[Mechanism of human airway epithelial cell injury induced by Candida albicans infection].

Objective: To investigate the immune mechanism of human airway epithelial cell injury induced by invasion of Candida albicans with different biofilm formation abilities. Methods: Twenty-five strains of Candida albicans isolated and cultured in General Hospital of Ningxia Medical University from June to December 2019 were selected, and quality control strain SC5314 was used as the standard strain. An in vitro model of Candida albicans biofilm was established, and the biofilm formation ability of different Candida albicans was detected by crystal violet staining and enzyme plate method. The absorbance value at 570 nm (A570) was determined by enzyme plate method. A570≥0.5, 0.250.05). Conclusion: Strong biofilm Candida albican can inhibit cell proliferation, disrupt the integrity of epithelial cells and induce cell damage by down-regulating the expression of cell proliferation-related protein.

3D Slicer and Sina appilication for surgical planning of giant invasive spinal schwannoma with scoliosis: A case report and literature review.

BACKGROUND: The surgical management of giant invasive spinal schwannomas (GISSs) has been discussed previously, and most cases are treated via the posterior approach. However, when the tumor grows beyond the spine and greatly pushes the surrounding tissues, the combined anterior-posterior approach may be a better choice. However, the anterior approach can be challenging when there is a lack of knowledge regarding the surrounding abdominal structures. CASE DESCRIPTION: A 67-year-old male suffered from slight scoliosis and an unstable spine due to GISS, which led to a long history of lower back pain and abnormal gait. Here, we report a novel method combining the use of 3D Slicer and the Sina application to help surgeons locate such lesions and better understand the three-dimensional (3D) relationship between the tumor and surrounding tissues. The proposed method promotes complete excision, shortens operation time, and reduces related complications. CONCLUSION: We recommend using the combination of 3D Slicer and Sina to assist surgeons in handling accurate 3D information of GISS while simultaneously simulating the surgery.

[Are various theoretical models of membrane anatomy mutually exclusive or inclusive?]

The theory of membrane anatomy is now widely accepted due to the observation of fine anatomical structure with the help of laparoscopic magnifying effect. From the perspective of systematic anatomy, the mesentery is considered as an integral organ in the theory of mesenteric anatomy. Interfascial anatomy belongs to regional anatomy, which focuses on the guiding significance of fascial space for operation. The theory of membrane anatomy belongs to surgical anatomy or applied anatomy, which emphasizes the anatomy of membrane and mesangial bed, and reveals the existence of 'metastasis V' in the mesentery. It is considered that the essence of membrane anatomy operation is to prevent cancer leakage. Various theories of membrane anatomy seek common ground while reserving differences, complement each other, and upgrade iteratively. They help to explain the structure and function of membrane from different perspectives and they are of great benefit to improve the quality of operations. Thus, they should be treated in an eclectic manner.

Trends in malignant melanoma mortality in 31 countries from 1985 to 2015.

BACKGROUND: Malignant melanoma (MM) causes the highest absolute number of deaths among skin cancers. An up-to-date analysis of international MM mortality trends is required for assessing the burden of disease, and may support the assessment of the effectiveness of new diagnostic, therapeutic and preventative strategies. OBJECTIVES: To report MM mortality trends between 1985 and 2015 using the World Health Organization (WHO) Mortality Database. MATERIALS AND METHODS: We used country-level MM mortality data from the WHO Mortality Database for all countries with high usability death registration data. Mortality trends were described using Joinpoint regression modelling. RESULTS: Thirty-one countries met the inclusion criteria. All countries, except the Czech Republic, demonstrated increased age-standardized death rates (ASDRs) in males over the observation period. More countries exhibited decreased or stable MM mortality in females. The median mortality rate for 2013-2015 was 2·57 deaths per 100 000 for males and 1·55 per 100 000 for females. Australia and Norway had the highest ASDRs for males (5·72 per 100 000 and 4·55 per 100 000, respectively). Norway and Slovenia had the highest ASDRs for females (3·02 per 100 000 and 2·58 per 100 000, respectively). MM mortality was greater for males than females in all countries, with sex disparity increasing across the period. Disparity in mortality between older and younger cohorts in several countries was also found. CONCLUSIONS: An overall increase in MM mortality over the past 30 years was observed. However, there was notable variation in mortality trends between countries, as well as between males and females, and between different age groups.

Improving diagnostic performance of 18F-FDG-PET/CT for assessment of regional nodal involvement in non-small cell lung cancer.

