Partial class activation mapping guided graph convolution cascaded U-Net for retinal vessel segmentation.

Accurate segmentation of retinal vessels in fundus images is of great importance for the diagnosis of numerous ocular diseases. However, due to the complex characteristics of fundus images, such as various lesions, image noise and complex background, the pixel features of some vessels have significant differences, which makes it easy for the segmentation networks to misjudge these vessels as noise, thus affecting the accuracy of the overall segmentation. Therefore, accurately segment retinal vessels in complex situations is still a great challenge. To address the problem, a partial class activation mapping guided graph convolution cascaded U-Net for retinal vessel segmentation is proposed. The core idea of the proposed network is first to use the partial class activation mapping guided graph convolutional network to eliminate the differences of local vessels and generate feature maps with global consistency, and subsequently these feature maps are further refined by segmentation network U-Net to achieve better segmentation results. Specifically, a new neural network block, called EdgeConv, is stacked multiple layers to form a graph convolutional network to realize the transfer an update of information from local to global, so as gradually enhance the feature consistency of graph nodes. Simultaneously, in an effort to suppress the noise information that may be transferred in graph convolution and thus reduce adverse effects of noise on segmentation results, the partial class activation mapping is introduced. The partial class activation mapping can guide the information transmission between graph nodes and effectively activate vessel feature through classification labels, thereby improving the accuracy of segmentation. The performance of the proposed method is validated on four different fundus image datasets. Compared with existing state-of-the-art methods, the proposed method can improve the integrity of vessel to a certain extent when the pixel features of local vessels are significantly different, caused by objective factors such as inappropriate illumination and exudates. Moreover, the proposed method shows robustness when segmenting complex retinal vessels.

Transcription of microRNAs is regulated by developmental signaling pathways and transcription factors.

In early embryonic development, the cross-regulation of transcription factors and signaling pathways are critical in mediating developmental and physiological processes. Additionally, many studies have shown the importance of post-transcriptional regulation of signaling and network components mediated by microRNAs (miRNAs); however, how miRNAs are transcriptionally regulated is poorly understood. miRNAs are critical fine-tuners of many biological processes and their dysregulation leads to a variety of diseases and developmental defects. Previously, we have shown that miRNAs are dynamically expressed throughout sea urchin development, suggesting that miRNAs are likely to be under transcriptional regulation. Here, we used pharmacological inhibitors, genetic constructs, and loss-of-function reagents to assess the impact of key signaling pathways (Wnt, Nodal, MAPK, Sonic Hedgehog, Delta/Notch, VEGF, and BMP) and transcription factors (Alx1, Ets1/2, and Tbr) on the transcript levels of the evolutionarily conserved miR-1, miR-31, miR-92 and miR-124; the invertebrate-specific miR-71; and the echinoderm-specific miR-2002, miR-2007, and miR-2012. We also used computational methods to identify potential transcription factor binding sites of these miRNAs. Lists of binding motifs for transcription factors (TFs) were acquired from the MEME-Suite Motif Database and used as inputs for the algorithm FIMO (Find Individual Motif Occurrences), which detects short nucleotide motifs within larger sequences. Based on experimental data on miRNA expression in conjunction with bioinformatic predictions, we propose that the transcription factors Tbr, Alx1, and Ets1 regulate SpmiR-1, SpmiR-31, and SpmiR-71, respectively. We additionally observed significant effects on miRNA levels as a result of perturbations to Wnt, Nodal, MAPK, and Sonic Hedgehog signaling pathways, while no significant change on miRNA levels were observed with perturbations to Delta/Notch, VEGF, or BMP signaling pathways. Overall, this study provides insights into the transcriptional regulation of miRNAs by signaling pathways and transcription factors and contribute to our overall understanding of the genetic regulation of developmental processes.

China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI) to Prevent Cognitive Decline: Study Design and Progress.

