Peripheral Neuropathy Associated with Higher Mortality in Population with Chronic Kidney Disease: National Health and Nutrition Examination Surveys.

Introduction: Peripheral neuropathy (PN), one of the commonest neurological complications of chronic kidney disease (CKD), was associated with physical limitation. Studies showed that a decrease in physical capability in patients with CKD is related with an increased risk of mortality. The objective of our research was to directly explore the relationship between PN and risk of mortality in patients with CKD. Method: 1,836 participants with CKD and 6,036 participants without CKD, which were classified by PN based on monofilament examination in National Health and Nutrition Examination Survey (NHANES), were collected from the 1999 to 2004 National Health and Nutrition Examination Surveys. Multivariable Cox proportional hazard models were conducted to assess the relationships of PN and deaths in patients with CKD and non-CKD. Results: During 14 years of a median follow-up from 1999 to 2015 and 2004 to 2015, 1,072 (58.4%) and 1,389 (23.0%) deaths were recorded in participants with CKD and without CKD, respectively. PN was related with increased all-cause mortality even after adjusting possible confounding factors in population with CKD (hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.17-1.53) and without CKD (HR 1.27, 95% CI 1.12-1.43). And the adjusted HRs (95% CI) for cardiovascular mortality of the people with CKD and without CKD who suffered from PN were 1.42 (1.07, 1.90) and 1.23 (0.91, 1.67), respectively, versus those without PN. Conclusion: PN was related with a higher risk of all-cause and cardiovascular death in people with CKD, which clinically suggests that the adverse prognostic impact of PN in the CKD population deserves attention and is an important target for intervention.

JunB: a paradigm for Jun family in immune response and cancer.

Jun B proto-oncogene (JunB) is a crucial member of dimeric activator protein-1 (AP-1) complex, which plays a significant role in various physiological processes, such as placental formation, cardiovascular development, myelopoiesis, angiogenesis, endochondral ossification and epidermis tissue homeostasis. Additionally, it has been reported that JunB has great regulatory functions in innate and adaptive immune responses by regulating the differentiation and cytokine secretion of immune cells including T cells, dendritic cells and macrophages, while also facilitating the effector of neutrophils and natural killer cells. Furthermore, a growing body of studies have shown that JunB is involved in tumorigenesis through regulating cell proliferation, differentiation, senescence and metastasis, particularly affecting the tumor microenvironment through transcriptional promotion or suppression of oncogenes in tumor cells or immune cells. This review summarizes the physiological function of JunB, its immune regulatory function, and its contribution to tumorigenesis, especially focusing on its regulatory mechanisms within tumor-associated immune processes.

Development of a new prognostic index PNPI for prognosis prediction of CKD patients with pneumonia at hospital admission.

Background: The aim of this study was to investigate the relationship between pneumonia and chronic kidney disease (CKD), to elucidate potential risk factors, and to develop a new predictive model for the poor prognosis of pneumonia in CKD patients. Method: We conducted a retrospective observational study of CKD patients admitted to Tongji Hospital between June 2012 and June 2022. Demographic information, comorbidities or laboratory tests were collected. Applying univariate and multivariate logistic regression analyses, independent risk factors associated with a poor prognosis (i.e., respiratory failure, shock, combined other organ failure, and/or death during hospitalization) for pneumonia in CKD patients were discovered, with nomogram model subsequently developed. Predictive model was compared with other commonly used pneumonia severity scores. Result: Of 3,193 CKD patients with pneumonia, 1,013 (31.7%) met the primary endpoint during hospitalization. Risk factors predicting poor prognosis of pneumonia in CKD patients were selected on the result of multivariate logistic regression models, including chronic cardiac disease; CKD stage; elevated neutrophil to lymphocyte ratio (NLR) and D-dimer; decreased platelets, PTA, and chloride iron; and significant symptom presence and GGO presentation on CT. The nomogram model outperformed other pneumonia severity indices with AUC of 0.82 (95% CI: 0.80, 0.84) in training set and 0.83 (95% CI: 0.80, 0.86) in testing set. In addition, calibration curve and decision curve analysis (DCA) proved its efficiency and adaptability. Conclusion: We designed a clinical prediction model PNPI (pneumonia in nephropathy patients prognostic index) to assess the risk of poor prognosis in CKD patients with pneumonia, which may be generalized after more external validation.

