ABSTRACTObjectiveThe primary aim of this research was to establish normative values for nuchal translucency (NT) thickness with crown‐rump length (CRL) ranging from 45 to 80 mm in a representative sample of the Chinese population.MethodsThe distributions of NT were derived for 24,892 unaffected fetuses with a CRL between 45 and 80 mm. The relationship between fetal NT thickness and CRL was assessed using linear regression analysis.ResultsThe regression equation describing the relationship between NT thickness and CRL was: NT thickness = 0.020 × CRL + 0.218, (R2 = 0.112, p < 0.001). The 50th percentile ranged from 1.12 to 1.82 mm and the 95th percentile ranged from 1.89 to 2.75 mm across 45–80 mm. The 95th percentile of NT MoM was 1.5375 over the CRL range of 45–80 mm.ConclusionsNormative values for NT thickness were established based on CRL measurements in a sample from the Chinese population. Due to physiological and ethnic variations in NT measurements, employing local CRL‐dependent cut‐offs for NT may offer advantages in anomaly screening during the first trimester of pregnancy compared to fixed cut‐off values.

Genotype-phenotype correlation and potential genetic risk in the compound heterozygosity for unstable hemoglobins (UHbs) and α0-thalassemia were discussed. Capillary electrophoresis and gene sequencing helped to establish the diagnosis. Hematological analysis showed the following findings: MCV 80.6 fL, MCH 27 pg, HGB 133 g/L, RBC 4.93 × 1012/L, Hb A: 94%, Hb X: 3.6% (zone 12) and Hb A2: 2.4%. DNA analysis revealed the patient was a Hb Pontoise carrier (HBA1: c.191C > A). Hb Pontoise resulted from an GCC > GAC substitution at codon 63 of the HBA1 genes, but carriers were usually asymptomatic or with only borderline hematological abnormalities. Due to mild instability of Hb Pontoise, its diagnosis relied on genetic diagnosis. Considering the high frequency of thalassemia in South China, accurate genotyping and appropriate genetic counseling should be performed for unstable hemoglobin carriers.

ABSTRACT Background Hb Chapel Hill [Alpha2 74(EF3) Asp > Gly] results from an GAC > GGC substitution at codon 74 of the HBA1 or HBA2 genes. Hb Chapel Hill has not been reported since 1986. Methods A heterozygous mutation, HBA2: c.224A > G, was identified in the proband, her father and sister. We compared the haematological and clinical data of this family with the data reported in the limited number of individuals. Results Having excluded iron deficiency, the Hb Chapel Hill was asymptomatic in heterozygous state. The cases presented here characterize cases in new techniques including capillary electrophoresis (CE). Two aberrant peaks were identified by CE, a major peak migrating in the zone 7 that correspond to Hb Chapel Hill (αChapel Hill 2β2) and a minor peak migrating in the zone 1 that correspond to Hb Chapel Hill2 (αChapel Hill 2δ2). Focusing on the variant expression, the Hb Chapel Hill plus Hb A2 variant were around 18.9–20.6% of total Hb in three members. Conclusion This data will be useful for providing up-to-date and high quality information on the Hb Chapel Hill.

Background: Genital Chlamydia trachomatis (CT) is one of the most common agents of sexually transmitted infections and can cause severe disorders. This study aimed to analyse the genetic and clinical characteristics of genital CT infection among women in Guangzhou, China. Methods: From September 2020 to August 2021, a total of 8955 female patients were enrolled in this study. The presence of genital CT was detected by real-time PCR, and 273 positive samples were randomly selected for further genetic and clinical characteristics analysis. Results: The positive rate of genital CT infection was 7.5% (670/8955), with the highest rate in women aged 21-30 years. A total of 8 genotypes were identified: D-H, J, K, and recombinant genotype Ba/D. The predominant genotype was J (n = 78, 28.6%), followed by E (n = 63, 23.1%), F (n = 48, 17.6%), and D (n = 38, 13.9%). Abnormal vaginal discharge (n = 165, 61.8%), cervical columnar epithelial ectopy (n = 124, 46.4%), vaginal itching (n = 77, 28.8%), and lower abdominal pain (n = 61, 22.8%) were the predominant symptoms. Additionally, genotype G infection exhibited a significantly higher rate of abnormal vaginal discharge (P = 0.03) and genotype D infection exhibited a higher white blood cell count (P = 0.01) than the other genotypes. Phylogenetic analysis revealed a total of 20 variants with 25 mutation positions and the H2 variant in four patients was first discovered in our study. Conclusions: Genotypes J, E, F, and D were the major genotypes of genital CT in Guangzhou, and they manifested as abnormal vaginal discharge, cervical columnar epithelial ectopy, vaginal itching, and lower abdominal pain. The present study provides guidance for future integrated interventions to reduce the burden of genital CT infection and accelerate the development of vaccines.