BACKGROUND: Alzheimer's disease (AD), the most common type of irreversible dementia, is predicted to affect 152 million people by 2050. Evidence from large-scale preventive randomized controlled trials (RCTs) on modifiable risk variables in Europe has shown that multi-domain lifestyle treatments for older persons at high risk of dementia may be practical and effective. Given the substantial differences between the Chinese and European populations in terms of demographics and living conditions, direct adoption of the European program in China remains unfeasible. Although a RCT has been conducted in China previously, its participants were mainly from rural areas in northern China and, thus, are not representative of the entire nation.There is an urgent need to establish cohorts that represent different economic, cultural, and geographical situations in order to explore implementation strategies and evaluate the effects of early multi-domain interventions more comprehensively and accurately. MEDTODS: We developed an integrated intervention procedure implemented in urban neighborhood settings, namely China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI). CHINA-IN-MUDI is a 2-year multicenter open-label cluster-randomised controlled trial centered around a Chinese-style multi-domain intervention to prevent cognitive decline. Participants aged 60-80 years were recruited from a nationally representative study, i.e. China Healthy Aging and Dementia Study cohort. An external harmonization process was carried out to preserve the original FINGER design. Subsequently, we standardized a series of Chinese-style intervention programs to align with cultural and socioeconomic status. Additionally, we expanded the secondary outcome list to include genomic and proteomic analyses. To enhance adherence and facilitate implementation, we leveraged an e-health application. RESULTS: Screening commenced in July 2022. Currently, 1,965 participants have been randomized into lifestyle intervention (n = 772) and control groups (n = 1,193). Both the intervention and control groups exhibited similar baseline characteristics. Several lifestyle and vascular risk factors were present, indicating a potential window of opportunity for intervention. The intervention will be completed by 2025. CONCLUSIONS: This project will contribute to the evaluation of the effectiveness and safety of intervention strategies in controlling AD risk and reducing clinical events, providing a basis for public health decision-making in China.

[Discussion on the status quo and problems of health risk management of hand-transmitted vibration in the workplace].

The risk management in workplace is an important measure to effectively prevent and control the harm of hand-transmitted vibration. Based on the relevant developments at home and abroad, this paper expounds the risk of manual vibration operation in workplace by taking contact assessment and hazard assessment as an example. On this basis, the limit management and hierarchical management related to risk management are discussed, and the existing problems are analyzed.

microRNA-1 regulates sea urchin skeletogenesis by directly targeting skeletogenic genes and modulating components of signaling pathways.

microRNAs are evolutionarily conserved non-coding RNAs that direct post-transcriptional regulation of target transcripts. In vertebrates, microRNA-1 (miR-1) is expressed in muscle and has been found to play critical regulatory roles in vertebrate angiogenesis, a process that has been proposed to be analogous to sea urchin skeletogenesis. Results indicate that both miR-1 inhibitor and miR-1 mimic-injected larvae have significantly less F-actin enriched circumpharyngeal muscle fibers and fewer gut contractions. In addition, miR-1 regulates the positioning of skeletogenic primary mesenchyme cells (PMCs) and skeletogenesis of the sea urchin embryo. Interestingly, the gain-of-function of miR-1 leads to more severe PMC patterning and skeletal branching defects than its loss-of-function. The results suggest that miR-1 directly suppresses Ets1/2, Tbr, and VegfR7 of the skeletogenic gene regulatory network, and Nodal, and Wnt1 signaling components. This study identifies potential targets of miR-1 that impacts skeletogenesis and muscle formation and contributes to a deeper understanding of miR-1's function during development.

[Mitigating metal artifacts from cobalt-chromium alloy crowns in cone-beam CT images through deep learning techniques].

