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Abstract Aims/Introduction Although patients with type 1 diabetes are medically exempt, many insist on fasting during Ramadan. Multiple daily insulin injections (MDI), premixed insulin and continuous subcutaneous insulin infusion (CSII) are commonly used. To date, little is known about the safety of Ramadan fasting in these patients. Materials and Methods We pooled data from 17 observational studies involving 1,699 patients treated with either CSII or non‐CSII (including premixed and MDI) regimen. The study outcomes were the frequencies of hypoglycemia, hyperglycemia and/or ketosis. Given the lack of patient‐level data, separate analyses for premixed and MDI regimen were not carried out. Results The CSII‐treated group (n = 203) was older (22.9 ± 6.9 vs 17.8 ± 4.0 years), and had longer diabetes duration (116.7 ± 66.5 vs 74.8 ± 59.2 months) and lower glycated hemoglobin (7.8 ± 1.1% vs 9.1 ± 2.0%) at baseline than the non‐CSII‐treated group (n = 1,496). The non‐CSII‐treated group had less non‐severe hypoglycemia than the CSII‐treated group (22%, 95% CI 13–34 vs 35%, 95% CI 17–55). Of the non‐CSII‐treated group, 7.1% (95% CI 5.8–8.5) developed severe hypoglycemia, but none from the CSII‐treated group did. The non‐CSII‐treated group was more likely to develop hyperglycemia (12%, 95% CI 3–25 vs 8.8%, 95% CI 0–31) and ketosis (2.5%, 95% CI 1.0–4.6 vs 1.6%, 95% CI 0.1–4.7), and discontinue fasting (55%, 95% CI 34–76 vs 31%, 95% CI 9–60) than the CSII‐treated group. Conclusions The CSII regimen had lower rates of severe hypoglycemia and hyperglycemia/ketosis, but a higher rate of non‐severe hyperglycemia than premixed/MDI regimens. These suggest that appropriate patient selection with regular, supervised fine‐tuning of the basal insulin rate with intensive glucose monitoring might mitigate the residual hypoglycemia risk during Ramadan.

Abstract Background Methadone is an effective therapy for opiate dependence. However, one of the commonest side effects is sexual dysfunction among male patients. Buprenorphine is an alternative to methadone. This study aimed to compare sexual desire among opiate-dependent male patients on buprenorphine (BMT) and methadone maintenance therapy (MMT). Methods This cross-sectional study involved 126 male opiate-dependent patient who were tested for total testosterone (TT) and prolactin levels, and were interviewed and completed the Sexual Desire Inventory-2 (SDI-2), Malay language of International Index of Erectile Function (Mal-IIEF-15) and the Malay version of the self-rated Montgomery-Asberg Depression Rating Scale (MADRS-BM) questionnaires. Results There were 95 (75.4%) patients on MMT and 31 (24.6%) on BMT. Patients on MMT scored significantly lower in the sexual desire domain (Mal-IIEF-15 scores) (p

Transcranial direct current stimulation (tDCS) is a non-invasive method to modulate cortical excitability in humans. Here, we examined the effects of anodal tDCS on suprahyoid motor evoked potentials (MEP) when applied over the hemisphere with stronger and weaker suprahyoid/submental projections, respectively, while study participants performed a swallowing task. 30 healthy volunteers were invited to two experimental sessions and randomly assigned to one of two different groups. While in the first group stimulation was targeted over the hemisphere with stronger suprahyoid projections, the second group received stimulation over the weaker suprahyoid projections. tDCS was applied either as anodal or sham stimulation in a random cross-over design. Suprahyoid MEPs were assessed immediately before intervention, as well as 5, 30, 60, and 90 min after discontinuation of stimulation from both the stimulated and non-stimulated contralateral hemisphere. We found that anodal tDCS (a-tDCS) had long-lasting effects on suprahyoid MEPs on the stimulated side in both groups (tDCS targeting the stronger projections: F(1,14) = 96.2, p < 0.001; tDCS targeting the weaker projections: F(1,14) = 37.45, p < 0.001). While MEPs did not increase when elicited from the non-targeted hemisphere after stimulation of the stronger projections (F(1,14) = 0.69, p = 0.42), we found increased MEPs elicited from the non-targeted hemisphere after stimulating the weaker projections (at time points 30 to 90 min) (F(1,14) = 18.26, p = 0.001). We conclude that anodal tDCS has differential effects on suprahyoid MEPs elicited from the targeted and non-targeted hemisphere depending on the site of stimulation. This finding may be important for the application of a-tDCS in patients with dysphagia, for example after stroke. [ABSTRACT FROM AUTHOR]

Abstract Background Although depression is associated with changes in the hypothalamic-pituitary-thyroid axis, its relationship with subclinical hypothyroidism (SCH) is controversial. To date, there is a lack of data on the improvement of depressive symptoms with levothyroxine therapy among individuals with coexistent SCH. Methods We conducted a meta-analysis to evaluate the association between SCH and depression including 1) the prevalence of depression in SCH (with a sub-analysis of the geriatric cohort), 2) thyroid stimulating hormone (TSH) level among patients with depression and 3) the effect of levothyroxine therapy among patients with SCH and coexistent depression. Results In a pooled analysis of 12,315 individuals, those with SCH had higher risk of depression than euthyroid controls (relative risk 2.35, 95% confidence intervals [CI], 1.84 to 3.02; p

Graphene oxide was prepared by ultrasonication of completely oxidized graphite and used to improve the flame retardancy of epoxy. The epoxy/graphene oxide nanocomposite was studied in terms of exfoliation/dispersion, thermal stability and flame retardancy. X-ray diffraction and transmission electron microscopy confirmed the exfoliation of the graphene oxide nanosheets in epoxy matrix. Cone calorimeter measurements showed that the time to ignition of the epoxy/graphene oxide nanocomposite was longer than that of neat epoxy. The heat release rate curve of the nanocomposite was broadened compared to that of neat epoxy and the peak heat release rate decreased as well. [ABSTRACT FROM AUTHOR]

