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A better understanding of the mechanisms underlying PD-L1 aberrant expression in head and neck squamous cell carcinoma (HNSCC) will help reveal predictive biomarkers and overcome resistance to treatment. In this study, the prognostic significance of PD-L1 in forty-five HNSCC archival samples was determined by qRT-PCR. The biological function associated with malignant behaviour was assessed by PD-L1 depletion, miR-382-3p re-expression and regulation of circ_0000052. The interactions of PD-L1-miRNA and miRNA-circRNA were determined by qRT-PCR, Western blot analysis, dual-luciferase reporter assays and RNA immunoprecipitation assays. PD-L1 was highly expressed in patient samples and cancer cell lines. Higher levels of PD-L1 were associated with patient recurrences and play a pivotal role in regulating cell proliferation, migration, invasion, clonogenicity and apoptosis. In addition to demonstrating that the IFN-γ/JAK2/STAT1 signalling pathway can induce PD-L1 overexpression in HNSCC, a novel mechanism by which upregulated circ_0000052 mediates PD-L1 overexpression was also demonstrated. To do this, circ_0000052 competitively binds to miR-382-3p and alleviates its repression of PD-L1. This leads to overexpression of PD-L1, causing the aggressiveness of the cells. Our data demonstrate that circ_0000052 is oncogenic, and the circ_0000052/miR-382-3p/PD-L1 axis is critical in HNSCC progression. The manipulation of circRNAs/miRNAs in combination with anti-PD-L1 therapy may improve personalized disease management.

Cardiovascular disease (CVD) is the most frequent cause of death in patients on maintenance peritoneal dialysis (PD). This study aimed to identify the risk factors associated with cardiac complications and establish a multivariate logistic regression model for cardiac complications in patients with end-stage renal disease (ESRD) requiring PD.This retrospective study included 232 patients undergoing PD. Data of sociodemographic information, comorbidities, medication history, laboratory examination, and medical history were extracted from the medical records of patients with ESRD who underwent maintenance PD between January 2015 and June 2020. Multivariate logistic regression analysis was performed to determine the independent risk factors.The mean age of the study participants was 51.29±13.17 years, with female: male ratio of 87:145. Multivariate logistic regression analysis indicated that lactate dehydrogenase (odds ratio, 1.002; 95% confidence interval, 1.001-1.004; P=0.004), albumin (odds ratio, 0.947; 95% confidence interval, 0.914-0.982; P=0.003), and left atrial diameter (odds ratio, 1.096; 95% confidence interval, 1.037-1.159; P=0.001) were independent risk factors associated with cardiac complications. The area under the receiver operating characteristic curve was 0.78.We identified the risk factors of cardiac complications in patients with ESRD requiring PD, which may be clinically useful to assess patients in PD and start their early treatment, which can help improve their prognosis.

Tzu Chi University's anatomy curriculum incorporates interaction with donors' families and regards body donors as silent teachers and altruistic role models. In this silent mentor program (SMP), students learn about their donor's life before dissection to better appreciate the selfless donation. This study explores the influence of the program on students' humanistic literacy based on student letters to silent mentors, which students wrote near the end of the program and laid by the silent mentor during the coffining ceremony.The study included 125 letters from third-year medical students who took the gross anatomy curriculum in academic years 2015, 2016, and 2017. With student consent, the program collated and published the letters in the open-access SMP yearbook. Using thematic analysis, the authors manually analyzed the letters in their original Mandarin, with the names of students made anonymous to ensure the authors were blind to students' identity throughout the study.The analysis identified 3 themes and 11 subthemes. Theme 1, my silent mentor, included 3 subthemes: life characteristics, altruistic attitude, and expectation of offering body. Theme 2, connection to silent mentor and family, included 4 subthemes: intersubjective bonding, emotive first encounter, spiritual communication, and encouragement from silent mentor. Theme 3, reflection and transformation, included 4 subthemes: reflection on life and death, professional self-expectation, inner transformation, and feedback action.The findings suggest that interactions with donors' families increased students' appreciation of the donation and enhanced students' humanistic literacy. Further, the letters seem to indicate that the SMP inspired students to develop a grateful, respectful, and empathic attitude toward life and their career. Thus, by implementing similar programs, gross anatomy curricula could go beyond the acquisition of structural knowledge to the cultivation of medical students' humanistic literacy.

Background. S100A4 is a member of the S100 calcium-binding protein family and is increased in patients with chronic obstructive pulmonary disease (COPD). Sphingosine-1-phosphate (S1P) is a naturally occurring bioactive sphingolipid, which regulates the adhesion between the cells and the extracellular matrix and affects cell migration and differentiation. The goal of this study was to analyze the correlations among S100A4, S1P, and pulmonary function among COPD patients. Methods. All 139 serum samples and 15 lung specimens were collected in COPD patients and control subjects. S100A4 and S1P were detected in two groups. The markers of fibrosis and epithelial-mesenchymal transition (EMT) were measured in the lungs of COPD patients and control subjects. Results. The protein expression of S100A4 was higher in the lungs and serum of COPD patients than control cases. Additionally, serum S100A4 was inversely associated with pulmonary function among COPD patients. Meanwhile, collagen deposition and EMT nuclear transcription factors were elevated in the lungs of COPD patients. Moreover, the protein expression of S1P was increased in the serum of COPD patients. Serum S1P was gradually increased along with pulmonary function decline in COPD patients. Further correlation analysis revealed that serum S1P was negatively associated with pulmonary function in COPD patients. Furthermore, there was a positive correlation between S1P and S100A4 in COPD patients. Conclusions. These results provide evidence that the elevation of S100A4 and S1P may be involved in the onset and progression of COPD.

The proportion assisted ventilation (PAV) can improve patient-ventilator interaction, reducing the incidence of end-expiratory asynchrony and increasing the time of synchrony. PAV could compensate for the leaks by elastic and resistive unloading and thus is ideal for neonates with uncuffed airways. The aim of this study was to compare the relevant clinical parameters of neonates with respiratory distress syndrome (RDS) who are supported by PAV plus synchronized intermittent mandatory ventilation (SIMV) and SIMV.Forty-six neonates diagnosed as RDS who required mechanical ventilation were randomly divided into observer group (support by PAV+SIMV mode, N.=23) and control group (support by SIMV mode, N.=23). The X-ray grading situation, the number of asynchrony-delayed trigger, mean arterial blood pressure (MABP), spontaneous respiratory rate (RR), heart rate (HR), blood gas analysis values and circulation and respiratory parameters at each timepoint after 30 minutes, 12, 24, 48 and 72 hours of mechanical ventilation were observed.The forty-four neonates in two groups have been cured, the other 2 neonates (one in each group) gave up treatment and automatically discharged. There were no statistically significant differences in male, gestational age, body weight, duration of mechanical ventilation, oxygen dependence and hospital stay between the two groups (all P0.05). There were no statistically significant differences in MABP, HR and ratio of arterial-to-alveolar partial pressure of oxygen (a/APOinf2/inf) at each time point after mechanical ventilation between the two groups(all P0.05). The number of asynchrony-delayed trigger in observer group was lower than that in control group, the difference was statistically significant (P0.05). The number of spontaneous RR in observer group was higher than that in control group. The difference was statistically significant (P0.05).The PAV plus SIMV shows a good clinical effect in treatment of neonates with RDS. It could be better to use neonatal spontaneous breathing and might cause less damage to the lung than SIMV mode.

