Altered Cell Clusters and Upregulated Aqp1 in Connexin 50 Knockout Lens Epithelium.

Purpose: To characterize the heterogeneity and cell clusters of postnatal lens epithelial cells (LECs) and to investigate the downstream targets of connexin 50 (Cx50) in the regulation of lens homeostasis and lens growth. To determine differentially expressed genes (DEGs) in the connexin 50 knockout (Cx50KO) lens epithelial cells that shed light on novel mechanism underlying the cataract and small size of the Cx50KO lenses. Methods: Single-cell RNA sequencing (scRNA-seq) of lens epithelial cells isolated from one-month-old Cx50KO and wild-type (WT) mice were performed. Differentially expressed genes were identified, and selected DEGs were further studied by quantitative real-time PCR (RT-qPCR) analysis and Western blot analysis. Results: The expression profiles of several thousand genes were identified by scRNA-seq data analysis. In comparison to the WT control, many DEGs were identified in the Cx50KO lens epithelial cells, including growth regulating transcriptional factors and genes encoding water channels. Significantly upregulated aquaporin 1 (Aqp1) gene expression was confirmed by RT-qPCR, and upregulated AQP1 protein expression was confirmed by Western blot analysis and immunostaining both in vivo and in vitro. Conclusions: Lens epithelial cells exhibit an intrinsic heterogeneity of different cell clusters in regulating lens homeostasis and lens growth. Upregulated Aqp1 in Cx50KO lens epithelial cells suggests that both connexin 50 and AQP1 likely play important roles in regulating water homeostasis in lens epithelial cells.

Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer.

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 .

Transcriptome analysis and functional verification reveal the roles of copper in resistance to potato virus Y infection in tobacco.

Potato virus Y (PVY) is one of the most important pathogens in the genus Potyvirus that seriously harms agricultural production. Copper (Cu), as a micronutrient, is closely related to plant immune response. In this study, we found that foliar application of Cu could inhibit PVY infection to some extent, especially at 7 days post inoculation (dpi). To explore the effect of Cu on PVY infection, transcriptome sequencing analysis was performed on PVY-infected tobacco with or without Cu application. Several key pathways regulated by Cu were identified, including plant-pathogen interaction, inorganic ion transport and metabolism, and photosynthesis. Moreover, the results of virus-induced gene silencing (VIGS) assays revealed that NbMLP423, NbPIP2, NbFd and NbEXPA played positive roles in resistance to PVY infection in Nicotiana benthamiana. In addition, transgenic tobacco plants overexpressing NtEXPA11 showed increased resistance to PVY infection. These results contribute to clarify the role and regulatory mechanism of Cu against PVY infection, and provide candidate genes for disease resistance breeding.

Identification and Characterization of Retinitis Pigmentosa in a Novel Mouse Model Caused by PDE6B-T592I.

The cGMP-phosphodiesterase 6 beta subunit (PDE6B) is an essential component in the phototransduction pathway for light responses in photoreceptor cells. PDE6B gene mutations cause the death of rod photoreceptors, named as hereditary retinitis pigmentosa (RP) in humans and retinal degeneration (RD) in rodents. Here, we report a new RD model, identified from a phenotypic screen of N-ethyl-N-nitrosourea (ENU)-induced mutant mice, which displays retinal degeneration caused by a point mutation in the Pde6b gene that results in PDE6B-T592I mutant protein. The homozygous mutant mice show an extensive loss of rod photoreceptors at the age of 3 weeks; unexpectedly, the loss of rod photoreceptors can be partly rescued by dark rearing. Thus, this RD mutant model displays a light-dependent loss of rod photoreceptors. Both western blot and immunostaining results show very low level of mutant PDE6B-T592I protein in the retina. Structure modeling suggests that the T592I mutation probably affects the function and stability of PDE6B protein by changing intramolecular interactions. We further demonstrate that the expression of wild-type PDE6B delivered by subretinally injected adeno-associated virus (rAAV) prevents photoreceptor cell death in this RD model in vivo. The PDE6B-T592I mutant is, therefore, a valuable RD model for evaluating rAAV-mediated treatment and for investigating the molecular mechanism of light-dependent rod photoreceptor cell death that is related to impaired PDE6B function.

