Single-cell RNA sequencing-guided fate-mapping toolkit delineates the contribution of yolk sac erythro-myeloid progenitors.

Erythro-myeloid progenitors of the yolk sac that originates during early embryo development has been suggested to generate tissue-resident macrophage, mast cell, and even endothelial cell populations from fetal to adult stages. However, the heterogeneity of erythro-myeloid progenitors (EMPs) is not well characterized. Here, we adapt single-cell RNA sequencing to dissect the heterogeneity of EMPs and establish several fate-mapping tools for each EMP subset to trace the contributions of different EMP subsets. We identify two primitive and one definitive EMP subsets from the yolk sac. In addition, we find that primitive EMPs are decoupled from definitive EMPs. Furthermore, we confirm that primitive and definitive EMPs give rise to microglia and other tissue-resident macrophages, respectively. In contrast, only Kit+ Csf1r- primitive EMPs generate endothelial cells transiently during early embryo development. Overall, our results delineate the contribution of yolk sac EMPs more clearly based on the single-cell RNA sequencing (scRNA-seq)-guided fate-mapping toolkit.

[Effect of recombinant human thrombin for hemostasis in liver resection: a randomized controlled phase â ¢ clinical trial].

Objective: To evaluate the hemostatic efficacy, safety and immunogenicity of recombinant human thrombin in the treatment of liver wounds that still ooze after conventional surgical hemostasis. Methods: A multicenter, stratified randomized, double-blind, placebo-controlled phase Ⅲ trial with a planned enrollment of 510 subjects at 33 centers, with a 2∶1 randomization to the thrombin group versus the placebo group. An interim analysis will be conducted after approximately 70% of the subjects have completed the observation period. The primary efficacy endpoint was the rate of hemostasis within 6 minutes at the point of bleeding that could be evaluated. Safety analysis was performed one month after surgery, and the positive rates of anti-drug antibody (ADA) and neutralizing antibody were evaluated. Results: At the interim analysis, a total of 348 subjects had been randomized and received the study drug (215 were male and 133 were female). They were aged 19-69 (52.9±10.9)years. Among them, 232 were in the thrombin group and 116 were in the placebo group, with balanced and comparable demographics and baseline characteristics between the two groups. The hemostasis rate at 6 minutes was 71.6% (95%CI:65.75%-77.36%) in the thrombin group and 44.0% (95%CI: 34.93%-53.00%) in the placebo group, respectively (P<0.001). No grade≥3 drug-related adverse events and no drug-related deaths were reported from the study.No recombinant human thrombin-induced immunologically-enhanced ADA or immunologically-induced ADA was detected after topical use in subjects. Conclusion: Recombinant human thrombin has shown significant hemostatic efficacy and good safety in controlling bleeding during liver resection surgery, while also demonstrating low immunogenicity characteristics.

Telemedicine acceptance by older adults in Hong Kong during a hypothetical severe outbreak and after the COVID-19 pandemic: a cross-sectional cohort survey.

INTRODUCTION: Telemedicine services worldwide have experienced unprecedented growth since the early days of the coronavirus disease 2019 (COVID-19) pandemic. Multiple studies have shown that telemedicine is an effective alternative to conventional in-person patient care. This study explored the public perception of telemedicine in Hong Kong, specifically among older adults who are most vulnerable to COVID-19. METHODS: Medical students from The Chinese University of Hong Kong conducted in-person surveys of older adults aged ≥60 years. Each survey collected socio-demographic information, medical history, and concerns regarding telemedicine use. Univariate and multivariate logistic regression analyses were conducted to identify statistically significant associations. The primary outcomes were acceptance of telemedicine use during a hypothetical severe outbreak and after the COVID-19 pandemic. RESULTS: There were 109 survey respondents. Multivariate logistic regression analyses revealed that the expectation of government subsidies for telemedicine services was the strongest common driver and the only positive independent predictor of telemedicine use during a hypothetical severe outbreak (P=0.016) and after the COVID-19 pandemic (P=0.003). No negative independent predictors of telemedicine use during a hypothetical severe outbreak were identified. Negative independent predictors of telemedicine use after the COVID-19 pandemic included older age and residence in the New Territories (both P=0.001). CONCLUSION: Government support, such as telemedicine-specific subsidies, will be important for efforts to promote telemedicine use in Hong Kong during future severe outbreaks and after the COVID-19 pandemic. Robust dissemination of information regarding the advantages and disadvantages of telemedicine for the public, especially older adults, is needed.

