This study reported two cases of distal 18q deletions identified through non-invasive prenatal testing (NIPT). Case 1 harbored a de novo 20.4 Mb deletion of 46, XY, del(18) (q21.32q23), classified as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Follow-up at five years of age revealed global developmental delay, congenital heart disease, and distinct facial features. Case 2 had a 5.71 Mb paternal-origin deletion of 46,XX,del(18)(q22.1q22.2), with only mild tricuspid regurgitation detected at eight months of age. These phenotypic discrepancies demonstrated that the clinical manifestations of 18q deletion syndrome were closely associated with the size of the deleted segment and the involved critical genes. Therefore, individualized genetic counseling and long-term follow-up were necessary for the affected children.

Objective To explore the relationship between serum levels of anterior gradient 2(AGR2)and trimethylamine N-oxide(TMAO)and gut microbiota in children with inflammatory bowel disease(IBD).Methods A total of 145 IBD children were selected as the observation group,and children were divided into the ulcerative colitis group(64 cases)and the Crohn's disease group(81 cases)according to the disease type.Meanwhile,140 healthy children underwent physical examination in our hospital were included as the control group.Serum AGR2 and TMAO levels were detected by enzyme-linked immunosorbent assay(ELISA).The disease activity of ulcerative colitis and Crohn's disease were evaluated using the modified Mayo score and the Crohn's Disease Activity Index(CDAI)score,and patients were divided into the active group(75 cases)and the remission group(70 cases)according to the disease activity.Fecal samples were collected for identification and count of intestinal flora.Receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic value of serum AGR2 and TMAO levels in ulcerative colitis and Crohn's disease.The correlation between serum AGR2 and TMAO levels and intestinal flora was analyzed by Pearson test.Logistic regression was used to analyze the relationship between serum AGR2 and TMAO levels and the disease stage of children with IBD.Results The serum AGR2 level was lower in the ulcerative colitis group and the Crohn's disease group than that in the control group,and the serum TMAO level was higher than that in the control group(P＜0.05).The areas under the curve(AUC)of serum AGR2 and TMAO levels were 0.835,0.836 and 0.896 for diagnosis of ulcerative colitis alone and 0.859,0.864 and 0.964 for diagnosis of Crohn's disease.The serum AGR2 level and numbers of lactobacillus and bifidobacterium were significantly lower in the active group than those in the remission group,and the serum TMAO level and numbers of Escherichia coli,enterococcus,Helicobacter pylori and streptococcus were significantly higher in the active group than those in the remission group(P＜0.05).Serum AGR2 levels in IBD children were positively correlated with numbers of lactobacillus and bifidobacterium,and negatively correlated with numbers of Escherichia coli,Enterococcus,Helicobacter pylori and streptococcus(P＜0.05).Serum TMAO level was negatively correlated with numbers of lactobacillus and bifidobacterium,and positively correlated with numbers of Escherichia coli,Enterococcus,Helicobacter pylori and streptococcus(P＜0.05).The decreased serum AGR2 level and the increased TMAO level were risk factors for the disease progression to active stage in children with IBD(P＜0.05).Conclusion The combination of serum AGR2 and TMAO can effectively diagnose ulcerative colitis and Crohn's disease,and it is more valuable in the diagnosis of Crohn's disease.Abnormal expression of both may participate in the progression of IBD disease by affecting changes in gut microbiota structure.

Objective To study the effects and the possible mechanism of the hearing loss of offspring mice with chronic intrauterine hypoxia.Methods Ten healthy SD pregnant mice with SPF level were selected to establish an intrauterine hypoxia model as the hypoxia group,while another ten healthy SD pregnant mice without hypoxia treatment were selected as the control group.Arterial blood gas analysis was performed on pregnant mice and audi-tory brainstem response(ABR)testing was performed on their offspring after birth,and the results of each group were compared.Results The PaO2 and SaO2 of the hypoxic group were significantly lower than those of in the con-trol group.The hearing loss rate and wave Ⅲ response threshold of the offspring mice of the hypoxia group were significantly higher than those of in the control group at 21 and 56 days,but over time,the hearing loss rate and wave Ⅲ response threshold of the hypoxia group improved compared to before.Although some offspring mice in the hypoxic group at 21 day and 56 day had normal Ⅲ wave response thresholds,their wave Ⅱ and Ⅲ latency,as well as the latency between Ⅰ-Ⅱ,Ⅱ-Ⅲ,and Ⅰ-Ⅲ,were still significantly higher,while the amplitude of wave Ⅲ and the ratio of Ⅲ/Ⅰ were significantly lower than those of in the control group during the same period.For hypoxic off-spring mice with abnormal wave Ⅲ response threshold at 21 days and normal wave Ⅲ response threshold at 56 days,the latency of waves Ⅱ and Ⅲ,as well as the latency between Ⅰ-Ⅱ,Ⅱ-Ⅲ,and Ⅰ-Ⅲ were significantly higher,while the amplitude of wave Ⅲ and the ratio of Ⅲ/Ⅰ were significantly lower than those of in the control group and hypoxic group with normal wave Ⅲ response thresholds at 21 days and 56 days.The hearing loss of offspring mice in the hypoxia group was mainly bilateral.Conclusion Chronic intrauterine hypoxia can lead to varying degrees of hearing loss,but this type of hearing loss has a certain degree of retrogression in the early stages,and the body can undergo limited developmental compensation and repair.