Objective: To develop and evaluate metal artifact removal systems (MARS) based on deep learning to assess their effectiveness in removing artifacts caused by different thicknesses of metals in cone-beam CT (CBCT) images. Methods: A full-mouth standard model (60 mm×75 mm×110 mm) was three-dimensional (3D) printed using photosensitive resin. The model included a removable and replaceable target tooth position where cobalt-chromium alloy crowns with varying thicknesses were inserted to generate matched CBCT images. The artifacts resulting from cobalt-chromium alloys with different thicknesses were evaluated using the structural similarity index measure (SSIM) and peak signal-to-noise ratio (PSNR). CNN-MARS and U-net-MARS were developed using a convolutional neural network and U-net architecture, respectively. The effectiveness of both MARSs were assessed through visualization and by measuring SSIM and PSNR values. The SSIM and PSNR values were statistically analyzed using one-way analysis of variance (α=0.05). Results: Significant differences were observed in the range of artifacts produced by different thicknesses of cobalt-chromium alloys (all P<0.05), with 1 mm resulting in the least artifacts. The SSIM values for specimens with thicknesses of 1.0, 1.5, and 2.0 mm were 0.916±0.019, 0.873±0.010, and 0.833±0.010, respectively (F=447.89, P<0.001). The corresponding PSNR values were 20.834±1.176, 17.002±0.427, and 14.673±0.429, respectively (F=796.51, P<0.001). After applying CNN-MARS and U-net-MARS to artifact removal, the SSIM and PSNR values significantly increased for images with the same thickness of metal (both P<0.05). When using the CNN-MARS for artifact removal, the SSIM values for 1.0, 1.5 and 2.0 mm were 0.938±0.023, 0.930±0.029, and 0.928±0.020 (F=2.22, P=0.112), while the PSNR values were 30.938±1.495, 30.578±2.154 and 30.553±2.355 (F=0.54, P=0.585). When using the U-net-MARS for artifact removal, the SSIM values for 1.0, 1.5 and 2.0 mm were 0.930±0.024, 0.932±0.017 and 0.930±0.012 (F=0.24, P=0.788), and the PSNR values were 30.291±0.934, 30.351±1.002 and 30.271±1.143 (F=0.07, P=0.929). No significant differences were found in SSIM and PSNR values after artifact removal using CNN-MARS and U-net-MARS for different thicknesses of cobalt-chromium alloys (all P>0.05). Visualization demonstrated a high degree of similarity between the images before and after artifact removal using both MARS. However, CNN-MARS displayed clearer metal edges and preserved more tissue details when compared with U-net-MARS. Conclusions: Both the CNN-MARS and U-net-MARS models developed in this study effectively remove the metal artifacts and enhance the image quality. CNN-MARS exhibited an advantage in restoring tissue structure information around the artifacts compared to U-net-MARS.

[Pathogenic agents causing acute respiratory tract infections in pediatric patients in Spring, 2023, in Beijing].

Objective: To explore the pathogenic agents of acute respiratory infection (ARI) in children in Beijing. Methods: In the cross-sectional study, 3 groups of children from different departments were enrolled from Feb 6th, 2023 (6th week) to May 28th (21th week), 2023, including influenza-like case group from emergency department for nucleic acid testing of influenza virus (Flu) and human metapneumovirus (HMPV), the outpatient ARI group under nucleic acid testing for Flu, respiratory syncytial virus (RSV), adenovirus (ADV), and parainfluenza virus (PIV), and the inpatient ARI group under nucleic acid testing for Flu, RSV, HMPV, ADV, human bocavirus (HBoV), Rhinovirus (Rh), PIV, coronavirus (HCoV), Mycoplasma pneumoniae (Mp) and Chlamydia pneumonia (Cp). Results: There were 320 influenza-like cases enrolled, including 192 males and 128 females, aged 4.7 (3.6, 6.9) years, and 117 cases (36.6%) positive for Flu A, which contained similar proportion of pandemic H1N1 (H1N1) 47.0% (55/117) and H3N2 53.0% (62/117), and 13 cases for HMPV 4.1% (13/320). The rate of Flu reached its peak at the 10th week, with H1N1 as the predominant one from the 6th to 9th week (10.0%-50.0%) and then H3N2 from the 10th to 16th week (15.0%-90.0%). HMPV was detected from the 15th week 5.0% (1/20), and then reached to 30.0% (6/20) at the 20th week. In the outpatient ARI group, 7 573 were enrolled, including 4 131 males and 3 442 females, aged 4.0 (2.1, 5.3) years, and the highest positive rate for RSV 32.9% (2 491/7 573), followed by Flu A 12.1% (915/7 573). The dominant one was Flu A in weeks 6-14 (23.2%-74.7%), then RSV in the 15th week 24.8% (36/145). In the inpatient ARI group, 1 391 patients were enrolled, including 804 males and 587 females, aged 3.3 (0.4, 5.8) years, and the highest positive rate for Rh 18.7% (260/1 391), followed by RSV 12.4% (173/1 391), Flu A 10.2% (142/1 391, of which 116 cases (81.7%) were H1N1, and 26 cases (18.3%) were H3N2) and HMPV 3.1% (43/1 391). H1N1 was detected from the 7th week 10% (6/60), to peak in the 11th week 31.8% (21/66). H3N2 was detected from the 8th week 1.5% (1/68), and then kept in low level. The proportion of H1N1 among Flu was 81.7% (116/142) in the inpatient ARI group. RSV was detected from 12th week 1.3% (1/80), reaching 30.4% (35/115) at 19th week. The positive rate of HMPV reached 12.1% (14/116) at 21th week. Conclusions: In the spring of 2023, the first one in Beijing is the Flu epidemic, with H1N1 being the predominant one in the early stage and H3N2 in the later stage. Then, there is a postponed RSV epidemic and an increased HMPV detection. In addition, nucleic acid testing for outpatient children should be strengthened to provide early warning of epidemics.

