Macrophage-specific FGF12 promotes liver fibrosis progression in mice.

BACKGROUND AND AIMS: Chronic liver diseases are associated with the development of liver fibrosis. Without treatment, liver fibrosis commonly leads to cirrhosis and HCC. FGF12 is an intracrine factor belonging to the FGF superfamily, but its role in liver homeostasis is largely unknown. This study aimed to investigate the role of FGF12 in the regulation of liver fibrosis. APPROACH AND RESULTS: FGF12 was up-regulated in bile duct ligation (BDL)-induced and CCL 4 -induced liver fibrosis mouse models. Expression of FGF12 was specifically up-regulated in nonparenchymal liver cells, especially in hepatic macrophages. By constructing myeloid-specific FGF12 knockout mice, we found that deletion of FGF12 in macrophages protected against BDL-induced and CCL 4 -induced liver fibrosis. Further results revealed that FGF12 deletion dramatically decreased the population of lymphocyte antigen 6 complex locus C high macrophages in mouse fibrotic liver tissue and reduced the expression of proinflammatory cytokines and chemokines. Meanwhile, loss-of-function and gain-of-function approaches revealed that FGF12 promoted the proinflammatory activation of macrophages, thus inducing HSC activation mainly through the monocyte chemoattractant protein-1/chemokine (C-C motif) receptor 2 axis. Further experiments indicated that the regulation of macrophage activation by FGF12 was mainly mediated through the Janus kinase-signal transducer of activators of transcription pathway. Finally, the results revealed that FGF12 expression correlates with the severity of fibrosis across the spectrum of fibrogenesis in human liver samples. CONCLUSIONS: FGF12 promotes liver fibrosis progression. Therapeutic approaches to inhibit macrophage FGF12 may be used to combat liver fibrosis in the future.

Sarcopenia negatively affects postoperative short-term outcomes of patients with non-cirrhosis liver cancer.

BACKGROUND: Literature review have shown that sarcopenia substantially alters the postoperative outcomes after liver resection for malignant tumors. However, these retrospective studies do not distinguish cirrhotic and non-cirrhotic liver cancer patients, nor combine the assessment of muscle strength in addition to muscle mass. The purpose of this study is to study the relationship between sarcopenia and short-term outcomes after hepatectomy in patients with non-cirrhotic liver cancer. METHODS: From December 2020 to October 2021, 431 consecutive inpatients were prospectively enrolled in this study. Muscle strength and mass were assessed by handgrip strength and the skeletal muscle index (SMI) on preoperative computed tomographic scans, respectively. Based on the SMI and the handgrip strength, patients were divided into four groups: group A (low muscle mass and strength), group B (low muscle mass and normal muscle strength), group C (low muscle strength and normal muscle mass), and group D (normal muscle mass and strength). The main outcome was major complications and the secondary outcome was 90-d Readmission rate. RESULTS: After strictly exclusion, 171 non-cirrhosis patients (median age, 59.00 [IQR, 50.00-67.00] years; 72 females [42.1%]) were selected in the final analysis. Patients in group A had a statistically significantly higher incidence of major postoperative complications (Clavien-Dindo classification ≥ III) (26.1%, p = 0.032), blood transfusion rate (65.2%, p < 0.001), 90-day readmission rate (21.7%, p = 0.037) and hospitalization expenses (60,842.00 [IQR, 35,563.10-87,575.30], p < 0.001) than other groups. Sarcopenia (hazard ratio, 4.21; 95% CI, 1.44-9.48; p = 0.025) and open approach (hazard ratio, 2.56; 95% CI, 1.01-6.49; p = 0.004) were independent risk factors associated with major postoperative complications. CONCLUSIONS: Sarcopenia is closely related to poor short-term postoperative outcomes in non-cirrhosis liver cancer patients and the assessment that combines muscle strength and muscle mass can simply and comprehensively identify it. TRIAL REGISTRATION: ClinicalTrials.gov identifiers NCT04637048 . (19/11/2020).

Fibroblast growth factor 18 attenuates liver fibrosis and HSCs activation via the SMO-LATS1-YAP pathway.