Abstract Background This study evaluates the psychometric properties of the Malay version of the Brief Psychiatric Rating Scale (BPRS-M) among patients with schizophrenia in a psychiatric outpatient clinic. Methods Ninety-nine schizophrenia outpatients were administered the Malay version of the Brief Psychiatric Rating Scale (BPRS-M), Malay version of Positive and Negative Syndrome Scale (PANSS), Malay version of Calgary Depression Scale for Schizophrenia (CDSS) and Malay version of World Health Organization Quality of Life – Brief Version (WHOQOL-BREF). Results An exploratory factor analysis (EFA) of BPRS-M produced a seven-factor solution which accounted for 71.4% of the total variance. It exhibited fair internal consistency (Cronbach’s alpha coefficient of 0.75). “Positive symptoms” and “Resistance” factors had association with unemployment and number of antipsychotics, positively correlated with PANSS but negatively correlated with WHOQOL-BREF. “Mood disturbance” factor correlated with lifetime history of suicide attempts, Malay version of CDSS and WHOQOL-BREF (psychological). Both “Negative symptoms” and “Activation” factors were associated with male, lower education, unemployment and positively correlated with Malay version of PANSS but negatively correlated with WHOQOL-BREF. Conclusions The BPRS-M demonstrated promising psychometric properties in terms of dimensionality, reliability, and validity that generally justifies its use in routine clinical practice in Malaysia.

Parathyroid carcinoma is a rare cause of hypercalcemia. Hypercalcemic crisis is a medical emergency. Hemodialysis is rarely needed to treat hypercalcaemia. We report a case of refractory hypercalcaemia secondary to parathyroid carcinoma requiring haemodialysis.

Abstract Hepatocyte nuclear factor alpha (HNF1α), endoplasmic reticulum (ER) stress, and hepatocyte apoptosis contribute to severe acute exacerbation (SAE) of liver injury. Here, we explore HNF1α–ER stress-hepatocyte apoptosis interaction in liver injury. LO2, HepG2 and SK-Hep1 cells were treated with thapsigargin (TG) or tunicamycin (TM) to induce ER stress. Carbon tetrachloride (CCl4) was used to induce acute liver injury in mice. Low-dose lipopolysaccharide (LPS) exacerbated liver injury in CCl4-induced mice. Significant apoptosis, HNF1α upregulation, and nuclear factor kappa B (NF-κB) activation were observed in human-derived hepatocytes during ER stress. Knockdown of Rela, NF-κB p65, inhibited the HNF1α upregulation. Following CCl4 treatment ER stress, apoptosis, HNF1α expression and RelA phosphorylation were significantly increased in mice. HNF1α knockdown reduced activating transcription factor 4 (ATF4) expression, and aggravated ER stress as well as hepatocyte apoptosis in vivo and in vitro. The double fluorescent reporter gene assay confirmed that HNF1α regulated the transcription of ATF4 promoter. LPS aggravated CCl4-induced liver injury and reduced HNF1α, and ATF4 expression. Therefore, in combination, HNF1α and ER stress could be mutually regulated forming a feedback loop, which helps in protecting the injured liver by down-regulating hepatocyte apoptosis. Low-dose LPS aggravates hepatocyte apoptosis and promotes the SAE of liver injury by interfering with the feedback regulation of HNF1α and ER stress in acute liver injury.

Objective: To explore the application value of MRI-based imaging histology and deep learning model in the identification and classification of breast phyllodes tumors., Methods: Seventy-seven patients diagnosed as breast phyllodes tumors and fibroadenomas by pathological examination were retrospectively analyzed, and traditional radiomics features, subregion radiomics features, and deep learning features were extracted from MRI images, respectively. The features were screened and modeled using variance selection method, statistical test, random forest importance ranking method, Spearman correlation analysis, least absolute shrinkage and selection operator (LASSO). The efficacy of each model was assessed using the subject operating characteristic (ROC) curve, The DeLong test was used to assess the differences in the AUC values of the different models, and the clinical benefit of each model was assessed using the decision curve (DCA), and the predictive accuracy of the model was assessed using the calibration curve (CCA)., Results: Among the constructed models for classification of breast phyllodes tumors, the fusion model (AUC: 0.97) had the best diagnostic efficacy and highest clinical benefit. The traditional radiomics model (AUC: 0.81) had better diagnostic efficacy compared with subregion radiomics model (AUC: 0.70). De-Long test, there is a statistical difference between the fusion model traditional radiomics model, and subregion radiomics model in the training group. Among the models constructed to distinguish phyllodes tumors from fibroadenomas in the breast, the TDT&#95;CIDL model (AUC: 0.974) had the best predictive efficacy and the highest clinical benefit. De-Long test, the TDT&#95;CI combination model was statistically different from the remaining five models in the training group., Conclusion: Traditional radiomics models, subregion radiomics models and deep learning models based on MRI sequences can help to differentiate benign from junctional phyllodes tumors, phyllodes tumors from fibroadenomas, and provide personalized treatment for patients., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ying Wang reports administrative support was provided by Health Commission of Henan Province. Reports a relationship with that includes:. Has patent pending to. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