Objective: To estimate a patient-specific reference bone shape model for a patient with craniomaxillofacial (CMF) defects due to facial trauma. Methods: We proposed an automatic facial bone shape estimation framework using pre-traumatic conventional portrait photos and post-traumatic head computed tomography (CT) scans via a 3D face reconstruction and a deformable shape model. Specifically, a three-dimensional (3D) face was first reconstructed from the patient's pre-traumatic portrait photos. Second, a correlation model between the skin and bone surfaces was constructed using a sparse representation based on the CT images of training normal subjects. Third, by feeding the reconstructed 3D face into the correlation model, an initial reference shape model was generated. In addition, we refined the initial estimation by applying non-rigid surface matching between the initially estimated shape and the patient's post-traumatic bone based on the adaptive-focus deformable shape model (AFDSM). Furthermore, a statistical shape model, built from the training normal subjects, was utilized to constrain the deformation process to avoid overfitting. Results and Conclusion: The proposed method was evaluated using both synthetic and real patient data. Experimental results show that the patient's abnormal facial bony structure can be recovered using our method, and the estimated reference shape model is considered clinically acceptable by an experienced CMF surgeon. Significance: The proposed method is more suitable to the complex CMF defects for CMF reconstructive surgical planning.

The main tendon of the extensor hallucis longus (EHL) muscle attaches to the dorsal aspect of the distal phalanx of the great toe. One or multiple accessory tendons of the EHL have been reported in several ethnic/regional groups, except Taiwan. This study aimed to investigate the incidence, length, and insertion of the accessory tendon of the EHL in Taiwanese people. Anatomical dissection was performed on 48 feet of 24 formalin-embalmed cadavers. The occurrence and morphological characteristics of the accessory tendon of the EHL were recorded and analyzed. The accessory tendon of the EHL was found in 97.92% (47/48) of the legs that were dissected. In one male cadaver, an independent muscle belly was identified in each leg, whereas all the other accessory tendons originated from the main tendon of the EHL. In this study, the insertion of the accessory tendon were classified into four patterns. The most common insertion sites were the first metatarsophalangeal (MTP) joint capsule and proximal phalanx of the great toe. The length of the accessory tendons did not correlate with age or with sex when the two tendons with independent muscle belly were excluded. The accessory tendon of the EHL appears to be a regular feature in Taiwanese people. Most accessory tendons of the EHL (85.7%) attached on the first MTP joint capsule may play a role in the prevention of capsular impingement during great toe extension.

Statins are a class of drug widely prescribed for the prevention of cardiovascular disease, with pleiotropic cellular effects. Statins inhibit HMG-CoA reductase (HMGCR), which converts the metabolite HMG-CoA into mevalonate. Recent discoveries have shown HMG-CoA is a reactive metabolite that can non-enzymatically modify proteins and impact their activity. Therefore, we predicted that inhibition of HMGCR by statins might increase HMG-CoA levels and protein modifications. Upon statin treatment, we observe a strong increase in HMG-CoA levels and modification of only a single protein. Mass spectrometry identifies this protein as fatty acid synthase (FAS), which is modified on active site residues and, importantly, on non-lysine side-chains. The dynamic modifications occur only on a sub-pool of FAS that is located near HMGCR and alters cellular signaling around the ER and Golgi. These results uncover communication between cholesterol and lipid biosynthesis by the substrate of one pathway inhibiting another in a rapid and reversible manner.

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Cerebellopontine angle meningiomas (CPAMs) are benign tumors that arise from the dura mater of the petrosal surface of the temporal bone, lateral to the trigeminal nerve. This study aimed to describe 1 case of CPAMs violating the mastoid and highlight the unique superiority of the presigmoid transmastoid approach for this type of CPAMs from an otologist's perspective.One case of specific CPAMs treated by total resection via presigmoid transmastoid approach in otomicrosurgery was described.A patient was referred for the left intracranial space-occupying lesion found in physical examination. Surgical resection via presigmoid transmastoid approach was performed and there was no sign of recurrence of tumor 2 years after the operation.Presigmoid transmastoid approach in otomicrosurgery is suitable for CPAMs invading the mastoid. It is suggested that neurosurgeons and ear surgeons should comprehensively analyze the type and extent of the tumor and flexibly adopt surgical methods to ensure it is the best for patients.

Enchondromas and chondrosarcomas are common cartilage neoplasms that are either benign or malignant, respectively. The majority of these tumors harbor mutations in either IDH1 or IDH2. Glutamine metabolism has been implicated as a critical regulator of tumors with IDH mutations. Using genetic and pharmacological approaches, we demonstrated that glutaminase-mediated glutamine metabolism played distinct roles in enchondromas and chondrosarcomas with IDH1 or IDH2 mutations. Glutamine affected cell differentiation and viability in these tumors differently through different downstream metabolites. During murine enchondroma-like lesion development, glutamine-derived α-ketoglutarate promoted hypertrophic chondrocyte differentiation and regulated chondrocyte proliferation. Deletion of glutaminase in chondrocytes with Idh1 mutation increased the number and size of enchondroma-like lesions. In contrast, pharmacological inhibition of glutaminase in chondrosarcoma xenografts reduced overall tumor burden partially because glutamine-derived non-essential amino acids played an important role in preventing cell apoptosis. This study demonstrates that glutamine metabolism plays different roles in tumor initiation and cancer maintenance. Supplementation of α-ketoglutarate and inhibiting GLS may provide a therapeutic approach to suppress enchondroma and chondrosarcoma tumor growth, respectively. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Background Granulomatous mastitis (GM) is a chronic inflammatory mastitis disease that requires long-term treatment and has a high recurrence rate. Case management has been proven to be an effective mechanism in assisting patients with chronic illness to receive regular and targeted disease monitoring and health care service. The aim of this study was to investigate the application of a hospital-to-community model of case management for granulomatous mastitis and explore the related factors associated with its recurrence. Methods This was a prospective study on patients with granulomatous mastitis based on a case management model. Data on demographic, clinical and laboratory information, treatment methods, follow-up time, and recurrence were collected and analyzed. The eight-item Morisky Medication Adherence Scale (MMAS-8) was used to investigate patients' adherence to medications. Logistic regression models were built for analysis of risk factors for the recurrence of granulomatous mastitis. Results By October 2021, a total of 152 female patients with a mean age of 32 years had undergone the entire case management process. The mean total course of case management was 24.54 (range 15–45) months. Almost all the patients received medication treatment, except for one pregnant patient who received observation therapy, and approximately 53.9% of the patients received medication and surgery. The overall recurrence rate was 11.2%, and “high” medication adherence (RR = 0.428, 95% CI 0.224–0.867, P = 0.015) was significantly associated with a lower rate of recurrence, while the rate of recurrence with a surgical procedure + medication was higher than that with medication alone (RR = 4.128, 95% CI 1.026–16.610, P = 0.046). Conclusion A case management model for patients with granulomatous mastitis was applied to effectively monitor changes in the disease and to identify factors associated with disease recurrence. “Low” medication adherence was a significant risk factor for the recurrence of granulomatous mastitis. Patients treated with medication and surgery were more likely to experience recurrence than those treated with medication alone. The optimal treatment approach should be planned for granulomatous mastitis patients, and patient medication adherence should be of concern to medical staff.