Clinical characteristics and risk factor analysis of Pneumocystis jirovecii pneumonia in patients with CKD: a machine learning-based approach.

Patients with chronic kidney disease (CKD) who are being treated with immunosuppressive medications are at risk for developing Pneumocystis jirovecii pneumonia (PCP). We attempted to characterize the clinical aspects of PCP in CKD patients in order to alert high-risk patients with bad prognosis. A retrospective study of CKD patients was conducted from June 2018 to June 2022. Based on PCP diagnostic criteria, these patients were divided into PCP and non-PCP groups. Using univariate and multivariate logistic regression analysis, risk indicators were evaluated, and nomogram and decision tree were developed. Of the CKD patients screened for Pneumocystis carinii nucleic acid, 1512 were included. Two-hundred forty four (16.14%) were diagnosed with PCP. Of the PCP, 88.5% was receiving glucocorticoid (GC) therapy, of which 66.3% received more than 0.5 mg/kg GC. Multivariate analysis showed that membranous nephropathy (OR 2.35, 95% CI 1.45-3.80), immunosuppressive therapy (OR 1.94, 95% CI 1.06-3.69), and ground glass opacity of CT scanning (OR 1.71, 95% CI 1.10-2.65) were associated with increased risk of Pneumocystis carinii infection. The AUC of nomogram based on logistics regression was 0.78 (0.75-0.81). The mortality in patients with PCP was 32.40%. Univariate analysis and decision tree showed that pulmonary insufficiency (PO2: OR 0.98, 95% CI 0.96-1.00), elevated APTT (OR 1.07, 95% CI 1.04-1.11), and reduced hemoglobin (OR 0.97, 95% CI 0.96-0.98) were associated with poor prognosis. PCP is not rare in CKD patients, particularly in those treated with immunosuppressive therapy. Considering the high mortality of the cases, further studies on the prevention and management of these patients are needed.

Prophylaxis with intraocular pressure lowering medication and glaucomatous progression in patients receiving intravitreal anti-VEGF therapy.

AIM: To investigate whether pretreatment with pressure-lowering medication prior to anti-vascular endothelial factor (VEGF) injections had an effect on glaucomatous progression in patients with preexisting glaucoma or ocular hypertension (OHT). METHODS: A total of 66 eyes from 54 patients with a preexisting diagnosis of glaucoma or OHT, treated with six or more anti-VEGF injections were selected for chart review. Primary outcome measures were rate of visual field loss in dB/year, rate of change in retinal nerve fiber layer (RNFL) thickness in microns/year, and need for additional glaucoma intervention. RESULTS: The number of eyes requiring additional glaucoma medication was 5 of 20 (25.0%) and 14 of 46 (30.4%) for the pretreated and non-pretreated groups, respectively. The number of eyes requiring glaucoma laser or surgery was 4 of 20 (20.0%) and 13 of 46 (28.3%) for the pretreated and non-pretreated groups, respectively. Estimated mean rate of pattern standard deviation decline was not significant in either group (P>0.073), with no difference between groups (P=0.332). Although both groups showed significant RNFL change from baseline (P<0.011), no difference was detected between groups (P=0.467). CONCLUSION: Pretreatment has no detectable effect on structural or functional glaucomatous progression. Patients receiving repeated injections may be at risk for glaucomatous complications requiring invasive intervention.

Identification of Hub Genes and Immune-Related Pathways for Membranous Nephropathy by Bioinformatics Analysis.

