Atrophy of the cholinergic regions advances from early to late mild cognitive impairment.

PURPOSE: We investigated the volumetric changes in the components of the cholinergic pathway for patients with early mild cognitive impairment (EMCI) and those with late mild cognitive impairment (LMCI). The effect of patients' apolipoprotein 4 (APOE-ε4) allele status on the structural changes were analyzed. METHODS: Structural magnetic resonance imaging data were collected. Patients' demographic information, plasma data, and validated global cognitive composite scores were included. Relevant features were extracted for constructing machine learning models to differentiate between EMCI (n = 312) and LMCI (n = 541) and predict patients' neurocognitive function. The data were analyzed primarily through one-way analysis of variance and two-way analysis of covariance. RESULTS: Considerable differences were observed in cholinergic structural changes between patients with EMCI and LMCI. Cholinergic atrophy was more prominent in the LMCI cohort than in the EMCI cohort (P < 0.05 family-wise error corrected). APOE-ε4 differentially affected cholinergic atrophy in the LMCI and EMCI cohorts. For LMCI cohort, APOE-ε4 carriers exhibited increased brain atrophy (left amygdala: P = 0.001; right amygdala: P = 0.006, and right Ch123, P = 0.032). EMCI and LCMI patients showed distinctive associations of gray matter volumes in cholinergic regions with executive (R2 = 0.063 and 0.030 for EMCI and LMCI, respectively) and language (R2 = 0.095 and 0.042 for EMCI and LMCI, respectively) function. CONCLUSIONS: Our data confirmed significant cholinergic atrophy differences between early and late stages of mild cognitive impairment. The impact of the APOE-ε4 allele on cholinergic atrophy varied between the LMCI and EMCI groups.

Sodium oligomannate activates the enteroendocrine-vagal afferent pathways in APP/PS1 mice.

Enteroendocrine cells (EECs) and vagal afferent neurons constitute functional sensory units of the gut, which have been implicated in bottom-up modulation of brain functions. Sodium oligomannate (GV-971) has been shown to improve cognitive functions in murine models of Alzheimer's disease (AD) and recently approved for the treatment of AD patients in China. In this study, we explored whether activation of the EECs-vagal afferent pathways was involved in the therapeutic effects of GV-971. We found that an enteroendocrine cell line RIN-14B displayed spontaneous calcium oscillations due to TRPA1-mediated calcium entry; perfusion of GV-971 (50, 100 mg/L) concentration-dependently enhanced the calcium oscillations in EECs. In ex vivo murine jejunum preparation, intraluminal infusion of GV-971 (500 mg/L) significantly increased the spontaneous and distension-induced discharge rate of the vagal afferent nerves. In wild-type mice, administration of GV-971 (100 mg· kg-1 ·d-1, i.g. for 7 days) significantly elevated serum serotonin and CCK levels and increased jejunal afferent nerve activity. In 7-month-old APP/PS1 mice, administration of GV-971 for 12 weeks significantly increased jejunal afferent nerve activity and improved the cognitive deficits in behavioral tests. Sweet taste receptor inhibitor Lactisole (0.5 mM) and the TRPA1 channel blocker HC-030031 (10 µM) negated the effects of GV-971 on calcium oscillations in RIN-14B cells as well as on jejunal afferent nerve activity. In APP/PS1 mice, co-administration of Lactisole (30 mg ·kg-1 ·d-1, i.g. for 12 weeks) attenuated the effects of GV-971 on serum serotonin and CCK levels, vagal afferent firing, and cognitive behaviors. We conclude that GV-971 activates sweet taste receptors and TRPA1, either directly or indirectly, to enhance calcium entry in enteroendocrine cells, resulting in increased CCK and 5-HT release and consequent increase of vagal afferent activity. GV-971 might activate the EECs-vagal afferent pathways to modulate cognitive functions.

Dibutyl phthalate (DBP) promotes Epithelial-Mesenchymal Transition (EMT) to aggravate liver fibrosis into cirrhosis and portal hypertension (PHT) via ROS/TGF-ß1/Snail-1 signalling pathway in adult rats.

