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Pythium species are distributed globally, with certain members playing significant roles as plant and animal pathogens. Pythium cedri Chen 4 has been identified as a pathogenic isolate responsible for causing root rot on Cedrus deodara. Here, a comprehensive genome-wide sequence of P. cedri strain Chen 4 utilizing the Illumina NovaSeq sequencing platform and a Pacific Biosciences Sequel sequencing platform is presented. The genome of P. cedri strain Chen 4 was assembled into 150 contigs containing a combined size of 41.25 Mb, N50 value of 1,717,859 bp and N90 value of 431,829 bp. Genome annotation revealed 14,077 protein-encoding genes and 364 of the 1016 predicted proteins were putative effectors. The present work enriches the genetic resources of P. cedri for studying its evolution and can contribute to a better understanding of P. cedri–host interaction.

Background: The occurrence of acne in patients treated with Janus kinase (JAK) inhibitors for skin diseases is a potential issue, which may reduce treatment adherence.Purpose: To systematically analyzes randomized clinical trials (RCTs) of JAK inhibitors in dermatological indications for the risk of acne as an adverse event.Methods: A meta-analysis of odds ratios (ORs) for acne incidence was conducted. Data were quantitatively synthesized using random-effects meta-analysis. Surface under the cumulative ranking curve (SUCRA) values representing the relative ranking probabilities of treatments were obtained. Analyses were performed using R statistical software version 4.4.0.Results: A total of 11,396 patients were included from 24 studies. The incidence of acne for JAK inhibitors was ranked according to the SUCRA as follows: JAK1 inhibitors > TYK2 inhibitors > combined JAK1 and JAK2 inhibitors > combined JAK1 and TYK2 inhibitors > JAK3 + TEC inhibitors > pan-JAK inhibitors. ORs were higher for longer durations of drug use and larger dosages. Subgroup analyses by disease indication revealed increased ORs for psoriasis (5.52 [95% CI, 1.39–21.88]), vitiligo (4.15 [95% CI, 1.27–13.58]), alopecia areata (3.86 [95% CI, 1.58–9.42]), and atopic dermatitis (2.82 [95% CI, 1.75–4.54]). The use of JAK inhibitors in patients with systemic lupus erythematosus (SLE) may not significantly increase the incidence of acne.Conclusions: There are higher rates of acne following treatment with JAK inhibitors for dermatologic indications, particularly with longer durations and larger dosages. Pan-JAK inhibitors exhibit the lowest incidence of acne.

Radiation-induced lung injury (RILI) is a common and fatal complication of chest radiotherapy. The underlying mechanisms include radiation-induced oxidative stress caused by damage to the deoxyribonucleic acid (DNA) and production of reactive oxygen species (ROS), resulting in apoptosis of lung and endothelial cells and recruitment of inflammatory cells and myofibroblasts expressing NADPH oxidase to the site of injury, which in turn contribute to oxidative stress and cytokine production. Nuclear factor erythroid 2-related factor 2 (Nrf-2) is a vital transcription factor that regulates oxidative stress and inhibits inflammation. Studies have shown that Nrf-2 protects against radiation-induced lung inflammation and fibrosis. This review discusses the protective role of Nrf-2 in RILI and its possible mechanisms.

Abstract Background and Aims Extrahepatic recurrence (EHR) is one of the major reasons for the poor prognosis of hepatocellular carcinoma (HCC). The present study aimed to develop and assess the performance of predictive models by using a combination of presurgical circulating tumor cell (CTCs) data and clinicopathological features to screen patients at high risk of EHR to achieve precise decision‐making. Patients and Methods A total of 227 patients with recurrent HCC and preoperative CTC data from January 2014 to August 2019 were enrolled. All patients were randomly assigned to one of two cohorts: development or validation. Two preoperative and postoperative nomogram models for EHR prediction were developed and multi‐dimensionally validated. Results Patients with EHR had generally lower recurrence‐free survival (p

Photocatalytic antibacterial materials have been popularized and widely used in the disinfection of municipal water, the large-scale wastewater sterilization treatment of industry, and medical treatment. Their antibacterial theory has also been continuously studied and improved, and the reactive oxygen species (ROS) antibacterial mechanism has the highest acceptance by the public. The role of ROS is the main bactericidal mechanism of photocatalytic antibacterial agents, and it is also the mechanism explanation at the molecular level in the fields of organic pollutant degradation and biological pathology. ROS at an abnormal steady-state concentration attacks the organic structure outside the cell and enters the cell, causing oxidative stress reactions inside the cell and irreversible damage to the cell until apoptosis. Therefore, a systematic analysis of the production pathways, principle of action, and corresponding detection methods of active oxygen is of great importance for improving the antibacterial activity of photocatalytic antibacterial agents and exploring the antibacterial mechanism of active oxygen. First, this article introduces the production mechanism of active oxygen in photocatalytic materials and its antibacterial performance. Particularly, the modification method of constructing heterojunctions and introducing oxygen vacancies is the main way to increase active oxygen production. Second, this article summarizes the production process and mechanisms of the main ROS, such as the superoxide anion radical (·O\begin{document}${}_2^- $\end{document}), hydrogen peroxide (H2O2), singlet oxygen (1O2), and the hydroxyl radical (·OH), as well as the antibacterial process. Detection methods are summarized for four ROS, including direct methods and indirect methods as well the specific and selective reaction principle of probe molecules with ROS. Furthermore, the influencing factors of the total concentration of ROS excited by photocatalytic materials are sorted out, and a modification direction for producing ROS is proposed. This paper proposes the problems existing in the research on the action mechanism of ROS and the deficiencies in the detection methods of ROS and their specific interaction with cells. It is suggested to carefully analyze the antibacterial mechanism of ROS at the biological component level under the guidance of the generation chain of ROS and the dynamic balance system of various ROS. Finally, suggestions are made on the design and application of active oxygen antibacterial materials, and the development prospects are addressed.

AbstractPurpose The purpose of this study was to estimate the clinical efficacy and identify the best beneficiaries of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) in hepatocellular carcinoma (HCC).Patients and methods A total of 749 HCC patients who underwent surgical resection (380 underwent PA-TACE, 369 had resection only) with a high risk of recurrence were reviewed retrospectively. Patients receiving PA-TACE were randomly split into development and validation cohorts. Univariate and multivariate analyses were performed in the development cohort. A novel model for PA-TACE-insensitivity prediction was built based on univariate and multivariate analysis and was multi-dimensionally validated in the validation set and all samples.Results After propensity score matching (PSM), in the early-recurrence group, no significant improvement in RFS was achieved with PA-TACE compared to radical hepatic resection alone. PA-TACE insensitive patients were considered as the PA-TACE non-benefit population and were associated with six clinicopathological factors: AFP, node number, tumor capsule, Ki-67 index, MVI, and complications in the development cohort. These factors were incorporated into a nomogram model, which reliably predicted PA-TACE insensitivity, with concordance indices of 0.874 and 0.897 for the development and validation cohort, respectively. In the overall sample, PA-TACE did not significantly improve patients’ RFS and OS in the high-score group, while the low-score group had statistical significance. Recurrence pattern diversity was also found to be a factor leading to PA-TACE insensitivity.Conclusion We constructed a new PA-TACE-insensitivity prediction model with potential clinical value. The good predictive performance and availability would allow this model to effectively screen PA-TACE beneficiaries.KEY MESSAGESThe independent influencing factors of PA-TACE insensitivity in patients who received PA-TACE were analyzed to construct a predictive model and its clinical application performance was verified with multi-dimensional methods.PA-TACE treatment should be avoided for patients with high scores according to this model, while it should be cautiously recommended for patients with low scores after multiple considerations.Compared with other related models, this model has obvious advantages in versatility and effectiveness. It can effectively screen the best benefit population of PA-TACE and provide a reliable reference for the selection of precise treatment plans for patients after radical resection of hepatocellular carcinoma.