The neonicotinoid pesticide, imidacloprid (IMI), is frequently detected in the environment and in foods. It is absorbed and metabolized by the intestine; however, its effects on intestinal barrier integrity are not well studied. We investigated whether IMI disrupts the permeability of the intestinal epithelial barrier via in vivo tests on male Wistar rats, in vitro assays using the human intestinal epithelial cell line, Caco-2, and in silico analyses. A repeated oral dose 90-day toxicity study was performed (0.06 mg/kg body weight/day). IMI exposure significantly increased intestinal permeability, which led to significantly elevated serum levels of endotoxin and inflammatory biomarkers (tumor necrosis factor-alpha and interleukin-1 beta) without any variation in body weight. Decreased transepithelial electrical resistance with increased permeability was also observed in 100 nM and 100 μM IMI-treated Caco-2 cell monolayers. Amounts of tight junction proteins in IMI-treated colon tissues and between IMI-treated Caco-2 cells were significantly lower than those of controls. Increased levels of myosin light chain phosphorylation, myosin light chain kinase (MLCK), and p65 subunit of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB p65) phosphorylation were found in IMI-exposed cells compared with control cells. Furthermore, the barrier loss caused by IMI was rescued by the MLCK inhibitor, ML-7, and cycloheximide. Pregnane X receptor (PXR, NR1I2) was inhibited by low-dose IMI treatment. In silico analysis indicated potent binding sites between PXR and IMI. Together, these data illustrate that IMI induces intestinal epithelial barrier disruption and produces an inflammatory response, involving the down-regulation of tight junctions and disturbance of the PXR-NF-κB p65-MLCK signaling pathway. The intestinal barrier disruption caused by IMI deserves attention in assessing the safety of this neonicotinoid pesticide.

Detecting pesticide residues in human serum is a challenging process due to trace-level chronic exposure. Several methods using magnetic adsorbents have been developed for analyzing pesticide residue levels in human serum, but it is still difficult to achieve lower quantitative levels, and the adsorption mechanism for extracting pesticides is unclear. Herein, we propose a feasibility concept of using C

PURPOSE: The purpose of this study was to reduce the experience dependence during the orthognathic surgical planning that involves virtually simulating the corrective procedure for jaw deformities. METHODS: We introduce a geometric deep learning framework for generating reference facial bone shape models for objective guidance in surgical planning. First, we propose a surface deformation network to warp a patient's deformed bone to a set of normal bones for generating a dictionary of patient-specific normal bony shapes. Subsequently, sparse representation learning is employed to estimate a reference shape model based on the dictionary. RESULTS: We evaluated our method on a clinical dataset containing 24 patients, and compared it with a state-of-the-art method that relies on landmark-based sparse representation. Our method yields significantly higher accuracy than the competing method for estimating normal jaws and maintains the midfaces of patients’ facial bones as well as the conventional way. CONCLUSIONS: Experimental results indicate that our method generates accurate shape models that meet clinical standards.

Diarrheal shellfish toxins (DSTs) are among the most widely distributed phytotoxins, and are associated with diarrheal shellfish poisoning (DSP) events in human beings all over the world. Therefore, it is urgent and necessary to identify an effective method for toxin removal in bivalves. In this paper, we found that curcumin (CUR), a phytopolylphenol pigment, can inhibit the accumulation of DSTs (okadaic acid-eq) in the digestive gland of Perna viridis after Prorocentrum lima exposure. qPCR results demonstrated that CUR inhibited the induction of DSTs on the aryl hydrocarbon receptor (AhR), hormone receptor 96 (HR96) and CYP3A4 mRNA, indicating that the CUR-induced reduction in DSTs may be correlated with the inhibition of transcriptional induction of AhR, HR96 and CYP3A4. The histological examination showed that P. lima cells caused severe damage to the digestive gland of P. viridis, and the addition of curcumin effectively alleviated the damage induced by P. lima. In conclusion, our findings provide a potential method for the effective removal of toxins from DST-contaminated shellfish.

The GLP‐1 receptor agonist exendin‐4 has recently shown good effects in a phase II clinical trial in Parkinson's disease (PD) patients. Here, a comparison of the new GLP‐1/GIP dual receptor agonist DA5‐CH and NLY01, a 40 kDa pegylated form of exendin‐4, on motor impairments and reducing inflammation in the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) PD mouse model is provided. The drug groups received either DA5‐CH or NLY01 (25 nmol/kg) i.p. after daily MPTP intraperitoneal injection. Both drugs showed improvements in motor activity, open field experiments, rotarod tests, and gait analysis, but DA5‐CH was more potent. Tyrosine hydroxylase expression in dopaminergic neurons was much reduced by MPTP and improved by DA5‐CH, while NLY01 showed weak effects. When analyzing levels of α‐synuclein (α‐Syn), DA5‐CH reduced levels effectively while NLY01 had no effect. When measuring the levels of the inflammation markers Toll‐like receptor 4 (TLR4), specific markers of microglia activation (Iba‐1), the marker of astrocyte activation glial fibrillary acidic protein (GFAP), nuclear factor‐κB (NF‐κB), tumor necrosis factor (TNF‐α), and transforming growth factor β1 (TGF‐β1), DA5‐CH was very effective in reducing the chronic inflammation response, while NLY01 did not show significant effects. Levels of key growth factors such as Glial cell‐derived neurotrophic factor (GDNF) and Brain‐derived neurotrophic factor (BDNF) were much reduced by MPTP, and DA5‐CH was able to normalize levels in the brain, while NLY01 showed little effect. The levels of pro‐inflammatory cytokines (IL‐6 and IL‐Iβ) were much reduced by DA5‐CH, too, while NLY01 showed no effect. In a separate experiment, we tested the ability of the two drugs to cross the blood‐brain barrier. After injecting fluorescin‐labelled peptides peripherally, the fluorescence in brain tissue was measured. It was found that the pegylated NLY01 peptide did not cross the BBB in meaningful quantities while exendin‐4 and the dual agonist DA5‐CH did. The results show that DA5‐CH shows promise as a therapeutic drug for PD., GLP‐1 analogues have been shown in clinical trials to reduce Parkinson disease progression. The study compares two drugs from this group in a mouse model of PD. The drug NLY01 which is currently tested in a clinical trial in PD patients showed only limited protective effects, compared to a novel drug that can cross the blood‐brain barrier.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by KRAS- and autophagy-dependent tumorigenic growth, but the role of KRAS in supporting autophagy has not been established. We show that, to our surprise, suppression of KRAS increased autophagic flux, as did pharmacological inhibition of its effector ERK MAPK. Furthermore, we demonstrate that either KRAS suppression or ERK inhibition decreased both glycolytic and mitochondrial functions. We speculated that ERK inhibition might thus enhance PDAC dependence on autophagy, in part by impairing other KRAS- or ERK-driven metabolic processes. Accordingly, we found that the autophagy inhibitor chloroquine and genetic or pharmacologic inhibition of specific autophagy regulators synergistically enhanced the ability of ERK inhibitors to mediate antitumor activity in KRAS-driven PDAC. We conclude that combinations of pharmacologic inhibitors that concurrently block both ERK MAPK and autophagic processes that are upregulated in response to ERK inhibition may be effective treatments for PDAC. Blockade of ERK signaling in KRAS-mutant pancreatic cancer increases the dependence on autophagic flux through different mechanisms and provides a rationale for combinatorial targeting with autophagy inhibitors.

