Mucosal Profiling of Pediatric-Onset Colitis and IBD Reveals Common Pathogenics and Therapeutic Pathways.

Pediatric-onset colitis and inflammatory bowel disease (IBD) have significant effects on the growth of infants and children, but the etiopathogenesis underlying disease subtypes remains incompletely understood. Here, we report single-cell clustering, immune phenotyping, and risk gene analysis for children with undifferentiated colitis, Crohn's disease, and ulcerative colitis. We demonstrate disease-specific characteristics, as well as common pathogenesis marked by impaired cyclic AMP (cAMP)-response signaling. Specifically, infiltration of PDE4B- and TNF-expressing macrophages, decreased abundance of CD39-expressing intraepithelial T cells, and platelet aggregation and release of 5-hydroxytryptamine at the colonic mucosae were common in colitis and IBD patients. Targeting these pathways by using the phosphodiesterase inhibitor dipyridamole restored immune homeostasis and improved colitis symptoms in a pilot study. In summary, comprehensive analysis of the colonic mucosae has uncovered common pathogenesis and therapeutic targets for children with colitis and IBD.

VAP-SCRN1 interaction regulates dynamic endoplasmic reticulum remodeling and presynaptic function.

In neurons, the continuous and dynamic endoplasmic reticulum (ER) network extends throughout the axon, and its dysfunction causes various axonopathies. However, it remains largely unknown how ER integrity and remodeling modulate presynaptic function in mammalian neurons. Here, we demonstrated that ER membrane receptors VAPA and VAPB are involved in modulating the synaptic vesicle (SV) cycle. VAP interacts with secernin-1 (SCRN1) at the ER membrane via a single FFAT-like motif. Similar to VAP, loss of SCRN1 or SCRN1-VAP interactions resulted in impaired SV cycling. Consistently, SCRN1 or VAP depletion was accompanied by decreased action potential-evoked Ca2+ responses. Additionally, we found that VAP-SCRN1 interactions play an important role in maintaining ER continuity and dynamics, as well as presynaptic Ca2+ homeostasis. Based on these findings, we propose a model where the ER-localized VAP-SCRN1 interactions provide a novel control mechanism to tune ER remodeling and thereby modulate Ca2+ dynamics and SV cycling at presynaptic sites. These data provide new insights into the molecular mechanisms controlling ER structure and dynamics, and highlight the relevance of ER function for SV cycling.

A Comprehensive Analysis of Clinical Crowns in Young of Han Nationality with Normal Occlusion Using Intraoral Scanning.

Background: The measurement and analysis of clinical crowns play a crucial role in stomatology, anthropology, and studies of genetic and environmental variables in oral and maxillofacial development. Purpose: The objective of the present study was to measure the parameters of clinical crowns of permanent dentition in youth of Han nationality using intraoral scanning and identify potential influencing factors. Materials and Methods: A total of 100 subjects (50 males and 50 females) of Han nationality aged 18-24 with normal occlusion were selected. An intraoral scanner was used to obtain the digital dental impressions, and Materialise Magics 21 software was used to measure the mesiodistal diameter (MDD), buccolingual diameter (BLD), height, mesiodistal angle (MDA), and vestibulo-oral angle (VOA) of clinical crowns. The central height was calculated based on the height of clinical crowns. SPSS 27.0 software was used for statistical analysis. The two-independent-samplet-test was used to assess discrepancies in clinical crowns between males and females. The paired t-test was used to determine differences between antimetric pairs of clinical crowns within the same arch. The repeatability of intraoral scanning was tested using the paired t-test between two measurements at one-month intervals. The overall estimated effect was considered significant where P < 0.05. Results: The MDD, BLD, height, MDA, and VOA of clinical crowns in the youth of Han nationality were measured, and the central height was calculated. No significant difference was found in terms of MDA and VOA between genders and antimetric pairs within the same arch. Regarding the distance parameters, the MDD, BLD, and height of clinical crowns in males were significantly larger than those in females (MDD: U1, U3, U7, L2, L3, L6, and L7: P < 0.01; BLD: U1: P=0.02; U3-U7 and L1-L7: P < 0.01; height: U2: P=0.03; and U1, U3-U7, and L3-L7: P < 0.01). No significant difference was found in clinical crowns between antimetric pairs within the same arch. Intraoral scanning demonstrated good repeatability in the measurement of clinical crowns. Conclusions: Apart from MDA and VOA, the parameters of clinical crowns in males were significantly larger than in females. Antimetric pairs of clinical crowns within the same arch demonstrated similar tooth dimensions. In future clinical practice and scientific research in the oral and maxillofacial region, a comprehensive design of sexual and ethnic characteristics should be considered.