AIM: To assess the diagnostic performance of combined 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) positron-emission tomography (PET)/computed tomography (CT) mediastinal blood pool (MBP) activity cut-off for staging nodal involvement, and to examine other variables that may improve the diagnostic performance of PET/CT in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: All patients diagnosed with NSCLC who underwent endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and 18F-FDG-PET/CT between June 2016 and August 2018 were included. Nodal station and nodal staging-based analyses were performed, comparing the MBP cut-off and five other PET/CT parameters (node maximum standardised uptake value [SUVmax], node/MBP SUVmax ratio, node/tumour SUVmax ratio, node short axis diameter, and node SUVmax/node short axis diameter ratio) with histopathology results. The optimal cut-off value for each PET/CT parameter was determined using receiver operating characteristic curve analysis. RESULTS: One hundred and thirteen patients with a total of 321 nodes with pathological sampling were included. Nodal activity above MBP on PET/CT demonstrated 97.4% sensitivity, 35.8% specificity, 32.8% positive predictive value, and 97.8% negative predictive value. Of the five other PET/CT parameters examined, the two most promising were node SUVmax and node/MBP SUVmax. The node SUVmax cut-off of 3.9 demonstrated 90.9% sensitivity and 61.9% specificity, and the node/MBP SUVmax cut-off of 1.7 demonstrated 90.9% sensitivity and 60.7% specificity. CONCLUSION: Compared to the MBP cut-off, use of a higher node/MBP SUVmax ratio cut-off and use of other PET/CT variables can improve the diagnostic performance of PET/CT for NSCLC nodal staging. In particular, specificity for detecting malignant nodal involvement is improved while maintaining high sensitivity.

Eosinophilic esophagitis: Pathophysiology, diagnosis, and management.

Eosinophilic esophagitis (EoE) is a multifactorial esophageal inflammation, with a genetic predisposition, which combines a deficient esophageal mucosal barrier, an abnormal immune reaction to environmental allergens mediated by Th2 interleukins, immediate esophageal lesions and dysmotility, with secondary remodeling and fibrosis. Symptoms include reflux, abdominal pain, and food impaction, with a variation according to age. Fibroscopy shows major and minor endoscopic and histologic criteria, with a mucosal count≥15 eosinophils/high power field (Eo/hpf). A new entity has been defined, where gastroesophageal reflux disease (GERD) and EoE share responsibility: the PPIs-sensitive form of EoE (PPI-REE). Children with fibroscopy showing≥15 Eo/hpf need a second endoscopy following 8 weeks of PPI treatment. EoE has a strong association with other atopic disorders. Allergy testing (specific IgE blood test and skin prick tests [SPTs]) identifies patients at risk of anaphylaxis (14.8% of cases). The dietary therapy is based on a 4- to 12-week elimination test followed by endoscopy to check the disappearance of eosinophilic infiltration. The "dietary approaches are the amino acid-based formula, the allergy testing-based targeted diet, and the six-food elimination diet (empirical elimination of milk, wheat, soy, eggs, peanut/nuts, and fish/seafood). A recent first-line trial elimination of milk has been suggested, with wheat as a second elimination, if necessary. Dietary therapy allows remission and catch-up growth in 65% of cases. Swallowed topical steroids (budesonide in viscous gel or fluticasone propionate for nebulization) are an alternative, for which efficacy varies according to clinical and/or histological criteria and with relapses occurring at dosage tapering. Their use may be restricted by side effects, such as oral and/or esophageal candidiasis. The impact on long-term bone health and growth is unknown. Maintenance therapy is not standardized and is team-dependent, combining or not elimination diets and long-term steroids. The long-term risk of EoE is esophageal stenosis (25%) and endoscopic dilation may be repeated. Biotherapies have shown isolated histological improvement without significant clinical efficacy.

Androgen deprivation therapy and risk of rheumatoid arthritis in patients with localized prostate cancer.