Liver fibrosis, which is characterized by excessive accumulation of extracellular matrix (ECM) primarily produced by hepatic stellate cells (HSCs), can eventually lead to cirrhosis. Fibroblast growth factor 18 (FGF18) mediates various biological activities. However, the precise role of FGF18 in the pathological process of liver fibrosis and the underlying mechanisms have not been elucidated. In this study, we found that FGF18 was markedly upregulated in carbon tetrachloride (CCl4)-induced fibrotic mouse liver tissues and transforming growth factor ß (TGF-ß) stimulated LX-2 cells. Furthermore, our studies demonstrated that overexpression of FGF18 in the liver significantly alleviated CCl4-induced fibrosis and inhibited the activation of HSCs, while exacerbated by HSC-specific deletion of FGF18. Mechanistically, FGF18 treatment dramatically activated Hippo signaling pathway by suppressing smoothened (SMO) both in vivo and in vitro. Moreover, the interaction between SMO and LATS1 was crucial for the FGF18 induced protective effects. In conclusion, these results indicated that FGF18 attenuates liver fibrosis at least partially via the SMO-LATS1-YAP signaling pathway and therefore may be a potential therapeutic target for liver fibrosis.

COVID-19 Patients' Views and Experiences of Traditional Chinese Medicine Treatment in South Africa.

Context: In 2020, the COVID-19 pandemic was declared a public health emergency of international concern. Since no effective and sustainable treatment was available for COVID-19, patients felt an overwhelming and desperate need to seek alternative treatments. Traditional Chinese medicine (TCM) has been gaining popularity outside of Asian countries, especially in Africa. However, no studies have been conducted on African patients' views of the use of TCM to treat various illnesses, including COVID-19. Objective: The study aimed to explore South African patients' views of and experiences with TCM for treating COVID-19 infections. Design: The study adopted a qualitative research approach located within the interpretivist paradigm. A single case-study design was employed to investigate the views and experiences of ten post-COVID patients on the use of TCM to treat the disease. Setting: The research setting was a TCM practice in Gauteng province in South Africa (SA), with two registered TCM practitioners. Participants: Participants were ten post-COVID patients who had had pneumonia and who used TCM to treat the disease. Results: TCM was effective and inexpensive for COVID-19 treatment. Some challenges were revealed for the adoption of TCM in SA, including patients' lack of TCM knowledge and the inaccessibility of TCM services. Conclusions: TCM was beneficial in treating COVID-19 pneumonia. Public awareness of TCM should be promoted, especially as an alternative treatment for COVID-19 in SA. Continuous professional training is recommended for TCM service providers.

Relationship between Renying pulse augmentation index and Cunkou pulse condition in different blood pressure groups.

OBJECTIVE: To explore the relationship between Renying pulse (carotid) augmentation index (AI) and Cunkou pulse condition in different blood pressure groups, and the clinical significance of Renying and Cunkou pulse parameters to reflect vascular function. METHODS: Eighty-six patients with essential hypertension (EH) and 52 individuals with normal blood pressure (control group) between September 2010 and January 2012 were included in this study. Renying pulse AI was examined by a new diagnostic tool (ALOKA ProSound Alpha 10)--wave intensity (WI) that is calculated as the product of the derivatives of the simultaneously recorded blood pressure changes (dP/dt) and blood-flow-velocity changes (dU/dt), while Cunkou pulse condition was detected by DDMX-100 Pulse Apparatus in both EH and control groups. A multifactorial correlation analysis was performed for data analysis. RESULTS: After adjusting for potential confounding variables, in the EH group, AI was positively correlated with t5, w2/t (r(t5) = 0.225, P < 0.05; r(w2/t) = 0.230, P < 0.05) and negatively correlated with h5, h5/h1 and w2 (r(h5) = -0.393, P < 0.01; r(h5)/h1) = -0.444, P < 0.01; r(w2) = -0.389, P < 0.01). In the control group, AI was positively correlated with t3, t4, t5 and w1 (r(t3) = 0.595, P < 0.01; r(t4) = 0.292, P < 0.05; r(t5) = 0.318, P < 0.05; r(w1) = 0.541, P < 0.01) and negatively correlated with h1, h2, h3, Ad and A (r(h1) = -0.368, P < 0.05; r(h2) = -0.330, P < 0.05; r(h3) = -0.327, P < 0.05; rAd = -0.322, P < 0.05; rA = -0.410, P < 0.01). In the total sample group (EH plus control group, n = 138), AI was positively correlated with t, t5, w1 and w2t (r(t) = 0.257, P < 0.01; r(t5) = 0.266, P < 0.01; r(w1) = 0.184, P < 0.05; r(w2/t) = 0.210, P < 0.05) and negatively correlated with h5, h5/h1, w2 and Ad (r(h5) = -0.230, P < 0.01; r(h5/h1) = -0.218, P < 0.05; r(w2) = -0.267, P < 0.01; rAd = -0.246, P < 0.01). Multiple linear regression analysis was carried out to model the relationship (F = 7.887, P < 0.001). CONCLUSION: Renying pulse AI can effectively predict arterial stiffness in synchrony with the manifestations of Cunkou pulse in elderly patients with hypertension. Cunkou pulse apparatus is a valuable tool for evaluating AI in clinical practice. The close correlations reported above reflect the holistic concept of Traditional Chinese Medicine.

