OBJECTIVE: In the developing liver, bipotent epithelial progenitor cells undergo lineage segregation to form hepatocytes, which constitute the bulk of the liver parenchyma, and biliary epithelial cells (cholangiocytes), which comprise the bile duct (a complex tubular network that is critical for normal liver function). Notch and TGFβ signalling promote the formation of a sheet of biliary epithelial cells, the ductal plate, that organises into discontinuous tubular structures. How these structures elongate and connect to form a continuous duct remains undefined. We aimed to define the mechanisms by which the ductal plate transitions from a simple sheet of epithelial cells into a complex and connected bile duct.
METHODS: By combining single-cell RNA sequencing of embryonic mouse livers with genetic tools and organoid models we functionally dissected the role of planar cell polarity in duct patterning.
RESULTS: We show that the planar cell polarity protein VANGL2 is expressed late in intrahepatic bile duct development and patterns the formation of cell-cell contacts between biliary cells. The patterning of these cell contacts regulates the normal polarisation of the actin cytoskeleton within biliary cells and loss of Vangl2 function results in the abnormal distribution of cortical actin remodelling, leading to the failure of bile duct formation.
CONCLUSIONS: Planar cell polarity is a critical step in the post-specification sculpture of the bile duct and is essential for establishing normal tissue architecture.
UNASSIGNED: Like other branched tissues, such as the lung and kidney, the bile ducts use planar cell polarity signalling to coordinate cell movements; however, how these biochemical signals are linked to ductular patterning remains unclear. Here we show that the core planar cell polarity protein VANGL2 patterns how cell-cell contacts form in the mammalian bile duct and how ductular cells transmit confluent mechanical changes along the length of a duct. This work sheds light on how biological tubes are patterned across mammalian tissues (including within the liver) and will be important in how we promote ductular growth in patients where the duct is mis-patterned or poorly formed.

Cystic fibrosis (CF) is a multi-organ disease caused by loss-of-function mutations in CFTR (which encodes the CF transmembrane conductance regulator ion channel). Cystic fibrosis related diabetes (CFRD) occurs in 40-50% of adults with CF and is associated with significantly increased morbidity and mortality. CFRD arises from insufficient insulin release from β cells in the pancreatic islet, but the mechanisms underlying the loss of β cell function remain understudied. Widespread pathological changes in the CF pancreas provide clues to these mechanisms. The exocrine pancreas is the epicenter of pancreas pathology in CF, with ductal pathology being the initiating event. Loss of CFTR function results in ductal plugging and subsequent obliteration. This in turn leads to destruction of acinar cells, fibrosis and fatty replacement. Despite this adverse environment, islets remain relatively well preserved. However, islet composition and arrangement are abnormal, including a modest decrease in β cells and an increase in α, δ and γ cell abundance. The small amount of available data suggest that substantial loss of pancreatic/islet microvasculature, autonomic nerve fibers and intra-islet macrophages occur. Conversely, T-cell infiltration is increased and, in CFRD, islet amyloid deposition is a frequent occurrence. Together, these pathological changes clearly demonstrate that CF is a disease of the pancreas/islet microenvironment. Any or all of these changes are likely to have a dramatic effect on the β cell, which relies on positive signals from all of these neighboring cell types for its normal function and survival. A thorough characterization of the CF pancreas microenvironment is needed to develop better therapies to treat, and ultimately prevent CFRD.

Laparoscopic cholecystectomy is the standard of care for cholecystolithiasis but carries an increased risk of biliary injury compared to open cholecystectomy. Complications from laparoscopic cholecystectomy can be related to several factors. These include - (i) technical factors that depend on the skill of the surgeon, (ii) pathologic factors such as associated inflammation and adhesions, and (iii) anatomic factors such as biliary anatomy. Aberrant biliary anatomy is a major cause of bile duct injury during surgery. To the best of our knowledge familial aberrant biliary anatomy has not been previously reported in the literature. We report a case series of two biological sisters with isolated posterior right duct syndrome and present a brief literature review of this medical condition.