Impaired autophagy contributes to the aggravated deterioration of osteoarthritis articular cartilage by peroxisome proliferator-activated receptor α deficiency, associated with decreased ERK and Akt activation.

BACKGROUND: Although the chondroprotection of peroxisome proliferator-activated receptor α (PPARα) activation against osteoarthritis (OA) has been revealed, the regulatory mechanism of PPARα deficiency to aggravate osteoarthritic cartilage deterioration remains unclear. Here, we aimed to investigate whether and how autophagy is involved in OA pathological progression. METHODS: Model of experimental OA was established using destabilization of the medial meniscus in PPARα-KO 129S4/SvJae male mice, followed by histopathological detection of articular cartilage and immunohistochemistry detection of extracellular matrix (ECM) or autophagy-related signal molecules. Meanwhile, human OA chondrocytes obtained from total knee replacement surgery patients with OA were cultured with the pretreatment of IL-1ß, followed with the treatment of PPARα agonist WY14643 and the detection of related signal molecules. RESULTS: PPARα deficiency aggravated cartilage damage with decreased LC3B level in combination with an increase in P62 level, accompanied with reduced p-Akt and p-ERK levels in PPARα-KO mouse model of experimental OA. On the contrary, PPARα activation by WY14643 promoted ECM synthesis in IL-1ß-treated human OA chondrocytes, accompanied with increased LC3B-II/I ratio and Beclin 1 level and decreased P62 and Bcl2 levels. Meanwhile, it was observed that activated ERK and Akt by PPARα activation contributed to the enhancement of autophagy and ECM synthesis in human OA chondrocytes. CONCLUSIONS: Impaired autophagy contributed to the aggravated deterioration of osteoarthritis articular cartilage by PPARα deficiency associated with the suppression of ERK and Akt, with an implication that triggering PPARα activation ought to be a potential promising therapeutic target for OA therapy.

Adaptive Optical Two-Photon Fluorescence Microscopy Probes Cellular Organization of Ocular Lenses In Vivo.

Purpose: The mammalian ocular lens is an avascular multicellular organ that grows continuously throughout life. Traditionally, its cellular organization is investigated using dissected lenses, which eliminates in vivo environmental and structural support. Therefore, in vivo optical imaging methods for studying lenses in their native context in live animals are urgently needed. Methods: Here, we demonstrated that two-photon fluorescence microscopy can visualize lens cells in vivo. To maintain subcellular resolution at depth, we used adaptive optics to correct aberrations owing to ocular and lens tissues, which led to substantial signal and resolution improvements. Results: Imaging lens cells up to 980 µm deep, we observed novel cellular organizations including suture-associated voids, enlarged vacuoles, and large cavities, contrary to the conventional view of a highly ordered organization. We tracked these features longitudinally over weeks and observed the incorporation of new cells during growth. Conclusions: Taken together, noninvasive longitudinal in vivo imaging of lens morphology using adaptive optics two-photon fluorescence microscopy will allow us to observe the development or alterations of lens cellular organization in living animals directly.

Crystal Structure of a Classical MHC Class I Molecule in Dogs; Comparison of DLA-88*0 and DLA-88*5 Category Molecules.

DLA-88 is a classical major histocompatibility complex (MHC) class I gene in dogs, and allelic DLA-88 molecules have been divided into two categories named "DLA-88*0" and "DLA-88*5." The defining difference between the two categories concerns an LQW motif in the α2 domain helical region of the DLA-88*5 molecules that includes the insertion of an extra amino acid compared to MHC class I consensus length. We here show that this motif has been exchanged by recombination between different DLA-88 evolutionary lineages. Previously, with pDLA-88*508:01, the structure of a molecule of the DLA-88*5 category was elucidated. The present study is the first to elucidate a structure, using X-ray crystallography, of the DLA-88*0 category, namely DLA-88*001:04 complexed with ß2m and a nonamer peptide derived from canine distemper virus (CDV). The LQW motif that distinguishes DLA-88*5 from DLA-88*0 causes a shallower peptide binding groove (PBG) and a leucine exposed at the top of the α2 domain helix expected to affect T cell selection. Peptide ligand amino acid substitution and pMHC-I complex formation and stability analyses revealed that P2 and P3 are the major anchor residue positions for binding to DLA-88*001:04. We speculate that the distribution pattern of the LQW motif among canine classical MHC class I alleles represents a strategy to enhance allogeneic rejection by T cells of transmissible cancers such as canine transmissible venereal tumor (CTVT).