Increased IL-1α expression in chronic rhinosinusitis with nasal polyps.

PURPOSE: To examine whether and how interleukin (IL)-1α is involved in chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: Nasal polyp (NP) and control tissues were collected from CRSwNP patients and control subjects. The expression of IL-1α and other proinflammatory cytokines (IL-1ß, IL-8 and IL-13, etc.), as well as neutrophil and eosinophil accumulation, were examined in sinonasal tissues using immunohistochemical (IHC), immunofluorescent (IF) staining, qPCR, and Luminex, respectively. Moreover, the regulation of IL-1α expression and its effects on other proinflammatory cytokines were evaluated in cultured nasal epithelial cells (NECs). RESULTS: The mRNA and protein levels of IL-1α were significantly higher in NP tissues compared to that in control tissues. IL-1α in polyp tissues was mainly located in epithelial cells and neutrophils. Polyps IL-1α level was significantly associated with IL-8, IL-1ß, IL-6, IL-4 and IL-13 production, as well as tissue neutrophil infiltration. Moreover, poly (I:C), lipopolysaccharides, Flagellin, R848 and cytokines (IL-4, IL-5, and IL-13) significantly increased the expression of IL-1α in cultured NECs in vitro, and recombinant IL-1α significantly promoted production of IL-8 and CXCL1 in cultured NECs. CONCLUSIONS: These findings provided the evidence that IL-1α were significantly increased in NP tissues, which may contribute to tissue neutrophilia in CRSwNP patients in China.

Roles and clinical application of exosomal circRNAs in the diagnosis and treatment of malignant tumors.

Exosomes are microvesicles secreted by cells. They contain a variety of bioactive substances with important roles in intercellular communication. Circular RNA (circRNA), a type of nucleic acid molecule found in exosomes, forms a covalently bonded closed loop without 5' caps or 3' poly(A) tails. It is structurally stable, widely distributed, and tissue specific. CircRNAs mainly act as microRNA sponges and have important regulatory roles in gene expression; they are superior to other non-coding RNAs as molecular diagnostic markers and drug treatment targets. Exosomal-derived circRNAs in the body fluids of tumor patients can modulate tumor proliferation, invasion, metastasis, and drug resistance. They can be used as effective biomarkers for early non-invasive diagnosis and prognostic evaluation of tumors, and also represent ideal targets for early precision therapeutic intervention. This review provides a theoretical basis for exploring the applications of exosomal circRNAs in malignant tumor diagnosis and treatment. We describe the biological functions of exosomal circRNAs in the occurrence and development of malignant tumors, their potential utility in diagnosis and treatment, and possible mechanisms.

Two novel phosphorus/potassium-degradation bacteria: Bacillus aerophilus SD-1/Bacillus altitudinis SD-3 and their application in two-stage composting of corncob residue.

