Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) for the prenatal diagnosis of a fetus with structural anomaly detected by ultrasonography. METHODS: The fetus and its parents were subjected to chromosomal karyotyping and CMA analysis. RESULTS: The fetus was found to carry a 46,XN,t(8;11)(q21.2;q13) translocation which was inherited from its mother. CMA has found no copy number variations (CNVs) in both parents but a de novo 2.00 Mb microdeletion in the fetus at 8q13.3. CONCLUSION CMA is capable of detecting microdeletions and microduplications in fetuses with translocations detected by karyotyping analysis.
Chromosome Aberrations ; Chromosome Deletion ; Chromosomes, Human, Pair 8 ; DNA Copy Number Variations ; Female ; Fetus ; Humans ; Karyotyping ; Microarray Analysis ; Pregnancy ; Prenatal Diagnosis

Limb and CNS expressed 1 like (LIX1L) is over-expressed in several types of tumors. However, the function of LIX1L in glucose metabolism and hepatocellular carcinoma (HCC) progression remains elusive. Here we report that LIX1L is over-expressed in human HCC tissues, which predicts unfavorable prognosis. LIX1L deficiency

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with N-acetylglutamate synthase deficiency. METHODS: Trio whole exome sequencing (WES) was carried out for the pedigree. Pathogenicity of the identified variant was predicted based on the latest recommendation of the American College of Medical Genetics and Genomics (ACMG). Prenatal diagnosis was provided for subsequent pregnancy through Sanger sequencing. RESULTS: Trio WES showed that the proband has carried compound heterozygous c.68delG and c.796G>C variants of NAGS gene, for which the mother and father were respectively heterozygous carriers. Neither variant was reported previously. Based on the ACMG guidelines, the c.68delG variant was classified as "likely pathogenic" (PVS1+PM2), while the c.796G>C variant was classified as with "uncertain significance" (PM2+BP4). Sanger sequencing validated the above findings, and only detected the heterozygous c.796G>C variant in the amniotic fluid sample. The fetus was followed up till 6 month after birth with no obvious abnormality. CONCLUSION The compound heterozygous c.68delG and c.796G>C variants of the NAGS gene probably underlay the disorder in this pedigree, and the resulth asenabled genetic counseling and prenatal diagnosis for this pedigree.
Amino-Acid N-Acetyltransferase/genetics* ; China ; Female ; Genetic Testing ; Humans ; Male ; Mutation/genetics* ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Urea Cycle Disorders, Inborn/genetics* ; Whole Exome Sequencing

【Objective】 To study the therapeutic effects of tetrahydrocurcumin(THC) via intraperitoneal(i.p.) injection on the respiratory symptoms and inflammatory responses in asthmatic mice. 【Methods】 BALB/c mice were randomly divided into 4 groups, including normal control group, ovalbumin(OVA) -induced model group, positive group and THC administration group. The latter two groups were treated with 2.5 mg/kg of dexamethasone(DEX) or 20 mg/kg of THC via i.p. injection from Day 21 to Day25. The weight changes and nasal symptoms were recorded before and after OVA challenge. The mice were sacrificed at the end of the experiment and the lung tissue and broncho-alveolar lavage fluid(BALF) were collected for assessment of histopathological alterations, Th cell subsets and related cytokine level. 【Results】 After THC treatment via i.p. injection, the asthmatic mice’s rubbing frequencies were reduced(P < 0.05) with a difference of 5.2 between the two means(95% CI = 0.66 to 9.74), lungs’pathological scores were reduced(P < 0.05) with a difference between the two means being 1.6(95% CI = 0.32 to 2.88), mucus production induced by hyperplasia of goblet cells was alleviated(P < 0.0001) with a difference between the two means being 9.56(95% CI = 5.05 to 14.07). Besides, compared with OVA group, the percentages of Th2 and Th17 cells were reduced(P < 0.01) with a difference between the two means being 1.49 and 2.15(95% CI = 0.50 to 2.49 and 0.72 to 3.58), respectively. The levels of interleukin(IL) -4, IL-5, IL-13 and IL-17A in BALF were decreased(P < 0.05) with a difference between the two means being 5.45, 4.13, 5.17 and 2.44 (95% CI = 1.95 to 8.94, 1.08 to 7.19, 0.80 to 9.54 and -0.30 to 5.17), respectively. The further comparison between THC and DEX groups showed no significant difference(P > 0.05) in the lung pathological change, Th17 cells, IL-13, and IL-17A levels. 【Conclusions】 It is concluded that i.p. injection of THC could effectively alleviate the respiratory symptoms and inhibit inflammatory reaction in asthmatic mice in short time with high safety. Therefore, i.p. injection of THC has the potential value to be the alternative therapeutic strategy for asthma.

Objective: To delineate the variants spectrum of phenytalanine hydroxylase (PAH) gene among 78 unrelated patients with phenylketonuria (PKU) from Jiangxi province. Methods: The 13 exons and flanking intronic regions of the PAH gene were subjected to PCR amplification and sequencing. Results: A total of 143 variants were detected among the 156 alleles, which included 54 types of variants, which yielded a detection rate of 91.7%. Common variants have included R243Q (26/143, 18.2%), R408Q (10/143, 7.0%), EX6-96A>G (8/143, 5.6%), IVS4-1G>A (7/143, 4.9%), R241C (7/143, 4.9%) and V399V (7/143, 4.9%). In addition, 6 novel variants were detected, which included IVS4-3T>G, Q172H, C284Y, V291L, V329del, and L430R. The variants consisted of missense, splicing, nonsense and deletion variants, which have mainly located in exons 7 (45, 31.5%), 12 (17, 11.9%), 11 (16, 11.2%) and 6 (14, 9.8%). Conclusion Variants of the PAH gene identified in Jiangxi province mainly involve exons 7, 12, 11 and 6, with the most common variants being R243Q and R408Q. Six novel variants were identified.

