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Although immune checkpoint inhibition in particular has shown promise in cancer immunotherapy, it is not always efficient. Recent studies suggest that SMARCAL1 may play a role in tumor immune evasion, yet its pan-cancer role is unclear. We conducted a comprehensive analysis of SMARCAL1 using TCGA, GTEx, and CCLE databases, evaluating its expression, genetic alterations, epigenetic modifications, and their clinical correlations across 33 cancer types. Our findings indicate that SMARCAL1 is overexpressed in several cancers, such as Glioma, LUAD, KIRC, and LIHC, impacting prognosis. Elevated SMARCAL1 is linked to poor outcomes in Glioma, LUAD, and LIHC but correlates with better survival in KIRC. We also found significant associations between SMARCAL1 expression and DNA methylation in 13 cancers. Furthermore, SMARCAL1 expression correlates with immune infiltration, suggesting it as a potential therapeutic target in cancer immunotherapy. This study underscores the need for further research on SMARCAL1 to enhance immunotherapeutic strategies., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

This study aimed to investigate the effects of dietary fluoride (F) and curcumin (Cur) supplementation on the tibial biomechanical performance, histopathology, and behavior of pullets. Four dietary F levels (0, 400, 800, 1200 mg/kg) supplemented with CUR (0, 200 mg/kg) were used to create 8 experimental groups in Hyline Brown pullets. Behavioral study results showed that supplements of 1200 mg/kg F reduced the percentages of feeding, walking, standing, and preening behaviors while increasing the percentage of lying behavior (P < 0.05). This is associated with F-induced tibial elastic modulus, maximum stress, and stiffness coefficient were reduced and toughness coefficient was increased (P < 0.05). F-induced tibial cortical bone thickened, trabecular bone widened, and excessive accumulation of bone collagen fibers (P < 0.05) in the tibia explained the biomechanical properties reduction in Hyline Brown pullets. Additionally, the loss of antioxidant capacity was mediated by excessive F-accelerated pathological damage to the bone (P < 0.05). Supplementation with 200 mg/kg CUR alleviated abnormal behavior, expansion of the trabecular bone, accumulation of collagen fibers, and loss of antioxidant capacity (P < 0.05). In conclusion, F reduced the antioxidant level of the body, caused tibia histopathological damage, destroyed the tibia biomechanical properties, and caused abnormal behavior of pullets. Supplementation with 200 mg/kg CUR attenuates F-induced oxidative and tibia damage and rectifies abnormal behavioral traits., Competing Interests: Declaration of competing interest The authors 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.)

To investigate the effect of trace element molybdenum (Mo) on the receptivity of porcine endometrial epithelial cells (PEECs) and evaluate Mo toxicity and its potential molecular mechanisms, Mo-treated PEECs models were established by incubating the cells with various concentrations of medium containing Mo (0, 0.005, 0.020, 0.200, and 5 mmol/L MoNa 2 O 4 ·2H 2 O). The results showed that Mo disrupted the morphology and ultrastructure of PEECs, triggered blurred cell edges, cell swelling, cell cycle arrest, and increased apoptosis. At the molecular level, Mo treatment activated the TGF-β1/SMAD2 and PI3K/AKT1 pathways, causing a significant increase in matrix metalloproteinase (MMP)-9 and MMP-2 protein expression. Accompanied by markedly increased tissue inhibitors matrix metalloproteinase (TIMP)-2 and decreased TIMP-1, the balance of MMP2/TIMP-2 and MMP-9/TIMP-1 were disrupted. Ultimately, the receptivity of PEECs was destroyed by excessive Mo, which is revealed by the significant decrease of receptive marker molecules, including leukemia inhibitory factor (LIF), integrins β3 (ITGβ3), heparin-binding epidermal growth factor (HB-EGF), and vascular endothelial growth factor (VEGF). To sum up, the current study demonstrated the potential toxicity of Mo to PEECs, indicating reproductive toxicity at high Mo concentrations and suggesting that the content of Mo should be evaluated as a potential risk factor., Competing Interests: Declaration of competing interest The authors 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 © 2024 Elsevier B.V. All rights reserved.)

Background: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is often combined with respiratory failure, which increases the patient's morbidity and mortality. Diaphragm ultrasound (DUS) has developed rapidly in the field of critical care in recent years. Studies with DUS monitoring diaphragm-related rapid shallow breathing index have demonstrated important results in guiding intensive care unit patients out of the ventilator. Early prediction of the indications for withdrawal of non-invasive ventilator and early evaluation of patients to avoid or reduce disease progression are very important., Aim: To explore the predictive value of DUS indexes for non-invasive ventilation outcome in patients with AECOPD., Methods: Ninety-four patients with AECOPD who received mechanical ventilation in our hospital from January 2022 to December 2023 were retrospectively analyzed, and they were divided into a successful ventilation group (68 cases) and a failed ventilation group (26 cases) according to the outcome of ventilation. The clinical data of patients with successful and failed noninvasive ventilation were compared, and the independent predictors of noninvasive ventilation outcomes in AECOPD patients were identified by multivariate logistic regression analysis., Results: There were no significant differences in gender, age, body mass index, complications, systolic pressure, heart rate, mean arterial pressure, respiratory rate, oxygen saturation, partial pressure of oxygen, oxygenation index, or time of inspiration between patients with successful and failed mechanical ventilation ( P > 0.05). The patients with successful noninvasive ventilation had shorter hospital stays and lower partial pressure of carbon dioxide (PaCO 2 ) than those with failed treatment, while potential of hydrogen (pH), diaphragm thickening fraction (DTF), diaphragm activity, and diaphragm movement time were significantly higher than those with failed treatment ( P < 0.05). pH [odds ratio (OR) = 0.005, P < 0.05], PaCO 2 (OR = 0.430, P < 0.05), and DTF (OR = 0.570, P < 0.05) were identified to be independent factors influencing the outcome of mechanical ventilation in AECOPD patients., Conclusion: The DUS index DTF can better predict the outcome of non-invasive ventilation in AECOPD patients., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: The aim of this study was to explore the factors influencing the treatment failure of high-flow nasal cannula (HFNC) therapy in patients with interstitial pneumonia (IP) complicated by respiratory failure., Patients and Methods: A total of 158 patients with IP and respiratory failure treated with HFNC in our hospital from January 2020 to August 2023 were selected as the study population. Based on treatment efficacy, they were categorized into the HFNC treatment failure group and the HFNC treatment success group. Clinical data were compared between the two groups. Multiple logistic regression analysis was employed to identify independent factors influencing treatment failure, and the predictive value of these factors for HFNC treatment failure was assessed using receiver operating characteristic (ROC) curve analysis., Results: After 7 days of HFNC treatment, among the 158 patients with IP and respiratory failure, 25 (15.8%) declared treatment failure, while the remaining 133 (84.2%) showed treatment success. Patients in the HFNC treatment failure group had significantly higher age, duration of IP, pre-treatment respiratory rate, C-reactive protein (CRP), and controlling nutritional status (CONUT) scores compared to the HFNC treatment success group. The PaO2/FiO2 ratio, left ventricular ejection fraction, and Glasgow Coma Scale (GCS) were significantly lower in the HFNC treatment failure group (p<0.05). Multiple logistic regression analysis revealed that pre-treatment PaO2/FiO2 ratio, CRP, CONUT, and GCS scores were independent factors influencing HFNC treatment failure in patients with IP and respiratory failure (p<0.05). Lower PaO2/FiO2 ratio and GCS scores, and higher CRP and CONUT scores were associated with an increased risk of HFNC treatment failure. ROC curve analysis indicated that pre-treatment PaO2/FiO2 ratio, CRP, CONUT, and GCS scores in patients with IP and respiratory failure had a high predictive value for HFNC treatment failure (p<0.05)., Conclusions: The HFNC failure rate in patients with IP and respiratory failure is 15.8%. Pre-treatment PaO2/FiO2 ratio, CRP, CONUT, and GCS scores are independent factors associated with HFNC treatment failure and warrant clinical attention.