For effective utilization of corncob residue to realize green circular production, using composting to obtain a high-quality and low-cost biomass fertilizer has become a very important transformation avenue. In this paper, two novel phosphorus/potassium-degradation bacterial strains were isolated from tobacco straw and identified as Bacillus aerophilus SD-1/Bacillus altitudinis SD-3 (abbreviated as SD-1/SD-3). These identified two novel bacteria SD-1/SD-3 show that the soluble phosphorus content of SD-1/SD-3 reached 360.89 mg L-1/403.56 mg L-1 in the shake flask test, and the mass concentration of soluble potassium is 136.56 mg L-1/139.89 mg L-1. In addition, the Laccase (Lac), Lignin peroxidase (LiP), and Manganese peroxidase (MnP) activities of SD-1 and SD-3 are 54.45 U L-1/394.84 U L-1/222.79 U L-1 and 46.27 U L-1/395.26 U L-1/203.98 U L-1 respectively, with the carboxy-methyl cellulase (CMCase) of 72.07 U mL-1 and 52.69 U mL-1. Meanwhile, the effects of three different combinations of cultures, i.e., no inoculation (K1), inoculation of SD-1/SD-3 on day 21 (K2) and on day 0 (G) are investigated to understand the influence on the degradation degree of corncob residue compost. The results of K2 compost treatment showed that the effective P/K content increased nearly 3.1/2.4 times, the degradation of cellulose/lignin was 49.1/68.0%, and the germination rate was 110.23%, which were higher than other experiment groups K1/G. In conclusion, knowledge of this paper will be very useful for the industrial sector for the treatment of complex corncob residue.

Expression profile and prognostic value of CXCR family members in head and neck squamous cell carcinoma.

BACKGROUND: CXC chemokine receptor gene family consists of seven well-established members which are broadly involved in biological functions of various cancers. Currently, limited studies have shed light on the expression profile of CXCR family members (CXCRs), as well as their prognostic value, in head and neck squamous cells carcinoma (HNSCC). METHODS: The data for this study were retrieved from the Cancer Genome Atlas database and other publicly available databases, including gene expression, methylation profiles, clinical information, immunological features, and prognoses. The expression pattern and prognostic values of CXCRs were identified, and the potential mechanism underlying CXCRs function in HNSCC was investigated by gene set enrichment analysis (GSEA). RESULTS: CXCRs were differentially expressed in HNSCC. As shown by Kaplan-Meier analysis, high CXCR3-6 expression was significantly associated with better prognostic outcomes of HNSCC patients, including overall survival and progression-free survival. According to the results of univariate and multivariate Cox proportional risk regression analysis, it was demonstrated that upregulation of CXCR3-6 was an independent factor for better prognosis, while the two other clinical features, age and stage, were factors for worse prognosis. A significant positive correlation between CXCR3-6 and tumor-infiltrated immune cells was revealed by results from Tumor Immune Estimation Resource and CIBERSORT analysis database. The main involvement of CXCRs in immune and inflammatory responses was further confirmed by GSEA. CONCLUSIONS: Overall, this study provided a rationale for targeting CXCRs as a promising therapeutic strategy of HNSCC.

Endoplasmic reticulum stress exacerbates inflammation in chronic rhinosinusitis with nasal polyps via the transcription factor XBP1.

Endoplasmic reticulum (ER) stress results in the activation of the unfolded protein response (UPR), a process that is involved in the pathogenesis of many inflammatory diseases. However, the role of ER stress in chronic rhinosinusitis with nasal polyps (CRSwNP) has yet to be elucidated. In this study, we found that the protein expression levels of a range of ER stress regulators, including p-PERK, ATF4, ATF6 and XBP1s, were significantly increased in CRSwNP compared to controls. Importantly, the expression of ATF4 and XBP1s was positively correlated with heightened inflammation in CRSwNP. In human nasal epithelial cells, the ER stress inducer tunicamycin (TM) could potentiate Toll-like receptors (TLRs) induced proinflammatory cytokines production. Furthermore, we found that the silencing of XBP1, but not ATF4 or ATF6, abrogated the proinflammatory effect of TM. Mechanistically, ER stress did not affect the NF-κB, MAPK or IRF3 signaling pathways. However, the ER stress regulator XBP1s was able to bind directly to the promoter region of inflammatory genes to modulate gene transcription. Besides, the commensal bacteria Staphylococcus aureus and several inflammatory factors, such as IL4, IL13, IL17 and IFNγ, could induce ER stress in epithelial cells. Collectively, ER stress plays a crucial role in facilitating TLR-induced inflammation. Targeting XBP1 can inhibit the inflammatory response, thus offering a potential approach to treat CRSwNP.