Background: Androgens are generally immunosuppressive, and men with untreated hypogonadism are at increased risk for autoimmune conditions. To date, there has been no evidence linking androgen deprivation therapy (ADT) to autoimmune diseases, including rheumatoid arthritis (RA). We investigated the association between ADT and RA in patients with prostate cancer. Patients and methods: We identified 105 303 men age 66 years or older who were diagnosed with stages I-III prostate cancer from 1992 through 2006 using the Surveillance, Epidemiology, and End Results-Medicare linked database, excluding patients with a history of RA. χ2 test was used to compare 5-year Kaplan-Meier rates of RA diagnoses. Competing risk Cox regression using inverse probability of treatment weighting was utilized to examine the association between pharmacologic ADT and diagnosis of RA. Results: The 43% of patients (N = 44 785) who received ADT experienced a higher 5-year rate of RA diagnoses compared with men who did not (5.4% versus 4.4%, P < 0.001). Receipt of any ADT was associated with a 23% increased risk of being diagnosed with RA (hazard ratio 1.23, 95% confidence interval 1.09-1.40, P = 0.001). The risk of being diagnosed with RA increased with a longer duration of ADT, from 19% with 1-6 months and 29% with 7-12 months to 33% with ≥13 months (Ptrend < 0.001). Conclusions: Consistent with the immunosuppressive properties of androgens, we demonstrated for the first time that ADT was associated with an elevated risk of being diagnosed with RA in this large cohort of elderly men with prostate cancer. The risk was higher with a longer duration of ADT. Linking ADT to an increased risk of being diagnosed with an autoimmune condition adds to mounting evidence of the adverse effects of ADT that should prompt physicians to thoughtfully weigh its risks and benefits.

Risk factors for pulmonary hypertension in patients receiving maintenance peritoneal dialysis

We investigated the risk factors for pulmonary hypertension (PH) in patients receiving maintenance peritoneal dialysis (MPD). A group of 180 end-stage renal disease patients (124 men and 56 women; mean age: 56.43±8.36) were enrolled in our study, which was conducted between January 2009 and June 2014. All of the patients received MPD treatment in the Dialysis Center of the Second Affiliated Hospital of Soochow University. Clinical data, laboratory indices, and echocardiographic data from these patients were collected, and follow-ups were scheduled bi-monthly. The incidence and relevant risk factors of PH were analyzed. The differences in measurement data were compared by t-test and enumeration data were compared with the χ2 test. Among the 180 patients receiving MPD, 60 were diagnosed with PH. The remaining 120 were regarded as the non-PH group. Significant differences were observed in the clinical data, laboratory indices, and echocardiographic data between the PH and non-PH patients (all P<0.05). Furthermore, hypertensive nephropathy patients on MPD showed a significantly higher incidence of PH compared with non-hypertensive nephropathy patients (P<0.05). Logistic regression analysis showed that the proportion of internal arteriovenous fistula, C-reactive protein levels, and ejection fraction were the highest risk factors for PH in patients receiving MPD. Our study shows that there is a high incidence of PH in patients receiving MPD and hypertensive nephropathy patients have an increased susceptibility to PH.

Risk factors for pulmonary hypertension in patients receiving maintenance peritoneal dialysis.

We investigated the risk factors for pulmonary hypertension (PH) in patients receiving maintenance peritoneal dialysis (MPD). A group of 180 end-stage renal disease patients (124 men and 56 women; mean age: 56.43±8.36) were enrolled in our study, which was conducted between January 2009 and June 2014. All of the patients received MPD treatment in the Dialysis Center of the Second Affiliated Hospital of Soochow University. Clinical data, laboratory indices, and echocardiographic data from these patients were collected, and follow-ups were scheduled bi-monthly. The incidence and relevant risk factors of PH were analyzed. The differences in measurement data were compared by t-test and enumeration data were compared with the χ2 test. Among the 180 patients receiving MPD, 60 were diagnosed with PH. The remaining 120 were regarded as the non-PH group. Significant differences were observed in the clinical data, laboratory indices, and echocardiographic data between the PH and non-PH patients (all P<0.05). Furthermore, hypertensive nephropathy patients on MPD showed a significantly higher incidence of PH compared with non-hypertensive nephropathy patients (P<0.05). Logistic regression analysis showed that the proportion of internal arteriovenous fistula, C-reactive protein levels, and ejection fraction were the highest risk factors for PH in patients receiving MPD. Our study shows that there is a high incidence of PH in patients receiving MPD and hypertensive nephropathy patients have an increased susceptibility to PH.

Effects of CD3McAb and rhIL-2 activated bone marrow on the killing and purging of leukemia cells.

