A 58-Year-Old Woman with Acute Torsion of the Small Bowel Due to Diffuse Intestinal Lipomatosis.

BACKGROUND Diffuse intestinal lipomatosis is a rare condition that infiltrates mature fatty tissue into the intestinal submucosa and subserosa of the small or large intestine and can present with intestinal obstruction or torsion. This report is of the case of a 58-year-old woman who had acute torsion of the small bowel due to diffuse small intestinal lipomatosis. CASE REPORT A 58-year-old woman, who was otherwise in good health, arrived at our Emergency Department experiencing sudden, intense pain in the lower abdomen. She also reported abdominal swelling, feelings of nausea, vomiting, and reduced ability to defecate for at least 2 days. The next morning, contrast-enhanced abdominal computed tomography (CT) scan was performed, showing diffuse thickening of the small intestinal wall with hypodensity, fatty density, lumen narrowing, and wall thinning. The small intestine demonstrated a whirlpool-like distribution in the lower right abdomen and localized thickening of the small intestinal wall, suggesting acute intestinal torsion. An hour later, an emergency operation was performed to remove part of the small intestine. Three days later, pathological results showed a thin intestinal wall, expansion of the mucosal layer and submucosa, and hyperplasia of adipose tissue. CONCLUSIONS This report presents a rare case of torsion and small bowel obstruction caused by diffuse intestinal lipomatosis and focuses on the abdominal enhanced CT scan, which showed diffuse thickening of the small intestine, with multiple areas of fat density and torsion of the small intestine in the right lower abdomen. Histopathology is also presented, with the result showing intestinal lipomatosis.

Toll-like receptor 2 deficiency promotes the generation of alloreactive γδT17 cells after cardiac transplantation in mice.

Homograft rejection is the main cause of heart transplantation failure. The role of TLR2, a major member of the toll-like receptor (TLR) family, in transplantation rejection is has yet to be elucidated. In this study, we used a mouse model of acute cardiac transplantation rejection to investigate whether the TLR2 signalling pathway can regulate cardiac transplantation rejection by regulating alloreactive IL-17+γδT (γδT17) cells. We found that the expression of TLR2 on the surface of dendritic cells (DCs) and macrophages increased during acute transplantation rejection. In addition, our investigation revealed that γδT17 cells exert a significant influence on acute cardiac transplantation rejection. TLR2 gene knockout resulted in an increase in alloreactive γδT17 cells in the spleen and heart grafts of recipient mice compared with wild-type recipient mice and an increase in the mRNA expression of IL-17, IL-1ß, CCR6, and CCL20 in the heart grafts. In an in vitro experiment, a mixed lymphocyte reaction was conducted to assess the impact of TLR2 deficiency on the generation of γδT17 cells, which further substantiated a significant increase compared to that in wild-type controls. Furthermore, the mixed lymphocyte reaction showed that TLR2 regulated the production of γδT17 cells by regulating the ability of DCs to secrete IL-1ß. These results suggest that TLR2 signalling is important for regulating the generation of γδT17 cells after cardiac allograft transplantation.

Improved maximum likelihood method for P-S-N curve fitting method with small number specimens and application in T-welded joint.

In fatigue data analysis, fitting accurate P-S-N curve is problematic if only a small number of specimen is available, especially to evaluate the relationship between the stress level and the standard deviation. This paper proposes a sample information reconstruction method that can effectively solve this problem. Based on this method and the life equivalent principle, a new maximum likelihood method (which is abbreviated to improved maximum likelihood method) is proposed for P-S-N curve fitting. T-joint specimens of Q450NQR1 steel were fabricated and tested, then the P-S-N curves was fitted by the improved maximum likelihood method, least square method, maximum likelihood method, standard BS7608 and standard IIW. Finally, P-S-N curves by three methods and two standards are compared and analyzed. The results show that the relevant parameters of the P-S-N curve with 99.9% survival probability fitted by the improved maximum likelihood method are similar to those in the two standards, and it is indicated that the improved maximum likelihood method is a better way for P-S-N curve fitting with the small number of fatigue test specimens.

Establishment and assessment of a nomogram for predicting prognosis in bone-metastatic prostate cancer.

