Search

This article discusses a study that examines the genetic and molecular characteristics of lung cancer patients who have transformed from one type of lung cancer to another. The study identifies two distinct subtypes based on the RB1 gene status of the patients. The findings suggest that RB1 and SMAD4 alterations are important factors in this transformation, and patients with RB1 mutations tend to have a longer time before the transformation occurs. The article highlights the importance of understanding the heterogeneity within this patient population in order to develop new treatments and improve outcomes. Additionally, the study develops a predictive model to assess the risk of transformation in patients with specific gene mutations. Overall, this research provides valuable insights into the biology of transformed lung cancer and potential targets for therapy. [Extracted from the article]

Background: Some studies of dual-targeted therapy (DTT) targeting epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET) have shown promising efficacy in non-small-cell lung cancer (NSCLC). Consequently, patient management following DTT resistance has gained significance. However, the underlying resistance mechanisms and clinical outcomes in these patients remain unclear. Objectives: This study aimed to delineate the molecular characteristics and survival outcomes of patients with NSCLC harboring EGFR mutations and acquired MET amplification after developing resistance to DTT. Design: We conducted a retrospective analysis of patients with NSCLC with EGFR mutations and acquired MET amplification who exhibited resistance to EGFR/MET DTT. Methods: Next-generation sequencing (NGS) was performed on patients with available tissue samples before and/or after the development of resistance to DTT. Stratified analyses were carried out based on data sources and subsequent salvage treatments. Univariate/multivariate Cox regression models and survival analyses were employed to explore potential independent prognostic factors. Results: The study included 77 NSCLC patients, with NGS conducted on 19 patients. We observed many resistance mechanisms, including EGFR-dependent pathways (4/19, 21.1%), MET-dependent pathways (2/19, 10.5%), EGFR/MET co-dependent pathways (2/19, 10.5%), and EGFR/MET-independent resistance mechanisms (11/19, 57.9%). Post-progression progression-free survival (pPFS) and post-progression overall survival (pOS) significantly varied among patients who received the best supportive care (BSC), targeted therapy, or chemotherapy (CT), with median pPFS of 1.5, 3.9, and 4.9 months, respectively (p = 0.003). Median pOS were 2.3, 7.7, and 9.2 months, respectively (p < 0.001). The number of treatment lines following DTT resistance and the Eastern Cooperative Oncology Group performance status emerged as the independent prognostic factors. Conclusion: This study revealed a heterogeneous landscape of resistance mechanisms to EGFR/MET DTT, with a similar prevalence of on- and off-target mechanisms. Targeted therapy or CT, as compared to BSC, exhibited the potential to improve survival outcomes for patients with advanced NSCLC following resistance to DTT. [ABSTRACT FROM AUTHOR]

We extend the concept of graph representations modulo integers introduced by Erdös and Evans to graph representations over finite rings and generalize it to representations of signed graphs. We introduce several representation numbers and product dimensions of graphs and signed graphs and compute these quantities for a few special classes of signed graphs. [ABSTRACT FROM AUTHOR]

Farmers' participation in food safety governance is an important part of food safety social co-governance, and the accurate identification of its influencing factors and their related paths is of guiding significance to the scientific decision-making of food safety governance. The system of influencing factors of farmers' participation in food safety governance was constructed from four dimensions, and the influence network of each dimension was revealed by decision laboratory analysis (DEMATEL). The hierarchical structure and correlation path of influencing factors were determined by interpretive structural model (ISM), and the attributes of influencing factors were further classified by cross influence matrix multiplication (MICMAC). The results show that the influencing factors of farmers' participation in food safety governance can be divided into seven levels, among which the level of education and the status of village cadres are the fundamental characteristic factors. The degree of rural informatization, the intensity of government supervision, the promotion of village committees, the response of the government and the degree of disclosure of government information are the deep core factors, and risk cognition, political trust and family eating habits are special factors. Taking the importance and attribute status of farmers' participation in food safety governance into decision-making considerations is of great significance to improve the efficiency of food safety governance. [ABSTRACT FROM AUTHOR]

Based on the first-principles of density functional theory, we use the PBEsol + U method to calculate the lattice and electronic structures, as well as mechanical and optical properties of ThO2, PaO2 and UO2 and (Th, Pa)O2 and (U, Pa)O2. The results of structural optimization indicate that the PBEsol + U method can provide more accurate lattice and mechanical parameters for actinidebased oxide ThO2, PaO2, and UO2. The calculation results show that the lattice parameters and the bandgaps of ThO2, PaO2, and UO2 are consistent with the experimental values and other related theoretical values. In the meanwhile? the lattice parameters of (Th, Pa)O2 and (U, Pa)O2 are between ThO2 and UO2, while predicting the band gaps of (Th, Pa)O2 and (U, Pa)O2 are also between ThO2 and UO2. Electronic properties calculations indicate that PaO2 and UO2 are Mott insulators, while ThO2 is a charge-transfer insulator. These are consistent with experiments and theoretical conclusions. (Th, Pa)O2 and (U, Pa)O2 have significant spin polarization effects near the Fermi energy level, and the bands are mainly occupied by Pa-5f and U5f electronic state, respectively. Lastly, the real and imaginary parts and optical parameters of the optical dielectric functions of these systems are compared and analyzed. [ABSTRACT FROM AUTHOR]

