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Alcoholic liver disease (ALD) caused by chronic alcohol abuse involves complex processes from steatosis to fibrosis, cirrhosis, and hepatocellular carcinoma, posing a global health issue. Bromodomain protein 4 (BRD4) typically serves as a "reader" modulating the functions of transcription factors involved in various biological processes and disease progression. However, the specific mechanisms underlying alcoholic liver injury remain unclear. In this study, we detected aberrant BRD4 expression in the alcohol-induced ALD mouse model of chronic and binge ethanol feeding developed by the National Institute on Alcohol Abuse and Alcoholism, consistent with the in vitro results in Aml-12 mouse hepatocytes. Blocking and inhibiting BRD4 restored the impaired autophagic flux and lysosomal functions in alcohol-treated Aml-12 cells, whereas BRD4 overexpression reduced the expression levels of autophagy marker and lysosomal genes. Furthermore, mouse BRD4 knockdown, mediated by a short hairpin RNA carried by the adeno-associated virus serotype 8, significantly attenuated the alcohol-induced hepatocyte damage, including lipid deposition and inflammatory cell infiltration. Mechanistically, BRD4 overexpression in alcoholic liver injury inhibited the expression of sirtuin (SIRT)1 in Aml-12 cells. Chromatin immunoprecipitation and dual-luciferase reporter assays revealed that BRD4 functions as a transcription factor and suppressor, actively binding to the SIRT1 promoter region and inhibiting its transcription. SIRT1 activated autophagy, which was suppressed in alcoholic liver injury via Beclin1 deacetylation. In conclusion, our study revealed that BRD4 negatively regulated the SIRT1/Beclin1 axis and that its deficiency alleviated alcohol-induced liver injury in mice, thus providing a new strategy for ALD treatment., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To evaluate the effect of preemptive analgesia with ibuprofen on postoperative pain following single posterior tooth implantation, aiming to provide a clinical reference for its application. Methods: A multicenter, randomized, double-blind, placebo-controlled parallel-group trial was conducted. A total of 82 participants were included in the trial, meeting the eligibility criteria from April 2022 to April 2024 at the Capital Medical University School of Stomatology (40 cases), Beijing TianTan Hospital, Capital Medical University (22 cases), Beijing Chao-Yang Hospital, Capital Medical University (20 cases). Participants were randomly assigned in a 1∶1 ratio to either the ibuprofen group or the control group, with each group comprising 41 individuals. Participants in the ibuprofen group received 300 mg of sustained-release ibuprofen capsules orally 15 min before surgery, while the control group received a placebo. Both groups received the same postoperative analgesic regimen for 3 days. Pain scores were assessed using the Numerical rating scale (NRS) at 30 min, 4 h, 6 h, 8 h, 24 h, 48 h, and 72 h postoperatively, and the additional use of analgesic medication was recorded from days 4 to 6 postoperatively. Results: A total of 82 participants were initially enrolled in the study, with 7 dropouts (4 from the control group and 3 from the ibuprofen group), resulting in 75 participants (37 in the control group and 38 in the ibuprofen group) completing the trial. There were no reports of adverse events such as nausea or vomiting among the participants. The ibuprofen group exhibited significantly lower pain scores at 4 h, 6 h and 8 h [1.0 (0.0, 2.0), 1.0 (0.0, 2.0), 1.5 (0.0, 3.0) ] postoperatively compared to the control group 4 h, 6 h and 8 h [2.0 (1.0, 3.0), 3.0 (1.5, 4.0), 2.0 (1.0, 4.0)] ( Z =-1.99, P =0.047; Z =-3.01, P =0.003; Z =2.10, P =0.036). The proportions of patients requiring additional analgesic medication between days 4 and 6 post-surgery were 18.4% (7/38) in the ibuprofen group and 27.0% (10/37) in the control group, with no significant difference (χ 2 =0.79, P =0.373). The median additional medication usage postoperatively was [0.0 (0.0, 0.0) pills] in the ibuprofen group and [0.0 (0.0, 1.0) pills] in the control group, with no significant difference ( Z =-0.78, P =0.439). Conclusions: Preemptive analgesia with ibuprofen effectively reduces postoperative pain following tooth implantation, representing a safe and effective perioperative pain management strategy.

Aims: This study aimed to elucidate the role of Interleukin-11 (IL-11) in hepatic fibrosis (HF) and its potential as a therapeutic target for HF treatment., Materials and Methods: We investigated IL-11 expression in patients with varying degrees of liver injury through ELISA and immunohistochemistry. A CCl 4 -induced HF mouse model was constructed to study IL-11 expression and cell apoptosis using Western blotting (WB) and other techniques. The expression of IL-11 was silenced using rAAV8 in the mouse model. In vitro stimulation of hepatic stellate cells (LX-2) with TGF-β1, and of LO-2 cells with exogenous IL-11, were performed. Cell supernatants of TGF-β1-stimulated LX-2 were used to culture LO-2 cells, with apoptosis monitored via flow cytometry and WB., Key Findings: Increased IL-11 levels were observed in patients and the HF mouse model, with silencing reducing IL-11 expression. In vitro experiments revealed increased endogenous IL-11 in TGF-β1-stimulated LX-2 cells and an increase in apoptotic index, IL11RA, and gp130 in IL-11-stimulated LO-2 cells. Cell apoptosis was reduced in the siRNA/IL11, siRNA/IL11RA, and anti-IL11 groups. WB and immunohistochemistry results showed upregulated p-JNK, p-ERK, and p-P53 expressions in the CCl 4 -induced HF mouse model and IL-11-treated LO-2 cells., Significance: Our findings suggest IL-11 enhances LX-2 cell activation and proliferation, and promotes LO-2 cell apoptosis through JNK/ERK signaling pathways. This suggests that targeting IL-11 secretion may serve as a potential therapeutic strategy for HF, providing a foundation for its clinical application in HF treatment., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Objective: This study aimed to investigate the clinical value of combined serum matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) for the prognosis of perianal fistula patients., Methods: Patients diagnosed and treated for perianal fistula by minimally invasive surgery (MIS) were enrolled. The concentrations of serum MMP-2, MMP-9 and TIMP-1 were measured at 24 h after surgery. Different levels of wound secretion, growth of granulation tissue and wound pain were used as criteria to evaluate surgical incision healing. The receiver operating characteristic curve was used to analyze the predicted assessment value., Results: The concentrations of serum MMP-2 and MMP-9 were significantly higher, while the concentrations of serum TIMP-1 at 24 h after surgery were significantly lower in the poor healing group than in the good healing group. It was further found that high levels of serum MMP-2 and MMP-9 were risk factors for poor healing, while high concentrations of serum TIMP-1 at 24 h after surgery were protective factors for poor healing., Conclusion: High concentrations of serum MMP-2 and MMP-9 and low concentrations of serum TIMP at 24 h after surgery are risk factors for poor healing in perianal fistula patients who receive MIS, and the combined test has a higher predictive value., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Ultra-precise reflectors in the advanced light source facilities urgently call for local slope error measurements with nano-radian precision. However, the existing methods currently utilized in the long trace profiler systems struggle to meet the requirements. In this paper, we present a weak-value amplification enhanced absolute local slope measurement scheme, in which the surface height difference between two adjacent points can be measured directly with precision on the pico-meter level. As a result, the absolute local slope measurement reaches a record precision level of 9.7 nrad (RMS) with a small lateral separation of 0.5 mm. Comparing to the existing methods, our scheme is more disturbance-resistant, more compact and cost-effective. The local curvature measuring capability is also validated with two synchronously parallel local slope measurement paths, between which the separation is set as 2mm. A local curvature measurement is obtained with precision of 3.4 × 10 -6 m -1 (RMS) and its corresponding slope variation is 6.8 nrad. Our method exhibits important application prospects in the field of ultra-precise surface fabrication inspection.

