目的 探讨暨南大学附属第一医院产检孕妇不同孕期、年龄段铁代谢相关指标血清铁(SI)、血清铁蛋白(SF)、转铁蛋白(TRF)、总铁结合力(TIBC)、可溶性转铁蛋白受体(sTfR)水平的改变.方法 检测30例健康非妊娠女性和128例不同孕期、不同年龄段妊娠妇女的血常规(RBC、Hb)和生化指标(SI、SF、TRF、TIBC、sTfR)并进行统计学分析.结果 除SI、sTfR外,妊娠妇女血清铁代谢指标(TRF、TIBC、SF)与正常对照组比较差异均有统计学意义(P＜0.05),TIBC、SF较对照组降低,TRF较对照组升高.孕晚期TRF较孕中期高,差异有统计学意义(P＜0.05).20～27岁和28～35岁年龄段的铁代谢指标TRF、TIBC、SF与正常对照组比较,差异均有统计学意义(P＜0.05).TRF和TIBC两者相关性显著.结论 通过分析暨南大学附属第一医院产检的妊娠妇女的铁储备水平,发现年龄、孕期均与孕妇体内铁代谢水平密切相关,TRF、TIBC、SF可作为临床有一定指导意义的指标,为临床评估孕妇体内真实的铁储备水平及后续诊疗提供依据.

Rationale Ligusticum chuanxiong Hort is a well-known herb medicine that has been widely prescribed to treat cardiovascular diseases in China for hundreds of years. Senkyunolide H (SNH) is one of the major bioactive ingredients extracted from L. chuanxiong, and it displayed neuroprotective effects. To fully understand its mechanism of action, the metabolism needs to be investigated. Methods In vitro studies were conducted by incubating SNH with rat and human hepatocytes, and the metabolites were identified and characterized using liquid chromatography in combination with hybrid quadrupole Orbitrap mass spectrometry (LC-Orbitrap-MS). The structures of the metabolites were proposed by accurate mass analysis of respective precursor ions, indicative product ions, and elemental compositions. Results Under the current conditions, a total of 10 metabolites were identified, and among these metabolites, M3 and M4 were the most abundant metabolites both in rat and human hepatocytes. Our results demonstrated that hydroxylation, hydration, glucuronidation, and GSH conjugation were the primary metabolic pathways of SNH. Conclusions The present study provides new information on the metabolism of SNH, which would help prospects of the disposition of SNH.

目的 探讨血清视黄醇结合蛋白(serum retinol binding protein,sRBP)与β2微球蛋白(sβ2-MG)联合检测在肾脏疾病的临床诊断价值.方法 检测162例肾脏病患者和100例正常体检者sRBP、尿素(Urea)、肌酐(Cr)、尿酸(UA)、sβ2-MG水平并作相关比较.结果 162例肾脏病患者sRBP、Urea、Cr、UA、sβ2-MG检测值高于对照组(P<0.01);sRBP、sβ2-MG水平在不同肾脏病组患者组别与正常对照组比较差异均有统计学意义(P<0.01);sRBP、Urea、Cr、UA、sβ2-MG的阳性率明显高于对照组(P<0.01);sRBP在各组的阳性率最高,与sβ2-MG联合检测的阳性检出率更高,ROC曲线下面积为0.89.结论 血清视黄醇结合蛋白是肾脏病的敏感指标,联合sβ2-MG检测可以为肾脏病的临床诊断提供更可靠的理论依据.

Neonatal Intrahepatic Cholestasis caused by Citrin Deficiency (NICCD) is an autosomal recessive disease resulting from biallelic SLC25A13 mutations, and its diagnosis relies on genetic analysis. This study aimed to characterize the pathogenicity of 2 novel splice-site variants of SLC25A13 gene. Two patients (C0476 and C0556) suspected to have NICCD, their family members and 9 healthy volunteers were recruited as the research subjects. The SLC25A13 genotypes NG_012247.2(NM_014251.3): c.[852_855del]; [69+5G > A] in patient C0476 and c.[1453-1G > A]; [1751-5_1751-4ins (2684)] in patient C0556 were identified by means of polymerase chain reaction, long and accurate polymerase chain reaction, as well as Sanger sequencing. The 2 splice-site variants were absent in control databases and predicted to be pathogenic by computational analysis. The alternative splice variants in monocyte-derived macrophages from patient C0476 demonstrated exon 2 skipping [r.16_69del; p.(Val6_Lys23del)] in vivo, while minigene analysis revealed both exon 2-skipping and retained products from c.69+5G > A in vitro. In the patient C0556, an aberrant transcript [r.1453del; p.(Gly485Valfs*22)] resulting from c.1453-1G > A was detected on minigene splicing study. Thus, c.69+5G > A and c.1453-1G > A were both proved to be pathogenic. The 2 novel splice-site variants expanded the SLC25A13 mutation spectrum and provided reliable molecular markers for the definite diagnosis and genetic counseling of NICCD in the affected families.