Genome-wide association study on Northern Chinese identifies KLF2, DOT1L and STAB2 associated with systemic lupus erythematosus.

OBJECTIVES: To identify novel genetic loci associated with systemic lupus erythematosus (SLE) and to evaluate potential genetic differences between ethnic Chinese and European populations in SLE susceptibility. METHODS: A new genome-wide association study (GWAS) was conducted from Jining, North China, on 1506 individuals (512 SLE cases and 994 matched healthy controls). The association results were meta-analysed with existing data on Chinese populations from Hong Kong, Guangzhou and Central China, as well as GWAS results from four cohorts of European ancestry. A total of 26 774 individuals (9310 SLE cases and 17 464 controls) were included in this study. RESULTS: Meta-analysis on four Chinese cohorts identifies KLF2 as a novel locus associated with SLE [rs2362475; odds ratio (OR) = 0.85, P=2.00E-09]. KLF2 is likely an Asian-specific locus as no evidence of association was detected in the four European cohorts (OR = 0.98, P =0.58), with evidence of heterogeneity (P=0.0019) between the two ancestral groups. Meta-analyses of results from both Chinese and Europeans identify STAB2 (rs10082873; OR= 0.89, P=4.08E-08) and DOT1L (rs4807205; OR= 1.12, P=8.17E-09) as trans-ancestral association loci, surpassing the genome-wide significance. CONCLUSIONS: We identified three loci associated with SLE, with KLF2 a likely Chinese-specific locus, highlighting the importance of studying diverse populations in SLE genetics. We hypothesize that DOT1L and KLF2 are plausible SLE treatment targets, with inhibitors of DOT1L and inducers of KLF2 already available clinically.

Hypertriglyceridemic waist phenotype and risk of chronic kidney disease in community-dwelling adults aged 60 years and older in Tianjin, China: a 7-year cohort study.

BACKGROUND: The hypertriglyceridemic waist (HTGW) phenotype has been proposed to be related to the occurrence and progression of chronic kidney disease (CKD). The ageing trend of the Chinese population continues to intensify, and elderly individuals are at high risk of CKD. The purpose of this study was to investigate the cross-sectional and longitudinal associations between the HTGW phenotype and the risk of CKD by following community-dwelling adults aged 60 years and older in Tianjin, China, for 7 years. METHODS: This study was an observational cohort study conducted between 2013 and 2019. Of 2050 participants aged 60 years and older who underwent an annual health examination in 2013, 1605 individuals with complete data were enrolled in the cross-sectional analysis. Among them, 1271 individuals were observed until 2019. Detailed follow-up records were available for 816 participants, of whom 600 participants without CKD at baseline were eligible for inclusion in the retrospective analysis. The HTGW phenotype was defined as a waist circumference of 90 cm or more and triglyceride concentrations of 2.0 mmol/L or more in males or a waist circumference of 85 cm or more and triglyceride concentrations of 1.5 mmol/L or more in females. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 and/or proteinuria (urinary albumin-to-creatinine ratio (ACR) ≥ 30 mg/g). Multivariable logistic regression analyses were performed to evaluate the relationship between the HTGW phenotype and CKD. RESULTS: In 2013, the prevalence of CKD among older adults was 31.03%, and the prevalence of CKD in the HTGW phenotype group was 37.81%. Over a 7-year observation period, 195 individuals developed CKD, with an incidence rate of 32.50%. Statistically significant associations were observed between the HTGW phenotype and CKD in older adults in both cross-sectional surveys and retrospective analyses, with odds ratios and 95% confidence intervals of 1.38 (95% CI: 1.03-1.86, P = 0.033) and 2.27 (95% CI: 1.30-3.97, P = 0.004), respectively, after adjustment for confounders. CONCLUSIONS: In this community-based cohort study, the HTGW phenotype was confirmed to be independently associated with an increased risk of prevalent and incident CKD in older adults aged 60 years and above in Tianjin, China.

