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Desde los años ochenta se ha explorado el tratamiento para el virus de la hepatitis C, aunque en ese entonces los medicamentos disponibles eran poco toleradas y poco eficaces. En el 2011, la introducción de antivirales de acción directa transformó significativamente el curso de la enfermedad, logrando tasas de curación superiores al 90 % en los pacientes. Este avance ha permitido prevenir complicaciones futuras con efectos adversos mínimos. La presente revisión aborda la línea de tiempo del descubrimiento de los antivirales, su mecanismo de acción, sus indicaciones y potencial impacto en la salud pública.
Since the 1980s, the treatment of hepatitis C has been explored, although at that time, the available medications were poorly tolerated and ineffective. In 2011, the introduction of direct-acting antivirals significantly transformed the course of the disease, achieving cure rates of over 90% in patients. This advance has made it possible to prevent future complications with minimal adverse effects. This review addresses the timeline of the discovery of antivirals, their mechanism of action, and their impact on medicine.
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RESUMEN Introducción: Se ha tratado de identificar los factores genéticos relacionados con susceptibilidad para enfermedad inflamatoria intestinal (EII), y los hallazgos actuales se inclinan por un modelo de patología complejo, sin un patrón hereditario claro. Objetivo: Realizar caracterización fenotípica y genotípica de pacientes con EII en población colombiana y describir su posible asociación con predisposición. Materiales y métodos: Serie de casos, 16 pacientes con EII por criterios clínicos y anatomopatológicos, inicio de síntomas gastrointestinales después de los 18 años. Todos tuvieron asesoramiento genético pre-test y se realizaron árboles genealógicos de mínimo tres generaciones. También, genotipificación, por medio de un panel de genes múltiples que incluía genes relacionados con EII y algunos trastornos autoinmunitarios. Finalmente, se realizó análisis genómico de variantes. Resultados: 9 mujeres y 7 hombres, con edad media de diagnóstico de EII 35 años, y 32 años para aparición de síntomas gastrointestinales. 11/16(68,75%) requirieron terapia biológica. 10/16 (62,5%) presentaron refractariedad a terapia estándar. 3/16 (18,75%) tenían antecedentes familiares positivos de EII. 100% casos presentaron al menos un single nucleotide polymorphism relacionado con riesgo de EII en más de un gen. Los genes más relacionados con colitis ulcerosa (CU), fueron CD48, CD6, y TYK2 para CU, y CD6 e ITGAM para la enfermedad de Crohn. El gen más frecuente fue CD6. Se observó en 3/16 (18,75%) presencia de hasta 5 genes, 4 en 3/16 (18,75%), y tres en 5/16 (31,25%). Conclusión: En EII hay presencia de variantes genéticas con predisposición asociada, pero sin patogenicidad confirmada, y cuya sumatoria parece contribuir en su fisiopatología.
ABSTRACT Introduction: Attempts have been made to identify the genetic factors related to susceptibility to inflammatory bowel disease (IBD), and the current conclusions are in favor of a complex pathology model, without a clear hereditary pattern. Objective: To perform phenotypic and genotypic characterization of patients with IBD in Colombian population and to describe its possible association with predisposition. Materials and methods: case series, 16 patients with IBD according to clinical and pathological criteria, onset of gastrointestinal symptoms after 18 years of age. All had pre-test genetic counseling and family trees of at least three generations were made. Also, genotyping, using a multigene panel that included genes related to IBD and some autoimmune disorders. Finally, a genomic analysis of variants was performed. Results: 9 women and 7 men, with mean age of diagnosis of IBD of 35 years, and gastrointestinal symptoms appearance of 32 years. 11/16 (68.75%) required biological therapy. 10/16 (62.5%) were refractory to standard therapy. 3/16 (18.75%) had positive family history of IBD. 100% cases presented at least one single nucleotide polymorphism related to IBD risk in more than one gene. The genes most related to ulcerative colitis (UC) were CD48, CD6, and TYK2 for UC, and CD6 and ITGAM for Crohn's disease. The most frequent gene was CD6. It was found presence of up to 5 genes in 3/16 (18.75%), 4 in 3/16 (18.75%), and three in 5/16 (31.25%). Conclusion: In IBD there is the presence of genetic variants with associated predisposition, but without confirmed pathogenicity, and whose sum seems to contribute to its pathophysiology.
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RESUMEN Objetivo: Determinar la prevalencia y las características genotípicas de la infección anal por papilomavirus en hombres que tienen sexo con hombres (HSH) VIH-positivos. Materiales y métodos: Es un estudio observacional prospectivo de corte transversal en HSH VIH-positivos del Hospital Nacional Guillermo Almenara Irigoyen, EsSalud, realizado entre setiembre del 2017 y diciembre del 2018. El estudio del papilomavirus se realizó con una técnica de reacción en cadena de polimerasa evaluando 21 genotipos estratificados según el riesgo oncogénico: seis de bajo riesgo y quince de alto riesgo. Resultados: Se evaluaron 214 HSH VIH-positivos. La prevalencia general de la infección anal por papilomavirus fue de 70% (150/214). 86% (129/150) tuvieron genotipos de alto riesgo oncogénico, de ellos 79% (102/129) tuvieron dos o más genotipos de papilomavirus. Los genotipos de alto riesgo oncogénico más frecuentes fueron: VPH-16, 31% (46/150); VPH-52, 22% (33/150); VPH-33, 21% (31/150); VPH-58, 21% (31/150) y VPH-31, 20% (30/150). El VPH-18 alcanzó el 7% (10/150). Los genotipos de bajo riesgo oncogénico más frecuentes fueron: VPH-6, 30% (45/150) y VPH-11, 29% (44/150). Conclusiones: La prevalencia de la infección anal por papilomavirus en HSH VIH-positivos es muy alta en el hospital investigado. La gran mayoría de estas infecciones se producen con genotipos de alto riesgo oncogénico. El papilomavirus 16 fue el genotipo de alto riesgo más frecuente.