Dendrobium officinale Kimura et Migo is a valuable and homologous medicine and food traditional Chinese medicine. Currently there are few studies on the anti-inflammatory activity of lipophilic components. The aim of this study was to explore the anti-inflammatory effect and mechanism of the lipophilic compounds in Dendrobium officinale. Six compounds were isolated and identified, including three bibenzyl compounds, dendrocandin U, dendronbibisline B, erianin, and three lignans, (-)-syringaresinol, (+)-syringaresinol-O-β-D-glucopyranoside, 5-methoxy-(+)-isolariciresinol. Among them, dendronbibisline B and 5-methoxy-(+)-isolariciresinol were isolated from Dendrobium officinale for the first time. Besides, we found dendrocandin U, dendronbibisline B and (-)-syringaresinol exhibited the anti-inflammation to inhibit nitric oxide secretion induced by lipopolysaccharide (LPS)/interferon (IFN-γ) in MH-S cells. Furthermore, dendrocandin U could inhibit the expression of tumor necrosis factor-α (TNF-α), Cluster of Differentiation 86 (CD86), and reduce inflammatory morphological changes of macrophages. Meanwhile, we confirmed that the anti-inflammation mechanism of dendrocandin U was to inhibit M1 polarization by suppressing toll-like receptor 4 (TLR4)/recombinant myeloid differentiation factor 88 (MyD88)/nuclear factor kappa B (NF-κB) signaling pathway. In this paper, dendrocandin U with significant anti-inflammatory activity was found from Dendrobium officinale, which could provide a basis for the study of its anti-inflammatory drugs., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Objective: To explore the role of transient elastography technology in the assessment of disease staging and treatment in patients with chronic hepatitis B virus (HBV) infection. Methods: Patients who were clinically diagnosed with chronic HBV infection at Beijing Tsinghua Changgung Hospital from January 2018 to December 2021 was collected. Liver stiffness measurement (LSM) examination was performed more than once by transient elastography. The count data were expressed as cases (%) and the χ (2) test was made. Fisher's exact test was used with theoretical frequency less than 5. The measurement data between two groups was compared by t-test. Multiple groups were compared with an analysis of variance. Results: 1 055 patients were included in this study, including 669 (63.4%) males and 386 (36.6%) females. 757 (71.8%) patients were untreated. Among the untreated patients, the LSM value in the immune clearance (10.2 ± 3.8) kPa (187 cases, 40.4%), and the reactivation stages (9.1 ± 3.4) kPa (114 cases, 24.6%) was significantly higher than that in the immune tolerance (8.7 ± 3.6) kPa (78 cases, 16.8%) and immune control stages (8.4 ± 3.5) KPa (84 cases, 18.1%), and the difference between the four groups was statistically significant ( F = 5.31 and P = 0.03). With ALT (male: 30 U/L, female: 19 U/L) as defined the normal value, the LSM value in the immune tolerance and the immune control stages were (5.8 ± 0.9) kPa and (7.1 ± 2.5) kPa, respectively, which were significantly lower than those of patients in the immune tolerance and immune control stages, and the difference was statistically significant ( P < 0.01). There were 294 (38.8%) patients with uncertain period, excluding patients with fatty liver. Patients with uncertain periods were divided into four gray zone (GZ) groups: immune tolerance stage: LSM (5.1 ± 1.3) kPa was significantly lower than GZ-A (6.5 ± 2.4) kPa, t = 2.06, P = 0.03, and the difference was statistically significant; immune control stage: LSM was (5.6 ± 1.5) kPa, which was also lower than GZ-C (6.8 ± 1.3) kPa, t = 3.08, P = 0.02, and the difference was statistically significant; immune clearance stage: LSM > 8.0 kPa. LSM values showed a year-by-year reduction in patients with expanded indications who started antiviral treatment and were followed up for three years. Conclusion: The LSM value is significantly lower after the decrease of the defined high-normal ALT value in patients with the immune tolerance and immune control stages of chronic HBV infection. The LSM values of GZ-A and GZ-C in the uncertain periods of chronic HBV infection are higher than those of patients in the immune tolerance and immune control stages.

This study was based on the observation of volatile organic compounds (VOCs), conventional gaseous air pollutants, and meteorological parameters observed at the Xinxiang Municipal Party School site from June to August 2021. The ozone (O 3 ) characteristics and sensitivity of O 3 pollution days and the control strategy of its precursors were studied using an observation-based model (OBM). It was found that the meteorological conditions were characterized by high temperature, low humidity, and low pressure in O 3 -pollution days. The concentrations of O 3 and its precursors all increased in the O 3 pollution days. Oxygenated volatile organic compounds (OVOCs) and alkanes were the highest-concentration components of VOCs on O 3 pollution days in Xinxiang, and OVOCs had the highest ozone formation potential (OFP) and hydroxyl (·OH) reactivity. According to the relative incremental reactivity (RIR) analysis, during the O 3 pollution days in Xinxiang, O 3 sensitivity was in the VOCs-limited regime in June and in the transitional regime in July and August. Ozone production was more sensitive to alkenes and OVOCs. The RIR values of the precursors in June changed throughout the day, but O 3 sensitivity remained the VOCs-limited regime. In July and August, O 3 sensitivity was the VOCs-limited regime in the morning, transitional regime at noon, transitional and NO x -limited regime, respectively in the afternoon. By simulating different precursor-reduction scenarios, the results showed that the reduction of VOCs was always beneficial to the control of O 3 , whereas the reduction of NO x had little effect on the control of O 3 and a risk of increasing O 3 .

Background: Sepsis is a systemic inflammatory response, and vascular leakage associated with acute lung injury (ALI) is an important pathophysiological process during sepsis. Schisandrin A (SchA) is a bioactive lignan which has been reported to have the anti-inflammatory effects in many studies, while whether SchA can ameliorate ALI-related vascular leakage caused by sepsis is unknown., Objective: To evaluate the role and the underlying mechanism of SchA in increase of pulmonary vascular permeability induced by sepsis., Methods: The effect of SchA on pulmonary vascular permeability was examined in rat acute lung injury model. The effect of SchA on skin vascular permeability of mice was investigated through Miles assay. MTT assay was performed to detect the cell activity, and transwell assay was used to detect the effect of SchA on cell permeability. The effects of SchA on junction proteins and RhoA/ROCK1/MLC signaling pathway were manifested by immunofluorescence staining and western blot., Results: The administration of SchA alleviated rat pulmonary endothelial dysfunction, relieved increased permeability in the mouse skin and HUVECs induced by lipopolysaccharide (LPS). Meanwhile, SchA inhibited the formation of stress fibers, reversed the decrease of expression of ZO-1 and VE-cadherin. Subsequent experiments confirmed that SchA inhibited RhoA/ROCK1/MLC canonical pathway in rat lungs and HUVECs induced by LPS. Moreover, overexpression of RhoA reversed the inhibitory effect of SchA in HUVECs, which suggested that SchA protected the pulmonary endothelial barrier by inhibiting RhoA/ROCK1/MLC pathway., Conclusion: In summary, our results indicate that SchA ameliorates the increase of pulmonary endothelial permeability induced by sepsis through inhibition of RhoA/ROCK1/MLC pathway, providing a potentially effective therapeutic strategy for sepsis., Competing Interests: Declaration of Competing Interest The authors 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 © 2023 Elsevier B.V. All rights reserved.)