TGF-ß1 induces epithelial-to-mesenchymal transition in chronic rhinosinusitis with nasal polyps through microRNA-182.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) in nasal epithelial cells is involved in tissue remodeling of chronic rhinosinusitis with nasal polyps (CRSwNP). Our study investigated the molecular mechanisms that microRNA-182 (miR-182) regulated EMT in eosinophilic (Eos) and non-eosinophilic (non-Eos) CRSwNP. OBJECTIVE: To investigate the mechanism by which miR-182 regulates EMT in human nasal epithelial cells (hNEPCs). METHODS: The expression of EMT markers (E-cadherin, N-cadherin and vimentin), transforming growth factor (TGF)-ß1, and miR-182 were determined by western blotting and reverse transcription-quantitative PCR (RT-qPCR). Fluorescence in situ hybridization (FISH) was used to detect the miR-182 localization. Additionally, EMT markers expression and cell morphology changes were checked upon treatment with TGF-ß1, or TGF-ß1 with miR-182 inhibitor, or miR-182 mimics, or miR-182 inhibitor alone in hNEPCs. RESULTS: In both Eos CRSwNP and non-Eos CRSwNP, the expression levels of E-cadherin were downregulated while the expression levels of N-cadherin, vimentin, TGF-ß1 and miR-182 were significantly upregulated compared with control nasal tissues. Additionally, more significant changes in these EMT markers were observed in the Eos-CRSwNP when compared with the non-Eos CRSwNP. Invitro hNEPCs model, TGF-ß1 upregulated miR-182 expression and promoted EMT in hNEPCs, indicated by changes in cell morphology and EMT markers expression. Furthermore, these upregulations were reversed by miR-182 inhibitor. CONCLUSIONS: This study showed that miR-182-induced EMT in response to TGF-ß1 might promote nasal polypogenesis in both Eos CRSwNP and non-Eos CRSwNP, thus providing potential targets for the future development of novel therapeutic approaches for the management of CRSwNP.

LL-37 promotes neutrophil extracellular trap formation in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Neutrophil accumulation has been observed in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the functions of neutrophils are poorly understood. Neutrophils produce neutrophil extracellular traps (NETs), which are involved in a variety of chronic inflammatory pathologies. LL-37 is the only member of the cathelicidin family in human. OBJECTIVE: Our aims were to examine the presence of NETs in CRSwNP and to investigate the regulatory effect of LL-37 on NET formation. METHODS: Nasal polyp tissues were investigated for the presence of NETs by using immunofluorescent (IF) staining. The expression and distribution of LL-37 were examined by using quantitative RT-PCR, ELISA, IF, and immunohistochemistry. Purified peripheral neutrophils were stimulated with LL-37 and stained with IF to identify NETs. NETs% was defined as percentage of NET-generating neutrophils to the total number of neutrophils. RESULTS: Neutrophil extracellular traps were located in the subepithelial layer of nasal polyps and control tissues. Nasal polyps had higher NETs% compared with that of controls (23.01% ± 3.43% vs 4.52% ± 1.33%, P < 0.0001). NET count was also increased in nasal polyps. NET count correlated with neutrophil count (r = 0.908, P < 0.001). LL-37 protein and mRNA levels were upregulated in nasal polyps. LL-37 was distributed in the epithelial and subepithelial layer and mainly expressed by neutrophils. Moreover, LL-37 promoted peripheral neutrophils to form NETs in a dose-dependent manner ex vivo. Interestingly, dexamethasone did not inhibit the effect of LL-37 on inducing NET formation. Furthermore, peripheral neutrophils from CRSwNP patients were more susceptible to LL-37-mediated NET formation, compared with neutrophils derived from control subjects. In addition, NETs released LL-37 in vivo and ex vivo. CONCLUSION: Neutrophil extracellular traps are significantly increased in nasal polyps and LL-37 induces NET formation in CRSwNP patients. These findings indicate that NETs may contribute to the pathogenesis of neutrophilic inflammation in CRSwNP.

