.Results:A total of 114 cases(mean age 6 years, 0~17 years)were enrolled in this study, including 53 males and 61 females.There were 107 cases(93.86%) in the mild group (38 cases of EBV infection and 69 cases of infectious mononucleosis) and 7 cases in the severe group (6.14%). Six cases of the severe group were T cell or NK cell proliferation.Compared with the mild group, the load of EBV-DNA was higher in the severe group, but there was no significant difference( χ2=0.957, P>0.05). The IgM in severe group was significantly lower( Z=-2.041, P<0.05). But the differences in the level of immune function including IgA, IgG, CD4 + cell and CD8 + cell between the severe group and the mild group were not significant.The cases in the mild group had improved after antiviral treatments.Among the severe group, 3 cases survived after treatment, another 1 case was diagnosed as hydroa vacciniforme-like EBV-related proliferative disease (HV-like LPD). After antiviral treatment, the effect was not good, then after high-dose IVIG treatment and Bortezomib combined with methylprednisolone treatment, the EBV-DNA load decreased and the condition improved.While 1 case lost to follow-up, there were 2 cases with EBV-associated hemophagocytic syndrome and 1 case with EBV-associated lymphoma died after chemotherapy or transplantation. Conclusion:EBV-associated lymphoproliferative disease may manifest as a condition similar to infectious mononucleosis.High IgE, low IgM or high DNA load may indicate poor prognosis.Immune function after EBV infection may have different effects on prognosis.When the infected lymphocyte types are NK or T cells, it may indicate poor prognosis.The efficacy of transplantation and chemotherapy in severe cases is still uncertain.

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome in two cases / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To report on two cases affected with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX).</p><p><b>METHODS</b>Two unrelated Chinese infants affected with IPEX were investigated. Case 1 was a 4-month-old boy with neonatal diabetes and severe enteropathy. Case 2 was a 6-day newborn boy with neonatal diabetes and ketoacidosis. DNA samples of the two infants and their parents were sequenced for FOXP3 gene mutations. Suspected mutations were verified among 100 unrelated healthy controls. The function of mutations was predicted with bioinformatics software.</p><p><b>RESULTS</b>Both infants had onset of the disease during neonatal period, and manifested insulin-dependent diabetes mellitus, persistent diarrhea, eczema and malnutrition. In case 1, a novel splice site mutation was identified in intron 9 (c.967+3A>T) of the FOXP3 gene, for which his mother was a carrier. For case 2, a missense mutation (c.1150G>A) was detected in exon 11 of the FOXP3 gene, for which his mother was also a carrier. The IVS9 c.967+3A mutation was not detected among the 100 healthy controls. As predicted with Human Splicing Finder software, the c.967+3A>T mutation may influence the splicing of mRNA and affect the function of protein.</p><p><b>CONCLUSION</b>Both cases had typical clinical manifestation of the IPEX syndrome, among whom a novel splice site mutation (IVS9 c.967+3A>T) and a missense mutation (c.1150G>A) of the FOXP3 gene were identified. The clinical manifestation of the IPEX syndrome may be variable and the mortality is high. FOXP3 gene sequencing is recommended when insulin-dependent diabetes mellitus is diagnosed during the neonatal period.</p>

Echocardiographic Manifestations of Congenital Quadricuspid Aortic Valves and Surgical Follow-ups / 中国医学影像学杂志

Purpose To summarize the clinical and echocardiographic characteristics of congenital quadricuspid aortic valves (QAV) so as to improve the understanding of QAV and the accuracy of preoperative diagnosis.Materials and Methods The clinical and echocardiographic data of 7 patients with QAV at the First Affiliated Hospital of Nanchang University were retrospectively studied,and the features such as the aortic valve (AV) leaf number,echo,shape,opening and closing movements,and its hemodynamics were observed and compared with surgical follow-ups.Results Five out of the 7 patients had chest tightness,chest pain,fluster,shortness of breath,and 2 others had no discomfort.The echocardiography presented that all the cases had moderate or severe aortic valve regurgitation.4 patients were diagnosed as QAV,2 patients were not diagnosed definitely,and the rest 1 was misdiagnosed.6 patients underwent aortic valve replacement and were all confirmed with QAV,among whom 2 patients were combined with infective endocarditis,and 1 patient was with aortic dilatation.All the surgical operations were successful and the patient's physical conditions were good after surgery.Conclusion Echocardiography plays an important role in diagnosis of aortic valve,but it is possible to be missed or misdiagnosed.Most QAV patients have good prognosis,but close follow-ups are needed when QAV is combined with other complex deformity or has induced secondary damages.