OBJECTIVE: For the purposes of patients' consultation, condition assessments, and guidance for clinicians' choices, we developed a prognostic predictive model to evaluate the 1-, 3-, and 5-year overall survival (OS) rates of bone-metastatic prostate cancer (PCa) patients. METHODS: We gathered data from 5522 patients with bone metastatic PCa registered in the Surveillance, Epidemiology, and End Results (SEER) database to develop a nomogram. A total of 359 bone metastatic PCas were collected from 2 hospitals to validate the nomogram and assess its discriminatory ability. In addition, we plotted the actual survival against the predicted risk to assess the calibration accuracy. Moreover, we designed a web calculator to quickly obtain accurate survival probability outcomes. RESULTS: Univariate and multivariate Cox hazard regression analyses suggested that age, marital status, prostate-specific antigen (PSA) level, Gleason score, clinical T stage, N stage, surgery, and chemotherapy were closely associated with OS rates. The calibration charts of the training and validation groups showed a high accuracy and reliability. The decision curve analysis (DCA) suggested a favorable clinical net benefit. CONCLUSION: Based on demography and clinical pathology, we developed a reliable nomogram to help clinicians more accurately predict the 1-, 3-, and 5-year OS rates of patients with bone metastatic PCa to guide evaluation and treatment.

Sodium nitroprusside improved the quality of Radix Saposhnikoviae through constructed physiological response under ecological stress.

The ecological significance of secondary metabolites is to improve the adaptive ability of plants. Secondary metabolites, usually medicinal ingredients, are triggered by unsuitable environment, thus the quality of medicinal materials under adversity being better. The quality of the cultivated was heavily declined due to its good conditions. Radix Saposhnikoviae, the dried root of Saposhnikovia divaricata (Turcz.) Schischk., is one of the most common botanicals in Asian countries, now basically comes from cultivation, resulting in the market price being only 1/10 to 1/3 of its wild counterpart, so improving the quality of cultivated Radix Saposhnikoviae is of urgency. Nitric oxide (NO) plays a crucial role in generating reactive oxygen species and modifying the secondary metabolism of plants. This study aims to enhance the quality of cultivated Radix Saposhnikoviae by supplementing exogenous NO. To achieve this, sodium nitroprusside (SNP) was utilized as an NO provider and applied to fresh roots of S. divaricata at concentrations of 0.03, 0.1, 0.5, and 1.0 mmol/L. This study measured parameters including the activities of antioxidant enzymes, secondary metabolite synthesis enzymes such as phenylalanine ammonia-lyase (PAL), 1-aminocyclopropane-1-carboxylic acid (ACC), and chalcone synthase (CHS), as well as the contents of NO, superoxide radicals (O2·-), hydrogen peroxide (H2O2), malondialdehyde (MDA), and four secondary metabolites. The quality of Radix Saposhnikoviae was evaluated with antipyretic, analgesic, anti-inflammatory effects, and inflammatory factors. As a result, the NO contents in the fresh roots were significantly increased under SNP, which led to a significant increase of O2·-, H2O2, and MDA. The activities of important antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD), were found to increase as well, with their peak levels observed on the 2nd and 3rd days. PAL, ACC, and CHS activities were also significantly enhanced, resulting in the increased secondary metabolite contents of Radix saposhnikoviae in all groups, especially the 0.5 mmol/L SNP. The four active ingredients, prim-O-glucosylcimifugin, cimifugin, 4'-O-ß-D-glucosyl-5-O-methylvisamminol, and sec-O-glucosylhamaudol, increased by 88.3%,325.0%, 55.4%, and 283.8%, respectively, on the 3rd day. The pharmaceutical effects of Radix Saposhnikoviae under 0.5 mmol/L SNP were significantly enhanced. Exogenous SNP can induce the physiological response of S. divaricata under adverse conditions and significantly improve the quality of Radix Saposhnikoviae.

Integration of Metabolome and Transcriptome Reveals the Major Metabolic Pathways and Potential Biomarkers in Response to Freeze-Stress Regulation in Apple (Malus domestica).