Sugar is crucial for grape berry, whether used for fresh food or wine. However, berry enlargement treatment with forchlorfenuron (N-(2-chloro4-pyridyl)-N'-phenylurea) (CPPU, a synthetic cytokinin) and gibberellin (GA) always had adverse effects on sugar accumulation in some grape varieties, especially CPPU. Therefore exploring the molecular mechanisms behind these adverse effects could provide a foundation for improving or developing technology to mitigate the effects of CPPU/GA treatments for grape growers. In the present study, invertase (INV) family, the key gene controlling sugar accumulation, was identified and characterized on the latest annotated grape genome. Their express pattern, as well as invertase activity and sugar content, were analyzed during grape berry development under CPPU and GA 3 treatment to explore the potential role of INV members under berry enlargement treatment in grapes. Eighteen INV genes were identified and divided into two sub-families: 10 neutral INV genes (Vv-A/N-INV1-10) and 8 acid INV genes containing 5 CWINV (VvCWINV1-5) and 3 VIN (VvVIN1-3). At the early development stage, both CPPU and GA 3 treatment decreased the hexose level in berries of 'Pinot Noir' grape, whereas the activity of three types inverstase (soluble acid INV, insoluble acid INV, and neutral INV) increased. Correspondingly, most of INV members were up-regulated by GA 3 /CPPU application at least one sampling time point during early berry development, including VvCWINV1, 2, 3, 4, 5, VvVIN1, 2, 3 and Vv-A/N-INV1, 2, 5, 6, 7, 8, 10. At maturity, the sugar content in CPPU-treated berries is still lower than that in the control. Soluble acid INV and neutral INV, rather than insoluble acid INV, presented lower activity in CPPU-treated berries. Meanwhile, several corresponding genes, such as VvVIN2 and Vv-A/N-INV2, 8, 10 in ripening berries were obviously down-regulated by CPPU treatment. These results suggested that most of INV members could be triggered by berry enlargement treatment during early berry development, whereas VvVINs and Vv-A/N-INVs, but not VvCWINVs, could be the limiting factor resulting in decreased sugar accumulation in CPPU-treated berries at maturity. In conclusion, this study identified the INV family on the latest annotated grape genome and selected several potential members involving in the limit of CPPU on final sugar accumulation in grape berry. These results provide candidate genes for further study of the molecular regulation of CPPU and GA on sugar accumulation in grape., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We prospectively studied 17 patients with spontaneous pneumothorax or giant emphysematous bulla at Rizhao Hospital of Traditional Chinese Medicine from October 2020 to March 2022. All patients underwent thoracoscopic interventional therapy, had experienced continued air leakage for 3 days with closed thoracic drainage postoperatively, had an unexpanded lung on CT, and/or failed to intervention with position selection combined with intra-pleural thrombin injection(referred to as "position plus1.0"). They were all treated with position selection combined with autologous blood (100 ml) and thrombin (5 000 U) intra-pleural injection(referred to as "position plus 2.0").The success rate of the "position plus 2.0" intervention was 16/17, and the recurrence rate was 3/17. There were four cases of fever, four cases of pleural effusion, one case of empyema, and no other adverse reactions. This study has shown that the "position plus 2.0" intervention is safe, effective, and simple for patient with persistent air leakage failed to intervention with"position plus 1.0" after thoracoscopic treatment of pulmonary and pleural diseases related to bulla.

Objective: To evaluate the effectiveness and safety of a new treatment protocol that combined "medical glue assisted argon plasma coagulation"(hereinafter called "APC plus") and "giant emphysematous bulla volume reduction"(hereinafter called "one thoracoscope plus one needle") via medical thoracoscopy on the spontaneous pneumothorax patients whose chest high resolution CT (HRCT) showed multiple subpleural bullae (SPB) and at least one SPB≥4 cm in diameter. Methods: A retrospective analysis was performed on the clinical data of 46 cases of spontaneous pneumothorax with multiple SPB(at least one SPB≥4 cm in diameter), 42 males and 4 females, aged from 31 to 79 (68.5±10.3) years,from June 2018 to December 2021 in Rizhao Hospital of Traditional Chinese Medicine. The time of air leakage discontinuance, the disappearance rate and reduction degree of target subpleural blebs one week after operation, the degree of reduction and the incidence of postoperative complications were observed. Two-year follow-up after operation was carried out to assess the recurrence rate and its short- and long-term complications. Results: Among the 46 patients, SPB disappeared or nearly disappeared in 39 cases (84.78%), decreased in number or reduced in volume in 5 cases (10.87%), and remained unchanged in 2 cases (4.35%) after the intervention of "APC Plus"; 40 patients stopped leaking within 1 week and 6 cases stopped leaking over a week. Eleven patients finished the 3-year follow-up, 13 finished 2-year follow-up and 6 finished 1-year follow-up, with only 1 relapse. No serious complications occurred in all these 46 patients. Conclusion: "APC plus" combining with "one thoracoscope plus one needle" is safe and effective in the treatment of pneumothorax patients with multiple subpleural bullae of varying sizes.

Background: An increased risk of lung cancer has been observed due to exposure to certain environmental heavy metals. This study elucidated the role of air-polluted heavy metals in the development of lung cancer., Methods: A longitudinal cohort study involving the general population was conducted to compare heavy metal content among lung cancer patients. The urine concentrations of heavy metals were measured. Questionnaire surveys were designed to collect exposure-related demographic and lifestyle data of the study subjects., Results: Participants residing near the petrochemical industrial area with higher air Cd concentration had relatively higher urinary concentration of Cd. After adjusting for sociodemographic and behavioral factors, tobacco smoking and air pollution remained as potential sources of Cd exposure. An increased prevalence of lung cancer was observed in the highly polluted zone. The risk of lung cancer incidence increased 1.25-fold for each 1 μg/g-creatinine increase in urine Cd level. Patients with lung cancer had significantly higher urinary Cd concentrations. Lung cancer patients with higher urinary Cd level had significantly poor survival (urine Cd level ≥ 1.58 vs <1.58 μg/g-creatinine; survival, medium, 192.0 vs 342.5 days, p < 0.001). At the longitudinal follow-up, participants with higher urinary Cd level had a higher risk of lung cancer incidence (urine Cd level ≥ 1.58 vs <1.58 μg/g-creatinine: 3.91% v.s. 0.87%, hazard ratio: 4.65, p < 0.001)., Conclusions: Accumulation of Cd could be a risk of lung cancer occurrence. High exposure to Cd may result in poor prognosis in lung cancer patients., 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 © 2021 Elsevier B.V. All rights reserved.)