A simple liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI/MS) method has been developed to analyze oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (ox-PAPC) products on the lipoproteins of uremic patients. The native PAPC standard was in vitro oxidized by the Fenton reaction, and the ox-PAPC products were analyzed by LC- ESI/MS. For LC, a C8 column and a mobile phase (acetonitrile-isopropanol containing 0.1% formic acid (70:30, v/v)) were selected. For ESI/MS, the optimal conditions included sheath gas pressure (10 psi), capillary temperature (270 °C), and injection time (1000 ms). The identification of ox-PAPC products on human lipoproteins was based on the extracted ion chromatograms (EICs) and the ESI-MS spectra of the in vitro oxidation products of PAPC standard. The EICs and ESI-MS spectra showed good repeatability and sensitivity. A total of 21 ox-PAPC products was determined. Linear analysis has been performed for the phospholipid standard, 1, 2-Di-O-hexadecyl-sn-glycero-3-phosphocholine (PC(O-16:0/O-16:0)). The linear range was 5.0–100.0 µg/mL, and the coefficient of determination (R2) was 0.989. The concentration limit of detection (LOD) was 1.50 µg/mL, and the concentration limit of quantitation (LOQ) was 4.54 µg/mL. The selected 21 ox-PAPC products have been identified and quantified in very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) of uremic and healthy subjects. Interestingly, the results showed that the levels of 18 products in VLDL, one product in LDL, and 19 products in HDL were significantly higher for uremic patients than healthy controls. This simple LC-ESI/MS method might accelerate the searching for biomarkers of uremia in the future. [ABSTRACT FROM AUTHOR]

Lung cancer is the most malignant form of cancer and has the highest morbidity and mortality worldwide. Due to drug resistance, the current chemotherapy for lung cancer is not effective and has poor therapeutic effects. Tripchlorolide (T4), a natural extract from the plant Tripterygium wilfordii, has powerful immunosuppressive and antitumour effects and may become a potential therapeutic agent for lung cancer. Therefore, this study aimed to investigate the effect of T4 on reducing chemoresistance in lung cancer cells and to explore the mechanism. 1. A549 and A549/DDP cells were separately transfected with AEG-1 overexpression and AEG-1 knockdown plasmids. A549/DDP cells were divided into the A549/DDP empty group, T4 group, and T4 + AEG-1 overexpression group. A CCK-8 assay was used to evaluate the proliferation of cells in each group. RT–qPCR and Western blotting were used to detect the expression of AEG-1 and MDR-1. Expression of AEG-1 in A549 and A549/DDP cells was positively correlated with cisplatin resistance. When the AEG-1 protein was overexpressed in A549 cells, the lethal effect of cisplatin on A549 cells was attenuated (all P < 0.05). After the AEG-1 protein was knocked down in A549/DDP cells, cisplatin was applied. The lethal effect was significantly increased compared to that in the corresponding control cells (all P < 0.05). AEG-1 protein expression gradually decreased with increasing T4 concentration in A549 and A549/DDP cells. Resistance to cisplatin was reduced after the addition of T4 to A549/DDP cells (P < 0.05), and this effect was enhanced after transfection with the AEG-1 knockdown plasmid. T4 plays an important role in increasing the sensitivity of lung cancer cells to cisplatin. [ABSTRACT FROM AUTHOR]

Lung cancer is the most malignant form of cancer and has the highest morbidity and mortality worldwide. Due to drug resistance, the current chemotherapy for lung cancer is not effective and has poor therapeutic effects. Tripchlorolide (T4), a natural extract from the plant Tripterygium wilfordii, has powerful immunosuppressive and antitumour effects and may become a potential therapeutic agent for lung cancer. Therefore, this study aimed to investigate the effect of T4 on reducing chemoresistance in lung cancer cells and to explore the mechanism. 1. A549 and A549/DDP cells were separately transfected with AEG-1 overexpression and AEG-1 knockdown plasmids. A549/DDP cells were divided into the A549/DDP empty group, T4 group, and T4 + AEG-1 overexpression group. A CCK-8 assay was used to evaluate the proliferation of cells in each group. RT–qPCR and Western blotting were used to detect the expression of AEG-1 and MDR-1. Expression of AEG-1 in A549 and A549/DDP cells was positively correlated with cisplatin resistance. When the AEG-1 protein was overexpressed in A549 cells, the lethal effect of cisplatin on A549 cells was attenuated (all P < 0.05). After the AEG-1 protein was knocked down in A549/DDP cells, cisplatin was applied. The lethal effect was significantly increased compared to that in the corresponding control cells (all P < 0.05). AEG-1 protein expression gradually decreased with increasing T4 concentration in A549 and A549/DDP cells. Resistance to cisplatin was reduced after the addition of T4 to A549/DDP cells (P < 0.05), and this effect was enhanced after transfection with the AEG-1 knockdown plasmid. T4 plays an important role in increasing the sensitivity of lung cancer cells to cisplatin. [ABSTRACT FROM AUTHOR]