Abstract Background The tumor‐stromal ratio (TSR) has been verified to be a prognostic factor in many solid tumors. In most studies, it was manually assessed on routinely stained H&E slides. This study aimed to assess the TSR using image analysis algorithms developed by the Qupath software, and integrate the TSR into a nomogram for prediction of the survival in invasive breast cancer (BC) patients. Methods A modified TSR assessment algorithm based on the recognition of tumor and stroma tissues was developed using the Qupath software. The TSR of 234 invasive BC specimens in H&E‐stained tissue microarrays (TMAs) were assessed with the algorithm and categorized as stroma‐low or stroma‐high. The consistency of TSR estimation between Qupath prediction and pathologist annotation was analyzed. Univariable and multivariable analyses were applied to select potential risk factors and a nomogram for predicting survival in invasive BC patients was constructed and validated. An extra TMA containing 110 specimens was obtained to validate the conclusion as an independent cohort. Results In the discovery cohort, stroma‐low and stroma‐high were identified in 43.6% and 56.4% cases, respectively. Good concordance was observed between the pathologist annotated and Qupath predicted TSR. The Kaplan–Meier curve showed that stroma‐high patients were associated with worse 5‐DFS compared to stroma‐low patients (p = 0.007). Multivariable analysis identified age, T stage, N status, histological grade, ER status, HER‐2 gene, and TSR as potential risk predictors, which were included in the nomogram. The nomogram was well calibrated and showed a favorable predictive value for the recurrence of BC. Kaplan–Meier curves showed that the nomogram had a better risk stratification capability than the TNM staging system. In the external validation of the nomogram, the results were further validated. Conclusions Based on H&E‐stained TMAs, this study successfully developed image analysis algorithms for TSR assessment and constructed a nomogram for predicting survival in invasive BC.

AIM: To analyze the role of complement system(CS)and its classical pathway in the pathogenesis of lacrimal gland benign lymphoepithelial lesions(LGBLEL).METHODS: The tissues of patients with LGBLEL or orbital cavernous hemangioma(CH)were collected. Proteomics analysis was used for the identification of different proteins. Reverse transcription-polymerase chain reaction(RT-PCR), immunohistochemical staining(IHC)and Western Blotting were employed to verify the changes of the differential proteins in CS signal pathway, in order to identify its role in the pathogenesis of LGBLEL.RESULTS: The results of proteomic analysis showed that the expression levels of proteins C3, C5, C9 and C1q in CS signal pathway in the lacrimal gland tissues of LGBLEL patients were all changed compared with those of orbital CH patients.The results of RT-PCR showed that the mRNA expression levels of C1qA, C5 and C9 in patients with LGBLEL were significantly higher than those patients with orbital CH. The results of IHC showed that the expression levels of C1qA, C3, C5 and C9 were significantly increased in patients with LGBLEL compared with those patients with orbital CH. The results of Western Blotting showed that the protein expression levels of C1qA, C3, and C9 were significantly increased in patients with LGBLEL compared with those patients with orbital CH.CONCLUSION: The CS has been shown to participate in the pathogenesis of LGBLEL and its classical pathway may be one of the pathways which plays a role.

IntroductionAlthough surgery is the preferred treatment for sarcomatoid hepatocellular carcinoma (SHC), the prognosis remains considerably poor due to early postoperative recurrence and metastasis. Reports on surgery after combined treatment with a tyrosine kinase inhibitor and anti-programmed cell death (PD)-1 antibody are unavailable.Case presentationA 69-year-old male patient with SHC was admitted to our hospital for treatment of a liver tumor that was detected on ultrasonography. Abdominal computed tomography with triple-phase enhancement revealed a lesion in the right hepatic lobe that measured 86.0 mm × 75.0 mm × 71.0 mm. Biopsy revealed a pathological diagnosis of liver sarcoma or sarcomatoid carcinoma. The patient subsequently received transcatheter arterial chemo-embolization, as he did not consent to surgery. More than two months later, he received a combination of lenvatinib with camrelizumab, as computed tomography showed an increase in the lesion size (to 123.0 mm × 90.0 mm × 80.0 mm) and lateral growth posterior to the upper pole of the right kidney. Liver resection was performed after 6 months of systemic therapy; pathological examination confirmed a diagnosis of SHC and showed extensive necrosis of tumor cells. Combined treatment with lenvatinib and camrelizumab was continued for 6 months after surgery. The patient has survived for over 24 months after initial diagnosis and is currently tumor-free.ConclusionCombined systemic therapy with a tyrosine kinase inhibitor and anti-PD-1 antibody may represent a feasible treatment strategy for improving resectability in cases of unresectable SHC. The outcomes with this combination may also be explored in cases of resectable SHC that have a high-risk of recurrence; this may improve the therapeutic effect.

Trametopsis is a worldwide genus belonging to Irpicaceae in the phlebioid clade, which can cause a white decay of wood. Previously, only three species were ascribed to the genus. In this study, we performed a morphological and phylogenetic study of Trametopsis. Molecular phylogenetic analyses of multiple loci included the internal transcribed spacer (ITS) regions, the large subunit nuclear ribosomal RNA gene (nLSU), the largest subunit of RNA polymerase II (RPB1), the second largest subunit of RNA polymerase II (RPB2) and the translation elongation factor 1-α gene (TEF1). Phylogenetic trees were inferred from the combined datasets of ITS+nLSU sequences and ITS+nLSU+RPB1+RPB2+TEF1 sequences by using maximum parsimony, maximum likelihood and Bayesian inference analyses. Combined with molecular data, morphological characters and ecological traits, two new species of Trametopsis are discovered. Trametopsis abieticola is characterised by its pileate, solitary or imbricate basidiomata, buff to buff-yellow pileal surface when fresh, becoming pinkish buff to clay-buff when dry, cream to buff pore surface when fresh, becoming pinkish buff to greyish brown upon drying, round to angular and large pores (0.5–1 per mm), cylindrical basidiospores (5.8–7.2 × 1.9–2.6 μm), distributed in the high altitude of mountains and grows on Abies sp. Trametopsis tasmanica is characterised by its resupinate basidiomata, cream to pinkish-buff pore surface when fresh, becoming honey-yellow to snuff brown upon drying, cylindrical basidiospores (5.2–6.3 × 1.8–2.2 μm), and by growing on Eucalyptus sp. Detailed descriptions and illustrations of the two novel species are provided.

Abstract Atom-transfer radical polymerization (ATRP) is a well-known technique for controlled polymer synthesis. However, the ATRP usually employed toxic heavy metal ionas as the catalyst and was susceptible to molecular oxygen, which made it should be conducted under strictly anoxic condition. Conducting ATRP under ambient and biocompatible conditions is the major challenge. In this study, cytochrome C was explored as an efficient biocatalyst for ATRP under biocompatible conditions. The cytochrome C catalyzed ATRP showed a relatively low polymer dispersity index of 1.19. More interestingly, the cytochrome C catalyzed ATRP showed superior oxygen resistance as it could be performed under aerobic conditions with high dissolved oxygen level. Further analysis suggested that the Fe(II) embed in the cytochrome C might serve as the catalytic center and methyl radical was responsible for the ATRP catalysis. This work explored new biocompatible catalyst for aerobic ATRP, which might open new dimension for practical ATRP and application of cytochrome C protein. Graphical Abstract

PurposeHead and neck squamous cell carcinoma (HNSCC) ranks sixth among all cancers globally regarding morbidity, and it has a poor prognosis, high mortality, and highly aggressive properties. In this study, we established a model for predicting prognosis based on immunohistochemical (IHC) scores.MethodsData on 402 HNSCC cases were collected, the glmnet Cox proportional hazards model was used, risk factors were analyzed for predicting the prognosis of survival, and the IHC score was established. We used the IHC score to predict disease-free survival (DFS) using training and independent validation cohorts, including 264 cases in total. Additionally, the accuracy of the IHC score and the TNM system (8th edition) was compared. A DFS prediction nomogram was established by combining the prognostic factors.ResultsThe IHC scores included CK, Ki-67, p16, and p40 staining intensity. The concordance index and the Kaplan-Meier survival analysis showed that the IHC scores had high predictive power for HNSCC. Our results showed that the IHC score is an independent factor that can predict prognosis in a multivariate Cox regression analysis. When predicting DFS, the IHC score had a significantly higher value for the area under the ROC curve (AUC) than that of the TNM system. A nomogram was established and included the IHC score, age, tumor location, and the TNM stage. The calibration curves exhibited high consistency between the prognosis predicted by our nomogram and the actual prognosis.ConclusionsThe IHC score was more accurate than the eighth edition of the TNM system in predicting HNSCC prognosis. Therefore, combining the two methods can facilitate individualized patient consultation and care.

