Effects of qufeng xuanfei formula in guinea pig model of airway hyperergy.

This work aimed to clarify the potential regulating effects of Qufeng Xuanfei formula (QFXF) on airway neurogenic inflammation and its underlying target signal pathway. Guinea pig model of airway hyperergy (AHR) was used. The relative susceptibility of major proteins to airway neurogenic inflammation was assessed using Western blot immunoassay followed by being separated by SDS-PAGE. Compared to the model group, QFXF of all concentrations effectively depressed the capsaicin enhanced cough in guinea pigs and the peak values of airway resistance significantly decreased. The results illustrated that QFXF alleviated cough symptom in guinea pigs and reduced airway neurogenic inflammation when compared to AHR model group. Airway inflammation and damage, as well as the levels of NGF, SP and c-Fos in QFXF decreased the most in the high-dose group. The mechanism of antitussive activity may be associated with reducing airway inflammation. QFXF displayed effect on chronic cough through reducing the levels of neuropeptides, attenuating airway inflammation and promoting recovery from disease to decrease the airway neuro sensitivity, suggesting that the potential mechanism may be related to Ras/ERK/c-Fos pathway.

Differences in the clinical characteristics and outcomes of COVID-19 patients in the epicenter and peripheral areas of the pandemic from China: a retrospective, large-sample, comparative analysis.

BACKGROUND: There is limited information on the difference in epidemiology, clinical characteristics and outcomes of the initial outbreak of the coronavirus disease (COVID-19) in Wuhan (the epicenter) and Sichuan (the peripheral area) in the early phase of the COVID-19 pandemic. This study was conducted to investigate the differences in the epidemiological and clinical characteristics of patients with COVID-19 between the epicenter and peripheral areas of pandemic and thereby generate information that would be potentially helpful in formulating clinical practice recommendations to tackle the COVID-19 pandemic. METHODS: The Sichuan & Wuhan Collaboration Research Group for COVID-19 established two retrospective cohorts that separately reflect the epicenter and peripheral area during the early pandemic. The epidemiology, clinical characteristics and outcomes of patients in the two groups were compared. Multivariate regression analyses were used to estimate the adjusted odds ratios (aOR) with regard to the outcomes. RESULTS: The Wuhan (epicenter) cohort included 710 randomly selected patients, and the peripheral (Sichuan) cohort included 474 consecutive patients. A higher proportion of patients from the periphery had upper airway symptoms, whereas a lower proportion of patients in the epicenter had lower airway symptoms and comorbidities. Patients in the epicenter had a higher risk of death (aOR=7.64), intensive care unit (ICU) admission (aOR=1.66), delayed time from illness onset to hospital and ICU admission (aOR=6.29 and aOR=8.03, respectively), and prolonged duration of viral shedding (aOR=1.64). CONCLUSIONS: The worse outcomes in the epicenter could be explained by the prolonged time from illness onset to hospital and ICU admission. This could potentially have been associated with elevated systemic inflammation secondary to organ dysfunction and prolonged duration of virus shedding independent of age and comorbidities. Thus, early supportive care could achieve better clinical outcomes.

An insight on the role of PVP in the synthesis of monoclinic WO3 with efficiently photocatalytic activity.

Nanoparticles of monoclinic WO3 were synthesized by a facile method using Na2WO4 as raw material and PVP 70 000 (polyvinylpyrrolidone) as surfactant and template. The effect of PVP on the structure and photocatalytic activity of the synthesized WO3 was discussed in detail. The prepared samples were characterized by XRD, SEM, FT-IR, UV-vis, XPS, PL techniques, and the results show that the visible light is strongly absorbed by the obtained samples, whose particle size varies from 38 to 85 nm. The photocatalytic properties of the resulted samples were evaluated using RhB in water as a target substance, and results illustrate that 30 mg l-1 of RhB can be efficiently photodegraded by nano WO3 under visible light irradiation. Based on the results of XPS, PL and photocalysis experiments, the reason of such improved photocatalytic efficiency may be attributed to the reducing activity of PVP, which leads to the formation of oxygen vacancies beneficial for the capture of photoelectrons and the generation of superoxide radicals. Furthermore, the results show that the photocatalytic efficiency is greatly influenced by the morphology of the synthesized WO3 samples, and the WO3 with a block-shaped morphology is an ideal photocatalyst for the degradation of RhB under visible light irradiation.