ABSTRACT Objective: To determine the prevalence and genotypic characteristics of anal papillomaviruses in HIV-positive men who have sex with men (MSM). Materials and methods: This is a prospective cross-sectional observational study of HIV-positive MSM at Almenara General Hospital between September 2017 and December 2018. HPV detection and typing was performed using a polymerase chain reaction technique that evaluated 21 genotypes stratified according to oncogenic risk into six low-risk and fifteen high-risk. Results: we evaluated 214 HIV-positive MSM. The overall prevalence of anal infection by papillomavirus infection was 70% (150/214). 86% (129/150) were caused by high-risk genotypes, 79% (102/129) of them were affected by a two or more-papillomavirus genotype. The most frequent high-risk genotypes were HPV-16, 31% (46/150); HPV-52, 22% (33/150); HPV-33, 21% (31/150); HPV-58, 21% (31/150) and HPV-31, 20% (30/150). In addition, HPV-18 reached 7% (10/150). The most frequent low-risk genotypes were HPV-6, 30% (45/150) and HPV 11, 29% (44/150). Conclusions: Prevalence of anal papillomavirus infection in HIV-positive MSM is very high in the hospital investigated. Most of these infections occurs with high-risk oncogenic genotypes. Papillomavirus 16 was the most frequent high-risk genotype.
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Objective To investigate the human papillomavirus(HPV)infection and genotype distribution characteristics among male reproductive health outpatients,and to compare the differences among different age groups of outpatients.Methods A total of 1 658 males,visited in the Affiliated Hospital of Shanghai Institute of Planned Parenthood Research from 2018 to 2022,were selected and 23 HPV genotypes were detected by PCR-reverse dot hybridization.Results Among the 1 658 subjects,the overall HPV infection rate was 22.50%.Single infection accounted for 66.76%,which was the main infection type.HPV infection among different age groups were statistically significant(P<0.001),with HPV infection of 16.83%,22.87%,34.63%,and 29.35%for 18-30,31-40,41-50,and≥51 years,respectively.The top 5 high risk HPV genotypes were HPV52(3.56%),HPV16(3.26%),HPV39(2.41%),HPV51(2.17%),HPV58(2.17%),and the top 1 low risk HPV genotype was HPV81(2.90%).The proportions of infected individuals in this study that could be completely covered by bivalent,quadrivalent,and nine-valent HPV vaccines were 7.77%,12.33%,and 26.27%,respectively.Conclusion The predominant infection type among male reproductive health outpatients was single infection type.HPV 52,16,39,51 and 58 were the most common high risk genotypes,while HPV 81 was the most common low risk genotype.Individuals aged 41-50 years had the highest HPV infection rate.
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Objective To explore the carrier rate of thalassemia in Laibin city,Guangxi Province,and provide a theoretical basis for the prevention and control of thalassemia.Methods From January 2020 to December 2021,88 152 patients were screened for thalassemia in the outpatient department of the Women's and Children's Hospital of 4 counties,1 city and 1 district in Laibin by blood cell detection and hemoglobin electrophoresis.The common and rare genes in initially screened positive individuals were detected by gap polymerase chain reaction(Gap-PCR)and reverse dot blot(RBD),and the results were conducted by statistical analysis.Results ① There were 22 553 positive cases in the preliminary screening and 8 327 positive cases received the diagnosis of thalassemia gene.A total of 4 944 thalassemia carriers of thalassemia genes were detected,deducing that the total thalassemia carrier rate in the population of childbearing age in this region was 15.19%,including 3 200 cases of α-thalassemia carriers(64.73%),1 424 cases of β-thalassemia carriers(28.80%),and 320 cases of were carriers α-thalassemia combined with β-thalassemia(6.47%).② There were 3 168 cases of common thalassemia(99.00%)and 32 cases of rare thalassemia(1.00%)among α-thalassemia gene carriers.A total of 13 mutant genes and 34 genotypes were detected,and genotype SEA/αα was the comes first.③ Among the β-thalassemia gene carriers,there were 1 411 cases of(99.09%)common thalassemia and 13 cases(0.91%)of rare thalassemia.A total of 19 mutant genes and 25 genotypes were detected,with CD41-42(-CTTT)being the most common.④ A total of 53 different genotypes were detected in the carriers of α-thalassemia combined with β-thalassemia,and the top genotype was--SEA/αα βCD41-42M/βN.⑤ The carrier rates of Yao and Han nationality were comparable,and the differences were not significant(χ2=0.300,P=0.584).The differences in carrying rates between Zhuang and Yao(χ2=23.66,P＜0.001),and between Zhuang and Han(χ2=116.98,P＜0.001)were significant.⑥ The carrier rate in Xiangzhou County was the highest(20.04%),while the carrier rate in Heshan City was the lowest(12.38%).⑦ The carrier rate of females was higher than that of males,and the difference was significant(χ2=182.03,P＜0.001).Conclusion The variants genotypes of thalassemia in Laibin were complex.This study was the first to investigate the carrier rate and gene mutation spectrum of thalassemia in Laibin Area,which provides valuable baseline data for genetic counseling and prenatal diagnosis.