目的 分析本地区某医院2013-2016年革兰阴性杆菌的分布及其对抗生素的耐药性,指导临床合理应用抗生素.方法 收集2013-2016年本院临床革兰阴杆菌4091株,采用VITEK-Compact2对临床分离菌株鉴定与药敏试验(MIC法)),按CLSI 2012年标准判断结果,WHONET 5.6软件统计分析.结果 临床分离革兰阴性杆菌4091株,标本来源主要是呼吸道分泌物、尿液和伤口拭子;其中肠杆菌科细菌比率较高(占62.04％),铜绿假单胞菌和鲍曼不动杆菌分别占19.09％和11.05％.大肠埃希菌、肺炎克雷伯菌和奇异变形杆菌产ESBLs依次为52.5％、46.7％和20.2％;肠杆菌对哌拉西林/他唑巴坦和亚胺培南耐药率低(<3％),且明显低于头孢吡肟、头孢他啶、氨曲南和头孢曲松,铜绿假单胞菌和鲍曼不动杆菌对亚胺培南耐药率高(分别为20.8％和62.7％).大肠埃希菌、肺炎克雷伯菌、鲍曼不动杆菌和铜绿假单胞菌出现少量泛耐药菌株,碳青霉烯类耐药铜绿假单胞菌和碳青霉烯类耐药鲍曼不动杆菌对阿米卡星敏感率高.结论 革兰阴性杆菌耐药性增加对临床感染治疗构成严重威胁,多重耐药菌和耐碳青霉烯类革兰阴性杆菌增多,应加强本地区耐药性监测和控制措施,按照药敏结果合理使用抗生素.

OBJECTIVE:To explore the clinical features and mutations of MYO5B gene in a family affected with microvillus inclusion disease.METHODS:Clinical data of an infant affected with microvillus inclusion disease was collected. Genomic DNA was extracted from peripheral blood samples from the patient and her parents. PCR amplification and Sanger sequencing were performed to analyze all the exons and their flanking sequences of the MYO5B gene.RESULTS:The patient presented with complicated manifestations including respiratory distress syndrome, dehydration, acidosis, bowel dilatation, liver and kidney dysfunction, and severe and intractable diarrhea. A compound mutation of the MYO5B gene, i.e., IVS37-1G>C/c.2729_2731delC (p.R911Afs916X), was discovered in the patient. The former was a splice-site mutation inherited from the mother, while the latter was a frameshift mutation inherited from the father. Both were not reported previously.CONCLUSION:Based on the clinical and molecular evidence, the patient was diagnosed with microvillus inclusion disease. Above finding has expanded the mutation spectrum of the MYO5B gene, which can provide valuable information for genetic counseling for the family.

Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is an autosomal recessive disorder resulting from biallelic mutations of the SLC25A13 gene. Due to the lack of well‑recognized clinical or biochemical diagnostic criteria, the definitive diagnosis of this disease relies on the genetic analysis of SLC25A13 at present. As novel large deletion/insertion mutations of the SLC25A13 gene are difficult to detect using routine DNA analytic approaches, the timely diagnosis of patients with these types of mutations remains a challenge. The present study aimed to examine SLC25A13 mutations in an infant with a suspected diagnosis of NICCD. DNA was extracted from blood samples, and SLC25A13 mutations were examined by screening for high‑frequency mutations and Sanger sequencing. Reverse transcription-polymerase chain reaction and cDNA cloning analyses were then performed using peripheral blood lymphocytes (PBLs) to identify the obscure mutation. The results demonstrated that the infant was heterozygous for a paternally‑inherited mutation, c.851_854del4, and a maternally‑inherited large deletion, c.1019_1177+893del, which has not been reported previously. A positive diagnosis of NICCD was made, and the infant responded favorably to a galactose‑free and medium‑chain triglyceride‑enriched formula. The present study confirmed the effectiveness of this formula in NICCD therapy, enriched the SLC25A13 mutational spectrum and supported the feasibility of cDNA cloning analysis using PBLs as a molecular tool for facilitating the identification of large SLC25A13 deletions.