Background: Macrophage infiltration around lipotoxic tubular epithelial cells (TECs) is a hallmark of diabetic nephropathy (DN). However, how these two types of cells communicate remains obscure. We previously demonstrated that LRG1 was elevated in the process of kidney injury. Here, we demonstrated that macrophage-derived, LRG1-enriched extracellular vesicles (EVs) exacerbated DN. Methods: We induced an experimental T2DM mouse model with a HFD diet for four months. Renal primary epithelial cells and macrophage-derived EVs were isolated from T2D mice by differential ultracentrifugation. To investigate whether lipotoxic TEC-derived EV (EV e ) activate macrophages, mouse bone marrow-derived macrophages (BMDMs) were incubated with EV e . To investigate whether activated macrophage-derived EVs (EV m ) induce lipotoxic TEC apoptosis, EV m were cocultured with primary renal tubular epithelial cells. Subsequently, we evaluated the effect of LRG1 in EV e by investigating the apoptosis mechanism. Results: We demonstrated that incubation of primary TECs of DN or HK-2 mTECs with lysophosphatidyl choline (LPC) increased the release of EV e . Interestingly, TEC-derived EV e activated an inflammatory phenotype in macrophages and induced the release of macrophage-derived EV m . Furthermore, EV m could induce apoptosis in TECs injured by LPC. Importantly, we found that leucine-rich α-2-glycoprotein 1 (LRG1)-enriched EV e activated macrophages via a TGFβR1-dependent process and that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-enriched EV m induced apoptosis in injured TECs via a death receptor 5 (DR5)-dependent process. Conclusion: Our findings indicated a novel cell communication mechanism between tubular epithelial cells and macrophages in DN, which could be a potential therapeutic target., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs) are commonly used drug-delivering devices for patients with chronic airway diseases. Appropriate peak inhalation flow rate (PIFR) and inhaler technique is essential for effective therapy. We aimed at optimizing inhalation therapy through the analysis of PIFRs in patients with chronic obstructive pulmonary disease (COPD) or asthma as well as the effect of technique training using In-Check DIAL® to help patients to achieve their optimal inspiratory flow rates., Methods: The study continuously enrolled patients who were diagnosed as COPD or asthma from respiratory clinics. PIFRs were described and analyzed between the newly-diagnosed and follow-up patients, and the stable and acute exacerbation patients, respectively. Every participant was trained inhaler technique using In-Check DIAL®. PIFRs before and after training was compared by self-control analysis., Results: Among a total of 209 patients, the average age was 56.9 years. For DPIs users, 10.8% patients had a PIFR < 30 L/min and 44.1% patients had a PIFR ≥ 60 L/min before technique training. After technique training, scarcely patient (1.5%) had a PIFR < 30 L/min, and 60.5% patients had a PIFR ≥ 60 L/min. The patient's average PIFR increased by 5.6L/min after training. The increase in PIFR before and after training was significant (p < 0.001) for most patients, but no significant variation was found in patients with acute exacerbation (p = 0.822)., Conclusions: A considerable number of patients with COPD or asthma were not able to achieve the minimum or optimal PIFR for DPIs. Inhaler training can increase patients' PIFRs and improve their ability to use DPIs. Trail registration The study has registered in chictr.org.cn (ChiCTR1900024707) and been approved by the Ethics Committee of Zhongshan Hospital of Fudan University (B2019-142)., (© 2021. The Author(s).)

Objective: To explore the efficacy and safety of position selection in combination with intra-pleural thrombin injection in the treatment of persistent air leakage (PAL) after medical thoracoscopic treatment of bullous pulmonary-pleural diseases (e.g. spontaneous pneumothorax or giant emphysematous bulla). Methods: This was a prospective study conducted in Rizhao Hospital of Traditional Chinese Medicine from August 2018 to November 2020. Twenty patients(19 males,1 female) with a mean age of (62.3±8.1) years met the diagnostic criteria for PAL which was defined as the air leak persisted more than 3 days despite of the closed thoracic drainage after medical thoracoscopic treatment of bullous pulmonary-pleural diseases.They received the following treatment procedures (referred to as "position plus"):①Pleural cavity injection (50% glucose 20 ml+thrombin 5 000 U).②Changing the patient's position under continuous negative pressure suction to find the position causing the complete stop or significant reduction of air leakage, and keeping in the position for 24-48 hours.③If the PAL wasn't stopped 48 hours later, the procedures above would be repeated.The duration of air leakage after "position plus", times of pleural cavity injection, condition of lung re-expansion, recurrence of air leakage and complications during hospitalization were recorded. Descriptive statistics were used to summarize the results: ¯x±s or M ( P 25 , P 75 ) for continuous variables; frequency and percentages for categoric variables. Results: A total of 20 patients were included. The average duration of air leakage after"position plus" was (1.32±0.97) days. The times of pleural cavity injection required were 1.0(1.0, 1.0).All the patients showed good lung re-expansion in review of imaging after PAL was stopped. One patient had recurrent air leakage during hospitalization. No serious complications occurred. Conclusion: The comprehensive "position plus" intervention method is effective, safe and easily operating for the treatment of PAL after medical thoracoscopic treatment of bullous pulmonary-pleural diseases.

Wastewater treatment plants (WWTPs) are considered important reservoirs of antibiotic resistance genes (ARGs) and function as the main sources of ARGs in the environment. Membrane bioreactors (MBRs) have been recognized as effective tools for removing ARGs in WWTPs.There are a large number of pathogens and resistance genes in colloids, particulate matter, suspended matter, and microbial metabolites in intercepted wastewater by MBR. However, the distribution characteristics of resistance genes in membrane cleaning sludge remains unclear. In this study, resistance genes of membrane cleaning sludge were analyzed using a metagenomic technique. The results showed that there were 39 phyla in the membrane cleaning sludge. Proteobacteria, Nitrospirae, and Actinobacteria were the dominant phyla. The dominant genera were Nitrospira , Pseudomonas , and Bradyrhizobium . The pathogens accounted for 10.54% of all bacteria in the sample, among which Pseudomonas had the highest abundance, accounting for 3.94%. A total of 17 types of antibiotic resistance genes and 16 types of metal resistance genes (MRGs) (15 types of single metal resistance genes and 1 types of multi-heavy metal resistance gene) were identified. Multidrug resistance genes had the highest abundance, accounting for 49.08%. Multi-heavy metal resistance genes were the most abundant, accounting for 34.58%. The copper resistance genes were the most abundant of the single metal resistance genes, accounting for 19.99%. The most important functional pathway of microbial community in the membrane cleaning sludge was metabolic related, and many genes identified were related to human diseases. The numbers of genes related to bacterial resistance and bacterial infectious diseases were the largest, accounting for 34.50% and 16.62%, respectively. These results indicate that there were abundant ARGs, MRGs, and pathogens in the membrane cleaning sludge, which has potential environmental health risks. It is necessary to strengthen the control of ARGs, MRGs, and pathogens in membrane cleaning sludge to provide guidance for selecting appropriate technologies for effectively removing ARGs, MRGs, and pathogens.

Objective: To investigate the epidemiology, clinical features, treatment and outcome of Noninvasive ventilation (NIV)-treated acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients in secondary hospitals of Shanghai., Method: Relying on Shanghai alliances for respiratory diseases, a retrospective observational study was performed in 34 secondary hospitals of Shanghai. The AECOPD patients treated with NIV and admitted to the respiratory department or respiratory intensive care unit were recruited between December 1, 2016, and November 30, 2017., Results: There were 555 patients finally recruited in this study. The age was 75.8 ± 9.6 years old and 380 patients (68.5%) were male. 70.5% of all patients had respiratory acidosis (pH <7.35). 55.3% of all patients received nebulised bronchodilator and 77.7% were treated with systemic or inhaled corticosteroids during hospitalisation. 525 patients (94.6%) recovered successfully and the mortality was 3.2%. The hospitalisation was 15.3 ± 6.7 days and hospital expenses were 22 911 ± 13 595 RMB. Inadequate and nonstandard drug treatments were the most important problems during management., Conclusion: The NIV can be successfully used for AECOP patients in local hospitals of Shanghai, but accompanied by high costs and long hospital stays. However, the treatments for exacerbation and stable COPD patients are still insufficient., (© 2021 John Wiley & Sons Ltd.)

