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Background Autosomal recessive or compound heterozygous mutations in KLHL40 cause nemaline myopathy 8, which is one of the most severe forms of nemaline myopathy. The KLHL40 c.1516A>C variant has recently been reported as a founder mutation in southern Chinese. Methods We report six cases of nemaline myopathy 8 which involves the c.1516A>C variant, from five unrelated families of non‐consanguineous southern Chinese. The pre‐ and postnatal phenotypes of these cases were reviewed with emphasis on prenatal clinical features. Genetic testing for the founder mutation was performed on three patients with homozygous mutations. Results Common prenatal features included reduced fetal movement, polyhydramnios, breech presentation, and clubfeet. Two pregnancies were terminated. Four live‐born patients had postnatal features typical of nemaline myopathy 8. The length of survival ranged from 49 days to 17 months, with respiratory failure and infections being the principal causes of death. Haplotype analysis in three patients with homozygous mutation showed a shared haplotype block of 1.1727 cM spanning over the c.1516A>C variant, suggesting it is a southern Chinese‐specific founder mutation. Conclusion Analysis of the KLHL40 c.1516A>C variant should be considered in prenatal diagnosis of Chinese pregnant patients with suspected congenital neuromuscular disorders or with significant family history of congenital myopathies. We reported six cases from five unrelated families of non‐consanguineous southern Chinese affected by nemaline myopathy 8, with either homozygous variants or compound heterozygous variants involving c.1516A>C in KLHL40. Pre‐ and postnatal phenotypes of the cases were reviewed, with emphasis on the prenatal clinical features.

OBJECTIVES. To review the characteristics of a series of obstetric patients admitted to the intensive care unit in a regional hospital in 2006-2010, to compare them with those of a similar series reported from the same hospital in 1989-1995 and a series reported from another regional hospital in 1998-2007. DESIGN. Retrospective case series. SETTING. A regional hospital in Hong Kong. PATIENTS. Obstetric patients admitted to the Intensive Care Unit of Kwong Wah Hospital from 1 January 2006 to 31 December 2010. RESULTS. From 2006 to 2010, there were 67 such patients admitted to the intensive care unit (0.23% of total maternities and 2.34% of total intensive care unit admission), which was a higher incidence than reported in two other local studies. As in the latter studies, the majority were admitted postpartum (n=65, 97%), with postpartum haemorrhage (n=39, 58%) being the commonest cause followed by pre-eclampsia/eclampsia (n=17, 25%). In the current study, significantly more patients had had elective caesarean sections for placenta praevia but fewer had had a hysterectomy. The duration of intensive care unit stay was shorter (mean, 1.8 days) with fewer invasive procedures performed than in the two previous studies, but maternal and neonatal mortality was similar (3% and 6%, respectively). CONCLUSION. Postpartum haemorrhage and pregnancy-induced hypertension were still the most common reasons for intensive care unit admission. There was an increasing trend of intensive care unit admissions following elective caesarean section for placenta praevia and for early aggressive intervention of pre-eclampsia. Maternal mortality remained low but had not decreased. The intensive care unit admission rate by itself might not be a helpful indicator of obstetric performance.

This study assessed the efficacy of induction of labour in twin pregnancies relative to singleton pregnancies within a predominantly Chinese patient population. This retrospective case-matched cohort study included patients with twin pregnancies who underwent induction of labour at our institution in Hong Kong between 2012 and 2020. Patients with twin pregnancies were matched one-to-one with singleton pregnancies based on parity, maternal age, and the indication for induction of labour. The primary outcome was the mode of delivery. Secondary outcomes included the time from oxytocin infusion to delivery, indications for caesarean or instrumental delivery, and maternal and neonatal outcomes. In total, 160 women with twin pregnancies met the inclusion criteria and were matched with 160 singleton pregnancies. Caesarean section was performed in 42 patients (26.3%) with twin pregnancies and 27 patients (16.9%) with singleton pregnancies undergoing induction of labour. Patients with twin pregnancies had a significantly higher risk of caesarean section relative to those with singleton pregnancies (odds ratio=2.14, 95% confidence interval =1.14-4.04; P=0.024). Internal podalic version was required in 13.6% of cases for the vaginal delivery of the second twin. There was no significant difference between the groups in the time from oxytocin administration to vaginal delivery (P=0.143). Despite a higher induction failure rate, about three quarters of twin pregnancy patients achieved successful vaginal deliveries. Our findings inform decision making for patients and obstetricians, emphasising the importance of training for internal podalic version to aid second twin delivery and reduce caesarean rates in twin pregnancies.