Background: MET dysregulation has been implicated in the development of primary and secondary resistance to EGFR tyrosine kinase inhibitor (TKI) therapy. However, the clinicopathological characteristics and outcomes of patients harboring EGFR‐sensitive mutations and de novo MET amplifications still need to be explored. Methods: A total of 54 patients from our hospital with non‐small cell lung cancer harboring EGFR‐sensitive mutations and/or de novo MET amplifications were included in this study. Survival rates were estimated by the Kaplan–Meier method with log‐rank statistics. Lung cancer organoids (LCOs) were generated from patient‐derived malignant pleural effusion to perform drug sensitivity assays. Results: Fifty‐four patients with the appropriate clinicopathological characteristics were enrolled. MET FISH was performed in 40 patients who were stratified accordingly into two groups: EGFR+/METamp‐ (n = 22) and EGFR+/METamp + (n = 18). Survival rates for EGFR+/METamp‐ and EGFR+/METamp + patients respectively, were as follows: the median progression‐free survival (PFS) was 12.1 and 1.9 months (p<0.001); the median post‐progression overall survival (pOS) was 25.6 and 11.6 months (p = 0.023); the median overall survival (OS) was 33.2 and 12.7 months (p = 0.013). Drug testing conducted in LCOs derived from malignant pleural effusion from EGFR+/METamp + patients showed that dual targeted therapy was more effective than TKI monotherapy. Conclusion: EGFR+/METamp + patients treated with first‐line TKI monotherapy had poor clinical outcomes. Dual targeted therapy showed potent anticancer activity in the LCO drug testing assay, suggesting that it is a promising first‐line treatment for EGFR+/METamp + patients. Randomized controlled trials are needed to further validate these results. [ABSTRACT FROM AUTHOR]

Proinflammatory immune cell subsets constitute the majority in the local microenvironment after spinal cord injury (SCI), leading to secondary pathological injury. Previous studies have demonstrated that inflammasomes act as an important part of the inflammatory process after SCI. Probenecid, an inhibitor of the Pannexin-1 channel, can inhibit the activation of inflammasomes. This article focuses on the effects of probenecid on the local immune microenvironment, histopathology, and behavior of SCI. Our data show that probenecid inhibited the expression and activation of nucleotide-binding oligomerization domain receptor pyrindomain-containing 1 (NLRP1), apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1, interleukin-1β (IL-1β), and caspase-3 proteins associated with inflammasomes, thereby suppressing the proportion of M1 cells. And consequently, probenecid reduced the lesion area and demyelination in SCI. Moreover, the drug increased the survival of motor neurons, which resulted in tissue repair and improved locomotor function in the injured SC. Altogether, existing studies indicated that probenecid can alleviate inflammation by blocking Pannexin-1 channels to inhibit the expression of caspase-1 and IL-1β, which in turn restores the balance of immune cell subsets and exerts neuroprotective effects in rats with SCI. [ABSTRACT FROM AUTHOR]

Aim: Hydroxychloroquine (HCQ) is used to control proteinuria in IgA Nephropathy (IgAN) However, its efficacy and safety in pregnant IgAN patients remains unknown. This study aimed to verify the safety of HCQ in pregnant IgAN patients and compare renal function and pregnancy outcomes with those of patients not treated with HCQ. Methods: We retrospectively reviewed medical records of all pregnant IgAN patients and singleton gestations at Peking University First Hospital from 2003–2021. Patients who did and did not receive HCQ treatment during pregnancy were compared. Results: We found no significant pre‐ or post‐pregnancy differences in proteinuria or renal function between the two groups. However, the HCQ (+) group had higher proteinuria at the time of kidney biopsy (2.04 [1.26, 2.56] g/d vs. 0.80 [0.44, 1.11] g/d, P <.001); the proteinuria level at HCQ therapy initiation was also higher than that at the beginning of pregnancy (1.87 [1.30, 2.59] g/d vs. 1.08 [0.75, 1.50] g/d, P =.001). Despite no difference in preterm birth, birth weight, preeclampsia or postpartum haemorrhage, the proportion of patients with a previous history of spontaneous abortion was higher in the HCQ (+) group than in the HCQ (−) group (48.0% vs. 20.6%, P =.010). The eGFR (regression coefficient, 0.981; 95%CI 0.964–0.998) was a predictive factor for obstetrical complications. Conclusion: HCQ is safe for IgAN treatment during pregnancy with effective reduction of proteinuria. HCQ might also be helpful in patients with a history of spontaneous abortion. SUMMARY AT A GLANCE: In this retrospective comparison of 25 pregnant patients with IgA nephropathy treated with hydroxychloroquine (HCQ) versus 65 other pregnant IgAN patients who were not given HCQ, it was found that HCQ is safe and effective in reducing proteinuria. Multivariate regression shows that baseline eGFR is a predictor of obstetric complications. [ABSTRACT FROM AUTHOR]