Objective To compare the pathological results between preoperative gastroscopy samples and postoperative samples of endoscopic resection from patients with gastric intraepithelial neoplasia, and further investigate the risk factors of pathological upgrading. Methods A retrospective analysis was performed on the data of 371 patients with gastric intraepithelial neoplasia confirmed by biopsy and undergoing endoscopic resection from January 2012 to December 2014 in Nanjing Drum Tower Hospital. The preoperative and postoperative pathological results were compared, and the risk factors for pathological upgrading after operation were analyzed. Results Among 371 patients, 173 and 198 cases were diagnosed as low-grade intraepithelial neoplasia ( LGIN ) and high-grade intraepithelial neoplasia ( HGIN ) , respectively, by preoperative endoscopic biopsy. By postoperative pathology of endoscopic resection, 113 ( 65. 3％) of 173 LGIN cases kept the diagnosis, while 46 ( 26. 6％) of 173 cases were upgraded to HGIN, and 10 ( 5. 8％) of 173 cases were finally upgraded to gastric cancer. The upgrade rate was 32. 4％(56/173). In the HGIN group, 107 ( 54. 0％) of 198 HGIN patients had the same diagnosis after endoscopic resection, 78 ( 39. 4％) of 198 cases were upgraded to cancer. Multivariate regression analysis showed that diameter of larger than 2 cm (P=0. 008), proximal stomach location (P=0. 011), mucosal surface redness ( P=0. 000 ) , and surface depression or ulcer ( P=0. 003 ) were independent factors of pathological upgrading for postoperative samples. Conclusion Preoperative biopsy for the diagnosis of gastric intraepithelial neoplasia has a certain misdiagnosis rate. More attentions should be paid on the lesion which is larger than 2 cm in diameter, located in the proximal stomach, or mucosa with red surface, depression or ulcer. Postoperative pathological examination can help to clarify the nature of the lesion.

Background:The occurrence of gastric cancer is a gradual process with multiple factors and multiple steps. In addition to cytological and structural abnormalities,there are abnormal molecular expressions,which involve the activation of many oncogenes and the inactivation of tumor suppressor genes. Aims:To explore the expressions and significance of Ki-67,p53 and P504s in normal gastric mucosa,atrophic gastritis with intestinal metaplasia,low-grade intraepithelial neoplasia,high-grade intraepithelial neoplasia and early gastric cancer. Methods:A total of 44 cases of normal gastric mucosa,44 cases of atrophic gastritis with intestinal metaplasia,41 cases of low-grade intraepithelial neoplasia,38 cases of high-grade intraepithelial neoplasia and 35 cases of early gastric cancer from Jan. 2015 to Dec. 2016 at the Affiliated Drum Tower Hospital of Nanjing University Medical School were collected. Expressions of Ki-67,p53 and P504s were detected by immunohistochemical staining. Results:Compared with normal gastric mucosal tissue,the positivity rates of expression of Ki-67,p53 and P504s in atrophic gastritis with intestinal metaplasia,low-grade intraepithelial neoplasia,high-grade intraepithelial neoplasia and early gastric cancer were obviously increased (P＜0.05). With the increasing of severity of the lesion,the positivity rate gradually increased. Conclusions:The expressions of Ki-67,p53 and P504s are closely related to the occurrence and development of gastric cancer,and are involved in the early process of gastric cancer. The detections of these molecular markers are helpful for determining the severity and trend of the lesion,and beneficial for improving the detection rates of gastric precancerous lesion and early gastric cancer.

Objective To observe and analyze the influence of mastoscopic axillary lymph node dissection on the inflammatory stress and immune stress of patients with breast cancer.Methods Sixty patients with breast cancer were selected and randomly divided into control group(open surgery group)and observation group(mastoscopy-assisted treatment group),30 cases in each group.The inflammatory stress and immune stress indexes of two groups before the surgery and 12,48 and 72 hours after the surgery were detected and compared.Results The inflammatory stress and immune stress indexes 12,48 and 72 hours after the surgery in observation group were significantly better than those in control group(P<0.05).Conclusion The influence of mastoscopic axillary lymph node dissection on the inflammatory stress and immune stress of patients with breast cancer is better than open surgery.

Objective To observe and analyze the influence of mastoscopic axillary lymph node dissection on the inflammatory stress and immune stress of patients with breast cancer.Methods Sixty patients with breast cancer were selected and randomly divided into control group(open surgery group)and observation group(mastoscopy-assisted treatment group),30 cases in each group.The inflammatory stress and immune stress indexes of two groups before the surgery and 12,48 and 72 hours after the surgery were detected and compared.Results The inflammatory stress and immune stress indexes 12,48 and 72 hours after the surgery in observation group were significantly better than those in control group(P<0.05).Conclusion The influence of mastoscopic axillary lymph node dissection on the inflammatory stress and immune stress of patients with breast cancer is better than open surgery.