OBJECTIVE: We aim to explore the detailed molecular mechanisms of membrane nephropathy (MN) related genes by bioinformatics analysis. METHODS: Two microarray datasets (GSE108109 and GSE104948) with glomerular gene expression data from 65 MN patients and 9 healthy donors were obtained from the Gene Expression Omnibus (GEO) database. After processing the raw data, DEGs screening was conducted using the LIMMA (linear model for microarray data) package and Gene set enrichment analysis (GSEA) was performed with GSEA software (v. 3.0), followed by gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. The protein-protein interaction (PPI) network analysis was carried out to determine the hub genes, by applying the maximal clique centrality (MCC) method, which was visualized by Cytoscape. Finally, utilizing the Nephroseq v5 online platform, we analyzed subgroups associated with hub genes. The findings were further validated by immunohistochemistry (IHC) staining in renal tissues from MN or control patients. RESULTS: A sum of 370 DEGs (188 up-regulated genes, 182 down-regulated genes) and 20 hub genes were ascertained. GO and KEGG enrichment analysis demonstrated that DEGs of MN were preponderantly associated with cell damage and complement cascade-related immune responses. Combined with literature data and hub gene-related MN subset analysis, CTSS, ITGB2, and HCK may play important roles in the pathological process of MN. CONCLUSION: This study identified novel hub genes in MN using bioinformatics. We found that some hub genes such as CTSS, ITGB2, and HCK might contribute to MN immunopathological process, providing new insights for further study of the molecular mechanisms underlying glomerular injury of MN.

Removal of Dinotefuran, Thiacloprid, and Imidaclothiz Neonicotinoids in Water Using a Novel Pseudomonas monteilii FC02-Duckweed (Lemna aequinoctialis) Partnership.

Neonicotinoids (NEOs) are the most widely used insecticides in the world and pose a serious threat to aquatic ecosystems. The combined use of free-floating aquatic plants and associated microorganisms has a tremendous potential for remediating water contaminated by pesticides. The aim of this study was to determine whether plant growth-promoting bacteria (PGPB) could enhance the phytoremediation efficiency of duckweed (Lemna aequinoctialis) in NEO-contaminated water. A total of 18 different bacteria were isolated from pesticide-stressed agricultural soil. One of the isolates, Pseudomonas monteilii FC02, exhibited an excellent ability to promote duckweed growth and was selected for the NEO removal experiment. The influence of strain FC02 inoculation on the accumulation of three typical NEOs (dinotefuran, thiacloprid, and imidaclothiz) in plant tissues, the removal efficiency in water, and plant growth parameters were evaluated during the 14-day experimental period. The results showed that strain FC02 inoculation significantly (p < 0.05) increased plant biomass production and NEO accumulation in plant tissues. The maximum NEO removal efficiencies were observed in the inoculated duckweed treatment after 14 days, with 92.23, 87.75, and 96.42% for dinotefuran, thiacloprid, and imidaclothiz, respectively. This study offers a novel view on the bioremediation of NEOs in aquatic environments by a PGPB-duckweed partnership.

Decreased INPP5B expression predicts poor prognosis in lung adenocarcinoma.

BACKGROUND: Inositol Polyphosphate-5-Phosphatase B (INPP5B), a inositol 5-phosphatase, plays an important role in many biological processes through phosphorylating PI(4,5)P2 and/or PI(3,4,5)P3 at the 5-position. Nevertheless, little is known about its function and cellular pathways in tumors. This study aims to investigate the potential role of INPP5B as a diagnostic and prognostic biomarker for lung adenocarcinoma (LUAD), as well as its biological functions and molecular mechanisms in LUAD. METHODS: TCGA, GEO, CTPAC, and HPA datasets were used for differential expression analysis and pathological stratification comparison. The prognostic and diagnostic role of INPP5B was determined by Kaplan-Meier curves, univariate and multivariate Cox regression analysis, and receiver operating characteristics (ROC) curve analyses. The potential mechanism of INPP5B was explored through GO, KEGG, and GSEA enrichment analysis, as well as GeneMANIA and STRING protein-protein interaction (PPI) network. PicTar, PITA, and miRmap databases were used for exploring miRNA targeting INPP5B. In molecular biology experiments, immunohistochemical analyses and Western blot analyses were used to determine protein expression. Co-immunoprecipitation assay was used to detect protein-protein interactions. CCK8 assays and colony formation assays were used for the measurement of cell proliferation. Cell cycle was assessed by PI staining with flow cytometry. Cell migration was performed by Transwell assays and wound healing assays. RESULT: INPP5B was decreased in LUAD tissues compared with normal adjacent tissues. And the low expression of INPP5B was associated with late-stage pathological features. In addition, INPP5B was found to be a significant independent prognostic and diagnostic factor for LUAD patients. Hsa-miR-582-5p was predicted as a negative regulator of INPP5B mRNA expression. INPP5B was significantly correlated with the expression of PTEN and the activity of PI3K/AKT signaling pathways, as determined by enrichment analysis and PPI network. In vitro experiments partially confirmed the aforementioned findings. INPP5B could interact directly with PTEN. INPP5B overexpression inhibited LUAD cell proliferation and migration while downregulating the AKT pathway. CONCLUSION: Our results demonstrated that INPP5B could inhibit the proliferation and metastasis of LUAD cells. It could serve as a novel diagnostic and prognostic biomarker for LUAD patients. Trial registration LUAD tissues and corresponding para-cancerous tissues were collected from 10 different LUAD patients at Hangzhou First People's Hospital. The Ethics Committee of Hangzhou First People's Hospital has approved this study. (registration number: IIT-20210907-0031-01; registration date: 2021.09.13).