Freezing stress is the main factor affecting the normal growth and distribution of plants. The safe overwintering of a perennial deciduous plant is a crucial link to ensuring its survival and yield. However, little is known about the molecular mechanism of its gene regulation metabolites as related to its freeze-tolerance. In order to enhance our comprehension of freeze-tolerance metabolites and gene expression in dormant apple trees, we examined the metabolic and transcriptomic differences between 'Ralls' and 'Fuji', two apple varieties with varying degrees of resistance to freezing. The results of the freezing treatment showed that 'Ralls' had stronger freeze-tolerance than 'Fuji'. We identified 302, 334, and 267 up-regulated differentially accumulated metabolites (DAMs) and 408, 387, and 497 down-regulated DAMs between 'Ralls' and 'Fuji' under -10, -15, and -20 °C treatment, respectively. A total of 359 shared metabolites were obtained in the upward trend modules, of which 62 metabolites were associated with 89 pathways. The number of up-regulated genes accounted for 50.2%, 45.6%, and 43.2% of the total number of differentially expressed genes (DEGs), respectively, at -10, -15, and -20 °C. Through combined transcriptome and metabolome analysis, we identified 12 pathways that included 16 DAMs and 65 DEGs. Meanwhile, we found that 20 DEGs were identified in the phenylpropanoid biosynthesis pathway and its related pathways, involving the metabolism of p-Coumaroyl-CoA, 7, 4'-Dihydroxyflavone, and scolymoside. These discoveries advance our comprehension of the molecular mechanism underlying apple freeze-tolerance and provide genetic material for breeding apple cultivars with enhanced freeze-tolerance.

PKMYT1: A Potential Target for CCNE1 Amplificated Colorectal Tumors.

Colorectal cancer is a malignant tumor with higher morbidity and mortality. The purpose of this study is to investigate whether inhibition of Protein Kinase, Membrane Associated Tyrosine/Threonine 1 (PKMYT1) affects tumor cell proliferation, survival and migration in colon tumors with high Cyclin E1 (CCNE1) expression. PcDNA3.1-CCNE1 vector and si-PKMYT1 were transfected in SW480 cells by Lipofectamine 2000. Q-PCR and western blot assay were processed to detect the expression. Transwell assay and Edu assay were undertaken to verify the migration and proliferation. CCNE1 promotes the proliferation and migration of SW480. Silencing of PKMYT1 inhibited the proliferation of tumor cells. Silencing the expression of PKMYT1 under the premise of overexpression of CCNE1, the level of Cyclin Dependent Kinase 1 (CDK1)-PT14 was reduced, indicating that the cell cycle was blocked. The expression of γH2AX increased significantly, indicating that the DDR pathway of tumor cells was activated and DNA damage accumulated. The results of immunofluorescence microscopy showed significantly increased expression of DNA damage-associated marker (γH2AX: H2AX Variant Histone). In CCNE1 amplificated colorectal tumor cells, knockdown of PKMYT1 reduced cells in S phase, inhibited cell proliferation and promoted cell apoptosis, confirming that PKMYT1 was a potential therapeutic target for colorectal tumor. This study may verify a potential therapeutic target and provide a new idea for the treatment of colorectal cancer in the future.

Preoperative sarcopenia combined with prognostic nutritional index predicts long-term prognosis of radical gastrectomy with advanced gastric cancer: a comprehensive analysis of two-center study.

PURPOSE: This study aims to investigate the predictive value of the combined index smni(skeletal muscle index (SMI)-prognostic nutrition index(PNI)) for the postoperative survival of patients with advanced gastric cancer(AGC). METHODS: 650 patients with AGC from two centers (290 cases from the First Affiliated Hospital of Dalian University and 360 points from the Fujian Medical University Union Hospital) were selected as the study subjects based on unified screening criteria. Clinical data, preoperative abdominal CT images, results of hematology-related examinations, tumor-related characteristics, and surgical and follow-up data of the patients were collected and organized. The L3 vertebral level muscle area was measured using computer-assisted measurement techniques, and the skeletal muscle index(SMI) was calculated based on this measurement. The prognostic nutrition index (PNI) was calculated based on serum albumin and lymphocyte count indicators. The Kaplan-Meier survival analysis of data from the First Affiliated Hospital was used to determine that SMI and PNI are significantly correlated with the postoperative survival rate of patients with advanced gastric cancer. Based on this, a novel combined index smni was fitted and stratified for risk. Cox proportional hazards regression analysis was used to determine that the index smni is an independent prognostic risk factor for patients with AGC after surgery. The ROC curve was used to describe the predictive ability of the new combined index and its importance and predictive power in predicting postoperative survival of patients with AGC, which was verified in the data of Fujian Medical University Union Hospital. RESULT: The Kaplan-Meier curve analysis of the combined indicator smni Is clearly associated with long-term survival(3-year OS (P < 0.001) and DSS (P < 0.001)), univariate analysis and multivariate analysis showed that smni was an independent prognostic risk factor, The ROC curve for the first center 3-year OS(AUC = 0.678), DSS(AUC = 0.662) show good predictive ability and were validated in the second center. CONCLUSION: The combined index smni has a good predictive ability for the postoperative survival rate of patients with AGC and is expected to provide a new reference basis and more accurate and scientific guidance for the postoperative management and treatment of patients with AGC.