OBJECTIVE: The primary objective of this study was to investigate the toxicological impact of Dibutyl phthalate (DBP) on the process of liver fibrosis transitioning into cirrhosis and the subsequent development of portal hypertension (PHT) through the mechanism of epithelial-mesenchymal transition (EMT) mediated by the ROS/TGF-ß/Snail-1 signaling pathway. METHOD: Carbon tetrachloride (CCl4) (1 mg/kg) was introduced in adult rats by oral feeding in CCl4 and CCl4+DBP groups twice a week for 8 weeks, and twice for another 8 week in CCl4 group. DBP was introduced by oral feeding in the CCl4+DBP group twice over the following 8 weeks. We subsequently analyzed hemodynamics measurements and liver cirrhosis degree, hepatic inflammation and liver function in the different groups. EMT related genes expression in rats in the groups of Control, DBP, CCl4 and CCl4+DBP were measured by immunohistochemistry (IHC). Enzyme-linked immunosorbent Assay (ELISA), qRT-PCR, western blot were used to detect the EMT related proteins and mRNA gene expression levels in rats and primary hepatocytes (PHCs). Reactive oxygen species (ROS) were examined with a ROS detection kit. RESULTS: The results showed that the CCl4+DBP group had higher portal pressure (PP) and lower mean arterial pressure (MAP) than the other groups. Elevated collagen deposition, profibrotic factor, inflammation, EMT levels were detected in DBP and CCl4+DBP groups. ROS, TGF-ß1 and Snail-1 were highly expressed after DBP exposure in vitro. TGF-ß1 had the potential to regulate Snail-1, and both of them were subject to regulation by ROS. CONCLUSION: DBP could influence the progression of EMT through its toxicological effect by ROS/TGF-ß1/Snail-1 signalling pathway, causing cirrhosis and PHT in final. The findings of this research might contribute to a novel comprehension of the underlying toxicological mechanisms and animal model involved in the progression of cirrhosis and PHT, and potentially offered a promising therapeutic target for the treatment of the disease.

Maternal exposure to dibutyl phthalate (DBP) impairs angiogenesis and AR signalling pathway through suppression of TGFB1I1 in hypospadias offspring.

Early exposure to dibutyl phthalate (DBP) can cause hypospadias in newborn foetuses. However, the underlying molecular mechanism is not well defined. Aberrant angiogenesis is associated with various dysplasias including urogenital deficits. In vivo and in vitro angiogenesis assays showed reduced angiogenesis in the hypospadias group and DBP exposed group. RNA-sequencing analysis of DBP-treated HUVECs revealed decreased expression of transforming growth factor beta 1-induced transcript 1 (TGFB1I1) and a significantly enriched angiogenesis-associated pathway. Further experiments revealed that decreased TGFB1I1 expression was associated with disrupted tube formation and migration, which resulted in decreased angiogenesis. Functional assays revealed that the overexpression of TGFB1I1 promoted tube formation and migration of HUVECs in the DBP-treated group. Moreover, we showed that the transcription factor AR was regulated by TGFB1I1 through inhibiting its translocation from the cytoplasm to the nucleus. Together, our results identified TGFB1I1 as a component of aberrant angiogenesis in hypospadias rats and its interaction with AR might be a potential target for hypospadias development.

Probing the Roles of Indium Oxides on Copper Catalysts for Enhanced Selectivity during CO2-to-CO Electrochemical Reduction.

The electrochemical CO2 reduction reaction (CO2RR) provides an alternative protocol to producing industrial chemicals with renewable electricity sources, and the highly selective, durable, and economic catalysts should expedite CO2RR applications. Here, we demonstrate a composite Cu-In2O3 catalyst in which a trace amount of In2O3 decorated on Cu surface greatly improves the selectivity and stability for CO2-to-CO reduction as compared to the counterparts (Cu or In2O3), realizing a CO faradaic efficiency (FECO) of 95% at -0.7 V (vs RHE) and no obvious degradation within 7 h. In situ X-ray absorption spectroscopy reveals that In2O3 undergoes the redox reaction and preserves the metallic state of Cu during the CO2RR process. Strong electronic interaction and coupling occur at the Cu/In2O3 interface which serves as the active site for selective CO2RR. Theoretical calculation confirms the roles of In2O3 in preventing oxidation and altering the electronic structure of Cu to assist COOH* formation and demote CO* adsorption at the Cu/In2O3 interface.

[Subverting the Future of Teaching: Artificial Intelligence Innovation in Nursing Education].