Sugar-sweetened beverage consumption and mortality of chronic kidney disease: results from the US National Health and Nutrition Examination Survey, 1999-2014.

Background: The relationship between intake of sugar-sweetened beverages (SSBs) and the risk of death in patients with chronic kidney disease (CKD) is unclear. We evaluated the association between SSB intake and subsequent overall mortality in CKD patients. Methods: We included data from 3996 CKD patients who participated in the 1999-2014 National Health and Nutrition Examination Survey (NHANES). SSB intake was assessed by a 24-h dietary recall, grouped as none, >0 to <1 serving/day, 1 to <2 servings/day and ≥2 servings/day. After adjusting for demographic variables, lifestyle, diet and comorbidities, Cox proportional risk regressions were applied to analyze the associations between the daily intake of SSBs as well as added sugar from beverages and all-cause mortality. Results: In the whole research population, the median age at baseline was 67 years, 22% were Black and 54% were female. A total of 42% had stage 3 CKD. During an average follow-up period of 8.3 years, a sum of 1137 (28%) deaths from all causes was recorded. The confounder-adjusted risk of mortality was associated with an increase of 1 serving/day of SSBs, with all-cause mortality of 1.18 [95% confidence interval (95% CI)1.08-1.28], and intakes of increased 20-g added sugar/1000 kcal of total energy per day were associated with all-cause mortality of 1.14 (1.05-1.24). Equivalently substituting 1 serving/day of SSBs with unsweetened coffee [HR (95% CI) 0.82 (0.74-0.91)], unsweetened tea [HR (95% CI) 0.86 (0.76-0.98)], plain water [HR (95% CI) 0.79 (0.71-0.88)], or non- or low-fat milk [HR (95% CI) 0.75 (0.60-0.93)] were related to a 14-25% reduced risk of all-cause mortality. Conclusion: Findings suggest that in the CKD population, increased SSB intake was associated with a higher risk of mortality and indicated a stratified association with dose. Plain water and unsweetened coffee/tea might be possible alternatives for SSBs to avert untimely deaths.

MiR-149-5p: An Important miRNA Regulated by Competing Endogenous RNAs in Diverse Human Cancers.

MicroRNAs (miRNAs) consist of a large family of small, non-coding RNAs with the ability to result in gene silencing post-transcriptionally. With recent advances in research technology over the past several years, the physiological and pathological potentials of miRNAs have been gradually uncovered. MiR-149-5p, a conserved miRNA, was found to regulate physiological processes, such as inflammatory response, adipogenesis and cell proliferation. Notably, increasing studies indicate miR-149-5p may act as an important regulator in solid tumors, especially cancers in reproductive system and digestive system. It has been acknowledged that miR-149-5p can function as an oncogene or tumor suppressor in different cancers, which is achieved by controlling a variety of genes expression and adjusting downstream signaling pathway. Moreover, the levels of miR-149-5p are influenced by several newly discovered long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). However, there is blank about systematic function and mechanism of miR-149-5p in human cancers. In this review, we firstly summarize the present comprehension of miR-149-5p at the molecular level, its vital role in tumor initiation and progression, as well as its potential roles in monitoring diverse reproductive and digestive malignancies.

The monomer derivative of paeoniflorin inhibits macrophage pyroptosis via regulating TLR4/ NLRP3/ GSDMD signaling pathway in adjuvant arthritis rats.