Strengthening critical thinking through debriefing - experiential learning theory: A case study.

BACKGROUND: There is a dire need to strengthen students' critical thinking in clinical training since it is an essential skill in clinical practice to optimize patient care. Debriefing is a formal or informal post-activity discussion that aims to improve learning outcomes, including critical thinking in clinical practice. There is a lack of research that focuses on students' experiences of debriefing to promote critical thinking in the South African context using experiential learning theory as a theoretical lens. OBJECTIVE: This study aimed to explore South African students' lived experiences of debriefing to improve critical thinking. MATERIALS AND METHOD: The author employed a qualitative single-case study design within an interpretivist paradigm. A purposive sampling technique was adopted. Six participants were recruited for this study. The author invited the participants to participate in semi-structured interviews. Data were analyzed through the six-step data analysis framework proposed by Creswell. To ensure the trustworthiness, the author employed multiple techniques to improve the credibility, conformability, dependability, and transferability of this study. These techniques included a well-planned research design and methods, thick descriptions of data, and an audit trail that was audited by a second coder. RESULTS: The findings revealed that participants shared positive experiences toward debriefing and furthermore debriefing through optimized student engagement and improved learning outcomes. This study also revealed that students experienced less stress in group debriefings. However, this study also identified some challenges in conducting debriefing. The challenges were primarily related to incompetent facilitators, inappropriate duration of debriefing sessions, and limited space in the clinic. Moreover, small group debriefing is recommended. CONCLUSION: Debriefing is an effective pedagogical approach to optimize critical thinking in clinical practice. It is recommended that debriefing should be implemented as a norm in clinical training at higher education institutions. Further studies are recommended to be conducted at national and international levels.

An enhanced multimode phase imaging method based on the transport of intensity equation.

Label-free biological cell imaging relies on rapid multimode phase imaging of biological samples in natural settings. To improve image contrast, phase is encoded into intensity information using the differential interference contrast (DIC) and Zernike phase contrast (ZPC) techniques. To enable multimode contrast-enhanced observation of unstained specimens, this paper proposes an improved multimode phase imaging method based on the transport of intensity equation (TIE), which combines conventional microscopy with computational imaging. The ZPC imaging module based on adaptive aperture adjustment is applied when the quantitative phase results of biological samples have been obtained by solving the TIE. Simultaneously, a rotationally symmetric shear-based technique is used that can yield isotropic DIC. In this paper, we describe numerical simulation and optical experiments carried out to validate the accuracy and viability of this technology. The calculated Michelson contrast of the ZPC image in the resolution plate experiment increased from 0.196 to 0.394.

Functional Diversity of Dopamine Axons in Prefrontal Cortex During Classical Conditioning.

Midbrain dopamine neurons impact neural processing in the prefrontal cortex (PFC) through mesocortical projections. However, the signals conveyed by dopamine projections to the PFC remain unclear, particularly at the single-axon level. Here, we investigated dopaminergic axonal activity in the medial PFC (mPFC) during reward and aversive processing. By optimizing microprism-mediated two-photon calcium imaging of dopamine axon terminals, we found diverse activity in dopamine axons responsive to both reward and aversive stimuli. Some axons exhibited a preference for reward, while others favored aversive stimuli, and there was a strong bias for the latter at the population level. Long-term longitudinal imaging revealed that the preference was maintained in reward- and aversive-preferring axons throughout classical conditioning in which rewarding and aversive stimuli were paired with preceding auditory cues. However, as mice learned to discriminate reward or aversive cues, a cue activity preference gradually developed only in aversive-preferring axons. We inferred the trial-by-trial cue discrimination based on machine learning using anticipatory licking or facial expressions, and found that successful discrimination was accompanied by sharper selectivity for the aversive cue in aversive-preferring axons. Our findings indicate that a group of mesocortical dopamine axons encodes aversive-related signals, which are modulated by both classical conditioning across days and trial-by-trial discrimination within a day.