ObjectiveTo evaluate the efficacy of acupuncture in treating Parkinson’s disease-related constipation (PDC).Materials and methodsThis was a randomized, controlled trial in which patients, outcome assessors, and statisticians were all blinded. Seventy-eight eligible patients were randomly assigned to either the manual acupuncture (MA) or sham acupuncture (SA) groups and received 12 sessions of treatment over a 4-week period. Following treatment, patients were monitored until the eighth week. The primary outcome was the change in weekly complete spontaneous bowel movements (CSBMs) from baseline after treatment and follow-up. The Constipation Symptom and Efficacy Assessment Scale (CSEAS), the Patient-Assessment of Constipation Quality of Life questionnaire (PAC-QOL), and the Unified Parkinson’s Disease Rating Scale (UPDRS) were used as secondary outcomes.ResultsIn the intention-to-treat analysis, 78 patients with PDC were included, with 71 completing the 4-week intervention and 4-week follow-up. When compared to the SA group, weekly CSBMs were significantly increased after treatment with the MA group (P < 0.001). Weekly CSBMs in the MA group were 3.36 [standard deviation (SD) 1.44] at baseline and increased to 4.62 (SD, 1.84) after treatment (week 4). The SA group’s weekly CSBMs were 3.10 (SD, 1.45) at baseline and 3.03 (SD, 1.25) after treatment, with no significant change from baseline. The effect on weekly CSBMs improvement in the MA group lasted through the follow-up period (P < 0.001).ConclusionAcupuncture was found to be effective and safe in treating PDC in this study, and the treatment effect lasted up to 4 weeks.Clinical trial registrationhttp://www.chictr.org.cn/index.aspx, identifier ChiCTR2200059979

Background: To report on a case of primary Umbilical Endometriosis (PUE). Case: We report a new rare case of PUE in a 45-year-old woman arising in the umbilicus, presenting as three purple-blue firm masses with a smooth surface, and clear borders. The patient presented to our hospital with a complaint of dark-red blood flowing out of the umbilical fossa accompanied by periodic menstrual pain for more than a year. PUE was initially diagnosed based on clinical signs and imaging studies and the mass was widely excised. The postoperative histologic examination of the tissue confirmed the diagnosis of PUE. Conclusion: PUE is a rare umbilical disorder. Its diagnosis may be complicated due to clinician lack of knowledge. The possibility of endometriosis must be considered during the evaluation of an umbilical mass despite the absence of any previous surgery, with special attention to menstrual symptoms or bloody discharge.

Background: Transforaminal endoscopic lumbar discectomy (TELD) has been widely used for lumbar disc herniation. However, in some challenging cases such as very highly migrated disc herniation (VHMDH), traditional TELD is difficult to access the pathology. Methods: From January 2016 to December 2019, 63 patients with single-level VHMDH underwent TELD using targeted puncture and foraminotomy techniques were included. All patients were followed up for 26.5 months on average (range, 24–48 months). Operative time, length of hospital stay, visual analog scale (VAS) score, Oswestry Disability Index (ODI), modified MacNab criteria and surgical complications were evaluated. Results: The operative time was 40–120 min (56.8 on average). The length of hospitalization was 2.5 days (range, 2–4 d). VAS score decreased significantly from 5.5 ± 1.3 preoperatively to 1.9 ± 1.30 (p < 0.001) 1 day postoperatively, and to 0.9 ± 0.8 (p < 0.001) at the final follow-up. ODI score improved significantly from 23.5 ± 3.2 preoperatively to 13.4 ± 3.0 (p < 0.001) 1 day postoperatively; and 3.1 ± 1.2 (p < 0.001) at the final follow-up. According to the modified MacNab criteria, 40 patients (63.5%) showed excellent results, 20 patients (31.7%) were rated as good, 2 patients (3.2%) were rated as fine, and 1 patient (1.6%) was rated as bad at the final follow-up. No residual fragments, nerve root or cauda equina injury was shown in this series. One recurrent case was resolved by open surgery. Conclusions: With modified targeted puncture and foraminotomy techniques, VHMDH can be accessed safely and effectively, and satisfactory clinical outcomes can be obtained for these patients.

Workplace social capital positively influences the quality but reduces the cost of healthcare services. Academic research suffers from limited and inadequate culturally sensitive nurses’ workplace social capital instruments. Here we report on the design and protocol of a culturally focused instrument development study in China. The overarching objective of our dual phase study is to develop and validate a questionnaire measuring nurses’ workplace social capital tailored toward Chinese cultural values and norms. In the first phase of INSTRUMENT DEVELOPMENT , the qualitative phase, we will conduct interviews with purposefully sampled nurses from five geographically diverse regions capturing 16 provinces in China to formulate the initial version of the Nurses’ Workplace Social Capital Questionnaire (NWSCQ). Data collection will be stopped at the saturation point and content analysis will be performed for interview data in parallel. The initial version of the NWSCQ will be evaluated and confirmed by two-rounds of expert consultation (target N = 20) and pre-tested among 70 nurses. During the second phase of INSTRUMENT VALIDATION or the quantitative phase, we will validate the psychometric properties of the NWSCQ. The validity and reliability of the questionnaire will be examined and validated through three cross-sectional surveys among nurses (target N = 1154) randomly selected from 12 tertiary hospitals. We have reported our study protocol with the intention of sharing our experience with researchers in other countries who are striving to advance the phenomenon of culturally sensitive and social normatively appropriate nurses’ workplace social capital. Findings from our study should advance the development of culturally appropriate and valid instrument of nurses’ workplace social capital, another important step toward recognition and incorporation of cultural diversity in the daily operation of healthcare industry.

Submerged macrophyte and periphyton are main primary producers which strongly interact with each other in clear water shallow lakes. In this study, the effects of genetic variation of the macrophyte species on periphyton biomass were studied in five submerged species. A two-year mesocosm study was conducted with four levels of genetic diversity (1, 4, 8 and 16 genotypes) for each submerged macrophyte, including 1600 individuals and 320 boxes in 20 mesocosms. Of the five submerged species, only Vallisneria spinulosa showed a positive correlation between its levels of genotype richness and the periphyton biomass. The correlation between genetic distance of genotypes and periphyton biomass was tested, which varied with the difference of seasons and species. In summary, we found that in freshwater mesocosms, the genetic diversity of submerged macrophytes may play a role in regulating the periphyton biomass, but the interaction between genetic diversity of macrophytes and periphyton biomass was not straightforward. This study will provide new insights into the interaction dynamics between the two primary producers in shallow lakes.

Background: We started to design and test health education Apps for self-management among patients to provide a rich source of clinical support and information for patients to increase their ability of self-management. Methods: First, a multidisciplinary research team worked together to design and conduct the research. With their help, we redesigned an apps to incorporate some personalized changes for patients’ needs. Second, we chose a questionnaire from the Comprehensive Service Platform for the Elderly self-designed by CHENYu. Finally, a purposive sample of 34 users were tested experiences and satisfaction of users in Jul 2021. Results: This research was successfully conducted in 22 wards among 23159 patients and 40440 chapters about healthy information sent to patients from Mar 2019 to January 2021 by smartphone. The data showed that 91.2% of participants resolved that the evaluation effect of the proposed application was better, in comparison with the paper version as routine verbal instruction. Additionally, 85.3% of participants wanted to continue to receive medical education information after discharge from the hospital. The top four most popular medical education information that they would like to receive included drug administration, disease prevention, nursing, and home care. Moreover, the top four most popular types of user suggestions were one-on-one online Q & A, continue to see every session, accelerate the speed of browsing and page updated, and free Wifi. The user satisfaction of the application was considerably high. Conclusion: The apps was welcomed by patients who wanted to increase their knowledge level of disease and perform self-management better.

