Clinical prediction models for cervical lymph node metastasis of papillary thyroid carcinoma.

PURPOSE: Accurate preoperative diagnosis of lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) remains an unsolved problem. This study aimed to construct a nomogram and scoring system for predicting LNM based on the clinical characteristics of patients with PTC. METHODS: 1400 patients with PTC who underwent thyroidectomy and lymph node dissection at the First Affiliated Hospital of Sun Yat-sen University were retrospectively enrolled and randomly divided into training and internal testing sets. Furthermore, 692 patients with PTC from three other medical centers were collected as external testing sets. Least absolute shrinkage and selection operator (LASSO) was used to screen the predictors, and a nomogram was constructed. In addition, a scoring system was constructed using 10-fold cross-validation. The performances of the two models were verified among datasets and compared with preoperative ultrasound (US). RESULTS: Six independent predictors were included in the multivariate logistic model: age, sex, US diagnosis of LNM, tumor diameter, location, and thyroid peroxidase antibody level. The areas under the receiver operating characteristic curve (AUROC) (95% confidence interval) of this nomogram in the training, internal testing, and three external testing sets were 0.816 (0.791-0.840), 0.782 (0.727-0.837), 0.759 (0.699-0.819), 0.749 (0.667-0.831), and 0.777 (0.726-0.828), respectively. The AUROC of the scoring system were 0.810 (0.785-0.835), 0.772 (0.718-0.826), 0.736 (0.675-0.798), 0.717 (0.635-0.799) and 0.756 (0.704-0.808), respectively. The prediction performances were both significantly superior to those of preoperative US (P < 0.001). CONCLUSION: The nomogram and scoring system performed well in different datasets and significantly improved the preoperative prediction of LNM than US alone.

Efficacy and acceptability of mobile application-delivered acceptance and commitment therapy for posttraumatic stress disorder in China: A randomized controlled trial.

Due to the COVID-19 pandemic and its extensive effects, the incidence of posttraumatic stress disorder (PTSD) symptoms is rapidly increasing in China. This research aimed to assess the efficacy and acceptability of a mobile application delivering Acceptance and Commitment Therapy (ACT) in reducing PTSD symptoms. 221 Chinese individuals with elevated PTSD symptoms were randomly assigned to app-delivered ACT (ACT condition), app-delivered mindfulness (MI condition), or a waitlist (WL condition). Assessments were performed pre- and post-intervention. The results showed that participants in both the ACT and MI groups had significantly greater improvements across mental health outcomes compared to the WL group. No significant differences were observed between the ACT and MI groups except for psychological flexibility, which improved more in ACT than MI (d = -0.37). Compared to WL, the ACT group showed a greater improvement in PTSD symptoms (d = -0.79), anxiety (d = -0.62), depression (d = -0.51), posttraumatic growth (d = 0.46), and psychological flexibility (d = 0.76). The drop-out rates in the ACT and MI were 25.76% and 39.71%, respectively. Participants in the ACT condition reported medium program satisfaction. The study suggests app-delivered ACT is efficacious in reducing PTSD symptoms and improving overall mental health among Chinese adults.

Activation of P2Y1R impedes intestinal mucosa repair during colitis.

Delayed intestinal mucosal healing is one of the pathogenic bases for the recurrence of inflammatory bowel disease (IBD), but how the IBD inflammatory environment impedes intestinal mucosa repair remains unclear. Adenosine diphosphate (ADP) is an endogenous ligand of P2Y1R that is highly produced at sites of inflammation. We herein identify a novel role of ADP to directly facilitate inflammation-induced epithelial permeability, delay wound healing, and disrupt tight junction integrity, and we found that P2Y1R, a receptor preferentially activated by ADP, was significantly upregulated in the colonic mucosa of ulcerative colitis (UC) patients and in colonic epithelial cells of colitis mice. Inhibition of P2Y1R significantly increased the epithelial permeability, decreased the wound healing capacity, and impaired the tight junction integrity in TNF-α-challenged Caco-2 cells. In parallel, the same effects in promoting intestinal mucosa repair were observed in DSS-induced colitis in P2Y1R-/- mice. Mechanistic investigation revealed that P2Y1R inhibition facilitated epithelial AMP-activated protein kinase (AMPK) phosphorylation and gut microbiota homeostasis reconstruction. Taken together, these findings highlight that P2Y1R activation plays an important role in impeding intestinal mucosa repair during colitis, and that P2Y1R is an attractive target for the therapy of IBD.