The aim of this study was to investigate the association of the formation of neutrophil extracellular traps (NETs) with gut leakage in type 1 (T1D) and type 2 diabetes (T2D).In all, 105 subjects (56 T1D, 49 T2D) were included in the study. Eight biomarkers of NET formation and gut leakage (ie, protein arginine deiminase type 4 [PAD4], neutrophil elastase [NE], proteinase 3 [PR3], complement 5a [C5a], αThere was an increase in NET-associated proteins (PAD4, NE, PR3, C5a, AAT and DNase I) in new-onset T1D patients but not in those with T2D. Of PAD4, NE, and PR3, PAD4 was found to be the most sensitive biomarker for the diagnosis of T1D. Furthermore, circulating levels of zonulin and LPS were not only increased, but were also strongly correlated with NET formation and ANCA generation in T1D patients.This study provides evidence that increased formation of NETs, particularly PAD4, is closely associated with gut leakage in T1D but not T2D, and suggests that microorganisms and the release of neutrophil cytoplasmic antigen during the formation of NETs may be involved in the pathogenesis of T1D.背景: 本研究旨在探索1型(T1D)和2型(T2D)糖尿病中中性粒细胞胞外诱捕网(neutrophil extracellular traps，NETs)的形成与肠道渗漏性是否具有相关性。 方法: 本研究对象共计有105例糖尿病患者，其中包括56例T1D患者与49例T2D患者。通过酶联免疫吸附法来测定患者血清中8种与NETs形成及肠道渗漏性相关的生物标志物含量，包括精氨酸脱亚氨酶4[PAD4]、中性细胞弹性蛋白酶[NE]、蛋白酶3[PR3]、补体5a[C5a]、α1-抗胰蛋白酶[AAT]、脱氧核糖核酸酶I[DNase I]、连蛋白[zonulin]及脂多糖[LPS]。此外，通过体外刺激中性粒细胞形成NETs并收集其形成过程中释放的细胞内容物，将其作为中性粒细胞胞质抗原来检测血清中抗中性粒细胞胞质抗体(anti-neutrophil cytoplasmic antibodies，ANCA)的含量。 结果: 与健康人相比，我们检测到在新发的T1D患者血清中，NETs相关蛋白(PAD4、NE、PR3、C5a、AAT和DNase I)的含量显著升高，但其在T2D患者血清中变化不明显。此外，在可能作为T1D诊断的生物标志物中，PAD4与NE和PR3相比，表现出更高的灵敏度。在T1D患者体内，我们不仅检测到高水平的zonulin和LPS的含量，还发现其与NETs及ANCA的形成具有极显著的相关性。 结论: 本研究表明在T1D而非T2D患者中，NETs的形成，特别是血清中PAD4含量的变化与肠道渗漏密切相关，并提示微生物入侵及NETs形成过程中中性粒细胞胞质抗原的释放可能是T1D的重要致病因素。.

Environmental cadmium (Cd) exposure can cause several pulmonary diseases. Epithelial-mesenchymal transition (EMT) involved in the process of chronic obstructive pulmonary disease (COPD). However, the association between environmental Cd exposure and EMT was unclear in COPD patients. This study aimed to analyze the associations among circulatory Cd, EMT and COPD based on case-control study. Four hundred COPD patients and 400 control subjects were recruited. Circulatory Cd was detected using atomic adsorption spectrometer. MicroRNA-30 (miR-30) was measured by RT-PCR and the markers of pulmonary EMT were evaluated through western blotting. Circulatory Cd concentration was increased and serum miR-30 was decreased in COPD patients. Circulatory Cd was inversely associated with pulmonary function in COPD patients. Moreover, serum miR-30 was gradually decreased in parallel with FEV1 in COPD patients. Meanwhile, there was a negative association between serum miR-30 and circulatory Cd in COPD patients. Further analysis found that E-cadherin, one of epithelial biomarkers, was reduced in lung tissues of COPD patients with higher circulatory Cd. On the contrary, pulmonary N-cadherin, Vimentin and α-SMA, three of mesenchymal biomarkers, were increased in COPD patients with higher circulatory Cd. In vitro experiments revealed that Cd exposure repressed miR-30 levels and promoted EMT in BEAS-2B cells. Our results provide evidence that miR-30 reduction contributing to pulmonary EMT may involve in the process of Cd-induced COPD.

The study aims at exploring the composition and characteristics of the medicinal plant resources of six major ethnic minorities living in Xishuangbanna, as well as the characteristics of traditional utilization of ethnic medicine, and promote the rational protection and inheritance and utilization of ethnic medicine resources and traditional knowledge. Based on the fourth survey of traditional Chinese medicine resources in Xishuangbanna, Yunnan province, through the methods of literature collection, interviewing and field investigation, this paper analyzed the data of the types, medicinal parts and attending diseases of medicinal plant resources of Dai, Hani, Jinuo, Wa, Lahu and Bulang nationalities. The results showed that there were 1 048 medicinal plant resources of the six ethnic minorities, and the medicinal plants were 735, 497, 272, 295, 280 and 49 in the six nationalities, respectively. The cross-use of medicinal plants among the six nationalities accounted for 62.45%, 78.07%, 88.60%, 87.46%, 82.25% and 95.92%, respectively. The main medicinal plants used by the six major ethnic minorities are root and rhizome, whole grass, leaf and stem. Various ethnic medicinal plants are mainly used in the treatment of diseases of digestive system, respiratory system, rheumatic disease, trauma, snake and insect bite and other external diseases. This study showed that Xishuangbanna has rich resources of ethnic medicinal plants. The ethnic medicine culture with Dai medicine as the main part has a long history and diversified theories, forming a unique ethnic characteristic culture. However, all ethnic medicine resources and the application of traditional knowledge are faced with the risk of gradually decreasing, it is suggested to strengthen the mining, Xishuangbanna folk medicine of ethnic culture protection and inheri-tance, and to develop regional economy and the international community has a positive influence.