Conversion Hip Arthroplasty Using Standard and Long Stems after Failed Internal Fixation of Intertrochanteric Fractures.

OBJECTIVE: Failed internal fixation of intertrochanteric fractures (FIF-ITF) is often treated by conversion hip arthroplasty (CHA). This study aimed to evaluate the results and complications of using standard and long femoral stems in this operation. METHODS: This retrospective, multi-center study enrolled 31 total hip arthroplasty (THA) and 23 hemiarthroplasties (HA) cases (30 women, 24 men; mean age 76 years) after FIF-ITF between 2012 and 2019, divided into two groups: standard stem group (n = 20) and long stem group (n = 34). The initial internal fixation includes 38 cases of proximal femoral nail anti-rotation (PFNA), eight cases of the dynamic hip screw (DHS), and eight cases of locking proximal femoral plate (LPFP). The indications for CHA included 38 cases of failure of fixation, seven cases of nonunion, and nine cases of avascular necrosis or posttraumatic osteoarthritis. Perioperative data and complications related to fracture and operation were collected, and preoperative and postoperative clinical and radiological data were analyzed. Clinical outcomes were assessed using Harris hip score (HHS) and 36-item Short Form survey (SF-36: including physical function (PF) score and body pain (BP) score). Statistical analyses were performed using the chi-square or Fisher's exact test, and the 2-sample t-test or Wilcoxon rank sum test. RESULTS: At an average of 5.6 years with a minimum of 2 years follow-up. A significant overall surgeon-related complication rate was detected (27.8% [15/54]), five cases had an intraoperative femur fracture, one case had a late periprosthetic femoral fracture, two cases had a stem penetration, one case had a cement leakage, and two patients had an early postoperative dislocation, one infection and three cases of stem loosening or subsidence. Long stems had an increased risk of complication (13/34) compared to standard stems (2/20) (P = 0.031). The operation time and blood loss in the long stem group were higher than those in the standard stem group (P = 0.002; 0.017). HHS and SF-36 significantly improved in both groups from preoperative to the final follow-up and did not present significant differences at the final follow-up (P > 0.05). CONCLUSION: CHA following FIF-ITF showed a successful mid-term clinical result, long stem arthroplasty should be approached with caution for the risks of higher complication rate, especially intraoperative femoral fractures.

Predicting malignancy in thyroid nodules based on conventional ultrasound and elastography: the value of predictive models in a multi-center study.

BACKGROUND: This study aimed to establish predictive models based on features of Conventional Ultrasound (CUS) and elastography in a multi-center study to determine appropriate preoperative diagnosis of malignancy in thyroid nodules with different risk stratification based on 2017 Thyroid Imaging Reporting and Data System by the American College of Radiology (ACR TI-RADS) guidelines. METHODS: Five hundred forty-eight thyroid nodules from three centers pathologically confirmed by the cytology or histology were retrospectively enrolled in the study, which were examined by CUS and elastography before fine needle aspiration (FNA) and surgery. Characteristics of CUS of thyroid nodules were reviewed according to 2017 ACR TI-RADS. Binary logistic regression analysis was used to develop the prediction models based on the different risk stratification of CUS features and elastography which were statistically significant. Values of predictive models were evaluated regarding the discrimination and calibration. RESULTS: Binary logistic regression showed that patients' age, taller-than-wider, lobulated or irregular boundary, extra-thyroid extension, microcalcification and the elastic parameter of Virtual touch tissue imaging quantification (VTIQ) max were independent predictors for thyroid malignancy (p < 0.05) in the ACR model and showed the area under the curve (AUC) in training (0.912) and validation cohort (internal and external: 0.877 vs 0.935). Predictive models showed predictors in ACR TR4 and TR5 for malignancy and diagnostic performance of AUC in training, internal and external validation cohort respectively: the VTIQ max (p < 0.001) with AUC of 0.809 vs 0.842 vs 0.705 and the age, taller than wide, VTIQ max variables with AUC of 0.859 vs 0.830 vs 0.906 in validation cohort. All predictive models have better calibration capabilities (p > 0.05). CONCLUSIONS: Predictive models combined CUS and elastography features would aid clinicians to make appropriate preoperative diagnosis of thyroid nodules among different risk stratification. The elastography parameter of VTIQ max has the priority in distinguishing thyroid malignancy with moderately suspicious (ACR TR4).