Objective To explore the relationship between serum levels of anterior gradient 2(AGR2)and trimethylamine N-oxide(TMAO)and gut microbiota in children with inflammatory bowel disease(IBD).Methods A total of 145 IBD children were selected as the observation group,and children were divided into the ulcerative colitis group(64 cases)and the Crohn's disease group(81 cases)according to the disease type.Meanwhile,140 healthy children underwent physical examination in our hospital were included as the control group.Serum AGR2 and TMAO levels were detected by enzyme-linked immunosorbent assay(ELISA).The disease activity of ulcerative colitis and Crohn's disease were evaluated using the modified Mayo score and the Crohn's Disease Activity Index(CDAI)score,and patients were divided into the active group(75 cases)and the remission group(70 cases)according to the disease activity.Fecal samples were collected for identification and count of intestinal flora.Receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic value of serum AGR2 and TMAO levels in ulcerative colitis and Crohn's disease.The correlation between serum AGR2 and TMAO levels and intestinal flora was analyzed by Pearson test.Logistic regression was used to analyze the relationship between serum AGR2 and TMAO levels and the disease stage of children with IBD.Results The serum AGR2 level was lower in the ulcerative colitis group and the Crohn's disease group than that in the control group,and the serum TMAO level was higher than that in the control group(P＜0.05).The areas under the curve(AUC)of serum AGR2 and TMAO levels were 0.835,0.836 and 0.896 for diagnosis of ulcerative colitis alone and 0.859,0.864 and 0.964 for diagnosis of Crohn's disease.The serum AGR2 level and numbers of lactobacillus and bifidobacterium were significantly lower in the active group than those in the remission group,and the serum TMAO level and numbers of Escherichia coli,enterococcus,Helicobacter pylori and streptococcus were significantly higher in the active group than those in the remission group(P＜0.05).Serum AGR2 levels in IBD children were positively correlated with numbers of lactobacillus and bifidobacterium,and negatively correlated with numbers of Escherichia coli,Enterococcus,Helicobacter pylori and streptococcus(P＜0.05).Serum TMAO level was negatively correlated with numbers of lactobacillus and bifidobacterium,and positively correlated with numbers of Escherichia coli,Enterococcus,Helicobacter pylori and streptococcus(P＜0.05).The decreased serum AGR2 level and the increased TMAO level were risk factors for the disease progression to active stage in children with IBD(P＜0.05).Conclusion The combination of serum AGR2 and TMAO can effectively diagnose ulcerative colitis and Crohn's disease,and it is more valuable in the diagnosis of Crohn's disease.Abnormal expression of both may participate in the progression of IBD disease by affecting changes in gut microbiota structure.

