Alzheimer's disease (AD) is characterized by accumulation and deposition of Aβ peptides in the brain. Aβ deposition in cerebrovessels occurs in many AD patients and results in cerebral amyloid angiopathy (AD/CAA). Since Aβ can be transported across blood–brain barrier (BBB), aberrant Aβ trafficking across BBB may contribute to Aβ accumulation in the brain and CAA development. Expression analyses of 273 BBB-related genes performed in this study showed that the drug transporter, ABCG2, was significantly upregulated in the brains of AD/CAA compared with age-matched controls. Increased ABCG2 expression was confirmed by Q-PCR, Western blot, and immunohistochemistry. Abcg2 was also increased in mouse AD models, Tg-SwDI and 3XTg. Aβ alone or in combination with hypoxia/ischemia failed to stimulate ABCG2 expression in BBB endothelial cells; however, conditioned media from Aβ-activated microglia strongly induced ABCG2 expression. ABCG2 protein in AD/CAA brains interacted and coimmunoprecipitated with Aβ. Overexpression of hABCG2 reduced drug uptake in cells; however, interaction of Aβ_1–40with ABCG2 impaired ABCG2-mediated drug efflux. The role of Abcg2 in Aβ transport at the BBB was investigated in Abcg2-null and wild-type mice after intravenous injection of Cy5.5-labeled Aβ_1–40or scrambled Aβ_40–1. Optical imaging analyses of live animals and their brains showed that Abcg2-null mice accumulated significantly more Aβ in their brains than wild-type mice. The finding was confirmed by immunohistochemistry. These results suggest that ABCG2 may act as a gatekeeper at the BBB to prevent blood Aβ from entering into brain. ABCG2 upregulation may serve as a biomarker of CAA vascular pathology in AD patients.

Dietary calcium supplements can prevent osteoporosis, and our previous investigation demonstrated a notable increase in duodenal calcium absorption due to the impact of estrogen. The decrease of estrogen level in postmenopausal women is significantly associated with an increased incidence of osteoporosis. In this study, we further investigated the role of estrogen regulating duodenal calcium absorption in osteoporosis and elucidated its underlying molecular mechanism. We recruited ten young women in the prefollicular stage and ten menopausal women for the study. Furthermore, we performed trials on mice, as well as human duodenal epithelial cells and SCBN cells. The measurement of calcium absorption in the duodenum of mice was conducted through single-pass perfusion in vivo. We used a calcium imaging system to evaluate calcium absorption in SCBN cells. The bone mineral density was measured using small animal computed tomography and a bone densitometer. Furthermore, The expression levels of calcium transport proteins, namely plasma membrane calcium pump (PMCA1b) and transient receptor potential cation channel (TRPV6), were evaluated using western blot analysis. Compared to young women, postmenopausal women exhibited significant reductions in estrogen levels, bone mineral density, and the expression of PMCA1b and TRPV6 in duodenal mucosal tissues (P < 0.05). A positive correlation was also observed between estrogen levels, the expression of PMCA1b and TRPV6, and bone mineral density (P < 0.05). The estrogen levels, the expression of PMCA1b and TRPV6 in the duodenal mucosa, calcium absorptions, and bone mineral density were observed to be decreased in ovariectomized mice based on in vivo animal experiments (P < 0.05). However, estrogen upplementation can enhance duodenal calcium absorptions and ameliorate osteoporosis in ovariectomized mice, with its primary mechanism of action being the regulation of PMCA1b expression and function (P < 0.05). The findings from SCBN cells further confirm that estrogen enhances duodenal calcium absorption through the effect of ERβ on PMCA1b. Estrogen enhances the expression and functionality of PMCA1b in duodenal mucosal cells via ERβ, promoting duodenal calcium absorption and ameliorating postmenopausal osteoporosis.

Background: High‐grade intraepithelial neoplasia (HIN) is the precursor of oesophageal squamous cell carcinoma. The molecular and functional properties of HIN are determined by intrinsic origin cells and the extrinsic microenvironment. Yet, these factors are poorly understood.Methods: We performed single‐cell RNA sequencing of cells from HINs and adjacent tissues from the human oesophagus. We analysed the heterogeneity of basal layer cells and confirmed it using immunostaining. Aneuploid cells in HIN were studied using primary cell culture combined with karyotype analysis. We reconstructed the lineage relationship between tumour and normal populations based on transcriptome similarity. Integration analysis was applied to our epithelial data and published invasive cancer data, and results were confirmed by immunostaining and 3D organoid functional experiments. We also analysed the tumour microenvironment of HIN.Results: The basal layer contained two cell populations: KRT15^highSTMN1^low and KRT15^highSTMN1^high cells, which were located mainly in the interpapillary and papillary zones, respectively. The KRT15^highSTMN1^low population more closely resembled stem cells and transcriptome similarity revealed that HIN probably originated from these slow‐cycling KRT15^highSTMN1^low cells. 3D Organoid experiments and RNA‐sequencing showed that basal‐cell features and the differentiation ability of the normal epithelium were largely retained in HIN, but may change dramatically in tumour invasion stage. Moreover, the tumour microenvironment of HIN was characterised by both inflammation and immunosuppression.Conclusions: Our study provides a comprehensive single‐cell transcriptome landscape of human oesophageal HIN. Our findings on the origin cells and unique microenvironment of HIN will allow for the development of strategies to block tumour progression and even prevent cancer initiation.