OBJECTIVE: This study was aimed to investigate the effect of monomer derivative of paeoniflorin (MDP) on macrophage pyroptosis mediated by TLR4/NLRP3/GSDMD signaling pathway in adjuvant arthritis (AA) rats. METHOD: Wistar rats were divided into normal group, AA model group, MDP (50 mg/kg) group and MTX (0.5 mg/kg) group. The expression of TLR4, NLRP3 and GSDMD in macrophage were detected by immunofluorescence assay. The expression of TLR4 and the ratio of macrophage pyroptosis were analyzed by flow cytometry. Cell morphology was observed by scanning electron microscopy. The cytokine levels of IL-18 and IL-1ß were detected by ELISA. The expressions of proteins related to macrophage pyroptosis were detected by western blot. RESULTS: MDP has a therapeutic effect on rats AA by reducing the secondary inflammation and improving pathological changes. The results of X-ray imaging and ultrasound images showed that MDP could inhibit bone erosion, soft tissue swelling, and joint space narrowing. Macrophage pyroptosis was found in secondary inflammation of AA rats. The expressions of TLR4, MyD88, NLRP3, Caspase-1, ASC, and GSDMD-N in macrophage were increased, the levels of IL-18 and IL-1ß were enhanced, and the morphology of pyroptosis could be observed. MDP could inhibit macrophage polarization and macrophage pyroptosis, and down-regulated the cytokine levels of IL-18 and IL-1ß in AA rats. MDP could regulate the M1/M2 ratio, decreased the ratio of macrophage pyroptosis and down-regulated the expressions of TLR4, MyD88, NLRP3, Caspase-1, ASC, and GSDMD-N in vivo and in vitro. CONCLUSION: Abnormal activation of TLR4/NLRP3/GSDMD signaling pathway may be involved in macrophage pyroptosis in AA rats. The therapeutic effect of MDP on AA rats is related to the inhibition of macrophage pyroptosis by regulating the TLR4/NLRP3/GSDMD signaling pathway.

Enhanced Biocontrol of Cucumber Fusarium Wilt by Combined Application of New Antagonistic Bacteria Bacillus amyloliquefaciens B2 and Phenolic Acid-Degrading Fungus Pleurotus ostreatus P5.

Continuous monoculture of cucumber (Cucumis sativus L.) typically leads to the frequent incidence of Fusarium wilt caused by Fusarium oxysporum f. sp. cucumerinum (FOC). As potent allelochemicals, phenolic acids are believed to be associated with soilborne diseases. This study aimed to investigate the effect of single or co-inoculation of antagonistic bacteria Bacillus amyloliquefaciens B2 and phenolic acid-degrading fungus Pleurotus ostreatus P5 on the suppression of cucumber Fusarium wilt. The strain B2 was identified as B. amyloliquefaciens based on biochemical, physiological, and 16S rDNA and gyrB gene sequence analyses. Strain B2 showed indole-3-acetic acid (IAA) and siderophore production and phosphate solubilization in in vitro assays. Scanning electron microscope (SEM) imaging showed the ability of strain B2 to adhere to the root surface of cucumber. P. ostreatus P5 could effectively degrade mixed phenolic acids as its sole source of carbon and energy for growth in liquid medium. In a pot experiment, four treatments were established as follows: (1) CK, uninoculated control; (2) B2, inoculation of strain B2; (3) P5, inoculation of strain P5; and (4) B2 + P5, co-inoculation of strain B2 and strain P5. At the end of the 60-day pot experiment, the B2, P5, and B2 + P5 treatments significantly reduced disease incidence by 48.1, 22.2, and 63.0%, respectively, compared to the CK treatment (p < 0.05). All three inoculation treatments significantly increased the growth of cucumber seedlings and suppressed the FOC population compared to the control (p < 0.05). High-performance liquid chromatography (HPLC) analysis showed that total phenolic acids were decreased by 18.9, 35.9, and 63.2% in the B2, P5, and B2 + P5 treatments, respectively. The results from this study suggest that combined application of B. amyloliquefaciens B2 and P. ostreatus P5 could be a promising strategy for suppressing Fusarium wilt and improving plant growth of cucumber seedlings under continuous cropping conditions.

Emerging Role of MiR-192-5p in Human Diseases.