Objective To study the effects and the possible mechanism of the hearing loss of offspring mice with chronic intrauterine hypoxia.Methods Ten healthy SD pregnant mice with SPF level were selected to establish an intrauterine hypoxia model as the hypoxia group,while another ten healthy SD pregnant mice without hypoxia treatment were selected as the control group.Arterial blood gas analysis was performed on pregnant mice and audi-tory brainstem response(ABR)testing was performed on their offspring after birth,and the results of each group were compared.Results The PaO2 and SaO2 of the hypoxic group were significantly lower than those of in the con-trol group.The hearing loss rate and wave Ⅲ response threshold of the offspring mice of the hypoxia group were significantly higher than those of in the control group at 21 and 56 days,but over time,the hearing loss rate and wave Ⅲ response threshold of the hypoxia group improved compared to before.Although some offspring mice in the hypoxic group at 21 day and 56 day had normal Ⅲ wave response thresholds,their wave Ⅱ and Ⅲ latency,as well as the latency between Ⅰ-Ⅱ,Ⅱ-Ⅲ,and Ⅰ-Ⅲ,were still significantly higher,while the amplitude of wave Ⅲ and the ratio of Ⅲ/Ⅰ were significantly lower than those of in the control group during the same period.For hypoxic off-spring mice with abnormal wave Ⅲ response threshold at 21 days and normal wave Ⅲ response threshold at 56 days,the latency of waves Ⅱ and Ⅲ,as well as the latency between Ⅰ-Ⅱ,Ⅱ-Ⅲ,and Ⅰ-Ⅲ were significantly higher,while the amplitude of wave Ⅲ and the ratio of Ⅲ/Ⅰ were significantly lower than those of in the control group and hypoxic group with normal wave Ⅲ response thresholds at 21 days and 56 days.The hearing loss of offspring mice in the hypoxia group was mainly bilateral.Conclusion Chronic intrauterine hypoxia can lead to varying degrees of hearing loss,but this type of hearing loss has a certain degree of retrogression in the early stages,and the body can undergo limited developmental compensation and repair.

This study reported two cases of distal 18q deletions identified through non-invasive prenatal testing (NIPT). Case 1 harbored a de novo 20.4 Mb deletion of 46, XY, del(18) (q21.32q23), classified as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Follow-up at five years of age revealed global developmental delay, congenital heart disease, and distinct facial features. Case 2 had a 5.71 Mb paternal-origin deletion of 46,XX,del(18)(q22.1q22.2), with only mild tricuspid regurgitation detected at eight months of age. These phenotypic discrepancies demonstrated that the clinical manifestations of 18q deletion syndrome were closely associated with the size of the deleted segment and the involved critical genes. Therefore, individualized genetic counseling and long-term follow-up were necessary for the affected children.

Objective:To observe the inhibitory effects of Huangqi Jiedu Decoction on lung metastasis of breast cancer in nude mice; To explore the mechanism of intervening epithelial mesenchymal transformation (EMT) induced by Wnt/β-catenin signaling pathway.Methods:Totally 30 nude mice were divided into model group, adriamycin group and Huangqi Jiedu Decoction low-, medium-, and high-dosage groups according to random number table method. Each group was injected subcutaneously with mouse breast cancer 4T1 cells to construct tumor - bearing nude mice model. Huangqi Jiedu Decoction low-, medium- and high-dosage groups were intragastrically administrated with Huangqi Jiedu Decoction 17.82, 35.64 and 71.28 g/kg; adriamycin group was injected intraperitoneally adriamycin 0.05 g/kg; model group was intragastrically administrated with normal saline of the same volume for 21 d. Tumor volume was measured at 9, 15, and 21 days after modeling. After the end of administration, the tumor tissue was separated, the tumor weight was measured, and the tumor inhibition rate was calculated. The lung tissue was Isolated,, the number of lung metastatic nodules and the inhibition rate of lung metastasis was counted. HE staining was used to observe the tissue morphology and evaluate the effectiveness of the model. The protein expressions of β-catenin, E-Cadherin and Vimentin in lung tissue were detected by Western Blot. The mRNA levels of β-catenin, E-Cadherin and Vimentin in lung tissue were detected by real-time fluorescent quantitative PCR.Results:Compared with the model group, the tumor volume and mass of Huangqi Jiedu Decoction low-, medium- and high-dosage groups decreased ( P<0.01); the number of pulmonary metastasis nodules in Huangqi Jiedu Decoction high-dosage group significantly decreased ( P<0.01); the mRNA and protein expressions of β-catenin and Vimentinm decreased in the Huangqi Jiedu Decoction low-, medium- and high-dosage groups ( P<0.01), and the protein and mRNA expressions of E-Cadherin increased in the Huangqi Jiedu Decoction high-dosage group ( P<0.01). Conclusion:Huangqi Jiedu Decoction can effectively inhibit the growth and lung metastasis of breast cancer transplanted tumor, and the mechanism may be to down-regulate the expression of key molecules in the Wnt/β-catanin signaling pathway, thereby inhibiting the EMT process, so as to inhibit the lung metastasis of breast cancer.