Effect of Cellulose Powder on Human Nasal Epithelial Cell Activity and Ciliary Beat Frequency.

BACKGROUND: Cellulose powder (CP) has been reported as a safe and effective complementary treatment for allergic rhinitis (AR). Currently, CP has gained increasing application for clinical management worldwide, particularly in China. However, studies focusing on the effect of CP on normal human nasal epithelial cells (hNECs) and ciliary function are lacking. Here, we aimed to explore the adverse effects of CP on the activity and ciliary function of hNECs. METHODS: We biopsied ethmoid sinus or middle turbinate tissues during surgical resection from control subjects who underwent endoscopic sinus surgery for diseases other than AR. Cells were isolated and passaged, followed by differentiation in an air-liquid interface (ALI). Flow cytometry and cell viability test (cell counting kit-8) were performed to detect the cytotoxicity of CP (effects on cell proliferation) on normal hNECs. By using the ALI culture model, we investigated the effects of CP on ciliary beat frequency (CBF). RESULTS: There was a significant reduction in hNEC count at high concentrations of CP (2.5 mg/mL) at days 3 and 7 (both p < 0.05). As the concentration increased, cell death increased progressively from day 3 to day 7. However, these effects were not evident at low concentrations (0.25 mg/mL, p > 0.05). High-dose CP (2.5 mg) significantly reduced the CBF (p < 0.05). At lower concentrations (0.25-2.5 mg/mL), CP initially increased but subsequently reduced the CBF of hNECs compared with control group. CONCLUSIONS: Cytotoxicity and the suppression of ciliary beat at high concentrations justify more prudent use of CP for the management of AR.

Negative transconductance in multi-layer organic thin-film transistors.

Negative transconductance (NTC) refers to the phenomenon of the N-shape transfer characteristic appearing with a current peak and valley. It has been extensively studied in the past few decades due to its applications in logic and memory devices. Here, we observe unique antibipolar transfer characteristics and NTC behavior in multi-layer 2,6-diphenyl anthracene organic thin-film transistors grown on h-BN, which is due to the vertical potential barrier between the charge accumulation region near the substrate and the neutral bulk region under the contacts. The applied extrinsic electric field could effectively modulate the barrier height, resulting in a competition for charge carrier transport between lateral and vertical directions. Based on the NTC and antibipolar properties, a frequency doubler has been fabricated on a single transistor, which provides a new building block for organic logic circuits.

The effects of endoscopic sinus surgery on pulmonary function in chronic rhinosinusitis patients with asthma: a systematic review and meta-analysis.

PURPOSE: Evidences showed improvements in clinical asthma outcomes following endoscopic sinus surgery (ESS) in chronic rhinosinusitis (CRS) patients with asthma. However, pulmonary function benefits have remained controversial up to date. The goal of this study was to conduct a systematic review and meta-analysis to investigate the effects of ESS on pulmonary function tests in CRS patients with asthma. METHODS: Pubmed, Embase and Cochrane Library were searched up to March 2018 to obtain relevant studies. The researches that evaluated the effects of ESS on pulmonary function in CRS patients with asthma and had at least one parameter of pulmonary function tests before and after surgery were included in the study. RESULTS: A total of 13 studies containing 421 patients satisfied the eligibility after judgment by 2 reviewers. These included three RCTs and ten case series. The heterogeneity in parameters of spirometry and difference in data presented forms across studies along with the lack of standard deviation of some data make it difficult to synthesize results. If data were unavailable for meta-analyses, descriptive statistics were used to report study outcomes. After qualitative and quantitative analysis, the weighted mean change after ESS in forced expiratory flow between 25% and 75% of vital capacity (FEF25-75%) was 0.21 L/s (95% CI 0.12-0.30); eight of ten studies supported that forced expiratory volume at 1 s (FEV1) improved after ESS; five of six studies supported that peak expiratory flow (PEF) improved after ESS. However, strength of evidence is generally low to insufficient. CONCLUSION: A generally low-quality evidence supports the association between ESS and improvements in FEF25-75%, FEV1 and PEF. A few studies met inclusion criteria for meta-analysis, which indicates the need for more high-quality studies to determine the effect of ESS.