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Objective To investigate the incidence and the types of gene mutations of α-thalassemia in the child-bearing pop-ulation of Conghua District,Guangzhou.Methods Blood samples from 24 083 people of childbearing age were screened by blood cell analysis and hemoglobin electrophoresis,α-globin gene variation was detected by GAP-PCR and PCR reverse dot blot in the positive cases,and 17 common β-globin gene mutations were detected by PCR reverse Dot blot.Results A total of 2 596 cases of α-thalassemia gene abnormality were detected by gene identification,and the abnormal rate was 10.78%.A sum of 170 cases(0.71%)had a compound mutation of α-β gene.There were 2 550 cases(98.23%)of deletion and 46 cases(1.77%)of non-deletion in the mutant genes.There were 14 types of gene mutation,including 5 types of HbH disease(with--SEA/-α3.7 primarily),4 mild types(with 68.61%of--SEA/αα genotype),and 5 quiescent types(the top two genotypes were-α3.7/αα and-α4.2/αα).A total of 23 types of αβ complex gene mutation were detected,and the top six types were--SEA/βCD41-42,-α3.7/βCD41-42,--SEA/β654,--SEA/-28,-α3.7/β654 and-α3.7/βCD17,which accounted for 75.27%of all the complex types.Conclusion The gene abnormality rate of α-thalassemia in Conghua District of Guangzhou City was high.The gene mutation type and constitu-ent ratio,which have their own characteristics,is a special region of α-thalassemia.
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Objective:To determine the erythromycin resistance of Bordetella pertussis isolates and their ptxP1 and ptxP3 phenotypic composition and compare clinical manifestations of children with pertussis caused by the two types of strains. Methods:This was a cross-sectional study, the pertussis cases diagnosed using bacterial culture from January 2019 to December 2022 in Beijing Children′s Hospital and the First People′s Hospital of Wuhu were collected.Any suspected Bordetella pertussis colonies were identified by the slide agglutination test.The susceptibility of isolates to erythromycin was detected by the E-test and K-B test.The ptxP gene was amplified by polymerase chain reaction and sequenced to determine its genotype. t-test, Mann-Whitney U-test, Chi-square test and Fisher′s exact test were use to statistical analysis. Results:A total of 192 strains of Bordetella pertussis were identified, including 188 (97.9%) erythromycin-resistant strains.Among the 188 strains, 30.3%(57/188) belonged to the ptxP1 genotype and 69.7%(131/188) belonged to the ptxP3 genotype.In children aged below 1 year old, the incidence of paroxysmal cough caused by infection with the ptxP3 strain was higher than that with the ptxP1 strain (57.1% vs.29.4%, P<0.05), and children infected with the ptxP3 strain were more likely to develop apnea or asphyxia (23.8% vs.17.6%), post-tussive vomiting (44.4% vs.32.4%), whooping cough (72.0% vs.50.0%) and pneumonia or bronchitis (85.7% vs.73.5%) compared to those infected with the ptxP1 strain, but the differences were not statistically significant(all P>0.05). In children aged 1 year old and above, the white blood cell count of children infected with the ptxP1 strain was higher than that of infections with the ptxP3 strain [13.5(9.9, 24.5)×10 9/L, 10.3 (7.0, 16.4)×10 9/L, P<0.05], and children infected with the ptxP1 strain were more likely to contract other pathogen infections than those infected with the ptxP3 strain (17.4% vs.4.4%, P>0.05). Conclusions:ptxP3 erythromycin-resistant Bordetella pertussis has become the main pathogen of pertussis.Infants with pertussis caused by the ptxP3 erythromycin-resistant strain show more significant manifestations and a higher possibility of severe symptoms than those infected with the ptxP1 erythromycin-resistant strain.
