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Local anesthetics are used clinically for the control of postoperative pain management. This study aimed to develop chitosan (CS) with genipin (GP) hydrogels as the hydrophilic lipid shell loaded poly(ε-caprolactone) (PC) nanocapsules as the hydrophobic polymeric core composites (CS-GP/PC) to deliver bupivacaine (BPV) for the prolongation of anesthesia and pain relief. The swelling ratio, in vitro degradation, and rheological properties enhancement of CS-GP/PC polymeric hydrogel. The incorporation of PC nanocapsules into CS-GP hydrogels was confirmed by SEM, FTIR, and XRD analysis. Scanning electron microscopy results demonstrated that the CS-GP hydrogels and CS-GP/PC polymeric hydrogels have a porous structure, the pore dimensions being non-uniform with diameters between 25 and 300 μm. The in vitro drug release profile of CS-GP/PC polymeric hydrogel has been achieved 99.2 ± 1.12% of BPV drug release in 36 h. Cellular viability was evaluated using the CCK-8 test on 3T3 fibroblast cells revealed that the obtained CS-GP/PC polymeric hydrogel with BPV exhibited no obvious cytotoxicity. The CS-GP/PC polymeric hydrogel loaded with BPV showed significant improvement in pain response compared to the control group animals for at least 7 days. When compared with BPV solution, CS-GP hydrogel and CS-GP/PC polymeric hydrogel improved the skin permeation of BPV 3-fold and 5-fold in 24 h, respectively. In vitro and in vivo results pointed out PC nanocapsules loaded CS-GP hydrogel can act as effective drug carriers, thus prolonging and enhancing the anesthetic effect of BPV. Histopathological results demonstrated the excellent biodegradability and biocompatibility of the BPV-loaded CS-GP/PC polymeric hydrogel system on 7, 14, and 21 days without neurotoxicity.HIGHLIGHTSPreparation and characterization of CS-GP/PC polymeric hydrogel system.BPV-loaded CS-GP/PC exhibited prolonged in vitro release in PBS solution.Cytotoxicity of BPV-loaded CS-GP/PC polymeric hydrogel against fibroblast (3T3) cells.Development of CS-GP/PC a promising skin drug-delivery system for local anesthetic BPV.

Since a portion of patients with nasopharyngeal carcinoma (NPC) do not benefit much from current standard treatments, it is still needed to discover new therapeutic drugs to improve the prognosis of the patients. Considering that Chinese traditional medicine plays a role in inhibiting tumor progression, in this study, we aimed to investigate whether a Chinese herbal formula, Qing Yan Li Ge Tang (QYLGT), has the anticancer activity in NPC cells and explore the underlying mechanism as well. MTT assay, colony formation assay, immunoblotting assay, and DNA laddering assay were performed to assess cell viability, cell colony formation, protein expression, and DNA fragmentation, respectively. Results show that QYLGT was able to inhibit the cell viability and decrease colony formation ability in NPC cells. QYLGT could also increase the formation of intracellular vacuoles and induce the autophagy-related protein expressions, including Atg3, Atg6, and Atg12-Atg5 conjugate in NPC cells. Treatment with an autophagy inhibitor, 3-methyladenine, could significantly recover QYLGT-inhibited cell viability of NPC cells. In addition, QYLGT did not significantly induce apoptosis in NPC cells. We also found that QYLGT had the ability to activate phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of the rapamycin (mTOR) pathway. Treatment with PI3K inhibitors, LY294002 and wortmannin, or mTOR inhibitors, rapamycin and Torin 1, could not only recover QYLGT-inhibited cell viability of NPC cells but also inhibit Atg3 expression. Taken together, our results demonstrated that QYLGT could induce autophagic cell death in NPC cells through the PI3K/Akt/mTOR pathway.