User perceptions of COVID-19 telemedicine testing services, disease risk, and pandemic preparedness: findings from a private clinic in Hong Kong.

INTRODUCTION: During the coronavirus disease 2019 (COVID-19) pandemic, telemedicine has been regarded as a method for providing safe access to healthcare. Here, we explored the experiences of individuals using telemedicine in Hong Kong during the COVID-19 pandemic to understand their risk perceptions and preparedness measures. METHODS: We conducted a cross-sectional online survey of telemedicine users of private clinic-based COVID-19 testing services from 6 April to 11 May 2020. All users were invited to complete an anonymous online survey regarding COVID-19 risk perception and preparedness measures. The results of the survey were compared with the findings of a previous territory-wide survey. RESULTS: In total, 141 of 187 telemedicine users agreed to participate; the response rate was 75.4%. Of the participants, 95.1% (116/122) believed that telemedicine consultations were useful. Nearly half of the participants (49.0%) agreed or strongly agreed that telemedicine consultations were appropriate during the COVID-19 pandemic. Most participants believed that telemedicine consultations could perform the functions of 'health protection, promotion and disease prevention' (73.6%) and 'diagnosis' (64.0%). Concerning the choice of telemedicine provider, almost all participants (99.2%) were willing to consult medical doctors; more than half of the participants (54.1%) were willing to consult registered nurses, but only 13.1% were willing to consult non-clinical staff who had been trained to provide telemedicine services. CONCLUSION: The use of telemedicine for screening and patient education can be encouraged during the COVID-19 pandemic in Hong Kong.

Two-Dimensional Terahertz Spectroscopy of Nonlinear Phononics in the Topological Insulator MnBi_{2}Te_{4}.

The interaction of a single-cycle terahertz electric field with the topological insulator MnBi_{2}Te_{4} triggers strongly anharmonic lattice dynamics, promoting fully coherent energy transfer between the otherwise noninteracting Raman-active E_{g} and infrared (IR)-active E_{u} phononic modes. Two-dimensional terahertz spectroscopy combined with modeling based on the classical equations of motion and symmetry analysis reveals the multistage process underlying the excitation of the Raman-active E_{g} phonon. In this nonlinear combined photophononic process, the terahertz electric field first prepares a coherent IR-active E_{u} phononic state and subsequently interacts with this state to efficiently excite the E_{g} phonon.

Consensus recommendations for the screening, diagnosis, and management of Helicobacter pylori infection in Hong Kong.

Helicobacter pylori infection causes chronic gastric inflammation that contributes to various gastroduodenal diseases, including peptic ulcer and gastric cancer. Despite broad regional variations, the prevalence of resistance to antibiotics used to manage H pylori infection is increasing worldwide; this trend could hinder the success of eradication therapy. To increase awareness of H pylori and improve the diagnosis and treatment of its infection in Hong Kong, our consensus panel proposed a set of guidance statements for disease management. We conducted a comprehensive review of literature published during 2011 and 2021, with a focus on articles from Hong Kong or other regions of China. We evaluated the evidence using the Oxford Centre for Evidence-Based Medicine's 2011 Levels of Evidence and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system and sought consensus through online voting and a subsequent face-to-face meeting, which enabled us to develop and refine the guidance statements. This report consists of 24 statements regarding the epidemiology and burden, screening and diagnosis, and treatment of H pylori. Key guidance statements include a recommendation to use the test-and-treat approach for high-risk individuals, as well as the confirmation that triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin remains a valid first-line option for adults and children in Hong Kong.

Circular RNA circCRIM1 suppresses lung adenocarcinoma cell migration, invasion, EMT, and glycolysis through regulating miR-125b-5p/BTG2 axis.

The article "Circular RNA circCRIM1 suppresses lung adenocarcinoma cell migration, invasion, EMT, and glycolysis through regulating miR-125b-5p/BTG2 axis, by S.-J. Zhang, J. Ma, J.-C. Wu, Z.-Z. Hao, Y.-A. Zhang, Y.-J. Zhang, published in Eur Rev Med Pharmacol Sci 2020; 24 (7): 3761-3774-DOI: 10.26355/eurrev_202004_20841-PMID: 32329853" has been withdrawn from the authors due to some technical reasons. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20841.

CircRNA EPB41L2 inhibits tumorigenicity of lung adenocarcinoma through regulating CDH4 by miR-211-5p.