双胎血清学筛查由于需要考虑合子性和绒毛膜性,唐氏综合征阳性病例的有限和多数研究依靠统计建模的局限性等原因,其筛查效率和价值的研究较为复杂.本文从双胎妊娠与非整倍体筛查的相关因素、双胎与单胎之间血清学水平的差异、筛查方案中涉及的颈项透明层厚度、血清学筛查方案在双胎妊娠中的研究、双胎之一消失、双胎血清学筛查方案的选择等方面,探讨基于唐氏综合征血清学筛查的双胎产前筛查在临床中的应用价值,以期为评估双胎唐氏综合征风险提供理论依据.

Genogroup II genotype 4 (GII.4) norovirus causes acute gastroenteritis in children, and its infection is more severe than that of other genotypes. Early and precise detection and treatment are critical for controlling its spread and reducing the severity of infection. In this study, a rapid and efficient isothermal assay for the GII.4 norovirus detection (GII.4-CRISPR detection) was developed based on the CRISPR/Cas13a system. The assay can be applied without expensive instrumentation, and the results can be read via both fluorescence and lateral flow strip (LFS). The analytical sensitivity of this assay was 5 copies/reaction, and there was no cross-reaction with other genotypes of norovirus or other clinically common pathogens. There was a coincidence rate of 100% between our assay and commercial quantitative polymerase chain reaction. GII.4-CRISPR detection improves upon the shortcomings of some previously established molecular methods of detection, particularly with regard to accessibility. It provides an alternative tool for outbreak control and early diagnosis of GII.4 norovirus infection.

Hand, foot, and mouth disease (HFMD) is a common infectious disease affecting mainly children under 5 years of age. Coxsackievirus A6 (CVA-6), a major causative pathogen of HFMD, has caused outbreaks in recent years. Currently, no effective vaccine or antiviral treatments are available. In this study, one-step reverse-transcription recombinase polymerase amplification (RT-RPA), combined with a disposable lateral flow strip (LFS) assay, was developed to detect CVA-6. This assay can be performed in less than 35 min at 37°C without expensive instruments, and the result can be observed directly with the naked eye. The sensitivity of the RT-RPA-LFS was 10 copies per reaction, which was comparable to that of the conventional real-time quantitative polymerase chain reaction (qPCR) assays. Moreover, the assay specificity was 100%. The clinical performance of the RT-RPA-LFS assay was evaluated using 142 clinical samples, and the coincidence rate between RT-RPA-LFS and qPCR was 100%. Therefore, our RT-RPA-LFS assay provides a simple and rapid approach for point-of-care CVA-6 diagnosis.

目的 分析广州市同德围地区女性生殖道支原体感染情况及耐药现状,并观察中西医结合治疗支原体感染的疗效,为临床提供参考依据.方法 选择2018年1月—2019年12月于广州医科大学附属中医医院同德围院区妇科门诊就诊的736例女性生殖道感染患者作为研究对象,采用支原体鉴定及药敏试剂盒对所有患者生殖道分泌物进行支原体培养及药敏试验;选择相应抗菌药物并针对病因采取清热解毒、健脾祛湿的中医方法加以中药汤剂完带汤治疗.结果 736例女性患者中检出泌尿生殖道支原体阳性77例,检出率为10.46％,其中解脲脲原体(Uu)阳性67例(占87.01％),人型支原体(Mh)阳性1例(占1.30％),Uu合并Mh阳性9例(占11.69％).感染人群中31～40岁年龄段支原体阳性者所占比例最高〔44.16％(34/77)〕.药敏试验结果显示,多数支原体感染患者对美满霉素、交沙霉素和克拉霉素敏感性较高.治疗后,同德围地区女性生殖道支原体感染的复发率为0.结论 同德围地区女性生殖道支原体感染以Uu为主,根据药敏试验结果合理使用抗菌药物,并加以中药辅助治疗效果更佳.