Plasma triglyceride levels and central obesity predict the development of kidney injury in Chinese community older adults.

Objective: Despite the achievement of blood glucose, blood pressure targets, the risk for kidney injury remains high among older adults. This observational retrospective study investigated whether high TG or high WC contribute to this high residual risk for kidney injury. Methods: A total of 843 elderly from Dongli Community, Tianjin, China, we selected 666 individuals with a baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 and negative microalbuminuria completing a 3-year follow-up. At baseline, subjects were grouped according to the levels of TG and WC. The primary outcome was the incidence of kidney injury, defined as low eGFR (eGFR <60 mL/min/1.73 m2) or reduced eGFR (eGFR reduced >25%) or UACR ≥30 mg/g. Results: Overall, 6.01% developed low eGFR, 11.11% reduced eGFR, 25.98% UACR ≥30 mg/g, and 3.45% low eGFR and UACR ≥30mg/g after 3-year follow-up. TG ≥1.7 mmol/L increased the risk of eGFR <60 mL/min/1.73 m2 by 1.44-fold, of UACR ≥30 mg/g by 32%, and of developing both abnormality by 1.41-fold in model 1; further adjustment for potential confounders factors, the association is slightly weakened in model 2 and 3; WC (≥90 cm in men and ≥85 cm in women) were associated with a 1.68-fold higher risk of eGFR <60 mL/min/1.73 m2 and a 1.43-fold risk of UACR ≥30 mg/g and a 1.89-fold risk of developing both abnormality in model 1. Further adjustment for potential confounders factors, the association is slightly weakened in model 2 and 3. Conclusions: In a population of Chinese community-dwelling older adults, high TG and central obesity were risk factors for the development of kidney injury over 3 years.

[Dose-toxicity-effect relationship between licorice combined with rhubarb in purgation].

The dose-toxicity-effect relationship between licorice combined with rhubarb in purgation was studied. A total of 108 ICR mice were divided into control group,model group,positive group,low,medium and high-dose rhubarb groups,and low,medium and high-dose rhubarb-liquorice decoction group. After 6 days of continuous administration of loperamide hydrochloride,the constipation model of mice was replicated,and each group was given lactulose,different doses of rhubarb and rhubarb-liquorice decoction for 14 days. After administration,the defecation characteristics,blood biochemistry,liver,kidney and colon pathological changes in each group were compared. Based on the objective weight given by factor analysis,the dose-toxicity-effect relationship was comprehensively analyzed by multi-index scoring method. Two common factors were extracted by factor analysis,representing effect and toxicity respectively. The results showed that rhubarb could exert a diarrhea effect at the dosage of 1/2,2 and 8 times of the high limit set forth in the Chinese Pharmacopoeia,increase the defecation volume and the intestinal tract propulsion rate,reduce the time of anal and the oral transmission,and increase the water content of feces. The combination with licorice could alleviate its diarrhea effect,especially at the dosage of 1/2 times of the high limit set forth in the Chinese Pharmacopoeia. However,rhubarb showed obvious hepatic and colon toxicities at the dosage of 2 and 8 times of the high limit set forth in the Chinese Pharmacopoeia,and the combination with licorice could significantly reduce its toxicity. It shows that licorice has a " mediating" effect on rhubarb by alleviating the purgation property and reducing the toxicity.