The Hong Kong Hospital Authority has newly introduced a new Down's syndrome screening algorithm that offers free-of-charge non-invasive prenatal testing (NIPT) to women who screen as high risk. In preparation for this public-funded second tier NIPT service, the present study was conducted to retrospectively analyse women eligible for NIPT and to review the local literature. Our retrospective study included women screened as high risk for Down's syndrome (adjusted term risk ≥1:250) during the period of 1 January 2015 to 31 December 2016. We performed descriptive statistics and multivariable logistic regression to examine the factors associated with women's choice between NIPT and invasive testing. We also reviewed existing local literature about second tier NIPT. The study included 525 women who screened positive: 67% chose NIPT; 31% chose invasive diagnostic tests; and 2% declined further testing. Our literature review showed that in non-research (self-financed NIPT) settings, NIPT uptake rates have been increasing since 2011. Nulliparity, first trimester status, higher education, maternal employment, and conception by assisted reproductive technology are common factors associated with self-financed NIPT after positive screening. Among women choosing NIPT, the rates of abnormal results have typically been around 8% in studies performed in Hong Kong. Implementation of second tier NIPT in the public setting is believed to be able to improve quality of care. We expect that the public in Hong Kong will welcome the new policy.

We conducted a pilot study of ultrasonographic tracking of anterior shoulder engagement at the second stage of labour to look for any warning sign for shoulder dystocia in 12 women.

We previously showed microRNAs (miRNAs) in plasma are potential biomarkers for colorectal cancer detection. Here, we aimed to develop specific blood-based miRNA assay for breast cancer detection. TaqMan-based miRNA profiling was performed in tumor, adjacent non-tumor, corresponding plasma from breast cancer patients, and plasma from matched healthy controls. All putative markers identified were verified in a training set of breast cancer patients. Selected markers were validated in a case-control cohort of 170 breast cancer patients, 100 controls, and 95 other types of cancers and then blindly validated in an independent set of 70 breast cancer patients and 50 healthy controls. Profiling results showed 8 miRNAs were concordantly up-regulated and 1 miRNA was concordantly down-regulated in both plasma and tumor tissue of breast cancer patients. Of the 8 up-regulated miRNAs, only 3 were significantly elevated (p<0.0001) before surgery and reduced after surgery in the training set. Results from the validation cohort showed that a combination of miR-145 and miR-451 was the best biomarker (p<0.0001) in discriminating breast cancer from healthy controls and all other types of cancers. In the blind validation, these plasma markers yielded Receiver Operating Characteristic (ROC) curve area of 0.931. The positive predictive value was 88% and the negative predictive value was 92%. Altered levels of these miRNAs in plasma have been detected not only in advanced stages but also early stages of tumors. The positive predictive value for ductal carcinoma in situ (DCIS) cases was 96%. These results suggested that these circulating miRNAs could be a potential specific biomarker for breast cancer screening.

Background Early-onset pre-eclampsia (ePE) is a severe pregnancy complication characterized by dysregulated trophoblast functions and impaired placentation during early pregnancy, leading to substantial maternal and fetal morbidity. While circumstantial evidence indicates defective secretion from endometrial glands impairs placental development, direct evidence linking maternal glandular dysfunction to ePE pathogenesis remains elusive. Methods We established endometrial glandular organoids from women with ePE and healthy pregnancies, analyzing their secretomes by iTRAQ-based proteomics, RNAseq, and spatial transcriptomics. Functional effects of organoid secretomes on trophoblasts were examined in vitro. An endometrial-specific apolipoprotein D (APOD) knock-in mouse model was studied in vivo. APOD levels in first-trimester serum samples from women who later developed ePE were compared to healthy pregnancies. Results Secretomes from ePE derived endometrial organoids impeded spiral artery remodeling. Multiomic analyses revealed increased APOD production in both ePE organoids and decidual tissues. APOD overexpression disrupted trophoblast functions and endothelial vascular remodeling in vitro, and recapitulated ePE phenotypes in an APOD knock-in mouse model through PI3K/Akt-mediated placental ferroptosis and potential ER stress induction. Ferroptosis inhibition with Fer-1 rescued placental defects and PE symptoms in APOD knock-in mice. Elevated APOD levels in first-trimester serum samples from women who later developed ePE suggest its potential as an early biomarker. Conclusion This study provides the first direct evidence linking dysregulated endometrial gland function to defective placentation and ePE. APOD was identified as a crucial endometrial gland-secreted factor contributing to ePE, suggesting its potential as an early biomarker and therapeutic target.