MicroRNAs (miRNAs) are a type of small non-coding RNAs that play an essential role in numerous biological processes by regulating the post-transcriptional expression of target genes. Recent studies have demonstrated that miR-192-5p, a member of the miR-192 family, partakes in several human diseases, especially various cancers, including cancers of the lung, liver, and breast. Importantly, the levels of miR-192-5p are abundant in biofluids, including the serum and urine, and the exosomal levels of miR-192-5p in circulation can aid in the diagnosis and prognosis of various diseases, such as chronic hepatitis B (CHB) infection disease. Notably, recent studies suggest that miR-192-5p is regulated by long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs). However, there are no comprehensive overviews on the role of miR-192-5p in human diseases. This review discusses the significant studies on the role of miR-192-5p in various human diseases, with special emphasis on the diseases of the respiratory and digestive systems.

Paeoniflorin-6'-o-benzene sulfonate (CP-25) improves vasculitis through inhibiting IL-17A/JAK/STAT3 signaling pathway in endothelial cells of HFD CIA rats.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects not only joints but also multiple organ systems including cardiovascular system. Endothelial dysfunction plays an important role in cardiovascular diseases (CVD). In RA, endothelial dysfunction exists at both the macrovascular and the microvascular levels, which is a precursor to vasculitis. This study aimed to investigate the pathogenesis of vasculitis and the therapeutic effect of CP-25 on vasculitis in high-fat diet (HFD) collagen-induced arthritis (CIA) rats. Experimental groups were divided into normal group, HFD group, CIA group, HFD CIA group, CP-25 group and MTX group. In vitro, IL-17A was used to stimulate human umbilical vein endothelial cells (HUVECs), and then CP-25 was used to intervene. Results showed that CP-25 reduced global scoring (GS), arthritis index (AI), and swollen joint count (SJC) scores, improved histopathological score, reduced T cells percentage, and decreased IL-17A and ICAM-1 levels. Besides, CP-25 reduced the expression of p-STAT3 to normal levels in vascular of HFD CIA rats. In vitro, IL-17A promoted the expression of p-JAK1, p-JAK2, p-JAK3, pSTAT3, and ICAM-1, and CP-25 inhibited the expression of p-JAK1, p-JAK2, p-JAK3, p-STAT3, and ICAM-1. In conclusion, CP-25 might inhibit endothelial cell activation through inhibiting IL-17A/JAK/STAT3 signaling pathway, which improves vasculitis in HFD CIA rats.

Etanercept Inhibits B Cell Differentiation by Regulating TNFRII/TRAF2/NF-κB Signaling Pathway in Rheumatoid Arthritis.

OBJECTIVE: To explore the role of B cells in rheumatoid arthritis (RA) and the potential effects and mechanisms of etanercept on B cells. METHODS: In RA patients, the levels of tumor necrosis factor-α (TNF-α) and B cell activating factor (BAFF) were detected by ELISA. The percentage of B cell subsets was measured by flow cytometry. Laboratory indicators (rheumatoid factor, C-reactive protein, erythrocyte sedimentation rate) and clinical indicators (disease activity score in 28 joints, health assessment questionnaire score, swollen joint counts, tender joint counts) were measured. The correlation between B cell subsets and laboratory indicators or clinical indicators was analyzed. In mice, B cells proliferation was detected by CCK-8 kit. The expression of TNFRII and the percentage of B cell subsets in spleen were detected by flow cytometry. The expressions of TRAF2, p38, P-p38, p65, P-p65 in B cells were detected by WB. RESULTS: The percentage of CD19-CD27+CD138+ plasma B cells was positively correlated with ESR or RF. Etanercept could decrease the percentage of CD19+ total B cells, CD19+CD27+ memory B cells and CD19-CD27+CD138+ plasma B cells, reduce the levels of TNF-α, BAFF, relieve clinical and laboratory indicators in RA patients. In addition, etanercept could inhibit the proliferation of B cells, bate the differentiation of transitional B cells to mature B cells, down-regulate the expression of TNFRII, TRAF2, P-p38, P-p65 in B cells. CONCLUSION: B cells act a key role in the pathogenesis of RA. Etanercept inhibits B cells differentiation by down-regulating TNFRII/TRAF2/NF-κB signaling pathway.

IgD-Fc-Ig fusion protein, a new biological agent, inhibits T cell function in CIA rats by inhibiting IgD-IgDR-Lck-NF-κB signaling pathways.