Association of PA X 4 R192S and R192H polymorphism with obesity in children and adolescents / 临床儿科杂志

Objective To investigate association of the paired box 4 (PA X 4) gene rs3824004 (574C>A; R192S) and rs2233580 (575G>A; R192H) polymorphism with obesity and metabolic markers in children and adolescents. Methods A total of 103 obese children were randomly selected, and an average age was (10.82±2.57) years, and body mass index (BMI) was (26.82±4.57) kg/m2. At the same period, 100 normal weight children were selected as the control group, and an average age of (10.60±2.84) years, and BMI was (16.79±2.13) kg/m2. The blood pressure, physical measurements, and blood metabolic parameters were measured and compared. The oral glucose tolerance test (OGTT) and insulin release test were performed in the obesity group. The homeostasis model insulin resistance index (HOMA-IR) and the overall insulin sensitivity index (WBISI) were calculated. PA X 4 rs3824004 and rs2233580 polymorphism were detected by PCR.The differences of allele frequency and genotype frequency of polymorphic loci were analyzed, and the correlation between different genotypes and metabolic indexes was analyzed. Results The height, weight, BMI, systolic blood pressure, diastolic blood pressure, waist circumference, hip circumference, waist to height ratio (WHtR), fasting blood glucose (FPG), total cholesterol (TC), low density lipoprotein (LDL), triacylglycerol (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in the obesity group were significantly higher than those in the control group, and the high density lipoprotein (HDL) was significantly lower than that in the control group (all P<0.05). The frequency of gene distribution was in accordance with the Hard-Weinberg balance. The frequencies of A allele of rs3824004 in obesity and control groups were 4.9% and 5.0%, respectively, and the frequencies of CA genotype were 9.7% and 10.0%, respectively, and there was no significant difference between two groups (P>0.05). The frequency of GA allele of rs2233580 in obesity group was 25.2%, which was significantly higher than that in control group (P<0.05). The BMI and waist in rs2233580 GA genotype were significantly higher than those in GG genotype (all P <0.05). However,logistic regression analysis showed that there was no correlation between PA X 4 rs2233580 genotype and metabolic markers (all P>0.05).There were no significantly differences in HOMA-IR and WBISI among different genotypes of PA X 4 rs2233580 in obesity group(all P>0.05).Conclusions PA X 4 rs2233580 affects children's BMI and waist circumference and may be involved in the development of childhood obesity, but it is not an independent risk factor for obesity in children and adolescents.

Analysis of PAX6 gene mutations in a Chinese family affected with congenital aniridia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the mutation of PAX6 gene in a Chinese family affected with congenital aniridia.</p><p><b>METHODS</b>Blood samples were drawn from family members, and DNA was analyzed by direct sequencing.</p><p><b>RESULTS</b>A heterozygous mutation (c.151 G>A) was identified in the PAX6 gene in the proband and other patients from the family. The same mutation was not found among unaffected family members and 160 unrelated healthy controls.</p><p><b>CONCLUSION</b>A novel mutation in the PAX6 gene has been identified in a Chinese family affected with aniridia.</p>

Clinical observation on acupuncture at Jiaji (EX-B 2) points plus tuina in treating thoracic facet joint disorder / 针灸推拿医学（英文版）

Objective:To observe the clinical effects of acupuncture at Jiaji (EX-B 2) points plus tuina manipulation for thoracic facet joint disorder, and get new clinical evidence for treatment of thoracic facet joint disorder. Methods:Totally 106 patients with thoracic facet joint disorder were randomly allocated into an observation group and a control group based on the random number table. Patients in the control group were treated by tuina manipulation, while those in the observation group were treated by acupuncture at Jiaji (EX-B 2) points before tuina manipulation. Patients in the two groups were treated once a day. The improvements of signs and symptoms and the efficacy were observed after 3 treatments. Results:After treatment, there were intra-group statistical differences in scores of 8 signs and symptoms in both groups (P<0.01); the score of each item in the observation group was lower than that in the control group, and there was statistical significance in the inter-group difference (P<0.05). The cure rate of the observation group was 50.9%, versus 26.4% in the control group, and there was a significant difference between the two groups (P<0.05). Conclusion:In treating thoracic facet joint disorder, acupuncture plus tuina manipulation can restore the biomechanical balance of thoracic vertebrae, fully maximized the combined effect, and significantly improve the clinical efficacy.