Objective: Testicular germ cell tumors (TGCT) are the most common cancer among men aged 15 to 39 years. Previous studies have considered factors related to TGCT survival rate and race/ethnicity, but histological type of the diagnosed cancer has not yet been thoroughly assessed., Methods: The data came from 42,854 eligible patients from 1992 to 2015 in the Surveillance Epidemiology and End Results 18. Frequencies and column percent by seminoma and nonseminoma subtypes were determined for each covariates. We used Cox proportional hazard regression to assess the impact of multiple factors on post-diagnostic mortality of TGCT., Results: Black males were diagnosed at a later stage, more commonly with local or distant metastases. The incidence of TGCT in black non-seminoma tumors increased most significantly. The difference in survival rates between different ethnic and histological subtypes, overall survival (OS) in patients with non-seminoma was significantly worse than in patients with seminoma. The most important quantitative predictor of death was the stage at the time of diagnosis, and older diagnostic age is also important factor affecting mortality., Conclusion: Histological type of testicular germ cell tumor is an important factor in determining the prognosis of testicular cancer in males of different ethnic groups., (Copyright © 2021 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Background: In March 2020, the World Health Organization (WHO) declared COVID-19 a public health emergency of international concern. A small proportion of patients infected with COVID-19 go on to develop pneumonia. We speculated that COVID-19 may be likely to result in psychological disorders such as anxiety and depression. In this study, we conducted an investigation of anxiety and depression in patients with COVID-19., Methods: Sixty-five COVID-19 patients were randomly enrolled into this study. Anxiety and depression among participants were measured through the completion of anonymous Chinese-language Zung self-rating anxiety scale and self-rating depression scale questionnaires. Data were analyzed using independent samples t-tests, Mann-Whitney U-tests, and χ2 tests., Results: The questionnaire results showed that 26.15% and 41.54% of participants suffered from anxiety and depression, respectively, although there was no significantly statistical difference between the proportions of COVID-19 patients with anxiety and depression. Statistically significant differences in employment status, partial pressure of oxygen, and corticosteroid application existed between moderate- and severe COVID-19 patients (P<0.05). In particular, the partial pressure of oxygen was significantly lower in severe COVID-19 patients than in their moderate counter parts (71.31±23.54 vs. 101.06±34.43, U=156, P=0.006). Total lymphocytes was lower in severe group than in moderate group [1.659±0.643 vs. 0.745 (0.645, 0.928), U=109, P=0.000]. Also, a higher proportion of female than male patients had anxiety (χ2=5.388, P=0.02). COVID-19 patients who received antiviral medications also displayed a higher rate of anxiety (χ2=4.481, P=0.034). Total lymphocytes between the non-anxiety and anxiety had statistical difference (U=321, P=0.019). Meanwhile, total lymphocytes between the non-depression and depression also had statistical difference (U=389.5, P=0.01)., Conclusions: Among patients with COVID-19, females and those treated with antiviral medications were more likely to experience anxiety. In addition, our findings reflected the effect of anxiety and depression on immune system.

Naturally occurring phenanthroindolizidine and phenanthroquinolizidine alkaloids (PIAs and PQAs) are two small groups of herbal metabolites sharing a similar pentacyclic structure with a highly oxygenated phenanthrene moiety fused with a saturated or an unsaturated N -heterocycle (indolizidine/quinolizidine moieties). Natural PIAs and PQAs only could be obtained from finite plant families (such as Asclepiadaceae, Lauraceae and Urticaceae families, etc.). Up to date, more than one hundred natural PIAs, while only nine natural PQAs had been described. PIA and PQA analogues have been applied to the development of potent anticancer agents all along because of their excellent cytotoxic activity. However, in the last two decades, other great biological properties, such as anti-inflammatory and antiviral activities were revealed successively by different pharmacological assays. Especially because of their potent antiviral activity against coronavirus (TGEV, SARS CoV and MHV) and tobacco mosaic virus, PIA and PQA analogues have attracted much pharmaceutical attention again, some of them have been used to present interesting targets for total or semi synthesis, and structure-activity relationship (SAR) study for the development of antiviral agents. In this review, natural PIA and PQA analogues obtained in the last two decades with their herbal origins, key spectroscopic characteristics for structural identification, biological activity with possible SARs and application prospects were systematically summarized. We hope this paper can stimulate further investigations on PIA and PQA analogues as an important source for potential drug discovery., (© Springer Nature B.V. 2020.)

Background: The outbreak of COVID-19 has led to international concern. We aimed to establish an effective screening strategy in Shanghai, China, to aid early identification of patients with COVID-19., Methods: We did a multicentre, observational cohort study in fever clinics of 25 hospitals in 16 districts of Shanghai. All patients visiting the clinics within the study period were included. A strategy for COVID-19 screening was presented and then suspected cases were monitored and analysed until they were confirmed as cases or excluded. Logistic regression was used to determine the risk factors of COVID-19., Findings: We enrolled patients visiting fever clinics from Jan 17 to Feb 16, 2020. Among 53 617 patients visiting fever clinics, 1004 (1·9%) were considered as suspected cases, with 188 (0·4% of all patients, 18·7% of suspected cases) eventually diagnosed as confirmed cases. 154 patients with missing data were excluded from the analysis. Exposure history (odds ratio [OR] 4·16, 95% CI 2·74-6·33; p<0·0001), fatigue (OR 1·56, 1·01-2·41; p=0·043), white blood cell count less than 4 × 10 9 per L (OR 2·44, 1·28-4·64; p=0·0066), lymphocyte count less than 0·8 × 10 9 per L (OR 1·82, 1·00-3·31; p=0·049), ground glass opacity (OR 1·95, 1·32-2·89; p=0·0009), and having both lungs affected (OR 1·54, 1·04-2·28; p=0·032) were independent risk factors for confirmed COVID-19., Interpretation: The screening strategy was effective for confirming or excluding COVID-19 during the spread of this contagious disease. Relevant independent risk factors identified in this study might be helpful for early recognition of the disease., Funding: National Natural Science Foundation of China., (© 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.)