Functional diversity of dopamine axons in prefrontal cortex during classical conditioning.

Midbrain dopamine neurons impact neural processing in the prefrontal cortex (PFC) through mesocortical projections. However, the signals conveyed by dopamine projections to the PFC remain unclear, particularly at the single-axon level. Here, we investigated dopaminergic axonal activity in the medial PFC (mPFC) during reward and aversive processing. By optimizing microprism-mediated two-photon calcium imaging of dopamine axon terminals, we found diverse activity in dopamine axons responsive to both reward and aversive stimuli. Some axons exhibited a preference for reward, while others favored aversive stimuli, and there was a strong bias for the latter at the population level. Long-term longitudinal imaging revealed that the preference was maintained in reward- and aversive-preferring axons throughout classical conditioning in which rewarding and aversive stimuli were paired with preceding auditory cues. However, as mice learned to discriminate reward or aversive cues, a cue activity preference gradually developed only in aversive-preferring axons. We inferred the trial-by-trial cue discrimination based on machine learning using anticipatory licking or facial expressions, and found that successful discrimination was accompanied by sharper selectivity for the aversive cue in aversive-preferring axons. Our findings indicate that a group of mesocortical dopamine axons encodes aversive-related signals, which are modulated by both classical conditioning across days and trial-by-trial discrimination within a day.

Polysulfide synthesis via visible-light-induced heteroarene-migratory dithiosulfonylation reaction.

A photocatalyzed heteroarene-migratory dithiosulfonylation of alkene-tethered sulfone using dithiosulfonate (ArSO2-SSR) has been reported, featuring mild conditions, and high atom economy. The resulting products can be converted into dihydrothiophenes and homoallyl disulfides, making the method highly valuable.

CK2 blockade alleviates liver fibrosis by suppressing activation of hepatic stellate cells via the Hedgehog pathway.

BACKGROUND AND PURPOSE: Liver fibrosis is a serious cause of morbidity and mortality worldwide characterized by accumulation of extracellular matrix produced by hepatic stellate cells (HSCs). The protein kinase CK2 is a pro-survival kinase overexpressed in human tumours. However, the biological role of CK2 in liver fibrosis is largely unknown. We aimed to investigate the mechanism by which CK2 promotes liver fibrosis. EXPERIMENTAL APPROACH: In vitro, LX-2 cells were stimulated with transforming growth factor-ß (TGF-ß). HSCs were also isolated for research. In vivo, the adeno-associated virus AAV-sh-csnk2a1 was used to knockdown CK2α specifically in HSCs, and CX-4945 was used to pharmacologically inhibit the enzymatic activity of CK2 in murine models of fibrosis induced by carbon tetrachloride (CCl4 ) and a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet. Histological and biochemical analyses were performed to study the involvement of CK2 in regulation of fibrogenic and fibrolytic factors as well as activation properties of HSCs. KEY RESULTS: HSC-specific genetic invalidation of CK2α or pharmacological inhibition of CK2 protected mice treated with CCl4 or fed a DDC diet against liver fibrosis and HSC accumulation. Mechanistically, CK2α, which bound to Smoothened (SMO), was a positive regulator of the Hedgehog signal transduction pathway. CK2 prevented ubiquitination and proteasomal degradation of SMO, which was abolished by knockdown of CK2α or pharmacological inhibition of CK2. CONCLUSIONS AND IMPLICATIONS: CK2 activation is critical to sustain the activated and fibrogenic phenotype of HSCs via SMO stabilization. Therefore, inactivation of CK2 by CX-4945 may be of therapeutic interest for liver fibrotic diseases.

FGF18 alleviates hepatic ischemia-reperfusion injury via the USP16-mediated KEAP1/Nrf2 signaling pathway in male mice.