This retrospective study assessed the feasible effect of Yiqihuoxue Formula (YQHXF) for the treatment of patients with ischemic stroke (IS). A total of 66 patients with IS were included in this retrospective study. All patients received routine treatment, and were divided into two groups: a treatment group (n = 33) and a control group (n = 33). In addition to the routine treatment, all patients in the treatment group also underwent YQHXF treatment. All patients in both groups were treated for a total of 8 weeks. The outcomes were assessed by National Institute of Health Stroke Scale (NIHSS), modified Rankin scale (mRS), Barthel index scale (BIS), stroke-specific quality of life (SS-QOL) scale, and adverse events. All outcomes were measured before and after the treatment. After treatment, patients in the treatment group showed better improvements in NIHSS scale (P = .01), mRS (P

Objectives Delay in diagnosis of tuberculosis (TB) is an important but under-appreciated problem. Our study aimed to analyse the patient pathway and possible risk factors of long diagnostic delay (LDD). Methods We enrolled 400 new bacteriologically diagnosed patients with pulmonary TB from 20 hospitals across China. LDD was defined as an interval between the initial care visit and the confirmation of diagnosis exceeding 14 days. Its potential risk factors were investigated by multivariate logistic regression and multilevel logistic regression. Hospitals in China were classified by increasing size, from level 0 to level 3. TB laboratory equipment in hospitals was also evaluated. Results The median diagnostic delay was 20 days (IQR: 7–72 days), and 229 of 400 patients (57.3%, 95%CI 52.4–62.1) had LDD; 15% of participants were diagnosed at the initial care visit. Compared to level 0 facilities, choosing level 2 (OR 0.27, 95%CI 0.12–0.62, p 0.002) and level 3 facilities (OR 0.34, 95%CI 0.14–0.84, p 0.019) for the initial care visit was independently associated with shorter LDD. Equipping with smear, culture, and Xpert at initial care visit simultaneously also helped to avoid LDD (OR 0.28, 95%CI 0.09–0.82, p 0.020). The multilevel logistic regression yielded similar results. Availability of smear, culture, and Xpert was lower in level 0–1 facilities than in level 2–3 facilities (p Conclusions Most patients failed to be diagnosed at the initial care visit. Patients who went to low-level facilities initially had a higher risk of LDD. Improvement of TB laboratory equipment, especially at low-level facilities, is urgently needed.

Cellular availability of acetyl-CoA, a central intermediate of metabolism, regulates histone acetylation. The impact of a high-fat diet (HFD) on the turnover rates of acetyl-CoA and acetylated histones is unknown. We developed a method for simultaneous measurement of acetyl-CoA and acetylated histones kinetics using a single 2H2O tracer, and used it to examine effect of HFD-induced perturbations on hepatic histone acetylation in LDLR−/- mice, a mouse model of non-alcoholic fatty liver disease (NAFLD). Mice were given 2H2O in the drinking water and the kinetics of hepatic acetyl-CoA, histones, and acetylated histones were quantified based on their 2H-labeling. Consumption of a high fat Western-diet (WD) for twelve weeks led to decreased acetylation of hepatic histones (p

Background and aims Diabetes is one of the most important risk factors and comorbidities of ischemic stroke. Endoplasmic reticulum stress (ERS) is considered to be the major injury mechanism of ischemic stroke with diabetes. Studies have found that incretin can inhibit ERS in ischemia-reperfusion injury of the liver and heart. We aimed to explore the effects of GLP-1/GIP double agonist DA3-CH and GLP-1 single agonist liraglutide on ERS and apoptosis in diabetic rats with cerebral ischemia-reperfusion injury. Methods and results 72 Sprague–Dawley (SD) male rats were randomly divided into 4 groups: ① blank group (Sham group, n = 18); model group (Saline group, n = 18); DA3 treatment group (DA3 group, n = 18); liraglutide treatment group (Lir group, n = 18). The Sham group was not given any treatment and was only raised in the same environment as the other groups. The remaining 3 groups used STZ-induced diabetes models. After the successful membrane formation of diabetes, DA3-CH and liraglutide (10 mmol/kg, once-daily for 14 days) were injected intraperitoneally. Thereafter, rats were subjected to middle cerebral artery occlusion followed by 24-h reperfusion. Animals were evaluated for neurologic deficit score, infarct volume, and biomarker analyses of the brain after ischemia. The DA3-CH-treated and liraglutide-treated groups showed significantly reduced scores of neurological dysfunction and cerebral infarction size, and reduced the expression of ERS markers GRP78, CHOP and Caspase-12, and the expression of apoptosis marker bax. Anti-apoptotic markers bcl-2 and neuronal numbers increased significantly. Conclusions DA3-CH and liraglutide have obvious neuroprotective effects in a rat model of cerebral ischemia-reperfusion injury with diabetes, which can reduce the infarct size and the neurological deficit score. Their exert neuroprotective effects in a rat model of cerebral ischemia-reperfusion injury with diabetes by inhibiting endoplasmic reticulum stress and thereby reducing apoptosis. DA3 is better than liraglutide.

Deformities of the maxillofacial region following trauma and ablative surgery are devastating and not uncommon. Reconstruction of such defects is a surgically challenging procedure. Conventionally, reconstruction of dental arch defects lacks preoperative customised planning and relies heavily on the surgeon experience to ensure optimum surgical outcomes. The restoration of the dental arch shape and function has taken precedence after an extensive tumour resection surgery, especially in the current age of technological advancement. Thus, personalised and accurate reconstruction of dental arch defects has become a new goal. Computer-assisted surgery, especially navigation-assisted surgery, has gained popularity of late, in reconstructing deformities and restoring facial symmetry, appearance and function in the maxillofacial region. This technology provides a clearer three-dimensional visualisation of the area of interest and its relationship with the adjacent vital structures. Together with preoperative virtual surgical planning, it allows more specific and accurate osteotomies, thus reducing the ischemia and total operating times substantially. The risk of complications is also minimised whilst improving the final surgical outcomes. The use of the intraoperative navigation system and other computer-assisted surgical techniques during surgery can significantly improve the precision of the reconstruction of dental arch deformities, and achieve personalised and functional reconstructive goals while enhancing the quality of life of patients postoperatively. The Society of Oral and Maxillofacial Surgery, Chinese Stomatological Association provides the present professional perspective and treatment protocol for navigation-guided reconstruction of dental arch defects, to allow standardisation of the technique while promoting its application among oral and maxillofacial surgeons.

Skull base surgery is an interdisciplinary subject. The anatomical structures in the skull base related to oral and maxillofacial surgery include the parapharyngeal space, the pterygopalatine fossa and the infratemporal space. This operative area is one of the most challenging surgical areas in oral and maxillofacial surgery due to its deep site, complex anatomy and high risk. Obtaining pathological information of the tumour preoperatively may help surgeons optimise their treatment plan. Needle biopsy is one of the major minimally invasive techniques that allows preoperative pathological results to be obtained. The navigation technology, which is developing rapidly nowadays, provides a reliable assistance for deep tissue biopsy surgery. Experts from the Society of Oral and Maxillofacial Surgery, Chinese Stomatological Association formulated an expert consensus on the procedures and operations of navigation-guided needle biopsy techniques for skull base tumours, so as to standardise and promote the application and operation of navigation-guided needle biopsy for skull base tumours.

Orbital fracture and orbital floor reconstruction surgery is characterised by limited surgical exposure and high risks. Before the advent of digital technology, the design and implementation of the surgical scheme for orbital floor reconstruction surgery mainly depended on the intuitive understanding of imaging and the clinical experience of surgeons, with strong unpredictability and experience dependence. Surgical navigation systems with real-time positioning and imaging functions, when used in orbital reconstruction surgery, can detect the real-time intraoperative position, avoid risks, and assist in locating the reconstruction position to ensure the accuracy of orbital reconstruction, with the help of a preoperative surgical plan. Many studies have confirmed its effect. Unilateral orbital fracture and orbital floor reconstruction surgery is one of the earliest and most widely used surgical techniques in maxillofacial surgery. Experts from the Society of Oral and Maxillofacial Surgery, Chinese Stomatological Association have fully discussed and formulated this expert consensus on navigation-guided unilateral orbital fracture and orbital floor reconstruction techniques to standardise the clinical surgical procedures and promote its application.