Rectal cancer is a life‑threatening disease worldwide. Chemotherapy resistance is common in rectal adenocarcinoma patients and has unfavorable survival outcomes; however, its related molecular mechanisms remain unknown. To identify genes related to the initiation and progression of rectal adenocarcinoma, three datasets were obtained from the Gene Expression Omnibus database. In total, differentially expressed genes were analyzed from 294 tumor and 277 para-carcinoma samples from patients with rectal cancer. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functions were investigated. Cytoscape software and MicroRNA Enrichment Turned Network were applied to construct a protein-protein interaction network of the dependent hub genes and related microRNAs. The Oncomine database was used to identify hub genes. Additionally, Gene Expression Profiling Interactive Analysis was applied to determine the RNA expression level. Tumor immune infiltration was assessed using the Tumor Immune Estimation Resource database. The expression profiles of hub genes between stages, and their prognostic value, were also evaluated. During this study, data from The Cancer Genome Atlas were utilized. In rectal adenocarcinoma, four hub genes including CXCL1, CXCL2, CXCL3, and GNG4 were highly expressed at the gene and RNA levels. The expression of CXCL1, CXCL2, and CXCL3 was regulated by has-miR-1-3p and had a strong positive correlation with macrophage and neutrophil. CXCL2 and CXCL3 were differentially expressed at different tumor stages. High expression levels of CXCL1 and CXCL3 predicted poor survival. In conclusion, the CXCL1 and CXCL3 genes may have potential for prognosis and molecular targeted therapy of rectal adenocarcinoma., Graphical abstract

Background No clinical trials have been specifically designed to compare medical treatments after surgery in Parkinson's disease (PD). Objective Study's objective was to compare the efficacy and safety of levodopa versus dopamine agonist monotherapy after deep brain stimulation (DBS) in PD. Methods Thirty-five surgical candidates were randomly assigned to receive postoperative monotherapy with either levodopa or dopamine agonist in a randomized, single-blind study. All patients were reevaluated in short- (3 months), mid- (6 months), and long-term (2.5 years) follow-up after surgery. The primary outcome measure was the change in the Non-Motor Symptoms Scale (NMSS) 3 months after surgery. Secondary outcome measures were the percentage of patients maintaining monotherapy, change in motor symptoms, and specific non-motor symptoms (NMS). Analysis was performed primarily in the intention-to-treat population. Results Randomization did not significantly affect the primary outcome (difference in NMSS between treatment groups was 4.88 [95% confidence interval: -11.78-21.53, P = 0.566]). In short- and mid-term follow-up, monotherapy was safe and feasible in more than half of patients (60% in short- and 51.5% in mid-term follow-up), but it was more often possible for patients on levodopa. The ability to maintain dopamine agonist monotherapy was related to optimal contact location. In the long term, levodopa monotherapy was feasible only in a minority of patients (34.2%), whereas dopamine agonist monotherapy was not tolerated due to worsening of motor conditions or occurrence of impulse control disorders. Conclusions This trial provides evidence for simplifying pharmacological treatment after functional neurosurgery for PD. The reduction in dopamine receptor agonists should be attempted while monitoring for occurrence of NMSs, such as apathy and sleep disturbances. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Molecular analysis of the genus Balsamia was conducted with ITS and 28S sequences available, including newly gained sequences from Chinese specimens. Combined with the morphological examinations, a new hypogeous species, Balsamia lishanensis was described and illustrated from North China, which is morphologically characterized by reddish brown ascomata covered with fine warts, the whitish gleba with numerous small chambers, 3–5 layers peridium with reddish brown polygonal cells and the smooth and regular ellipsoid ascospores with one large oil drop. Two species previously described as Barssia were transferred to Balsamia. Balsamia platyspora was confirmed to be in existence in China based on newly collected specimen. A key to the Chinese Balsamia species was provided.