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Objective To understand the molecular characteristics of Streptomycin(SM)resistance in multidrug-resistant tuberculosis(MDR-TB)in Jiangxi Province,and to explore the relationship between SM resistant genes(rpsL,rrs and gidB)mutations and SM resistant phenotypes in Beijing genotype TB.Methods 106 non-replicated MDR-TB isolates were collected from Gaoxin Branch of The First Affiliated Hospital of Nanchang University and Jiangxi Provincial Chest Hospital from January to December 2021,and tested for drug-resistance phenotypes,whether they were Beijing genotype or not and the characteristics of rpsL,rrs and gidB gene mutations.Chi-square test was performed to determine whether rpsL,rrs and gidB mutations were related to genotypes and drug-resistance phenotypes.Results Among 106 cases of MDR-TB,76 cases were resistant to SM.A total of 58 cases had rpsL 43A>G mutation,8 cases had 88A>G mutation,5 cases had rrs mutation,and 3 cases had gidB mutation.Statistical analysis showed that the coincidence rate of gene mutation and phenotypic drug-resistance detection was 89.6%,and the specificity and sensitivity were 86.7%and 90.8%,respectively.The isolated rate of Beijing genotype TB was 88.7%,and the drug-resistant gene mutations were mainly concentrated in rpsL and rrs,while the drug-resistant mutations of non-Beijing genotype were mainly concentrated in gidB;in addition,Beijing genotype bacteria were more prone to gene mutations(P = 0.013),but there was no difference in phenotypic drug-resistance.Conclusions Mutations in rpsL,rrs,and gidB genes have a good coincidence rate with phenotypic drug-resistance,and molecular biology can be used to detect directly drug-resistance genes to predict bacterial resistance;TB genotypes are strongly associated with streptomycin resistance characteristics.
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BACKGROUND:A large number of domestic and international documents have confirmed that elevated interleukin-1β is associated with primary frozen shoulder.Interleukin-1B gene polymorphisms can affect the transcription and protein expression of interleukin 1β-related genes,resulting in altered levels of cytokines in vivo,and thus altering the incidence of primary frozen shoulder.Through the study of interleukin-1B gene polymorphism and susceptibility to primary frozen shoulder,this study aimed to explore new breakthroughs in the pathogenesis of primary frozen shoulder from the perspective of molecular biology,and to search for susceptibility genes of primary frozen shoulder. OBJECTIVE:To explore the association between linkage disequilibrium of three gene loci in interleukin-1B gene and susceptibility to primary frozen shoulder. METHODS:A case-control study was conducted.There were two groups in this study.One group consisted of 184 patients with primary frozen shoulder,while the other group included 260 healthy controls.The genotypes of interleukin-1B gene loci-511C/T(rs16944),+3954C/T(rs1143634),and-31C/T(rs1143627)were detected by polymerase chain reaction and restriction fragment length polymorphism.The correlation between the probability of linkage disequilibrium and haplotypes and the risk of primary frozen shoulder disease was compared and analyzed. RESULTS AND CONCLUSION:Unconditional Logistic regression analysis showed that the proportion of CT genotypes at rs1143634 and rs1143627 sites increased significantly in the primary frozen shoulder.Linkage disequilibrium analysis showed that rs16944,rs1143634 and rs1143627 tended to be balanced in the control group(D'value<0.1),while there was a certain degree of linkage disequilibrium at rs1143627 and rs1143634 sites in the primary frozen shoulder group(D'value=0.595).Haplotype TTT increased the risk of primary frozen shoulder by 6.66 times compared with CCT type(TTT,OR=6.66,95%CI=1.59-27.88,P=0.009 7).To conclude,there is a certain degree of linkage disequilibrium between interleukin-1B gene loci rs1143627and rs1143634 in patients with primary frozen shoulder;haplotype TTT formed by these three gene loci may increase the risk of developing primary frozen shoulder.
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Objective:To analyze the positive detection rate, main genotypes of β-thalassemia in western region of Guangxi Zhuang Autonomous Region (referred to as Guangxi).Methods:Retrospective analysis of 26 189 individuals who underwent gene testing for thalassemia at the Affiliated Hospital of Youjiang Medical University for Nationalities from January 2013 to December 2019. Using the crossing breakpoint PCR (Gap-PCR) and reverse dot blot (RDB) techniques to detect Chinese common type of 7 kinds of α-thalassemia and 17 kinds of β-thalassemia genotypes, high-throughput sequencing(Sanger) was performed for suspected rare β-thalassemia. Gap-PCR was used for suspected deletion β-thalassemia types.Results:β-thalassemia was diagnosed in 4 495 (17.16%) of 26 189 samples. A total of 6 177 alleles of 20 types of β-thalassemia were detected, mainly CD17 (2 712 cases, 43.90%) and CD41-42 (2 240 cases, 36.26%), including 7 rare alleles: Gγ +( Aγδβ) 0, SEA-HPFH, Hb New York, Hb G-Taipei, Hb Hezhou, Hb G-Coushatta and IVS-Ⅱ-81. There were 3 903 case (86.83%) heterozygous, 273 case (6.07%) double heterozygous, and 319 case (7.10%) homozygous among 4 495 β-thalassaemia subjects. A total of 48 genotypes were detected. The two most common genotypes were CD17/β N (1 890 cases, 42.05%) and CD41-42/β N (1 212 cases, 26.96%), accounted for 69.01% (3 102/4 495). Seven rare genotypes were detected: Gγ +( Aγδβ) 0/β N in 3 cases, Hb New York/β N in 3 cases, Hb G-Taipei/β N in 2 cases, SEA-HPFH/β N, Hb Hezhou/β N, Hb G-Coushatta/β N and IVS-Ⅱ-81/β N in 1 case each. A total of 1 041 cases (3.97%, 1 041/26 189) of 116 types of αβ-thalassemia were detected, mainly -- SEA/αα composite CD17/β N (144 cases, 13.83%), followed by -α 3.7/αα composite CD17/β N (112 cases, 10.76%). Conclusions:Western region of Guangxi is a high prevalence area of β-thalassemia, CD17/β N and CD41-42/β N are the main genotypes. The variation spectrum of β-thalassemia is complex and diverse, with rich genotype.