[Spatial-temporal Variations and Pollution Assessment of Heavy Metals in Sediments of Qionghai Lake in Xichang City].

Based on the analysis of the total concentrations of 10 metals in the sediment core and total concentrations and chemical fractions of seven metals in the surface sediments of Qionghai Lake in Xichang City, Sichuan Province, the spatial-temporal characteristics of metal accumulation and pollution over the past century and the potential ecological risk of metals in surface sediments were studied. Before the 1970s, metal concentrations in the sediment core were stable. The total concentrations of Al, Fe, K, and Cr in the sediment core exhibited visible peaks in the 1970s, which were related to the enhanced input of fine-grained topsoil caused by increasing precipitation, lake reclamation, and deforestation. Since the 1990s, the total concentrations of Al, Fe, K, and Cr decreased with the reduced topsoil erosion, whereas the total concentrations of As, Cd, Cu, Pb, and Zn gradually increased or remained stable. The enrichment factor results showed that Cd, Pb, and Zn were the main contaminants, with Cd as the typical contaminant in the sediment core. The Cd contamination started in the 1960s and has remained at a moderate level since the 1990s. In the surface sediments, the total concentrations of Cd were higher in the northwest lake area, and no visible spatial concentration trends of the other metals were displayed. The bioavailable fractions of Cd, Pb, and Zn accounted for 95%, 63%, and 48% of the total metal concentrations on average. Among the bioavailable fractions, Cd was mainly in the acid-soluble fraction, and Pb and Zn were mainly in the reducible and oxidized fractions. The bioavailable fractions of the other metals were less than 27%. The results of total concentrations and bioavailable fractions of metals revealed that Pb and Zn in the surface sediments were slightly or moderately contaminated, and Cd was moderately contaminated on average. Cd contamination was at a severe level in the northwest lake area. The concentrations of anthropogenic Cd, Pb, and Zn in the surface sediments estimated from the total and bioavailable concentrations were comparable (P>0.05), indicating that anthropogenic metals primarily existed in bioavailable fractions in the sediment. Integrating the assessment results from sediment quality guidelines, potential ecological risk index, and chemical forms of metals, Cd in surface sediments may pose a high ecological risk, whereas the other metals has a low ecological risk.

Effects of digital psychological interventions on physical symptoms in cancer patients: A systematic review and meta-analysis.

PURPOSE: This meta-analysis was to assess the efficacy of digital psychological interventions to improve physical symptoms (i.e., fatigue, pain, disturbed sleep, and physical well-being) among cancer patients, as well as to evaluate the variables that possibly moderate intervention effects. METHODS: Nine databases were searched for the literature up to February 2023. Two reviewers independently conducted a quality assessment. Effect sizes were reported as the standardized mean difference (Hedge's g) and estimated using a random-effects model. RESULTS: The meta-analysis included 44 randomized clinical trials comprising 7200 adults with cancer. Digital psychological interventions were associated with significant improvements in short-term fatigue (g = -0.33; 95% CI, -0.58 to -0.07) and disturbed sleep (g = -0.36; 95% CI, -0.57 to -0.15), but with non-significant changes in pain (g = -0.23; 95% CI, -0.68 to 0.21) and physical well-being (g = 0.31; 95% CI, -0.18 to 0.80). Additionally, no alleviation in long-term physical symptoms was observed. In subgroup analysis, results suggest that the country significantly moderated the effectiveness of digital psychological interventions in alleviating fatigue. CONCLUSIONS: Digital psychological interventions can be effective for improving short-term fatigue and disturbed sleep in patients with cancer. Clinicians could consider digital psychological interventions as a possible and efficient addition to better manage some of the physical symptoms during and after cancer treatment.