RRBP1 depletion of bone metastatic cancer cells contributes to enhanced expression of the osteoblastic phenotype.

Bone metastatic cancer-secreted extracellular factors are capable of modifying the bone microenvironment through interacting with bone cells, including osteoblasts. Reticulum ribosome-binding protein 1 (RRBP1) is substantially expressed in certain bone metastatic cancer cells. This study was undertaken to determine whether RRBP1 from bone metastatic cancer cells affects the osteoblastic phenotype expression. Breast and prostate cancer cells, MDA-MB-231 and PC3, were cultured, respectively, followed by collecting conditioned mediums (CMs) and identifying the abundance of RRBP1 in CMs using LC-MS/MS. MC3T3-E1 cells were cultured with a mixed medium (including CMs from shRRBP1-transduced two-type cancer cells) with or without endoplasmic reticulum (ER) stress inhibitor 4-PBA, followed by measuring the levels of osteoblastic phenotype expression and biomarkers of ER stress using western blotting, qPCR, and ARS staining, respectively. Similar experiments were performed in shRrbp1-transduced MC3T3-E1 cells cultured with a mixed medium (including CMs from the two-type cancer cells). Bone formation parameters were measured in the tibia of nude mice injected with shRRBP1-transduced two-type cancer cells using micro-CT analysis. These results showed that RRBP1 is the sole shared high-abundance protein in CMs from the two-type cancer cells, involving osteoblast differentiation. CMs from shRRBP1-transduced two-type cells boosted the osteoblastic phenotype expression partially through increasing ER stress. CMs from the two-type cancer cells partially offset the similar alterations induced by shRrbp1 in MC3T3-E1 cells. Injection with shRRBP1-transduced two-type cells ameliorated the bone lesions in nude mice. Therefore, RRBP1 depletion of bone metastatic cancer enhanced the osteoblastic phenotype expression, suggesting a role of RRBP1 in the bone microenvironment.

The Inhibitory Role of Hydrogen Sulfide in UII-Induced Cardiovascular Effects and the Underlying Signaling Pathways.

Urotensin II (UII) could increase blood pressure and heart rate via increased central reactive oxygen species (ROS) levels. We reported previously that hydrogen sulfide (H2S) exerts an antihypertensive effect by suppressing ROS production. The aim of the current study is to further examine the effects of endogenous and exogenous H2S on UII-induced cardiovascular effects by using an integrated physiology approach. We also use cell culture and molecular biological techniques to explore the inhibitory role of H2S on UII-induced cardiovascular effects. In this study, we found that cystathionine-ß-synthase (CBS), the main H2S synthesizing enzyme in CNS, was expressed in neuronal cells of the rostral ventrolateral medulla (RVLM) area. Cellular distribution of CBS and urotensin II receptor (UT) in SH-SY5Y cells that are confirmed as glutamatergic were identified by immunofluorescent and Western blots assay. In Sprague-Dawley rats, administration of UII into the RVLM resulted in an increase in mean arterial pressure (MAP), heart rate (HR), ROS production, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and phosphorylation of p47phox, extracellular signal-regulated protein kinase (ERK)1/2 and p38MAPK, but not stress-activated protein kinase/Jun N-terminal kinase (SAPK/JNK). These effects of UII were attenuated by application into the RVLM of endogenous (L-cysteine, SAM) or exogenous (NaHS) H2S. These results were confirmed in SH-SY5Y cells. UII-induced cardiovascular effects were also significantly abolished by pretreatment with microinjection of Tempol, Apocynin, SB203580, or PD98059 into the RVLM. Preincubated SH-SY5Y cells with Apocynin before administration of UII followed by Western blots assay showed that ROS is in the upstream of p38MAPK/ERK1/2. Gao activation assay in SH-SY5Y cells suggested that H2S may exert an inhibitory role on UII-induced cardiovascular effects by inhibiting the activity of Gαo. These results suggest that both endogenous and exogenous H2S attenuate UII-induced cardiovascular effects via Gαo-ROS-p38MAPK/ERK1/2 pathway.