Artificial intelligence (AI) technologies, including machine learning, deep learning, natural language processing, generative AI, the metaverse and other iterations, are rapidly changing the landscape of education. Related technologies not only enhance the teaching and learning process but also improve the quality and availability of educational content. AI facilitates educational transformation, reshapes teaching models, and helps students achieve their personalized learning needs, thus improving learning outcomes, learning efficiencies, and teaching practices. Despite the many AI application cases in nursing management and clinical practice, the application of AI in nursing education remains in its infancy. Machine learning has been used to predict the academic performance and graduation results of nursing students, thereby facilitating the early identification of additional support needs. Natural language processing technology has been used to develop chatbots and virtual teachers to assist learning, providing personalized learning support to help students overcome learning obstacles. Also, generative AI technologies such as ChatGPT (chat generative pre-trained transformer) have been used to create simulated patient cases and as a tool for grading academic writing automatically. Moreover, the combination of generative AI technology and the metaverse has introduced new possibilities to nursing education, allowing students to learn in a more-immersive virtual environment. Despite the significant benefits brought by AI to nursing education, its implementation and integration still face multiple challenges, including high costs, the need to provide technical training to teachers, and the need to address issues such as academic integrity and data privacy. The authors hope this article will help promote interdisciplinary cooperation between nursing educators and information and communication experts and the development of AI-assisted teaching to open a new chapter in nursing education.

A novel protein encoded by circINSIG1 reprograms cholesterol metabolism by promoting the ubiquitin-dependent degradation of INSIG1 in colorectal cancer.

BACKGROUND: Hypoxia is a hallmark of solid tumors and leads to the metabolic reprogramming of cancer cells. The role of epigenetic regulation between hypoxia and aberrant cholesterol metabolism in colorectal cancer (CRC) remains elusive. METHODS: Hypoxia-responsive circular RNAs (circRNAs) were identified by high throughput RNA sequencing between CRC cells cultured under normoxia or hypoxia. The protein-coding potential of circINSIG1 was identified by polysome profiling and LC-MS. The function of circINSIG1 was validated in vitro and in vivo by gain or loss of function assays. Mechanistic results were concluded by immunoprecipitation analyses. RESULTS: A novel hypoxia-responsive circRNA named circINSIG1 was identified, which was upregulated in CRC tissues and correlated with advanced clinical stages and poor survival. Mechanistically, circINSIG1 encoded a 121 amino acid protein circINSIG1-121 to promote K48-linked ubiquitination of the critical cholesterol metabolism regulator INSIG1 at lysine 156 and 158 by recruiting CUL5-ASB6 complex, a ubiquitin E3 ligase complex, thereby inducing cholesterol biosynthesis to promote CRC proliferation and metastasis. The orthotopic xenograft tumor models and patient-derived xenograft models further identified the role of circINSIG1 in CRC progression and potential therapeutic target of CRC. CONCLUSIONS: circINSIG1 presents an epigenetic mechanism which provides insights into the crosstalk between hypoxia and cholesterol metabolism, and provides a promising therapeutic target for the treatment of CRC.

Diagnostic accuracy of ultrasound-based multimodal radiomics modeling for fibrosis detection in chronic kidney disease.