In this randomized study of patients with upper gastrointestinal bleeding, infusion of omeprazole, as compared with placebo, before endoscopy reduced the incidence of endoscopic treatment (19.1% vs. 28.4%, P=0.007) and, among patients with peptic ulcers, resulted in fewer actively bleeding ulcers and more ulcers with clean bases. These findings suggest that infused omeprazole is beneficial for patients with upper gastrointestinal bleeding who are awaiting endoscopy. In patients with upper gastrointestinal bleeding, infusion of omeprazole before endoscopy reduced the incidence of endoscopic treatment (19.1% vs. 28.4%) and, among patients with peptic ulcers, resulted in fewer actively bleeding ulcers and more ulcers with clean bases. In patients with bleeding peptic ulcers, we previously showed that infusion of a high-dose proton-pump inhibitor after hemostasis had been achieved during endoscopy reduced recurrent bleeding and improved clinical outcomes. 1 The adjuvant use of high-dose proton-pump inhibitors in endoscopic therapy has also been endorsed in two consensus statements 2 , 3 and confirmed in two meta-analyses. 4 , 5 Clot formation over arteries is pH dependent; a gastric pH above 6 is thought to be critical for platelet aggregation. 6 When given intravenously and at a high dose, proton-pump inhibitors can be used to maintain a neutral gastric pH. 7 In clinical practice, treatment with proton-pump . . .

Background Despite the declining incidence of gastric cancer, mortality rate remains high due to late presentation. We aimed to evaluate the sensitivity of miRNA as a diagnostic marker for gastric cancer in the circulation. Methods Plasma samples from 3 independent groups comprise 123 gastric cancer patients and 111 healthy controls for miRNA profiling from microarray screening. Results Microarray data showed that 25 miRNAs were upregulated in gastric cancer patients and 6 highly expressed miRNAs (miR-18a, miR-140-5p, miR-199a-3p, miR-627, miR-629 and miR-652) were selected for validation. In an independent validation set, levels of miR-627, miR-629 and miR-652 were significantly higher in gastric cancer patients than healthy controls ( P <0.0001). An algorithm with improved sensitivity and specificity as gastric cancer classifier was adopted and validated in another random set of 15 plasma samples. Results showed that combination of 3 miRNAs obtained the highest area under curve, with a cut-off at 0.373, with a sensitivity of 86.7 % and a specificity of 85.5 %. Conclusion This study revealed a three-miRNA signature as a promising classifier for gastric cancer, and greatly enhances the feasibility of circulating miRNAs as non-invasive diagnostic marker for this disease.

Dysbiosis of the human oral microbiota has been reported to be associated with oral cavity squamous cell carcinoma (OSCC) while the host-microbiota interactions with respect to the potential impact of pathogenic bacteria on host genomic and epigenomic abnormalities remain poorly studied. In this study, the mucosal bacterial community, host genome-wide transcriptome and DNA CpG methylation were simultaneously profiled in tumors and their adjacent normal tissues of OSCC patients. Significant enrichment in the relative abundance of seven bacteria species (Fusobacterium nucleatum, Treponema medium, Peptostreptococcus stomatis, Gemella morbillorum, Catonella morbi, Peptoanaerobacter yurli and Peptococcus simiae) were observed in OSCC tumor microenvironment. These tumor-enriched bacteria formed 254 positive correlations with 206 up-regulated host genes, mainly involving signaling pathways related to cell adhesion, migration and proliferation. Integrative analysis of bacteria-transcriptome and bacteria-methylation correlations identified at least 20 dysregulated host genes with inverted CpG methylation in their promoter regions associated with enrichment of bacterial pathogens, implying a potential of pathogenic bacteria to regulate gene expression, in part, through epigenetic alterations. An in vitro model further confirmed that Fusobacterium nucleatum might contribute to cellular invasion via crosstalk with E-cadherin/β-catenin signaling, TNFα/NF-κB pathway and extracellular matrix remodeling by up-regulating SNAI2 gene, a key transcription factor of epithelial-mesenchymal transition (EMT). Our work using multi-omics approaches explored complex host-microbiota interactions and provided important insights into genetic and functional basis in OSCC tumorigenesis, which may serve as a precursor for hypothesis-driven study to better understand the causational relationship of pathogenic bacteria in this deadly cancer.