IgD-Fc-Ig fusion protein, a new biological agent, is constructed by linking a segment of human IgD-Fc with a segment of human IgG1-Fc, which specifically blocks the IgD-IgDR pathway and selectively inhibits the abnormal proliferation, activation, and differentiation of T cells. In this study we investigated whether IgD-Fc-Ig exerted therapeutic effects in collagen-induced arthritis (CIA) rats. CIA rats were treated with IgD-Fc-Ig (1, 3, and 9 mg/kg) or injected with biological agents etanercept (3 mg/kg) once every 3 days for 40 days. In the PBMCs and spleen lymphocytes of CIA rats, both T and B cells exhibited abnormal proliferation; the percentages of CD3+ total T cells, CD3+CD4+ Th cells, CD3+CD4+CD25+-activated Th cells, Th1(CD4+IFN-γ+), and Th17(CD4+IL-17+) were significantly increased, whereas the Treg (CD4+CD25+Foxp3+) cell percentage was decreased. IgD-Fc-Ig administration dose-dependently decreased the indicators of arthritis; alleviated the histopathology of spleen and joint; reduced serum inflammatory cytokines levels; decreased the percentages of CD3+ total T cells, CD3+CD4+ Th cells, CD3+CD4+CD25+-activated Th cells, Th1 (CD4+IFN-γ+), and Th17(CD4+IL-17+); increased Treg (CD4+CD25+Foxp3+) cell percentage; and down-regulated the expression of key molecules in IgD-IgDR-Lck-NF-κB signaling (p-Lck, p-ZAP70, p-P38, p-NF-κB65). Treatment of normal T cells with IgD (9 µg/mL) in vitro promoted their proliferation. Co-treatment with IgD-Fc-Ig (0.1-10 µg/mL) dose-dependently decreased IgD-stimulated T cell subsets percentages and down-regulated the IgD-IgDR-Lck-NF-κB signaling. In summary, this study demonstrates that IgD-Fc-Ig alleviates CIA and regulates the functions of T cells through inhibiting IgD-IgDR-Lck-NF-κB signaling.

[Identification of the characteristic vibrations for 16 PAHs based on Raman spectrum].

In the present paper, by means of density functional theory in B3LYP/6-311++G(d, p) method, 16 kinds of pollutants, i. e. polycyclic aromatic hydrocarbons (PAHs): naphthalene (Nap), acenaphthylene (AcPy), acenaphthene (Acp), fluorene (Flu), phenanthrene (PA), anthracene (Ant), fluoranthene (Fl), pyrene (Pyr), benzo [a] anthracene (BaA), fused two naphthalene (CHR), benzo [b] fluoranthene (BbF), benzo [k] fluoranthene (BkF), benzo [a] pyrene (BaP), dibenzo (a, h) anthracene (DahA), dibenzo [g, h, i] pyrene (BghiP) and indene benzene (1, 2, 3-cd) pyrene (IcdP) among the U. S. EPA priority pollutants were selected, whose structures were optimized and Raman vibrational frequencies and depolarization were calculated. The structure, Raman vibrational frequencies and depolarization were basis of identification of PAHs. Studies have shown that Raman vibrations of 16 PAHs are mainly distributed in three frequency regions: 200-1 000 cm(-1) (fingerprint region), 1 000-1 700 cm(-1) and 3 000-3 200 cm(-1) (group frequency region), corresponding vibrations were assigned to ring deformation (ring def), C-C stretching (CCStr), C-H wiggle (CHw) and of these two patterns (CCStrCCw), and C-H stretching (CHStr). Further analysis showed that in fingerprint region the depolarization of 16 PAHs was reduced with the symmetry of benzene deformation vibration enhanced. At the point of minimum depolarization, symmetry and Raman peak of benzene ring breathing vibration were found strongest. At the minimum differential wave number the strongest peak in fingerprint region was distinguishable by micro-Raman spectroscopy. Therefore, 16 PAHs can be individually identified by depolarization and the strongest peak in fringerprint region. Vibration frequencies and peak intensity distribution of alkanes (Akn), olefin (Oe), alkyne (Aye), alcohols and phenols (Aap), aliphatic ether (Ape), arylalkyl ether (Aae), aldehydes (Ahd), ketones (Ktn), carboxylic acid (Cba), esters (Etr), amines (Aie), nitriles (Nte), amides (Aid), acid anhydride (Ahr), aromatic hydrocarbons (Ahc) were not completely consistent with each other, and interference can be discharged by the differences of frequency and peak intensity distribution.