This research applies experimental measurements and NUBEAM, ONETWO and TRANSP modules to investigate the shine-through (ST) loss ratio and beam heating percentage of neutral beam injection on EAST. Measurements and simulations confirm that the ST loss ratio increases linearly with beam energy, and decreases exponentially with plasma density. Moreover, using the multi-step fitting method, we present analytical quantitative expressions of ST loss ratio and beam heating percentage, which are valuable for the high parameter long-pulse experiments of EAST. [ABSTRACT FROM AUTHOR]

Summary: The isolation of male and female gametes is an effective method to study the fertilization mechanisms of higher plants. An osmotic shock method was used to rupture pollen grains of Allium tuberosum Roxb and release the pollen contents, including generative cells, which were mass collected. The pollinated styles were cut following 3 h of in vivo growth, and cultured in medium for 6–8 h, during which time pollen tubes grew out of the cut end of the style. After pollen tubes were transferred into a solution containing 6% mannitol, tubes burst and released pairs of sperm cells. Ovules of A. tuberosum were incubated in an enzyme solution for 30 min, and then dissected to remove the integuments. Following transfer to a dissecting solution free of enzymes, each nucellus was cut in the middle, and squeezed gently on the micropylar end, resulting in the liberation of the egg, zygote and proembryo from ovules at selected stages. These cells can be used to explore fertilization and embryonic development using molecular biological methods for each cell type and development stage. [ABSTRACT FROM AUTHOR]

Previous studies have shown that caspase-1 plays an important role in the acute inflammatory response of spinal cord injury (SCI). VX-765, a novel and irreversible caspase-1 inhibitor, has been reported to effectively intervene in inflammation. However, the effect of VX-765 on genome-wide transcription in acutely injured spinal cords remains unknown. Therefore, in the present study, RNA-sequencing (RNA-Seq) was used to analyze the effect of VX-765 on the local expression of gene transcription 8 h following injury. The differentially expressed genes (DEGs) underwent enrichment analysis of functions and pathways by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, respectively. Parallel analysis of western blot confirmed that VX-765 can effectively inhibit the expression and activation of caspase-1. RNA-Seq showed that VX-765 treatment resulted in 1,137 upregulated and 1,762 downregulated DEGs. These downregulated DEGs and their associated signaling pathways, such as focal adhesion, cytokine-cytokine receptor interaction, leukocyte transendothelial migration, extracellular matrix-receptor interaction, phosphatidylinositol 3-kinase-protein kinase B, Rap1 and hypoxia inducible factor-1 signaling pathway, are mainly associated with inflammatory response, local hypoxia, macrophage differentiation, adhesion migration and apoptosis of local cells. This suggests that the application of VX-765 in the acute phase can improve the local microenvironment of SCI by inhibiting caspase-1. However, whether VX-765 can be used as a therapeutic drug for SCI requires further exploration. The sequence data have been deposited into the Sequence Read Archive (https://www.ncbi.nlm.nih.gov/sra/PRJNA548970). [ABSTRACT FROM AUTHOR]

Purpose This study aimed to investigate the influence of diagnosis, body weight, sex, age, smoking, formulations, and concomitant drugs on steady‐state dose‐corrected serum concentrations (C/D) of venlafaxine (VEN) and O‐desmethylvenlafaxine (ODV). Methods: A retrospective analysis of therapeutic drug monitoring (TDM) was carried out. Patients' demographic data, therapeutic regimens, and concentrations were collected. Results: We included 91 verified samples from 80 patients. Females had by average 13% smaller body weight, 50% higher C/D of VEN, and VEN + ODV and 25% smaller ODV/VEN than males. Patients >60 years had by average 33–59% higher C/D levels of ODV and VEN + ODV than younger patients. The concomitant use of valproic acid caused an average 51% higher C/D of ODV and a 2.2‐fold larger ODV/VEN, while clozapine was related with 40% smaller ratio of ODV/VEN and 38% lower C/D levels of ODV. Positive correlations were detected between valproic acid concentrations and the C/D of VEN and VEN + ODV. In a multiple linear regression analysis, variance in the C/D of VEN + ODV was partly attributed to the daily dose of VEN, sex, age and valproic acid concentration. Conclusion: Our results suggested daily dose of VEN, sex, age, and valproic acid as indicators for the C/D of VEN + ODV in Chinese patients. TDM as a valuable tool was suggested in elderly female patients and patients receiving polypharmacy. [ABSTRACT FROM AUTHOR]

In this paper, we consider regular automorphism groups of graphs in the RT2 family and the Davis‐Xiang family and amorphic abelian Cayley schemes from these graphs. We derive general results on the existence of non‐abelian regular automorphism groups from abelian regular automorphism groups and apply them to the RT2 family and Davis‐Xiang family and their amorphic abelian Cayley schemes to produce amorphic non‐abelian Cayley schemes. [ABSTRACT FROM AUTHOR]

In this paper, the dispersion properties of three-dimensional function magnetized plasma photonic crystals (FMPPCs) are theoretically studied by a modified plane wave expansion method, when the magneto-optical Faraday effect is considered, and the directions of the electromagnetic wave vector and the extrinsic magnetic field are always parallel to each other. The arrangement of these FMPPCs is that the function dielectric square columns are embedded into the plasma background, and the inserted dielectric columns are arranged by woodpile lattices with face-centered-tetragonal symmetry. The relative permittivity of function square columns depends on the space coordinates. The relationships between the parameters of FMPPCs and the photonic bandgaps (PBGs) for the right and left circular polarization waves also are investigated. The calculated results demonstrate that those PBGs can be tailored by those parameters, and the right and left circular polarization waves can be split when the extrinsic magnetic field is large enough. [ABSTRACT FROM AUTHOR]