The zygoma is located in the medial and lateral parts of the face, supporting the midfacial contour. The forward projection of the zygoma and the zygomatic arch often expose them to injury. Fractures of the zygoma can lead to the displacement of the zygoma and the zygomatic arch, causing facial collapse deformity. For delayed zygomatic fractures, the loss of normal anatomical landmarks caused by the malunion of the fracture lines and remodelling of the bony contour makes it difficult to determine the correct positions of the zygomatic bones. In such cases, ideal and steady outcomes with satisfactory midface symmetry have been difficult to obtain using traditional surgical methods. Nowadays, the application of digital surgical software and surgical navigation helps surgeons to perform accurate preoperative simulations to obtain ideal three-dimensional virtual surgical plans and achieve accurate reduction by intraoperative navigation systems, which increase the accuracy and predictability of fracture reduction outcomes. Experts from the Society of Oral and Maxillofacial Surgery, Chinese Stomatological Association have fully discussed and formulated an expert consensus on navigation-guided unilateral delayed zygomatic fracture reconstruction techniques to standardise the clinical operation procedures and promote the application.

Neonicotinoids are a widely used class of pesticides. Co-exposure to neonicotinoids and other classes of pesticides can exert potentiating or synergistic effects, and these mixtures have been detected in human bodily fluids. The present review summarizes studies into the effects of neonicotinoid-containing pesticide mixtures on humans and other nontarget organisms. Exposure to these mixtures has been reported to result in reproductive and hormonal toxicity, genotoxicity, neurotoxicity, hepatotoxicity, and immunotoxicity in vertebrates. Mortality of pollinators and toxicity in other organisms has also been reported. The underlying mechanism of pesticide mixture toxicity may be associated with impairment of cytochrome 450 enzymes, which are involved in metabolizing pesticides. However, a comprehensive explanation of the adverse effects of neonicotinoid-containing pesticide mixtures is still required so that effective prevention and control measures can be formulated. Environ Toxicol Chem 2020;39:1884-1893. © 2020 SETAC.

General anesthetics-induced changes of electrical oscillations in the basal ganglia may render the identification of the stimulation targets difficult. The authors hypothesized that while sevoflurane anesthesia entrains coherent lower frequency oscillations, it does not affect the identification of the subthalamic nucleus and clinical outcome.A cohort of 19 patients with Parkinson's disease with comparable disability underwent placement of electrodes under either sevoflurane general anesthesia (n = 10) or local anesthesia (n = 9). Microelectrode recordings during targeting were compared for neuronal spiking characteristics and oscillatory dynamics. Clinical outcomes were compared at 5-yr follow-up.Under sevoflurane anesthesia, subbeta frequency oscillations predominated (general vs. local anesthesia, mean ± SD; delta: 13 ± 7.3% vs. 7.8 ± 4.8%; theta: 8.4 ± 4.1% vs. 3.9 ± 1.6%; alpha: 8.1 ± 4.1% vs. 4.8 ± 1.5%; all P0.001). In addition, distinct dorsolateral beta and ventromedial gamma oscillations were detected in the subthalamic nucleus solely in awake surgery (mean ± SD; dorsal vs. ventral beta band power: 20.5 ± 6.6% vs. 15.4 ± 4.3%; P0.001). Firing properties of subthalamic neurons did not show significant difference between groups. Clinical outcomes with regard to improvement in motor and psychiatric symptoms and adverse effects were comparable for both groups. Tract numbers of microelectrode recording, active contact coordinates, and stimulation parameters were also equivalent.Sevoflurane general anesthesia decreased beta-frequency oscillations by inducing coherent lower frequency oscillations, comparable to the pattern seen in the scalp electroencephalogram. Nevertheless, sevoflurane-induced changes in electrical activity patterns did not reduce electrode placement accuracy and clinical effect. These observations suggest that microelectrode-guided deep brain stimulation under sevoflurane anesthesia is a feasible clinical option.

Similar to diethylphosphate (DEP), 3,5,6-trichloro-2-pyridinol (TCP) is also a characteristic chemical substance and ultimate transformation product of chlorpyrifos (CPF) because the structure of TCP is equivalent to the trichloro pyridine structure of CPF. TCP is often used as a biomarker of CPF exposure. TCP and DEP are often detected in human blood and urine due to the widespread use of CPF. No studies have sufficiently clarified which structure contributes to the negative effect of CPF on testosterone synthesis. This study aims to explain which structure promotes the inhibitory effect of CPF on testosterone synthesis and the related influence mechanisms. After 20 weeks of exposure, the testosterone level in testes was significantly reduced by different doses of CPF (0.3 mg/kg body weight CPF and 3.0 mg/kg body weight CPF). Meanwhile, the level of testosterone synthesized by isolated primary Leydig cells was also reduced by CPF. In addition, TCP but not DEP aggravated the decrease in testosterone synthesis in isolated primary Leydig cells. On the other hand, CPF and TCP significantly decreased the levels of the Star protein, CREB phosphorylation and PKA phosphorylation, which are important in regulating testosterone synthesis. Based on these results, TCP is a key structure that mediates the CPF-induced decrease in testosterone synthesis by terminating the signal transmission of the LH-LHR-PKA-CREB-Star pathway. Thus, chemicals with the TCP structure may be potential endocrine disruptors that decrease fertility. Chemicals that can be converted to TCP or achieve a trichloro pyridine structure must be considered during reproductive toxicity risk assessment.

Disturbances in cardiac metabolism underlie most cardiovascular diseases. Metabolomics, one of the newer omics technologies, has emerged as a powerful tool for defining changes in both global and cardiac-specific metabolism that occur across a spectrum of cardiovascular disease states. Findings from metabolomics studies have contributed to better understanding of the metabolic changes that occur in heart failure and ischemic heart disease and have identified new cardiovascular disease biomarkers. As technologies advance, the metabolomics field continues to evolve rapidly. In this review, we will discuss the current state of metabolomics technologies, including consideration of various metabolomics platforms and elements of study design; the emerging utility of stable isotopes for metabolic flux studies; and the use of metabolomics to better understand specific cardiovascular diseases, with an emphasis on recent advances in the field.