Abstract. Background. Myocardial infarction occurs due to insufficient (ischemia) blood supply to heart for long time; plasmacytoma variant translocation 1 (PVT1) is a long non-coding RNAs (lncRNAs) involved in the pathogenesis of various diseases, including heart disease; However, few studies have explored its role. The present study evaluated the effects of lncRNA PVT1 on hypoxic rat H9c2 cells. Methods. Hypoxic injury was examined by measuring cell viability and apoptosis by using cell counting kit-8 activity and flow cytometry assays. Gene expressions after hypoxia were estimated by quantitative real time polymerase chain reaction and the signaling pathway were explored by Western blot analysis. RNA immunoprecipitation and luciferase reporter assays were applied to examine the interactions among genes. Data were analyzed using t-test with one-way or two-way analysis of variance. Results. The lncRNA PVT1 is up-regulated in hypoxia-stressed H9c2 cells and knockdown of PVT1 mitigates hypoxia-induced injury in H9c2 cells. PVT1 acts as a sponge for miR-135a-5p and knockdown of PVT1 attenuated the increased hypoxia-induced injury by up-regulating miR-135a-5p. Forkhead box O1 (FOXO1) was identified as a target of miR-135a-5p, and the expression was negatively regulated by miR-135a-5p. The exploration of the underlying mechanism demonstrated that knockdown of FOXO1 reversed PVT1/miR-135a-5p mediated hypoxia-induced injury in H9c2 cells. Conclusions. PVT1 plays a crucial role in hypoxia-injured H9c2 cells through sponging miR-135a-5p and then positively regulating FOXO1.

Abstract. Background. Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs. Methods. We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%. Results. At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group. Conclusions. The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure. Trial registration. ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov. Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx

Abstract Aging and average life expectancy have been increasing at a rapid rate, while there is an exponential risk to suffer from brain-related frailties and neurodegenerative diseases as the population ages. Alzheimer’s disease (AD) is the most common neurodegenerative disease worldwide with a projected expectation to blossom into the major challenge in elders and the cases are forecasted to increase about 3-fold in the next 40 years. Considering the etiological factors of AD are too complex to be completely understood, there is almost no effective cure to date, suggesting deeper pathomechanism insights are urgently needed. Metabolites are able to reflect the dynamic processes that are in progress or have happened, and metabolomic may therefore provide a more cost-effective and productive route to disease intervention, especially in the arena for pathomechanism exploration and new biomarker identification. In this review, we primarily focused on how redox signaling was involved in AD-related pathologies and the association between redox signaling and altered metabolic pathways. Moreover, we also expatiated the main redox signaling-associated mechanisms and their cross-talk that may be amenable to mechanism-based therapies. Five natural products with promising efficacy on AD inhibition and the benefit of AD intervention on its complications were highlighted as well. Graphical Abstract

High‐mobility group protein B1 (HMGB1) has important functions in cancer cell proliferation and metastasis. However, the mechanisms of HMGB1 function in non‐small‐cell lung cancer (NSCLC) remain unclear. This study aimed to investigate the underlying mechanism of HMGB1‐dependent tumor cell proliferation and NSCLC metastasis. Firstly, we found high HMGB1 expression in NSCLC and showed that HMBG1 promoted proliferation, migration, and invasion of NSCLC cells. HMGB1 could bind to SNAI1 promoter and activate the expression of SNAI1. In addition, HMGB1 could transcriptionally regulate the lncRNA RSF1‐IT2. RSF1‐IT2 was found to function as ceRNA, sponging miR‐129‐5p, which targets SNAI1. Notably, HMGB1 was also identified as a target of miR‐129‐5p, which indicates the establishment of a positive feedback loop. Consequently, high expression of RSF1‐IT2 and SNAI1 was found to closely correlate with tumor progression in both HMGB1‐overexpressing xenograft nude mice and patients with NSCLC. Taken together, our findings provide new insights into molecular mechanisms of HMGB1‐dependent tumor metastasis. Components of the HMGB1–RSF1‐IT2–miR‐129‐5p–SNAI1 pathway may have a potential as prognostic and therapeutic targets in NSCLC.

Abstract Background We investigated the risk factors of radiation-induced thyroid dysfunction, then combined the clinical factors and optimum thyroid dosimetric parameters to predict the incidence rate of hypothyroidism (HT) and to guide individualized treatment. Methods A total of 206 patients with histologically proven nasopharyngeal carcinoma (NPC) treated at the Cancer Hospital of the University of Chinese Academy of Sciences between January 2015 and August 2018 were included. Dose–volume histogram (DVH) data, including mean dose, absolute volume, V20, V25, V30, V35, V40, V45, V50, V55, and V60 were extracted and used as dosimetric parameters. A logistic regression analysis model was built to identify predictors related to HT occurring within 2 years. Results Sex, N stage, thyroid volume, mean thyroid dose, and thyroid V20 and V50 were significantly different between patients with and without HT. Logistic regression analysis showed that N stage, thyroid volume, and thyroid V50 were independent predictors of HT. The radiosensitivity of the thyroid decreased as the thyroid volume increased. Patients with N stage > 1 had significantly higher HT incidence (37.38%) than patients with N stage ≤1 (13.11%). The incidence of HT was 54.55% in patients with thyroid V50 > 24% and was 34.15% in patients with thyroid V50 ≤ 24%. Conclusions The incidence of HT is significantly associated with N stage, thyroid volume, and thyroid V50. More attention should be paid to patients with NPC with thyroid volume ≤ 12.82 cm3 and advanced N stage disease.

The purpose of this study was to screen a bronchodilator from old drugs and elucidate the underlying mechanism. Paracetamol (acetaminophen) is a widely used analgesic and antipyretic drug. It has been reported that it inhibits the generation of prostaglandin and histamine, which play roles in asthma. These findings led us to explore whether paracetamol could be a potential bronchodilator. Paracetamol inhibited high K+- and acetylcholine (ACH)-induced precontraction of mouse tracheal and bronchial smooth muscles. Moreover, the ACH-induced contraction was partially inhibited by nifedipine (selective blocker of LVDCCs), YM-58483 (selective inhibitor of store-operated Ca2+ entry (SOCE), canonical transient receptor potential 3 (TRPC3) and TRPC5 channels) and Y-27632 (selective blocker of ROCK, a linker of the Ca2+ sensitization pathway). In single airway smooth muscle cells, paracetamol blocked the currents sensitive to nifedipine and YM-58483, and inhibited intracellular Ca2+ increases. In addition, paracetamol inhibited ACH-induced phosphorylation of myosin phosphatase target subunit 1 (MYPT1, another linker of the Ca2+ sensitization pathway). Finally, in vivo paracetamol inhibited ACH-induced increases of mouse respirator system resistance. Collectively, we conclude that paracetamol inhibits ASM contraction through blocking LVDCCs, SOCE and/or TRPC3 and/or TRPC5 channels, and Ca2+ sensitization. These results suggest that paracetamol might be a new bronchodilator. Keywords: Paracetamol, Airway smooth muscle, Canonical transient receptor potential channel, L-type voltage dependent Ca2+ channel, Store-operated Ca2+ channel, Ca2+ sensitization

Tumor microenvironment (TME) is the ecosystem surrounding a tumor to influence tumor cells’ growth, metastasis and immunological battlefield, in which the tumor systems fight against the body system. TME has been considered as the essential link between the tumorigenesis and development of neoplasm. Both nutrients intake and tumor progression to malignancy require the participation of components in TME. Epithelial-mesenchymal transition (EMT) is a key step in the metastasis of tumor cells. Cells that lost polarity and acquired migration ability are prone to metastasize. Autophagy is an important self-protective mechanism in tumor cells and a necessity for the tumor cells to respond to harmful stress. Protective autophagy benefits tumor cells while abnormal autophagy leads to cell injury or death. EMT and autophagy are directly regulated by TME. To date, there are numerous studies on TME, autophagy and EMT separately, but few on their complex interrelationships. This review aims to comprehensively analyze the existing mechanisms and convincing evidence so far to seek novel therapeutic strategies and research directions.