The human solute carrier family 10 member 1 (SLC10A1) gene encodes sodium taurocholate cotransporting polypeptide (NTCP), the principal transporter of conjugated bile salts from the plasma into hepatocytes. Although the function of NTCP has been studied extensively and a number of SLC10A1 variations have been identified in humans, information regarding NTCP deficiency is limited. To date, only one patient with NTCP deficiency has been described; however, in the present study a pediatric patient who experienced intractable and striking hypercholanemia is presented. Analysis of the SLC10A1 gene in the patient revealed a homozygous p.Ser267Phe (c.800C>T) variation, which proved to be a single-nucleotide polymorphism (SNP) in the allele frequency of 4.7% of healthy controls. This variation involved a conserved amino acid residue on the orthologous alignment that was predicted to be 'disease-causing' by functional analysis using a number of bioinformatic tools. Next generation sequencing was performed; however, no other genetic causes were identified that would affect the bile acid homeostasis in the patient. Moreover, an adult, with the same genotype as the pediatric patient, was identified for the first time as experiencing mild hypercholanemia. The molecular and clinical findings in the present study suggest, for the first time, that there is an association between p.Ser267Phe SNP and hypercholanemia, and this information may be used to clinically identify NTCP deficiency worldwide.

目的：探讨采用高速离心法、乙醚抽提法及生理盐水稀释法消除高脂血标本对生化酶类指标测定结果干扰的可行性，并比较3种方法的优劣。方法收集2014年8月至2015年3月广东省广州市天河区石牌街社区卫生服务中心采集的明显高脂血标本52份，以3000 r/min离心10 min得到原高脂血浆。采用MINDRAY BS-390全自动生化分析仪测定原高脂血浆、高速离心血浆、乙醚抽提血浆及生理盐水稀释血浆中丙氨酸氨基转移酶、天门冬氨酸氨基转移酶、碱性磷酸酶、γ-谷氨酰转移酶、乳酸脱氢酶、肌酸激酶同工酶及淀粉酶水平，并分析比较3种方法对各种酶类指标检测结果的影响。结果原高脂血浆与高速离心血浆、乙醚抽提血浆及生理盐水稀释血浆中各种酶类指标测定结果比较，差异均有统计学意义（P<0.01）；且各种酶类指标测定值由高至低依次为高速离心血浆、乙醚抽提血浆、生理盐水稀释血浆和原高脂血浆。结论高速离心法相对乙醚抽提法及生理盐水稀释法处理高脂血标本能明显减轻高脂血标本混浊对生化分析仪测定酶类结果的干扰和影响。

Citrin deficiency (CD) is a Mendelian disease due to biallelic mutations of SLC25A13 gene. Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is the major pediatric CD phenotype, and its definite diagnosis relies on SLC25A13 genetic analysis. China is a vast country with a huge population, but the SLC25A13 genotypic features of CD patients in our country remains far from being well clarified. Via sophisticated molecular analysis, this study diagnosed 154 new CD patients in mainland China and identified 9 novel deleterious SLC25A13 mutations, i.e. c.103A > G, [c.329 − 154_c.468 + 2352del2646; c.468 + 2392_c.468 + 2393ins23], c.493C > T, c.755 − 1G > C, c.845_c.848 + 1delG, c.933_c.933 + 1insGCAG, c.1381G > T, c.1452 + 1G > A and c.1706_1707delTA. Among the 274 CD patients diagnosed by our group thus far, 41 SLC25A13 mutations/variations were detected. The 7 mutations c.775C > T, c.851_854del4, c.1078C > T, IVS11 + 1G > A, c.1364G > T, c.1399C > T and IVS16ins3kb demonstrated significantly different geographic distribution. Among the total 53 identified genotypes, only c.851_854del4/c.851_854del4 and c.851_854del4/c.1399C > T presented different geographic distribution. The northern population had a higher level of SLC25A13 allelic heterogeneity than those in the south. These findings enriched the SLC25A13 mutation spectrum and brought new insights into the geographic distribution of the variations and genotypes, providing reliable evidences for NICCD definite diagnosis and for the determination of relevant molecular targets in different Chinese areas.