We investigated the roles of CD3McAb and rhIL-2 activated bone marrow in the killing and purging of leukemia cells. Cytotoxicity of activated bone marrow was detected with MTT assay. CFU-GM level in activated bone marrow and the destruction of leukemia cells were measured using the semi-solid cell culture. Immune activation markers in activated bone marrow were detected by indirect immunofluorescence assay. Bone marrow activated by CD3McAb and rhIL-2 displayed significantly upregulated the killing and purging abilities on the leukemia cell line K562 and HL-60. Such effects were superior to that of bone marrow activated by rhIL-2 or CD3McAb alone (P < 0.05, P < 0.01). Activation by rhIL-2 and (or) CD3McAb exerted no obvious influence on CFU-GM level in bone marrow. Compared with bone marrow activated by rhIL-2 or CD3McAb alone, the synergistic effect of both CD3McAb+ and hIL-2 caused significant increase of CD3(+), CD8(+), CD19(+), CD25(+), CD38(+), and CD56(+) levels. Our study indicates that CD3McAb enhanced the killing and purging effects of rhIL-2 activated bone marrow on leukemia cells.

The ground state van der Waals potentials of the calcium dimer and calcium rare-gas complexes.

The entire potential energy curve of the Ca(2) ground state generated by the Tang-Toennies potential model with its parameters specified by the three theoretical dispersion coefficients and the experimentally determined equilibrium distance and well depth is in excellent agreement with the accurate experimental potential of Allard et al. [Phys. Rev. A 66, 042503 (2002)]. The reduced potential of Ca(2) is almost identical with that of Hg(2). This leads to the conjecture that the ground state van der Waals dimer potentials of group IIA, except Be, and group IIB elements have the same shape, which is different from that of the rare-gas dimers. The potentials of Ca-RG complexes (RG=He,Ne,Ar,Kr,Xe) are generated by the same potential model with its parameters calculated from the homonuclear potentials of calcium and rare-gas dimers with combining rules. The predicted spectroscopic constants are comparable to other theoretical computations.

BDNF improves the effects of neural stem cells on the rat model of Alzheimer's disease with unilateral lesion of fimbria-fornix.

In this study, neural stem cells (NSCs) were obtained from the hippocampus using the serum-free culturing. NSCs labeled with 5'-bromo-2'-deoxyuridine (BrdU) were transplanted into transected rat basal forebrain followed by the injection of brain-derived neurotrophic factor (BDNF) into the lateral ventricle. Nestin staining and double-labeling immunohistochemistry were used to detect cell survival and neuronal differentiation of the BrdU labeled cells in the basal forebrain and it was observed that labeled NSCs differentiated into neurons and astrocytes in the basal forebrain. Immunohistochemical detection of p75(NGFR) indicated that the number of cholinergic neurons of the combination groups treated by NSCs, BDNF, and NSCs groups had more significant improvement than that of the injured groups in medial septum (MS) and vertical diagonal branch (VDB). Learning and memory abilities were also measured by Y-maze test and the results support that BDNF can enhance the treatment effects of NSCs transplanted into brain lesion model.

Enhanced CD4+ T cell proliferation and Th2 cytokine production in DR6-deficient mice.

We have found that DR6, a member of the TNF receptor family, is highly expressed in resting T cells and downregulated in activated T cells. DR6-targeted mutant mice were generated and showed normal development. However, DR6(-/-) CD4(+) T cells hyperproliferated in response to TCR-mediated stimulation and protein antigen challenge. Activated DR6(-/-) CD4(+) T cells exhibited upregulated CD25 expression and enhanced proliferation in response to exogenous IL-2 stimulation. In addition, increased CD28 and reduced CTLA-4 expression were observed in these cells. Enhanced Th2 cytokine production by activated DR6(-/-) CD4(+) T cells was associated with the increased transcription factor NF-ATc in nuclei. DR6, therefore, functions as a regulatory receptor for mediating CD4(+) T cell activation and maintaining proper immune responses.

Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway.

The c-Jun NH2-terminal kinase (JNK) is activated when cells are exposed to ultraviolet (UV) radiation. However, the functional consequence of JNK activation in UV-irradiated cells has not been established. It is shown here that JNK is required for UV-induced apoptosis in primary murine embryonic fibroblasts. Fibroblasts with simultaneous targeted disruptions of all the functional Jnk genes were protected against UV-stimulated apoptosis. The absence of JNK caused a defect in the mitochondrial death signaling pathway, including the failure to release cytochrome c. These data indicate that mitochondria are influenced by proapoptotic signal transduction through the JNK pathway.

Selective expression of JNK isoforms and stress-specific JNK activity in different neural cell lines.