The Diagnostic Value of Mitochondrial Mass of Peripheral T Lymphocytes in Early Sepsis.

Background: Studies have shown that lymphocyte dysfunction can occur during the early stages of sepsis and that cell dysfunction is associated with mitochondrial dysfunction. Therefore, quantifying the mitochondrial function of lymphocytes in patients with sepsis could be valuable for the early diagnosis of sepsis. Methods: Seventy-nine patients hospitalized from September 2020 to September 2021 with Sepsis-3 were retrospectively analyzed and subsequently compared with those without sepsis. Results: Univariate analysis showed statistical differences between the data of the two groups regarding age, neutrophil/lymphocyte, procalcitonin (PCT), C-reactive protein, total bilirubin, serum creatinine, type B natriuretic peptide, albumin, prothrombin time, activated partial thromboplastin time, lactic acid, single-cell mitochondrial mass (SCMM)-CD3, SCMM-CD4, SCMM-CD8, and Acute Physiology and Chronic Health Evaluation II score (P < 0.05). Multivariate logistic regression analysis performed on the indicators mentioned above demonstrated a statistical difference in PCT, lactic acid, SCMM-CD4, and SCMM-CD8 levels between the two groups (P < 0.05). The receiver operating characteristic curves of five models were subsequently compared [area under the curve: 0.740 (PCT) vs. 0.933 (SCMM-CD4) vs. 0.881 (SCMM-CD8) vs. 0.961 (PCT + SCMM-CD4) vs. 0.915 (PCT+SCMM-CD8), P < 0.001]. Conclusion: SCMM-CD4 was shown to be a better diagnostic biomarker of early sepsis when compared with the traditional biomarker, PCT. Furthermore, the value of the combination of PCT and SCMM-CD4 in the diagnosis of early sepsis was better than that of SCMM-CD4 alone.

Centranthera grandiflore alleviates alcohol-induced oxidative stress and cell apoptosis.

Alcohol liver disease (ALD) has become a global threat to human health. It is associated with a wide range of liver diseases including alcohol fatty liver, steatosis, fibrosis and cirrhosis, and finally leads to liver cancer and even death. Centranthera grandiflora is a traditional Chinese medicinal herb commonly used to treat ALD, but no research about its mechanism is available. This study evaluated the hepatoprotective effect and mechanism of C. grandiflora against alcohol-induced liver injury in mice. We found that the ethanol extracts of C. grandiflora (CgW) alleviated the alcohol-induced liver injury, enhanced the levels of antioxidant enzymes, and reduced the amount of lipid peroxides. CgW also affected cell apoptosis by inhibiting the activity of Bax, cleaved-caspase 3 and cleaved-caspase 9, and increasing the activity of Bcl-2. In conclusion, the results showed that CgW can effectively improve ALD through alleviating oxidative stress and inhibiting cell apoptosis for the first time. This study suggested that C. grandiflora is a promising herbal medicine for ALD treatment.

A case of CIC-rearranged sarcoma with CIC-LEUTX gene fusion in spinal cord.