β-Globin gene mutations reduce or terminate the production of beta globin chains, of which approximately 10% are large deletions within the β-globin gene cluster. Because gene deletion leads to loss of heterozygosity at single nucleotide polymorphism (SNP), a novel method for detecting β-globin gene cluster deletions based on SNP heterozygosity analysis was established in this study. The location range of SNPs was selected according to the breakpoint of β-globin gene cluster deletions. SNPs were screened using bioinformatics analysis and population sequencing data. A novel method which enables genotyping of multiplex SNPs based on tetra-primer ARMS-PCR was designed and optimized. Forty clinical samples were tested in parallel by this method and MLPA to verify the performance of this method for detecting β-globin gene cluster deletion. Six informative SNPs were obtained, achieving heterozygote coverage of 93.3% in normal individuals. Genotyping of six SNPs were successfully integrated into two multiplex tetra-primer ARMS-PCR reactions. The sensitivity, specificity, positive predictive value and negative predictive value of the method for detecting β-globin gene cluster deletion were 100%, 96.30%, 92.86%, and 100%, respectively. This is a simple, cost-effective and novel method for detecting β-globin gene cluster deletions, which may be suitable for use in combination with MLPA for thalassemia molecular testing.

Background Hand, foot, and mouth disease (HFMD) is a common infectious disease occurring in children under 5 years of age worldwide, and Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CVA-16) are identified as the predominant pathogens. In recent years, Coxsackievirus A6 (CVA-6) and Coxsackievirus A10 (CVA-10) have played more and more important role in a series of HFMD outbreaks. This study aimed to understand the epidemic characteristics associated with HFMD outbreak in Guangzhou, 2018. Methods The clinical and laboratory data of 1220 enterovirus-associated HFMD patients in 2018 were analysed in this study. Molecular diagnostic methods were performed to identify its serotypes. Phylogenetic analyses were depicted based on the complete VP1 gene. Results There were 21 enterovirus serotypes detected in Guangzhou in 2018. Three serotypes of enterovirus, CVA-6 (364/1220, 29.8%), CVA-10 (305/1220, 25.0%), and CVA-16 (397/1220, 32.5%), were identified as the causative pathogens and accounted for 87.3% among all 1220 HFMD patients. In different seasons, CVA-6 was the predominant pathogen of HFMD during autumn, and CVA-10 as well as CVA-16 were more prevalent in summer. Patients infected by CVA-6, CVA-10 or CVA-16 showed similar clinical features and laboratory characteristics, and the ratios of severe HFMD were 5.8, 5.9, and 1.5% in the three serotypes. Phylogenetic analyses of VP1 sequences showed that the CVA-6, CVA-10, and CVA-16 sequences belonged to the sub-genogroup E2, genogroup E, and genogroup B1, respectively. Conclusions CVA-6, CVA-10, and CVA-16 were the predominant and co-circulated serotypes in Guangzhou China, 2018, which should be the new target for prevention and control of HFMD. Our findings provide useful information for diagnosis, treatment, and prevention of HFMD.

目的 报道我院2014年下半年收治新生儿肠道病毒(EV)感染6例,探讨新生儿肠道病毒感染的临床特点、诊治方法及危险因素控制.方法 2014年7月至12月我院NICU收治的新生儿感染病例,取脑脊液(CSF)行EV通用序列RT-PCR检测判别是否EV感染,阳性病例进一步对EV衣壳蛋白VP1编码基因进行部分测序以确定血清型.查阅EV感染阳性病例的病案资料,作回顾性分析.结果 研究期间共收治108例新生儿感染病例,CSF检出EV阳性6例(阳性率5.5％),其中3例经VP1基因部分测序成功定型为柯萨奇病毒B组5型(CVB5),其余3例无法定型.6例EV感染新生儿均出现黄疸,其中5例发热>39℃,2例喂养困难,1例有呕吐,2例有反应差等症状.实验室检查中,6例血培养均未见细菌生长;C反应蛋白增高5例;心肌酶CK-MB增高2例;CSF检查见蛋白质增高5例,白细胞增高3例,潘迪氏试验阳性3例.6例明确EV感染诊断前均使用抗生素,效果不佳.3例CVB5阳性患儿母亲均自诉分娩前有发热症状,3例未定血清型EV感染患儿中,2例在出生后母婴同室期间出现39℃以上的发热.结论 新生儿EV感染临床症状多为发热,与其他病原感染难以鉴别.一般生化指标对EV辅助鉴别诊断无特异性.对于新生儿出现发热症状,有必要及时进行EV RT-PCR检测以排查感染.本报道6例新生儿EV感染中血清型CVB5占一半,提示CVB5可能是2014下半年广东地区人群中引起新生儿EV感染的主要血清型,应引起产房和新生儿病房重视,对其严密监控.对新生儿EV感染,临床上应严谨地控制抗生素使用.EV感染危险因素的控制须重视新生儿照护者(包括母亲、护理人员等)的EV可疑感染排查,尤其是隐性感染者.孕妇在分娩前或产时出现发热症状时,应采取合适的预防措施规避母婴同室致新生儿EV感染的风险.