The management of hemorrhagic diseases and other commonly refractory diseases (including gout, inflammatory diseases, cancer, pain of various forms and causes) are very challenging in clinical practice. Charcoal medicine is a frequently used complementary and alternative drug therapy for hemorrhagic diseases. However, studies (other than those assessing effects on hemostasis) on charcoal-processed medicines are limited. Carbon dots (CDs) are quasi-spherical nanoparticles that are biocompatible and have high stability, low toxicity, unique optical properties. Currently, there are various studies carried out to evaluate their efficacy and safety. The exploration of using traditional Chinese medicine (TCM) -based CDs for the treatment of common diseases has received great attention. This review summarizes the literatures on medicinal herbs-derived CDs for the treatment of the difficult-to-treat diseases, and explored the possible mechanisms involved in the process of treatment., 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 Li, Xu, Zhao, Liu, Feng, Li, Bai and Du.)

Colon microenvironment and microbiota dysbiosis are closely related to various human metabolic diseases. In this study, a total of 72 healthy female mice were exposed to fluoride (F) (0, 25, 50 and 100 mg/L F - ) in drinking water for 70 days. The effect of F on intestinal barrier and the diversity and composition in colon microbiota have been evaluated. Meanwhile, the relationship among F-induced colon microbiota alterations and antimicrobial peptides (AMPs) expression and short-chain fatty acids (SCFAs) level also been assessed. The results suggested that F decreased the goblet cells number and glycoprotein expression in colon. And further high-throughput 16S rRNA gene sequencing result demonstrated that F exposure induced the diversity and community composition of colonic microbiota significantly changes. Linear Discriminant Analysis Effect Size (LEfSe) analysis identified 11 predominantly characteristic taxa which may be the biomarker in response to F exposure. F-induced intestinal microbiota perturbations lead to the significantly decreased SCFAs levels in colon. Immunofluorescence results showed that F increased the protein expression of interleukin-17A (IL-17A) and IL-22 (P < 0.01) and disturbed the expression of interleukin-17 receptor A (IL-17RA) and IL-22R (P < 0.05 or P < 0.01). In addition, the increased expression of IL-17A and IL-22 cooperatively enhanced the mRNA expression of AMPs which response to F-induced microbiota perturbations. Collectively, destroyed microenvironment and disturbed AMPs are the primary reason of microbiota dysbiosis in colon after F exposure. Colonic homoeostasis imbalance would be helpful for finding the source of F-induced chronic systemic diseases., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To use evidence-based medicine to systematically evaluate the effectiveness and safety of acupuncture therapy for improving anorexia in tumor patients., Methods: We queried the China National Knowledge Infrastructure Database (CNKI), China Science and Technology Journal Database (VIP), Wanfang Data, PubMed, Cochrane Library, and Embase databases to identify reports of randomized controlled trials (RCTs) that applied acupuncture therapy to improve anorexia in tumor patients, and used Rev Man 5.3 software to conduct a Meta-analysis of the effective rate, appetite score, Karnofsky Performance Status (KPS) score, Functional Assessment of Anorexia/Cachexia Therapy (FAACT) appetite scale, and body weight in each study. Subgroup analysis was conducted based on whether radiotherapy or chemotherapy were also administered., Results: A total of 10 RCTs were included with a total of 648 patients, including 343 patients in the treatment group and 305 patients in the control group. The Meta-analysis results showed that the clinical efficacy, appetite score, KPS score, and FAACT score of the treatment group (which received acupuncture to improve appetite) were better than those of the control group, and the difference was statistically significant (P < 0.05); however, there was no statistically significant difference in body weight between the treatment group and the control group (P > 0.05). The results of the subgroup analysis showed that the effective rate and appetite score for patients with long-term and chronic loss of appetite who underwent acupuncture were better than those of the control group, and the difference was statistically significant (P < 0.05)., Conclusions: Acupuncture therapy has good efficacy and safety in the treatment of anorexia in tumor patients, and it also has good efficacy and safety for long-term and chronic loss of appetite. The reliability and stability of the above results need to be confirmed by high-quality RCTs with larger sample sizes.

Taking the main production area of yam in North China Plain as the research area, we analyzed the status of soil fertility and fertilizer application in yam production through field investigation and tracking monitoring, examined soil nutrient balance using the input-output model of nutrients in agricultural system, and assessed the environmental risks in the yam planting system. The results showed that: 1) the contents of soil organic matter and total N were extremely low, and the contents of available P and available Zn were both low; both nitrate and available Cu contents were at the middle level, the contents of soil slowly available K, available S, and exchangeable Ca and Mg were all extremely high, the contents of available K, available Fe, and available Mn were all at high level; 2) The nitrogen (N), phosphorus (P 2 O 5 ), and potassium (K 2 O) inputs were 575-943 kg·hm -2 , 341-981 kg·hm -2 , and 655-1219 kg·hm -2 during the whole growth period of yam, with chemical fertilizer accounting for 83.0%, 88.6%, and 91.3%, respectively; The input imbalance between organic and inorganic fertilizer, as well as the excessive nutrients input were prominent; 3) The surplus rate of soil nitrogen, phosphorus and potassium reached 271.14 kg·hm -2 , 466.34 kg·hm -2 , and 739.97 kg·hm -2 , with corresponding surplus ratio of 48.7%, 258.1%, and 324.5%, respectively, which all exceeded the environmental safety threshold and were classified as moderate risk, severe risk, and severe risk, respectively. The overall environmental risk caused by chemical fertilizer application in yam production had reached severe risk level.

Objective: To evaluate the use of transarterial chemoembolisation (TACE) combined with microwave ablation (MWA) to treat patients with hepatocellular carcinoma (HCC) and type Ⅱ-Ⅲ portal vein tumour thrombosis (PVTT) intolerant to targeted drug (TG) therapy., Methods: A total of 18 patients with HCC and type Ⅱ-Ⅲ PVTT intolerant to TG were enrolled between June 2015 and December 2019, who were treated with TACE + MWA (MWA group). 24 patients were treated with TACE + TG (TG group; control cohort). Time to progression and overall survival (OS) were analysed along with the incidence of adverse events., Results: The median follow-up time was 19.0 months (9.0-32.0 months). The median OS was 17.0 months (8.3-29.3 months; MWA group) and 13.5 months (5.5-22.5 months; TG group) and was not significantly different. The 1- and 2 year OS was also comparable (MWA group: 66.7%, 44.4% vs Target group: 41.7%, 29.2%). Time to progression showed no distinct differences (MWA group: 11.5 months; TG group: 9.0 months) between the two groups. Moreover, the incidence of major Grade 3-4 adverse events in the MWA group (5.6%) was similar to those in the TG group (8.3%)., Conclusion: TACE + MWA and TACE + TG were comparable in their safety and efficacy in patients with HCC, type Ⅱ-Ⅲ PVTT, and intolerance to TG., Advances in Knowledge: TACE + MWA can be used as a palliative treatment alternative for TACE + TG in patients with HCC, type Ⅱ-Ⅲ PVTT, and intolerance to TG.