A 16-year-old male was admitted to the hospital for weakness of both lower extremities. Magnetic resonance imaging revealed an intraspinal extramedullary subdural mass at the thoracic 9 level. Microscopically, the tumor cells were small to medium sized and round to ovoid in shape. They were distributed in diffuse sheets or showed nodular appearance. The nucleus of the tumor had mild-to-moderate atypia, with vesicular chromatin and prominent nucleoli. A smaller proportion of tumor cells demonstrated rhabdoid morphology. Focal myxoid stromal change was present, in which tumor cells exhibited spindle shapes. Approximately two mitoses were counted per 10 high-power fields. No necrosis was observed. The tumor cells were focal positive for CD99; multifocal positive for WT1; diffuse positive for nestin, synaptophysin, and D2-40; partial positive for GFAP; focal positive for desmin and SSTR2; and scattered positive for S-100 protein. The Ki-67 labeling index was approximately 20%. Genetic testing revealed CIC-LEUTX gene fusion. Considering the patient's history, clinical data, pathological findings and genetic findings, we rendered a rare tumor named CIC-rearranged sarcoma with CIC-LEUTX gene fusion.

Association Between Passive Smoking and Menstrual Discomfort: A Cross-Sectional Study of 2,571 Non-smoking Chinese Nurses.

Introduction: Menstrual discomfort affects women's quality of life, which is an important public health issue. Evidence confirming the link between passive smoking and menstrual discomfort is limited. Therefore, the aim of this study is to investigate the aforementioned topic on the basis of a cross-sectional study of 2,571 non-smoking Chinese nurses. Methods: Demographic information and passive smoking were assessed using a self-administered questionnaire. Menstrual discomfort was characterized as dysmenorrhea, illness or weakness, bed rest, and restlessness during menstruation, which was assessed using a modified version of the Cornell Medical Index-Health Questionnaire. Multivariate-adjusted odds ratio (OR) and 95% confidence intervals (CIs) were estimated using the logistic regression model. Results: A total of 1:195 nurses (46.48%) were exposed to passive smoking. Compared with non-passive smoking nurses, passive smoking nurses were more likely to have menstrual discomfort symptoms (72.38 vs. 64.39%), especially symptoms of dysmenorrhea (49.54 vs. 42.08%), illnesses or weakness (48.28 vs. 42.08%), and restlessness during menstruation (53.05 vs. 46.22%). Exposure to passive smoking was significantly associated with menstrual discomfort (OR = 1.41, 95%CI: 1.19-1.67), especially symptoms of dysmenorrhea (OR = 1.32, 95%CI: 1.13-1.56), illness or weakness (OR = 1.24, 95%CI: 1.06-1.46), and restlessness (OR = 1.26, 95%CI: 1.08-1.48) during menstruation. The subgroup analyses, stratified by age, children, and marital status, agreed with the main findings. Conclusions: Exposure to passive smoking was related to symptoms of dysmenorrhea and menstrual discomfort.

Possible causes of atherosclerosis: lncRNA COLCA1 induces oxidative stress in human coronary artery endothelial cells and impairs wound healing.

Background: Atherosclerosis is the most common cause of cardiovascular disease, accompanied by high mortality and poor prognosis. Low-density lipoprotein (LDL) and its oxidized form oxidized low-density lipoprotein (oxLDL) play an important role in atherosclerosis. This article will explore the role of the lncRNA COLCA1 (colorectal cancer associated 1)/hsa-miR-371a-5p/SPP1 (secreted phosphoprotein 1) pathway in oxLDL in causing human coronary artery endothelial cells (HCAECs) inflammation and related biological function changes. Methods: OxLDL was used to stimulate HCAECs. The inflammatory response and biological function changes of HCAECs were analyzed, total RNA-seq was performed on HCAECs before and after stimulation, and RT-Qpcr (real-time quantitative PCR) was used to verify the differential genes. Interference of the expression of COLCA1 in HCAECs was performed by siRNA interference technology to verify the role of COLCA1 in the biological function changes of HCAECs after oxLDL stimulation, and further prove that COLCA1 affects SPP1 through hsa-miR-371a-5p. Results: OxLDL can affect the oxidative stress response of HCAECs, which in turn affects the apoptosis and wound healing ability of HCAECs. COLCA1 and SPP1 were highly expressed after oxLDL stimulation, while hsa-miR-371a-5p was the opposite. After COLCA1 interference, the oxidative stress level of HCAECs stimulated by oxLDL decreased, the apoptosis level also significantly decreased, and the wound healing ability was enhanced. After simultaneous COLCA1 interference and recovery of the expression of hsa-miR-371a-5p, these improved functions disappeared. The dual-luciferase assay confirmed that hsa-miR-371a-5p and COLCA1, hsa-miR-371a-5p and SPP1 has binding targets. Conclusions: OxLDL can up-regulate the expression of COLCA1 in HCAECs, which in turn affects the intracellular COLCA1/hsa-miR-371a-5p/SPP1 pathway to regulate the level of oxidative stress in cells. This in turn affects the level of apoptosis and wound healing ability, which causes cells to produce a continuous inflammatory response.