孕 11～13+6周测量胎儿颈项透明层厚度(nuchal translucency,NT)是早孕期筛查唐氏综合征的重要指标.NT联合血清学筛查策略,提高了唐氏综合征患儿的检出率,降低了假阳性率.NT增厚还与先天性心脏病、淋巴系统发育不良、宫内生长受限、其他结构异常及多种遗传综合征等有明显相关性,风险大小与 NT增厚程度呈正相关.本文从 NT增厚的病因学、NT增厚的范围、NT增厚与非整倍体、结构畸形、遗传学综合征的关系等方面探讨 NT在产前筛查中的应用价值,以期为评估胎儿 NT增厚风险提供理论依据.

BACKGROUND:Coxsackievirus A6 (CA6) infection may lead to high hand-foot-and-mouth disease (HFMD) aggregation in children. We aimed to analyze the clinical and phylogenetic features of severe CA6-associated pediatric HFMD.METHODS:The clinical and laboratory features of 206 and 55 children with mild and severe CA6-associated HFMD, respectively, were summarized. The CA6 phylogenetic tree was depicted using combinatorial analysis of the VP1-encoding regions and neighbor-joining method.RESULTS:CA6 was the major pathogen both in mild and severe HFMD in 2017. Most CA6-associated severe HFMD cases showed high fever, skin rash, age younger than 36 months, and elevated white blood cell and C-reactive protein levels, and there were no significant differences compared to the mild cases (p > 0.05). The severe cases were significantly more likely (p < 0.05) to show male sex, long fever duration, decreased oral intake, tonsil enlargement, diarrhea, vomiting, elevated levels of creatine kinase and blood glucose, and positive fecal occult-blood test results. Severe complications included aseptic meningitis (29/55, 52.7%) and pulmonary edema (6/55, 10.9%) were observed in severe cases. Furthermore, genetic analyses showed all CA6 isolates belonged to lineage E2, and two amino acid changes of V174I and T283A in VP1 may be associated with the severity of HFMD.CONCLUSIONS:CA6 has become a major cause of HFMD with severe systemic disorders. V174I and T283A of VP1 may be associated with the severity of CA6 infection. These findings could raise awareness of the clinical importance of CA6 infection among practitioners.

目的 探讨孕早中期阶段性序贯筛查唐氏综合征血清学筛查的临床效果.方法 回顾性分析2013年1月至2015年12月在广东省妇幼保健院进行唐氏综合征血清学筛查的病例.共对146 190例标本进行了孕早期(9～13+6周)唐氏综合征血清学筛查.136 471例早期筛查为阴性,其中33 587例进行了孕早中期阶段性序贯筛查的中期筛查.结果 146 190例早期筛查标本中,筛查阳性病例为9719例,其中确诊阳性85例,确诊阴性9634例;筛查阴性病例为136 471例,其中确诊阳性数为11例,确诊阴性数为136 460例.早期筛查方法的灵敏度为88.54％,假阳性率为6.59％.在上述早期筛查的基础上,其中33 587例进行了孕早中期阶段性序贯筛查的中期筛查,中期筛查阳性病例为640例,其中确诊阳性6例,确诊阴性634例;筛查阴性病例为32 947例,其中确诊阳性数为2例,确诊阴性数为32 945例.结合上述早期筛查的结果,阶段性序贯筛查方案的筛查阳性病例为10 359例,其中确诊阳性91例,确诊阴性10 268例;筛查阴性病例为135 831例,其中确诊阳性数为5例,确诊阴性数为135 826例;阶段性序贯筛查方案的阳性率灵敏度为94.79％,假阳性率为7.03％.结论 孕早中期阶段性序贯筛查方案能大大提高唐氏综合征血清学筛查的灵敏度;3年筛查工作中,本实验室数据虽然仅有部分病例采用孕早中期阶段性序贯筛查方案,但灵敏度提高了6.25％,防止了6例漏筛病例.综上,孕早中期阶段性序贯筛查方案应进行广泛的临床推广应用,可有效地减少唐氏综合征胎儿的漏筛.

Conventional culture method for detecting Group B streptococcus (GBS), a common pathogen of neonatal meningitis and sepsis, is time-consuming and unsensitive. Even though real-time fluorescence PCR-based molecular method is more accurate, it need special instrument and elaborate protocol. Here, we established a novel molecular method combining recombinase polymerase amplification with lateral flow strips for detecting GBS. The cAMP factor (cfb) gene is a highly specific and sensitive biomarker to identify GBS and is detectable by using 100 genomic copies as the amplification template. Clinical performance of this assay was evaluated by testing 130 samples, in comparison with culture method and real-time fluorescence PCR, and the results achieved 100% accuracy, which were the same with those of real-time fluorescence PCR, and were better than those of culture method with false-negative detection. This study provides a rapid and visual method, with clinical potential, for the detection of GBS infection of patients.