[Study on the Influence of Mineralizer on the Preparation of Calcium Aluminates Based on Infrared Spectroscopy].

In this study, effect of mineralizer on the structure and spectraproperties of calcium aluminates formation was extensively studied. Medium or low-grade bauxite and calcium carbonate were used as raw material and mineralizer CaF2 as additive. Calcium aluminates can be obtained after mixing fully, calcination and grinding. The prepared calcium aluminates can be directly used for the production of polyaluminiumchloride (PAC), polymeric aluminum sulfate, sodium aluminate and some other water treatment agents. The calcium aluminates preparation technology was optimized by investigating the mass ratio of raw materials (bauxiteand calcium carbonate) and mineralizer CaF2 dosage. The structure and spectra properties of bauxite and calcium aluminates were characterized by Fourier transform infrared(FTIR) spectroscopy analysis and the mineralization mechanism of the mineralizer was studied. FTIR spectra indicated that the addition of mineralizer promoted the decomposition and transformation of the diaspore, gibbsite and kaolinite, the decomposition of calcium carbonate, and more adequately reaction between bauxite and calcium carbonate. In addition, not only Ca in calcium carbonate and Si in bauxite were more readily reacted, but also Si-O, Si-O-Al and Al-Si bonds in the bauxite were more fractured which contributed to the release of Al in bauxite, and therefore, the dissolution rate of Al2O3 could be improved. The dissolution rate of Al2O3 can be promoted effectively when the mineralizer CaF2 was added in a mass ratio amount of 3%. And the mineralizer CaF2 cannot be fully functioned, when its dosage was in a mass percent of 1. 5%. Low-grade bauxite was easier to sinter for the preparation of calcium aluminates comparing with the highgrade one. The optimum material ratio for the preparation of calcium aluminates calcium at 1 250 °C was the mass ratio between bauxite and calcium carbonate of 1 : 0. 6 and mineralizer CaF2 mass ratio percent of 3%.

Palbociclib induces cell senescence and apoptosis of gastric cancer cells by inhibiting the Notch pathway.

Palbociclib (PD0332991), a selective cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, has been reported to exert anticancer activity in some cancers, including gastric cancer (GC). However, the role of palbociclib in GC remains largely unknown. The present study aimed to investigate the effects of palbociclib on the progression of GC and the potential mechanisms underlying its effects. The colony formation, proliferation, senescence, as well as apoptosis and cell cycle progression of AGS and HGC-27 cells following treatment with palbociclib were analyzed using colony formation assays, MTT assays, senescence-associated ß-galactosidase (SA-ß-gal) staining and flow cytometry, respectively. The protein expression levels of Bax, Caspase-3, Bcl-2, p16, p21, p53, Notch1, Notch2 and hairy and enhancer of split 1 (Hes1) were measured in AGS and HGC-27 cells using western blotting. Moreover, the mRNA expression levels of Notch1, Notch2 and Hes1 in AGS and HGC-27 cells were determined by reverse transcription-quantitative PCR. In the present study, palbociclib significantly inhibited cell proliferation and induced cell senescence, cell cycle arrest and apoptosis in both cell lines in a dose-dependent manner. Additionally, palbociclib significantly increased the expression levels of Bax, Caspase-3, p16, p21 and p53, whilst decreasing the expression of Bcl-2, Notch1, Notch2 and Hes1 in AGS and HGC-27 cells. Furthermore, the Notch pathway activator Jagged-1/FC reversed the effects of palbociclib on cell proliferation, apoptosis, senescence and cell cycle progression. These findings demonstrated that palbociclib could inhibit proliferation and induce senescence, cell cycle arrest and apoptosis in GC cells by inhibiting the Notch pathway.