A Novel Fibromodulin Antagonist Peptide RP4 Exerts Antitumor Effects on Colorectal Cancer.

Colorectal cancer (CRC) is the leading cause of cancer-related deaths worldwide. Fibromodulin (FMOD) is the main proteoglycan that contributes to extracellular matrix (ECM) remodeling by binding to matrix molecules, thereby playing an essential role in tumor growth and metastasis. There are still no useful drugs that target FMOD for CRC treatment in clinics. Here, we first used public whole-genome expression datasets to analyze the expression level of FMOD in CRC and found that FMOD was upregulated in CRC and associated with poor patient prognosis. We then used the Ph.D.-12 phage display peptide library to obtain a novel FMOD antagonist peptide, named RP4, and tested its anti-cancer effects of RP4 in vitro and in vivo. These results showed that RP4 inhibited CRC cell growth and metastasis, and promoted apoptosis both in vitro and in vivo by binding to FMOD. In addition, RP4 treatment affected the CRC-associated immune microenvironment in a tumor model by promoting cytotoxic CD8+ T and NKT (natural killer T) cells and inhibiting CD25+ Foxp3+ Treg cells. Mechanistically, RP4 exerted anti-tumor effects by blocking the Akt and Wnt/ß-catenin signaling pathways. This study implies that FMOD is a potential target for CRC treatment, and the novel FMOD antagonist peptide RP4 can be developed as a clinical drug for CRC treatment.

Effects of cross-sectional area and aspect ratio coupled with orientation on mechanical properties and deformation behavior of Cu nanowires.

Metal nanomaterials exhibit excellent mechanical properties compared with corresponding bulk materials and have potential applications in various areas. Despite a number of studies of the size effect on Cu nanowires mechanical properties with square cross-sectional, investigations of them in rectangular cross-sectional with various sizes at constant volume are rare, and lack of multifactor coupling effect on mechanical properties and quantitative investigation. In this work, the dependence of mechanical properties and deformation mechanisms of Cu nanowires/nanoplates under tension on cross-sessional area, aspect ratio of cross-sectional coupled with orientation were investigated using molecular dynamics simulations and the semi-empirical expressions related to mechanical properties were proposed. The simulation results show that the Young's modulus and the yield stress sharply increase with the aspect ratio except for the 〈110〉{110}{001} Cu nanowires/nanoplates at the same cross-sectional area. And the Young's modulus increases while the yield stress decreases with the cross-sectional area of Cu nanowires. However, both of them increase with the cross-sectional area of Cu nanoplates. Besides, the Young's modulus increases with the cross-sectional area at all the orientations. The yield stress shows a mildly downward trend except for the 〈111〉 Cu nanowires with increased cross-sectional area. For the Cu nanowires with a small cross-sectional area, the surface force increases with the aspect ratio. In contrast, it decreases with the aspect ratio increase at a large cross-sectional area. At the cross-sectional area of 13.068 nm2, the surface force decreases with the aspect ratio of the 〈110〉 Cu nanowires while it increases at other orientations. The surface force is a linearly decreasing function of the cross-sectional area at different orientations. Quantitative studies show that Young's modulus and yield stress to the aspect ratio of the Cu nanowires satisfy exponent relationship. In addition, the main deformation mechanism of Cu nanowires is the nucleation and propagation of partial dislocations while it is the twinning-dominated reorientation for Cu nanoplates.

A Ship Trajectory Prediction Framework Based on a Recurrent Neural Network.