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Objective @#To construct hepatocyte-specific silence information regulator 3 ( Sirt3 ) gene knockout (Sirt3Δhep ) mice by Cre-loxP technique , and to provide an important animal model for further studying the biological function of the hepatocyte Sirt3 gene in diseases . @*Methods @#LoxP-labeled Sirt3flox/flox mice were mated with Alb-Cre homozygous (Alb-Cre + / + ) mice , and the F1 generation Sirt3flox/ - /Alb-Cre + / - mice were then mated with Sirt3flox/flox mice , and the F2 genotype of Sirt3flox/flox/Alb-Cre + / - mice were the Sirt3Δhep mice constructed in this ex- periment. Sirt3flox/flox/Alb-Cre - / - (Sirt3flox/flox ) mice were the control mice . Mouse tail genome DNA was extracted and PCR was used to identify the genotypes of the offspring mice . Immunofluorescence was used to detect Sirt3 ex- pression in mouse hepatocytes . Primary hepatocytes and tissue proteins of Sirt3Δhep mice were extracted , and the ex- pression of Sirt3 in mouse hepatocytes and other tissues was verified by Western blot. HE staining was used to ob- serve mice ′s liver , heart , spleen , and lung tissue structure . @*Results @#Sirt3Δhep mice were successfully identified .Immunofluorescence and Western blot results demonstrated a significant decrease in the expression of Sirt3 in the hepatocytes of these mice compared to the control group ( P < 0. 01) . At the same time , there was no significant difference in the expression of Sirt3 in the heart , spleen , kidney , and lung tissues of Sirt3Δhep mice compared with the control group (P > 0. 05) . The results of HE staining showed that the histological characteristics of the liver , heart , spleen , lungs , kidneys , and other major organs of Sirt3Δhep mice were not significantly different from those of the control group mice . @*Conclusion @#Hepatocyte-specific Sirt3 gene knockout mice are successfully constructed , which provides an animal model to explore further the role and molecular mechanism of the hepatocyte Sirt3 gene in diseases .
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Objective:To investigate the relation between rs2298771 genotype in voltage-gated sodium channels 1A ( SCN1A) polymorphism and antiepileptic drug (AED) response in children with epilepsy. Methods:Sixty-two children with epilepsy admitted to Department of Neurology, Zhangjiakou First Hospital from June 2022 to December 2023 were divided into AED response group and AED resistance group ( n=31) according to their response to AED. In addition, 31 children with pharyngitis or mild gastroenteritis admitted to Department of Pediatrics at the same period were selected as control group. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to analyze the rs2298771 genotype in SCN1A polymorphism, and differences in rs2298771 genotype and allele in SCN1A polymorphism were compared among the 3 groups. Relation between rs2298771 genotype in SCN1A polymorphism and AED response was analyzed. Multivariate Logistic regression was used to analyze the influencing factors for AED response in children with epilepsy. Results:(1) Significant differences in type of first seizure and AEDs were noted between AED response group and AED resistance group ( P<0.05); compared with the AED resistance group, the AED response group had significantly lower seizure frequency, significantly longer duration after last seizure, and statistically higher proportions of children with normal EEG or with one kind of AED ( P?0.05). (2) Compared with the control group and AED response group, the AED resistance group had significantly higher rs2298771 GC genotype and G allele, and statistically lower rs2298771 AA genotype and A allele in SCN1A polymorphism ( P?0.05). (3) In the AED response group, rs2298771 AA and AG genotype in SCN1A polymorphism were positively correlated with levetiracetam ( P?0.05); in AED resistance group, rs2298771 AG genotype in SCN1A polymorphism was positively correlated with topiramate and valproic acid ( P<0.05). (4) Multivariate Logistic regression analysis showed that duration after last seizure ( OR=3.249, 95% CI=1.097-9.621, P=0.033), rs2298771 genotype in SCN1A polymorphism ( OR=9.660, 95% CI=4.680-19.970, P=0.011) and seizure frequency ( OR=0.160, 95% CI=0.032-0.804, P=0.026) were independent influencing factors for AED response in children with epilepsy. Conclusion:Epilepsy children with shorter duration after last seizure, rs2298771 GG genotype in SCN1A polymorphism, and high seizure frequency are susceptible to AED resistance; especially, AG genotype is correlated with topiramate and valproic acid.