Background: Immunophenotyping of blood lymphocytes is an essential tool to evaluate the immune function of patients with immunodeficiency or autoimmunity. Predominately identified CD4 + T cell subsets, Th1, Th2, Th17, as well as regulatory T (Treg) cells, play crucial roles in several immunological and pathological conditions. Considering the variations in cell counts among populations and ethnicities, specific CD4 + T cell subset reference values need to be locally established to enable meaningful comparisons and accurate data interpretation in clinical and research settings. Therefore, the aim of this study was to establish distributions and reference ranges for blood CD4 + T cell subpopulations in age- and sex-balanced healthy adults of a Han Chinese population in Shanxi Province, North China., Methods: Peripheral blood CD4 + T cell subsets were examined in 150 healthy volunteers (75 males, 75 females) aged 20-70 years with a four-color FACSCalibur flow cytometer., Results: Reference value percentages (absolute counts, cells/μl) were defined as 95% of the population for cell types as follows: CD4 + T, 23.78-51.07 (360-1127); Th1, 0.43-39.62 (2.64-276.21); Th2, 0.27-3.57 (1.80-27.14); Th17, 0.22-2.62 (1.10-19.54); and Treg, 2.17-7.94 (13.47-64.58). The ranges for the Th1:Th2 and Th17:Treg ratios were 0.59-52.37 and 0.04-0.76, respectively. Notably, a significant increase was observed in the values of Treg cells in older individuals, and the numbers of Treg cells in females also tended to decrease when compared to those in males. Therefore, we established the distribution and reference range of CD4 + T cell subsets based on age and sex, demonstrating the lowest values of Treg cells in younger females., Conclusions: Collectively, our data provide population-, age-, and sex-specific distributions and reference ranges of circulating CD4 + T cell subpopulations, which can be adopted to guide clinical decisions and interpretation of immunophenotyping data in the Han Chinese population in Taiyuan, Shanxi Province, China. In addition, the low expression of peripheral Treg cells in younger females may be associated with the predisposition of females to autoimmune diseases.

With the continuous development of the earth observation technology, the spatial resolution of remote sensing images is also continuously improved. As one of the key problems in remote sensing images interpretation, the classification of high-resolution remote sensing images has been widely concerned by scholars at home and abroad. With the improvement of science and technology, deep learning has provided new ideas for the development of image classification, but it has not been widely used in remote sensing images processing. In the background of remote sensing huge data, the remote sensing images classification based on deep learning proposed in the study has more research significance and application value. The study proposes a high-resolution remote sensing images classification method based on an improved convolutional neural network. The traditional convolutional neural network framework is optimized and the initial structure is added. The actual classification results of radial basis functions and support vector machine are compared horizontally. The classification results of hyperspectral images were presented that the improved method can perform better in overall accuracy and Kappa coefficient. The commission errors of support vector machine classification method are more than 6 times of that of the improved convolutional neural network classification method and the overall accuracy of the improved convolutional neural network classification method has reached 97% above.

Our previous study showed that excessive fluoride (F) intake can induce liver dysfunction. The aim of this study was to investigate the mechanisms of F-induced mitochondrial damage resulting in liver dysfunction. Damaged mitochondrial ultrastructure and state of liver cells were estimated by TEM, TUNEL staining and BrdU measurement. The ROS level and ATP content in the liver tissue were measured by ELISA kit. Meanwhile, optic atrophy (OPA1), mitofusin-1 (Mfn1), NDUFV2, SDHA, CYC1, and COX Ⅳ expression levels were measured through real-time PCR and Western-blot. Results showed that the ROS level increased, thereby resulting in mitochondrial ultrastructure damage and abundant liver cells presented evident apoptotic characteristics after F treatment. Decreased ATP content and the abnormal expression of OPA1, Mfn1, NDUFV2, SDHA, CYC1, and COX Ⅳ of the liver tissue were observed. In conclusion, excessive F-induced mitochondrial respiratory chain damaged and mitochondrial fusion disorder resulted in liver dysfunction., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: Regulatory T (Treg) cells are crucial players in the prevention of autoimmunity. Mechanistic target of rapamycin (mTOR) signalling negatively controls the development and function of Treg cells. The aim of the present study was to evaluate the effects of rapamycin, under the generic name sirolimus, on CD4+CD25+FoxP3+ Treg cells in rheumatoid arthritis (RA) patients with low disease activity or in DAS28 remission., Methods: Fifty-five RA patients and 60 healthy controls were enrolled in this study. All patients had previously received conventional disease-modifying anti-rheumatic drugs (DMARDs) and were considered to have a low DAS28 score (≤3.2). Peripheral blood samples and clinical information were obtained at baseline and following 6 and 12 weeks of sirolimus treatment, or after 12 weeks of conventional treatment. Peripheral blood samples were also obtained from the healthy controls. The circulating levels of lymphocyte subpopulations were assessed by flow cytometry., Results: Thirty-five patients received sirolimus and 20 patients continued treatment with conventional DMARDs. The absolute counts and proportions of CD4+CD25+FoxP3+ Treg cells were significantly lower in all RA patients with DAS28 ≤ 3.2 as compared with those in healthy controls. By contrast, the difference in circulating Th17 cell numbers was not significant. Sirolimus administration resulted in elevations in circulating Treg cell numbers and significant reductions in the Th17/Treg cell ratio, whereas the circulating level of Treg cells and the Th17/Treg cell ratio in patients under conventional treatment both showed a tendency of reduction. Furthermore, a greater proportion of patients under sirolimus treatment achieved DAS28-based remission at 12 weeks., Conclusions: Sirolimus can favourably expand Treg cells in RA patients with DAS28 ≤3.2, consequently restoring a healthy balance of Th17/Treg cells, which might improve the likelihood of long-term and sustained clinical remission and reduce the probability of disease flare-ups in RA.

Objective: To analyze the clinical characteristics of oral candidiasis (OC) in in-patients with rheumatism, in order to provide theoretical basis for the prevention and treatment of OC in rheumatism patients. Methods: One thousand eight hundred and eight in-patients were recruited in the Department of Rheumatology, the Second Hospital of Shanxi Medical University from January 2017 to December 2017. The patients included 607 males and 1 201 females. Their average age was (49.5±15.5) years old with a ranging from 14 to 81 years. According to occurrence of OC or not, the patients were divided into OC group and non-OC group. The differences of general data, primary diseases, laboratory examinations, usage of glucocorticoid and immunosuppressant therapy were compared between the two groups, and the risk factors of OC occurrence were analyzed. Results: Two hundred and sixty-nine patients had OC and 1 539 patients had no OC. Age [(54.9±14.7) years], duration of illness [(9.4±4.4) years] and hospital stay [(15.3±5.7) d] in OC group were significantly longer than those in non-OC group. OC incidence in patients with connective tissue disease (CTD) [17.40% (193/1 109)] was higher than that in non-CTD patients [10.87% (75/699)] ( P< 0.001). OC most likely occurred in patients with such CTD as Sjögren syndrome (SS) and Behcet syndrome. OC incidence in non-CTD patients with osteoarthritis (OA) was highest. The salivary flow rate in OC group [(0.65±0.45) ml/min] was significantly lower than that in non-OC group [(0.78± 0.39) ml/min] ( t= 2.394, P= 0.017). There was no statistical differences in other laboratory examinations between the two groups, including white blood cells (WBC), lymphocyte, platelet count, liver function, renal function, erythrocyte sedimentation rate, C-reactive protein, procalcitonin, immunoglobulin G, immunoglobulin M, immunoglobulin A, C(3), C(4) and so on. OC incidence in patients using prednisone≥15 mg/d [17.16% (133/775)] was higher than that in patients using prednisone<15 mg/d [12.53% (94/750)] and patients not using prednisone [14.84% (42/283)] ( P< 0.05). The incidence of OC in patients with immunosuppressant therapy [16.11% (226/1 403)] was statistically higher than that in non-immunosuppressant patients [10.62% (43/405)] ( P< 0.01). Logistic regression analysis showed that the risk factors of OC occurrence included primary diseases ( P< 0.001), age ( P< 0.001), duration of illness ( P= 0.001) and duration of hospitalization ( P= 0.002). Conclusions: OC occurred commonly in rheumatism in-patients, especially in elder patients, patients with long duration of illness and hospital stay. OC incidence in CTD patients is significantly higher than that in non-CTD patients. Glucocorticoid and immunosuppressant therapy might significantly reduce the anti-fungal immunity of the patients.