Circular RNA_0000326 accelerates breast cancer development via modulation of the miR-9-3p/YAP1 axis.

Circular RNA (circ)_0000326 has been reported in bladder cancer and cervical cancer and is concerned to be involved with the development of cancerous cells. Whereas, there have been no reports concentrating on the influences of circ_0000326 in breast cancer (BC). Therefore, the latent modulatory mechanisms of circ_0000326 in BC are researched. circ_0000326 expression in BC tissues and correlative cells was evaluated via RT-qPCR, and the relevance between circ_0000326 expression and overall survival and the clinicopathological feature was also investigated. After a series of transfection, the effects of circ_0000326, microRNA-9-3p (miR-9-3p), and Yes-associated protein 1 (YAP1) in BC cell growth, invasion, and stemness were studied by CCK-8, flow cytometry, Transwell, and sphere-forming assays. The binding sites and correlation of circ_0000326, miR-9-3p, and YAP1 were certified via starBase website, luciferase reporter assay, and Pearson's χ2 test. The in vivo experiment was evaluated by establishing a subcutaneous tumorigenesis model. High-expressed circ_0000326 in BC tissues and cells was discovered, which was connected with an undesirable prognosis. Silencing of circ_0000326 visibly inhibited MCF-7 and BT549 cell growth, invasion, stemness, meanwhile declining the protein levels of SRY-related high-mobility group box gene 2 (SOX2) and octamer binding transcription factor 4 (OCT4). miR-9-3p was a sponger of circ_0000326, which was negatively regulated by circ_0000326. Moreover, YAP1 was confirmed as a target gene of miR-9-3p. circ_0000326 affected BC cell behaviors via mediating miR-9-3p and YAP1. Furthermore, circ_0000326 silencing prohibited tumor growth of BC in vivo. The research uncovered that circ_0000326 facilitated BC development via mediating the miR-9-3p/YAP1 axis.

Toll-like receptor 2 deficiency alleviates acute pancreatitis by inactivating the NF-κB/NLRP3 pathway.

The early aseptic immune response is the key factor leading to the aggravation of acute pancreatitis (AP). Toll-like receptor (TLR) 2 is an important member of the TLR family, but the role of TLR2 in AP remains to be investigated. In the present study, we found that TLR2 expression was significantly increased in AP patients. In a mouse model of cerulein-induced AP, TLR2 deficiency resulted in reduced inflammation, reduced infiltration of pancreatic neutrophils and macrophages, and decreased expression of proinflammatory cytokines such as interleukin (IL)-1ß, IL-6, IL-17 and IL-18. In addition, transcriptomic analysis revealed that nod-like receptor family pyrin domain-containing 3 (NLRP3) expression was increased in AP, and there was a significant correlation between NLRP3 and TLR2. This study found that TLR2 deficiency can lead to a decrease in the activation of the NF-κB/NLRP3 signalling pathway, and the NLRP3 inhibitor MCC950 can alleviate AP in mice. Therefore, this study confirmed that TLR2 participates in the development of AP by activating the NF-κB/NLRP3 pathway. This study suggested that TLR2 might be a novel therapeutic target for AP.

Removal Performance of KOH-Modified Biochar from Tropical Biomass on Tetracycline and Cr(VI).