Liquid crystal terahertz modulator with plasmon-induced transparency metamaterial.

An electrically tunable terahertz (THz) modulator with large modulation depth and low insertion loss is performed with liquid crystal (LC) metamaterial. The modulation depth beyond 90% and insertion loss below 0.5 dB are achievable at normal incidence by exploiting plasmon-induced transparency (PIT) effect. The PIT spectra can be manipulated by actively controlling the interference between dipole mode and nonlocal surface-Bloch mode with LC. The incident angle tuning effect on PIT spectra shows that the large modulation depth and low insertion loss can remain over a wide range of working angles. The superior property and simplicity of design make this modulator promising in advanced terahertz communication.

Computed Tomographic Studies of Noncalcified Nodules Related to Neuroendocrine Lung Tumor Using 68Gallium-Tagged Somatostatin Variant for Improvement in Diagnosis: A Non-Experimental, Non-Randomized, Cross-Sectional Study.

BACKGROUND 18Fluoro-fluorodeoxyglucose (FDG)- based positron-emission computed tomography (PET) has less specificity for noncalcified nodules (NNs). Somatostatin receptors affect the expression of normal and malignant cells. The purpose of the study was to compare the sensitivity, specificity, and accuracy of 68Gallium-tagged DOTA-octreotate (Ga-tDO) with that of FDG PET for diagnosis of newly detected and/or untreated NNs in lung cancer patients. MATERIAL AND METHODS A total of 45 patients with lung cancer were included in the cross-sectional study and underwent Ga-tDO and FDG PET. We further confirmed observed outcomes by testing immune histochemical staining for subtype 2A of somatostatin receptor in a granuloma tissue array. The chi-square test was performed for sensitivity and specificity of predictive values among the 3 diagnostic modalities. McNemar's test was performed to compare accuracy between Ga-tDO and FDG PET. Results were considered significant at 95% confidence level. RESULTS Ga-tDO had less sensitivity (69% vs. 89%) but more specificity (91% vs. 78%) than FDG PET. Ga-tDO and FDG PET were characterized as 36 and 6 and in 36 and 3 lesions as accurate and inaccurate, respectively. There was an insignificant difference between Ga-tDO and FDG PET regarding diagnostic accuracy (p=0.7). Dosimetry results showed that the lungs were one of the least critically affected organs. CONCLUSIONS Ga-tDO was more specific but less sensitive than FDG PET scanning and imaging.

Carboxylesterase and UDP-glucuronosyltransferases mediated metabolism of irinotecan: In vitro and in vivo insights from quantitative ultra-performance liquid chromatography-mass spectrometry analysis.

Carboxylesterase and UDP-glucuronosyltransferase-mediated metabolism of irinotecan (CPT-11) has long been proposed to be responsible for its anti-tumor activity and toxicity, like delayed-onset diarrhea. However, recent studies failed to gain more comprehensive in vivo and in vitro pharmacokinetic profiles of irinotecan. Herein, we use rat plasma, human liver microsomes and immortalized HepG2 cell as experimental subjects to describe a sensitive and versatile UHPLC-MS/MS method for simultaneously quantifying CPT-11 and its metabolites, including SN-38 and SN-38G. The method was applied to investigate the pharmacokinetic and metabolic behavior of CPT-11 in the biological samples. Calibration curves for all bio-matrices showed acceptable linearity (r2 > 0.99). The intra- and inter-day precisions (RSD, %) were within 15% and the excellent accuracy (RE) was between 2.96 and 14.12%. In addition, the specificity, matrix effect and extraction recovery all met the requirements of biological sample analysis. We successfully applied this method to investigate the pharmacokinetics of irinotecan in various biological samples, mediated by carboxylesterase and UDP-glucuronosyltransferase. This method could be employed in monitoring the metabolic status and clinical efficacy of irinotecan in the future.