Objective: Rivaroxaban and dabigatran are approved to reduce the risk of stroke in patients with nonvalvular atrial fibrillation (NVAF). However, the clinical benefits of rivaroxaban and dabigatran in people with high bleeding risk are unclear., Methods: A retrospective study was conducted on NVAF patients admitted to the First Affiliated Hospital of Zhengzhou University from May 31, 2016 to May 31, 2019. These patients had a high risk of bleeding and were taking at least one study medication. The aim of the study was to evaluate clinical benefits by comparing the efficacy and safety risks of these two medications., Results: A total of 1,301 patients with high bleeding risk were enrolled, including 787 patients in the rivaroxaban group and 514 patients in the dabigatran group. Results of the primary efficacy benefit endpoint were obtained from 104 patients (13.21%) in the rivaroxaban group and 81 (15.76%) patients in the dabigatran group [hazard ratio (HR): 0.860; 95% confidence interval (CI): 0.637-1.162; P  = 0.327], this indicates that there was no significant difference between dabigatran and rivaroxaban in preventing stroke and systemic embolism in patients with high bleeding risk NVAF. The principal safety end points were observed in 49 (6.23%) patients in the rivaroxaban group and in 36 (7.00%) patients in the dabigatran group (HR: 0.801 in the rivaroxaban group; 95% CI: 0.512-1.255; P  = 0.333), this indicates that there was no a significant difference in reducing fatal bleeding and critical organ bleeding. With respect to secondary efficacy and benefit endpoints, 28 (3.56%) patients in the rivaroxaban group and 26 (5.06%) patients in the dabigatran group died, with an HR of 0.725 (95% CI: 0.425-1.238; P  = 0.239); 32 (4.07%) patients in the rivaroxaban group; and 31 (6.03%) patients in the dabigatran group had myocardial infarction (MI), with an HR of 0.668 (95% CI: 0.405-1.102, P  = 0.114) in the rivaroxaban group, this indicates that there was no significant difference between dabigatran and rivaroxaban in preventing all-cause death and MI., Conclusions: In NVAF patients with high bleeding risk, there was no significant difference between dabigatran and rivaroxaban in preventing stroke and systemic embolism. There was also no significant difference between dabigatran and rivaroxaban in reducing fatal and critical organ bleeding., Clinical Trial Registration: Chinese Clinical Trials Registry, identifier ChiCTR2100052454., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Liu.)

Aim: To investigate the effect of the gp130/STAT3-endoplasmic reticulum (ER) stress axis on hepatocyte necroptosis during acute liver injury., Methods: ER stress and liver injury in LO2 cells were induced with thapsigargin, and in BALB/c mice with tunicamycin and carbon tetrachloride (CCl4). Glycoprotein 130 (gp130) expression, the degrees of ER stress, and hepatocyte necroptosis were assessed., Results: ER stress significantly upregulated gp130 expression in LO2 cells and mouse livers. The silencing of activating transcription factor 6 (ATF6), but not of ATF4, increased hepatocyte necroptosis and mitigated gp130 expression in LO2 cells and mice. Gp130 silencing reduced the phosphorylation of CCl4-induced signal transducer and activator of transcription 3 (STAT3), and aggravated ER stress, necroptosis, and liver injury in mice., Conclusion: ATF6/gp130/STAT3 signaling attenuates necroptosis in hepatocytes through the negative regulation of ER stress during liver injury. Hepatocyte ATF6/gp130/STAT3 signaling may be used as a therapeutic target in acute liver injury.

Glucokinase variant-induced maturity-onset diabetes of the young (GCK-MODY) exhibits the unique clinical features of mild fasting hyperglycemia. However, formal studies of its glucose excursion pattern in daily life in comparison with those with or without other types of diabetes are lacking. We conducted a case-control study including 25 patients with GCK-MODY, 25 A1C-matched, drug-naive patients with type 2 diabetes (T2DM), and 25 age-, BMI-, and sex-matched subjects with normal glucose tolerance (NGT). All the subjects wore flash glucose monitoring (FGM) sensors for 2 weeks, and glucose readings were masked. Glucose excursion was significantly lower in the GCK-MODY than that in A1C-matched T2DM during the daytime, but was similar during the nighttime. The daytime coefficient of variation (CV) driven by postprandial glucose could separate GCK-MODY from well-controlled T2DM, but the nighttime CV could not. In discriminating between GCK-MODY and T2DM, the area under the curve of the CV was 0.875. However, in GCK-MODY and NGT subjects, the CVs were similar at 24 h, whereas the other four excursion parameters were significantly higher in GCK-MODY than those in NGT subjects. FGM confirmed the stability and mildness of hyperglycemia in GCK-MODY patients. Postprandial regulation is a key driver of the difference in excursion between GCK-MODY and T2DM., (© 2023 by the American Diabetes Association.)