A random-effects meta-analysis was performed in English and Chinese databases since its inception to August 2020 to assess the incidence, causes and severity of acute pancreatitis (AP) at various stages of pregnancy, maternal and foetal mortality. A total of 154 articles representing 4034 patients with AP during pregnancy in China were included for the analysis. The incidence of AP during pregnancy was 0.0469 (95% confidence interval [CI], 0.0349; 0.0627) in the first trimester, whereas it was 0.2518 (95% CI, 0.2210; 0.2854) and 0.6323 (95% CI, 0.5870; 0.6753) in the second and third trimester, respectively. The major causes of AP were hypertriglyceridaemia (0.351 [95% CI, 0.3202; 0.3834]) and biliary pancreatitis (0.424 [95% CI, 0.4094; 0.5002]). The severity of AP was mild in majority of the patients. The incidence of AP at maternal mortality was 0.0184 (95% CI, 0.0126; 0.0269) and foetal mortality was 0.1018 (95% CI, 0.0867; 0.1192). Our meta-analysis revealed that hypertriglyceridaemia and biliary pancreatitis remain the major causes of AP during pregnancy. Foetal mortality requires further investigation.

Background. The study is aimed at evaluating the clinical attributes, types, and risk factors associated with poor outcomes in women with acute pancreatitis (AP) during pregnancy. Methods. From 2011 to 2020, 45 antenatal mothers with AP were included in this noninterventional, retrospective study. The correlation between etiology of AP, its severity, biochemical parameters, length of stay, and treatment was analyzed. Based on the presence of organ failure and systemic complications, the severity of AP was classified according to the revised Atlantic criteria. Results. In total, 19 (42.2%), 15 (33.3%), and 11 (24.2%) patients had mild AP (MAP), moderately severe AP (MSAP), and severe AP (SAP), respectively. The major cause of AP in these patients was hypertriglyceridemia (26.6%), while only 2 (4.44%) suffered from biliary pancreatitis. The median length of stay at hospital was significantly longer in patients with SAP ( ), and these patients had significantly higher triglycerides and total cholesterol levels when compared to MAP and MSAP. It was observed that levels of liver function enzymes such as alanine aminotransferase serum levels and aspartate aminotransferase serum levels were significantly higher in patients who stayed in hospital for >13 days. The presence of hypertriglyceridemia significantly increased the duration of stay (>13 days, ) and induced SAP ( ). Majority of patients with SAP received blood purification than those with MAP and MSAP ( ). Conclusion. Hypertriglyceridemia was associated with AP during pregnancy in our study. Early diagnosis of AP and assessment of its severity are very important for the general management of this disease.

Goal: The objective of this study was to investigate the clinical efficacy of endoscopic submucosal dissection (ESD) in the treatment of giant lateral developing rectal-type tumors (laterally spreading tumors, LSTs). Background: There are no specialized studies on the efficacy of ESD in the treatment of LSTs measuring >5 cm in diameter, surgery was often used in the past, but it has the disadvantages of large trauma, many complications, and high cost. Methods: The data of 185 patients with rectal LSTs who had undergone ESD in the digestive endoscopy center of our hospital from January 2012 to June 2020 were retrospectively analyzed. Based on the size of the lesions, the patients were divided into 2 groups: diameter ≤5 cm (110 cases) and diameter >5 cm (75 cases), and we summarized and analyzed the en bloc resection rate, curative resection rate, procedure time, muscle injury, bleeding, perforation, postoperative stricture, and recurrence. Results: There was no difference in the en bloc resection rate and R0 resection rate between the 2 groups (P=0.531). Moreover, there was no difference in the incidence of delayed perforation, postoperative stenosis, and recurrence, but the incidence of delayed bleeding was significantly higher in the giant LST group than the small LST group (P=0.001). Moreover, for giant rectal LSTs, the growth pattern of the lesion, JNET classification, and the extent of postoperative mucosal defect do not significantly affect the efficacy of ESD. It is worth mentioning that the operation time was longer in the group with a diameter >5 cm, in which perforation was more frequent and the muscle layer was more likely to be injured during ESD (P5 cm) is relatively difficult and can easily lead to intraoperative muscle injury, perforation, and late postoperative bleeding. However, if active intervention is performed, patients can still achieve good efficacy and prognosis, which can be applied in hospitals with certain conditions.