OBJECTIVE: To present on a prenatally diagnosed case with complex structural rearrangements of chromosome 8. METHODS: Chromosome karyotyping, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) were carried out for a fetus with increased nuchal thickness. RESULTS: The karyotype of the amniotic fluid sample showed extra materials on 8p. FISH revealed a centromeric signal at the terminal of 8p with absence of telomeric signal. CMA revealed partial deletion of 8p23.3 [(208049_2256732)×1], partial duplication of 8p23.3p23.2 [(2259519_3016818)×3], and partial duplication of 8q [8q11.1q12.2(45951900_60989083)×3]. CONCLUSION The complex structural rearrangements of chromosome 8 in this case has differed from the commonly seen inv dup del(8p).
Female ; Pregnancy ; Humans ; Chromosomes, Human, Pair 8/genetics* ; In Situ Hybridization, Fluorescence ; Gene Rearrangement ; Prenatal Diagnosis ; Centromere

ObjectiveTo determine the epidemiological characteristics and risk factors of a norovirus GII.17 outbreak in Minhang District of Shanghai in 2018， and provide evidence for prevention and control measures of norovirus infection. MethodsDescriptive epidemiological analysis was performed. In addition， a retrospective cohort study was conducted to determine the risk factors. ResultsFrom May 30^th to June 1^st of 2018， a total of 132 cases （126 clinical cases and 6 confirmed cases） were documented，with an attack rate of 29.20%（132/452）.All cases were children in a kindergarten， with the average age of 5 years and 43.9% being male. The cases were reported in all the classes， with no clustering by class or floor．The epidemic curve was characterized by a point source exposure， which was estimated to be probably between 7 AM on May 30^thand 0：30 AM on May 31^st. The retrospective cohort study showed that the attack rate significantly differed between the children who had taken and did not take the school lunch （RR=∞） on May 30^th，and those who had taken and did not take seafood noodles （RR=4.11， 95%CI：1.09-15.55） （P<0.05）. Among a total of 73 specimens， six specimens collected in child cases and one specimen in an asymptomatic chef tested positive for GII.17 type of norovirus. In addition， one retained food specimen of seafood noodles was positive for Aeromonas hydrophila. Viral shedding in the asymptomatic chef remained over 30 days. ConclusionThe outbreak was caused by seafood noodles contaminated by norovirus. It warrants enhancement in the regulation of food safety in canteens and regular examination of norovirus infection in catering industry employees.

Objective:To develop a self-made plasma quality control material for non-invasive prenatal testing (NIPT) and evaluate its performance.Methods:139 NIPT-negative maternal plasmas stored in the genetic department of Shaoxing maternal and child health hospital from January 1, 2019 to June 30, 2021 were divided into male groups (19 cases) and female groups (120 cases) according to the neonatal gender. 9360 cases from September 2020 to September 2021 were enrolled as clinical validation cases.First step, 200 μl plasma from a 47 years-old non-pregnant healthy women was used as a matrix. Different amounts (0.1, 0.2, 0.5, 2.5, and 5 μl) of positive DNA from fetal chromosome aneuploidy (T21, T18, T13) detection kit were added. The appropriate volume of positive DNA was 0.5 μl according to the test results. Second step,Plasma in male and female group was treated as matrix. 0.5 μl positive DNA was added per 205 μl. Plasma matrix from female group showed good repeatability and the sensitivity was 100%.Third step, evaluate the self-made plasma quality control material, including storage stability, matrix uniformity and repeatability, and the effect of different batch numbers of positive DNA, by calculating Z score and the CV of fetal DNA concentration (FF).Results:Plasma matrix from female group showed good repeatability and the sensitivity was 100%, while the sensitivity of male group was only 84%. The CV of FF in female matrix was 3.9% in the repetitive experiments. After adding 0.5 μl positive DNA, the mean FF of self-made positive plasma quality control was 5.63%±0.42%, Z values>6, and the CV was 7% after storage of three months. Considering the concentration variation of positive DNA in different lots, 1 μl of positive DNA should be added when the FF of positive DNA is lower than 10%.Used in 9360 clinical cases from September 2020 to September 2021, all positive plasma quality control materials showed positive results, and the positive predictive value of trisomy 21 was 100%.Conclusions:The NIPT self-made positive plasma quality control material has been successfully developed in this study. The preliminary experimental results show that it has good repeatability and stability, which is suitable for clinical application.