Background & Aims: It is unclear whether vitamin D supplementation contributes to gestational glucose control and whether the specific effects vary in individuals with diverse genetic and metabolic contexts. The study aimed to assess the effect of vitamin D supplementation during pregnancy on subsequent glucose levels and to identify factors modulating the response to vitamin D3 intake., Methods: We conducted a multicenter randomized controlled trial, 1720 pregnant women recruited from the three antenatal clinics of Hefei city, China, who were allocated to receive either 1600 IU/d vitamin D3 (n = 858) or 400 IU/d vitamin D3 (n = 862) for 2 months at 24-28 weeks' gestation. Outcomes were changes in serum 25-hydroxyvitamin D (25(OH)D) and fasting plasma glucose (FPG) levels from baseline, 32-36 weeks' gestation to delivery (37-41 weeks) quantified using a linear mixed model., Results: After 2 months, FPG levels of the control group significantly increased by 0.22 mmol/L (from 4.6 [0.4] mmol/L to 4.8 [1.2] mmol/L, P < 0.001) at delivery, but that of the intervention group had no significant variation (from 4.6 [0.4] mmol/L to 4.7 [1.1] mmol/L; between-group difference in changes, -0.2 mmol/L, 95% CI, -0.3 to -0.08, P = 0.015). And differences in FPG variation were found in participants with the ApaI SNP CC genotype, or BsmI-CC, TaqI-AA, FokI-AA, respectively. Pregnant women with basal 25(OH)D concentrations higher than 50 nmol/L subgroup showed the greatest decline in FPG levels (between-group difference, -0.3 mmol/L; 95% CI, -0.5 to -0.1, P < 0.001). Moreover, pregnant women with GDM, multiple pregnancies or who were overweight were more likely to have FPG decline from vitamin D treatment., Conclusions: Vitamin D supplementation significantly protected glucose homeostasis in mid-late gestation, and glycemic response to vitamin D may be dependent on basal 25(OH)D status, VDR gene polymorphism or their metabolic profiles., Trial Registration Number: ChiCTR2100051914. URL OF REGISTRATION: http://www.chictr.org.cn/showproj.aspx?proj=134700., Competing Interests: Conflict of interest All authors have no conflicts of interest or financial relationships relevant to this article to disclose., (Copyright © 2023 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: An increasing number of lung cancer patients are opting for lobectomy for oncological treatment. However, due to the unique organismal condition of elderly patients, their short-term postoperative mortality is significantly higher than that of non-elderly patients. Therefore, there is a need to develop a personalised predictive tool to assess the risk of postoperative mortality in elderly patients., Methods: Information on the diagnosis and survival of 35,411 older patients with confirmed lobectomy NSCLC from 2009 to 2019 was screened from the SEER database. The surgical group was divided into a high-risk mortality population group (≤90 days) and a non-high-risk mortality population group using a 90-day criterion. Survival curves were plotted using the Kaplan-Meier method to compare the differences in overall survival (OS) and lung cancer-specific survival (LCSS) between the two groups. The data set was split into modelling and validation groups in a ratio of 7.5:2.5, and model risk predictors of postoperative death in elderly patients with NSCLC were screened using univariate and multifactorial logistic regression. Columnar plots were constructed for model visualisation, and the area under the subject operating characteristic curve (AUC), DCA decision curve and clinical impact curve were used to assess model predictiveness and clinical utility., Results: Multi-factor logistic regression results showed that sex, age, race, histology and grade were independent predictors of the risk of postoperative death in elderly patients with NSCLC. The above factors were imported into R software to construct a line graph model for predicting the risk of postoperative death in elderly patients with NSCLC. The AUCs of the modelling and validation groups were 0.711 and 0.713 respectively, indicating that the model performed well in terms of predictive performance. The DCA decision curve and clinical impact curve showed that the model had a high net clinical benefit and was of clinical application., Conclusion: The construction and validation of a predictive model for death within 90 days of lobectomy in elderly patients with lung cancer will help the clinic to identify high-risk groups and give timely intervention or adjust treatment decisions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Zhang, Ren, Cheng, Wang, Li, Wang, Lu and Zhao.)

Background: Nodular thyroid disease is by far the most common thyroid disease and is closely associated with the development of thyroid cancer. Coal miners with chronic coal dust exposure are at higher risk of developing nodular thyroid disease. There are few studies that use machine learning models to predict the occurrence of nodular thyroid disease in coal miners. The aim of this study was to predict the high risk of nodular thyroid disease in coal miners based on five different Machine learning (ML) models., Methods: This is a retrospective clinical study in which 1,708 coal miners who were examined at the Huaihe Energy Occupational Disease Control Hospital in Anhui Province in April 2021 were selected and their clinical physical examination data, including general information, laboratory tests and imaging findings, were collected. A synthetic minority oversampling technique (SMOTE) was used for sample balancing, and the data set was randomly split into a training and Test dataset in a ratio of 8:2. Lasso regression and correlation heat map were used to screen the predictors of the models, and five ML models, including Extreme Gradient Augmentation (XGBoost), Logistic Classification (LR), Gaussian Parsimonious Bayesian Classification (GNB), Neural Network Classification (MLP), and Complementary Parsimonious Bayesian Classification (CNB) for their predictive efficacy, and the model with the highest AUC was selected as the optimal model for predicting the occurrence of nodular thyroid disease in coal miners., Result: Lasso regression analysis showed Age, H-DLC, HCT, MCH, PLT, and GGT as predictor variables for the ML models; in addition, heat maps showed no significant correlation between the six variables. In the prediction of nodular thyroid disease, the AUC results of the five ML models, XGBoost (0.892), LR (0.577), GNB (0.603), MLP (0.601), and CNB (0.543), with the XGBoost model having the largest AUC, the model can be applied in clinical practice., Conclusion: In this research, all five ML models were found to predict the risk of nodular thyroid disease in coal miners, with the XGBoost model having the best overall predictive performance. The model can assist clinicians in quickly and accurately predicting the occurrence of nodular thyroid disease in coal miners, and in adopting individualized clinical prevention and treatment strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhao, Zhang, Cheng, Wang, Li, Wang, Lu, Dong, Ren and Yang.)

Background: To evaluate the effect of arterial bicarbonate (HCO 3 - ) concentration on the accuracy of STOP-Bang questionnaire (SBQ) screening for obstructive sleep apnea (OSA)., Methods: A total of 144 patients with suspected OSA were included. Polysomnograms (PSG) and blood gas analysis were performed, and the Epworth Sleepiness Scale (ESS), STOP-Bang questionnaire, and Berlin questionnaire were completed. The correlation between the arterial HCO 3 - concentration, apnea hypopnea index (AHI), and other related indicators was analyzed. The scoring results of the ESS, SBQ, and Berlin questionnaire were compared with the PSG results, and the sensitivity and specificity were calculated in the form of a four-cell table. The changes in the sensitivity and specificity of OSA screening after SBQ alone and combined with HCO 3 - concentration were compared, and ROC curves were drawn., Results: Arterial HCO 3 - concentration was positively correlated with AHI (r = 0.537, P < 0.001). The ratio of HCO 3 - concentration ≥ 24.6 mmol/L in the non-OSA group was significantly lower than that in the OSA group (25.0% VS 80.8%, P < 0.001). The sensitivity of the SBQ was higher than that of the ESS (97.5% VS 81.7%, P < 0.001) and the Berlin questionnaire (97.5% VS 79.2%, P < 0.001). There was no statistical significance in the specificity of the three scales (25%, 37.5%, 37.5%). A combined SBQ score ≥ 3 and HCO 3 - concentration ≥ 24.6 mmol/L showed increased specificity and decreased sensitivity compared with an SBQ score ≥ 3 alone, with a corresponding AUC of 0.771 (P < 0.01) and 0.613 (P > 0.05), respectively., Conclusion: The sensitivity of the SBQ was better than that of the Berlin questionnaire and ESS. After combining arterial blood HCO 3 - concentration, the SBQ questionnaire increased the specificity of OSA prediction and decreased the sensitivity, which improved the accuracy of screening., (© 2021. The Author(s).)