The article "CircRNA EPB41L2 inhibits tumorigenicity of lung adenocarcinoma through regulating CDH4 by miR-211-5p, by S.-J. Zhang, J. Ma, J.-C. Wu, Z.-Z. Hao, Y.-N. Zhang, Y.-J. Zhang, published in Eur Rev Med Pharmacol Sci 2020; 24 (7): 3749-3760-DOI: 10.26355/eurrev_202004_20839-PMID: 32329852" has been withdrawn from the authors due to inaccuracies and mistakes. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20839.

[Cone-beam CT evaluation of the Monson's spherical radius of young adults in Guangdong].

Objective: To measure and analyze the spherical radius of Monson of normal young people in Guangdong province using cone-beam CT (CBCT), and to establish a personalized measurement method of the spherical radius of Monson to provide a reference for clinical application of Monson spherical radius in occlusal reconstruction. Methods: Sixty healthy young adults from physical examination population at Stomatology Hospital of Guangzhou Medical University [30 males and 30 females, aged (22.1±2.0) years 18-26 years) were recruited, and their CBCT were taken. Three-dimensional reconstruction of CBCT data was carried out, and the reconstructed models were fixed, traced and measured. The difference of Monson spherical radius between male and female was compared by using a single sample t-test. Results: The Monson spherical radius was (100.72±4.89) mm. The Monson spherical radius of male and female were (103.48±4.19) mm and (97.97±3.93) mm respectively. The difference between male and female was statistically significant (P<0.01). Conclusions: CBCT can be used to accurately measure the spherical radius of Monson and can be used as a reference for reconstruction of occlusal plane.

CircRNA EPB41L2 inhibits tumorigenicity of lung adenocarcinoma through regulating CDH4 by miR-211-5p.

OBJECTIVE: Circular RNAs (circRNAs) can make contributions to cell proliferation, migration and invasion in lung adenocarcinoma (LUAD). Circ_Band 4.1-like protein 2 (circ_EPB41L2) was found to have anti-tumor roles in lung cancer. Herein, we investigated the roles of circ_EPB41L2 in LUAD tumorigenicity. PATIENTS AND METHODS: The expression of circ_EPB41L2, microRNA (miR)-211-5p, and Cadherin-4 (CDH4) was measured using quantitative real-time polymerase chain reaction. Western blot was used to detect the levels of CDH4, Ki67, and E-cadherin. Cell proliferation, migration and invasion were examined using 3-(4,5)-dimethylthiazol(-z-y1)-3,5-di-phenyltetrazoliumbromide (MTT) assay and transwell assay, respectively. The interaction between miR-211-5p and circ_EPB41L2 or CDH4 was confirmed by Dual-Luciferase reporter assay. In vivo experiments were conducted using the murine xenograft model. RESULTS: Circ_EPB41L2 and CDH4 were down-regulated in LUAD tissues and cell lines. Overexpressed circ_EPB41L2 or CDH4 acted as a suppressor in the LUAD cell proliferation, invasion and migration in vitro. MiR-211-5p directly bound to circRNA_EPB41L2 and CDH4 3'-UTR, and circ_EPB41L2 indirectly regulated CDH4 expression by binding to miR-211-5p in LUAD cells. Furthermore, rescue assay showed circ_EPB41L2 played a protective role by repressing proliferation, migration and invasion through regulating CDH4 and miR-211-5p in LUAD cells. Besides, in vivo experiments indicated circ_EPB41L2 overexpression also inhibited tumor growth through regulating miR-211-5p and CDH4. CONCLUSIONS: Circ_EPB41L2 functioned as a tumor suppressor to inhibit the proliferation, migration and invasion through regulating CDH4 by miR-211-5p in LUAD cells, suggesting a new understanding on the tumorigenesis of LUAD and novel molecular therapeutic targets.

Circular RNA circCRIM1 suppresses lung adenocarcinoma cell migration, invasion, EMT, and glycolysis through regulating miR-125b-5p/BTG2 axis.