Abstract A total of 20 novel aryl piperazine derivatives were designed and synthesized, and their structures were confirmed by mass spectrometry and nuclear magnetic resonance analyses. Their 5-HT1A and sigma-1 receptor affinities were determined, and six of them showed high affinities (K i

Background and aims: Hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) is a complicated syndrome with extremely high short-term mortality. Whether plasma exchange (PE) improves HBV-ACLF outcomes remains controversial. Here, PE-based non-bioartificial liver support system (NB-ALSS) effects on short-term HBV-ACLF patient outcomes were investigated.Materials and methods: HBV-ACLF patients from Chinese Acute-on-chronic Liver Failure (CATCH-LIFE) cohort receiving standard medical therapy (SMT) alone or PE-based NB-ALSS in addition to SMT were allocated to SMT and SMT+PE groups, respectively; propensity score matching (PSM) was used to eliminate confounding bias. Short-term (28/90-day and 1-year) survival rates were calculated (Kaplan-Meier).Results: In total, 524 patients with HBV-ACLF were enrolled in this study; 358 received SMT alone (SMT group), and the remaining 166 received PE-based NB-ALSS in addition to SMT (SMT+PE group). PSM generated 166 pairs of cases. In the SMT+PE group, 28-day, 90-day, and 1-year survival rates were 11.90, 8.00, and 10.90%, respectively, higher than those in the SMT group. Subgroup analysis revealed that PE-based NB-ALSS had the best efficacy in patients with ACLF grade 2 or MELD scores of 30–40 (MELD grade 3). In MELD grade 3 patients who received SMT+PE, 28-day, 90-day, and 1-year survival rates were improved by 18.60, 14.20, and 20.10%, respectively. According to multivariate Cox regression analysis, PE-based NB-ALSS was the only independent protective factor for HBV-ACLF patient prognosis at 28 days, 90 days, and 1 year (28 days, HR = 0.516, p = 0.001; 90 days, HR = 0.663, p = 0.010; 1 year, HR = 0.610, p = 0.051). For those who received SMT+PE therapy, PE-based NB-ALSS therapy frequency was the only independent protective factor for short-term prognosis (28-day, HR = 0.597, p = 0.001; 90-day, HR = 0.772, p = 0.018).Conclusions: This multicenter prospective study showed that the addition of PE-based NB-ALSS to SMT improves short-term (28/90 days and 1-year) outcomes in patients with HBV-ACLF, especially in MELD grade 3 patients. Optimization of PE-based NB-ALSS may improve prognosis or even save lives among HBV-ACLF patients.

Phellodon is a genus of ectomycorrhizal fungi with important ecological roles and exploitable biological activities. In this study, four new species of Phellodon, P. caesius, P. henanensis, P. concentricus and P. subgriseofuscus, are described from China based on morphological characters and molecular evidence. The phylogenetic analyses of Phellodon were carried out based on the ITS + nLSU gene regions and the combined sequence dataset of ITS + nLSU + nSSU + RPB1 + RPB2 gene regions. Phellodon caesius is characterized by its dark bluish-grey, dark grey to black grey pileus, ash grey to dark bluish-grey spines, and the presence of both simple septa and clamp connections on generative hyphae of stipe. Phellodon concentricus is characterized by its zonate pileal surface, dark grey context in pileus, and spongy basidiomata. Phellodon henanensis is characterized by its ash grey, light vinaceous grey to light brown pileal surface, thin context in pileus, and the presence of both simple septa and clamp connections on generative hyphae of spines. Phellodon subgriseofuscus is characterized by its fuscous to black pileal surface, white to light brown spines, and vinaceous grey context. Illustrated descriptions and the ecological habits of the novel species are provided.

Objective: This study aims to compare the treatment outcomes of concurrent chemoradiotherapy (CCRT) versus radiotherapy (RT) alone in stage II nasopharyngeal carcinoma (NPC) patients.Methods: We retrospectively collected 601 stage II NPC patients treated in two hospitals between June 2003 to June 2016. All patients were divided into the CCRT group (n = 255) and the RT group (n = 346). Overall survival (OS), locoregional failure-free survival (LRFFS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) were assessed using the Kaplan-Meier method. The log-rank test was used to compare the differences between the groups. The Cox-regression hazards model was performed to determine potential prognostic factors.Results: The median follow-up was 99 months. No significant difference was found in locoregional recurrence, distant metastasis, disease progression, and death between the two groups (all p > 0.05). In univariate analysis, the 5-years OS, PFS, LRFFS, and DMFS had no significant differences between the CCRT and RT groups (all p > 0.05). Two-dimensional radiotherapy (2DRT) sub-analysis showed that CCRT remarkably increased DMFS, PFS, and OS rates (all p < 0.05) but not LRFFS (p = 0.258) compared with RT alone. While intensity-modulated radiotherapy (IMRT) sub-analysis showed that the prognosis of the two groups had no significant differences (all p > 0.05). In multivariate analyses, age was significantly and inversely related to OS, PFS, LRFFS, and DMFS. IMRT was an independent favorable factor for improving LRFFS, PFS, and OS. Concurrent chemotherapy was an independent protective factor for DMFS.Conclusion: In the context of 2DRT, it is definite that concurrent chemotherapy provides survival benefits for patients with stage II NPC. While in the IMRT era, the impact of chemotherapy on survival in patients with stage II NPC is weakened. Prospective randomized controlled studies are required to confirm these results.

Objectives To evaluate the cost-effectiveness of four different primary screening strategies: high-risk factor questionnaire (HRFQ) alone, single immunochemical faecal occult blood test (iFOBT), double iFOBT and HRFQ+double iFOBT for colorectal cancer (CRC) screening compared with no screening using the Markov model.Methods Treeage Pro V.2011 software was used to simulate the Markov model. The incremental cost-effectiveness ratio, which was compared with the willingness-to-pay (WTP) threshold, was used to reflect the cost-effectiveness of the CRC screening method. One-way sensitivity analysis and probabilistic sensitivity analysis were used for parameter uncertainty.Results All strategies had greater effectiveness because they had more quality-adjusted life years (QALYs) than no screening. When the WTP was ¥435 762/QALY, all screening strategies were cost-effective compared with no screening. The double iFOBT strategy was the best-buy option compared with all other strategies because it had the most QALYs and the least cost. One-way sensitivity analysis showed that the sensitivity of low-risk adenoma, compliance with colonoscopy and primary screening cost were the main influencing factors comparing single iFOBT, double iFOBT and HRFQ+double iFOBT with no screening. However, within the scope of this study, there was no fundamental impact on cost-effectiveness. Probabilistic sensitivity analysis showed that when the WTP was ¥435 762/QALY, the probabilities of the cost-effectiveness acceptability curve with HRFQ alone, single iFOBT, double iFOBT and HRFQ+double iFOBT were 0.0%, 5.3%, 69.3% and 25.4%, respectively.Conclusions All screening strategies for CRC were cost-effective compared with no screening strategy. Double iFOBT was the best-buy option compared with all other strategies. The significant influencing factors were the sensitivity of low-risk polyps, compliance with colonoscopy and cost of primary screening.

AimsThe present study aimed to investigate alterations in neuroinflammation after heart failure (HF) and explore the potential mechanisms.MethodsMale wild-type (WT) and Toll-like receptor 4 (TLR4)-knockout (KO) mice were subjected to sham operation or ligation of the left anterior descending coronary artery to induce HF. 8 weeks later, cardiac functions were analyzed by echocardiography, and intestinal barrier functions were examined by measuring tight junction protein expression, intestinal permeability and plasma metabolite levels. Alterations in neuroinflammation in the brain were examined by measuring microglial activation, inflammatory cytokine levels and the proinflammatory signaling pathway. The intestinal barrier protector intestinal alkaline phosphatase (IAP) and intestinal homeostasis inhibitor L-phenylalanine (L-Phe) were used to examine the relationship between intestinal barrier dysfunction and neuroinflammation in mice with HF.ResultsEight weeks later, WT mice with HF displayed obvious increases in intestinal permeability and plasma lipopolysaccharide (LPS) levels, which were accompanied by elevated expression of TLR4 in the brain and enhanced neuroinflammation. Treatment with the intestinal barrier protector IAP significantly attenuated neuroinflammation after HF while effectively increasing plasma LPS levels. TLR4-KO mice showed significant improvements in HF-induced neuroinflammation, which was not markedly affected by intestinal barrier inhibitors or protectors.ConclusionHF could induce intestinal barrier dysfunction and increase gut-to-blood translocation of LPS, which could further promote neuroinflammation through the TLR4 pathway.