Renal tubular epithelial-myofibroblast transdifferentiation (EMT) plays a central role in the development of renal interstitial fibrosis (RIF). The profibrotic cytokine interleukin (IL)-1 and the IL-1 receptor (IL-1R) also participate in RIF development, and Toll/IL-1R 8 (TIR8), a member of the Toll-like receptor superfamily, has been identified as a negative regulator of IL-1R signaling. However, the functions of TIR8 in IL-1-induced RIF remain unknown. Here, human embryonic kidney epithelial cells (HKC) and unilateral ureteric obstruction (UUO)-induced RIF models on SD rats were used to investigate the functions of TIR8 involving IL-1β-induced EMT. We showed that IL-1β primarily triggers TIR8 expression by activating nuclear factor-κB (NF-κB) in HKC cells. Conversely, high levels of TIR8 in HKC cells repress IL-1β-induced NF-κB activation and inhibit IL-1β-induced EMT. Moreover, in vitro and in vivo findings revealed that TIR8 downregulation facilitated IL-1β-induced NF-κB activation and contributed to TGF-β1-mediated EMT in renal tubular epithelial cells. These results suggested that TIR8 exerts a protective role in IL-1β-mediated EMT and potentially represents a new target for RIF treatment.

Manure, soil, and vegetable samples were collected from different-sized livestock farms in Xinxiang, China. The residues of sulfadiazine, sulfamonomethoxine, and sulfamethoxazole were analyzed by high-performance liquid chromatography. The results indicated that the concentration ranges of the three total sulfonamides in manure, soil, and vegetables were 10.13-566.23 µg kg -1 , 7.60-176.26 µg kg -1 , and 0-32.70 µg kg -1 , respectively. The mean concentrations were 219.71 µg kg -1 , 70.73 µg kg -1 , and 7.08 µg kg -1 for manure, soil, and vegetables, respectively. The mean concentrations in soil were lower than the ecotoxic effect trigger value (100 µg kg -1 ), indicating a low risk for organisms in soil. The concentrations of the three sulfonamides varied significantly in different types of vegetables and all were lower than the acceptable daily intake value (50 µg (kg day) -1 ). However, the potential ecotoxicity and danger to human and animal health via accumulation of the antibiotic in the food chain cannot be ignored.

Background: Osteoporosis is a systemic skeletal disorder that can impact a variety of bones throughout the body. Astrocyte-elevated gene-1 (AEG-1) is involved in multiple pro-tumorigenic functions and participates in various inflammatory reactions. However, whether it has an impact on osteoporosis-related cartilage repair and bone remodeling remains unknown., Methods: We utilized an ovariectomy mouse model with AEG-1 deletion to investigate the role of AEG-1 in osteoporosis. The mRNA level of AEG-1 was detected by RT-PCR, bone markers, bone volume/total volume (BV/TV), trabecular bone surface/bone volume (BSA/BV) and trabecular bone thickness (Tb. Th) were detected by micro computed tomography (µCT), bone injury was observed by HE and alcian blue staining. The contents of IL-6, IL-17, iNOS and IL-10 in peripheral blood of the three groups were detected by ELISA. The expression of OSX, coi1a1, OC, TLR4, MyD88 and NF-κB were detected by Western Blot., Results: µCT revealed increased bone volume in the AEG-1 knockout (KO) ovariectomy (OVX) group compared to the wildtype (WT) OVX group 4 weeks after surgery, indicating restored bone formation after AEG-1 deletion. Flow sorting revealed that AEG-1 deletion inhibited the production of inflammatory factors. Western blot demonstrated activation of the TLR4/MyD88/NF-κB pathway after LPS exposure, which was reduced by AEG-1 deletion. AEG-1 deletion also improved lipopolysaccharide (LPS) induced adverse reactions., Conclusions: Taken together, these findings indicate that AEG-1 deletion improves cartilage repair and bone remodeling during osteoporosis, which may partly occur through the inhibition of the TLR4/MyD88/NF-κB signaling pathway., Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-5842). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Objective: Coronavirus disease 2019 (COVID-19) is currently the most serious infectious disease in the world. An accurate diagnosis of this disease in the clinic is very important. This study aims to improve the differential ability of computed tomography (CT) to diagnose COVID-19 and other community-acquired pneumonias (CAPs) and evaluate the short-term prognosis of these patients., Methods: The clinical and imaging data of 165 COVID-19 and 118 CAP patients diagnosed in seven hospitals in Anhui Province, China from January 21 to February 28, 2020 were retrospectively analysed. The CT manifestations of the two groups were recorded and compared. A correlation analysis was used to examine the relationship between COVID-19 and age, size of lung lesions, number of involved lobes, and CT findings of patients. The factors that were helpful in diagnosing the two groups of patients were identified based on specificity and sensitivity., Results: The typical CT findings of COVID-19 are simple ground-glass opacities (GGO), GGO with consolidation or grid-like changes. The sensitivity and specificity of the combination of age, white blood cell count, and ground-glass opacity in the diagnosis of COVID-19 were 92.7 and 66.1%, respectively. Pulmonary consolidation, fibrous cords, and bronchial wall thickening were used as indicators to exclude COVID-19. The sensitivity and specificity of the combination of these findings were 78.0 and 63.6%, respectively. The follow-up results showed that 67.8% (112/165) of COVID-19 patients had abnormal changes in their lung parameters, and the severity of the pulmonary sequelae of patients over 60 years of age worsened with age., Conclusions: Age, white blood cell count and ground-glass opacity have high accuracy in the early diagnosis of COVID-19 and the differential diagnosis from CAP. Patients aged over 60 years with COVID-19 have a poor prognosis. This result provides certain significant guidance for the diagnosis and treatment of new coronavirus pneumonia.