Deletion Detection Method Using the Distribution of Insert Size and a Precise Alignment Strategy.

Homozygous and heterozygous deletions commonly exist in the human genome. For current structural variation detection tools, it is significant to determine whether a deletion is homozygous or heterozygous. However, the problems of sequencing errors, micro-homologies, and micro-insertions prohibit common alignment tools from identifying accurate breakpoint locations, and often result in detecting false structural variations. In this study, we present a novel deletion detection tool called Sprites2. Comparing with Sprites, Sprites2 makes the following modifications: (1) The distribution of insert size is used in Sprites2, which can identify the type of deletions and improve the accuracy of deletion calls. (2) A precise alignment method based on AGE (one algorithm simultaneously aligning 5' and 3' ends between two sequences) is adopted in Sprites2 to identify breakpoints, which is helpful to resolve the problems introduced by sequencing errors, micro-homologies, and micro-insertions. In order to test and verify the performance of Sprites2, some simulated and real datasets are adopted in our experiments, and Sprites2 is compared with five popular tools. The experimental results show that Sprites2 can improve the performance of deletion detection. Sprites2 can be downloaded from https://github.com/zhangzhen/sprites2.

Sinomenine Attenuated Capsaicin-Induced Increase in Cough Sensitivity in Guinea Pigs by Inhibiting SOX5/TRPV1 Axis and Inflammatory Response.

BACKGROUND: Chronic cough is a common complaint which affects a large number of patients worldwide. Increased cough sensitivity is a very important cause of chronic persistent cough. However, there are limited clinical diagnosis and treatment for increased cough sensitivity. Transient receptor potential vanilloid-1 (TRPVl) is a member of the transient receptor potential (TRP) family of channels which is very closely associated with respiratory diseases. However, the mechanism through which TRPV1 that influences downstream events is still poorly understood. RESULTS: Capsaicin induced increase in cough sensitivity by upregulating the protein level of TRPV1, leading to the secretions of Substance P and neurokinin A which stimulated neurogenic inflammation. However, sinomenine, a component of traditional Chinese medicine, significantly attenuated the capsaicin-induced cough by inhibiting the expression of TRPV1 in guinea pigs. In addition, capsaicin increased the expression of SOX5 which mediated the transcriptional upregulation of TRPV1. However, pretreatment with sinomenine reduced the expression of SOX5. CONCLUSION: These results indicate that capsaicin induced increase in cough sensitivity by activating neurogenic inflammation, while sinomenine attenuated the increase in cough sensitivity by inhibiting the expressions of SOX5 and TRPV1 in guinea pigs. This finding may provide a novel target for the treatment of aggravated cough sensitivity.

Tear cytokine profile in medicated glaucoma patients: effect of monocyte chemoattractant protein 1 on early posttrabeculectomy outcome.

PURPOSE: To determine the tear cytokine profile from medicated glaucoma patients scheduled for trabeculectomy and to establish whether a specifically elevated cytokine level is related to early postoperative scarring. DESIGN: Prospective case-control study. PARTICIPANTS: Sixty-one patients treated with topical antiglaucoma medications and 29 normal subjects with no prior topical treatment were recruited for the study. METHODS: Schirmer strips were used to collect tear samples. A multiplex bead assay was used to quantify the presence of proinflammatory cytokines in the tears. The patients were followed up for 6 months after surgery to determine whether any postoperative intervention to maintain filtering bleb function was required. MAIN OUTCOME MEASURES: The level of cytokines in tear specimens from medicated glaucoma patients was the main outcome measure for the study. The need for postoperative bleb needling within 6 months was a secondary outcome measure. RESULTS: Of the 17 cytokines assayed, only monocyte chemoattractant protein 1 (MCP-1) was elevated significantly in the medicated eyes compared with the unmedicated eyes (P < 0.0004). At 6 months after surgery, 18 (30%) of the 61 eyes required postoperative intervention. A much higher MCP-1 level was detected in these eyes compared with the remaining 43 that did not require intervention (P < 0.0001). The duration of use of topical medication correlated with increasing levels of MCP-1, although the types of glaucoma medication and the number of bottles of medications did not have any significant relationship with the level of MCP-1. CONCLUSIONS: In tears from topically medicated glaucoma eyes in an Asian population, MCP-1 was found to be the predominant cytokine elevated. Eyes with a propensity to scar in the early postoperative period have a significantly raised level of MCP-1. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