Background: Hydroxychloroquine (HCQ) is a well-known immunomodulator that is useful as in the treatment for lupus because of its inhibitory effect on toll-like receptors and cytokines, which are speculated to play a role in the pathogenesis of Immunoglobulin A (IgA) nephropathy (IgAN). However, there was only one study that investigated the effect of HCQ on proteinuria in patients with IgAN.Methods: Ninety patients with IgAN who received HCQ in addition to optimized dosage of renin-angiotensin-aldosterone system inhibitors (RAASi) were recruited for this study, and 90 matched historical controls who received RAASi alone were selected from our registry by the propensity score matching method. Their clinical data were compared at baseline and during follow-up till the termination of HCQ or addition of immunosuppressive agents.Results: The median baseline proteinuria level of the 90 patients who received HCQ was comparable with the RAASi-alone group (1.5 [1.2, 2.1] vs. 1.5 [1.2, 1.9] g/day, p = 0.74). At 6 months post-study initiation, the median proteinuria level in the HCQ group was lower than that in the RAASi-alone group (0.8 [0.7, 1.2] vs. 1.2 [0.8, 1.8] g/day, p = 0.02). The percentage by which proteinuria was reduced in the HCQ group was significantly higher than that in the RAASi-alone group (-43% [-57, -12] vs. -19% [-46, 17], p = 0.01). No serious adverse effects were documented during treatment with HCQ.Conclusion: The addition of HCQ to RAASi resulted in a significant and safe reduction in proteinuria in patients with IgAN. [ABSTRACT FROM AUTHOR]

Background:Limb-girdle muscular dystrophy type 2I (LGMD2I) is an autosomal recessive hereditary disorder caused by mutations in the fukutin-related protein (FKRP) gene. Although the features of the disorder in European patients have been summarized, Asian patients with LGMD2I have rarely been reported. Thus, the clinical differences in LGMD2I between Asian and European patients and the associated genetic changes remain unclear. Methods:We reported detailed clinical data as well as results from muscle biopsy, muscle MRI and genetic analysis of theFKRPgene in two unrelated Chinese families with LGMD2I. Additionally, a review of the literature focusing on the clinical and mutational features of LGMD2I in Asian patients was performed. Results:The muscle biopsy results showed dystrophic features. Immunohistochemical staining revealed decreased glycosylations on α-dystroglycan. The muscle MRI results showed that the gluteus maximus, adductor, biceps femoris, vastus intermedius and vastus lateralis were severely affected. The patients in the two families harbored the same compound heterozygous mutations (c.545A>G and c.948delC). One patient showed significant clinical improvement after corticosteroid treatment. Conclusion:Our study expanded the reported spectrum of Asian LGMD2I patients. Our literature review revealed that pathogenic mutations in theFKRPgene in Asian LGMD2I patients are compound heterozygous rather than homozygous. Compound heterozygous Asian patients have a mild phenotype but frequently show respiratory and cardiac impairments. Corticosteroids may be beneficial for the treatment of LGMD2I and should be further investigated. [ABSTRACT FROM AUTHOR]

Background/Aims: Cognitive impairment and abnormal structural neuroimaging is common in chronic kidney disease patients. We aimed to explore its association with dialysis modality and the relationship between cognitive impairment and abnormal structural neuroimaging. Methods: Sixty peritoneal dialysis patients and 30 hemodialysis and 30 non-dialyzed stage 3-5 chronic kidney disease patients without history of stroke were enrolled for the study. Participants were matched for age, gender, education, diabetes status, and dialysis duration (if appropriate). Cognitive functions were measured using a battery of recognized instruments. Brain features were examined with 3-dimensional magnetic resonance imaging. Results: Cognitive impairment was significantly more severe in dialysis patients than in non-dialyzed patients. The global and specific cognitive function were not significantly different between patients on peritoneal dialysis and hemodialysis. Hemodialysis patients had more severe white matter hyperintensity, sulcal and ventricular atrophy, and SVIs than other patients. In all groups, higher white matter grade, ventricular grade, and hippocampal atrophy were significantly associated with global cognitive impairment, with hazard ratios of 1.80 (1.22-2.64), 1.67 (1.09-2.57), and 2.49 (1.07-5.77), respectively. White matter grade was also significantly associated with delayed memory (hazard ratio 1.63; 1.12-2.39). Conclusion: Dialysis modality showed no association with cognitive impairment, although hemodialysis patients had more severe neuroimaging abnormalities. For the whole group, white matter hyperintensity, and ventricular and hippocampal atrophy, were independently associated with global cognitive impairment in chronic kidney disease patients. [ABSTRACT FROM AUTHOR]