Plasmacytoma variability translocation 1 (PVT1), an oncogene, has been reported to be highly expressed in many tumors, including human glioma, gastric cancer, and non-small cell lung cancer. Functionally, it could also regulate the development of tumor cells. However, its specific roles and pathogenesis in human gliomas are still not clear. This study investigated the function and mechanism of PVT1 knockdown in the proliferation and malignant transformation of human gliomas. We first examined the expression levels of PVT1 and miR-424 in human glioma tissues and cell lines. We also used gene manipulation techniques to explore the effects of PVT1 knockdown on cell viability, migration, invasion, and miR-424. We found that PVT1 knockdown effectively inhibited cell viability, migration, and invasion of human glioma cells and increased miR-424 expression. Based on the negative correlation between PVT1 and miR-424, we then confirmed the direct interaction between PVT1 and miR-424 using RNA immunoprecipitation (RIP) and luciferase reporter assays. Further, we established a xenograft nude mouse model to determine the role and mechanism of PVT1 on tumor growth in vivo. In addition, PVT1 knockdown was shown to promote miR-424 in vivo. In summary, the present study demonstrated that PVT1 knockdown could negatively regulate miR-424 to inhibit human glioma cell activity, migration, and invasiveness. PVT1 knockdown could negatively regulate miR-424 to inhibit cellular activity, migration, and invasiveness in human gliomas, which explained the oncogenic mechanism of PVT1 in human gliomas. It also suggested that PVT1 might be a novel therapeutic target for human gliomas.

Early neurological deterioration (END) is associated with increased risk of functional disability and mortality. However, data are limited regarding the long-term risk of poor functional outcomes. Thus we explored the association between END and long-term outcomes in patients with acute ischemic stroke.A total of 1064 patients were enrolled with acute ischemic stroke who were consecutively admitted to the 3 stroke units of Huai-He Hospital, Kaifeng, China. END was defined as an increment change of at least one point in motor power or total National Institute of Health Stroke Scale (NIHSS) score deterioration ≥2 points within the first week after admission. We retrospectively assessed the risk factors of END and prospectively explored the relationship between END and the long-term outcomes by multivariable regression models after adjusting the potential confounding factors. Outcomes were evaluated at 18 months based on modified Rankin scale (MRS) scores.Approximately 32% of first-ever ischemic stroke patients experienced END during the acute phase. END was associated with diabetes (odds ratio [OR], 2.218; 95% confidence interval [CI] 1.619-3.037), NIHSS score at admission (OR, 1.052; 95% CI 1.023-1.082), C-reactive protein (CRP) levels (OR, 1.224; 95% CI 1.066-1.406]), and homocysteine (HCY) levels (OR, 1.203; 95% CI 1.061-1.365) after adjusting related factors, such as hypertension, diabetes, NIHSS at admission, and some blood laboratory values, including direct bilirubin, total cholesterol, low-density lipoprotein, glucose, CRP, HCY, and D-dimer levels. During the follow-up period, 52 (4.9%) patients died, 160 (15.0%) recrudesced, and 317 (29.8%) suffered poor outcomes. Multivariate logistic regression analyses revealed that poor outcome was associated with END (OR, 3.366; 95% CI 2.495-4.542), age (OR, 1.028; 95% CI 1.015-1.041), body mass index (OR, 1.096; 95% CI 1.051-1.144), coronary heart disease (OR, 1.637; 95% CI 1.108-2.416), and CRP (OR, 2.474; 95% CI 1.840-3.326).The risk factors of END are multifaceted. Diabetes, NIHSS score at admission, CRP, and HCY are independent predictors of END. In addition, the results of this study indicate that END is an important predictor of poor functional outcome., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background/aims: Inhibition of the repair of 5-fluorouracil (5-FU)-induced DNA lesions may improve the responses of tumors to anticancer agents. XRCC2 is a key factor in DNA repair. However, the role of XRCC2 in the chemoresistance of colorectal cancer (CRC) treated with 5-FU remains unclear. The aim of this study is to investigate whether XRCC2 expression affects the chemosensitivity of colorectal cancer., Methods: XRCC2 expression in CRC tissues was assessed, and the outcomes were analyzed to determine the clinical importance of XRCC2 expression. Following treatment with 5-FU, the effect of XRCC2 on proliferation was evaluated via a CCK-8 assay, the effects on cell cycle distribution and apoptosis were analyzed using flow cytometry, and γH2AX foci formation assays were performed to examine the influence of 5-FU on DNA Double-strand breaks(DSBs) repair in CRC cells., Results: XRCC2 expression in CRC tissues was significantly higher than that in normal tissues, and this increased XRCC2 expression was associated with advanced T staging, M staging, TNM staging, Duke's staging, and greater liver and lymph node metastases. XRCC2 expression might be an independent prognostic indicator for CRC patients. Patients with negative XRCC2 expression exhibit greater sensitivity to treatment with 5-FU-based chemotherapy than those with positive XRCC2 expression. Moreover, our observations revealed that the knockdown of XRCC2 in CRC cells increased the sensitivities to 5-FU in terms of cell proliferation, apoptosis and cell cycle arrest. DNA DSBs repair was slower in the XRCC2-deficient cells than in the XRCC2-wild type cells., Conclusion: Our study demonstrated that XRCC2 might play an important role in CRC and function as a novel prognostic indicator and that the down-regulation of XRCC2 may be useful for sensitizing CRC cells during 5-FU chemotherapy., (© 2017 The Author(s). Published by S. Karger AG, Basel.)