Efficacy of acupuncture on moderate and severe allergic rhinitis / 中国针灸

<p><b>OBJECTIVE</b>To observe the efficacy and safety of acupuncture therapy on moderate and severe allergic rhinitis via the comparison evaluation of western medicine.</p><p><b>METHODS</b>Sixty cases of moderate and severe allergic rhinitis were divided into an acupuncture group (30 cases) and a western medicine group (30 cases). In the acupuncture group, the main acupoints included Yingxiang (LI 20), Shangxing (GV 23), Fengchi (GB 20), Quchi (LI 11), Xuehai (SP 10), Feishu (BL 13), Geshu (BL 17), Pishu (BL 20), etc. The supplementary points were selected according to syndrome differentiation. In the western medicine group, budesonide nasal spray and cetirizine tablets were prescribed. All the cases were treated for 8 weeks in the two groups. Separately, before treatment, in 4 weeks and 8 weeks of treatment, the scores of clinical symptoms and physical signs were observed and the clinical efficacy and safety were compared between the two groups.</p><p><b>RESULTS</b>In 4 weeks and 8 weeks of treatment, the scores of symptoms such as sneezing, nasal discharge, nasal obstruction, nasal itching, eye itching and turbinate hypertrophy, the score of physical signs and total score were all reduced apparently as compared with those before treatment (all P<0. 05). The differences were not significant between the acupuncture group and the western medicine group (all P>0. 05). The total effective rates were 90. 0% (27/30) and 93. 4% (28/30) in the acupuncture group after 4 and 8 weeks of treatment, and were 76. 6% (23/30) and 80. 0% (24/30) in the western medicine group separately, without significant difference in comparison (all P>0. 05).</p><p><b>CONCLUSION</b>Acupuncture achieves the similar efficacy on moderate and severe allergic rhinitis as western medicine. It is the safe therapy and has no apparent adverse reactions.</p>

Detection of dystrophin gene mutation in a Chinese pedigree affected with Duchenne muscular dystrophy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify mutations of dystrophin gene in a Chinese pedigree affected with Duchenne muscular dystrophy (DMD).</p><p><b>METHODS</b>Clinical data from the pedigree was collected. Subsequently, polymerase chain reaction and DNA sequencing analysis were applied to detect the potential mutations. Restriction enzyme digestion was carried out to determine whether the mutation was present in 118 healthy controls. Clustal software was applied for analyzing the conservation of altered amino acids.</p><p><b>RESULTS</b>DNA sequencing analysis has identified a heterozygous missense mutation c.7578G>C (p.Gln2526His) mutation in exon 52 of the dystrophin gene in the proband and his mother. The same mutation was absent in the 118 healthy controls. Restriction enzyme digestion has confirmed above result. Clustal analysis indicated that the altered amino acid is highly conserved in mammals.</p><p><b>CONCLUSION</b>The results revealed a novel missense mutation (c.7578G>C) of the dystrophin gene in DMD patients.</p>

Expression of CD226 mRNA in the peripheral blood mononuclear cells of patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective To investigate the expression level of CD226 mRNA in the peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE) and explore the relation between the gene expression and disease activity, and the relation between the gene expression and Gly307Ser polymorphism of CD226 was also examined. Methods CD226 gene was measured with real-time polymerase chain reaction (qRT- PCR) in PBMCs. The expression levels of CD226 gene in PBMCs were compared between 90 SLE patients and 30 healthy individuals. One-way ANOVA and pearson correlation were used for statistical analysis. Results The expression level of CD226 in the PBMCs of SLE patients (6.8±1.1) was significantly decreased compared to healthy individuals (26.5±6.7) (P＜0.01), while there was no association between mRNA level and genotype (P＞0.05). No correlation between ESR, CRP, ANA, SLEDAI scores, C3 and the expression level of CD226 gene was discovered. Conclusion In Hubei Chinese Han population, CD226-Gly307Ser locus is associated with the development of SLE, while T allele does not impact the expression of CD226 gene, thus the role of CD226 gene in autoimmune diseases should be explored in the future.