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Objective To investigate the distribution of the thalassemia genotypes and the characteristics of blood cell parameters in Changshou District,Chongqing.Methods Totally 4126 samples sent to our hospital were studied from June 2018 to March 2023.All samples were detected for thalassemia genotype and blood cells.The parameters of blood cells:redblood cell(RBC),hemoglobin(Hb),mean corpuscular volume(MCV),mean corpuscular hemoglobin(MCH),mean corpuscular hemoglobin concentration(MCHC),red blood cell distribution width CV(RDW-CV),red blood cell distribution width SD(RDW-SD)were detected.Gap polymerase chain reaction(Gap-PCR)combined with reverse dot blot hybridization were used to detect alpha and beta thalassemia genotype.The rate and distribution characteristics of thalassemia gene in Changshou district were analyzed.Results Among 4126 samples,408 cases of α and β thalassemia were detected,accounting for 9.89%.Among these,there were 255 α-thalassemia cases.-α3.7/αα was the most common genotype.Two cases of--αSEA/-α3.7 and one cases of--SEA/HKαα were also detected.There were 153 cases of β-thalassemia and CD17 accounted for the highest proportion.The date of MCV,MCH,MCHC in-α3.7/αα,--SEA/αα,-α4.2/αα and ααCS/αα groups was significantly difference compared with control group(P<0.05).Parameters of MCV and MCH in CD17,CD41-42 and Ivs-2-654 groups were lower than those in control group(P<0.05),while RBC,RDW-CV and RDW-SD were higher than those in control group,the difference was statistically significant.Conclusion The most common genotype in thalassemia were-α3.7/αα,--SEA/αα,-α4.2/αα,CD17,CD41-42 and Ivs-2-654 in Changshou District,Chongqing.The parameters of MCV,MCHC,MCH,Hb,RBC,RDW-CV and RDW-SD have important clinical significance for the screening of thalassemia.
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ObjectiveTo investigate the pathogenic spectrum and molecular characteristics of infectious diarrhea among children in Putuo District of Shanghai from 2018 to 2023， and to provide scientific basis for the prevention and control of infectious diarrhea in children. MethodsFecal samples from the cases visited sentinel hospitals for children’s diarrheal disease in Putuo District， Shanghai， were collected from January 2018 to December 2023. A total of 11 species of bacteria were isolated and cultured， and 5 species of viruses were detected by real-time fluorescent polymerase chain reaction （PCR）. The molecular typing of some positive strains was analyzed by the standard pulsed-field gel electrophoresis （PFGE） method. The polymerase-capsid protein linkage region of some norovirus-positive samples was amplified by reverse transcription PCR， and was sequenced and analyzed by bioinformatics software. The Chi-square test and Fisher’s exact probability test were used to compare the pathogen-positive rates in 2018‒2019 and 2020‒2023. ResultsOf the 707 cases of children with infectious diarrhea， the total positive rate was 47.67%， with a single bacterial positivity rate of 16.27%， a single viral positivity rate of 22.63%， and a mixed positivity rate of 8.77%， respectively. The dominant pathogens were rotavirus （10.75%）， norovirus （10.33%）， enteropathogenic Escherichia coli （8.06%）， Salmonella （6.36%）， enteroaggregative Escherichia coli （5.52%）， and Campylobacter （5.23%）. Bacterial infections were predominant in summer and fall， and viral infections were predominant in winter and spring. The total positive rate decreased in 2020‒2023 compared with that of 2018‒2019 （χ2=5.753，P<0.05）. Thirty-seven strains of Salmonella， 81 strains of diarrheagenic Escherichia coli， and 19 strains of Campylobacter were completed for the molecular typing analysis by PFGE， which were classified into 28， 80 and 18 banding types， respectively， with a wide range of banding similarity. Nineteen copies of norovirus GⅡ group gene sequences were analyzed and classified into 5 genotypes， which were mainly GⅡ.Pe-GⅡ.4 and GⅡ.P16-GⅡ.2 types. ConclusionRotavirus， norovirus， diarrheagenic Escherichia coli， Salmonella， and Campylobacter are the dominant pathogens of infectious diarrhea in children in Putuo District of Shanghai. The pathogen spectrum shows a trend of seasonal epidemic characteristics， with a diversity of molecular characteristics of some pathogens. Surveillance and monitoring on molecular characteristics of the pathogens of infectious diarrhea in children should be strengthened in different seasons， so as to provide a laboratory basis for the prevention and control of infectious diarrhea.
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Objective To analyze the genetic characteristics of B19 parvovirus in a human parvovirus outbreak in Hubei Province in 2019, and to provide scientific basis for the prevention and control of parvovirus outbreaks. Methods Among of the 17 serum specimens and 20 throat swab specimens from a parvovirus B19 outbreak were collected in Hubei Province in 2019. The nucleic acid-positive specimens were identified by fluorescence quantitative RT-PCR. The specific sequences of NS1-VP1u (1157 bp) of B19 positive specimens were amplified by nested PCR to determine B19 genotype. Results The genotype of B19 virus in 17 patients were subgenotype 1a, and the nucleotide homology of subgenotype 1a was 99.90% - 100%. The B19 subgenotype 1a was located in the same small branch as the Chinese Beijing strain KR819772, the Chinese Beijing strain KR819773 and the Chinese Hangzhou strain KT310174, and the distance was the closest. Conclusion The B19 virus in a human parvovirus outbreak in Hubei Province in 2019 belongs to subgenotype 1a.