Biochar can be used to address the excessive use of tetracycline and micronutrient chromium (Cr) in wastewater that potentially threatens human health. However, there is little information about how the biochar, made from different tropical biomass, facilitates tetracycline and hexavalent chromium (Cr(VI)) removal from aqueous solution. In this study, biochar was prepared from cassava stalk, rubber wood and sugarcane bagasse, then further modified with KOH to remove tetracycline and Cr(VI). Results showed that pore characteristics and redox capacity of biochar were improved after modification. KOH-modified rubber wood biochar had the highest removal of tetracycline and Cr(VI), 1.85 times and 6 times higher than unmodified biochar. Tetracycline and Cr(VI) can be removed by electrostatic adsorption, reduction reaction, π-π stacking interaction, hydrogen bonding, pore filling effect and surface complexation. These observations will improve the understanding of the simultaneous removal of tetracycline and anionic heavy metals from wastewater.

Commercial dishes with gelatin-free microstructured inserts for elongated stem cell self-renewal and pluripotency.

Here, we report the scalable fabrication of 2i-functionalized micro-pyramid-array (µPyA/+2i) inserts for use in commercial multi-well plates, as the alternative cultivation platform for maintaining long-term self-renewal and pluripotency of multiple mESCs and mouse induced pluripotent stem cells. Relevant evidence including cell morphology characterization increased alkaline phosphatase activity, high expression of mESC self-renewal markers, decreased levels of differentiation-associated markers, and high proportion of self-renewal marker cells are provided. Further studies demonstrated that µPyA/+2i could cause a higher cell density in mESC colony, and induce gene expression changes. Subsequent studies showed that µPyA/+2i can influence the cytoskeleton and promote cell adhesion through Cldn-7 upregulation. In summary, these µPyA/+2i inserts offer flexible and gelatin-free micro-envriomnets to maintain long-term self-renewal and pluripotency of mESCs. Enabled by the microstructured inserst, the facile stem cell manipulation and transfer among culture dishes will broaden stem cells both in routine and translational applications.

Squeeze Behaviors of Magnetorheological Fluids under Different Compressive Speeds.

The compression tests under the unidirection for magnetorheological (MR) fluids have been studied at different compressive speeds. The results indicated that curves of compressive stress under different compression speeds at the applied magnetic field of 0.15 T overlapped well and were shown to be an exponent of about 1 of the initial gap distance in the elastic deformation region and accorded well with the description of continuous media theory. The difference in compressive stress curves increases significantly with an increasing magnetic field. At this time, the continuous media theory description could not be accounted for the effect of compressive speed on the compression of MR fluid, which seems to deviate from the Deborah number prediction under the lower compressive speeds. An explanation based on the two-phase flow due to aggregations of particle chains resulting in much longer relaxation times at a lower compressive speed was proposed to explain this deviation. The results have guiding significance for the theoretical design and process parameter optimization for the squeeze-assisted MR devices such as MR dampers and MR clutches based on the compressive resistance.

ITGA9-AS1 up-regulates ITGA9 by targeting miR-4765 and recruiting HNRNPU to affect the proliferation and apoptosis of non-small cell lung cancer cells.

Long non-coding RNAs (lncRNAs) have been regarded as promising biomarkers in the regulation of various biological and pathological processes of non-small cell lung cancer (NSCLC). LncRNAITGA9-AS1 has been reported to be down-regulated in elderly patients with lung cancer, but how it may influence NSCLC remains to be identified. Therefore, we aim to explore the specific mechanism involving ITGA9-AS1 and ITGA9 in NSCLC. A functional assay was conducted to verify ITGA9-AS1's proliferative effects on NSCLC cells. Mechanism experiments with bioinformatics predictions were performed to explore the interaction of ITGA9-AS1 and ITGA9 in NSCLC cells. ITGA9-AS1 inhibited NSCLC cell proliferation while enhancing cell apoptosis. It up-regulated ITGA9 by competitively sponging miR-4765, and it stabilizedITGA9 mRNA by recruiting a RNA-binding protein (RBP)-HNRNPU (heterogeneous nuclear ribonucleoprotein U) in NSCLC cells. ITGA9-AS1 suppressed NSCLC progression by the up-regulation of ITGA9 via targeting miR-4765 and recruiting HNRNPU.

Development of a joint diagnostic model of thyroid papillary carcinoma with artificial neural network and random forest.