Hepatic ischemia-reperfusion injury (IRI) is a common complication occurs during hepatic resection and transplantation. However, the mechanisms underlying hepatic IRI have not been fully elucidated. Here, we aim to explore the role of fibroblast growth factor 18 (FGF18) in hepatic IRI. In this work, we find that Hepatic stellate cells (HSCs) secrete FGF18 and alleviates hepatocytes injury. HSCs-specific FGF18 deletion largely aggravates hepatic IRI. Mechanistically, FGF18 treatment reduces the levels of ubiquitin carboxyl-terminal hydrolase 16 (USP16), leading to increased ubiquitination levels of Kelch Like ECH Associated Protein 1 (KEAP1) and the activation of nuclear factor erythroid 2-related factor 2 (Nrf2). Furthermore, USP16 interacts and deubiquitinates KEAP1. More importantly, Nrf2 directly binds to the promoter of USP16 and forms a negative feedback loop with USP16. Collectively, our results show FGF18 alleviates hepatic IRI by USP16/KEAP1/Nrf2 signaling pathway in male mice, suggesting that FGF18 represents a promising therapeutic approach for hepatic IRI.

Traditional Chinese medicine to improve rural health in South Africa: A case study for Gauteng.

Background: Rural health is a global crisis across different continents. Most of Africa is predominantly rural and is experiencing financial constraints. Medical support and supplies are a dire need in rural Africa. An alternative option to support the rural population is through traditional Chinese medicine (TCM). Studies have highlighted the efficacy and cost-effectiveness of Chinese medicine in improving health. Aim: This article aims to investigate how rural health can be improved through alternative medicine options, focusing primarily on TCM. Setting: An identified TCM practice in Gauteng province was selected as the research setting. Methods: This study adopted a qualitative case study design to explore 10 participants' views on TCM to improve rural health. The health belief model was used as a theoretical framework, and thematic analysis was used for this study. Results: Findings revealed that most participants accepted TCM as an alternative medical health care option as it resonated with African herbal medicine. Participants agreed that TCM is cheaper and has no side effects. Conclusion: There is a lack of appropriate medical service providers in most rural areas, and often, people depend on traditional medicines as a quick remedy. As TCM is cost-effective and has proven to treat numerous ailments successfully, it is recommended that it be further explored as a health care option available to rural populations. Contribution: This was the first study on South African patients' views on TCM in the South African context.

FGF21 promotes migration and differentiation of epidermal cells during wound healing via SIRT1-dependent autophagy.

BACKGROUND AND PURPOSE: Migration and differentiation of epidermal cells are essential for epidermal regeneration during wound healing. Fibroblast growth factor 21 (FGF21) plays key roles in mediating a variety of biological activities. However, its role in skin wound healing remains unknown. EXPERIMENTAL APPROACH: Fgf21 knockout (Fgf21 KO) mice were used to determine the effect of FGF21 on wound healing. The source of FGF21 and its target cells were determined by immunohistochemistry, immunoblotting, and ELISA assay. Moreover, Sirt1flox/flox and Atg7flox/flox mice were constructed and injected with the epidermal-specific Cre virus to elucidate the underlying mechanisms. Migration and differentiation of keratinocytes were evaluated in vitro by cell scratch assays, immunofluorescence, and qRT-RCR. The effects were further assessed when SIRT1, ATG7, ATG5, BECN1, and P53 were silenced. Interactions between SIRT1 and autophagy-related genes were assessed using immunoprecipitation assays. KEY RESULTS: FGF21 was active in fibroblasts and promoted migration and differentiation of keratinocytes following injury. After wounding, SIRT1 expression and autophagosome synthesis were lower in Fgf21 KO mice. Depletion of ATG7 in keratinocytes counteracted the FGF21-induced increases in migration and differentiation, suggesting that autophagy is required for the FGF21-mediated pro-healing effects. Furthermore, epithelial-specific Sirt1 knockout abolished the FGF21-mediated improvements of autophagy and wound healing. Silencing of SIRT1 in keratinocytes, which decreased deacetylation of p53 and autophagy-related proteins, revealed that FGF21-induced autophagy during wound healing was SIRT1-dependent. CONCLUSIONS AND IMPLICATIONS: FGF21 is a key regulator of keratinocyte migration and differentiation during wound healing. FGF21 may be a novel therapeutic target to accelerate would healing.

Beetroot as a functional food with huge health benefits: Antioxidant, antitumor, physical function, and chronic metabolomics activity.