Previous studies showed that C-reactive protein (CRP), an inflammatory marker, was associated with stroke severity and long-term outcome. However, the relationship between the acute-phase CRP level and discharge outcome has received little attention. We prospectively studied 301 patients with acute ischemic stroke (over a period of two weeks) from two hospital stroke wards and one rehabilitation department in Henan, China. Patients' demographic and clinical data were collected and evaluated at admission. Poor discharge outcome was assessed in patients at discharge using the Modified Rankin Scale (MRS > 2). Multivariate logistic regression analysis was performed to determine the risk factors of poor discharge outcome after adjusting for potential confounders. Poor discharge outcome was observed in 78 patients (25.9%). Univariate analyses showed that factors significantly influencing poor discharge outcome were age, residence, recurrent acute ischemic stroke, coronary heart disease, the National Institutes of Health Stroke Scale (NIHSS) score at admission, non-lacunar stroke, time from onset of stroke to admission, CRP, TBIL (total bilirubin), direct bilirubin (DBIL), ALB (albumin), FIB (fibrinogen) and D-dimer (p < 0.05). After adjusting for age, residence, recurrent ischemic stroke, coronary heart disease, NIHSS score at admission, lacunar stroke, time from onset of stroke to admission, CRP, TBIL, DBIL, ALB, FIB and D-dimer, multivariate logistic regression analyses revealed that poor outcome at discharge was associated with recurrent acute ischemic stroke (OR, 2.115; 95% CI, 1.094-4.087), non-lacunar stroke (OR, 2.943; 95% CI, 1.436-6.032), DBIL (OR, 1.795; 95% CI, 1.311-2.458), and CRP (OR, 4.890; 95% CI, 3.063-7.808). In conclusion, the CRP level measured at admission was found to be an independent predictor of poor outcome at discharge. Recurrent acute ischemic stroke, non-lacunar stroke and DBIL were also significantly associated with discharge outcome in acute ischemic stroke.

HSF1-mediated heat shock response is activated in most tumors and plays important roles in regulating tumor homeostasis. However, the signals underlying HSF1 activation is still not completely understood. In this paper, we find that glucose, the dominant tumor energy supplement, participates in regulating HSF1's activation in HCC cell lines. The immunoblotting results indicate that the phosphorylation of HSF1/S326, a hallmark of HSF1 activation, varies between the HCC cell lines (e.g., SMMC7721, HapG2, plc/prf5, and Chang-liver). Glucose, but not 2D-glucose, can induce the phosphorylation of HSF1 at S326 and upregulate the expression of HSF1's downstream alpha B-crystallin and Hsp70 as well as the none-heat shock proteins CSK2 and RBM23 in two tested hepatocellular carcinoma cell lines (prl/prf5 and SMMC7721). Rapamycin, an inhibitor of mTOR, can suppress the glucose-induced phosphorylation of HSF1/S326 and the expression of alpha B-crystallin. Knockdown of HSF1 with shRNA enhances the glucose-depletion-mediated inhibition of plc/prf5 cell proliferation. Our data reveal that HSF1 can be activated by glucose-mTOR pathway, providing an alternative pathway for targeting HSF1 in tumor therapy., (© 2015 International Federation for Cell Biology.)

Estrogen receptor-alpha (ER-α) gene PvuII (T/C) and XbaI (A/G) polymorphisms have been hypothesized to be associated with osteoarthritis (OA) risk by several epidemiological studies, however, the available results were inconclusive and conflicting. We conducted a meta-analysis of 10 case-control studies that included 3328 osteoarthritis cases and 6390 case-free controls. We assessed the strength of the association, using odds ratios (ORs) with 95% confidence intervals (CIs). This meta-analysis showed that the ER-α PvuII and XbaI polymorphisms were not associated with OA risk in overall population. For the PvuII (T/C) polymorphism, however, in the subgroup analysis by country, a significantly reduced risk was observed among Chinese (TC vs. CC: OR = 0.73, 95% CI 0.54-0.99, I (2) = 0%, P heterogeneity = 0.498; dominant model, OR = 0.73, 95% CI = 0.55-0.98, I (2) = 0%, P heterogeneity = 0.555). For the XbaI (A/G) polymorphism, when stratifying by sample size, a significantly elevated risk was found in sample size ≤ 500 (AA vs. GG: OR = 2.60, 95% CI 1.10-6.18, I (2) = 42.9%, P heterogeneity = 0.135; dominant model: OR = 2.04, 95% CI 1.12-3.71, I (2) = 11.4%, P heterogeneity = 0.341; and recessive model: OR = 1.69, 95% CI 1.12-2.55, I (2) = 40.2%, P heterogeneity = 0.154). No publication bias was found in the present study. This meta-analysis suggests that ER-α PvuII (T/C) polymorphism may be associated with a reduced OA risk among Chinese and the XbaI (A/G) polymorphism may not be associated with OA risk, while the observed increase in OA risk for XbaI polymorphism may be due to small-study bias.

The objective of the present study was to examine the antitumor efficacy of the ethanol extract from Artemisia dracunculus as well as the compounds isolated from it on cultured EC‑109 esophageal squamous cell carcinoma (ESCC) cells. Apoptotic activities of the compounds were also studied using flow cytometry. EC‑109 esophageal cancer cells were treated with varying concentrations of compounds 1-7 isolated from the plant as well as the ethanol extract of Artemisia dracunculus. The cytotoxicity was evaluated by MTT assay and the apoptotic studies of the compounds were determined using flow-cytometry. Effect on mitochondrial membrane potential loss ΛΨ m induced by compounds 2 and 4 was also studied in these cells. Bioassay-guided fractionation of the ethanol extract from the shoot and root parts of Artemisia dracunculus led to the isolation of 7-methoxycoumarin (1), scopoletin (2), dracumerin (3), sakuranetin (4), elimicin (5), davidigenin (6) and 6-methoxycapillarisin (7). All the compounds as well as the extract showed mild to potent cell proliferation inhibitory activities against the esophageal cell line. Sakuranetin and 6-methoxycapillarisin were found to have the most potent effects in inhibiting the cell proliferation. The 2 potent compounds, sakuranetin and 6-methoxycapillarisin were evaluated for their effects on cell cycle phase distribution (DNA damage) as well as their effects on mitochondrial membrane potential loss ΛΨ m. Both compounds induced DNA damage as well as mitochondrial membrane potential loss in esophageal cancer cells. The study suggests that compounds, Sakuranetin and 6-methoxycapillarisin isolated from Artemisia dracunculus possess potent anticancer effects by inducing DNA damage in these cells., (© Georg Thieme Verlag KG Stuttgart · New York.)