OBJECTIVES: To predict kidney fibrosis in patients with chronic kidney disease using radiomics of two-dimensional ultrasound (B-mode) and Sound Touch Elastography (STE) images in combination with clinical features. METHODS: The Mindray Resona 7 ultrasonic diagnostic apparatus with SC5-1U convex array probe (bandwidth frequency of 1-5 MHz) was used to perform two-dimensional ultrasound and STE software. The severity of cortical tubulointerstitial fibrosis was divided into three grades: mild interstitial fibrosis and tubular atrophy (IFTA), fibrotic area < 25%; moderate IFTA, fibrotic area 26-50%; and severe IFTA, fibrotic area > 50%. After extracting radiomics from B-mode and STE images in these patients, we analyzed two classification schemes: mild versus moderate-to-severe IFTA, and mild-to-moderate versus severe IFTA. A nomogram was constructed based on multiple logistic regression analyses, combining clinical and radiomics. The performance of the nomogram for differentiation was evaluated using receiver operating characteristic (ROC), calibration, and decision curves. RESULTS: A total of 150 patients undergoing kidney biopsy were enrolled (mild IFTA: n = 74; moderate IFTA: n = 33; severe IFTA: n = 43) and randomized into training (n = 105) and validation cohorts (n = 45). To differentiate between mild and moderate-to-severe IFTA, a nomogram incorporating STE radiomics, albumin, and estimated glomerular filtration (eGFR) rate achieved an area under the ROC curve (AUC) of 0.91 (95% confidence interval [CI]: 0.85-0.97) and 0.85 (95% CI: 0.77-0.98) in the training and validation cohorts, respectively. Between mild-to-moderate and severe IFTA, the nomogram incorporating B-mode and STE radiomics features, age, and eGFR achieved an AUC of 0.93 (95% CI: 0.89-0.98) and 0.83 (95% CI: 0.70-0.95) in the training and validation cohorts, respectively. Finally, we performed a decision curve analysis and found that the nomogram using both radiomics and clinical features exhibited better predictability than any other model (DeLong test, p < 0.05 for the training and validation cohorts). CONCLUSION: A nomogram based on two-dimensional ultrasound and STE radiomics and clinical features served as a non-invasive tool capable of differentiating kidney fibrosis of different severities. KEY POINTS: • Radiomics calculated based on the ultrasound imaging may be used to predict the severities of kidney fibrosis. • Radiomics may be used to identify clinical features associated with the progression of tubulointerstitial fibrosis in patients with CKD. • Non-invasive ultrasound imaging-based radiomics method with accuracy aids in detecting renal fibrosis with different IFTA severities.

Di-n-butyl phthalate induces oversecretion of vascular endothelium-derived NAP-2 and promotes epithelial-mesenchymal transition of urothelial cells in newborn hypospadias rats.

Di-n-butyl phthalate (DBP) is a plasticizer commonly used in industrial production and is present in our daily life. It has been confirmed that DBP causes genitourinary malformations, especially hypospadias. However, the research of hypospadias mainly focusses on the genital tubercle in previous studies. In this study, we found DBP could affect the exocrine function of the vascular endothelium which disturb the development of genital nodules and induced hypospadias. We used cytokine array to find that vascular endothelium-derived NAP-2 may be a major abnormal secreted cytokine with biological functions. The transcriptomic sequencing analysis showed that abnormal activation of the RhoA/ROCK signaling pathway was the main reason for increased NAP-2 secretion. The expression levels of epithelial-mesenchymal transition (EMT) biomarkers and NAP-2 in hypospadias animal models were detected with Immunohistochemistry, Western blot, Immunofluorescence, and ELISA methods. The expression levels of NAP-2, RhoA/ROCK signaling pathway related proteins, reactive oxygen species (ROS) levels in HUVEC cells, EMT biomarkers and migration capacity of urothelial cells cocultured with HUVEC were measured with ELISA, flow cytometry, Western blot or Transwell assay for further cell experiments. The results showed that DBP leaded to NAP-2 oversecretion from vascular endothelium mainly rely on the activation of RhoA/ROCK signaling pathway and ROS accumulation. The RhoA/ROCK inhibitor fasudil could partially decrease ROS production, and both fasudil and N-acetyl-L-cysteine (NAC) could decrease NAP-2 secretion. Meanwhile, the oversecretion of NAP-2 from HUVEC in coculture system promoted EMT and migration capacity of urothelial cells, and TGF-ß inhibitor LY219761 could block the aberrant activation of EMT process. Therefore, it could be concluded that DBP increase NAP-2 secretion from vascular endothelium by RhoA/ROCK/ROS pathway, and further promote EMT in urothelial cells through TGF-ß pathway. This study provided a novel direction for studying the occurrence of hypospadias and may provide a hypospadias predictive marker in the future.

Nomogram based on clinical and preoperative CT features for predicting the early recurrence of combined hepatocellular-cholangiocarcinoma: a multicenter study.