Previously, beetroot is mainly consumed as a food additive. In recent years, the beetroot, especially the betalains (betanin) and nitrates it contains, now has received increasing attention for their effective biological activity. Betalains have been proven to eliminate oxidative and nitrative stress by scavenging DPPH, preventing DNA damage, and reducing LDL. It also has been found to exert antitumor activity by inhibiting cell proliferation, angiogenesis, inducing cell apoptosis, and autophagy. In some chronic diseases, nitrate is the main component for lowing blood lipids, glucose, and pressure, while its role in treating hypertension and hyperglycemia has not been clearly stated. Moreover, the intake of nitrate-rich beetroot could enhance athletic performance and attenuate muscle soreness in certain types of exercise. The objective of this review is to provide sufficient evidence for the clarification of health benefits of beetroot, especially in the aspect of biooxidation, neoplastic diseases, some chronic diseases, and energy supplementation.

Progressive and Prognostic Performance of an Extracellular Matrix-Receptor Interaction Signature in Gastric Cancer.

The role of an extracellular matrix- (ECM-) receptor interaction signature has not been fully clarified in gastric cancer. This study performed comprehensive analyses on the differentially expressed ECM-related genes, clinicopathologic features, and prognostic application in gastric cancer. The differentially expressed genes between tumorous and matched normal tissues in The Cancer Genome Atlas (TCGA) and validation cohorts were identified by a paired t-test. Consensus clusters were built to find the correlation between clinicopathologic features and subclusters. Then, the least absolute shrinkage and selection operator (lasso) method was used to construct a risk score model. Correlation analyses were made to reveal the relation between risk score-stratified subgroups and clinicopathologic features or significant signatures. In TCGA (26 pairs) and validation cohort (134 pairs), 25 ECM-related genes were significantly highly expressed and 11 genes were downexpressed in gastric cancer. ECM-based subclusters were slightly related to clinicopathologic features. We constructed a risk score model = 0.081∗log2 (CD36) + 0.043∗log2 (COL5A2) + 0.001∗log2 (ITGB5) + 0.039∗log2 (SDC2) + 0.135∗log2 (SV2B) + 0.012∗log2 (THBS1) + 0.068∗log2 (VTN) + 0.023∗log2 (VWF). The risk score model could well predict the outcome of patients with gastric cancer in both training (n = 351, HR: 1.807, 95% CI: 1.292-2.528, P = 0.00046) and validation (n = 300, HR: 1.866, 95% CI: 1.347-2.584, P = 0.00014) cohorts. Besides, risk score-based subgroups were associated with angiogenesis, cell adhesion molecules, complement and coagulation cascades, TGF-beta signaling, and mismatch repair-relevant signatures (P < 0.0001). By univariate (1.845, 95% CI: 1.382-2.462, P < 0.001) and multivariate (1.756, 95% CI: 1.284-2.402, P < 0.001) analyses, we regarded the risk score as an independent risk factor in gastric cancer. Our findings revealed that ECM compositions became accomplices in the tumorigenesis, progression, and poor survival of gastric cancer.

FGF/FGFR signaling pathway involved resistance in various cancer types.

Resistance becomes major clinical issue in cancer treatment, which strongly limits patients to benefit from oncotherapy. Growing evidences have been indicative of the critical role of fibroblast growth factor (FGF)/receptor (FGFR) signaling played in resistance to oncotherapy. In this review we discussed the underlying mechanisms of FGF/FGFR signaling mediated resistance to chemotherapy, radiotherapy and target therapy in various cancers. Meanwhile, we summarized the reported mechanism of FGF/FGFR inhibitors resistance in cancers.

Comparative morphology of the internal elastic lamina of cerebral and peripheral arteries.

BACKGROUND: Atherosclerosis progresses later and with fewer complicated plaques in cerebral arteries than in peripheral arteries. The internal elastic lamina has been proposed to be important for the migration of smooth muscle cells into the intima during intimal thickening and atherosclerosis. METHODS: A total of 280 segments were retrieved from 14 autopsy specimens. Five sites were selected for analysis in each case: the middle cerebral artery, basilar artery, coronary artery, iliac artery and renal artery. We investigated the differences in the internal elastic lamina of cerebral and peripheral arteries. RESULTS: The average thickness of the internal elastic lamina of the cerebral arteries was larger than that of the peripheral arteries in both the early and advanced atherosclerotic plaque groups. Among the cerebral arteries, the basilar arteries had a thicker internal elastic lamina than the middle cerebral arteries. Among the peripheral arteries, the renal arteries had the thickest internal elastic lamina, followed by the iliac arteries and coronary arteries. Atherosclerosis led to a reduction in the thickness of the internal elastic lamina of the basilar, middle cerebral, and renal arteries. The stratification of the internal elastic lamina of iliac arteries significantly affected its measurement. The internal elastic lamina of coronary arteries was not affected by atherosclerosis, but it appeared fragmented. CONCLUSION: The results suggest that the characteristics of atherosclerotic plaques in cerebral and peripheral arteries may be related to the characteristics of the internal elastic lamina.