Background Sporobolomyces pararoseus is regarded as an oleaginous red yeast, which synthesizes numerous valuable compounds with wide industrial usages. This species hold biotechnological interests in biodiesel, food and cosmetics industries. Moreover, the ballistospores-shooting promotes the colonizing of S. pararoseus in most terrestrial and marine ecosystems. However, very little is known about the basic genomic features of S. pararoseus. To assess the biotechnological potential and ballistospores-shooting mechanism of S. pararoseus on genome-scale, the whole genome sequencing was performed by next-generation sequencing technology. Results Here, we used Illumina Hiseq platform to firstly assemble S. pararoseus genome into 20.9 Mb containing 54 scaffolds and 5963 predicted genes with a N50 length of 2,038,020 bp and GC content of 47.59%. Genome completeness (BUSCO alignment: 95.4%) and RNA-seq analysis (expressed genes: 98.68%) indicated the high-quality features of the current genome. Through the annotation information of the genome, we screened many key genes involved in carotenoids, lipids, carbohydrate metabolism and signal transduction pathways. A phylogenetic assessment suggested that the evolutionary trajectory of the order Sporidiobolales species was evolved from genus Sporobolomyces to Rhodotorula through the mediator Rhodosporidiobolus. Compared to the lacking ballistospores Rhodotorula toruloides and Saccharomyces cerevisiae, we found genes enriched for spore germination and sugar metabolism. These genes might be responsible for the ballistospores-shooting in S. pararoseus NGR. Conclusion These results greatly advance our understanding of S. pararoseus NGR in biotechnological potential and ballistospores-shooting, which help further research of genetic manipulation, metabolic engineering as well as its evolutionary direction.

Background Tuberculosis poses a severe threat to human health. At present, compared with the traditional diagnostic methods for tuberculosis pleural effusion, such as Löwenstein–Jensen culture, pleural biopsy, and Ziehl–Neelsen smear microscopy, Xpert MTB/RIF was regarded as an emerging technology for its efficiency. The Xpert MTB/RIF accuracy for tuberculous pleural effusion diagnosis was evaluated in this systematic study. Materials and methods We searched the relevant literature published before January 2021 in PubMed, Cochrane, EMBASE, and Web of Science databases. Utilizing Review Manager 5.3 software, the quality of the included literature was evaluated based on the Quality Assessment of Diagnostic Accuracy Studies criteria. Sensitivity, specificity, and the summary receiver operating characteristic curves were plotted and analyzed with Metadisc 1.40 software. We used Stata 12.0 software to evaluate the publication bias of this study. Results Eighteen articles were identified in total. The sensitivity of Xpert MTB/RIF in the pleural effusion was 0.24, and specificity was 1.00, respectively. The area under the summary receiver operating characteristic curve was 0.9737, which indicated that the overall accuracy of the Xpert MTB/RIF was high. In addition, based on the Deeks funnel plot, no publication bias of the study was found. Conclusion Xpert MTB/RIF is a rapid method with high specificity but relatively low sensitivity for detecting Mycobacterium tuberculosis in pleural effusion. Its less sensitivity made it difficult to be used clinically, but the high specificity suggests that it can be used as a specific diagnostic method for tuberculous pleural effusion., SROC curve was plotted, and the following parameters were obtained: AUC of 0.9737 and Q of 0.9260 (SE = 0.0512). The SROC turn was near the top left corner, and the AUC was close to 1, which suggested that Xpert MTB/RIF had a comparatively overall high diagnostic accuracy for pleural effusion.

Background The clinical outcome of Philadelphia chromosome-negative B cell acute lymphoblastic leukemia (Ph-neg B-ALL) varies considerably from one person to another after clinical treatment due to lack of targeted therapies and leukemia’s heterogeneity. Ferroptosis is a recently discovered programmed cell death strongly correlated with cancers. Nevertheless, few related studies have reported its significance in acute lymphoblastic leukemia. Methods Herein, we collected clinical data of 80 Ph-neg B-ALL patients diagnosed in our center and performed RNA-seq with their initial bone marrow fluid samples. Throughout unsupervised machine learning K-means clustering with 24 ferroptosis related genes (FRGs), the clustered patients were parted into three variant risk groups and were performed with bioinformatics analysis. Results As a result, we discovered significant heterogeneity of both immune microenvironment and genomic variance. Furthermore, the immune check point inhibitors response and potential implementation of Sorafenib in Ph-neg B-ALL was also analyzed in our cohort. Lastly, one prognostic model based on 8 FRGs was developed to evaluate the risk of Ph-neg B-ALL patients. Conclusion Jointly, our study proved the crucial role of ferroptosis in Ph-neg B-ALL and Sorafenib is likely to improve the survival of high-risk Ph-neg B-ALL patients.