Development and Validation of Potential Molecular Subtypes and Signatures of Thyroid Carcinoma Based on Aging-related Gene Analysis.

BACKGROUND/AIM: Thyroid carcinoma (THCA) is a cancer of the endocrine system that most commonly affects women. Aging-associated genes play a critical role in various cancers. Therefore, we aimed to gain insight into the molecular subtypes of thyroid cancer and whether senescence-related genes can predict the overall prognosis of THCA patients. MATERIALS AND METHODS: Thyroid carcinoma (THCA) transcriptome-related expression profiles were obtained from The Cancer Genome Atlas (TCGA) database. These profiles were randomly divided into training and validation subsets at a ratio of 1:1. Unsupervised clustering algorithms were used to compare differences between the two subtypes; prognosis-related senescence genes were used to further construct our prognostic models by univariate and multivariate Cox analyses and construct a nomogram to predict the 1-, 3-, and 5-year overall survival probability of THCA patients. In addition, we performed gene set enrichment analysis (GSEA) to predict the immune microenvironment and somatic mutations between the different risk groups. Finally, real-time PCR was used to verify the expression levels of key model genes. RESULTS: The 'ConsensusClusterPlus' R package was used to cluster thyroid cancer into two categories (Cluster1 and Cluster2) on the basis of 46 differentially expressed aging-related genes (DE-ARGs); patients in Cluster1 demonstrated a better prognosis than those in Cluster2. Cox analysis was used to screen six prognosis-related DE-ARGs. Finally, our real-time PCR results confirmed our hypothesis. CONCLUSION: Differences exist between the two subtypes of thyroid cancer that help guide treatment decisions. The six DE-ARG genes have a high predictive value for risk stratifying THCA patients.

[Association between remnant cholesterol levels and incident diabetic retinopathy in middle-aged and older patients with diabetes].

Objective: To investigate the association between remnant cholesterol (RC) and the risk of diabetic retinopathy (DR) in middle-aged and older individuals with diabetes. Methods: Based on the Shanghai Nicheng Cohort Study database, the data of 1 255 individuals with diabetes aged 55-70 years at baseline (2013-2014) with complete fundus photographs and serum cholesterol data in Nicheng, Shanghai, were analyzed. Multinomial logistic regression models were used to evaluate risk ratios (RRs) and their 95% confidence intervals (CIs) between baseline RC level and incident DR. Results: The median age of the subjects was 61.9 years, and 60.4% were women. After a 4.6-year follow-up, 79 (6.3%) patients developed DR, including 50 (4.0%) mild non-proliferative DR and 29 (2.3%) referable DR (RDR). Multivariable logistic regression showed that each mmol/L increase of RC was associated with a 40% higher risk of RDR (RR=1.40, 95%CI 1.03-1.90). Compared with the lowest tertile of RC (<0.63 mmol/L), the risk of RDR in the highest tertile (≥0.85 mmol/L) increased by 4.59 times (RR=5.59, 95%CI 1.51-20.73). Conclusion: The RC level may help identify individuals at high risk of incident RDR in middle-aged and older Chinese adults with diabetes.

Norovirus outbreaks in hospitals in China: a systematic review.

BACKGROUND: Norovirus outbreaks in hospitals can potentially impair patient care and result in significant financial expenses. There is currently limited information on hospital norovirus outbreaks in the Chinese mainland. AIM: To systematically review the published literature to describe the characteristics of norovirus outbreaks in Chinese mainland hospitals to facilitate prompt identification and control of outbreaks. METHODS: A systematic review was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis standards. Databases including PubMed, Web of Science, and Chinese Journals Online databases (China National Knowledge Infrastructure (CNKI), Chinese Wan Fang digital database (WANFANG) were searched from inception to July 18th, 2022. FINDINGS: A total of 41 norovirus Chinese hospital outbreaks occurring before July 18th, 2022 were reported in 32 articles. Most reported outbreaks were from Shanghai and Beijing, and occurred in December and January. Cases were mainly adults. The male:female ratio was 1.22:1. The majority of cases in norovirus outbreaks were hospitalized patients (56.82%); medical staff were affected in 15 outbreaks. Norovirus outbreaks occurred in both private and public hospitals, and in secondary and tertiary care centres, and occurred mainly in internal medicine and geriatric departments. Person-to-person transmission was the primary transmission mode and GII was more prevalent. CONCLUSION: Norovirus outbreaks in hospitals can affect both patients and healthcare workers, sometimes causing serious financial losses. In order to have a more complete understanding of the disease burden caused by norovirus outbreaks, surveillance needs to be established in hospitals.