目的 通过对广东地区育龄女性TORCH感染筛查结果进行分析,了解广东地区育龄女性TORCH感染情况.方法 采用化学发光免疫分析法筛查广东地区育龄女性TORCH感染,并对筛查结果进行分析.结果 广东地区育龄女性的弓形虫、风疹病毒、巨细胞病毒、单纯疱疹病毒IgM抗体阳性率分别为0.17％(47/26 708)、1.57％(429/27 368)、0.68％(184/26 987)和4.20％(1 154/27 489);弓形虫、风疹病毒、巨细胞病毒、单纯疱疹病毒IgG抗体阳性率分别为4.86％(43/885)、79.18％(9 444/11 928)、98.31％(1 108/1 127)和92.43％(1 502/1 625).结论 开展育龄女性TORCH感染筛查工作,对优生优育、提高人口素质具有非常重要意义.

目的 通过对广东地区育龄妇女人细小病毒B19(human parvovirus B19,B19)感染筛查结果进行分析,了解广东地区育龄妇女人细小病毒B19感染情况. 方法 采用酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测广东地区育龄妇女血清中人细小病毒B19特异性IgM和IgG抗体,并对检测结果进行分析. 结果 广东地区育龄妇女血清中人细小病毒B19特异性IgM和IgG抗体阳性率分别为1.40％(700/50 086)、16.72％ (341/2 039).结论 开展育龄妇女人细小病毒B19感染筛查工作,对优生优育、提高人口素质具有非常重要意义.

目的 探讨孕早期一站式唐氏筛查模式的临床应用价值及其筛查结果与胎儿染色体异常的关系.方法 对2012年1月至2014年9月之间在本院进行孕早期一站式唐氏筛查的20 323例孕妇的产前筛查、产前诊断和妊娠结局进行分析.结果 20 323例孕早期一站式筛查孕妇筛出高风险孕妇539例,阳性率为2.65％,高风险孕妇通过产前诊断21-三体综合征胎儿19例、18-三体综合征胎儿5例和其他染色体异常胎儿9例;19 794例筛查低风险孕妇中随访妊娠结局发现4例染色体异常,其中21-三体综合征1例,18-三体综合征1例,其他染色体异常2例.结论 孕早期一站式唐氏筛查是产前筛查重要筛查模式,对预测胎儿染色体异常有的临床价值.

Objectives: The aim of this study was to determine whether the concentration of disintegrin and metalloprotease protein12 (ADAM12) in first trimester maternal serum can be used as a marker for first-trimester complete spontaneous abortions, missed abortions, ectopic pregnancies and hydatidiform moles.Methods: The maternal serum concentrations of ADAM12 were measured in the range of 5-9(+6) weeks of gestation using an automated AutoDelfia immunoassay platform in 9 cases of complete spontaneous abortion, 27 cases of missed abortions, 56 cases of ectopic pregnancies, 12 cases of hydatidiform moles, and 100 controls. Logistic regression analysis was used to determine significant factors for predicting adverse pregnancy outcomes in early pregnancy. Screening performance was assessed using receiver operating characteristic curves.Results: Two hundred and four women were enrolled in the study. In the control group, the level of ADAM12 increased with gestational age. The median ADAM12 levels in the spontaneous abortion (0.430 MoM), ectopic pregnancy (0.460 MoM) and hydatidiform mole (0.037 MoM) groups were lower than that in the control group, while the median ADAM12 level in the missed abortion group (1.062 MoM) was not significant from the controls (1.002 MoM). Logistic regression analysis demonstrated that the level of ADAM12 in maternal serum facilitated the detection of ectopic pregnancies (OR = 0.909; 95% CI = 0.841 similar to 0.982) and complete spontaneous abortion (OR = 0.863; 95% CI = 0.787 similar to 0.946).Conclusions: In complete spontaneous abortion and ectopic pregnancy, ADAM12 maintained at low levels in early pregnancies, and there were significant differences compared to normal pregnancies. ADAM12 is a promising marker for the diagnosis of complete spontaneous abortion and ectopic pregnancy in symptomatic women, and under certain conditions, ADAM12 can diagnose ectopic pregnancy and spontaneous abortion before an ultrasonographic detection of the conditions.