Introduction: Acute exacerbation (AE) is a major cause of disease progression and death in patients with chronic obstructive pulmonary disease (COPD), accounting for majority of medical expenditures. Correct inhalation therapy is effective in preventing AE attacks. However, inappropriate usage of dry powder inhaler, partially due to the unrecovered peak inhalation flow rate (PIFR) after acute exacerbation of COPD (AECOPD), results in increased risk of early treatment failure. Therefore, we designed a multicentre, randomised clinical trial to determine whether PIFR-based optimised inhalation therapy and training on inhaler usage at discharge could effectively reduce early treatment failure events., Methods and Analysis: A total of 416 hospitalised patients just recovering from AECOPD will be recruited and equally randomised into the PIFR group and the control group at a 1:1 ratio. The PIFR group will receive additive support before discharge, including choice of PIFR-guided inhaler and education on its usage. PIFR is measured by InCheck DIAL. In comparison, the control group will receive inhalers based on judgement of the respiratory physician. The primary outcome of the study is 30-day treatment failure rate. Other endpoints include PIFR, error rate of inhalation device use, satisfaction with inhalation devices, 30-day mortality, 90-day mortality, symptoms and quality of life of patients, and COPD-related treatment costs., Ethics and Dissemination: The trial has been approved by the Ethics Committee of Zhongshan Hospital of Fudan University (B2019-142). Participants will be screened and enrolled from hospitalised patients with AECOPD by clinicians, with no public advertisement for recruitment. After the trial has completed, the results will be reported to the public through conference presentations and peer-reviewed journals., Trial Registration Number: NCT04000958., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Despite the release of a national guideline in 2016, the actual practices with respect to adult community-acquired pneumonia (CAP) remain unknown in China. We aimed to investigate CAP patient management practices in Shanghai to identify potential problems and provide evidence for policy making., Methods: A short-period, 5-day prospective cross-sectional study was performed with sampled pulmonologists from 36 hospitals, encompassing all the administrative districts of Shanghai, during January 8-12, 2018. The medical information was recorded and analyzed for the patients with the diagnosis of CAP who were cared for by 46 pulmonologists during the study period., Results: Overall, 435 patients were included in the final analysis, and 94.3% had a low risk of death in terms of CRB-65 criteria (C: disturbance of consciousness, R: respiratory rate, B: blood pressure, 65: age). When diagnosed with CAP, 70.1% of patients were not evaluated using the CURB-65 score (CRB-65 + U: urea nitrogen), but most patients (95.4%) were evaluated using CRB-65. Time to achieve clinical stability was longer in patients with hypoxemia than in those without hypoxemia (8.42±6.36 vs. 5.53±4.12 days, P=0.004). Overall, 84.4% of patients with a CRB-65 score of 0 were administered antibiotics intravenously, and 19.4% were still hospitalized after excluding hypoxemia and comorbidities. The average duration of antibiotic treatment was 10.4±4.9 days. Overall, 72.6% of patients received antibiotics covering atypical pathogens whose time to clinical stability was significantly shortened compared with those without coverage, but the antibiotic duration was similar and not correspondingly shortened., Conclusions: CRB-65 seems to be more practical than CURB-65 for the initial evaluation of CAP in the context of local practice, and oxygenation assessment should be included in the evaluation of severity. Overtreatment may be relatively common in patients at low risk of death, including unreasonable hospitalization, intravenous administration, and antibiotic duration., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd.2020.03.02). The authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

Dianshan Lake, a subtropical shallow lake, is the largest freshwater body located in Shanghai. To reveal the temporal and spatial variation of zooplankton community structure and its relationships with environmental factors, monthly data of zooplankton and phytoplankton content and associated physicochemical parameters for 2017 were analyzed using multivariate regression trees (MRT) and principal coordinates analysis (PCoA). The results indicated that there were significant seasonal differences in the community structure of zooplankton ( P <0.05). However, spatial variations were significant only in spring and summer ( P <0.05). The results indicated that water temperature (WT), chlorophyll-a (Chla), ammonia nitrogen, and cyanobacteria were the key driving factors in the observed spatial and temporal variations in the zooplankton community structure. The MRT analysis illustrated that zooplankton community structure varied strongly across four groups, including spring (13.07℃ ≤ WT<19.57℃), summer (WT ≥ 19.57℃, Chla ≥ 9.03 μg·L -1 ), autumn (WT ≥ 19.57℃, Chla<9.03 μg·L -1 ), and winter (WT<13.07℃). In addition, three distinct regions were identified by the cluster analysis. The MRT analysis illustrated that the zooplankton community structure was distinct between samples with relatively lower (<1.11 mg·L -1 ) and higher concentrations (≥ 1.11 mg·L -1 ) of ammonia nitrogen in spring. Furthermore, cyanobacteria were identified as a major stressor on zooplankton in summer. These observations further show that that zooplankton community structure in area I (with a cyanobacterial biomass of ≥ 2.58 mg·L -1 ) was significantly different from other regions (with a cyanobacterial biomass of <2.58 mg·L -1 ).

miR-517a has been reported to act as an oncogenic miRNA in human hepatocellular carcinoma and lung cancer. However, the roles and underlying molecular mechanism of miR-517a in glioma remain unclear. In the present study, the expression of miR-517a in clinical glioma tissues and glioma cell lines was examined by quantitative real-time PCR (qRT-PCR). Transfected with knockdown or forced expression of miR-517a, the effects of miR-517a on cell proliferation, migration, and invasion were detected through in vitro and in vivo tumorigenesis assays. Here, we report that miR-517a expression was up-regulated in glioma tissues when compared with normal brain tissues, and up-regulation of miR-517a level is tightly correlated with the status of pathology classification of glioma. A functional assay found that overexpression of miR-517a in glioma cells markedly promoted or suppressed cell proliferation, colony formation, migration and invasion, respectively. Moreover, we revealed that the knockdown of miR-517a dramatically suppressed glioma cell growth, migration, and invasion in vitro and in vivo Furthermore, we found that knockdown of miR-517a significantly induced apoptosis. Therefore, miR-517a acts an oncogenic miRNA that promotes tumor progression in glioma, and thus may become a promising therapeutic candidate for glioma., (© 2019 The Author(s).)

Six undescribed C-geranylated flavonoids, including five C-geranylflavanones named as paucatalinones F - J, one C-geranylflavonol named as paucatalinone K, along with seven known geranylated flavanones, were isolated from the fruit peel of Paulownia catalpifolia T. Gong ex D.Y. Hong. Their structures were elucidated distinctly according to their UV, IR, MS, NMR, and CD data. Among them, two compounds were substituted with unusual modified geranyl groups, namely paucatalinone F with an oxygenated cyclogeranyl substituent and paucatalinone H with a terminal pyranoid geranyl substituent. Furthermore, the protective effects on human umbilical vein endothelial cells (HUVECs) injury induced by H 2 O 2 were evaluated, and paucatalinone F showed the most potential activity. The bioactive results suggested that the geranyl substituent may be an important factor for restraining oxidative HUVECs damage and Paulownia C-geranylated flavonoids might have the potential for preventing cardiovascular complications., (Copyright © 2018. Published by Elsevier Ltd.)

An in-situ mesocosm experiment was conducted to study the growth dynamic of Chrysosporum ovalisporum and the other phytoplankton organisms under accelerated eutrophication conditions by using 39 buckets (100 L) in Lake Dishui, Shanghai. The results showed that the growth of both filamentous cyanobacteria ( C. ovalisporum ) and green algae were promoted with nutrient enrichment. The increase in the algal biomass rate in N plus P addition treatments was significantly higher than in treatments with N or P alone ( P <0.05). Although the increasing biomass rate with P addition alone was higher than with N alone, there was no statistically significant difference ( P> 0.05). The relevant abundance of C. ovalisporum showed a significantly decreasing trend with N addition treatments and N plus P additions treatments ( P <0.05), although it was slightly increased with the treatments with P alone ( P> 0.05). Nutrient addition could significantly improve the growth of small sized algae organisms ( Chroococcus spp., Coelastrum spp., Chlorella spp., Tetraedron spp., and Scenedesmus spp.) rather than C. ovalisporum in all treatments ( P <0.05). The small sized green algae overcoming C. ovalisporum indicated that small sized algae were more favored by hyper-eutrophicated, high water temperature and relatively undisturbed conditions. This is because small sized algal organisms have higher metabolic and growth rates compared to other sized algae, especially in stationary water regimens and high, light density conditions. We foresee that the small sized algae, Chlorophyte, dominating the small hyper-eutrophic aquatic system may be a potential succession pattern in the high water temperature seasons.