PURPOSE: In contrast to other studies, our previous study showed that adding induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) significantly worsened the prognosis of patients with stage II nasopharyngeal carcinoma (NPC). However, the population used was small; therefore, there is an urgent need to confirm the result in a larger population because IC is still widely used in certain sections of china for stage II NPC. METHODS AND MATERIALS: We retrospectively analyzed an additional 272 patients. Therefore, in total, we report the results for 445 patients with stage II NPC treated with IC + CCRT or CCRT between June 2003 to June 2016 at the Zhejiang Cancer Hospital and Sun Yat-Sen University Cancer Center. RESULTS: This study included 445 patients treated with IC + CCRT (n = 195) or CCRT (n = 250). By last analysis, 22 (11.3%) patients in the IC + CCRT group developed local-regional recurrence and 23 (11.8%) patients developed distant metastases. Twenty-four (9.6%) patients in the CCRT group developed local-regional recurrence and 12 (4.8%) patients developed distant metastases. Univariate analyses showed that adding IC to CCRT significantly decreased the 5-year disease-free survival (DFS) (80.6% vs. 88.5%, P = .043); however, there was no statistically significant difference in 5-year overall survival (OS) (90.5% vs. 95.0%, P = .375). CONCLUSION: Using a larger population, the present study showed that adding IC to CCRT had a negative effect on patients with stage II NPC, which warrants further investigation.

Aims: The development of neuroinflammation deteriorates the prognosis of myocardial infarction (MI). We aimed to investigate the effect of renal denervation (RDN) on post-MI neuroinflammation in rats and the related mechanisms.Methods and Results: Male adult Sprague-Dawley rats were subjected to sham or ligation of the left anterior descending coronary artery to induce MI. One week later, the MI rats received a sham or RDN procedure. Their cardiac functions were analyzed by echocardiography, and their intestinal structures, permeability, and inflammatory cytokines were tested. The intestinal microbiota were characterized by 16S rDNA sequencing. The degrees of neuroinflammation in the brains of rats were analyzed for microglia activation, inflammatory cytokines, and inflammation-related signal pathways. In comparison with the Control rats, the MI rats exhibited impaired cardiac functions, intestinal injury, increased intestinal barrier permeability, and microbial dysbiosis, accompanied by increased microglia activation and pro-inflammatory cytokine levels in the brain. A RDN procedure dramatically decreased the levels of renal and intestinal sympathetic nerve activity, improved cardiac functions, and mitigated the MI-related intestinal injury and neuroinflammation in the brain of MI rats. Interestingly, the RDN procedure mitigated the MI-increased intestinal barrier permeability and pro-inflammatory cytokines and plasma LPS as well as ameliorated the gut microbial dysbiosis in MI rats. The protective effect of RDN was not significantly affected by treatment with intestinal alkaline phosphatase but significantly reduced by L-phenylalanine treatment in MI rats.Conclusions: RDN attenuated the neuroinflammation in the brain of MI rats, associated with mitigating the MI-related intestinal injury.

Knowledge of genetic variation and connectivity is of great importance to protect endangered species. The region of East Sichuan and West Hubei in China is the biodiversity center of broad-leaved trees in the world, which experienced severe forest fragmentation during the past several decades. Magnolia patungensis is an endangered horticultural tree species endemic to this area. For 16 microsatellite markers, low genetic variations (HE = 0.228–0.364) and high genetic differentiation (FST = 34.0%, G″ST = 53.4%) were found in the four extant M. patungensis populations. These were explained by the genetic bottleneck, genetic drift, inbreeding and restricted gene flow. The low level of historical gene flow (Nmhis = 0.762) among M. patungensis populations was attributed to its limited dispersal ability of pollens and seeds, and the complex terrains of habitats (high mountains, deep valleys, and dense forests). Lower contemporary gene flow (Nmcon = 0.474) suggested that the gene flow was further hindered by recent habitat fragmentations. As for conservation strategies, all remaining populations should be protected to maximize gene representation of the tree species; the artificial pollination is recommended within each population in order to increase seed setting.

PurposeTo explore risk factors for severe acute oral mucositis of nasopharyngeal carcinoma (NPC) patients receiving chemo-radiotherapy, build predictive models and determine preventive measures.Methods and MaterialsTwo hundred and seventy NPC patients receiving radical chemo-radiotherapy were included. Oral mucosa structure was contoured by oral cavity contour (OCC) and mucosa surface contour (MSC) methods. Oral mucositis during treatment was prospectively evaluated and divided into severe mucositis group (grade ≥ 3) and non-severe mucositis group (grade < 3) according to RTOG Acute Reaction Scoring System. Nineteen clinical features and nineteen dosimetric parameters were included in analysis, least absolute shrinkage and selection operator (LASSO) logistic regression model was used to construct a risk score (RS) system.ResultsTwo predictive models were built based on the two delineation methods. MSC based model is more simplified one, it includes body mass index (BMI) classification before radiation, retropharyngeal lymph node (RLN) area irradiation status and MSC V55%, RS = −1.480 + (0.021 × BMI classification before RT) + (0.126 × RLN irradiation) + (0.052 × MSC V55%). The cut-off of MSC based RS is −1.011, with an area under curve (AUC) of 0.737 (95%CI: 0.672-0.801), a specificity of 0.595 and a sensitivity of 0.786. OCC based model involved more variables, RS= −4.805+ (0.152 × BMI classification before RT) + (0.080 × RT Technique) + (0.097 × Concurrent Nimotuzumab) + (0.163 × RLN irradiation) + (0.028 × OCC V15%) + (0.120 × OCC V60%). The cut-off of OCC based RS is −0.950, with an AUC of 0.767 (95%CI: 0.702–0.831), a specificity of 0.602 and a sensitivity of 0.819. Analysis in testing set shown higher AUC of MSC based model than that of OCC based model (AUC: 0.782 vs 0.553). Analysis in entire set shown AUC in these two method-based models were close (AUC: 0.744 vs 0.717).ConclusionWe constructed two risk score predictive models for severe oral mucositis based on clinical features and dosimetric parameters of nasopharyngeal carcinoma patients receiving chemo-radiotherapy. These models might help to discriminate high risk population in clinical practice that susceptible to severe oral mucositis and individualize treatment plan to prevent it.

Background: Increasing evidence suggests a link between the gut microbiome and various diseases including hypertension and chronic kidney disease (CKD). However, studies examining the efficacy of controlling blood pressure and inhibiting the renin–angiotensin system (RAS) in preventing CKD progression are limited. Methods: In the present study, we used 5/6 nephrectomised (NX) and unilateral ureteral obstructed (UUO) rat models and cultured renal tubular epithelial cells and fibroblasts to test whether alisol B 23-acetate (ABA) can attenuate renal fibrogenesis by regulating blood pressure and inhibiting RAS. Results: ABA treatment re-established dysbiosis of the gut microbiome, lowered blood pressure, reduced serum creatinine and proteinuria, suppressed expression of RAS constituents and inhibited the epithelial-to-mesenchymal transition in NX rats. Similarly, ABA treatment inhibited expression of collagen I, fibronectin, vimentin, α-smooth muscle actin and fibroblast-specific protein 1 at both mRNA and protein levels in UUO rats. ABA was also effective in suppressing activation of the transforming growth factor-β (TGF-β)/Smad3 and preserving Smad7 expression in both NX and UUO rats. In vitro experiments demonstrated that ABA treatment inhibited the Wnt/β-catenin and mitochondrial-associated caspase pathways. Conclusion: These data suggest that ABA attenuated renal fibrosis through a mechanism associated with re-establishing dysbiosis of the gut microbiome and regulating blood pressure, and Smad7-mediated inhibition of Smad3 phosphorylation. Thus, we demonstrate ABA as a promising candidate for treatment of CKD by improving the gut microbiome and regulating blood pressure.

Abstract Dysbiosis represents changes in composition and structure of the gut microbiome community (microbiome), which may dictate the physiological phenotype (health or disease). Recent technological advances and efforts in metagenomic and metabolomic analyses have led to a dramatical growth in our understanding of microbiome, but still, the mechanisms underlying gut microbiome–host interactions in healthy or diseased state remain elusive and their elucidation is in infancy. Disruption of the normal gut microbiota may lead to intestinal dysbiosis, intestinal barrier dysfunction, and bacterial translocation. Excessive uremic toxins are produced as a result of gut microbiota alteration, including indoxyl sulphate, p-cresyl sulphate, and trimethylamine-N-oxide, all implicated in the variant processes of kidney diseases development. This review focuses on the pathogenic association between gut microbiota and kidney diseases (the gut–kidney axis), covering CKD, IgA nephropathy, nephrolithiasis, hypertension, acute kidney injury, hemodialysis and peritoneal dialysis in clinic. Targeted interventions including probiotic, prebiotic and symbiotic measures are discussed for their potential of re-establishing symbiosis, and more effective strategies for the treatment of kidney diseases patients are suggested. The novel insights into the dysbiosis of the gut microbiota in kidney diseases are helpful to develop novel therapeutic strategies for preventing or attenuating kidney diseases and complications.