[Synthesis and biological evaluation of nitrate-oleanolic acid hybrids as inhibitors of HepG2 cell apoptosis].

To find novel antihepatitis drugs, a series of nitrate-oleanolic acid (OA) hybrids (10a, 10b, 11a-11e and 12a-12c) were designed and synthesized on the basis of previous studies using OA as lead compound, which is widely found in natural plants and liver-specific metabolism. In the present study, ten novel NO-releasing derivatives of OA were synthesized by connecting nitrate to the OA-3-OH through varying lengths of linkers containing antioxidants which were designed to increase the ability of these target compounds to scavenge free radicals. The structures of these objective compounds were determined by IR, MS, 1H NMR and elemental analysis. Their protective effects on anti-Fas mediated HepG2 cell apoptosis were in vitro evaluated by LDH assay. Compound 12a is the most potent inhibitor. Its effect on anti-Fas mediated HepG2 cell apoptosis and amount of NO-releasing in vitro are similar to those of positive control NCX-1000.

Can conventional DWI accurately assess the size of endometrial cancer?

PURPOSE: To compare T2-weighted image (T2WI) and conventional Diffusion-weighted image (cDWI) of magnetic resonance imaging (MRI) for sensitivity of qualitative diagnosis and accuracy of tumor size (TS) measurement in endometrial cancer (EC). Meanwhile, the effect of the lesion size itself and tumor grade on the ability of T2WI and cDWI of TS assessment was explored. Ultimately, the reason of deviation on size evaluation was studied. MATERIALS AND METHODS: 34 patients with EC were enrolled. They were all treated with radical hysterectomy and performed MR examinations before operation. Firstly, the sensitivity of T2WI alone and T2WI-DWI in qualitative diagnosis of EC were compared according to pathology. Secondly, TS on T2WI and cDWI described with longitudinal (LD) and horizontal diameter (HD) were compared to macroscopic surgical specimen (MSS) quantitatively in the entire lesions and the subgroup lesions which grouped by postoperative tumor size itself and tumor grade. Thirdly, the discrepancy of mean ADC values (ADC mean) and range ADC values (ADC range) between different zones of EC were explored. RESULTS: For qualitative diagnosis, the sensitivity of T2WI-DWI (97%) was higher than T2WI alone (85%) (p = 0.046).For TS estimation, no significant difference (PLD = 0.579; PHD = 0.261) was observed between T2WI (LDT2WI = 3.90 cm; HDT2WI = 2.88 cm) and MSS (LD = 4.00 cm; HD = 3.06 cm), whereas TS of cDWI (LDDWI = 3.01 cm; HDDWI = 2.54 cm) were smaller than MSS (PLD = 0.002; PHD = 0.002) in all lesions. In subgroup of tumor with G1 (grade 1) and small lesion (defined as maximum diameter < 3 cm), both T2WI and cDWI were not significantly different from MSS; In subgroup of tumor with G2 + 3 (grade 2 and grade 3) and big lesion (maximum diameter ≥ 3 cm), T2WI matched well with MSS still, but DWI lost accuracy significantly. The result of ADC values between different zones of tumor showed ADC mean of EC rose from central zone to peripheral zone of tumor gradually and ADC range widened gradually. CONCLUSION: cDWI can detect EC very sensitively. The TS on cDWI was smaller than the fact for the ECs with G2/3 and big size. The TS of T2WI was in accordance with the actual size for all ECs. The heterogeneity may be responsible for the inaccuracy of cDWI.