Identification of a new lamin A/C mutation in a chinese family affected with atrioventricular block as the prominent phenotype / 华中科技大学学报（医学）（英德文版）

Even though mutations in LMNA have been reported in patients with typical dilated cardiomyopathy (DCM) and atrioventricular block (AVB) previously, the purpose of this study was to disclose this novel genetic abnormality in one Chinese family with the atypical phenotype of progressive AVB followed by DCM with normal QRS interval. Genome-wide linkage analysis mapped the AVB gene in this family to a marker at chromosome 1q21.2, where the LMNA gene was located. Direct DNA sequence analysis revealed a heterozygous G to A transition at nucleotide 244 in exon 1 of LMNA, which resulted in an E82K mutation. The E82K mutation co-segregated with all affected individuals in the family, and was not present in 200 normal controls. Further clinical evaluation of mutation carriers showed that 5 of 6 AVB patients exhibited mild DCM with a late onset of age in the fourth and fifth decades. Ejection fractions were documented in 5 patients with DCM, but 4 showed a normal value of [Symbol: see text]50%. Echocardiography showed that atrial dilatation occurred earlier than ventricular dilatation in the patients. This study suggests that progressive AVB with normal QRS interval and accompanying DCM at later stages may represent a distinct type of DCM. The molecular mechanism by which the E82K mutation causes AVB as the prominent phenotype in DCM may be a focus of future studies.

Effects of focused ultrasound on biological characteristics of cervical tumor transplanted subcutaneously in nude mice / 重庆医科大学学报

Objective:To observe the treating effect of focused ultrasound on human cervical tumor transplanted subcutaneously in nude mice.Methods:After irradiated with different dose of focused ultrasound,the thirty-two nude mice which transplanted subcutaneously with human cervical cancer were observed for the growth of the subcutaneously transplanted tumor and general vital sign and its effects on the biological characteristics of tumor tissues on the rim of the targeted areas at the different time.Target areas and the rim of the targeted areas in tumor samples were examined by light microscope and electron microscope for the change of histopathology and ultra-structure.Apoptosis was detected by TUNEL.The immunohistochemical method was applied to investigate the expressions of Bax,Bcl-2,PCNA and MMP-9.Results:Focused ultrasound had evident inhibitory effect on the growth of transplanted subcutaneously human cervical tumor in nude mice and the effect was positively related to the dose.Denaturation,necrosis and the damage of nuclear structure were found in targeted areas of each treatment group through pathohistological observation.Tumor cell that on the rim of the targeted areas were swelling and loosing arranged.Ultrastructural investigations showed mitochondrion swelling and the formation of cytoplasm cavitations bubbles,but the change of nuclear structure was not significant.Compared with that of unirradiated areas,apoptosis rate of tumor cell in the rim of the targeted areas was increasing,the expression of Bax was up-regulated and Bcl-2 was down regulated,and the expressions of PCNA and MMP-9 protein weakened.Conclusions:Focused ultrasound could significantly damage the tumor cells of human cervical cancer transplanted subcutaneously in nude mice tumor and induced apoptosis of tumor cell on the rim of the targeted areas significantly.The process maybe related to the mitochondria-mediated cell apoptosis signal passage that activated by the thermal effect of focused ultrasound.

Relationship between changes of portal system hemodynamics and levels of plasma glucagon in patients with liver cirrhosis / 中国实用内科杂志

Objective To investigate the changes of plasma levels of glucagon in cirrhotic patients and its effect in the pathogenesis of portal hemodynamics.Methods Plasma levels of glueagon were measured by radioimmunoassay(RIA)in 42 patients with liver cirrhosis and 20 healthy controls.The max diameters,mean flow velocity,flow rate of the portal vein trunks(PV)and splenic veins(SV)were detected by Color Doppler Ultrasound.Results Plasma levels of glucagon in cir- rhotic patients were significantly higher than those in controls and were increased with the severity of hepatic function im- pairment as assessed by Child-Pugh grade.Patients with ascites showed signifieanthigher plasma glucagon levels than those without ascites.Plasma levels of glueagon were positively correlated with portal vein diameters,splenic vein diame- ters and splenic vein flows.Conclusion The increase of plasma glucagon levels reflects,in part,the severity of impair- ment of hepaticfunction.In addition,it may contribute to the pathogenesis of portal hypertension.