Electroacupuncture stimulating Neixiyan (EX-LE5) and Dubi (ST35) alleviates osteoarthritis in rats induced by anterior cruciate ligament transaction affecting DNA methylation regulated transcription of miR-146a and miR-140-5p.

OBJECTIVE: To explore whether electroacupuncture (EA) could alleviate osteoarthritis (OA) through affecting the DNA methylation regulated transcription of miR-146a and miR-140-5p. METHODS: Sixty male eight-week-old Sprague-Dawley rats were divided into three groups: normal group (normal healthy rats; no treatment), model group (OA rats; no treatment) and EA group (OA rats treated with EA). Safranin O staining and modified Mankin's score were performed to evaluate the histopathological alterations and degeneration of cartilage 8 weeks after 8 consecutive weeks of treatment. Quantitative real time polymerase chain reaction (qRT-PCR) assay was employed to evaluate the expression of miR-146a in the cartilage tissue and miR-140-5p in the synovium tissue, respectively. The bisulfite sequencing analysis and quantitative methylation specific PCR (qMSP) were used to analyze the status of methylation in the regulatory regions of miR-146a and miR-140-5p. Chromatin immunoprecipitation (ChIP) assay were performed to assess the binding of nuclear factor-kappa B (NF-κB) and signal transducer and activator of transcription 3 (SMAD-3) in the regulatory regions of miR-146a and miR-140-5p. Western blot analysis was performed to detect the expressions of DNA Methyltransferase 1 (DMNT1), DNA Methyltransferase 3A (DMNT3A), and DNA Methyltransferase 3A (DMNT3b), NF-κB, SMAD3 levels. RESULTS: Our results showed that EA treatment significantly upregulated miR-146a and miR-140-5p expressions. qMSP analysis showed that EA significantly decreased methylation levels of miR-140-5p regulated region and miR-146a promoter in OA cartilage and synovium. Bisulfite DNA sequencing (BDS) and ChIP analysis showed that EA significantly increased binding affinity of SMAD3 and NF-kB on the hypermethylated miR-140 regulatory region and miR-146a promoter, respectively. Western Blot analysis demonstrated that EA also significantly decreased expressions of methylation related proteins- DMNT1, DMNT3a, and DMNT3b as well as NF-κB and SMAD3. CONCLUSIONS: Electroacupuncture stimulating Neixiyan (EX-LE5) and Dubi (ST35) may alleviate OA affecting the DNA methylation regulated transcription of miR-146a and miR-140-5p.

[Predictive value of plasma exosomal miR-124-3p for the risk of chronic cerebral hypoperfusion].