Background Dental pulp stem cells (DPSCs) are multipotent and play an important role in repairing damaged and/or defective dentinogenesis/osteogenesis. Recent studies have documented the implication of miR-143 in osteogenic differentiation of DPSCs. Nevertheless, the detailed mechanisms of miR-143 involved in the osteogenic differentiation of DPSCs remain to be further elaborated. Methods Isolated DPSCs were incubated with osteogenic differentiation medium to induce osteogenic differentiation. qRT-PCR and western blot were performed to determine the expressions of miR-143 and tumor necrosis factor α (TNF-α). Luciferase reporter assay was used to confirm whether TNF-α was a target of miR-143. Osteogenic differentiation of DPSCs was evaluated by alkaline phosphatase (ALP) activity assay, ALP staining, and western blot analyses of osteogenic-markers including bone morphogenetic protein 2 (BMP2), ALP, runt-related transcription factor 2 (RUNX2) and collagen type I (COLI). Results miR-143 was downregulated and TNF-α was upregulated during osteogenic differentiation of DPSCs. miR-143 posttranscriptionally regulated TNF-α expression in DPSCs by binding to its 3′UTR. miR-143 overexpression suppressed osteogenic differentiation of DPSCs, as demonstrated by the decrease of ALP activity, ALP positive cell ratio, as well as BMP2, ALP, RUNX2, and COLI expressions. Moreover, miR-143 reversed TNF-α-induced osteogenic differentiation of DPSCs. Finally, the osteogenic differentiation of DPSCs induced by miR-143 inhibitor was attenuated following inactivation of nuclear factor kappa B (NF-κB) signaling pathway. Conclusion miR-143 suppressed the osteogenic differentiation of DPSCs by blockade of NF-κB signaling pathway via targeting TNF-α.

Currently, the road safety performance of a national- or province-level is absorbing much attention from practitioners and academics. A variety of models based on Data Envelopment Analysis (DEA) have been presented to appraise road safety performance in previous literature. However, the main weakness of these methods is that the decision-maker's psychological behavior is neglected. Besides, Cross Efficiency Method (CEM) adopts the weighted average to aggregate the cross efficiencies which may lead to information loss. To address these limitations, a hybrid road safety evaluation model was constructed by integrating CEM, regret theory, and Weighted Aggregated Sum Product Assessment (WASPAS) to appraise the road safety performance of Chinese provinces. In the presented model, regret theory is employed to depict the psychological behavior of the decision-maker. Then entropy weight method is utilized to calculate the weight of self-evaluation and peer-evaluation. To reduce information loss, WASPAS is adopted to fuse the cross efficiencies and derive the ranking of decision-making units. Finally, the presented model is employed to assess the road safety efficiency in the province of mainland China. The results show that the mean of road safety efficiency score for the eastern, central, and western areas is gradually decreasing. Furthermore, the outcomes of a comparative analysis represent that the results obtained by the proposed model outperform the CEM and DEA road safety model.

This study investigated the levels of highly toxic pesticides (HTPs) in 6554 vegetable and fruit samples from 31 regions of China, along with the associated risk of dietary exposure for the population between 2014 and 2017. 18 HTPs were detected in 325 (4.96%) samples, and the levels of HTPs in 103 (1.57%) samples were found to be higher than the maximum residue limits (MRLs) of China. The rate of detection of HTPs in six types of vegetables and fruits, in a decreasing order, was found to be as follows: eggplant (8.84%) >grape (5.58%) >tomato (5.43%) >cucumber (5.43%) >pear (3.12%) >apple (2.30%). The level of contamination of HTPs was found to be higher in vegetables compared with fruits. The vegetable and fruit samples with the highest percentages of HTPs exceeding MRLs were found in eggplants from Guangxi (20%) and grapes from Inner Mongolia (12.5%), respectively. Both, the average target hazard quotient (THQ) of a single highly toxic pesticide (HTP) and the average hazard index (HI) of the mixture of HTPs for adults and children from vegetables and fruits from the 31 regions were found to be less than one. Omethoate, carbofuran, ethoprophos, triazophos, and phorate were identified as the major contributors to the average HI for vegetables, and carbofuran, ethoprophos, omethoate, phorate, and phosphamidon were identified as the primary contributors to the average HI for fruits. The results of this study revealed that HTPs in vegetables and fruits did not cause any significant chronic risk of dietary exposure. The detection of HTPs exceeding MRLs in some of the samples implied that appropriate management guidelines for HTPs should be implemented to protect the health of the consumers.

BackgroundThe incidence of liver disease is increasing in USA. Animal models had shown glutathione species in plasma reflects liver glutathione state and it could be a surrogate for the detection of hepatocellular carcinoma (HCC).MethodsThe present study aimed to translate methods to the human and to explore the role of glutathione/metabolic prints in the progression of liver dysfunction and in the detection of HCC. Treated plasma from healthy subjects (n = 20), patients with liver disease (ESLD, n = 99) and patients after transplantation (LTx, n = 7) were analyzed by GC- or LC/MS. Glutathione labeling profile was measured by isotopomer analyzes of 2H2O enriched plasma. Principal Component Analyzes (PCA) were used to determined metabolic prints.ResultsThere was a significant difference in glutathione/metabolic profiles from patients with ESLD vs healthy subjects and patients after LTx. Similar significant differences were noted on patients with ESLD when stratified by the MELD score. PCA analyses showed myristic acid, citric acid, succinic acid, l-methionine, d-threitol, fumaric acid, pipecolic acid, isoleucine, hydroxy-butyrate and glycolic, steraric and hexanoic acids were discriminative metabolites for ESLD-HCC+ vs ESLD-HCC− subject status.ConclusionsGlutathione species and metabolic prints defined liver disease severity and may serve as surrogate for the detection of HCC in patients with established cirrhosis.

This study explores the safety and effect of acute cerebral infarction treatment by microcatheter injection of tirofiban combined with a Solitaire AB stent and/or stent implantation. Emergency cerebral angiograms showing the responsible vascular occlusion of 120 acute cerebral infarction patients who underwent emergency endovascular thrombectomy were included in the study. These patients were randomly divided into two groups using the random number table method: treatment group (n=60) that received thrombectomy (with cerebral artery stents) combined with intracerebral injection of tirofiban and control group (n=60) that only received thrombectomy (with cerebral artery stents alone). The baseline data, cerebral angiography before and after surgery, hospitalization, and follow-up results of patients in these two groups were compared. Furthermore, the incidence of major adverse cerebrovascular events of these two groups was compared (90-day modified Rankin scale, a score of 0–2 indicates a good prognosis). The difference between baseline clinical data and brain angiography between these two groups was not statistically significant. Patients in the treatment group had a higher prevalence of thrombolysis in cerebral infarction grade 2b/3 than patients in the control group (88.3% (53/60) vs 66.7% (40/60), P=0.036). Moreover, the National Institutes of Health Stroke Scale scores 7 days after surgery and the 90-day prognosis were all better for the patients who received tirofiban (P=0.048 and P=0.024). Mechanical thrombectomy with Solitaire AB stents in combination with the injection of tirofiban through a microcatheter appears to be safe and effective for the endovascular treatment of acute ischemic stroke.

Chlorpyrifos (CPF) is a widely used organophosphorus pesticide and detected frequently in fruits, vegetables, as well as in urine and blood in humans. Studies have suggested that CPF can induce metabolic disruption, such as type-2 diabetes mellitus and changed body weight. The main mechanisms are based on oxidative damage, fatty-acid synthesis, and lipid peroxidation. Studies have also shown that CPF can change reproductive hormone (RH) levels. CPF might result in metabolic disorders through altered RH levels. Here, we review the studies showing that CFP causes metabolic disruption. Then, we present the studies showing that CFP changes RH levels. Finally, we discuss a potential pathway of how CPF elicits metabolic disruption.