Background: To investigate the role of CD138 immunohistochemistry in the diagnosis of chronic endometritis (CE) and the risk factors for assisted conception patients having CE complications.Methods: Ninety-three patients, with normal uterine shape confirmed by examination and who were planning to undergo assisted conception treatments, were selected as research subjects. Endometrial tissue was isolated for routine hematoxylin and eosin (HE) and CD138 immunohistochemical staining. Additionally, the disease histories of patients were collected, and the reproductive prognosis was followed up.Results: ① CE detection rate: The rate of CD138 immunohistochemical staining was greater than that of HE staining (27.96 % vs. 26.89 %, P <0.05); ② Pregnancy rate: the pregnancy rate of CD138-positive patients (7.7 %) was lower than the pregnancy rate of CD138-negative patients (31.3 %) (p = 0.017 < 0.05); ③ The results from univariate analysis showed that a previous history of prolonged menstrual bleeding episodes, an abortion history, and complications of fallopian tube obstruction were associated with CE (P <0.05). The results of logistic regression analysis confirmed that prolonged menstrual bleeding episodes (P = 0.014, OR = 5.394, 95 % CI 1.405-20.699), a previous abortion history (P = 0.029, OR = 3.194, 95 % CI 1.125-9.073), and fallopian tube obstruction (P = 0.028, OR = 3.274, 95 % CI 1.139-9.415) were independent risk factors for positive CD138 results.Conclusions: CD138 immunohistochemistry can improve the CE diagnosis rate. A previous history of prolonged menstrual bleeding episodes, an abortion history, and a history of fallopian tube obstruction are risk factors for chronic endometritis, and a CD138 immunohistochemical examination should be advised among them. [ABSTRACT FROM AUTHOR]

Eye-specific segregation in the dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC) starts from the embryonic stage and continues to develop postnatally until eye-opening in mice. However, there have been few systematic studies on the details of this developmental process. Here, we carried out time-dependent studies of eye-specific segregation in the dLGN and SC. Our results demonstrated that the development of eye-specific segregation in the SC is completed before postnatal day 12 (P12), which is earlier than in the dLGN (P20). During the whole period, ipsilateral and overlapping axonal projections decreased continuously in both the dLGN and SC. On the other hand, contralateral axonal projections showed little change, except for a slight decrease between P8 and P20 in the dLGN. [ABSTRACT FROM AUTHOR]

The properties of the reflectance for a superconductor multilayer structure with periodically varying ambient temperature have been theoretically investigated by the transfer matrix method (TMM). From the numerical results, it has been shown that such system has the photonic band gap (PBG) properties of photonic crystals (PCs), so it can also be called superconductor photonic crystals (SPCs). It is found that the locations and bandwidths of PBGs can be modulated by the incident angle. The frequency ranges and central frequencies of PBGs can be tuned by the temperature and thickness of superconductor layer A (higher temperature superconductor layer), respectively. The bandwidths of PBGs can be notably enlarged with increasing the temperature of superconductor layer A. The frequency ranges of PBGs can be controlled by increasing the thickness of superconductor layer A, and the more PBGs appear. The damping coefficient of superconductor and the number of periods have little effect on the bandwidths of PBGs under low-temperature conditions. It is shown that this kind of SPCs has potential applications in filters, microcavities, and fibers, etc. [ABSTRACT FROM AUTHOR]

We report on a molecular dynamics study of the swelling patterns of an Na-rich/Cs-poor montomorillonite and a Csmontomorillonite. The recently developed CLAYFF force field is used to predict the basal spacing as a function of the water content in the interlayer. The simulations reproduce the swelling patterns of the Na and Cs-montomorillonite, suggesting a mechanism of its hydration different from that of the montomorillonite. In addition, we find that the differences in size and hydration energy of Na and Cs ions have strong implications for the structure and the internal energy of interlayer water. In particular, our results indicate that the hydrate difference in the presence of coexistent Na and Cs has a larger influence on the behavior of a clay-water system. For Na-rich/Cs-poor montomorillonite, the hydration energy values of Na ions and water molecules each have a dramatic increase compared with those in Na-montomorillonite on the interlayer spacing, and the hydration energy values of Cs ions and water molecules decrease somewhat compared with those in Cs-montomorillonite. [ABSTRACT FROM AUTHOR]

Among new biological markers that could become useful prognostic factors for non-small cell lung cancer (NSCLC). Survivin is one of the most commonly over-expressed oncogenes, however, its role in NSCLC remains controversial. We performed a systematic review of the literature with meta-analysis to clarify this issue. Electronic databases were used to identify published studies before August 2011. Pooled hazard ratio ( HR) with 95 % confidence interval (95 % CI) was used to estimate the strength of the association of survivin expression with survival of NSCLC patients. Heterogeneity and publication bias were also assessed. Overall 29 relevant published studies including 2,517 lung cancer patients were identified from electronic databases. We found that overexpression of survivin in NSCLC patients might be a poor prognostic factor for survival 1.95 (95 % CI: 1.65-2.29; P < 0.001). Heterogeneity testing indicated that there was heterogeneity among studies. When stratified by histology types, the heterogeneity was absent. We should point out that the publication bias may partly account for the result, but the conclusion might not be affected deeply by the publication bias. When we accounted for publication bias using the trim and fill method, the results remained significant ( HR = 1.71, 95 % CI: 1.44-2.02, P < 0.001), suggesting the stability of our results. Therefore, our study suggested that survivin overexpression had a poor prognosis value in patients with NSCLC. [ABSTRACT FROM AUTHOR]