In this study, phylogenetic analyses of Phellodon from China were carried out based on sequences from the internal transcribed spacer (ITS) regions, the large subunit of nuclear ribosomal RNA gene (nLSU), the small subunit of nuclear ribosomal RNA gene (nSSU), the largest subunit of RNA polymerase II (RPB1), and the second largest subunit of RNA polymerase II (RPB2), combined with morphological characters of the collected specimens in China. The fruiting bodies of the specimens were used to observe their characteristics, and three new species of Phellodon are discovered. Phellodon crassipileatus is characterized by its pale brown to dark brown pileal surface, tomentose pileal margin, white spines, and the presence of clamp connections in generative hyphae of pileal surface, context, and stipe. Phellodon griseofuscus is characterized by its dark brown to black pileal surface, white to pale brown pileal margin, the presence of both simple septa and clamp connections in generative hyphae of spines, and moderately long basidia. Phellodon perchocolatus is characterized by its woody and broad pileus, brown to greyish brown pileal surface when fresh, tomentose pileal margin when young, which becomes glabrous with age, and the presence of both simple septa and clamp connections in the generative hyphae of the spines. This is the first time both single and multi-genes analysis is used in such a phylogenetic and taxonomic study on Phellodon, which can provide the basis for the phylogenetic study of the genus.

Background/Aims: Tetraethylammonium chloride (TEA) induces oscillatory contractions in mouse airway smooth muscle (ASM); however, the generation and maintenance of oscillatory contractions and their role in ASM are unclear. Methods: In this study, oscillations of ASM contraction and intracellular Ca2+ were measured using force measuring and Ca2+ imaging technique, respectively. TEA, nifedipine, niflumic acid, acetylcholine chloride, lithium chloride, KB-R7943, ouabain, 2-Aminoethoxydiphenyl borate, thapsigargin, tetrodotoxin, and ryanodine were used to assess the mechanism of oscillatory contractions. Results: TEA induced depolarization, resulting in activation of L-type voltage-dependent Ca2+ channels (LVDCCs) and voltage-dependent Na+ (VNa) channels. The former mediated Ca2+ influx to trigger a contraction and the latter mediated Na+ entry to enhance the contraction via activating LVDCCs. Meanwhile, increased Ca2+-activated Cl- channels, inducing depolarization that resulted in contraction through LVDCCs. In addition, the contraction was enhanced by intracellular Ca2+ release from Ca2+ stores mediated by inositol (1,4,5)-trisphosphate receptors (IP3Rs). These pathways together produce the contractile phase of the oscillatory contractions. Furthermore, the increased Ca2+ activated the Na+-Ca2+ exchanger (NCX), which transferred Ca2+ out of and Na+ into the cells. The former induced relaxation and the latter activated Na+/K+-ATPase that induced hypopolarization to inactivate LVDCCs causing further relaxation. This can also explain the relaxant phase of the oscillatory contractions. Moreover, the depolarization induced by VNa channels and NCX might be greater than the hypopolarization caused by Na+/K+-ATPase alone, inducing LVDCC activation and resulting in further contraction. Conclusions: These data indicate that the TEA-induced oscillatory contractions were cooperatively produced by LVDCCs, VNa channels, Ca2+-activated Cl- channels, NCX, Na+/K+ ATPase, IP3Rs-mediated Ca2+ release, and extracellular Ca2+.

Objective To estimate the accuracy and stability of capillary electrophoresis fragment analysis and clone sequencing in detecting dynamic mutations of spinocerebellar ataxia (SCA). Methods Capillary electrophoresis fragment analysis and clone sequencing were used in detecting trinucleotide repeated sequence of 14 SCA patients (3 cases of SCA2, 2 cases of SCA7, 7 cases of SCA8 and 2 cases of SCA17). Results Capillary electrophoresis fragment analysis of 3 SCA2 cases showed the expanded cytosine-adenine-guanine (CAG) repeats were 31, 30 and 32, and the copy numbers of 3 clone sequencing for 3 colonies in each case were 37/40/40, 37/38/39 and 38/39/40 respectively. Capillary electrophoresis fragment analysis of 2 SCA7 cases showed the expanded CAG repeats were 57 and 34, and the copy numbers of repeats were 69, 74, 75 in 3 colonies of one case, and was 45 in the other case. For the 7 SCA8 cases with the expanded cytosine-thymine-adenine (CTA)/cytosine-thymine-guanine (CTG) repeats of 99, 111, 104, 92, 89, 104 and 75, the results of clone sequencing were 97, 116, 104, 90, 90, 102 and 76 respectively. For 2 SCA17 cases with the short/expanded CAG repeats of 37/50 and 36/45, the results of clone sequencing were 51/50/52 and 45/44 for 3 and 2 colonies. Conclusions Although the higher mobility of polymerase chain reaction (PCR) products containing dynamic mutation in the capillary electrophoresis fragment analysis might cause the deviation for analysis of copy numbers, the deviation was predictable and the results were repeatable. The clone sequencing results showed obvious instability, especially for SCA2 and SCA7 genes, which might owing to their simple CAG repeats. Consequently, clone sequencing is not suited for detection of dynamic mutation, not to mention the quantitative criteria of dynamic mutation sequencing. DOI: 10.3969/j.issn.1672-6731.2018.03.008

AIM: To observe the clinical efficacy of limbal-conjunctival autograft transplant(LCAT)for double-head pterygium.METHODS: Prospective case study. Totally 46 patients(54 eyes)diagnosed with double-head pterygium collected in PLA 474 Hospital from January 2014 to July 2015, including 8 patients(16 eyes)with binocular double-head pterygium, 11 patients(11 eyes)with monocular double-head pterygium and the other eye with nasal side pterygium, pterygiun eyes only included as study subject, and 27 patients(27 eyes)with monocular double-head pterygium. The eyes with double-head pterygium underwent pterygium resection and autologous corneal limbal stem cell transplantation, nasal conjunctival flap was gotten from the superior bulbar conjunctiva of affected eye, and temporal conjunctival flap was gotten from the inferior bulbar conjunctiva of other eye. Follow-up the patients on 1d, 7d, 1mo and 1a after operation to complete the vision and slit lamps to observe the complications and pterygium recurrence.RESULTS: Forty-four patients(52 eyes)completed the follow-up of 1a, while 2 patients(2 eyes)were lost. Three patients(3 eyes)developed recurrence, and the recurrence rate was 6%. Two eyes with nasal side pterygium developed recurrence and 1 eye with temporal side pterygium developed recurrence, while there was no complication observed.CONCLUSION: Nasal conjunctival flap was gotten from the superior bulbar conjunctiva of affected eye, and temporal conjunctival flap was gotten from the inferior bulbar conjunctiva of other eye for double-head pterygium had good clinical effect and low recurrence rate, which provide a better way to treat double-head pterygium.