PURPOSE: To establish and validate a multiparameter prediction model for early recurrence after radical resection in patients diagnosed with combined hepatocellular-cholangiocarcinoma (cHCC-CC). MATERIALS AND METHODS: This study reviewed the clinical characteristics and preoperative CT images of 143 cHCC-CC patients who underwent radical resection from three institutions. A total of 110 patients from institution 1 were randomly divided into training set (n = 78) and testing set (n = 32) in the ratio of 7-3. Univariate and multivariate logistic regression analysis were used to construct a nomogram prediction model in the training set, which was internally and externally validated in the testing set and the validation set (n = 33) from institutions 2 and 3. The area under the curve (AUC) of receiver operating characteristics (ROC), decision curve analysis (DCA), and calibration analysis were used to evaluate the model's performance. RESULTS: The combined model demonstrated superior predictive performance compared to the clinical model, the CT model, the pathological model and the clinic-CT model in predicting the early postoperative recurrence. The nomogram based on the combined model included AST, ALP, tumor size, tumor margin, arterial phase peritumoral enhancement, and MVI (Microvascular invasion). The model had AUCs of 0.89 (95% CI 0.81-0.96), 0.85 (95% CI 0.70-0.99), and 0.86 (95% CI 0.72-1.00) in the training, testing, and validation sets, respectively, indicating high predictive power. DCA showed that the combined model had good clinical value and correction effect. CONCLUSION: A nomogram incorporating clinical characteristics and preoperative CT features can be utilized to effectively predict the early postoperative recurrence in patients with cHCC-CC.

Numerical simulation analysis of heat and mass transfer of saline wastewater in a falling film evaporation tube based on different inlet modes.

Falling film evaporation technology is widely used in the treatment of salt-containing wastewater in coal chemical industry. However, there is still a lack of research on the inlet method of vertical falling film evaporation tubes. In this paper, the heat and mass transfer processes of saline wastewater under vertical and tangential inlets were investigated using numerical simulations. On this basis, the differences in flow and heat transfer processes between saline wastewater and pure water under tangential inlet were investigated. The results showed that the flow velocity of saline wastewater with a falling film evaporation tube in a tangential inlet mode was larger. Meanwhile, the turbulence in this way was more intense and the fluid temperature in the vertical tube was higher. Saline wastewater has higher temperature and smaller liquid volume fraction than pure water liquid membrane in the range of 193-1,000 mm from the inlet. The use of tangential inlet method to treat salt-containing wastewater has higher evaporation efficiency and is a very effective way to guide the improvement of heat transfer efficiency.

[Clinical efficacy of omalizumab for treatment of moderate or severe allergic asthma in children with serum immunoglobulin E levels >1 500 IU/mL: a prospective study]. / å¥¥é©¬ç å•æŠ—æ²»ç–—è¡€æ¸ æ€»IgE>1 500 IU/mLçš„ä¸­é‡åº¦è¿‡æ•æ€§å“®å–˜å„¿ç«¥çš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To evaluate the clinical efficacy of omalizumab in the treatment of moderate or severe allergic asthma in children with serum total immunoglobulin E (IgE) levels >1 500 IU/mL. METHODS: A total of 95 children with moderate or severe allergic asthma, who were treated at the Department of Respiratory Medicine in Anhui Provincial Children's Hospital from December 2020 to May 2022, were enrolled. Based on their serum total IgE levels and whether they received omalizumab treatment, they were divided into a control group (IgE >1 500 IU/mL, no omalizumab treatment), a normal treatment group (IgE levels between 30 and 1 500 IU/mL, omalizumab treatment), and an ultra-high IgE treatment group (IgE >1 500 IU/mL, omalizumab treatment). The differences in clinical characteristics, Childhood Asthma Control Test (C-ACT) scores before and after treatment, the proportion of acute attacks, IgE levels, pulmonary function indicators, and fractional exhaled nitric oxide (FeNO) concentrations were analyzed among the three groups. RESULTS: At the 8th week of treatment, the normal treatment group and the ultra-high IgE treatment group had higher C-ACT scores, forced expiratory volume in first second (FEV1) as a percentage of predicted value (FEV1%pred), FEV1/forced vital capacity (FVC) ratio (FEV1/FVC), and peak expiratory flow (PEF) as a percentage of predicted value (PEF%pred), as well as a lower proportion of acute attacks and FeNO concentration compared to the control group (P<0.05). There were no statistically significant differences in the comparison of various indicators between the ultra-high IgE treatment group and the normal treatment group (P>0.05). At the 16th week of treatment, the normal treatment group and the ultra-high IgE treatment group had higher C-ACT scores and pulmonary function indicators including FEV1%pred, FEV1/FVC, PEF%pred, and forced expiratory flow at 25% vital capacity (FEF25) as a percentage of predicted value (FEF25%pred) compared to the control group (P<0.05). The proportion of acute attacks and FeNO concentration in the ultra-high IgE treatment group were lower than those in the control group (P<0.05). There were no statistically significant differences in the comparison of various indicators between the ultra-high IgE treatment group and the normal treatment group (P>0.05). CONCLUSIONS: Omalizumab therapy has a certain clinical efficacy in children with moderate or severe allergic asthma and serum total IgE levels >1 500 IU/mL, with no significant difference in efficacy compared to children with serum total IgE levels between 30 and 1 500 IU/mL.