Distinguishing Cardiac Amyloidosis and Hypertrophic Cardiomyopathy by Thickness and Myocardial Deformation of the Right Ventricle.

OBJECTIVES: To compare right ventricular thickness (RVT) and deformation of cardiac amyloidosis (CA) and hypertrophic cardiomyopathy (HCM) patients. METHODS: Sixty CA (mean age 58 ± 10 years; 33 males (55%)) and sixty HCM patients (mean age 55 ± 14 years; 27 males (45%)) were retrospectively enrolled. RVT, global radical peak strain (GRPS), global longitudinal peak strain (GLPS), and global circumferential peak stain (GCPS) were analyzed. To determine the cutoff values of the RVT and RV strain parameters for distinguishing CA from HCM, the areas under the receiver operating characteristic curve (AUCs) were analyzed. RESULTS: RVT of CA patients was significantly thicker than that of HCM patients (7.8 ± 2.1 vs 5.9 ± 1.3, p < 0.001). Moreover, significantly decreased RV-GRPS (12.1 ± 6.9 vs 23.5 ± 12.1, p < 0.001), RV-GCPS (-3.4 ± 2.2 vs -5.6 ± 3.5, p < 0.001), and RV-GLPS (-4.6 ± 2.3 vs -11.1 ± 4.9, p < 0.001) were observed in CA patients compared with HCM patients. RVT and RV strain demonstrate comparable diagnostic accuracy in differentiating CA from HCM. In particular, RV-GLPS combined with RVT showed the best performance for discriminating CA from HCM (AUC = 0.92, 95% CI: 0.85 to 0.96, p = 0.0001). CONCLUSIONS: Right ventricular myocardial thickness and deformation of CA patients was more severe than HCM patients. RV-GLPS combined with RVT presents an excellent diagnostic performance in distinguishing CA and HCM.

Association Between Passive Smoking and Health Among Chinese Nurses: A Cross-Sectional Study.

This study aimed to investigate the association between passive smoking and physical and psychological health in Chinese nurses. Participants of this cross-sectional study comprised 2,484 non-smoking nurses. Passive smoking and demographic information were assessed using a self-administered questionnaire. Physical, psychological, and overall health status of nurses were measured using the Cornell Medical Index (CMI) health questionnaire. Multivariate-adjusted odds ratio (OR) and 95% confidence interval (CI) for nurses' health were estimated by exposure to passive smoking using unconditional logistic regression models. A total of 1,219 nurses (49.07%) were exposed to passive smoking. Of these, 609 (24.52%), 160 (6.44%), and 587 (23.63%) nurses had poorer physical, mental, and overall health, respectively. After adjusting for other confounding factors, compared with the non-passive smoking group, passive smoking was associated with poor physical (OR = 1.51, 95% CI: 1.25-1.83), mental (OR = 1.48, 95% CI: 1.07-2.07), and overall (OR = 1.58, 95% CI: 1.30-1.93) health of nurses, respectively. We also carried out subgroup analyses stratified by age, department, and professional title, which showed that most findings supported the main results. This study demonstrated that exposure to passive smoking was a risk factor for overall decreased physical and mental health status among Chinese nurses.

Reticulocalbin 1 is required for proliferation and migration of non-small cell lung cancer cells regulated by osteoblast-conditioned medium.