目的 探讨血清三酰甘油脂肪酶(ATGL)、血脂及血糖水平与非酒精性脂肪肝(NAFLD)相关性.方法 选择经超声确诊的NAFLD患者86例及健康对照者65例,测量腰围、臀围、腰臀比及体质量指数(BMI),检测血清ATGL、总胆同醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)及空腹血糖(FBG)水平.结果 与健康对照者比较,NAFLD患者ATGL水平显著降低,而BMI、腰围、臀围、腰臀比、TC、TG、LDL-C水平均明显增高(P＜0.01);NAFLD患者ATGL水平与BMI、TC及TG呈负相关(r分别为-0.210、-0.221、-0.432,P＜0.01).结论 ATGL、BMI、TC、TG及LDL-C均是影响NAFLD的相关因素.

Citrin is the liver-type aspartate/glutamate carrier isoform 2 (AGC2) encoded by SLC25A13 gene, playing important roles in the urea cycle and the malate-aspartate shuttle. Citrin deficiency (CD) has proven a disease entity with high prevalence in south China, including Guangdong with the largest population, but CD epidemiology in this province has not been well characterized. This study aims to screen for five prevalent SLC25A13 mutations, c.851_854del (p.R284fs286X), c.1638_1660dup (p.A554fs570X), c.615+5G>A (p.A206fs212X), IVS16ins3kb (p.A584fs585X) and c.1399C>T (p.R467X), to calculate the mutation carrier rate in Guangdong. A total of 2,428 used blood samples for health examination were collected as the research subjects, including 1,558 from 5 cities in the Pearl River Delta area and the remaining 870 from 4 peripheral cities, and the 5 mutations screened using High Resolution Melting Assay and HybProbe assay. A total of 52 carriers were detected, including 2 carriers of a novel c.1420G>A (p.V474M) mutation that impairs citrin function, as judged by the functional analysis in the yeast system. The carrier rate was higher in Pearl River Delta area than that in the peripheral cities (26/1,558 vs. 26/870, with χ2 = 4.639 and P < 0.05). The carrier rate was around 1/47 (52/2,428), theoretically with the CD morbidity of 1/8,800 and the number of CD patients over 11,800 in Guangdong population. This study has provided primary epidemiologic data for the evaluation of CD effect in Guangdong province. Moreover, the newly identified c.1420G>A mutation that impairs AGC2 function has enriched the mutation spectrum of human SLC25A13 gene.

Biallelic mutations of the SLC25A13 gene result in citrin deficiency (CD) in humans. Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is the major CD phenotype in pediatrics; however, knowledge on its genotypic and phenotypic characteristics remains limited. The present study aimed to explore novel molecular and clinical characteristics of CD. An infant suspected to have NICCD as well as her parents were enrolled as the research subjects. SLC25A13 mutations were investigated using various methods, including cDNA cloning and sequencing. The pathogenicity of a novel mutation was analyzed bioinformatically and functionally with a yeast model. Both the infant and her father were heterozygous for c.2T>C and c.790G>A, while the mother was only a c.2T>C carrier. The novel c.790G>A mutation proved bioinformatically and functionally pathogenic. The infant had esophageal atresia and an accessory hepatic duct, along with bile plug formation confirmed by laparoscopic surgery. However, the father seemed to be healthy thus far. The findings of the present study enrich the genotypic and phenotypic characteristics of CD patients, and provided clinical and molecular evidence suggesting the possible non-penetrance of SLC25A13 mutations and the likely involvement of this gene in primitive foregut development during early embryonic life.

目的 研究UF-500i尿液分析仪及SE-9000i型血细胞分析仪在浆膜腔积液白细胞计数中的应用.方法 应用UF-500i尿液分析仪及SE-9000i型血细胞分析仪对浆膜腔进行白细胞计数检测,并作统计学分析.结果 手工计数法、UF-500i尿液分析仪及SE-9000i型血细胞分析仪检测法比较差异无统计学意义(P＞0.05).结论 Sysmex UF-500i尿液分析仪用于浆膜腔积液标本的细胞计数,简便、快速、重复性好,可以替代显微镜计数法测定浆膜腔积液白细胞数、上皮细胞数和非肉眼血性标本的红细胞数,而肉眼血性浆膜腔积液的红细胞计数不能用UF-500i尿沉渣分析仪检测.