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【Objective】 To correctly identify the blood group of ABO and study its molecular biological characteristics. 【Methods】 Blood samples from blood donors with discrepancies in forward and reverse typing using the microplate method were subjected to both saline tube agglutination test for serological identification and polymerase chain reaction-sequence specific primers (PCR-SSP) for genotyping. Additionally, direct sequencing of exons 1 to 7 of the ABO gene was performed on some donor samples to analyze their blood phenotype, genotype and gene sequence. 【Results】 For 256 samples showing discrepancy between forward and reverse typing in microwell method, 119 were identified as normal ABO blood types, 90 were weakened ABO antibodies and 47 were ABO subtypes by serology tube test. According to the PCR-SSP genotyping test, 233 of 256 (91.02%) were consistent with serological phenotype and genotype, 17 of 256 (6.64%) were inconsistent, and 6 samples can′t read genotype based on the kit result typing table.A total of 17 genotypes were identified in 250 samples as AO1 in 56, AO2 in 58, AA in 50, BO1 in 31, BO2 in 17, BB in 8, O1O1 in 2, O1O2 in 7, AB in 13, AO4 in 1, A205O2 in 1, A205A in 1, A201A in 1, O1O4 in 1, O2O2 in 1, A201B in 1 and A205B in 1. Sequencing of exons 1 to 7 of the ABO gene was carried out in 78 samples, and 29 ABO alleles were detected, seven of which were common alleles (*A101, *A102, *A104, *B101, *O01, *O02, *O04), 22 of which were rare alleles (*A201, *A205, *Ax01, *Ax03, *Ax13, *Ax19, *Ax22, *Ael10, *B305, *Bel03, *Bel06/*Bx02, *Bw07, *Bw12, *Bw17, *Bw37, *O05, *O26, *O61, *B(A)04, *B(A)07, *cisAB01 and *cisAB01var). In addition, six rare allele mutation sites were identified (c.101A>G; c. 103_106delG; c. 146_147insGC; c. 259G>T; c. 322C>T; c. 932T>C). 【Conclusion】 The identification of ambiguous ABO blood group requires the combination of serological testing and molecular biological examination to correctly identify the blood type and ensure the safety of clinical blood transfusion.
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Objective:To identify pathogenic genes in 3 cases of piebaldism, and to explore the genotype-phenotype relationships in piebaldism.Methods:Clinical data were collected from 3 patients with piebaldism and their parents at the Department of Dermatology, Henan Provincial People′s Hospital from January 2019 to December 2021. Peripheral blood samples were obtained from them and 100 unrelated healthy controls, and DNA was extracted. Whole-exome sequencing technology was used to screen genetic variation sites, and then Sanger sequencing was performed for verification. The deleteriousness of genetic variants was evaluated by using pathogenicity analysis software tools.Results:Case 1: a 23-year-old male patient presented with white patches on the forehead, chest, and abdomen for 23 years, and his parents had no similar symptoms; case 2: a 1-year- and 5-month-old male infant presented with white patches on the forehead and abdomen for 1 year, and his parents had no similar symptoms; case 3: a 6-year-old male child presented with white patches on the forehead and limbs for 6 years, and his parents had no similar clinical manifestations. Genetic testing showed that a missense mutation c.2033T>C (p.L678P) in exon 14 of the KIT gene, a splice site mutation c.2485-1G>C in exon 18 of the KIT gene, and a heterozygous missense mutation c.2346C>G (p.F782L) in exon 16 of the KIT gene were identified in the case 1, 2, 3 respectively, but no above mutations were identified in the patients′ parents or 100 unrelated healthy controls. The 3 genetic variants were all novel pathogenic mutations, and all were deleterious mutations.Conclusions:Three novel pathogenic mutations in the KIT gene were identified in the 3 cases of piebaldism, namely c.2033T>C (p.L678P), c.2485-1G>C, and c.2346C>G (p.F782L). It was further verified that the severity of piebaldism was closely related to the type and location of KIT gene mutations.
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Objective:To analyze the clinical phenotypes and TSC1/TSC2 gene variations in 52 children with tuberous sclerosis complex. Methods:The clinical data of 59 children with tuberous sclerosis complex hospitalized in Linyi People′s Hospital between January 2017 and October 2022 were collected. The analysis of TSC1 and TSC2 gene variations on main family members was performed, and then bioinformatics analysis followed. The positive children were divided into TSC1 gene group and TSC2 gene group, and the difference of clinical characteristics between the two groups was analyzed. Results:Among 59 children, 52 cases were detected TSC1/ TSC2 gene variations (17 cases in the TSC1 gene group and 35 cases in the TSC2 gene group). Of the 52 children, 28 (53.8%) were male, 24 were female (46.2%); 17 (32.7%) were familial cases (10 with TSC1 gene variations and 7 with TSC2 gene variations), 35 (67.3%) were sporadic cases; 46 (88.5%) had hypomelanotic macules, 13 (25.0%) had facial angiofibromas, 5 (9.6%) had shagreen patches, 49 (94.2%) had subependymal nodules/calcifications, 47 (90.4%) had cortical nodules, 2 (3.8%) had subependymal giant cell astrocytomas, 39 (75.0%) had intellectual/developmental disabilities, 49 (94.2%) had epileptic seizures, 8 (15.4%) had cardiac rhabdomyomas, 9 (17.3%) had renal angiomyolipomas, and 4 (7.7%) had retinal hamartomas. Of the 52 children, 49 variations were detected, including 4 large fragment deletion/duplication variations, and 45 point variations; 41 pathogenic variations, 7 likely pathogenic variations, and 1 variation of uncertain significance. In this study, 16 point mutations and 1 large fragment duplication mutation which had not been reported at home and abroad, and 3 high-frequency mutation sites (p.Arg692 *, p.Arg228 *, and p.Arg1200Try) were found. There was a statistically significant difference in the proportion of familial cases [10/17 vs 7/35(20%), χ2=7.838, P=0.005], median onset age of epilepsy [38.0(0.5-134.0) months vs 8.0(0.1-63.0) months, Z=3.506 , P<0.001] and the incidence of developmental retardation/intellectual impairment [8/17 vs 31/35(88.6%), χadj2=8.423, P=0.004] between the TSC1 gene and TSC2 gene groups. Conclusions:Tuberous sclerosis compiex has widespread phenotypes, can affect every body system, especially the skin and nervous system. The pathogenic gene is TSC1/ TSC2. The TSC1 gene group has more familial cases. The TSC2 gene group has an earlier onset age of epilepsy and a higher incidence of developmental retardation/intellectual impairment. In this study, 16 novel point mutations, 1 novel large fragment duplication mutation, and 3 hotspot mutations were identified, expanding the gene variation spectrum of tuberous sclerosis complex.