Background: Excretory/secretory products (ESPs) released by parasites influence the development and functions of host dendritic cells (DCs). However, little is known about changes of DNA (hydroxy)methylation on DC development during Fasciola gigantica infection. The present study aimed to investigate whether F. gigantica ESPs (FgESPs) affects the development and functions of buffalo DCs through altering the DNA (hydroxy)methylation of DCs., Methods: Buffalo DCs were prepared from peripheral blood mononuclear cells (PBMCs) and characterized using scanning and transmission electron microscopy (SEM/TEM) and quantitative reverse transcriptional PCR (qRT-RCR). DCs were treated with 200 μg/ml of FgESPs in vitro, following DNA extraction. The DNA methylome and hydroxymethylome were profiled based on (hydroxy)methylated DNA immunoprecipitation sequencing [(h)MeDIP-Seq] and bioinformatics analyses. qRT-RCR was also performed to assess the gene transcription levels of interest., Results: FgESPs markedly suppressed DC maturation evidenced by morphological changes and downregulated gene expression of CD1a and MHC II. Totals of 5432 and 360 genes with significant changes in the 5-methylcytosine (5-mC) and the 5-hydroxymethylcytosine (5-hmC) levels, respectively, were identified in buffalo DCs in response to FgESPs challenge. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that these differentially expressed genes were highly enriched in pathways associated with immune response. Some cancer-related pathways were also indicated. There were 111 genes demonstrating changes in both 5-mC and 5-hmC levels, 12 of which were interconnected and enriched in 12 pathways. The transcription of hypermethylated genes TLR2, TLR4 and IL-12B were downregulated or in a decreasing trend, while the mRNA level of high-hydroxymethylated TNF gene was upregulated in buffalo DCs post-exposure to FgESPs in vitro., Conclusions: To our knowledge, the present study provides for the first time a unique genome-wide profile of DNA (hydroxy)methylation for DCs that interact with FgESPs, and suggests a possible mechanism of FgESPs in suppressing DC maturation and functions that are involved in TLR signaling.

This study aimed to determine the effect of excessive fluoride (F) on the morphological characteristics of the small intestine and the contents of serum cytokines in rats. A total of 48 3-week-old healthy female Sprague-Dawley rats were randomly divided into four groups (n = 12). The control group was given deionized distilled water, while the F treatment groups were treated with water containing 25, 50, and 100 mg F - /L. After 70 days of treatment, the duodenum, the jejunum, and the ileum were collected to measure the developmental parameters and the distribution of intestinal glycoproteins, goblet cells, and mast cells through Pannoramic Viewer, Periodic Acid-Schiff (PAS) staining, Alcian blue and periodic acid-Schiff (AB-PAS) staining, and toluidine blue staining, respectively. The contents of cytokines, namely, interleukin (IL)-1β, IL-2, IL-6, and tumor necrosis factor (TNF)-α, in serum were detected via enzyme-linked immunosorbent assay (ELISA). Results showed that the villus height, crypt depth, villus height to crypt depth ratio, goblet cells, glycoproteins, and mast cells of the small intestine significantly decreased (P < 0.05 or P < 0.01) in the F treatment group. The contents of IL-1β, IL-2, IL-6, and TNF-α were significantly lower in the F treatment group than in the control group (P < 0.05 or P < 0.01). In summary, excessive F intake impaired intestinal development and immune function by decreasing the developmental parameters and the distribution of immune cells, glycoproteins, and cytokines.

Background and Objective: Bevacizumab (BVZ) is a recombinant humanized antibody that inhibits the vascular endothelial growth factor A (VEGFA) and is used for the treatment of various types of cancer. BVZ is primarily given by the intravenous drip (I.V.), which often leads to low efficacy and various side effects. Therefore, the present study was to evaluate the effect of local delivery of BVZ against triple-negative breast cancer (TNBC) xenograft tumors., Methods: Mice 4T1 TNBC cells were engrafted in female BALB/c mice. After the tumors reached about 5 mm (diameter), animals were treated with BVZ through the local injection from four directions around the tumors. The tumor growth, survival and potential mechanisms of action were evaluated., Results: The growth and microvessel density of engrafted tumors were dramatically reduced with the tumor inhibition rate of 32.8 ± 3%. No obvious side effects were observed. The expression of VEGFA, VEGF receptor (VEGFR), matrix metalloproteinase (MMP)-2, MMP-9, Delta-like ligand 4 (DLL4) and Integrin-5 was significantly reduced in TNBC tumor tissues. In contrast, tissue inhibitor of matrix metalloproteinase (TIMP)-2 was significantly upregulated in xenograft tumors. Additionally, local delivery of BVZ led to the reduction of VEGFA and tumor necrosis factor (TNF)-alpha in the serum. Protein-protein interaction (PPI) analysis revealed that the proteins altered by the local delivery of BVZ were associated with angiogenesis and regulation of cell migration., Conclusion: This study provided evidence associated with local delivery of BVZ against TNBC tumors supporting the use of BVZ local injections to overcome some of the disadvantages associated with I.V. therapy with BVZ., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This study was designed to investigate the effects of excessive fluoride on spleen toxicity. Twenty-four healthy female rats were randomly divided into two groups, each of 12 rats. Each group of female rats was given a control diet and either F - = 0 mg/L or an excessive F - = 150 mg/L in the drinking water for 120 days. The histomorphological and ultrastructural changes in their splenic tissues were observed under light and transmission electron microscopes. DNA damage and splenocyte apoptosis were examined using the micronucleus (MN) assay, single-cell gel electrophoresis (SCGE), and flow cytometry. The expression levels of cytokines, including interleukin (IL)-1β, IL-2, IL-6, and tumor necrosis factor (TNF)-α, were determined through immunohistochemistry and Western-blot analysis. Results demonstrated that the histomorphological characteristics and ultrastructure of the splenic tissues were affected by excessive fluoride. Nuclear dying, nuclear membrane dissolution, mitochondrial vacuolation, and endoplasmic reticulum dilation were observed. SCGE and MN assays showed that the nuclear DNA of splenocytes was damaged by fluoride treatment, and splenocyte apoptosis was exacerbated in the fluoride group. With damage to the splenocyte structure and DNA, the protein expression levels of IL-1β, IL-2, IL-6, and TNF-α were significantly downregulated by exposure to fluoride. Excessive fluoride ingestion caused splenic pathological damage and abnormal cytokine expression in female rats.