Ship trajectory prediction is a key requisite for maritime navigation early warning and safety, but accuracy and computation efficiency are major issues still to be resolved. The research presented in this paper introduces a deep learning framework and a Gate Recurrent Unit (GRU) model to predict vessel trajectories. First, series of trajectories are extracted from Automatic Identification System (AIS) ship data (i.e., longitude, latitude, speed, and course). Secondly, main trajectories are derived by applying the Density-Based Spatial Clustering of Applications with Noise (DBSCAN) algorithm. Next, a trajectory information correction algorithm is applied based on a symmetric segmented-path distance to eliminate the influence of a large number of redundant data and to optimize incoming trajectories. A recurrent neural network is applied to predict real-time ship trajectories and is successively trained. Ground truth data from AIS raw data in the port of Zhangzhou, China were used to train and verify the validity of the proposed model. Further comparison was made with the Long Short-Term Memory (LSTM) network. The experiments showed that the ship's trajectory prediction method can improve computational time efficiency even though the prediction accuracy is similar to that of LSTM.

New serum biomarker identification and analysis by mass spectrometry in cervical precancerous lesion and acute cervicitis in South China.

Background: According to the statistics of WHO/IARC, cervical cancer (CC) has become the fourth malignant cancer of female worldwide and it is one of the main causes of death of women in developing countries. Purpose: Potential plasma and metabolic biomarkers for CC precancerous lesions and cervicitis were indicated by LC-MS techniques, and their underlying mechanisms and functions were analyzed. Methods: Plasma samples were selected from healthy people (control), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), CC, and post-treatment patients. All polypeptide types and sequences were detected by LC-MS/MS and the results were normalized by using Pareto-scaling. Potential metabolic biomarkers were screened by applying MetaboAnalyst 4.0 software and XCMS software, and analysis of variance and enrichment analysis were performed. Metabolic pathway analysis and functional enrichment analysis were used to further investigate the significance and pathological mechanisms of potential biomarkers. Results: Compared with healthy people, 9 differentially expressed metabolites were screened, 4 of which were up-regulated and 5 were down-regulated. LSIL group screened 7 differentially expressed metabolites, 5 of which were up-regulated and 2 were down-regulated; CC group screened 12 differentially expressed metabolites were screened, of which 9 were up-regulated and 3 were down-regulated. Eight differentially expressed metabolites were screened in the IF group, of which 5 showed up-regulation and 3 showed down-regulation. In functional enrichment analysis, differential metabolism was found to be associated with addition and coagulation cascades. Among all potential biomarkers, 2-amino-3-methyl-1-butanol, L-carnitine, Asn Asn Gln Arg, Ala Cys Ser Trp, Soladulcidine, Ala Ile Gln Arg, 2-amino-3 -Methyl-1-butanol, L-carnitine, Asn Asn Gln Arg, Ala Cys Ser Trp, Soladulcidine, Ala Ile Gln Arg can be used as predictors of precancerous lesions at different stages of CC. Among all biomarkers, 6α-fluoro-11ß1,17-dihydroxypren-4-ene-3,20-dione has higher expression in the CC and HSIL groups and lower expression in the treatment group. Conclusion: By applying molecular markers to assess the progression of the disease, the accuracy and specificity of the diagnosis can be improved, which has certain prospects in clinical applications.

[Therapeutic effects of insulin-sensitizing drugs on nonalcoholic fatty liver disease: experiment with rats].