Researches have showed that interleukin family or receptors play a role in many human tumor progressions including esophageal carcinoma. In this study, we examined the expression of interleukin-8 receptor 2 (IL-8R2) and analyze the relationship between it and esophageal carcinoma clinical characteristics. IL-8R2 protein expression was confirmed by immunohistochemistry and immunofluorescence arrays and was analyzed further via Western blot and qRT-PCR analysis in frozen tissues. The correlation between their expression levels and clinical characteristics were evaluated by Mann-Whitney and Kruskal-Wallis test. Via Kaplan-Meier plots and Cox proportional hazard models, overall survival (OS) was analyzed. Compared with normal esophageal tissue, IL-8R2 protein was overexpressed significantly in esophageal cancer (p < 0.05) and was observed both in cytoplasm and nuclear. The lower expression of IL-8R2 protein was observed with higher p staging of esophageal cancer, and the significant association between them was confirmed (p = 0.000), and in advanced p T stage, the similar result was obtained (p = 0.015); however, compared with lymph node metastasis-negative group, it is no significant difference in positive group (p = 0.152). In a Kaplan-Meier analysis, compared with IL-8R2 low expression, IL-8R2 high expression identified a group of patients with the longest OS. Cox proportional hazard models revealed that IL-8R2 predicted long time to OS. The higher expression of IL-8R2 was found in early esophageal carcinoma, which may indicate that IL-8R2 plays an important role and is better prognostic factor in esophageal cancer development.

Objective. Preoperative radio(chemo)therapy (pR(C)T) appears to increase postoperative complications of rectal cancer resection, but clinical trials have reported conflicting results. The objective of this meta-analysis was performed to assess the effects of pR(C)T on anastomotic leak after rectal cancer resection. Methods. PubMed, Embase, and the Cochrane Library were searched from January 1980 to January 2014. Randomized controlled trials included all original articles reporting anastomotic leak in patients with rectal cancer, among whom some received preoperative radiotherapy or chemoradiotherapy while others did not. The analysed end-points were the anastomotic leak. Result. Seven randomized controlled trials with 3375 patients were included in the meta-analysis. 1660 forming the group undergoing preoperative radiotherapy or chemoradiotherapy versus 1715 patients undergoing without preoperative radiotherapy or chemoradiotherapy. The meta-analyses found that pR(C)T was not an independent risk factor for anastomotic leakage (OR 1.02, 95% CI 0.80-1.30; P = 0.88). Subgroups analysis was performed and the result was not altered. Conclusions. Current evidence demonstrates that pR(C)T did not increase the risk of postoperative anastomotic leak after rectal cancer resection in patients.

This work was designed to study the interaction between 5-Methyluridine and human serum albumin (HSA) under simulative physiological conditions using fluorescence spectroscopy in combination with molecular modeling technique for the first time. Static quenching was suggested by the fluorescence measurement. The binding constants (K) were calculated according to the relevant fluorescence data at different conditions including temperature. Thermodynamic parameter, different conditions including temperature to determine enthalpy change and entropy change, indicating the hydrophobic force played a major role in the binding interaction between 5-Methyluridine and HSA. The experimental result was in correspondence with molecular modeling theory.

This study was designed to investigate the interaction between (S)-2-(9H-purin-6-ylamino)-4-(methylthio) butanoic acid (PYMBA) and human serum albumin (HSA) using fluorescence spectroscopy. The combination of UV absorption and molecular docking under simulative physiological conditions was also applied to comprehensively understand the binding mechanism of PYMBA to HSA. Fluorescence data indicated that PYMBA has a strong ability to quench the intrinsic fluorescence of HSA. The binding constants (K) at different temperatures, thermodynamic parameters including enthalpy change (DeltaH) and entropy change (DeltaS) of PYMBA-HSA were correlated to the relevant fluorescence data, which suggested that the hydrophobic force played a very important role for the PYMBA binding to the HSA. The experimental results were in agreement with the results obtained via a molecular docking study. The effects of other ions on the binding constants were also studied.

This study was designed to examine the interaction of 8-bromoadenosine with human serum albumin (HSA) by fluorescence spectroscopy in combination with molecular modeling under simulative physiological conditions. The results of fluorescence measurements indicate that 8-bromoadenosine has a strong ability to quench the intrinsic fluorescence of HSA through static quenching procedure. The binding constants (K) at different temperatures and thermodynamic parameters, enthalpy changes (DeltaH) and entropy changes (DeltaS) were calculated according to the fluorescence data. The results showed that the hydrophobic force played the major role in the binding of 8-bromoadenosine to HSA. The fluorescence experimental results were in agreement with the results obtained by molecular modeling study. The effects of some normal positive and negative ions on the binding constants were also discussed. Moreover, the synchronous fluorescence technique was used to characterize the interaction of 8-bromoadenosine to HSA and successfully applied to determine the total proteins in human serum, urine and saliva samples at room temperature under the optimum conditions with a wide linear range and satisfactory results.

The binding of 2'-deoxyuridine to human serum albumin (HSA) was investigated by fluorescence spectroscopy in combination with molecular modeling under simulation of physiological conditions. The quenching mechanism was suggested to be static according to the fluorescence measurement. The thermodynamic parameters: enthalpy change (DeltaH) and entropy change (DeltaS) were calculated to be -18.87kJ/mol and 24.00J/(molK) according to the Vant'Hoff equation. These data suggest that hydrophobic interactions are the predominant intermolecular forces stabilizing the complex. Experimental results are in agreement with the results obtained by molecular modeling study. In addition, the effects of common ions on the binding constants were also studied at room temperature.

This paper reports the determination of calcium in brains of rat by ICP-AES. The recovery rate is 97%, the RSD is 1.16%, and the results are satisfactory. The interference effects of phosphor on the calcium under various operating conditions in ICP-AES were studied.