Background The human SLC25A13 gene encodes citrin, the liver-type mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), and SLC25A13 mutations cause citrin deficiency (CD), a disease entity that encompasses different age-dependant clinical phenotypes such as Adult-onset Citrullinemia Type II (CTLN2) and Neonatal Intrahepatic Cholestasis caused by Citrin Deficiency (NICCD). The analyses of SLC25A13 gene and its protein/mRNA products remain reliable tools for the definitive diagnoses of CD patients, and so far, the SLC25A13 mutation spectrum in Chinese CD patients has not been well-characterized yet. Methods and Results By means of direct DNA sequencing, cDNA cloning and SNP analyses, 16 novel pathogenic mutations, including 9 missense, 4 nonsense, 1 splice-site, 1 deletion and 1 large transposal insertion IVS4ins6kb (GenBank accession number KF425758), were identified in CTLN2 or NICCD patients from China, Japan and Malaysia, respectively, making the SLC25A13 variations worldwide reach the total number of 81. A large NICCD cohort of 116 Chinese cases was also established, and the 4 high-frequency mutations contributed a much larger proportion of the mutated alleles in the patients from south China than in those from the north (χ2 = 14.93, P<0.01), with the latitude of 30°N as the geographic dividing line in mainland China. Conclusions This paper further enriched the SLC25A13 variation spectrum worldwide, and formed a substantial contribution to the in-depth understanding of the genotypic feature of Chinese CD patients.

>Citrin缺陷导致的新生儿肝内胆汁淤积症(neonatal intrahepatic cholestasis caused by citrin deficiency,NICCD)是近几年来新发现的一种常染色体隐性遗传病,属于Citrin缺陷病(citrin deficiency,CD)的一种临床表型。国内首例NICCD的确诊见于2006年。目前,NICCD目前缺乏公认的临床或生化诊断标准,其确诊主要依赖于基因诊断。国内外有关文献报道多侧重于如何通过基因检测突变确诊NICCD,对患者血生化指标改变的报道尚不系统深入,故检测并总结NICCD生化指标的动态变化特征并比较临床症状相似的疾病生化指标有望为本病的病情判断及疗效观察临床诊断提供有价值的线索。本研究根据NICCD患者临床表现及病程,采用

<正>患儿男,11岁,因反复发热伴鼻塞、流涕1个月入院。患儿于1个月前无明显诱因出现发热,体温高达39.2℃,伴有鼻塞、流涕,无咳嗽、咳痰,无寒战、抽搐,无腹痛及腹泻。病后食欲欠佳,身体较前消瘦。在当地医院做胸片检查提示心肺及隔未见明显异常;做鼻部CT检查,意见为:右侧额窦炎,双侧鼻息肉。曾用抗生素、中药及对症治疗,病情无好

Citrin is a liver-type aspartate/glutamate carrier (AGC) encoded by the gene SLC25A13. Two phenotypes for human citrin deficiency have been described, namely the adult-onset citrullinemia type II (CTLN2) and the neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). However, citrin deficiency currently remains a perplexing and poorly recognized disorder. In particular, description of post-NICCD clinical presentations before CTLN2 onset is rather limited. Analysis of SLC25A13 mutations, identification of dysmorphic erythrocytes, hepatobiliary scintigraphic imaging and investigation of post-NICCD clinical presentations were performed in a citrin-deficient cohort comprised of 51 cases of children diagnosed with citrin deficiency in a Chinese pediatric center. Twelve SLC25A13 mutations were detected in this cohort, including the novel V411M and G283X mutations. Among the 51 citrin-deficient subjects, 7 cases had echinocytosis, which was associated with more severe biochemical abnormalities. Delayed hepatic discharge and bile duct/bowel visualization were common scintigraphic findings. Moreover, 9 of the 34 post-NICCD cases demonstrated concurrent failure to thrive and dyslipidemia, constituting a clinical phenotype different from NICCD and CTLN2. The novel mutations, echinocytosis, hepatobiliary scintigraphic features and the novel clinical phenotype in this study expanded the genotypic and phenotypic spectrum of citrin deficiency, and challenge the traditionally-assumed 'apparently healthy' period after the NICCD state for this disease entity.

<正>急性心肌梗死(AMI)是内科急危重症之一,严重危害人们健康,近年来研究发现,我国中青年AMI的发病率有上升的趋势。中青年AMI患者是指年龄在59岁及以下的患者(年龄的划分:沿用我国对年龄的划分标准[1]),其发生率占AMI患者的3-6%。现将我院心内科2006年1