Excessive fluoride intake has a strong female reproductive toxicity, which can result in follicular developmental dysplasia and decrease oocytes developmental potential. The underlying mechanisms of fluoride-induced mitochondrial dysfunction in ovarian granulosa cells remain largely unknown. In this study, the ultrastructure changes of mitochondria and DNA damage in ovarian granulosa cells were observed under transmission electron microscope and TUNEL staining. Then, the ATP content and ROS level in granulosa cells were measured. The expression of mitochondrial fusion proteins and mitochondrial respiratory chain complexes, including OPA1 and Mfn1, and NDUFV2, SDHA and CYC1, in the ovarian tissues were measured by immunohistochemistry, Western blot and Quantitative real-time PCR analyses. The expression of ATP5j and ATP5h in the ovarian tissues was also measured. Results show that fluoride treatment considerably damages mitochondrial ultrastructure and enhances the apoptosis of granulosa cells. The ATP content greatly decreased, whereas the ROS level increased after fluoride treatment. The expression level of Mfn1 in the ovarian tissue was up-regulated, whereas OPA1 expression had no significant change. The expression levels of NDUFV2, SDHA and CYC1 were considerably up-regulated, and the expression of ATP5j and ATP5h were down-regulated after fluoride treatment. In summary, the damage in the mitochondrial ultrastructure, ATP content decrease, ROS level increase and the abnormal expression of OPA1, Mfn1, NDUFV2, SDHA, CYC1, ATP5j and ATP5h in ovary tissue are closely associated with fluoride-induced mitochondrial dysfunction, which might be responsible for the follicular developmental dysplasia and the potential decrease in oocyte development induced by fluoride in female mice., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The present study aimed to evaluate the effect of fluoride (F) on spermatogenesis in male rats. F - at 50 and 100 mg/L was administered for 70 days, after which the testicular and epididymis tissues were collected to observe the histopathological structure under a light microscope. The ultrastructure of the testis and sperm was also examined via transmission electron microscopy. The apoptosis of spermatogenic cells was measured through terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The expression of proliferation factors, namely, proliferating cell nuclear antigen (PCNA) and Ki-67, in the testicular and epididymis tissues, were assayed through immunohistochemistry. F - at 50 and 100 mg/L significantly damaged the structure of the testis and epididymis, and the testis and sperm ultrastructure exhibited various changes, including mitochondrial swelling and vacuolization, and apsilated and raised sperm membrane. F treatment significantly increased spermatogenic cell apoptosis in the testis. PCNA (P < 0.01) and Ki-67 (P < 0.01) also presented positive expression in the testis. By comparison, no significant changes occurred in the epididymis. In summary, excessive F intake results in spermatogenesis dysfunction by damaging the testicular structure and inducing spermatogenic cell apoptosis in male rats. The positive expression level of PCNA and Ki-67 was a good response to spermatogenesis dysfunction.

In the original publication, conclusion was incorrectly updated in the article main text. The complete statement is given below.

This study was designed to investigate the mechanisms of excessive fluoride-induced apoptosis via mitochondria-mediated pathway in skeletal muscle cells (C2C12 cells). C2C12 cells were cultured with the fluoride concentrations (0, 1, and 2.5 mmol/L) for 48 h. The morphology and ultrastructural changes of C2C12 cells were observed using a light microscope and transmission electron microscope (TEM). The protein expression levels of apoptosis factors, including Bax, Bcl-2, cytochrome c (Cyt c), caspase-3, and caspase-9, were measured using real-time polymerase chain reaction (real-time PCR) and immunocytofluorescence. The morphology and ultrastructure of C2C12 cells were seriously damaged by fluoride at 1 and 2.5 mmol/L doses, including swollen mitochondria, vacuolization, ridge breakage, and disappearance of the nuclear membrane. Simultaneously, compared with the control group, the expression levels of Bax, Bcl-2, Cyt c, caspase-3, and caspase-9 were up-regulated after fluoride treatment. Excessive fluoride damages the ultrastructure in mitochondria, leading to the release of Cyt c from the mitochondria to cytoplasm in C2C12 cells; thereby, activated caspases cascade apoptosis process through a mitochondria-mediated pathway.

Excessive fluoride (F) intake decreases the development of potential oocytes by inducing oxidative stress and apoptosis in female mice in our previous study. This study aims to investigate the underlying mechanisms of F-induced follicular developmental dysplasia. Pathomorphological changes in the ovary tissues were observed under light and transmission electron microscopes. DNA damage and proliferation in granulosa cells were analysed by TUNEL staining and BrdU measurement. The protein expression of cell proliferation related regulatory factors including JNK, STAT3, STAT5, CDK2, CDK4, PCNA and Ki67 in the ovary tissues was measured by immunohistochemistry and Western blot analyses. Results indicated that the structure of granulosa cells in the ovary was seriously damaged by excessive F, evident by the swollen endoplasmic reticulum, mitochondria with vacuoles and nucleus shrinkage. F treatment also considerably enhanced the apoptosis and inhibited the proliferation of granulosa cells. The number of granulosa cells around the oocyte decreased after F treatment. The expression levels of STAT3, CDK2, CDK4 and Ki67 in the ovary tissues were up-regulated, and STAT5 and PCNA did not change significantly after F treatment, whereas JNK expression was down-regulated with increasing F dose. In summary, changes in the expression levels of JNK, STAT3, STAT5, CDK2, CDK4, PCNA and Ki67 in the JNK/STAT signalling pathway are involved in F-induced follicular dysplasia in the ovary., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: In this analysis, we aimed to systematically compare percutaneous coronary intervention (PCI) versus coronary artery bypass surgery (CABG) in terms of adverse outcomes utilizing data from a recent (2015-2017) population of patients with type 2 diabetes mellitus (T2DM)., Methods: An electronic search of recent studies (2015-2017) was carried out using 'diabetes mellitus,' 'coronary artery bypass surgery,' and 'percutaneous coronary intervention' as the main search terms. Uncomplicated T2DM patients with stable coronary artery disease (CAD), left main CAD, and multi-vessel disease were included. RevMan software (version 5.3) was used to calculate odds ratios (OR) and 95% confidence intervals (CIs)., Results: Among a total of 13,114 T2DM patients, CABG and PCI patients did not differ significantly in their rates of mortality (OR 0.90, 95% CI 0.61-1.31; P = 0.57) and cardiac death (OR 1.00, 95% CI 0.78-1.30; P = 0.98). However, rates of major adverse events, repeat revascularization, and myocardial infarction were significantly higher in the PCI group. Stroke rates did not significantly differ between the two groups., Conclusion: Mortality (1-5 years) did not significantly differ between the CABG and PCI patients with T2DM. However, rates of other major adverse events were significantly higher in the PCI patients, suggesting that CABG is more advantageous than PCI in patients with T2DM.

Objective: To analyze and summarize the surgical experience of robotic-assisted laparoscopic partial nephrectomy (RAPN) for treating renal hilar tumors, and assess the efficacy and safety of this surgery. Methods: The clinical data of 22 renal hilar tumor patients who underwent RAPN in Sir Run Run Shaw Hospital, Zhejiang University School of Medicine between September 2015 and September 2017 was analyzed. The patients included 19 males and 3 females, with an average age of (55.6 ±13.0) years old and the age range was 28-75 years. In 13 cases, the tumors were in left kidney, and 9 in the right. There were 10 large tumors (>4 cm diameter), the average tumor size was (3.7±1.9) cm. Preoperative glomerular filtration rate was normal in all cases. Results: The surgery was successfully finished in all of the cases, with no conversion to open surgery. The mean duration of the surgery was 80-270 min, with an average of (134.7±44.5) min. The blood loss was 80-500 ml, with an average of (135.9±130.7) ml, and none of the cases needed intraoperative blood transfusion. The warm ischemia time was 8-25 min, with an average of (18.2±4.0) min. The postoperative length of hospitalization was 7-23 d, with an average of (11.5±4.1) d. Serious gross hematuria occurred in 1 patient, and paroxysmal atrial fibrillation occurred in 1 patient after surgery. The post-operative pathology showed renal clear cell carcinoma in 18 cases, papillary renal cell carcinoma in 2 cases, chromophobe cell carcinoma in 1 case and well differentiated neuroendocrine tumor in 1 case. The tumor resection margin was negative in all cases. Neither local recurrence nor metastasis was observed during a follow-up of 1 to 15 months. Renal function of all the patients was in normal range. Conclusion: RAPN is a safe, useful approach and a minimally invasive operation for treating renal hilar tumors and it owns crucial advantages in complete and accurate resection of the renal hilar tumors and the reconstruction of the kidney.