Experimental Demonstration of Bulk-Hinge Correspondence in a Three-Dimensional Topological Dirac Acoustic Crystal.

Three-dimensional topological Dirac semimetal (DSM) is a vital state to explore topological phases and phase transitions. However, its bulk-boundary correspondence is elusive. Here, we experimentally investigate the higher-order hinge states in an acoustic DSM. Not only removable trivial surface states but also robust nontrivial hinge arcs are observed, attributed to the direct correspondence between bulk polarization and hinge charge. We further reveal that a pair of zigzag and bearded hinges possess arcs located in complementary momentum regions. Our work provides solid proof of the bulk-hinge correspondence in DSM and sheds light on the study of topological hierarchy across dimensions.

A novel NF-κB regulator encoded by circPLCE1 inhibits colorectal carcinoma progression by promoting RPS3 ubiquitin-dependent degradation.

BACKGROUND: Constitutive activation of nuclear factor-κB (NF-κB) signaling plays a key role in the development and progression of colorectal carcinoma (CRC). However, the underlying mechanisms of excessive activation of NF-κB signaling remain largely unknown. METHODS: We used high throughput RNA sequencing to identify differentially expressed circular RNAs (circRNAs) between normal human intestinal epithelial cell lines and CRC cell lines. The identification of protein encoded by circPLCE1 was performed using LC-MS. The function of novel protein was validated in vitro and in vivo by gain or loss of function assays. Mechanistic results were concluded by immunoprecipitation analyses. RESULTS: A novel protein circPLCE1-411 encoded by circular RNA circPLCE1 was identified as a crucial player in the NF-κB activation of CRC. Mechanistically, circPLCE1-411 promoted the ubiquitin-dependent degradation of the critical NF-κB regulator RPS3 via directly binding the HSP90α/RPS3 complex to facilitate the dissociation of RPS3 from the complex, thereby reducing NF-κB nuclear translocation in CRC cells. Functionally, circPLCE1 inhibited tumor proliferation and metastasis in CRC cells, as well as patient-derived xenograft and orthotopic xenograft tumor models. Clinically, circPLCE1 was downregulated in CRC tissues and correlated with advanced clinical stages and poor survival. CONCLUSIONS: circPLCE1 presents an epigenetic mechanism which disrupts NF-κB nuclear translocation and serves as a novel and promising therapeutic target and prognostic marker.

Impact of pelvic dimensions on anastomotic leak after anterior resection for patients with rectal cancer.

AIM: The impact of pelvis on the development of anastomotic leak (AL) in rectal cancer (RC) patients who underwent anterior resection (AR) remains unclear. The aim of this study was to evaluate the impact of pelvic dimensions on the risk of AL. METHODS: A total of 1058 RC patients undergoing AR from January 2013 to January 2016 were enrolled. Pelvimetric parameters were obtained using abdominopelvic computed tomography scans. RESULTS: Univariate analyses showed that pelvic inlet, pelvic outlet, interspinous distance, and intertuberous distance were significantly associated with the risk for AL (P < 0.05). Multivariate analysis confirmed that pelvic inlet and intertuberous distance were independent risk factors for AL (P < 0.05). Significant factors from multivariate analysis were assembled into the nomogram A (without pelvic dimensions) and nomogram B (with pelvic dimensions). The area under curve (AUC) of nomogram B was 0.72 (95% CI 0.67-0.77), which was better than the AUC of nomogram A (0.69, [95% CI 0.65-0.74]), but didn't reach a statistical significance (P = 0.199). Decision curve supported that nomogram B was better than nomogram A. CONCLUSION: Pelvic dimensions, specifically pelvic inlet and intertuberous distance, seemed to be independent predictors for postoperative AL in RC patients. Pelvic inlet and intertuberous distance incorporated with preoperative radiotherapy, preoperative albumin, conversion, and tumor diameter in the nomogram might provide a clinical tool for predicting AL.

circCAMSAP1 Promotes Tumor Growth in Colorectal Cancer via the miR-328-5p/E2F1 Axis.