Reticulocalbin1 (RCN1) is implicated in tumorigenesis and tumour progression. However, whether RCN1-mediated bone metastasis of non-small cell lung cancer (NSCLC) cells was elusive. Here, we assessed the effect of osteoblast-conditioned medium (CM) on proliferation and migration of NSCLC cell line, NCI-H1299 and NCI-H460 cells, and identified the soluble mediators in CMs from osteoblasts and NSCLC cells using MTT, Clonogenicity, Transwell, wound healing, RT-PCR, and Western blotting assays, and LC-MS/MS analysis, respectively. Furthermore, the role of RCN1 was investigated in NSCLC cells cultured with or without osteoblast-CM. Tumour growth and bone resorption were measured in a nude mouse model bearing NCI-H1299 cells transduced with shRNA/RCN1 vector using in vivo imaging technique and micro-CT. The results showed that RCN1 with a higher abundance in osteoblast-CM, which was present in extracellular vesicles (EVs), enhanced RCN1 expression in NSCLC cells. Osteoblast-CM partially offset the inhibitory effect of RCN1 depletion on proliferation and migration of NSCLC cells. RCN1 depletion-induced endoplasmic reticulum (ER) stress caused by increasing GRP78, CHOP, IRE1α, p-IRE1α, p-PERK and p-JNK, which was positively regulated by self-induced autophagy, contributed to suppression of proliferation and migration in NCI-H1299 cells. Therefore, osteoblasts produced RCN1 to transfer into NSCLC cells partially through EVs, facilitating proliferation and migration of NSCLC cells via blocking ER stress. RCN1 could be required for proliferation and migration of NSCLC cells regulated by osteoblast-CM.

[Application of Automated Machine Learning Based on Radiomics Features of T2WI and RS-EPI DWI to Predict Preoperative T Staging of Rectal Cancer].

OBJECTIVE: To explore the radiomics features of T2 weighted image (T2WI) and readout-segmented echo-planar imaging (RS-EPI) plus difusion-weighted imaging (DWI), to develop an automated mahchine-learning model based on the said radiomics features, and to test the value of this model in predicting preoperative T staging of rectal cancer. METHODS: The study retrospectively reviewed 131 patients who were diagnosed with rectal cancer confirmed by the pathology results of their surgical specimens at West China Hospital of Sichuan University between October, 2017 and December, 2018. In addition, these patients had preoperative rectal MRI. Tumor regions from preoperative MRI were manually segmented by radiologists with the ITK-SNAP software from T2WI and RS-EPI DWI images. PyRadiomics was used to extract 200 features-100 from T2WI and 100 from the apparent diffusion coefficient (ADC) calculated from the RS-EPI DWI. MWMOTE and NEATER were used to resample and balance the dataset, and 13 cases of T 1-2 stage simulation cases were added. The overall dataset was divided into a training set (111 cases) and a test set (37 cases) by a ratio of 3∶1. Tree-based Pipeline Optimization Tool (TPOT) was applied on the training set to optimize model parameters and to select the most important radiomics features for modeling. Five independent T stage models were developed accordingly. Accuracy and the area under the curve ( AUC) of receiver operating characteristic (ROC) were used to pick out the optimal model, which was then applied on the training set and the original dataset to predict the T stage of rectal cancer. RESULTS: The performance of the the five T staging models recommended by automated machine learning were as follows: The accuracy for the training set ranged from 0.802 to 0.838, sensitivity, from 0.762 to 0.825, specificity, from 0.833 to 0.896, AUC, from 0.841 to 0.893, and average precision (AP) from 0.870 to 0.901. After comparison, an optimal model was picked out, with sensitivity, specificity and AUC for the training set reaching 0.810, 0.875, and 0.893, respectively. The sensitivity, specificity and AUC for the test set were 0.810, 0.813, and 0.810, respectively. The sensitivity, specificity and AUC for the original dataset were 0.810, 0.830, and 0.860, respectively. CONCLUSION: Based on the radiomics data of T2WI and RS-EPI DWI, the model established by automated machine learning showed a fairly high accuracy in predicting rectal cancer T stage.