Objective: To study the phenotype of memory CD4(+) T cells in peripheral blood of asthmatics and its relationship with asthma severity. Methods: From Dec 2014 to Aug 2015, thirty-three asthmatics, twenty-six chronic obstructive pulmonary disease (COPD) patients and twenty-two healthy volunteers were enrolled in Respiratory Clinics of Zhongshan Hospital, Fudan University. Peripheral blood mononuclear cells (PBMCs) were isolated from peripheral blood. Cell surface markers (CD45RO, CRTH2, CD62L, and CCR7) and intracellular protein[interleukin (IL)-5, IL-17, interferon (IFN)-γ]staining was performed using flow-cytometric techniques. CD4(+) T cells were cultured under neutralization and then Th2, Th2+ Lipopolysaccharide (LPS), Th2+ Home dust mite (HDM) conditions for 6 days and then intracellular proteins were analyzed using flow cytometry. Correlation analysis between memory CD4(+) T cells, asthma severity and drug consumption were performed. Results: The percentage of memory CD4(+) T (CD4(+) Tm) cells in circulating white blood cells was higher in asthmatics, than that in healthy subjects (48.0%±5.7% vs 32.0%±4.1%, P <0.05). The cytokine profiles of CD4(+) Tm cells in asthma patients were substantially different from those of COPD and healthy subjects, with increased IL-5 and IL-17 production. For COPD patients, the predominant cytokines were IFN-γ instead. IL-17-producing CD4(+) Tm cells were associated with the severity of disease and the level of medication consumption in asthma patients ( R (2)=0.829 6, P <0.05). Conclusions: The cytokine profile is IL-5 and IL-17 predominant in memory CD4(+) T cells from asthmatics. The amount of IL-17(+) CD4(+) memory T cells is positively correlated with asthma severity.

Osteoarthritis is a common arthritis disease caused by cartilage tissue damage and degeneration, which is one of the large epidemics that affect human health. The early detection of the pathological changes of articular cartilage can greatly improve the cure rate of disease, but the relevant clinical diagnosis technology has not been developed. In recent years, the applications and researches of terahertz technology are increasingly valued and it has drawn great attention in the field of medicine. Compared with traditional methods, the terahertz radiation is low-energy and non-ionizing whose spectral-fingerprinting capability is well-known in the biological world. Meanwhile, THz technology has a great potential in diagnosis of articular cartilage early degeneration. This paper briefly introduces the physiological and pathological conditions of the articular cartilage, the current clinical techniques of articular cartilage detection. It mainly summarizes the terahertz technology used for detecting articular cartilage, including detection of animal and human cartilage respectively. At last, the challenges and development prospects of terahertz technology in articular cartilage detection are discussed.

Terahertz Time-Domain Spectroscopy (THz-TDS) is one of the effective coherent detection techniques. It has been widely applied in materials, chemistry, biology, security and other fields due to its capabilities such as high signal-to-noise ratio (SNR), broadband detection, working at room temperature, time resolved measurement and others. Limited by the spectrum bandwidth of THz radiation and detection techniques, the measuring range of the traditional THz-TDS system is generally less than several THz, thus the spectral information of high frequencies cannot be obtained. In order to expand its application, there is an urgent need for the development of ultra-broadband (≥10 THz) THz-TDS detection techniques. This paper reviews the development and applications of main detection techniques in ultra-broadband THz-TDS. The advantages and disadvantages of these techniques are also analyzed.

Early in prostate cancer development, tumor cells express vascular endothelial growth factor C (VEGF-C), a secreted molecule that is important in angiogenesis progression. CC-chemokine receptor 7 (CCR7), another protein involved in angiogenesis, is strongly expressed in most human cancers, where it activated promotes tumor growth as well as favoring tumor cell invasion and migration. The present study aimed to investigate the effect of down-regulating CCR7 expression on the growth of human prostate cancer cells stimulated by VEGFC. The CCR7-specific small interfering RNA (siRNA) plasmid vector was constructed and then transfected into prostate cancer cells. The expression of CCR7 mRNA and protein was detected by quantitative polymerase chain reaction and western blot analysis, respectively. Cell proliferation, apoptosis, cell cycle distribution and cell migration were assessed following knockdown of CCR7 by RNA interference (RNAi). Western blot analysis was used to identify differentially expressed angiogenesis- and cell cycle-associated proteins in cells with silenced CCR7. The expression levels of CCR7 in prostate cancer cells transfected with siRNA were decreased, leading to a significant inhibition of prostate cancer cell proliferation, migration and invasion induced by VEGFC. Western blot analysis revealed that silencing of CCR7 may inhibit vascular endothelial growth factor, matrix metalloproteinase (MMP)-2 and MMP-9 protein expression. In conclusion, the present study demonstrated that RNAi can effectively silence CCR7 gene expression and inhibit the growth of prostate cancer cells, which indicates that there is a potential of targeting CCR7 as a novel gene therapy approach for the treatment of prostate cancer.

Systemic sclerosis (SSc) is an autoimmune disease characterized by immune disorders, vascular obliteration, excessive extracellular matrix deposition, skin fibrosis, and further pathological change of internal organs. To date, the exact etiology of this complicated disease remains unknown. Over the past few years, the roles of epigenetic modifications caused by environmental factors have been intensively studied in relation to the disease pathogenesis, and important advances have been made. This review focuses on the new advances of microRNAs (miRNAs) in the field of SSc research, including the upstream regulatory factors of miRNAs, the downstream targets, and the feedback mechanisms between miRNAs and their targets. We also discussed the correlation of miRNAs and DNA methylation, the miRNAs and the gene polymorphism. Overall, the findings presented in this review illustrated how miRNAs play important roles in the pathogenesis of SSc. However, several unanswered questions continue to impede our understanding of this complex disease. Future research should focus on the identification of new biomarkers for early diagnosis and prognosis, which will help us improve the clinical treatment of patients with SSc. In addition, we discussed the challenges of miRNA study in SSc in the future. Since the miRNA injection may be a promising therapeutic approach for SSc treatment, one of the challenges in the future is to evaluate the therapeutic effects of miRNA and anti-miRNAs using SSc model animals. In light of the fact that one miRNA can target many mRNAs, and one mRNA is targeted by many miRNAs, the effect of miRNA changes on other gene expression should be investigated to evaluate the treatment safety of miRNA injection in vivo., (Copyright © 2015 Elsevier B.V. All rights reserved.)