Increasing studies indicated that circular RNAs (circRNAs) play important roles in cancer progression. However, the roles of circRNAs in colorectal cancer (CRC) remain largely unknown. In this study, we determined the circRNA expression profile by next-generation RNA sequencing from eight CRC and paired non-cancerous matched tissues. circCAMSAP1 (originating from exon 2 to exon 3 of the CAMSAP1 gene, hsa_circ_0001900) was significantly upregulated in CRC tissues. Increased circCAMSAP1 expression was significantly correlated with advanced tumor/node/metastasis (TNM) stage and shortened overall survival. An elevation of circCAMSAP1 expression was detected via droplet digital PCR in the serum of CRC patients prior to surgery. Functionally, circCAMSAP1 promoted the malignant behavior of CRC. Mechanism study of upstream biogenesis of circCAMSAP1 indicated that circCAMSAP1 cyclization in CRC was mediated by splicing factor epithelial-splicing regulatory protein 1. Moreover, circCAMSAP1 acted as a sponge for miR-328-5p and abrogated its suppression on transcription factor E2F1. Taken together, our data indicated an essential role of the circCAMSAP1/miR-328-5p/E2F1 axis in the progression of CRC, which implied that circCAMSAP1 could serve as a diagnostic and prognostic biomarker as well as a potential therapeutic target for CRC.

Career choice and influential factors among medical students majoring in psychiatry in China.

BACKGROUND: The undergraduate program of psychiatry has been widely established in recent years to improve the education and recruitment of psychiatrists in China. We aim to investigate the career choice of medical students majoring in psychiatry in China and the influential factors. METHOD: This multicenter study was conducted in 26 medical schools in China from May to October of 2019. Participants included 4610 medical students majoring in psychiatry and 3857 medical students majoring in clinical medicine. Multivariable logistic regression was used to investigate the influential factors of students' choices of psychiatry at matriculation and as a career. RESULTS: 44.08% of psychiatry majored students gave psychiatry as a first choice at matriculation, and 56.67% of them would choose psychiatry as a career, which was in sharp contrast to the proportion of clinical medicine majored students who would choose psychiatry as a career (0.69%). Personal interest (59.61%), suggestions from family members (27.96%), and experiencing mental problems (23.19%) were main reasons for choosing psychiatry major at matriculation. Personal interest (odds ratio [OR] = 2.12, 95% confidence interval [CI] = 1.87-2.40), experiencing a psychiatry clerkship (OR = 1.99, 95% CI = 1.28-3.08), being female (OR = 1.50, 95% CI = 1.30-1.68), experiencing mental problems (OR = 1.33, 95% CI = 1.28-1.56), and suggestions from family members (OR = 1.25, 95% CI = 1.08-1.46) correlated positively with students' choice of psychiatry as career. Students who lacked psychiatry knowledge (OR = 0.49, 95% CI = 0.29-0.85) or chose psychiatry because of lower admission scores (OR = 0.80, 95% CI = 0.63-0.97) were less likely to choose psychiatry as a career. CONCLUSION: More than half of psychiatry majored medical school students planned to choose psychiatry as their career, whereas very few students in the clinic medicine major would make this choice. Increasing students' interest in psychiatry, strengthening psychiatry clerkships, and popularizing psychiatric knowledge are modifiable factors to increase the psychiatry career intention. The extent to which medical students' attitudes toward psychiatry can be changed through medical school education and greater exposure to psychiatry will need further investigation.

[Effect of Huangqin Decoction on pyroptosis pathway of NLRP3/caspase-1 in mice with ulcerative colitis].