Objective: Papillary thyroid carcinoma (PTC) accounts for 80% of thyroid malignancy, and the occurrence of PTC is increasing rapidly. The present study was conducted with the purpose of identifying novel and important gene panels and developing an early diagnostic model for PTC by combining artificial neural network (ANN) and random forest (RF). Methods and results: Samples were searched from the Gene Expression Omnibus (GEO) database, and gene expression datasets (GSE27155, GSE60542, and GSE33630) were collected and processed. GSE27155 and GSE60542 were merged into the training set, and GSE33630 was defined as the validation set. Differentially expressed genes (DEGs) in the training set were obtained by "limma" of R software. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis as well as immune cell infiltration analysis were conducted based on DEGs. Important genes were identified from the DEGs by random forest. Finally, an artificial neural network was used to develop a diagnostic model. Also, the diagnostic model was validated by the validation set, and the area under the receiver operating characteristic curve (AUC) value was satisfactory. Conclusion: A diagnostic model was established by a joint of random forest and artificial neural network based on a novel gene panel. The AUC showed that the diagnostic model had significantly excellent performance.

Preparation and characterization of pure phase CdMnTe nanopowders by a hydrothermal route.

In this paper, CdMnTe nanopowders with uniform shapes were prepared through a facile hydrothermal route using 3-mercaptopropionic acid (MPA) as the stabilizer and modifier. The effects of different experimental conditions including Cd-to-MPA ratio, pH value and reaction temperature on the phase composition and formation mechanism of as-prepared nanopowders were studied. XRD results indicated as-prepared CdMnTe nanopowders were pure phase and had cubic sphalerite structure with high crystallinity. SEM and Rietveld refinement clearly showed that the powders were about 10-100 nm in size. In PL measurement, there was a strong luminescence peak in the infrared region 1.717-1.826 eV. Compared with the CdMnTe single crystal, a blue shift of about 0.109 eV indicated a wider band gap. In UV-vis spectra, the absorption peak of the sample blue shifted with the decrease of crystal size, which indicated an obvious quantum confinement effect (QCE) in nanopowders. The optimal conditions for the preparation of CdMnTe nanopowders are 180 °C for 24 h with the molar ratio 1 : 1 of Cd : MPA at pH 13. In particular, the growth kinetics and possible formation mechanism of the nanopowders were proposed.

High N Storage but Low N Recovery After Long-Term N-Fertilization in a Subtropical Cunninghamia lanceolata Plantation Ecosystem: A 14-Year Case Study.

Forests are among the most important N pools of all terrestrial ecosystems. Elevated atmospheric N deposition in recent decades has led to increased interest in the influences of N application on forest N cycles. However, accurate assessments of N storage in forest ecosystems remain elusive. We used a 14-year experiment of a Chinese fir [Cunninghamia lanceolata (Lamb.) Hook] plantation to explore how long-term N fertilization affected N storage and recovery rates. Our study plots were located in a field that had been continuously fertilized over 14 years (2004-2017) with urea at rates of 0 (N0, control), 60 (N60, low-N), 120 (N120, medium-N), and 240 (N240, high-N) kg N hm-2a-1. Data were collected that included N content and biomass in the understory, litter, and various plant organs (i.e., leaves, branches, stems, roots, and bark), as well as soil N content and density at different depths. Results showed that the total ecosystem N storage in the N-fertilized plots was 1.1-1.4 times higher than that in the control plots. About 12.36% of the total ecosystem N was stored in vegetation (plant organs, litter, and understory) and 87.64% was stored in soil (0-60 cm). Plant organs, litter, and soil had higher N storage than the understory layer. Significantly higher plant N uptake was found in the medium-N (1.2 times) and high-N (1.4 times) treatments relative to the control. The N recovery rate of the understory layer in the N-fertilized treatments was negative and less than that in the control. Application of long-term N fertilizer to this stand led to a low N recovery rate (average 11.39%) and high loss of N (average 91.86%), which indicate low N use efficiency in the Chinese fir plantation ecosystem. Our findings further clarify the distribution of N in an important terrestrial ecosystem and improve our understanding of regional N cycles.

The Prognostic Implication of the BRAF V600E Mutation in Papillary Thyroid Cancer in a Chinese Population.