Objective: To investigate the predictive value of plasma exosomal microRNA (miR)-124-3p in the risk of chronic cerebral hypoperfusion (CCH). Methods: A case-control study. Thirty patients who were diagnosed with CCH (CCH group) based on cranial artery spin labeling (ASL) in the neurology outpatient clinic of Sichuan Provincial People's Hospital from March 2022 to June 2022 and 30 healthy volunteers (control group) were included. Age, gender, smoking history, alcohol consumption history, diabetes history, hypertension, hyperlipidemia history, uric acid, fasting blood glucose, homocysteine and plasma exosomal miR-124-3p expression level were compared between the two groups. Comparisons of categorical variables were analyzed by either χ2 test or Fisher's exact test. If the data of continuous variables followed a normal distribution, they were expressed as mean±standard deviation (SD) and compared by t-test for two independent samples; otherwise, the data were expressed as M(Q1, Q3), and analyzed by Mann-Whitney U test for comparison between two groups. The correlation between cerebral blood flow and exosomal miR-124-3p levels was analyzed by Pearson's correlation. Binary multifactorial logistic regression analysis was used to determine the risk factors associated with CCH, and corresponding odds ratios (OR) and 95% confidence intervals (CI) were calculated. P<0.05 was considered significant. Results: There was no significant difference in age (64±8 vs. 60±8 years old), gender (33.3% vs. 30.0%), history of smoking (20.0% vs. 3.3%), alcohol consumption (20.0% vs. 6.7%), diabetes mellitus (13.3% vs. 13.3%), hypertension (53.3% vs. 30.0%), history of hyperlipidemia (46.7% vs. 36.7%), uric acid (288±60 vs.319±67 µmol/L), and fasting glucose [4.99(4.63, 5.91) vs. 5.28(5.09, 6.05) mmol/L] and homocysteine [11.35(10.18, 13.08) vs.11.00(9.78, 13.03) µmol/L] between the CCH and control groups (P>0.05). Plasma exosomal miR-124-3p expression was significantly higher in the CCH group than in the control group [13.08 (8.59, 21.55) vs. 2.85 (1.44, 5.10), respectively; U=169.50, P<0.001]. Pearson's correlation test showed that the level of exosomal miR-124-3p was negatively correlated with cerebral blood flow in the hypoperfused region in patients with CCH (r=-0.932, P<0.001). Multi-factor logistic regression analysis showed that plasma exosomal miR-124-3p was independently associated with the risk of CCH (OR=1.169,95%CI 1.063-1.286,P=0.001). Conclusions: The expression of plasma exosomal miR-124-3p is negatively correlated with cerebral blood flow in areas of low perfusion and is an independent risk factor for CCH. Plasma exosomal miR-124-3p may thus serve as a valid biomarker for CCH risk prediction.

miR-31-mediated local translation at the mitotic spindle is important for early development.

miR-31 is a highly conserved microRNA that plays critical roles in cell proliferation, migration, and differentiation. We discovered miR-31 and some of its validated targets are enriched on the mitotic spindle of the dividing sea urchin embryo and mammalian cells. Using the sea urchin embryo, we found that miR-31 inhibition led to developmental delay correlated with increased cytoskeleton and chromosomal defects. We identified miR-31 to directly suppress several actin remodeling transcripts, ß-actin, Gelsolin, Rab35 and Fascin, which were localized to the mitotic spindle. miR-31 inhibition leads to increased newly translated Fascin at the spindles. Forced ectopic localization of Fascin transcripts to the cell membrane and translation led to significant developmental and chromosomal segregation defects, leading to our hypothesis that miR-31 regulates local translation at the mitotic spindle to ensure proper cell division. Furthermore, miR-31-mediated post-transcriptional regulation at the mitotic spindle may be an evolutionarily conserved regulatory paradigm of mitosis.

microRNA-124 directly suppresses Nodal and Notch to regulate mesodermal development.

MicroRNAs regulate gene expression post-transcriptionally by destabilizing and/or inhibiting translation of target mRNAs in animal cells. MicroRNA-124 (miR-124) has been examined mostly in the context of neurogenesis. This study discovers a novel role of miR-124 in regulating mesodermal cell differentiation in the sea urchin embryo. The expression of miR-124 is first detectable at 12hours post fertilization at the early blastula stage, during endomesodermal specification. Mesodermally-derived immune cells come from the same progenitor cells that give rise to blastocoelar cells (BCs) and pigment cells (PCs) that must make a binary fate decision. We determined that miR-124 directly represses Nodal and Notch to regulate BC and PC differentiation. miR-124 inhibition does not impact the dorsal-ventral axis formation, but result in a significant increase in number of cells expressing BC-specific transcription factors (TFs) and a concurrent reduction of differentiated PCs. In general, removing miR-124's suppression of Nodal phenocopies miR124 inhibition. Interestingly, removing miR-124's suppression of Notch leads to an increased number of both BCs and PCs, with a subset of hybrid cells that express both BC- and PC-specific TFs in the larvae. Removal of miR-124's suppression of Notch not only affects differentiation of both BCs and PCs, but also induces cell proliferation of these cells during the first wave of Notch signaling. This study demonstrates that post-transcriptional regulation by miR-124 impacts differentiation of BCs and PCs by regulating the Nodal and Notch signaling pathways.

Recent Advances in Understanding the Molecular Pathophysiology of Angiotensin II Receptors: Lessons From Cell-Selective Receptor Deletion in Mice.