The development of the mouse salivary gland involves a tip-driven process of branching morphogenesis that takes place in concert with differentiation into acinar, myoepithelial, and ductal (basal and luminal) sub-lineages. By combining clonal lineage tracing with a three-dimensional (3D) reconstruction of the branched epithelial network and single-cell RNA-seq analysis, we show that in tips, a heterogeneous population of renewing progenitors transition from a Krt14+ multipotent state to unipotent states via two transcriptionally distinct bipotent states, one restricted to the Krt14+ basal and myoepithelial lineage and the other to the Krt8+ acinar and luminal lineage. Using genetic perturbations, we show how the differential expression of Notch signaling correlates with spatial segregation, exits from multipotency, and promotes the Krt8+ lineage, whereas Kras activation promotes proacinar fate. These findings provide a mechanistic basis for how positional cues within growing tips regulate the process of lineage segregation and ductal patterning.

A report on the primary application of the modern technique of plastic removal of stricture of the Stenonic duct. A clinical case of surgical intervention in the localization of stricture and salivary stone is considered. The analysis of the patient\'s medical history, ultrasound diagnostics, multispiral computed tomography of the maxillofacial region was carried out. Based on the results of the examination, the choice of the surgical intervention technique was made.
Сообщение о первичном применении современной методики пластического устранения стриктуры стенонова протока. Рассмотрен клинический случай проведения оперативного вмешательства при локализации стриктуры и слюнного камня. Проведены анализ истории заболевания пациента, ультразвуковая диагностика, мультиспиральная компьютерная томография челюстно-лицевой области. На основании результатов обследования определена методика оперативного вмешательства.

暂无摘要。

Allergic rhinitis (AR) is a type I hypersensitivity reaction of the nasal mucosa, primarily mediated by IgE, with a complex etiology, determined by genetic and environmental interactions. Several mechanisms by which AR affect middle ear and cause conductive hearing loss have been well described. There is paucity of data regarding involvement of inner ear in AR patients leading to sensorineural hearing loss. However, endolymphatic sac and outer hair cells have been hypothesized to be the seat of immunoreactivity. To study the audiological profile in AR and effect of AR on inner ear functions. 100 cases of AR patients (55 males, 45 females, mean age group 21-30 years) and 100 controls (65 males, 35 females, mean age group 41-50 years) were enrolled in study. All underwent thorough clinical ear, nose and throat examination, diagnostic nasal endoscopy and otoendoscopy, followed by audiological assessment including pure tone audiometry, tympanometry and oto-acoustic emission test. Hearing results of both the groups were compared and analysed statistically. Thirty two patients among case group had sensorineural hearing loss, pronounced at 4000 and 8000 Hz frequencies. 18 patients showed conductive hearing loss in the form of type B or type C tympanogram. 32 patients of AR patients showed unusual oto-acoustic emission test. We found higher prevalence of high frequency sensorineural hearing loss in pure tone audiometry and abnormal OAEs in patients having upper airway allergy. The likely seat of damage appears to be the inner ear as evidenced by recordings of OAE in allergic patients.

BACKGROUND: The objectives of this study were to evaluate the relationship between ductal morphometry and ramification patterns in the submandibular gland and pancreas in order to validate their common fractal dimension.
METHODS: X-ray ductography with software-aided morphometry were obtained by injecting barium sulphate in the ducts of post-mortem submandibular gland and pancreas specimens harvested from 42 adult individuals.
RESULTS: Three cases were excluded from the study because of underlying pathology. There was a significant correlation between the length of the main pancreatic duct (MPD) and the intraglandular portion of the right submandibular duct (SMD) (r = 0.3616; p = 0.028), and left SMD (r = 0.595; p < 0.01), respectively, but their maximal diameters did not correlate (r = 0.139-0.311; p > 0.05). Both dimensions of the SMD showed a significant right-left correlation (p < 0.05). The number of MPD side branches (mean = 37) correlated with the number of side branches of left SMD, but not with the right one (mean = 9). Tortuosity was observed in 54% of the MPD, 32% of the right SMD, and 24% of the left SMD, with mutual association only between the two salivary glands.
CONCLUSIONS: Although the length of intraglandular SMD and MPD correlate, other morphometric ductal features do not, thus suggesting a more complex relationship between the two digestive glands.