Background: Tacrolimus has been reported to be effective in refractory nephrotic syndrome, such as focal segmental glomerulosclerosis and membranous nephropathy. Some IgA nephropathy (IgAN) patients with massive proteinuria showed resistance to steroids and/or cytotoxic immunosuppressants based on the supportive therapy with renin- angiotensin system blockade. The efficacy and safety of tacrolimus in such refractory IgAN patients are extremely ambiguous, and the mechanism of tacrolimus improving proteinuria remission needs to be investigated. Methods: 14 refractory IgAN patients were enrolled. The patients received tacrolimus (0.05-0.1 mg/kg/day) and prednisone (0.5 mg/kg/day) for at least 6 months. Synaptopodin and calcineurin expression were detected in renal tissues of patients who received re-biopsy. A puromycin aminonucleoside (PAN)-induced human podocyte injury model was applied to investigate the possible role of tacrolimus in proteinuria remission. Results: Of the 14 patients enrolled, 3 were withdrawn because serum creatinine increased over 30% baseline. In 11 patients treated with tacrolimus over 6 months, 9 showed complete or partial remission and 7 achieved remission within 1 month. In renal tissues, the expression of calcineurin increased while synaptopodin decreased and recovered partially after tacrolimus therapy. In an in vitro study, F-actin disrupted in human podocytes after stimulation of PAN, while calcineurin increased and synaptopodin decreased. After co-treatment with tacrolimus the reorganization of F-actin and the expression of calcineurin and synaptopodin recovered. Conclusions: Tacrolimus showed a rapid proteinuria remission in refractory IgAN patients. The possible mechanism of tacrolimus to proteinuria remission might be podocyte cytoskeleton stabilization through inhibition of calcineurin expression. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We report a 41-year-old Chinese female with Fabry disease and diffuse thinning of the glomerular basement membrane (GBM). The patient presented with peripheral edema, mild proteinuria, microscopic hematuria, normal renal function, hypertension and tinnitus. Family screening showed that her daughter had microscopic hematuria, tinnitus and neuropathic pain. Renal biopsy of the proband showed focal segmental glomerulosclerosis with cytoplasmic vacuolization of the glomerular visceral epithelial cells by light microscopy. Laminated myelin inclusions in some of the glomerular podocytes, parietal epithelia, distal tubular epithelial cells and vascular endothelial cells along with diffuse thinning of the GBM (mean thickness of GBM: 216 ± 31 nm) were identified by electron microscopy. Genetic analysis detected a de novo novel GLA mutation, 1208 ins 21 bp, while a new variant of COL4A3 SNP M1209I was carried by mother and daughter as well as the proband’s father (I-1) and one sister (II-4). The coexistence of thinned GBM should be considered in patients with Fabry disease-manifested familial hematuria. [ABSTRACT FROM AUTHOR]

In this paper, we give an affirmative answer to a fixed point problem of S. Reich. [ABSTRACT FROM AUTHOR]

Background: Hydroxychloroquine (HCQ) is a well-known immunomodulator that was recently used in immunoglobulin A (IgA) nephropathy (IgAN) due to its antiproteinuric effects. We investigated the effects of HCQ in patients with IgAN whose proteinuria remained above 1 g/d after conventional immunosuppressive (IS) therapy.Methods: This study was a retrospective case-control study. Twenty-six patients with IgAN who received HCQ and had insufficient responses to IS therapy (corticosteroid (CS) therapy with/without IS agents) were included. Twenty-six matched historical controls who received conventional IS therapy were selected using propensity score matching. The clinical data from 6 months were compared.Results: Proteinuria at baseline was comparable between the "IS therapy plus HCQ" and "conventional IS therapy" groups (2.35 [interquartile range (IQR), 1.47, 2.98] vs. 2.35 [IQR, 1.54, 2.98] g/d, p = 0.920). A significant reduction in proteinuria was noted in IgAN patients with HCQ treatment (2.35 [IQR, 1.47, 2.98] vs. 1.10 [IQR, 0.85, 1.61] g/d, p = 0.002). The percent reduction in proteinuria at 6 months was similar between the two groups (- 39.81% [- 66.26, - 12.37] vs. -31.99% [- 67.08, - 9.14], p = 0.968). The cumulative frequency of patients with a 50% reduction in proteinuria during the study was also comparable between the two groups (53.8% vs. 57.7%, p = 0.780). No serious adverse events (SAEs) were observed during the study.Conclusions: Use of HCQ achieved has similar reduction in proteinuria compared to conventional IS therapy in patients with IgAN who had insufficient responses to IS therapy. [ABSTRACT FROM AUTHOR]