The renin-angiotensin system (RAS) is an essential hormonal system involved in water and sodium reabsorption, renal blood flow regulation, and arterial constriction. Systemic stimulation of the RAS with infusion of the main peptide angiotensin II (Ang II) in animals as well as pathological elevation of renin (ie, renovascular hypertension) to increase circulatory Ang II in humans ultimately lead to hypertension and end organ damage. In addition to hypertension, accumulating evidence supports that the Ang II type 1 receptor exerts a critical role in cardiovascular and kidney diseases independent of blood pressure elevation. In the past 2 decades, the identification of an increased number of peptides and receptors has facilitated the concept that the RAS has detrimental and beneficial effects on the cardiovascular system depending on which RAS components are activated. For example, angiotensin 1-7 and Ang II type 2 receptors act as a counter-regulatory system against the classical RAS by mediating vasodilation. Although the RAS as an endocrine system for regulation of blood pressure is well established, there remain many unanswered questions and controversial findings regarding blood pressure regulation and pathophysiological regulation of cardiovascular diseases at the tissue level. This review article includes the latest knowledge gleaned from cell type-selective gene deleted mice regarding cell type-specific roles of Ang II receptors and their significance in health and diseases are discussed. In particular, we focus on the roles of these receptors expressed in vascular, cardiac, and kidney epithelial cells.

[C2 pedicle screw insertion assisted by mobilization of the vertebral artery in cases with high-riding vertebral artery].

Objective: To examine the feasibility, safety, and efficacy of mobilization of the vertebral artery for C2 pedicle screws in cases with high-riding vertebral artery (HRVA). Methods: The clinical data of 12 patients with basilar invagination and atlantoaxial dislocation underwent atlantoaxial reduction and fixation in the Department of Neurosurgery, the First Affiliated Hospital of University of Science and Technology of China between January 2020 and November 2021 were retrospectively analyzed. All patients had high-riding vertebral artery on at least one side that prohibited the insertion of C2 pedicle screws. There were 2 males and 10 females aged (48.0±12.8) years (range: 17 to 67 years). After correction of vertical dislocation during the operation, the C2 pedicle screw insertion and occipitocervical fixation and fusion were performed using the vertebral artery mobilization technique. Neurological function was assessed using the Japanese Orthopedic Association (JOA) scale. The preoperative and postoperative JOA score and the main radiological measurements, including the anterior atlantodental interval (ADI), the distance of the odontoid tip above the Chamberlain line, the clivus-canal angle, were collected and compared by paired t-test. Results: Mobilization of the high-riding vertebral artery was successfully completed, and C2 pedicle screws were then fulfilled after the vertebral artery was protected. There was no injury to the vertebral artery during the operation. Meanwhile, no severe surgical complications such as cerebral infarction or aggravated neurological dysfunction occurred during the perioperative period. Satisfactory C2 pedicle screw placement and reduction were achieved in all 12 patients. All patients achieved bone fusion 6 months after surgery. No looseness and shift in internal fixation or reduction loss was observed during the follow-up period. Compared to the preoperative, the postoperative ADI decreased from (6.1±1.9) mm to (2.0±1.2) mm (t=6.73, P<0.01), the distance of the odontoid tip above the Chamberlain line decreased from (10.4±2.5) mm to (5.5±2.3) mm (t=7.12, P<0.01), the clivus-canal angle increased from (123.4±11.1) ° to (134.7±9.6) ° (t=2.50, P=0.032), the JOA score increased from 13.3±2.1 to 15.6±1.2 (t=6.99, P<0.01). Conclusion: The C2 pedicle screw insertion assisted by mobilization of the vertebral artery is safe and considerably effective, providing a choice for internal fixation in cases with high-riding vertebral arteries.

[Construction and prospect of healthy enterprises in the new era].

The construction of health enterprises practice the concept of big health. It is an important solution to protect the overall health of occupational groups in the new era, which is of great significance to promoting a healthy city and helping to build a healthy China. This paper clarifies the connotation of healthy enterprises in the new era, discusses the key points of healthy enterprise construction around the "four in one" construction content, "PDCA" construction procedures, and evaluation methods of healthy enterprises. It focuses on the progress of healthy enterprise construction, analyzes the problems faced by the construction of health enterprises in China, and puts forward suggestions to improve the construction efficiency, with a view to providing ideas for further promoting the construction of health enterprises in China.