Leucine rich repeat containing G protein-coupled receptor 5(Lgr5) is widely expressed in multiple tissues and can be used as a stem cell marker in a variety of epithelial organs (including the small intestine, colon, stomach and hair follicles). In this study, we used Lgr5-CreERT2+/- and Rosa26-mTmG hybridized transgenic mice to investigate the expression of Lgr5 in both ductal epithelial cells during pancreas development and in vitro cultured pancreatic duct organoids. After induction with Tamoxifen, the Lgr5 expression was analyzed by detecting the enhanced green fluorescence protein in the pancreatic tissue sections in adult animals and embryos at different developmental stages. The results showed that Lgr5 expression was detected neither in adult pancreatic duct epithelia nor in the embryonic pancreatic tissues at day 15.5 or in newborn mice. However, when 4-hydroxy-Tamoxifen was supplemented to the culture medium, EGFP could be detected in the primary pancreatic duct organoids from Lgr5-Cre ERT2+/-; Rosa26-mTmG mice. These results suggested that Lgr5 was not expressed in adult and embryonic pancreatic tissues; but could be expressed in the cultured pancreas ductal organoids. The research lays the foundation for exploring specific gene expression patterns in stem/progenitor cells during pancreatic development.
富含亮氨酸重复序列G蛋白偶联受体5 (leucine-rich repeat containing G protein-coupled receptor 5, Lgr5)在体内分布广泛,可以作为多种上皮组织(包括小肠、结肠、胃和毛囊)中干细胞的标记物。为了探究小鼠(Mus musculus)胰腺发育过程中导管上皮细胞及体外培养的胰腺导管类器官中Lgr5的表达情况,本研究利用Lgr5-CreERT2+/-和Rosa26-mTmG杂交后的转基因小鼠,经Tamoxifen (他莫昔芬)诱导后,观察不同发育阶段胰腺组织切片的荧光表达情况,并通过三维培养建立成体小鼠胰腺导管类器官,观察诱导后类器官细胞中的荧光变化。结果显示：Tamoxifen诱导的正常成体转基因小鼠胰腺导管内未检测到表达Lgr5的细胞;通过对孕鼠及哺乳母鼠注射Tamoxifen,在胚胎发育15.5 d和新生小鼠胰腺中也未发现Lgr5阳性细胞;但是将4-hydroxy- Tamoxifen (4-羟基-他莫昔芬)添加到培养基中,在Lgr5-CreERT2+/-;Rosa26-mTmG转基因小鼠胰腺导管来源的类器官中检测到部分细胞表达Lgr5。本研究结果证实,在成体及胚胎胰腺组织中没有检测到Lgr5表达,但在体外培养的胰腺导管类器官细胞中检测到Lgr5表达。本研究为探索胰腺发育过程中干/祖细胞特异性表达基因奠定了基础。.

Duct air quality monitoring (DAQM) is a typical process for building controls, with multiple infections outbreaks reported over time linked with duct system defilement. Various research works have been published with analyses on the air quality inside ducting systems using microcontrollers and low-cost smart sensors instead of conventional meters. However, researchers face problems sending data within limited range and cross-sections inside the duct to the gateway using available wireless technologies, as the transmission is entirely a non-line-of-sight. Therefore, this study developed a new instrument for DAQM to integrate microcontrollers and sensors with a mobile robot using LoRa as the wireless communication medium. The main contribution of this paper is the evaluation of mesh LoRa strategies using our instrument to overcome network disruption problems at the cross-sections and extend the coverage area within the duct environment. A mobile LoRa-based data collection technique is implemented for various data sensors such as DHT22, MQ7, MQ2, MQ135, and DSM50A to identify carbon monoxide, carbon dioxide, smoke, and PM2.5 levels. This study analyzed the efficiency of data transmission and signal strength to cover the air duct environment using several network topologies. The experimental design covered four different scenarios with different configurations in a multi-story building. The network performance evaluations focused on the packet delivery ratio (PDR) and the received signal strength indicator (RSSI). Experimental results in all scenarios showed an improvement in Packet Delivery Ratio (PDR) and significant improvement in the coverage area in the mesh network setup. The results conclude that the transmission efficiency and coverage area are significantly enhanced using the proposed LoRa mesh network and potentially expanded in larger duct environments.