Diagnostic, progressive and prognostic performance of m6A methylation RNA regulators in lung adenocarcinoma.

Background: N6-methyladenosine (m6A) RNA methylation is dynamically and reversibly regulated by methyl-transferases ("writers"), binding proteins ("readers"), and demethylases ("erasers"). The m6A is restored to adenosine and thus to achieve demethylation modification. The abnormality of m6A epigenetic modification in cancer has been increasingly attended. However, we are rarely aware of its diagnostic, progressive and prognostic performance in lung adenocarcinoma (LUAD). Methods and Results: The expression of 13 widely reported m6A RNA regulators in LUAD and normal samples were systematically analyzed. There were 12 m6A RNA methylation genes displaying aberrant expressions, and an 11-gene diagnostic score model was finally built (Diagnostic score =0.033*KIAA1429+0.116*HNRNPC+0.115*RBM15-0.067* METTL3-0.048*ZC3H13-0.221*WTAP+0.213*YTHDF1-0.132*YTHDC1-0.135* FTO+0.078*YTHDF2+0.014*ALKBH5). Receiver operating characteristic (ROC) analysis was performed to demonstrate superiority of the diagnostic score model (Area under the curve (AUC) was 0.996 of training cohort, P<0.0001; AUC was 0.971 of one validation cohort-GSE75037, P<0.0001; AUC was 0.878 of another validation cohort-GSE63459, P<0.0001). In both training and validation cohorts, YTHDC2 was associated with tumor stage (P<0.01), while HNRNPC was up expressed in progressed tumor (P<0.05). Besides, WTAP, RBM15, KIAA1429, YTHDF1, and YTHDF2 were all up expressed for TP53 mutation. Furthermore, using least absolute shrinkage and selection operator (lasso) regression analysis, a ten-gene risk score model was built. Risk score=0.169*ALKBH5-0.159*FTO+0.581*HNRNPC-0.348* YTHDF2-0.265*YTHDF1-0.123*YTHDC2+0.434*RBM15+0.143*KIAA1429-0.200*WTAP-0.310*METTL3. There existed correlation between the risk score and TNM stage (P<0.01), lymph node stage (P<0.05), gender (P<0.05), living status (P<0.001). Univariate and multivariate Cox regression analyses of relevant clinicopathological characters and the risk score revealed risk score was an independent risk factor of lung adenocarcinoma (HR: 2.181, 95%CI (1.594-2.984), P<0.001). Finally, a nomogram was built to facilitate clinicians to predict outcome. Conclusions: m6A epigenetic modification took part in the progression, and provided auxiliary diagnosis and prognosis of LUAD.

A Feasible Method of Angiogenesis Assessment in Gastric Cancer Using 3D Microvessel Density.

BACKGROUND: Cancer stem cell (CSC) promotes angiogenesis which plays an important role in tumor occurrence, growth, and metastasis. Accurately, quantifying the tumor vasculature can help understanding CSC characteristics and improve cancer diagnosis, therapy planning, and evaluation. The objective of this study is to present a method for improved angiogenesis assessment. METHODS: We proposed a three-dimensional microvessel density (3D MVD) to evaluate tumor angiogenesis and tested it in animal models. Six male Balb/c nude mice were divided into normal group and tumor group. The mice in tumor group were orthotopically implanted human gastric cancer, cell line BGC-823. The phase-contrast images were collected at Shanghai Synchrotron Radiation Facility BL13W beamline, which has much higher soft-tissue contrast and spatial resolution than conventional X-ray. After volume reconstruction and vessel extraction, the 3D models of the angiogenesis were established for MVD calculation. RESULTS: The results showed that the proposed 3D MVD is positively correlated with the pathological changes of the microvessels. It took the advantage of high resolution of the phase-contrast imaging and added three-dimensional information to the existing MVD measure. CONCLUSIONS: Our study presents a feasible approach for better understanding of tumor angiogenesis. It may provide doctors and scientists a better tool for cancer investigation and improving medical outcomes.