OBJECTIVE: The present studies indicate that circRNAs play pivotal roles in human cancers. Lung adenocarcinoma (LUAC), one of lung cancer types, has high metastasis rate. Herein, we focused our study on the function and mechanism of circular RNA circCRIM1 in LUAC development. PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction (qRT-PCR) was performed to detect the levels of circCRIM1, miR-125b-5p, and BTG anti-proliferation factor 2 (BTG2). Transwell assay was carried out to assess cell migration and invasion. The protein levels of BTG2, EMT markers, and HK2 were measured by Western blot. Glycolysis was analyzed through determining glucose consumption and lactate production. Furthermore, the targets of circCRIM1 and miR-125b-5p were predicted and verified by starBase and the dual-luciferase reporter assay, respectively. Also, whether circCRIM1 affecting tumor growth in vivo was explored using mouse xenograft assay. RESULTS: CircCRIM1 and BTG2 were downregulated, and miR-125b-5p was upregulated in LUAC tissues/cells. CircCRIM1 upregulation inhibited LUAC cell migration, invasion, epithelial-mesenchymal transition (EMT), glycolysis, and tumor growth. Moreover, circCRIM1 regulated LUAC cell development through targeting miR-125b-5p. MiR-125b-5p affected LUAC cell growth via binding to BTG2. Also, circCRIM1 promoted BTG2 expression by inhibiting miR-125b-5p expression in LUAC cells. CONCLUSIONS: CircCRIM1 was lowly expressed in LUAC. Moreover, circCRIM1 functioned as a sponge of miR-125b-5p to improve BTG2 expression, thereby suppressing LUAC development. Our finding indicated that circCRIM1 could be considered as a biomarker and target for the diagnosis and therapy of LUAC patients.

[An in vitro study of zinc-alpha-2-glycoprotein inhibits activation and proliferation of hepatic stellate cells].

Objective: To investigate the mechanism of occurrence and development of zinc-alpha-2-glycoprotein (AZGP1) in the activated hepatic stellate cells (HSCs) and liver fibrosis. Methods: The activated human hepatic stellate cell line LX2 was induced by the stimulation of transforming growth factor - ß1 to construct carbon tetrachloride liver fibrosis mice model. The situation expression of AZGP1 in liver cells and tissues were observed. Plasmid transfection method was used to detect the activation, proliferation, apoptotic functions and changes in related factors of LX2 cells, respectively, after the overexpression and inhibition of AZGP1expression. Univariate analysis of variance was used for multiple group comparison. Results: The results of immunofluorescence staining showed that AZGP1 protein was decreased and α-smooth muscle actin was increased in the activated LX2 cells, and the two were negatively correlated. AZGP1 gene and protein were significantly under-expressed in activated LX2 cells and liver tissues of mice with carbon tetrachloride liver fibrosis. Collagen I, matrix metalloproteinase-2, and α-smooth muscle actin genes and proteins were significantly down-regulated in LX2 cells after over-expression of AZGP1. Cell fluorescence showed that AZGP1-overexpressing cells were activated and α-smooth muscle actin protein was reduced. In addition, the proliferative activity and G1/S-specific cyclin D1 protein of LX2 cells were significantly reduced after overexpression of AZGP1, while cell cycle experiments showed that the proportion of cells overexpressing AZGP1 was significantly increased in the G0/G1 phase, and the proportion of S phase was significantly reduced. AZGP1 had no significant effect on the apoptosis of LX2 cells. Conclusion: AZGP1 can reverse liver fibrosis by inhibiting the activation and proliferation of hepatic stellate cells, and thereby overexpression of AZGP1 is expected to become a new target for liver fibrosis treatment.

Faecal microbiota transplantation for treatment of recurrent or refractory Clostridioides difficile infection in Hong Kong.

INTRODUCTION: Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated infection globally, causing significant morbidity and mortality. Faecal microbiota transplantation (FMT) has emerged as a promising option for recurrent and refractory CDI. This study aimed to assess the safety, efficacy, and feasibility of FMT for CDI in Hong Kong. METHODS: We conducted a single-centre, retrospective study for all consecutive cases of recurrent or refractory CDI who underwent FMT from 2013 to 2018. Clinical demographics, outcome, and safety parameters were collected. RESULTS: A total of 24 patients with recurrent or refractory CDI (median age 70 years, interquartile range=45.0-78.3 years; 67% male) were included. Over 80% had been recently hospitalised or were long-term care facility residents. Faecal microbiota transplantation was delivered by feeding tube in 11 (45.8%), oesophagogastroduodenoscopy in eight (33.3%), and colonoscopy in six (25%) of the patients. Resolution of diarrhoea without relapse within 8 weeks was achieved in 21 out of 24 patients (87.5%) after FMT. No deaths occurred within 30 days. The FMT was well tolerated and no serious adverse events attributable to FMT were reported. CONCLUSION: Our results confirm that FMT is a safe, efficacious, and feasible intervention for patients with refractory or recurrent CDI in Hong Kong. Given the increasing disease burden and the lack of effective alternatives in Hong Kong for difficult-to-treat cases of CDI, we recommend that a territory-wide FMT service be established to address increasing demand for this treatment.

Associations between Gastro-oesophageal Reflux Disease, Generalised Anxiety Disorder, Major Depressive Episodes, and Healthcare Utilisation: a Community-based Study.