The value of the soluable intercellular adhesion molecule-1 levels in matermal serum for determination of occult chorioamnionitis in premature rupture of membranes / 华中科技大学学报（医学）（英德文版）

To compare the diagnostic value of soluble intercellular adhesion molecule 1 (sICAM-1) with that of c-reactive protein (CRP) for detecting chorioamnionitis (CAM) in serum of women with premature rupture of membranes (PROM), 55 pregnant women with PROM, including 18 pregnant women with preterm premature rupture of membranes (PPROM) and 20 normal pregnant women at term (TPROM) were studied. Maternal serum were measured by Sandwish enzyme-linked immunoabsorbent assay (ELISA) for sICAM. CAM was histologically confirmed after delivery. The results revealed that (1) maternal serum levels of sICAM-1 and CRP were significantly higher in women with PROM than those without it; (2) maternal serum levels of sICAM-1 and CRP were significantly higher in women with CAM than those without it; (3) serum levels of sICAM-1 in PPROM women were similar to those in TPROM women, whereas serum levels of CRP in PPROM women were significantly higher than those in TPROM women; (4) the sensitivity, specificity, positive predictive value, negative predictive value, Kappa index and area under receiver operating characteristic (ROC) curve of maternal serum sICAM-1 (cutoff 104.7 ng/ml) and CRP (cutoff 1.03 mg/dl) for diagnosing CAM were 100%, 91.2%, 87.5%, 100%, 0.20, 0.995 and 81.0%, 73.5%, 65.4%, 86.2%, 0.13, 0.811, respectively; (5) among the mild histological CAM group, severe histological CAM group and clinical CAM group, the difference in maternal serum levels of sICAM-1 were significantly (P<0.001), with the order of concentration from high level to low level corresponding to the severity of CAM. It is concluded that maternal serum level of ICAM-1 is superior to that of CRP as biomarker for diagnosing intraamniotic infection in pregnant women with PROM.

The value of the soluable intercellular adhesion molecule-1 levels in matermal serum for determination of occult chorioamnionitis in premature rupture of membranes / 华中科技大学学报（医学）（英德文版）

To compare the diagnostic value of soluble intercellular adhesion molecule 1 (sICAM-1) with that of c-reactive protein (CRP) for detecting chorioamnionitis (CAM) in serum of women with premature rupture of membranes (PROM), 55 pregnant women with PROM, including 18 pregnant women with preterm premature rupture of membranes (PPROM) and 20 normal pregnant women at term (TPROM) were studied. Maternal serum were measured by Sandwish enzyme-linked immunoabsorbent assay (ELISA) for sICAM. CAM was histologically confirmed after delivery. The results revealed that (1) maternal serum levels of sICAM-1 and CRP were significantly higher in women with PROM than those without it; (2) maternal serum levels of sICAM-1 and CRP were significantly higher in women with CAM than those without it; (3) serum levels of sICAM-1 in PPROM women were similar to those in TPROM women, whereas serum levels of CRP in PPROM women were significantly higher than those in TPROM women; (4) the sensitivity, specificity, positive predictive value, negative predictive value, Kappa index and area under receiver operating characteristic (ROC) curve of maternal serum sICAM-1 (cutoff 104.7 ng/ml) and CRP (cutoff 1.03 mg/dl) for diagnosing CAM were 100%, 91.2%, 87.5%, 100%, 0.20, 0.995 and 81.0%, 73.5%, 65.4%, 86.2%, 0.13, 0.811, respectively; (5) among the mild histological CAM group, severe histological CAM group and clinical CAM group, the difference in maternal serum levels of sICAM-1 were significantly (P<0.001), with the order of concentration from high level to low level corresponding to the severity of CAM. It is concluded that maternal serum level of ICAM-1 is superior to that of CRP as biomarker for diagnosing intraamniotic infection in pregnant women with PROM.