Fabrication of a Novel Antifouling Polysulfone Membrane with in Situ Embedment of Mxene Nanosheets.

Membrane fouling is still a critical issue for the application of ultrafiltration, which has been widely used in water treatment due to its efficiency and simplicity. In order to improve the antifouling property, a new 2D material MXene was used to fabricate composite ultrafiltration membrane with the approach of in situ embedment during the phase inversion process in this study. Scanning electron microscopy (SEM), atomic force microscopy (AFM), thermogravimetric analysis (TGA), energy dispersive spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR), water contact angle, bovine serum albumin rejection and porosity measurements were utilized to characterize the prepared membranes. Due to the hydrophilicity of the MXene, the composite membranes obtained higher hydrophilicity, confirmed by the decreased water contact angle. All the modified membranes had a high bovine serum albumin rejection above 90% while that of the pristine polysulfone membrane was 77.48%. The flux recovery ratio and the reversible fouling ratio of the membranes were also improved along with the increasing content of the MXene. Furthermore, the highest flux recovery ratio could also reach 76.1%. These indicated the good antifouling properties of MXene composite membranes. The enhanced water permeability and protein rejection and excellent antifouling properties make MXene a promising material for antifouling membrane modification.

GapReduce: a gap filling algorithm based on partitioned read sets.

With the advances in technologies of sequencing and assembly, draft sequences of more and more genomes are available. However, there commonly exist gaps in these draft sequences which influence various downstream analysis of biological studies. Gap filling methods can shorten the length of gaps and improve the completion of these draft sequences of genomes. Although some gap filling tools have been developed, their effectiveness and accuracy need to be improved. In this study, we develop a novel tool, called GapReduce, which can fill the gaps using the paired reads. For a gap, GapReduce selects the reads whose mate reads are aligned on the left or the right flanking region, and partitions the reads to two sets. Then GapReduce adopts different values and frequency thresholds to iteratively construct De Bruijn graphs, which are used for finding the correct path to fill the gap. For overcoming the branching problems caused by repetitive regions and sequencing errors in the procedure of path selection, GapReduce designs a novel approach that simultaneously considers frequency and distribution of paired reads based on the partitioned read sets. We compare the performance of GapReduce with current popular gap filling tools. The experimental results demonstrate that GapReduce can produce satisfactory gap filling results, especially for long insert size datasets. GapReduce is publicly available for downloading at https://github.com/bioinfomaticsCSU/GapReduce.

Multidisciplinary approach to understand the pathogenesis of gastric cancer.

Gastric carcinoma remains a common disease worldwide with a dismal prognosis. Therefore, it represents a very important health problem. It occurs with a high incidence in Asia and is one of the leading causes of cancer death in the world. Although the incidence and mortality of gastric carcinoma are decreasing in many countries, gastric cancer still represents the second most frequent malignancies in the world and the fourth in Europe. The 5-year survival rate of gastric carcinoma is low. The etiology and pathogenesis are not yet fully known. The study of gastric cancer is important in clinical medicine as well as in public health. Over the past 15 years, integrated research in molecular pathology has clarified the details of genetic and epigenetic abnormalities of cancer-related genes in the course of the development and progression of gastric cancer. Gastric cancer, as all cancers, is the end result of the interplay of many risk factors as well as protective factors. Although epidemiological evidence indicates that environmental factors play a major role in gastric carcinogenesis, the role of immunological, genetic, and immunogenetic factors are thought to contribute to the pathogenesis of gastric carcinoma. Among the environmental factors, diet and Helicobacter pylori are more amenable to intervention aimed at the prevention of gastric cancer. The aim of the present paper is to review and include the most recent published evidence to demonstrate that only a multidisciplinary approach will lead to the advancement of the pathogenesis and prevention of gastric cancer. On the immunogenetic research it is clear that evidence is accumulating to suggest that a genetic profile favoring the proinflammatory response increases the risk of gastric carcinoma.