OBJECTIVE: To examine the prevalence and comorbidity of gastro-oesophageal reflux disease (GORD) with generalised anxiety disorder (GAD) and major depressive episodes (MDE) in a general population using DSM-IV, and to evaluate the associations between these conditions and healthcare utilisation. METHODS: A random population-based telephone survey was conducted to record frequency of GORD symptoms, symptoms of GAD and MDE based on DSM-IV, and healthcare utilisation. RESULTS: Of 2011 respondents, 4.2% had weekly GORD and 13.9% had monthly GORD, whereas 3.8% reported GAD and 12.4% reported MDE. Those with monthly GORD had higher risk of GAD (p = 0.01) and MDE (p < 0.001). GORD symptom frequency was independently correlated with MDE and GAD in a dose-response manner. The number of psychiatric diagnoses was independently correlated with GORD. GORD symptom frequency, GAD, and MDE were correlated with consultation frequency. GORD symptom frequency was corelated with high investigation expenditure. CONCLUSION: GORD had a strong dose-response relationship with GAD and MDE in a Hong Kong population. Excessive healthcare utilisation should alert clinicians to the risk of psychiatric comorbidity.

4-dehydroxyepisarcovagine A, a new steroidal alkaloid from Sarcococca pruniformis Lindl.

A new steroidal alkaloid, 4-dehydroxyepisarcovagine A (1), along with seven known alkaloids, sarcovagine D (2), sarcovagenine C (3), epoxysarcovagenine D (4), Pachysamine L (5), Pachysamine E (6), sarcovagine A (7) and sarcovagine B (8), was isolated from the roots and stems of Sarcococca pruniformis Lindl. The structure of compound 1 was elucidated by means of spectroscopic analysis.

Universal intracellular biomolecule delivery with precise dosage control.

Intracellular delivery of mRNA, DNA, and other large macromolecules into cells plays an essential role in an array of biological research and clinical therapies. However, current methods yield a wide variation in the amount of material delivered, as well as limitations on the cell types and cargoes possible. Here, we demonstrate quantitatively controlled delivery into a range of primary cells and cell lines with a tight dosage distribution using a nanostraw-electroporation system (NES). In NES, cells are cultured onto track-etched membranes with protruding nanostraws that connect to the fluidic environment beneath the membrane. The tight cell-nanostraw interface focuses applied electric fields to the cell membrane, enabling low-voltage and nondamaging local poration of the cell membrane. Concurrently, the field electrophoretically injects biomolecular cargoes through the nanostraws and into the cell at the same location. We show that the amount of material delivered is precisely controlled by the applied voltage, delivery duration, and reagent concentration. NES is highly effective even for primary cell types or different cell densities, is largely cargo agnostic, and can simultaneously deliver specific ratios of different molecules. Using a simple cell culture well format, the NES delivers into >100,000 cells within 20 s with >95% cell viability, enabling facile, dosage-controlled intracellular delivery for a wide variety of biological applications.

Protein kinase C -activating isophthalate derivatives mitigate Alzheimer's disease-related cellular alterations.

Abnormal protein kinase C (PKC) function contributes to many pathophysiological processes relevant for Alzheimer's disease (AD), such as amyloid precursor protein (APP) processing. Phorbol esters and other PKC activators have been demonstrated to enhance the secretion of soluble APPα (sAPPα), reduce the levels of ß-amyloid (Aß), induce synaptogenesis, and promote neuroprotection. We have previously described isophthalate derivatives as a structurally simple family of PKC activators. Here, we characterised the effects of isophthalate derivatives HMI-1a3 and HMI-1b11 on neuronal viability, neuroinflammatory response, processing of APP and dendritic spine density and morphology in in vitro. HMI-1a3 increased the viability of embryonic primary cortical neurons and decreased the production of the pro-inflammatory mediator TNFα, but not that of nitric oxide, in mouse neuron-BV2 microglia co-cultures upon LPS- and IFN-γ-induced neuroinflammation. Furthermore, both HMI-1a3 and HMI-1b11 increased the levels of sAPPα relative to total sAPP and the ratio of Aß42/Aß40 in human SH-SY5Y neuroblastoma cells. Finally, bryostatin-1, but not HMI-1a3, increased the number of mushroom spines in proportion to total spine density in mature mouse hippocampal neuron cultures. These results suggest that the PKC activator HMI-1a3 exerts neuroprotective functions in the in vitro models relevant for AD by reducing the production of TNFα and increasing the secretion of neuroprotective sAPPα.