Optical coherence tomography and ultrasound biomicroscopy imaging of opaque corneas.

PURPOSE: The purpose was to determine the interchangeability of ultrasound biomicroscopy (UBM) and anterior segment optical coherence tomography (AS-OCT) for corneal opacity depth measurement. METHODS: Twenty-six eyes of 26 consecutive patients with corneal opacities were examined by both AS-OCT and UBM. The corneal thickness and the corneal opacity depth were measured and compared. The interchangeability was determined by Bland-Altman plotting. RESULTS: The difference in the full corneal thickness and in the corneal opacity depth between OCT and UBM was 5 ± 7 µm and -1 ± 8 µm, respectively. There were strong correlations and no significant differences between the paired parameters (all r > 0.99, P < 0.01). The limits of agreement were 5 ± 14 µm for the corneal thickness and -1 ± 14.8 µm for the corneal opacity depth. CONCLUSIONS: AS-OCT and UBM may be used interchangeably for measuring both full corneal thickness and corneal opacity depth in patients with corneal opacity.

[Study on structure, charge and spectrum for para-halogenated diphenyl ethers through density functional theory].

The present paper mainly researched the molecular geometry, charge distribution and spectrum vibration of diphenyl ether and its 3 kinds of para-halogenated diphenyl ethers based on density functional theory (DFT). The infrared and Raman spectrum vibration frequency for para-halogenated diphenyl ethers was calculated based on respective optimal molecular geometry with the same method which was carried out at the B3LYP/6-31(d) level, then spectrum vibration of para-halogenated diphenyl ethers was assigned in detail for the first time. Combined with charge distribution of diphenyl ether and by the nuclear magnetic resonance and Milliken charge distribution, the authors also analyzed the effect of different para-halogenated substituent on charge distribution, at last the vibration mechanism and change rule of of para-halogenated diphenyl ethers' characteristic vibrations were analyzed in the view of charge distribution innovatively. From the research we can see that the more the electronegativity of para-halogenated substituent, the bigger the atomic radius, and the longer the C-X bond, the easier they are degraded in the environment; para-halogenated substituent affected the charge distribution greatly especially to para-carbon relative to ether bond, and meta-carbon was controlled by the combination electronic effect of para-halogenated substituent and oxygen atom, meanwhile ortho-carbon didn't have distinct change; charge gap between bond atoms played significant role in the stability of bonds and vibration frequency of characteristic vibration, and the larger the electronegativity of para-halogenated substituent, the larger the vibration frequency.

[The correlative factors of darkroom provocative test in anterior segment parameters].

OBJECTIVE: To investigate the correlative anterior segment parameters of positive darkroom provocative test in patients with narrow anterior chamber angles. METHODS: It was a retrospective case series study. Two hundred and sixty patients [36 males and 224 females, mean age (59.6 ± 9.3) years] with narrow anterior chamber angles underwent darkroom provocative test and UBM scan were analyzed retrospectively. Anterior segment parameters including anterior chamber depth (ACD), pupil diameter (PD), lens vault (LV), peripheral iris thickness (IT), iris convex (IC), anterior chamber angle open distance (AOD), trabecular-meshwork ciliary process angle (TCPA) and the number of appositional angle closure (NPAC) were quantitatively analyzed. Correlative factors of positive results were analysis by both single factor and multiple-factor analysis. RESULTS: Seventy-one (27.3%) of the 260 patients had positive results in the darkroom provocative test. Males (15 out of 36) had statistically higher positive result rate than females (56 out of 224) (M: 41.7% vs. F:25.0%, χ(2) = 4.340, P = 0.037). In single factor analysis, male (OR = 2.14), AOD (OR = 0.98), IT (OR = 1.68) and NPAC (OR = 2.24) were correlative factors for positive results. In multiple-factor analysis, only IT (OR = 1.47) and NPAC (OR = 1.70) were independent risk factors of positive results. CONCLUSIONS: Positive darkroom provocative test is correlated to parameters of anterior chamber angle and iris, while IT and NPAC are independent correlative factors in patients with narrow anterior chamber angle.