Proteomic profiling of inflammatory signaling molecules in the tears of patients on chronic glaucoma medication.

PURPOSE: To identify the tear proteins associated with the long-term use of glaucoma medication by using proteomic analysis and to compare these proteins to those previously reported in primary dry eye disease. METHODS: Eighteen patients treated with topical antiglaucoma medications and 10 normal age-matched subjects with no prior topical treatment were recruited for the study. Tears were collected by using Schirmer's strip and analyzed by iTRAQ (isobaric tag for relative and absolute quantitation) for tear proteins by mass spectrometry. Conjunctival samples were collected and RNA expression determined by PCR. RESULTS: Of the 124 identified tear proteins (99% confidence, ProtScore ≥ 2.0), we found that the tear levels of S100-A8, S100-A9, mammaglobin B, and 14-3-3 ζ/δ were significantly increased in the medicated group compared with levels in the nonmedicated group (P < 0.05). For S100-A9, mammaglobin B, and 14-3-3 ζ/δ, use of topical medication for less than 1 year did not reach statistical significance compared with that in the nonmedicated group. Eyes on topical medication for less than 1 year showed a decrease in proline-rich 4 protein tear level (P = 0.0049) compared to nonmedicated group. The tear proteins detected in the medicated group differed from those in the primary dry eye group. CONCLUSIONS: Treatment with topical antiglaucoma medications for longer than 1 year may start to induce ocular surface inflammation. The inflammatory tear protein profile present in chronically medicated glaucomatous eyes appears to be different from that found in primary dry eye. Identification of tear proteins specific to medicated glaucomatous eyes will help to specifically develop targeted screening modalities and therapeutic agents different from current conventional dry eye management.

Aberrant DNA methylation of matrix remodeling and cell adhesion related genes in pterygium.

BACKGROUND: Pterygium is a common ocular surface disease characterized by abnormal epithelial and fibrovascular proliferation, invasion, and matrix remodeling. This lesion, which migrates from the periphery to the center of the cornea, impairs vision and causes considerable irritation. The mechanism of pterygium formation remains ambiguous, and current treatment is solely surgical excision, with a significant risk of recurrence after surgery. Here, we investigate the role of methylation in DNA sequences that regulate matrix remodeling and cell adhesion in pterygium formation. METHODOLOGY/PRINCIPAL FINDINGS: Pterygium and uninvolved conjunctiva samples were obtained from the same eye of patients undergoing surgery. The EpiTYPER Sequenom technology, based on differential base cleavage and bisulfite sequencing was used to evaluate the extent of methylation of 29 matrix and adhesion related genes. In pterygium, three CpG sites at -268, -32 and -29 bp upstream of transglutaminase 2 (TGM-2) transcription initiation were significantly hypermethylated (p<0.05), whereas hypomethylation was detected at CpGs +484 and +602 bp downstream of matrix metalloproteinase 2 (MMP-2) transcription start site, and -809, -762, -631 and -629 bp upstream of the CD24 transcription start site. RT-qPCR, western blot and immunofluorescent staining showed that transcript and protein expression were reduced for TGM-2 and increased for MMP-2 and CD24. Inhibition of methylation in cultured conjunctival epithelial cells increased these transcripts. CONCLUSIONS/SIGNIFICANCE: We found regions of aberrant DNA methylation which were consistent with alteration of TGM-2, MMP-2, and CD24 transcript and protein expression, and that inhibition of methylation in cultured cells can increase the expression of these genes. Since these genes were related to cell adhesion and matrix remodeling, dysregulation may lead to fibroblastic and neovascular changes and pterygium formation. These results have implications for the prognostication of pterygium in clinical practice, for example, detection of epigenetic changes may have a role in predicting post surgical recurrence of aggressive lesions.