To explore the effect of Huangqin Decoction on ulcerative colitis(UC) pyroptosis, and to explain the mechanism of pyroptosis based on NOD-like receptor thermoprotein domain 3(NLRP3)/cysteine proteinase 1(caspase-1) pathway. The animal model of UC induced with 3% dextran sodium sulfate(DSS) was established. The experimental animals were divided into control group, model group, low-dose(4.55 g·kg~(-1)), medium-dose(9.1 g·kg~(-1)) and high-dose(18.2 g·kg~(-1)) Huangqin Decoction groups and salazosulfapyridine group(0.45 g·kg~(-1)). While modeling, intragastric administration was given for 7 consecutive days. On the 8 th day, the mice were euthanized, the colon length was collected, and the histopathological changes were observed by HE staining. The content of interleukin-18(IL-18) was observed by ELISA. The content of lactatedehydrogenase(LDH)was determined by microplate method. TUNEL assay kit was used to detect the cell death. The immunohistochemical staining was used to detect the expressions of NLRP3 and apoptosis-associated speck-like protein containing a CARD(ASC). Western blot was used to detect the expressions of interleukin-1ß(IL-1ß), caspase-1 and gasdermin D(GSDMD).The experimental study showed that compared with normal group, the LDH content, TUNEL positive staining, inflammatory factors(IL-18, IL-1ß), and proteins associated with pyroptosis were significantly increased(P<0.05). Compared with model control group, the LDH content, TUNEL positive staining, inflammatory factors(IL-18, IL-1ß), and proteins associated with pyroptosis were decreased, and these results were more significant in high-dose groups(P<0.05). The results of HE staining showed that Huangqin Decoction could improve the pathological changes of colon. Huangqin Decoction could inhibit UC cell pyroptosis, and the mechanism may be closely related to NLRP3/caspase-1 signaling pathway.

Efficacy of Huaiqihuang granules as adjuvant therapy for bronchial asthma in children: a real-world study. / æ§æžé»„é¢—ç²’è¾ åŠ©æ²»ç–—å„¿ç«¥æ”¯æ°”ç®¡å“®å–˜ç–—æ•ˆçš„çœŸå®žä¸–ç•Œç ”ç©¶.

OBJECTIVES: To study the efficacy of Huaiqihuang granules as adjuvant therapy for bronchial asthma in children. METHODS: A multicenter, prospective, and registered real-world study was performed for the children, aged 2-5 years, who had a confirmed diagnosis of bronchial asthma in the outpatient service of 21 hospitals in China. Among these children, the children treated with medications for long-term asthma control (inhaled corticosteroid and/or leukotriene receptor antagonist) without Huaiqihuang granules were enrolled as the control treatment group, and those treated with medications for long-term asthma control combined with Huaiqihuang granules were enrolled as the combined treatment group. The medical data of all children were collected. Outpatient or telephone follow-up was performed at weeks 4, 8, 12, 20, 28, and 36 after treatment, including asthma attacks and rhinitis symptoms. A statistical analysis was performed for the changes in these indices. RESULTS: There was no significant difference in the frequency of asthma attacks or rhinitis attacks between the two groups before treatment (P>0.05). After treatment, the combined treatment group had significantly lower frequencies of asthma attacks, severe asthma attacks, and rhinitis attacks compared with the control treatment group (P<0.05). There was no signification difference in the incidence rate of adverse reactions between the two groups (P=0.667). CONCLUSIONS: Huaiqihuang granules in addition to medications for long-term asthma control can alleviate the symptoms of bronchial asthma and rhinitis and improve the level of asthma control in children with bronchial asthma, with good safety and little adverse effect. Citation.

Circular RNA circ-RELL1 regulates inflammatory response by miR-6873-3p/MyD88/NF-κB axis in endothelial cells.

Endothelial inflammation is an important contributor to the pathology of atherosclerotic cardiovascular disease (ASCVD). Circular RNAs (circRNAs) function and role in endothelium inflammation still unknown. In our present study, we firstly identified that circ-RELL1 plays a proinflammatory role in ox-LDL-induced HUVECs through high-throughput circRNA microarray assays. Knockdown circ-RELL1 can reduce the expression of ICAM1 and VCAM1 in ox-LDL induced endothelium inflammation. Mechanistically, circ-RELL1 directly bound to miR-6873-3p in cytoplasm. Subsequently miR-6873-3p reduced MyD88 (myeloid differentiation primary response 88) protein expression and alleviated MyD88 medicated NF-κB activation. Furthermore, circ-RELL1 can abolish the inhibition of inflammation response by miR-6873-3p. Our findings illustrate a novel regulatory pathway that circ-RELL1 modulate inflammatory response by miR-6873-3p/MyD88/NF-κB axis in ox-LDL induced endothelial cells, which provides a potential therapeutic candidate for endothelium inflammation in atherosclerotic cardiovascular disease.