Perioperative redox changes in patients undergoing hepato-pancreatico-biliary cancer surgery.

BACKGROUND: Tissue injury induces inflammation and the surgical stress response, which are thought to be central to the orchestration of recovery or deterioration after surgery. Enhanced formation of reactive oxygen and nitrogen species accompanies the inflammatory response and triggers separate but integrated reduction/oxidation (redox) pathways that lead to oxidative and/or nitrosative stress (ONS). Quantitative information on ONS in the perioperative period is scarce. This single-centre exploratory study investigated the effects of major surgery on ONS and systemic redox status and their potential associations with postoperative morbidity. METHODS: Blood was collected from 56 patients at baseline, end of surgery (EoS) and the first postoperative day (day-1). Postoperative morbidity was recorded using the Clavien-Dindo classification and further categorised into minor, moderate and severe. Plasma/serum measures included markers of lipid oxidation (thiobarbituric acid-reactive substances; TBARS, 4-hydroxynonenal; 4-HNE, 8-iso-prostaglandin F2⍺; 8-isoprostanes). Total reducing capacity was measured using total free thiols (TFTs) and ferric-reducing ability of plasma (FRAP). Nitric oxide (NO) formation/metabolism was measured using cyclic guanosine monophosphate (cGMP), nitrite, nitrate and total nitroso-species (RxNO). Interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-⍺) were measured to evaluate inflammation. RESULTS: Both oxidative stress (TBARS) and nitrosative stress (total nitroso-species) increased from baseline to EoS (+14%, P = 0.003 and +138%, P < 0.001, respectively), along with an increase in overall reducing capacity (+9%, P = 0.03) at EoS and protein-adjusted total free thiols (+12%, P = 0.001) at day-1 after surgery. Nitrite, nitrate and cGMP concentrations declined concomitantly from baseline to day-1. Baseline nitrate was 60% higher in the minor morbidity group compared to severe (P = 0.003). The increase in intraoperative TBARS was greater in severe compared to minor morbidity (P = 0.01). The decline in intraoperative nitrate was more marked in the minor morbidity group compared to severe (P < 0.001), whereas the cGMP decline was greatest in the severe morbidity group (P = 0.006). CONCLUSION: In patients undergoing major HPB surgery, intraoperative oxidative and nitrosative stress increased, with a concomitant increase in reductive capacity. Baseline nitrate was inversely associated with postoperative morbidity, and the hallmarks of poor postoperative outcome include changes in both oxidative stress and NO metabolism.

Chronic Kidney Disease Transdifferentiates Veins into a Specialized Immune-Endocrine Organ with Increased MYCN-AP1 Signaling.

Most patients with end-stage renal disease (ESRD) and advanced chronic kidney disease (CKD) choose hemodialysis as their treatment of choice. Thus, upper-extremity veins provide a functioning arteriovenous access to reduce dependence on central venous catheters. However, it is unknown whether CKD reprograms the transcriptome of veins and primes them for arteriovenous fistula (AVF) failure. To examine this, we performed transcriptomic analyses of bulk RNA sequencing data of veins isolated from 48 CKD patients and 20 non-CKD controls and made the following findings: (1) CKD converts veins into immune organs by upregulating 13 cytokine and chemokine genes, and over 50 canonical and noncanonical secretome genes; (2) CKD increases innate immune responses by upregulating 12 innate immune response genes and 18 cell membrane protein genes for increased intercellular communication, such as CX3CR1 chemokine signaling; (3) CKD upregulates five endoplasmic reticulum protein-coding genes and three mitochondrial genes, impairing mitochondrial bioenergetics and inducing immunometabolic reprogramming; (4) CKD reprograms fibrogenic processes in veins by upregulating 20 fibroblast genes and 6 fibrogenic factors, priming the vein for AVF failure; (5) CKD reprograms numerous cell death and survival programs; (6) CKD reprograms protein kinase signal transduction pathways and upregulates SRPK3 and CHKB; and (7) CKD reprograms vein transcriptomes and upregulates MYCN, AP1, and 11 other transcription factors for embryonic organ development, positive regulation of developmental growth, and muscle structure development in veins. These results provide novel insights on the roles of veins as immune endocrine organs and the effect of CKD in upregulating secretomes and driving immune and vascular cell differentiation.