Background: After spinal cord injury (SCI), destructive immune cell subsets are dominant in the local microenvironment, which are the important mechanism of injury. Studies have shown that inflammasomes play an important role in the inflammation following SCI, and apoptosis-associated speck-like protein containing a card (ASC) is the adaptor protein shared by inflammasomes. Therefore, we speculated that inhibiting ASC may improve the local microenvironment of injured spinal cord. Here, CRID3, a blocker of ASC oligomerization, was used to study its effect on the local microenvironment and the possible role in neuroprotection following SCI.Methods: Murine SCI model was created using an Infinite Horizon impactor at T9 vertebral level with a force of 50 kdynes and CRID3 (50 mg/kg) was intraperitoneally injected following injury. ASC and its downstream molecules in inflammasome signaling pathway were measured by western blot. The immune cell subsets were detected by immunohistofluorescence (IHF) and flow cytometry (FCM). The spinal cord fibrosis area, neuron survival, myelin preservation, and functional recovery were assessed.Results: Following SCI, CRID3 administration inhibited inflammasome-related ASC and caspase-1, IL-1β, and IL-18 activation, which consequently suppressed M1 microglia, Th1 and Th1Th17 differentiation, and increased M2 microglia and Th2 differentiation. Accordingly, the improved histology and behavior have also been found.Conclusions: CRID3 may ameliorate murine SCI by inhibiting inflammasome activation, reducing proinflammatory factor production, restoring immune cell subset balance, and improving local immune microenvironment, and early administration may be a promising therapeutic strategy for SCI. [ABSTRACT FROM AUTHOR]

In this article, a multilayer dielectric antenna with an air layer is used to realize a strain sensor, which can be utilized to measure the pressure. The springs are sandwiched between a parasitic plate and the designed antenna, where an air layer exists. The pressure can be measured by the relationship between the thickness of the air layer and the S‐parameter of the designed antenna. When the springs are deformed within a certain range, the center frequency of the designed antenna (S‐parameter is less than −10 dB) is correlated with the length of deformation, which can be marked by the thickness of the air layer between the parasitic patch and the antenna. The influence of the air layer thickness on the S‐parameter of this antenna is investigated. The results show that the deformation of the springs has an approximate linear relationship with the center frequency of return loss. The design provides a new idea about stress measurement. [ABSTRACT FROM AUTHOR]

Many delicious and nutritional macrofungi are widely distributed and used in East Asian regions, considered as edible and medicinal foods. In this study, 11 species of dried and fresh, edible and medicinal macrofungi, Ganoderma amboinense, Agaricus subrufescens, Dictyophora indusiata, Pleurotus sajor-caju, Pleurotus ostreatus, Pleurotus geesteranu, Hericium erinaceus, Stropharia rugosoannulata, Pleurotus sapidus, Antrodia camphorata, and Lentinus edodes (Berk.) Sing, were investigated to determine the content of their nutritional components, including proteins, fat, carbohydrates, trace minerals, coarse cellulose, vitamins, and amino acids. The amino acid patterns and similarity of macrofungi were distinguished through principal component analysis and hierarchical cluster analyses, respectively. A total of 103 metabolic small molecules of macrofungi were identified by nuclear magnetic resonance spectroscopy and were aggregated by heatmap. Moreover, the macrofungi were classified by principal component analysis based on these metabolites. The results show that carbohydrates and proteins are two main components, as well as the nutritional ingredients, that differ among various species and varied between fresh and dried macrofungi. The amino acid patterns in L. edodes and A. subrufescens were different compared with that of the other tested mushrooms. [ABSTRACT FROM AUTHOR]

Background: Hydroxychloroquine (HCQ), a well-known immunomodulator, has recently been found to be a promising and safe anti-proteinuric agent for treating IgA nephropathy (IgAN). We aimed to compare the efficacy and safety of HCQ and corticosteroid treatment in patients with IgAN.Methods: This is a case-control study. Ninety-two patients with IgAN who received HCQ in addition to routine renin-angiotensin-aldosterone system inhibitors (RAASi) therapy were included. Ninety-two matched historical controls who received corticosteroids were selected by propensity score matching. The clinical data over 6 months were compared.Results: Baseline proteinuria levels were comparable between the HCQ and corticosteroid groups (1.7 [1.2, 2.3] vs. 1.8 [1.3, 2.5] g/d, p = 0.96). The percentage reduction in proteinuria at 6 months was smaller in the HCQ group than in the corticosteroid group (- 48.5% [- 62.6, - 31.4] vs. -62.9% [- 81.1, - 34.9], p = 0.006). The time averaged proteinuria within the 6 months of observation was comparable for the HCQ and corticosteroid groups (1.1 [0.8, 1.5] vs. 1.1 [0.5, 1.8] g/d, p = 0.48). The cumulative frequency of patients with a 50% reduction in proteinuria during the study was also comparable between the two groups (52.2% vs. 62.0%, p = 0.25). However, six of the 92 (6.5%) patients suffered from severe adverse events (SAEs) in the corticosteroid group, while no SAEs were observed in the HCQ group (6.5% vs. 0%, p = 0.03).Conclusions: The antiproteinuric effect of HCQ might be slightly inferior to that of corticosteroids over 6 months in patients with IgAN who were deemed to be candidates for HCQ and not corticosteroids treatment. However, HCQ treatment was safer than corticosteroid treatment. [ABSTRACT FROM AUTHOR]