Although conventional combination therapy is effective for most patients with rheumatoid arthritis (RA), many still do not respond to current therapies. Therefore, novel combination regimens that better target cellular processes involved in RA pathogenesis are required. Preliminary studies have demonstrated the beneficial effects of a combination of cyclophosphamide (CTX) and methotrexate (MTX) in models of RA. Using western blotting, real-time polymerase chain reaction, enzyme-linked immunosorbent assays, and immunofluorescent staining, we demonstrated that the combination of 4-hydroperoxy CTX (4-H-CTX) and MTX inhibited the expression of receptor activator of nuclear factor-κB ligand (RANKL) in fibroblast-like synoviocytes (FLS) treated with the interleukin (IL)-6/soluble IL-6 receptor (sIL-6R) complex. To elucidate the mechanisms underlying this effect, we treated RA-FLS with the JAK2/STAT3 inhibitor AG490 or p38MAPK inhibitor SB203580. The results showed that IL-6/sIL-6R-induced RANKL upregulation required phosphorylation-mediated activation of STAT3 and p38 signaling, and that 4-H-CTX and/or MTX inhibited RANKL expression in IL-6/sIL-6R-stimulated FLS by suppressing JAK2/STAT3 and p38MAPK signaling. This study demonstrated for the first time the inhibitory effects of 4-H-CTX and MTX on RANKL expression in IL-6/sIL-6R-stimulated FLS via suppression of STAT3 and p38MAPK phosphorylation. These results identify promising therapeutic agents that might have clinical applications in patients with RA who are at high risk of bone erosion or do not respond well to conventional therapy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Insulin injection is the main treatment in patients with type 1 diabetes mellitus (T1DM). Even though continuous glucose monitoring has significantly improved the conditions of these patients, limitations still exist. To further enhance glucose control in patients with T1DM, an artificial pancreas has been developed. We aimed to systematically compare artificial pancreas with its control group during a 24-h basis in patients with T1DM., Methods: Electronic databases were carefully searched for English publications comparing artificial pancreas with its control group. Overall daytime and nighttime glucose parameters were considered as the endpoints. Data were evaluated by means of weighted mean differences (WMDs) and 95% confidence intervals (CIs) generated by RevMan 5.3 software., Results: A total number of 354 patients were included. Artificial pancreas significantly maintained a better mean concentration of glucose (WMD - 1.03, 95% CI - 1.32 to - 0.75; P = 0.00001). Time spent in the hypoglycemic phase was also significantly lower (WMD - 1.23, 95% CI - 1.56 to - 0.91; P = 0.00001). Daily insulin requirement also significantly favored artificial pancreas (WMD - 3.43, 95% CI - 4.27 to - 2.59; P = 0.00001). Time spent outside the euglycemic phase and hyperglycemia phase (glucose > 10.0 mmol/L) also significantly favored artificial pancreas. Also, the numbers of hypoglycemic events were not significantly different., Conclusion: Artificial pancreas might be considered an effective and safe alternative to be used during a 24-h basis in patients with T1DM.

Our previous study indicated that excessive fluoride (F) induces ATP5J and ATP5H proactive expression by interfering cardiomyocyte mitochondrial dysfunction in mice. This study aimed to investigate underlying mechanisms of F ¯ induced damage to cardiomyocytes. A total of 100 mg/L F ¯ was added to distilled water to treat Kunming mice for 70 days. Pathological and morphological changes in myocardial tissues were observed under transmission electron microscope and light microscope. Content of ATP and ATP enzyme distributed in cardiomyocytes were determined by fluorescence and ATP enzyme staining. Expression levels of troponin (Tn) C, TnI, TnT and tropomyosin (TPM) were measured by immunofluorescence, western blot, and real-time polymerase chain reaction. Contents of Ca 2+ in blood, myocardial cells and faeces were also detected by confocal microscopy and ethylenediaminetetraacetic acid. Using 100 mg/L F ¯ resulted in nuclaer enrichment, the myocardial fibre breakage and mitochondrial lysis. Following mitochondrial structure damage, contents of ATP and ATP enzyme significantly decreased in the fluoride group. Expression levels of TnT and TnI were significantly down-regulated, whereas that of TPM was up-regulated. Content of Ca 2+ in cardiomyocytes of fluoride group visibly increased. Interestingly, contents of Ca 2+ in blood and faeces decreased. These findings reveal that excessive F ingestion induces Ca 2+ metabolic disorder, and an abnormal expression of cardiac Tn are involved in F-induced cardiomyocyte damage., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

To investigate the mechanisms of fluoride-induced apoptosis, a fluoride-induced C2C12 skeletal muscle cell (C2C12 cell) model was established in this study, and the viability of the C2C12 cells was measured using an MTT assay. Cell morphological changes were observed via haematoxylin and eosin staining and transmission electron microscopy. Apoptosis was monitored through Hoechst staining. The mRNA and protein expression of PI3K, PDK1, AKT1, BAD, Bcl-2, Bax and caspase-9 were detected through real-time PCR and western blotting, respectively. The results showed that the survival rates of C2C12 cells decreased gradually with an increasing fluoride doses. The C2C12 cell structure was seriously damaged by fluoride, presenting with pyknosis, mitochondrial ridge disruption and swollen endoplasmic reticulum. Furthermore, the expression of mRNA in PI3K, BAD, Bcl-2, Bax and caspase-9 were significantly increased in the fluoride group (P < 0.01), while the expression of PDK1 was markedly decreased (P < 0.01). The expression of protein in BAD, Bcl-2 and Bax were significantly increased in the fluoride group (P < 0.01), while the expression of PDK1 and P-AKT1 was markedly decreased (P < 0.01). In conclusion, fluoride-induced apoptosis in C2C12 cells is related to the PI3K/AKT signaling pathway., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: Empagliflozin is a new, emerging oral hypoglycemic agent (OHA) which has shown significant benefits in type 2 diabetes mellitus (T2DM) patients with cardiovascular disease. In this analysis, our aim was to systematically compare the adverse drug events (ADEs) associated with a low (10 mg) versus a high (25 mg) dose of empagliflozin as (1) monotherapy, (2) as an add-on to other OHAs, and (3) as an add-on specifically to metformin, in patients who were treated for T2DM., Methods: This was a systematic review and meta-analysis of randomized controlled trials that compared empagliflozin 10 mg versus 25 mg in patients who were treated for T2DM and which reported adverse drug reactions as their clinical endpoints. Statistical analysis was carried out using the latest version of the RevMan software (ver. 5.3) whereby odds ratios (OR) and 95% confidence intervals (CI) were generated., Results: Eight trials with a total number of 8514 patients treated for T2DM were included in this meta-analysis and systematic review, of whom 4261 patients received 10 mg empagliflozin and 4253 patients received 25 mg empagliflozin. Our results showed that there were no significant differences between the patients with T2DM receiving 10 empagliflozin and those receiving 25 mg empagliflozin in terms of drug-related adverse effects (OR 1.06, 95% CI 0.93-1.21; P = 0.40, I 2  = 0%), adverse events leading to drug discontinuation (OR 0.99, 95% CI 0.86-1.14; P = 0.87, I 2  = 0%), and serious adverse events (OR 1.06, 95% CI 0.95-1.18; P = 0.31, I 2  = 0%) when empagliflozin was provided as monotherapy or as an add-on to other anti-diabetic medications. The same results were obtained when empagliflozin was used as an add-on to metformin or as monotherapy. The duration of the follow-up periods did not affect the results. However, the incidence of genital and urinary tract infections (UTIs) was significantly higher in female patients than in male patients with 10 or 25 mg empagliflozin., Conclusions: The incidence of ADEs was not significantly different in T2DM patients receiving 10 versus 25 mg empagliflozin as monotherapy or as add-on to metformin or other anti-diabetic drugs during a shorter or longer follow-up period. However, genital and UTIs were more common in female patients with T2DM irrespective of empagliflozin dosage.