The function of c-Jun N-terminal kinases (JNKs) in the nervous system is poorly understood and the majority of the data has been gained in neuronal and non-neuronal cell lines. Thus, it is not clear to which extent the expression pattern and the degree of activation of the three JNK isoforms in different cell lines are representative for their activation in the adult brain. In the present study, the expression of JNK isoforms and the activity of JNK1 were determined following UV irradiation and exposure to H(2)O(2) and TNFalpha in three neural cell lines, rat PC12, murine Neuro2A and human SHSY5Y. These cell lines differ in their expression of JNK isoforms: PC12 cells express JNK1 and JNK2, whereas Neuro2A and SHSY5Y cells displays the expression of JNK1, JNK2 and JNK3. JNK3 was not inducible following stress and differentiation in PC12 cells. The stimulation paradigms evoked different degree of cell death: UV irradiation resulted in death of around 50% in all three cell lines; exposure to 200 microM H(2)O(2) for 6 h resulted in the death of 43% Neuro2A cells and 31% PC12 cells, SHSY5Y cells are less sensitive to H(2)O(2) since only 5 mM H(2)O(2) killed 59% of SHSY5Y cells after 6 h. Exposure to 50 ng/ml TNFalpha did not induce cell death in SHSY5Y, Neuro2A and naive PC12 cells. Although differentiated PC12 cells exhibit a similar activation of JNK1 compared to naive PC12 cells after exposure to TNFalpha, 42% of differentiated PC12 cells died after 24 h. H(2)O(2) that evoked only a moderate JNK1 activity in Neuro2A and PC12 cells induced only a moderate cell death. In contrast, SHSY5Y cells exhibit a much stronger JNK1 activation accompanied with a higher degree in cell death after exposure to H(2)O(2). JNK1 activity induced by UV irradiation, however, could not be correlated with the extend of cell death. These data clearly demonstrate that expression and activation of JNK depends on the neuronal cell type and the applied stress paradigms, and that JNK activity is not simply linked to cell death.

Requirement of mitogen-activated protein kinase kinase 3 (MKK3) for tumor necrosis factor-induced cytokine expression.

The p38 mitogen-activated protein kinase is activated by treatment of cells with cytokines and by exposure to environmental stress. The effects of these stimuli on p38 MAP kinase are mediated by the MAP kinase kinases (MKKs) MKK3, MKK4, and MKK6. We have examined the function of the p38 MAP kinase signaling pathway by investigating the effect of targeted disruption of the Mkk3 gene. Here we report that Mkk3 gene disruption caused a selective defect in the response of fibroblasts to the proinflammatory cytokine tumor necrosis factor, including reduced p38 MAP kinase activation and cytokine expression. These data demonstrate that the MKK3 protein kinase is a critical component of a tumor necrosis factor-stimulated signaling pathway that causes increased expression of inflammatory cytokines.

Differentiation of CD4+ T cells to Th1 cells requires MAP kinase JNK2.

Precursor CD4+ T cells develop into effector Th1 and Th2 cells that play a central role in the immune response. We show that the JNK MAP kinase pathway is induced in Th1 but not in Th2 effector cells upon antigen stimulation. Further, the differentiation of precursor CD4+ T cells into effector Th1 but not Th2 cells is impaired in JNK2-deficient mice. The inability of IL-12 to differentiate JNK2-deficient CD4+ T cells fully into effector Th1 cells is caused by a defect in IFNgamma production during the early stages of differentiation. The addition of exogenous IFNgamma during differentiation restores IL-12-mediated Th1 polarization in the JNK2-deficient mice. The JNK MAP kinase signaling pathway, therefore, plays an important role in the balance of Th1 and Th2 immune responses.

Absence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the Jnk3 gene.

Excitatory amino acids induce both acute membrane depolarization and latent cellular toxicity, which often leads to apoptosis in many neurological disorders. Recent studies indicate that glutamate toxicity may involve the c-Jun amino-terminal kinase (JNK) group of mitogen-activated protein (MAP) kinases. One member of the JNK family, Jnk3, may be required for stress-induced neuronal apoptosis, as it is selectively expressed in the nervous system. Here we report that disruption of the gene encoding Jnk3 in mice caused the mice to be resistant to the excitotoxic glutamate-receptor agonist kainic acid: they showed a reduction in seizure activity and hippocampal neuron apoptosis was prevented. Although application of kainic acid imposed the same level of noxious stress, the phosphorylation of c-Jun and the transcriptional activity of the AP-1 transcription factor complex were markedly reduced in the mutant mice. These data indicate that the observed neuroprotection is due to the extinction of a Jnk3-mediated signalling pathway, which is an important component in the pathogenesis of glutamate neurotoxicity.