Abstract To evaluate acoustic radiation force impulse (ARFI) inthe differential diagnosis of small (≤20 mm) solid breast lesions and identify the most efficient ARFI parameters. Conventional ultrasonography and ARFIwere performed in 120 patients with 121 small solid breast lesions. The area ratios (ARs) of the lesion on virtual touch tissue compared to B-mode were calculated. The shear wave velocity of the inner (SWVi) and boundary (SWVb) of the lesions and surrounding fatty tissue (SWVf) was measured. The ratio of SWVi to SWVf (SWVrat) was calculated. AR, SWVi, SWVb, and SWVrat were significantly larger in malignant lesions (all P

Objective To investigate the clinical features and dynamic mutation of 10 cases with juvenile-onset Huntington's disease (HD). Methods The cytosine-adenine-guanine (CAG) repeats of IT15 gene were detected by polymerase chain reaction (PCR) and capillary electrophoresis in 272 individuals of 159 pedigrees with preliminary diagnosis of HD. The correlation between clinical features and expanded CAG repeats in the IT15 gene of 10 cases with juvenile-onset HD were studied carefully. Results Among 211 individuals carried expanded CAG repeats, 10 cases onset before 20 years of age. The predominant clinical manifestations were involuntary movement and cognitive impairment. The average age of onset was (12.50 ± 4.55) years, and the average CAG repeat number of IT15 gene was 63.70 ± 14.83. Pearson correlation analysis showed that the age of onset was significantly and negatively correlated with the CAG repeat number (r = - 0.865, P = 0.001). Conclusions 1) The juvenile?onset case of HD presented with different clinical features compared with adult - onset cases. The most common presentation is cognitive decline. 2) Analysis of CAG repeats of IT15 gene is necessary for the diagnosis of juvenile-onset case of HD with no family history. 3) The variability in age of onset is not completely explained by the effects of expanded CAG repeats of IT15 gene, which is more prominently for the juvenile?onset cases, therefore, it is suggested that other factors may modulate the age of onset. DOI: 10.3969/j.issn.1672-6731.2017.08.008

Objective To make the diagnosis for a patient presented with head tremor and cerebellar atrophy by integrating clinical features and accessory examination with genetic testing and to explore the interpretation of genetic testing results. Methods A 30-year-old male patient's medical information, clinical pheontype, family history and accessory examinations were collected. The next?generation sequencing (NGS) of exons in 3994 causative genes of Mendelian inheritance diseases and the family tree verification were carried out. China Human Phenotype Ontology (CHPO), Phenomizer, Ensembl and Online Mendelian Inheritance in Man (OMIM) database were used to interpret the genetic test results. Results The patient carried heterozygous mutation of spinocerebellar ataxia type 19 (SCA19) related KCND3 gene c.1057A > G (p. Ser353Gly), but his parents did not carry this mutation. The patient also carried heterozygous mutation of parkinsonism type 20 (PARK20) related SYNJ1 gene c.4436C > T (p.Thr1479Ile) which was also seen in his mother. Phenotypic similarity analysis showed the patient's phenotype was correspond with the phenotype of SCA19, and the variation locus of KCND3 gene c.1057A > G was highly conservative with homologous gene in different species. Conclusions By means of the integration of clinical phenotype with the result of genetic test, KCND3 gene c.1057A > G (p.Ser353Gly) carried in the patient is the pathogenic mutation. DOI: 10.3969/j.issn.1672-6731.2017.07.007

The complete mitochondrial genome of Argas persicus isolate China is reported for the first time in this study. Its entire mitogenome is 14, 426 bp in length, contained 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and 1D-loop regions. The phylogenetic analysis by maximum likelihood method show that A. persicus isolate China and the others of genus Argas are in the same clade. This is the first complete mitochondrial genome of soft tick in China.

AIM: To investigate the clinical efficacy of multimedia training system in the treatment of ametropic amblyopic in children of different ages. METHODS: One hundred and twenty children(161 eyes)with ametropic amblyopia were selected from March 2015 to March 2016 in our hospital. According to their age, they were divided into three groups: 40 cases(54 eyes)with 4-6 years of age as pre-school group and 40 cases(52 eyes)with 7-9 years of age as school age group A, and 55 eyes(40 cases)with 10-12 years of age as school age group B. All of them were treated with multimedia training system. The clinical efficacy and compliance were analyzed. RESULTS: After one course of treatment, the total effective rate of preschool group, school age group A, and school age group B was 96.3%, 82.7%, and 78.2%, respectively, and the difference was statistically significant(χ2=7.875, Pχ2=7.875, P=0.017). Pearson column number r=0.216. The treatment adherence rates of preschool group, school age group A, and school age group B were 85.0%, 87.5%, and 90.0%, respectively, and the difference was not statistically significant(χ2=1.142, P>0.05). CONCLUSION: Multimedia training system can improve the compliance of children with ametropic amblyopia. The efficacy is more remarkable in children of 4-6 year old.

Fasciola hepatica is a widespread pathogen that is known for its harmful effects on the health and productivity of ruminant animals. To identify the proteins present in all periods of infection with F. hepatica but not in those with Fasciola gigantica by shotgun liquid chromatography–tandem mass spectrometry (LC–MS/MS), we collected the ESPs and sera of F. hepatica and F. gigantica. In this study, the sheep were artificially infected with F. hepatica and the sera were collected at five different periods: 3 days post-infection (dpi), 7 dpi, 21 dpi, 63 dpi, and 112 dpi. The interacting proteins were pulled down from the sheep sera of all five periods and the sera with F. gigantica by co-immunoprecipitation (Co-IP) assay, before being identified by LC–MS/MS analysis. Thirty, twenty-two, twenty-three, twenty-seven, and twenty-two proteins were pulled down by the infected sera at 3 dpi, 7 dpi, 21 dpi, 63 dpi, and 112 dpi, respectively. Among them, 12 proteins existed in all periods, while six proteins could be detected in all periods in F. hepatica but not in F. gigantica. Protein relative pathway analysis revealed that these proteins mainly refer to the metabolism, regulation of genetic activity, and signal transduction of F. hepatica. In conclusion, this study provides meaningful data for the diagnosis of fasciolosis and to understand the interactions between F. hepatica and the host.

β2-adrenoceptor agonists are commonly used as bronchodilators to treat obstructive lung diseases such as asthma and chronic obstructive pulmonary disease (COPD), however, they induce severe side effects. Therefore, developing new bronchodilators is essential. Herbal plants were extracted and the extracts’ effect on airway smooth muscle (ASM) precontraction was assessed. The ethyl alcohol extract of semen cassiae (EESC) was extracted from Semen cassia. The effects of EESC on the ACh- and 80 mM K+-induced sustained precontraction in mouse and human ASM were evaluated. Ca2+ permeant ion channel currents and intracellular Ca2+ concentration were measured. HPLC analysis was employed to determine which compound was responsible for the EESC-induced relaxation. The EESC reversibly inhibited the ACh- and 80 mM K+-induced precontraction. The sustained precontraction depends on Ca2+ influx, and it was mediated by voltage-dependent L-type Ca2+ channels (LVDCCs), store-operated channels (SOCs), TRPC3/STIM/Orai channels. These channels were inhibited by aurantio-obtusin, one component of EESC. When aurantio-obtusin removed, EESC’s action disappeared. In addition, aurantio-obtusin inhibited the precontraction of mouse and human ASM and intracellular Ca2+ increases. These results indicate that Semen cassia-contained aurantio-obtusin inhibits sustained precontraction of ASM via inhibiting Ca2+-permeant ion channels, thereby, which could be used to develop new bronchodilators.

Cyclohexylamine (CHAM) is widely used in various industries, but it is harmful to human beings and the environment. Acinetobacter sp. YT-02 can degrade CHAM via cyclohexanone as an intermediate. In this study, the cyclohexylamine oxidase (CHAO) gene from Acinetobacter sp. YT-02 was cloned. Amino acid sequence alignment indicated that the cyclohexylamine oxidase (CHAOYT–02) was 48% identical to its homolog from Brevibacterium oxydans IH-35A (CHAOIH–35). The enzyme was expressed in Escherichia coli BL21 (DE3), and purified to apparent homogeneity by Ni-affinity chromatography. The purified enzyme was proposed to be a dimer of molecular mass of approximately 91 kDa. The enzyme exhibited its maximum activity at 50°C and at pH 7.0. The enzyme was thermolabile as demonstrated by loss of important percentage of its maximal activity after 30 min incubation at 50°C. Metal ions Mg2+, Co2+, and K+ had certain inhibitory effect on the enzyme activity. The kinetic parameters Km and Vmax were 0.25 ± 0.02 mM and 4.3 ± 0.083 μM min−1, respectively. The biochemical properties, substrate specificities, and three-dimensional structures of CHAOYT–02 and CHAOIH–35 were compared. Our results are helpful to elucidate the mechanism of microbial degradation of CHAM in the strain YT-02. In addition, CHAOYT–02, as a potential biocatalyst, is promising in controlling CHAM pollution and deracemization of chiral amines.