Objective: The aim of this study was to evaluate right ventricular (RV) regional systolic function and dyssynchrony in patients with newly diagnosed obstructive sleep apnea using real-time three-dimensional (3D) echocardiography., Methods: Eighty-two subjects without hypertension, diabetes mellitus or any cardiac or pulmonary disease referred for evaluation of obstructive sleep apnea (OSA) had overnight polysomnography and complete echocardiographic assessment. According to the apnea hypopnea index (AHI), subjects were divided into four groups: group 1: control subjects (AHI < 5, n = 19), group 2: patients with mild OSA (AHI: 5-14, n = 21), group 3: moderate OSA (AHI: 15-30, n = 18), group 4: severe OSA (AHI > 30, n = 24). Real-time three-dimensional echocardiographic images were acquired to obtain RV regional (inflow, body and outflow) ejection fraction (EF) and time to minimum systolic volume in all subjects., Results: Body weight and body mass index were greater in the severe and moderate OSA group than those of mild and controls group (P < 0.05). There was a significant decrease in mean SaO2 and the lowest SaO2 in severe OSA when compared to other groups (P < 0.001). Inflow EF and global EF were significantly lower in moderate and severe OSA patients than in controls (P < 0.05). Inflow EF and global EF were negatively correlated with AHI (r = -0.534 and r = -0.479, respectively, P < 0.001)., Conclusions: In patients with OSA, RV inflow and global systolic function were impaired and were in inverse relationship with AHI. Evaluation of RV regional systolic function using real-time three-dimensional echocardiography may play a potential role in the noninvasive assessment of the severity of OSA., (© 2016 John Wiley & Sons Ltd.)

To investigate the effect of excessive fluoride on the mitochondrial function of cardiomyocytes, 20 healthy male mice were randomly divided into 2 groups of 10, as follows: control group (animals were provided with distilled water) and fluoride group (animals were provided with 150 mg/L F - drinking water). Ultrastructure and pathological morphological changes of myocardial tissue were observed under the transmission electron and light microscopes, respectively. The content of hydrolysis ATP enzyme was observed by ATP enzyme staining. The expression levels of ATP5J and ATP5H were measured by Western blot and quantitative real-time PCR. The morphology and ultrastructure of cardiomyocytes mitochondrial were seriously damaged by fluoride, including the following: concentration of cardiomyocytes and inflammatory infiltration, vague myofilaments, and mitochondrial ridge. The damage of mitochondrial structure was accompanied by the significant decrease in the content of ATP enzyme for ATP hydrolysis in the fluoride group. ATP5J and ATP5H expressions were significantly increased in the fluoride group. Thus, fluoride induced the mitochondrial dysfunction in cardiomyocytes by damaging the structure of mitochondrial and interfering with the synthesis of ATP. The proactive ATP5J and ATP5H expression levels were a good response to the mitochondrial dysfunction in cardiomyocytes.

The present study was conducted to investigate the mechanisms of excessive-fluoride-induced reduction of oocyte development potential in mice. The development morphology of oocyte and the changes of pathomorphology in ovary were observed. The protein expression levels of apoptosis factors, including Bax, Bcl-2, casepase-3, casepase-9 and cytochrome c, and the mRNA expression levels of antioxidant enzymes, including SOD1, GSH-Px1, CAT and inducible nitric oxide synthase were measured by Western blot and real-time PCR, respectively. DNA damage in the ovary was analysed by single cell gel electrophoresis and TUNEL staining. Results indicated that the structure and function of ovarian cells were seriously damaged, followed, the development potential of oocyte was reduced by excessive fluoride. The expression levels of apoptosis factors were up-regulated and antioxidant enzymes were significantly down-regulated. Meanwhile, the contents of ROS, MDA, NO and iNOS were significantly increased. Whereas, the activities of SOD1, GSH-Px1 and CAT was significantly decreased compared with the control group. Simultaneously, the results of DNA analysis indicated that the tail length and tailing ratio of ovarian cells were significantly increased in the fluoride group. In summary, the results provided compelling evidence that excessive fluoride intake can reduce the development potential of oocyte by inducing oxidative stress and apoptosis in the ovary of female mice., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Clinical data from 172 cases of uterine fibroids with different appearances on MRI-T2WI and accepted ultrasound guided high intensity focused ultrasound (USgHIFU) treatment were retrospectively analyzed. This study aimed to evaluate the clinical safety and efficacy of ablating different types of fibroids, classified by T2-weighted magnetic resonance imaging (MRI-T2WI). Based on MRI-T2WI signal intensities, uterine fibroids were classified as three types: hypointensive (52 cases), isointensive (64 cases) and hyperintensive (56 cases). Evaluation parameters including treatment time, ablation efficiency, percentage non-perfused volume, fibroid reduction rate, adverse reactions, symptom severity scores (SSS) and re-intervention rate were assessed from 3 months to 1 year. The percentage non-perfused volume and ablation efficiency of hyperintensive uterine fibroids were lower than those of isointensive and hypointensive uterine fibroids. All fibroids shrunk and the SSS continued to reduce at 3 and 6 months after treatment respectively. At 12-month postoperative assessments, hypointensive fibroids continued to shrink, while the isointensive fibroids enlarged but remained smaller than pre-treatment. The incident rate of postoperative Society of Interventional Radiology B-class (SIRB-class) adverse events showed no significant differences. The re-interventional rate of hyperintensive fibroids was higher than in isointensive and hypointensive groups. USgHIFU ablation of all types of fibroids were safe and effective.

The present study aims to explore the effectiveness of decompressive craniectomy with bifrontal coronal incision in the management of severe contusion and laceration of bilateral fronto-temporal lobes, as well as the outcomes of early cranioplasty. The authors performed the bifrontal decompressive craniectomy on 56 patients with contusion and laceration of bilateral frontal and temporal lobes, and their follow-up treatment outcomes were tracked within 6 months using Glasgow Outcome Scale. The results showed that 33 patients (out of 56, 58.9%) have recovered, 12 patients (out of 56, 21.4%) have moderate defects, 5 patients (out of 56, 8.9%) have severe defects, 3 patients (out of 56, 5.3%) stayed in persistent vegetative status, and the remaining 3 patients (out of 56, 5.3%) have been dead. There was no persistent temporal hollowing. No patients required revision surgery with modified titanium mesh in this study. Particularly, 28 patients have successfully accepted the early cranioplasty with bone flap or computer-assisted design titanium mesh, and showed good recovery. These results together indicated that the decompressive craniectomy with bifrontal coronal incision in the management of severe contusion and laceration of bilateral fronto-temporal lobes can significantly relieve the comorbidity of intracranial hypertension, and improve the prognosis obviously, thus finally increasing the probability of successful rescue and decreasing the probability of mortality and disability.

A total of 84 healthy female mice were kept with various concentrations of sodium fluoride (F) (0, 50, 100, 150 mg F - /L in drinking water for 90 days) and were then mated with healthy male mice for 1 week to study the effect of excessive fluoride on female reproductive function, particularly in embryo implantation. The rate of pregnancy, litter size, and the birth weight of female mice were evaluated. Ultrastructural changes of uteri tissues were observed by transmission electron microscopy (TEM). The mRNA expression levels of MMP-9 and TIMP-1 were determined by quantitative real-time PCR. The protein expression levels of MMP-9 and TIMP-1 were analyzed by western blotting. Results showed a significant decrease of litter size in mice exposed to fluoride. TEM images of uteri tissue of mice that underwent a 150 mg/L F - treatment for 90 days showed a vague nucleus, reduced microvilli, increased lysosomes, a dilated endoplasmic reticulum, and a vacuolization mitochondrion when compared with the control group. Following the damage of the structure, the expression levels of MMP-9 and TIMP-1 in uteri tissues were significantly unregulated in the F 150 group. These results show that MMP-9/TIMP-1 system disturbance and changes of histological structure in uteri tissue are involved in fluoride-induced reproductive dysfunctions.