Background: The BRAF V600E mutation is an important genetic event in papillary thyroid cancer (PTC). This study aimed to provide additional information regarding the association of the BRAF V600E mutation with PTC prognosis. Methods: A retrospective single-center study based on a Chinese population was performed to analyze the association of the BRAF V600E mutation with several clinicopathological features. Kaplan-Meier survival curves and Cox proportional hazards regression analysis were applied to implement the survival analysis. Results: The BRAF V600E mutation was present in 1102 (87.7%) of the 1257 patients and was significantly associated with older age, conventional subtype, multifocality, advanced TNM stage, and a reduced prevalence of Hashimoto's thyroiditis. The Kaplan-Meier survival curves demonstrated that the difference between the BRAF V600E-positive and BRAF V600E-negative groups was significant with a log-rank P-value of 0.048. The Cox proportional hazards regression analysis adjusted HR was 3.731 (95% CI, 1.457 to 9.554). We further demonstrated that larger tumor size (>1 cm), extrathyroidal extension (ETE), and lateral lymph node metastasis (LNM) were associated with a higher probability of PTC recurrence in patients harboring the BRAF V600E mutation. Conclusions: The BRAF V600E mutation remains an independent risk factor for PTC recurrence and may be useful for clinical decisions when it combines with some pathological factors.

Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women.

BACKGROUND: Osteoporosis is an abnormal reduction in bone mass and bone deterioration leading to increased fracture risk. Risedronate belongs to the bisphosphonate class of drugs which act to inhibit bone resorption by interfering with the activity of osteoclasts. This is an update of a Cochrane Review that was originally published in 2003. OBJECTIVES: We assessed the benefits and harms of risedronate in the primary and secondary prevention of osteoporotic fractures for postmenopausal women at lower and higher risk for fractures, respectively. SEARCH METHODS: With broader and updated strategies, we searched the Cochrane Central Register of Control Trials (CENTRAL), MEDLINE and Embase. A grey literature search, including the online databases ClinicalTrials.gov, International Clinical Trials Registry Platform (ICTRP), and drug approval agencies, as well as bibliography checks of relevant systematic reviews was also performed. Eligible trials published between 1966 to 24 March 2021 were identified. SELECTION CRITERIA: We included randomised controlled trials that assessed the benefits and harms of risedronate in the prevention of fractures for postmenopausal women. Participants must have received at least one year of risedronate, placebo or other anti-osteoporotic drugs, with or without concurrent calcium/vitamin D. Major outcomes were clinical vertebral, non-vertebral, hip and wrist fractures, withdrawals due to adverse events, and serious adverse events. In the interest of clinical relevance and applicability, we classified a study as secondary prevention if its population fulfilled more than one of the following hierarchical criteria: a diagnosis of osteoporosis, a history of vertebral fractures, low bone mineral density (BMD)T score ≤ -2.5, and age ≥ 75 years old. If none of these criteria was met, the study was considered to be primary prevention. DATA COLLECTION AND ANALYSIS: We used standard methodology expected by Cochrane. We pooled the relative risk (RR) of fractures using a fixed-effect model based on the expectation that the clinical and methodological characteristics of the respective primary and secondary prevention studies would be homogeneous, and the experience from the previous review suggesting that there would be a small number of studies. The base case included the data available for the longest treatment period in each placebo-controlled trial and a >15% relative change was considered clinically important. The main findings of the review were presented in summary of findings tables, using the GRADE approach. In addition, we looked at benefit and harm comparisons between different dosage regimens for risedronate and between risedronate and other anti-osteoporotic drugs. MAIN RESULTS: Forty-three trials fulfilled the eligibility criteria, among which 33 studies (27,348 participants) reported data that could be extracted and quantitatively synthesized. We had concerns about particular domains of risk of bias in each trial. Selection bias was the most frequent concern, with only 24% of the studies describing appropriate methods for both sequence generation and allocation concealment. Fifty per cent and 39% of the studies reporting benefit and harm outcomes, respectively, were subject to high risk. None of the studies included in the quantitative syntheses were judged to be at low risk of bias in all seven domains. The results described below pertain to the comparisons for daily risedronate 5 mg versus placebo which reported major outcomes. Other comparisons are described in the full text. For primary prevention, low- to very low-certainty evidence was collected from four studies (one to two years in length) including 989 postmenopausal women at lower risk of fractures. Risedronate 5 mg/day may make little or no difference to wrist fractures [RR 0.48 ( 95% CI 0.03 to 7.50; two studies, 243 participants); absolute risk reduction (ARR) 0.6% fewer (95% CI 1% fewer to 7% more)] and withdrawals due to adverse events [RR 0.67 (95% CI 0.38 to 1.18; three studies, 748 participants); ARR 2% fewer (95% CI 5% fewer to 1% more)], based on low-certainty evidence. However, its preventive effects on non-vertebral fractures and serious adverse events are not known due to the very low-certainty evidence. There were zero clinical vertebral and hip fractures reported therefore the effects of risedronate for these outcomes are not estimable.  For secondary prevention, nine studies (one to three years in length) including 14,354 postmenopausal women at higher risk of fractures provided evidence. Risedronate 5 mg/day probably prevents non-vertebral fractures [RR 0.80 (95% CI 0.72 to 0.90; six studies, 12,173 participants); RRR 20% (95% CI 10% to 28%) and ARR 2% fewer (95% CI 1% fewer to 3% fewer), moderate certainty], and may reduce hip fractures [RR 0.73 (95% CI 0.56 to 0.94); RRR 27% (95% CI 6% to 44%) and ARR 1% fewer (95% CI 0.2% fewer to 1% fewer), low certainty]. Both of these effects are probably clinically important. However, risedronate's effects are not known for wrist fractures [RR 0.64 (95% CI 0.33 to 1.24); three studies,1746 participants); ARR 1% fewer (95% CI 2% fewer to 1% more), very-low certainty] and not estimable for clinical vertebral fractures due to zero events reported (low certainty). Risedronate results in little to no difference in withdrawals due to adverse events [RR 0.98 (95% CI 0.90 to 1.07; eight studies, 9529 participants); ARR 0.3% fewer (95% CI 2% fewer to 1% more); 16.9% in risedronate versus 17.2% in control, high certainty] and probably results in little to no difference in serious adverse events [RR 1.00 (95% CI 0.94 to 1.07; six studies, 9435 participants); ARR 0% fewer (95% CI 2% fewer to 2% more; 29.2% in both groups, moderate certainty). AUTHORS' CONCLUSIONS: This update recaps the key findings from our previous review that, for secondary prevention, risedronate 5 mg/day probably prevents non-vertebral fracture, and may reduce the risk of hip fractures. We are uncertain on whether risedronate 5mg/day reduces clinical vertebral and wrist fractures.  Compared to placebo, risedronate probably does not increase the risk of serious adverse events.  For primary prevention, the benefit and harms of risedronate were supported by limited evidence with high uncertainty.