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Objective:To analyze and summarize the clinical, genotypic and pathological characteristics of children with PAX2 gene mutation in China, and to provide information for the monitoring, treatment and prognosis of the disease. Methods:It was a case series analysis study. The clinical data of children with PAX2 gene mutation in Pediatric Nephrology Department, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from January 2014 to December 2022 were collected, and peripheral blood gene DNA was extracted and sequenced for whole exome sequencing. The clinical, pathological and genotypic characteristics of PAX2 gene variation of children in China were summarized by searching PubMed, Medline, China National Knowledge Infrastructure and Wanfang database and compared with the cases in this single center. Results:Among the 13 children with PAX2 gene mutation, there were 9 males and 4 females, 12 patients with abnormal urine tests, 7 patients with small kidney volume by imaging examination, and 5 patients with renal cysts. The clinical phenotypes were congenital renal and urinary tract malformations in 8 cases, renal coloboma syndrome in 1 case, and hematuria or proteinuria in 3 cases. Five patients underwent renal biopsies, showing focal segmental glomerulosclerosis and C3 glomerulopathy in 1 case, focal segmental glomerulosclerosis in 1 case, thin basement membrane lesion in 1 case, and IgA nephropathy in 2 cases. The genetic testing in 13 children showed 9 de novo mutations and 4 new mutations of c.321G>A, c.213-8C>G, c.63C>A and c.449C>T. There were 2 cases of 76dupG (p.V26Gfs*28) mutant. A total of 51 Chinese children with PAX2 gene mutation were found in the literature search. There were 32 males and 19 females, 8 cases with small kidney volume and 12 cases with renal cysts. The clinical phenotypes were congenital anomalies of kidney and urinary tract in 28 cases, renal coloboma syndrome in 17 cases, and hematuria or proteinuria in 6 cases. Seven patients underwent renal biopsies, including 2 cases with focal segmental glomerulosclerosis, 1 case with minimal lesion, 1 case with mesangial proliferative glomerulonephritis, 1 case with IgA nephropathy, 1 case with membranous nephropathy and a case with focal proliferative sclerosing purpura nephritis combined with glomerular hypertrophy. Thirty-four cases were de novo mutations, and 12 mutations were from the father or mother. The father or mother of 5 children had no clinical manifestations, with normal renal function. There were 11 cases of 76dupG (p.V26Gfs*28) mutant. Conclusions:The clinical phenotypes and genotypes of PAX2 gene variation in Chinese children are diverse. The most common clinical phenotype of PAX2 gene variation is congenital anomalies of kidney and urinary tract. c.76dupG (p.V26Gfs*28) is the most common of PAX2 gene variant.
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Objective:To analyze the differentially expressed genes of human respiratory syncytial virus (RSV) subtype A genotype ON1, a predominant genotype in Beijing, after infecting A549 cells using transcriptomic sequencing, and provide potential targets for RSV prevention and treatment.Methods:A local strain (61397-ON1) identified by whole-genome sequencing as ON1 genotype of RSV subtype A was selected to infect A549 cells. Total mRNA was extracted, and the differentially expressed genes in infected and uninfected A549 cells were screened by transcriptomic sequencing. GO analysis and KEGG pathway analysis were performed. Besides, six genes with differential expression ratio greater than two times were randomly selected for qRT-PCR verification.Results:There were 1 632 differentially expressed genes between infected and uninfected A549 cells, of which 807 genes were up-regulated and 825 genes were down-regulated. The differentially expressed genes were mainly involved in immune response-related biological processes such as cytokine response and positive regulation of MAPK cascades, and were enriched in MAPK signaling pathway, NOD-like receptor signaling pathway, p53 signaling pathway, TNF signaling pathway, IL-17 signaling pathway and NF-κB signaling pathway. The results of qRT-PCR for six differentially expressed genes were consistent with the trend of transcriptome data.Conclusions:The differentially expressed genes of RSV A subtype ON1 genotype after infecting A549 cells are mainly involved in cytokine response and immune-related signaling pathways. This study provides basic data for further study of the molecular mechanism of RSV infection and the development of prevention and treatment strategies.