Acute (e.g., traumatic brain injury or stroke) and chronic (e.g., dementia or Parkinson’s disease dementia) neurological disorders that involve cognitive impairment and dysfunctional neural circuits always lead to a dreadful and costly experience for patients and their families. The application of deep brain stimulation for the treatment of neuropsychiatric disorders has shown great potential to modulate pathological neural circuits and trigger endogenous neurogenesis. We summarize several important clinical and translational studies that utilize deep brain stimulation to improve cognition based on the potentiation of neural plasticity and neurogenesis. In addition, we discuss the neuroanatomy and cerebral circuits implicated in such studies as well as the potential mechanisms underlying therapeutic benefits.

Triazophos (TAP) was a widely used organophosphorus insecticide in developing countries. TAP could produce specific metabolites triazophos-oxon (TAPO) and 1-phenyl-3-hydroxy-1,2,4-triazole (PHT) and non-specific metabolites diethylthiophosphate (DETP) and diethylphosphate (DEP). The objective of this study involved computational approaches to discover potential mechanisms of molecular interaction of TAP and its major metabolites with endocrine hormone-related proteins using molecular docking in silico. We found that TAP, TAPO and DEP showed high binding affinity with more proteins and enzymes than PHT and DETP. TAP might interfere with the endocrine function of the adrenal gland, and TAP might also bind strongly with glucocorticoid receptors and thyroid hormone receptors. TAPO might disrupt the normal binding of androgen receptor, estrogen receptor, progesterone receptor and adrenergic receptor to their natural hormone ligands. DEP might affect biosynthesis of steroid hormones and thyroid hormones. Meanwhile, DEP might disrupt the binding and transport of thyroid hormones in the blood and the normal binding of thyroid hormones to their receptors. These results suggested that TAP and DEP might have endocrine disrupting activities and were potential endocrine disrupting chemicals. Our results provided further reference for the comprehensive evaluation of toxicity of organophosphorus chemicals and their metabolites.

BACKGROUND: Disulfiram (DSF) is a drug used for treatment of alcoholism that has also displayed promising anti-cancer activity. It unfolds its effects by inhibiting the enzyme activity of aldehyde dehydrogenase (ALDH) isoforms. METHODS: MTT assay, spheroid formation, clonogenicity assay, qRT-PCR, and ALDH enzyme activity analysis were performed using ovarian cancer cell lines IGROV1, SKOV3 and SKOV3IP1. Cell cycle analyses and measurement of intracellular reactive oxygen species (ROS) were carried out by flow cytometry. ALDH+ and ALDH- cells were isolated by FACS sorting. RESULTS: ALDH activity was inhibited in ovarian cancer stem cells (the proportion of ALDH+ cells was reduced from 21.7% to 0.391%, 8.4% to 0%, 6.88% to 0.05% in cell lines IGROV1, SKOV3, and SKOV3IP1, respectively). DSF with or without the cofactor copper (Cu2+) exhibited cytotoxicity dose- and time-dependent and enhanced cisplatin-induced apoptosis. DSF + Cu2+ increased intracellular ROS levels triggering apoptosis of ovarian cancer stem cells (CSC). Significantly more colony and spheroid formation was observed in ALDH+ compared with ALDH- cells (P

Background: Globally, the proportion of child deaths that occur in the neonatal period remains a high level of 37–41%. Differences of cause in neonate death exist in different regions as well as in different economic development countries. The specific aim of this study was to investigate the causes, characteristics, and differences of death in neonates during hospitalization in the tertiary Neonatal Intensive Care Unit (NICU) of China. Methods: All the dead neonates admitted to 26 NICUs were included between January l, 2011, and December 31, 2011. All the data were collected retrospectively from clinical records by a designed questionnaire. Data collected from each NICU were delivered to the leading institution where the results were analyzed. Results: A total of 744 newborns died during the 1-year survey, accounting for 1.2% of all the neonates admitted to 26 NICUs and 37.6% of all the deaths in children under 5 years of age in these hospitals. Preterm neonate death accounted for 59.3% of all the death. The leading causes of death in preterm and term infants were pulmonary disease and infection, respectively. In early neonate period, pulmonary diseases (56.5%) occupied the largest proportion of preterm deaths while infection (27%) and neurologic diseases (22%) were the two main causes of term deaths. In late neonate period, infection was the leading cause of both preterm and term neonate deaths. About two-thirds of neonate death occurred after medical care withdrawal. Of the cases who might survive if receiving continuing treatment, parents' concern about the long-term outcomes was the main reason of medical care withdrawal. Conclusions: Neonate death still accounts for a high proportion of all the deaths in children under 5 years of age. Our study showed the majority of neonate death occurred in preterm infants. Cause of death varied with the age of death and gestational age. Accurate and prompt evaluation of the long-term outcomes should be carried out to guide the critical decision.

In silico drug design using virtual screening, absorption, distribution, metabolism and excretion (ADME)/Tox data analysis, automated docking and molecular dynamics simulations for the determination of lead compounds for further in vitro analysis is a cost effective strategy. The present study used this strategy to discover novel lead compounds from an in-house database of Traditional Chinese Medicinal (TCM) compounds against epithelial growth factor receptor (EGFR) protein for targeting non-small cell lung cancer (NSCLC). After virtual screening of an initial dataset of 2,242 TCM compounds, leads were identified based on binding energy and ADME/Tox data and subjected to automated docking followed by molecular dynamics simulation. Triptolide, a top compound identified by this vigorous in silico screening, was then tested in vitro on the H2347 cell line carrying wild-type EGFR, revealing an anti-proliferative potency similar to that of known drugs against NSCLC.

The outcome of early intravenous thrombolysis for ischemic stroke in patients with atrial fibrillation (AF) is worse than that without thrombosis. How to increase the efficacy of intravenous thrombolysis for AF-related ischemic stroke remains largely unknown. In this study, we investigated factors that influence the effect of intravenous thrombolysis in these patients. Our results showed that thrombolysis was independently associated with a favorable outcome (P

Cone-beam computed tomography (CBCT) scans are commonly used in diagnosing and planning surgical or orthodontic treatment to correct craniomaxillofacial (CMF) deformities. Based on CBCT images, it is clinically essential to generate an accurate 3D model of CMF structures (e.g., midface, and mandible) and digitize anatomical landmarks. This process often involves two tasks, i.e., bone segmentation and anatomical landmark digitization. Because landmarks usually lie on the boundaries of segmented bone regions, the tasks of bone segmentation and landmark digitization could be highly associated. Also, the spatial context information (e.g., displacements from voxels to landmarks) in CBCT images is intuitively important for accurately indicating the spatial association between voxels and landmarks. However, most of the existing studies simply treat bone segmentation and landmark digitization as two standalone tasks without considering their inherent relationship, and rarely take advantage of the spatial context information contained in CBCT images. To address these issues, we propose a Joint bone Segmentation and landmark Digitization (JSD) framework via context-guided fully convolutional networks (FCNs). Specifically, we first utilize displacement maps to model the spatial context information in CBCT images, where each element in the displacement map denotes the displacement from a voxel to a particular landmark. An FCN is learned to construct the mapping from the input image to its corresponding displacement maps. Using the learned displacement maps as guidance, we further develop a multi-task FCN model to perform bone segmentation and landmark digitization jointly. We validate the proposed JSD method on 107 subjects, and the experimental results demonstrate that our method is superior to the state-of-the-art approaches in both tasks of bone segmentation and landmark digitization.