A Proposed Heterogeneous Ensemble Algorithm Model for Predicting Central Lymph Node Metastasis in Papillary Thyroid Cancer.

Purpose: To develop a heterogeneous ensemble algorithm model to precisely predict central lymph node metastasis (CLNM), which can provide a reference value on controversial topics of performing prophylactic central lymph node dissection for patients with papillary thyroid cancer (PTC). Methods: The study included patients with PTC who underwent an initial thyroid resection in a single-center medical institution between January 2014 and December 2018. A total of 18 variables, including clinical features and ultrasound (US) features, were used in the univariate analysis, multivariate analysis, and feature selection and were also used to develop a heterogeneous ensemble model based on five basic machine learning models, including extreme gradient boosting, k-nearest neighbors, random forest, gradient boosting, and AdaBoost. Moreover, a partial dependent plot was used to explain the heterogeneous ensemble model. Results: The area under the receiver operating characteristic curve of the heterogeneous ensemble algorithm model was 0.67, which is significantly better than that of the basic machine models in predicting CLNM. All machine learning models performed better than US. Based on multivariate analysis and receiver operating characteristic curve analysis, age ≤33 years, tumor size ≥0.8 cm, US-suspected CLNM, and microcalcification were risk factors for CLNM, and anti-thyroid peroxidase antibody and serum thyroglobulin levels were favorable factors for CLNM. Conclusion: The proposed heterogeneous ensemble algorithm model may be optimal tool to predict CLNM by integrating clinical and US features.