In previous study, we identified that microRNA (miR)-152 expression was down-regulated in RA model rats, and overexpression of miR-152 inhibited the canonical Wnt signaling through the DNA methyltransferase (DNMT1) inhibition. However, the exact molecular mechanisms of DNMT1 were unclear. In this work, we investigate whether DNMT1 affects the pathogenesis of RA model rats and targets the miR-152 promoter. The effects of DNMT1 on the canonical Wnt signaling, the pathogenesis of RA model rats and the SFRP1 expression were detected by the real time qPCR, Western blotting, ELISA, MTT and viable cell number assay. The interaction between miR-152 and DNMT1, methyl CpG binding protein 2 (MeCP2) was investigated by real time qPCR and chromatin immunoprecipitation (ChIP). Our results revealed that increased DNMT1 activated the canonical Wnt signaling could not only by targeting SFRP4 may also by SFRP1 in RA model rats. Furthermore, treatment of DNMT1 inhibitor, 5-aza-2'-deoxycytidine (5-azadC), or knockdown of DNMT1, or knockdown of MeCP2 led to increased miR-152 expression by reversion of its promoter hypermethylation, DNMT1 and MeCP2 binding to the CpG islands of miR-152 promoter. Interestingly, it is proved a synergistic inhibition effect of DNMT1 and MeCP2 in this process. Moreover, overexpression of miR-152 could inhibit DNMT1 expression and result in a decrease of DNMT1 and MeCP2 binding to miR-152 promoter, and inhibition of miR-152 expression would reverse it. These observations demonstrate a crucial functional crosstalk between miR-152 and the DNMT1, MeCP2 by a double-negative circuit involved in the pathogenesis of RA model rats., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The purpose of this study was to employ a new three-dimensional (3D) reconstruction and modeling method to measure displacement of undisplaced femoral neck fractures (Garden stages I and II). We also aimed to evaluate the effectiveness of the Garden classification for determining the displacement of undisplaced femoral neck fractures. A total of 120 consecutive patients with undisplaced femoral neck fractures were enrolled between 2012 and 2014, including 60 within the Garden I group and 60 within the Garden II group. The displacements of the femoral head center (d1) and the lowest point of the fovea capitis femoris (d2) and rotational displacement of the femoral head (α) in the 3D model were measured with 3D computed tomography reconstruction and modeling. Five observers, trauma surgeons, were asked to found the centers of the femoral heads and the deepest points of the foveae. The intraobserver and inter-observer agreements were calculated using Fleiss' kappa. The inter-observer and intra-observer kappa values were 0.937 and 0.985, respectively. Current method has good reliability. We discovered that many participants in our study had been misclassified by an anterior-posterior radiograph as having an "incomplete" fracture. In incomplete fracture of Garden stage I group, the average displacements d1 and d2 were 3.69 ± 1.77 mm and 14.51 ± 1.91 mm, respectively. The mean α was 4.91° ± 2.49°. For impacted fracture of Garden stage I, significant spatial displacement in the impacted fractures was observed (d1: 6.22 ± 3.36 mm; d2: 10.30 ± 5.73 mm; and α: 17.83° ± 10.72°). Similarly, significant spatial displacement was observed among the Garden stage II group (d1: 7.16 ± 4.58 mm; d2: 12.95 ± 8.25 mm; and α: 18.77° ± 9.10°). There was no significant difference in α, d1, and d2 between impacted fracture and Garden stage II groups (P > 0.05). However, significant differences were found between incomplete fracture and Garden stage II groups (P < 0.05). Our findings suggest that 3D reconstruction and modeling may be a better tool for assessing femoral neck fractures than the Garden classification. Undisplaced femoral neck fractures showed variable degrees of displacement and were not undisplaced, stable fractures. Garden classification for undisplaced femoral neck fractures has certain limitations.

Rheumatoid arthritis (RA) is a symmetrical polyarticular autoimmune disease of unknown etiology. In this present study, we observed that the adenomatous polyposis coli (APC) expression is down-regulated and the expression of microRNA (miR)-663 increased significantly in synovium from RA patients compared with control. Target gene prediction for miR-663 revealed that the mRNA of APC gene, which is a member of the canonical Wnt signaling pathway, has a miR-663 binding site in its 3'-untranslated region (3'UTR). The result showed that increased miR-663 suppressed the APC expression significantly, and this down-regulation of APC expression triggered the activation of canonical Wnt signaling through accumulation of β-catenin in fibroblast-like synoviocytes (FLS). In addition, increased miR-663 induced the FLS proliferation and the expression MMP3 and fibronectin during disease development. Therefore, miR-663 can be considered as a critical regulator of RA pathogenesis and can be utilized for developing miRNA-based therapeutic agents for RA patients., (Copyright © 2015 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

Whether the rheumatoid arthritis (RA) pathogenesis is regulated by microRNA (miRNA) is not entirely clear. In this study, we found that miR-375 was down-regulated significantly in fibroblast-like synoviocytes (FLS) in adjuvant-induced arthritis (AIA) rat model compared with control. Because the web-based software TargetScan and PicTar predict Frizzled 8 (FZD8) as the target of miR-375, we investigated whether up-regulated miR-375 plays a role in the activation of the canonical Wnt signaling by targeting the FZD8. Furthermore, the purpose of the present experiments was also to determine the role of miR-375 in the pathogenesis of AIA rat model and to ascertain the effects of FZD8 in this process. Real time qPCR, Western blotting, ELISA and ChIP assay were used to assess the inhibited role of miR-375 in the pathogenesis of AIA rat model and the canonical Wnt signaling. RNA interference was also used to detect the role of knockdown of dephosphorylated β-catenin. Luciferase reporter gene and related methods were performed to determine the FZD8 as the target of miR-375. The increased miR-375 inhibited the pathogenesis of AIA rat model as indicated by decreases in the several disease markers, such as MMP3 and fibronectin. Interestingly, miR-375 also inhibited the canonical Wnt signaling, and the stabilized form of β-catenin blocked the miR-375 effects. FZD8 was identified as the target of miR-375 in AIA rat model by the firefly luciferase reporter gene. In summary, our results demonstrate that miR-375 regulates the pathogenesis of AIA rat model through the canonical Wnt signaling pathway. This discovery may provide new targets for therapeutic intervention to benefit RA patients., (Copyright © 2015 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

Rheumatoid arthritis (RA) is an autoimmune and progressive systemic disease of unknown etiology. Research shows that fibroblast-like synoviocytes (FLS) participate in the cartilage erosion, synovial hyperplasia, inflammatory cytokine secretion and suggests that fibroblast-like synoviocytes (FLS) display a crucial role in RA pathogenesis. Recent studies have suggested the role of the Wnt signaling pathway in the pathogenesis of RA. In previous study, we identified that increased methyl-CpG-binding protein 2 (MeCP2) reduced the secreted frizzled-related protein 4 (SFRP4) expression in FLS in Arthritic rat model and the DNA methyltransferase (DNMT) inhibitor 5-Aza-2'-deoxycytidine (5-azadC) could induce the SFRP4 expression, indicating that DNMT has a key role in the differential expression of SFRP4. MicroRNAs (MiRNAs), which are small non-coding RNAs, are involved in diverse biological functions, regulation of gene expression, pathogenesis of autoimmune disease and carcinogenesis. In light of the directly down-regulation of miR-152 on DNMT1 expression by targeting the 3' untranslated regions of its transcript in nickel sulfide (NiS)-transformed human bronchial epithelial cells, we investigated whether miR-152 is aberrantly expressed and targets DNMT1 in FLS in Arthritic rat model. Our results demonstrated that the expression of miR-152 was specifically down-regulated in Arthritic rat model, whereas up-regulation of miR-152 in FLS resulted in a marked reduction of DNMT1 expression. Further experiments revealed that increased miR-152 indirectly up-regulated the SFRP4 expression, a negative regulator of WNT signaling pathway, by targeting the DNMT1. Moreover, activation of miR-152 expression in FLS could inhibit the canonical Wnt pathway activation and result in a significant decrease of FLS proliferation. MiR-152 and DNA methylation may provide molecular mechanisms for the activation of canonical Wnt pathway in RA. Combination of miR-152 and DNMT1 may be a promising treatment strategy for RA patients in which SFRP4 is inactivated., (Copyright © 2014 Elsevier B.V. and Société française de biochimie et biologie Moléculaire (SFBBM). All rights reserved.)