OBJECTIVE: To investigate the therapeutic effects of insulin-sensitizing drugs, rosiglitazone and metformin, on nonalcoholic fatty liver disease (NAFLD). METHODS: Forty-four male SD rats were randomized into 4 groups: normal control group (n = 8, fed with normal food) and NAFLD rats (n = 36, fed with high-fat food). Eight weeks later 4 rats were randomly selected from the NAFLD group and were killed to undergo pathological examination of the liver. When the establishment of experimental model of NAFLD rats was confirmed the remaining 32 NAFLD rats were subdivided into 4 equal subgroups: NAFLD control group (to be fed continuously with high-fat food), rosiglitazone treatment group (fed with normal food and rosiglitazone 1.5 mg x kg(-1) x d(-1) by gastric perfusion), metformin treatment group (fed with normal food and metformin 150 mg x kg(-1) x d(-1) by gastric perfusion), and dietary treatment group (fed with normal food and normal saline by gastric perfusion). By the end of the 12th week, all rats were killed to isolate the samples of serum to test the levels of total cholesterol (TC), triglyceride (TG), alanine transaminase (ALT), aspartate transaminase (AST), and tumor necrosis factor-alpha (TNF-alpha). Samples of liver tissue were taken to undergo pathology to examine fatty degeneration and inflammatory cell infiltration and detection of the levels of TC and TG. In the liver the weights of body and liver were measured so as to calculate the liver index. RESULTS: (1) The levels of serum TC, TG, ALT, and AST, liver TC and TG, and liver index of the NAFLD control group increased significantly, and the liver histology of the NAFLD control group expressed moderate to severe fatty degeneration. (2) The serum TC levels of the rosiglitazone and metformin groups were 2.49 mmol/L +/- 0.68 mmol/L and 2.49 mmol/L +/- 0.58 mmol/L, both significantly lower than that of the NAFLD control group (4.55 mmol/L +/- 1.58 mmol/L, both P < 0.001). The serum TG levels of the rosiglitazone and metformin groups were 0.61 mmol/L +/- 0.17 mmol/L and 0.63 mmol/L +/- 0.16 mmol/L respectively, both significantly lower than that of the NAFLD control group (0.85 mmol/L +/- 0.15 mmol/L, both P < 0.001). The serum level of ALT of the rosiglitazone and metformin groups were 38.3 U/L +/- 10.6 U/L and 43.3 U/L +/- 27.5 U/L respectively, both significantly lower than that of the NAFLD control group (110.6 U/L +/- 44.2 U/L, P < 0.001 and P < 0.05). The serum levels of AST of the rosiglitazone and metformin groups were 141.7 U/L +/- 14.3 U/L and 174.5 U/L +/- 57.9 U/L, both significantly lower than that of the NAFLD control group (251.8 U/L +/- 91.0 U/L, both P < 0.05). The liver TG levels of the rosiglitazone and metformin groups were 18.9 mg/g +/- 2.7 mg/g and 20.4 mg/g +/- 3.6 mg/g respectively, both significantly lower than that of the NAFLD control group (54.8 mg/g +/- 7.6 mg/g, both P < 0.05). The fatty degeneration grades of liver tissues of the rosiglitazone and metformin groups were grade: 0.8 +/- 0.3 and 1.0 +/- 0.2, both significantly lower than that of the NAFLD control group (grade 2.8 +/- 0.5, both P < 0.05). The hepatic inflammation scores of: the rosiglitazone and metformin groups were 0.8 +/- 0.2 and 1.0 +/- 0.3 respectively, both significantly lower than that of the NAFLD control group (1.8 +/- 0.4, both P < 0.05). The levels of abnormality in serum TC and TG, liver TG, and liver histology of the dietary treatment group were all alleviated in comparison with the NAFLD control group, but were somewhat severer than those of the rosiglitazone and metformin treatment groups. (3) The serum TNF-alpha levels of the rosiglitazone and metformin treatment groups were 124.6 pg/mL +/- 21.0 pg/mL, 154.9 pg/mL +/- 32.5 pg/mL respectively, both significantly lower than that of the NAFLD group (324.2 pg/mL +/- 34.2 pg/mL, P < 0.001 and P < 0.05). The liver TNF-alpha levels of the rosiglitazone and metformin treatment groups were 0.24 +/- 0.14 and 0.30 +/- 0.12 respectively, both significantly lower than that of the NAFLD group (0.85 +/- 0.12, both P < 0.001). The levels of FAS mRNA expression of the rosiglitazone and metformin treatment groups were 0.22 +/- 0.14 and 0.29 +/- 0.16 respectively, both significantly lower than that of the NAFLD group (0.68 +/- 0.23, P < 0.001 and P < 0.005). CONCLUSION: The insulin-sensitizing drugs, rosiglitazone and metformin, are effective in the treatment of NAFLD.