Systemic lupus erythematosus (SLE) is a systemic multi-organ autoimmune disease with different immunological characteristics and clinical manifestations characterized by an autoantibody response to nuclear and cytoplasmic antigens; the etiology of this disease remains largely unknown. Most recent genome-wide association studies demonstrate that genetics significantly predispose to SLE onset, but the incomplete disease concordance rates between monozygotic twins indicates a role for other complementary factors in SLE pathogenesis. Recently, much evidence strongly supports other molecular mechanisms involved in the regulation of gene expression ultimately causing autoimmune disease, and several studies, both in clinical settings and experimental models, have demonstrated that epigenetic modifications may hold the key to a better understanding of SLE initiation and development. DNA methylation changes the structure of chromatin, being typically able to modulate the fine interactions between promoter-transcription factors and encoding genes within the transcription machinery. Alteration in DNA methylation has been confirmed as a major epigenetic mechanism that may potentially cause a breakdown of immune tolerance and perpetuation of SLE. Based on recent findings, DNA methylation treatments already being used in oncology may soon prove beneficial to patients with SLE. We herein discuss what we currently know, and what we expect in the future., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Uric acid is the end product of nucleic acid catabolism for humanity. Serum uric acid level has been suggested to be associated with nonalcoholic fatty liver disease (NAFLD). This study aims to examine the association between serum uric acid levels and NAFLD in subjects of different ages. A cross-sectional study was performed among the patients of different ages with NAFLD (abnormal group) or without NAFLD (normal group) in Lianyungang, Jiangsu, China. The levels of serum uric acid, total cholesterol, triglyceride, and low density lipoprotein in the abnormal group were significantly higher than those in the normal group, while the level of high density lipoprotein in the abnormal group was significantly lower than that in the normal group (p<0.05). The serum uric acid prevalence, total cholesterol, triglyceride, high density lipoprotein, and low density lipoprotein in the abnormal group was significantly higher than those in the normal group (p<0.05). The serum uric acid, total cholesterol, triglyceride, and low density lipoprotein levels and prevalence rates in elderly patients were higher than younger and middle aged patients. Serum uric acid level is highly associated with NAFLD in patients of different ages., (Copyright © 2014 Elsevier B.V. All rights reserved.)

In this study, we prepared oligosaccharides from dandelion (Taraxacum officinale) by hydrolysis with hydrogen peroxide (H2O2) and investigated their antibacterial activity. The optimum hydrolysis conditions, as determined using the response surface methodology, were as follows: reaction time, 5.12h; reaction temperature, 65.53 °C and H2O2 concentration, 3.16%. Under these conditions, the maximum yield of the oligosaccharides reached 25.43%. The sugar content in the sample was 96.8%, and the average degree of polymerisation was approximately 9. The oligosaccharides showed high antibacterial activity against Escherichia coli, Bacillus subtilis and Staphylococcus aureus, indicating that dandelion-derived oligosaccharides have the potential to be used as antibacterial agents., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: This study aimed to examine whether long working hours and short sleep duration were associated with an increased risk of acute myocardial infarction (AMI) or severe coronary heart diseases (SCHD), independent of established psychosocial work-related factors., Methods: A case-control study was conducted. Cases were 322 men, aged <60 years and economically active, who were admitted to hospital with a first diagnosed AMI or SCHD during 2008-2011, of whom 134 were confirmed AMI and the other 188 were angiography-confirmed SCHD. Controls were 644 men who were drawn from a national survey and were matched to the cases on age, education and area of residence. Odds ratios of total CHD and confirmed AMI in relation to average weekly working hours and daily hours of sleep were calculated., Results: Men with average working hours longer than 60 h/week were found to have significantly increased risks for total CHD (OR=2.2) as compared to those with weekly working hours in 40-48 h, and those with daily hours of sleep fewer than 6 h were found to have increased risks for CHD (OR=3.0) as compared to those with sleeping hours in 6-9 h. Restriction to confirmed AMI yielded a greater risk and these associations remained consistent with adjustment of smoking status, body mass index and psychosocial work factors including job demands, job control, workplace justice, job insecurity and shift work., Conclusion: The results support the hypothesis that long working hours and short sleep duration contribute independently to the risk of cardiovascular diseases in men., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Underreporting occupational disease cases has been a long-standing problem in Taiwan, which hinders the progress in occupational health and safety. To address this problem, the government has founded the Network of Occupational Diseases and Injuries Service (NODIS) for occupational disease and injury services and established a new Internet-based reporting system., Objectives: The aims of this study are to analyze the possible influence of the NODIS, comprised of Center for Occupational Disease and Injury Services and their local network hospitals, on compensable occupational diseases and describe the distribution of occupational diseases across occupations and industries from 2005 to 2010 in Taiwan., Methods: We conducted a secondary analysis of two datasets, including the NODIS reporting dataset and the National Labor Insurance scheme's dataset of compensated cases. For the NODIS dataset, demographics, disease distribution, and the time trends of occupational diseases were analyzed. The data of the Labor Insurance dataset was used to calculate the annual incidence of compensated cases. Furthermore, the annual incidence of reported occupational diseases from the NODIS was further compared with the annual incidence of compensable occupational diseases from the compensated dataset during the same period., Results: After the establishment of the NODIS, the two annual incidence rates of reported and compensable occupational disease cases have increased by 1.2 and 2.0 folds from 2007 to 2010, respectively. The reason for this increased reporting may be the implementation of the new government-funded Internet-based system. The reason for the increased compensable cases may be the increasing availability of hospitals and clinics to provide occupational health services. During the 2008-2010 period, the most frequently reported occupational diseases were carpal tunnel syndrome, lumbar disc disorder, upper limb musculoskeletal disorders, and contact dermatitis., Conclusions: The new network and reporting system was successful in providing more occupational health services, providing more workers with compensation for occupational diseases, and reducing underreporting of occupational diseases. Therefore, the experience in Taiwan could serve as an example for other newly developed countries in a similar situation.

Garden type I fractures include incomplete fractures and impacted fractures. With advances in scientific technology and medical treatment, certain deficiencies of the Garden classification have become apparent. The authors hypothesized that the incidence of incomplete femoral neck fractures was low and that impacted femoral neck fractures were not undisplaced and stable fractures. A new method was developed to precisely measure the spatial displacement of the femoral head in impacted femoral neck fractures. Between 2008 and 2011, nine hundred sixty-six patients with femoral neck fractures were treated, 48 of whom had Garden type I fractures, as seen on anteroposterior radiographs. Seven fractures were classified as incomplete on radiographs; however, after 3-dimensional reconstruction, 3 were classified as incomplete and 4 as complete fractures. Furthermore, the remaining 41 Garden I fractures that were classified as impacted on radiographs showed large spatial displacement on 3-dimensional reconstruction. The average rotational displacement of the femoral head was 19.29°±10.51°, and the average displacements of the femoral head center and the lowest point of the fovea capitis were 8.76±4.45 and 14.39±8.08 mm, respectively. This study showed that the incidence of incomplete femoral neck fractures was low. Impacted femoral neck fractures showed variable degrees of displacement and were not undisplaced, stable fractures. Garden classification for impacted femoral neck fractures has certain limitations. Impacted femoral neck fractures should be differentiated from Garden type I fractures so clinicians can select appropriate treatments for these fractures., (Copyright 2013, SLACK Incorporated.)

A white organic light-emitting device (WOLED) with a yellow phosphorescence material, bis[2-(4-tertbutylphenyl) benzothiazolato-N,C2 '] iridium (acetylacetonate) [(t-bt)2Ir(acac)], and two blue phosphorescence materials, iridium(Ill) bis (4', 6'-difluorophenylpyridinato) tetrakis(1-pyrazolyl) borate (FIr6) and bis[(4, 6-difluorophenyl)-pyridinato-N, C2 '] (picolinate) iridium (III) (FIrpic), were fabricated. Stable white emission was realized by using undoped ultrathin yellow emissive layer (EML), two doped blue EMLs together with the proper thickness of an interlayer confining the exciton. The WOLED performed pure white light emission with the Commissions Internationale de l'Eclairage (CIE) coordinates of (0.29+/-0.01, 0.34+/-0.01) from 6 to 14 V. Moreover, electroluminescence (EL) characteristics of the devices were also studied to verify the emissive mechanism from a phosphorescent system consisting of three iridium chelates. Also, the results showed that the triple-phosphor-element EMLs WOLED had lower efficiency roll-off owing to the stable recombination zone.