Tuberculosis (TB), a contagious disease mainly caused by Mycobacterium tuberculosis (M. tb), Mycobacterium bovis (M. bovis), and Mycobacterium caprae (M. caprae), poses a major global threat to the health of humans and many species of animals. Developing an ante-mortem detection technique for different species would be of significance in improving the surveillance employing a One Health strategy. To achieve this goal, a universal indirect ELISA was established for serologically detecting Mycobacterium tuberculosis complex infection for multiple live hosts by using a fusion protein of MPB70, MPB83, ESAT6, and CFP10 common in M. tb, M. bovis, and M. caprae as the coating antigen (MMEC) and HRP-labeled fusion protein A and G as a secondary antibody. After testing the known positive and negative sera, the receiver operating characteristic curves were constructed to decide the cut-off values. Then, the diagnostic sensitivity and specificity of MMEC/AG-iELISA were determined as 100.00% (95% CI: 96.90%, 100.00%) and 100.00% (95% CI: 98.44%, 100.00%) for M. bovis infection of cattle, 100.00% (95% CI: 95.00%, 100.00%) and 100.0% (95% CI: 96.80%, 100.00%) for M. bovis infection of sheep, 90.74% (95% CI: 80.09%, 95.98%) and 98.63% (95% CI: 95.14%, 99.76%) for M. bovis infection of cervids, 100.00% (95% CI: 15.81%, 100.00%) and 98.81% (95% CI: 93.54%, 99.97%) for M. bovis infection of monkeys, 100.00% (95% CI: 86.82%, 100.00%) and 94.85% (95% CI: 91.22%, 97.03%) for M. tb infection of humans. Furthermore, this MMEC/AG-iELISA likely detects M. caprae infection in roe deer. Thus this method has a promising application in serological TB surveillance for multiple animal species thereby providing evidence for taking further action in TB control.

Background Cervical cancer continues to be one of the leading causes of cancer deaths among females in low and middle-income countries. In this study, we aimed to assess the independent prognostic value of clinical and potential prognostic factors in progression-free survival (PFS) in cervical cancer. Methods We conducted a retrospective study on 92 cervical cancer patients treated from 2017 to 2019 at the Zhuhai Hospital of Traditional Chinese and Western Medicine. Tumor characteristics, treatment options, progression-free survival and follow-up information were collected. Kaplan–Meier method was used to assess the PFS. Results Results showed that the number of retrieved lymph nodes had a statistically significant effect on PFS of cervical cancer patients (P = 0.002). Kaplan-Meier survival curve analysis showed that cervical cancer patients with initial symptoms age 25–39 had worse survival prognoses (P = 0.020). And the using of uterine manipulator in laparoscopic treatment showed a better prognosis (P P Conclusion Number of retrieved lymph nodes, initial symptoms age, uterine manipulator, and retrieved lymph nodes count combining with FIGO staging system could be potential prognostic factors for cervical cancer patients.

Background Intravenous immunoglobulin (IVIG) resistance prediction is one of the primary clinical issues and study hotspots in KD. This study aimed to prospectively investigate the value of albumin-bilirubin grade (ALBI) in predicting IVIG resistance in KD and to assess whether ALBI has more predictive value or accuracy than either ALB or TBil alone in predicting IVIG resistance. Methods A total of 823 patients with KD were prospectively enrolled. The clinical and laboratory data were compared between the IVIG-response group (n = 708) and the IVIG-resistance group (n = 115). Multivariate logistic regression analysis was performed to identify the independent risk factors for IVIG resistance. Receiver operating characteristic (ROC) curves analysis was applied to assess the validity of ALBI, ALB, and TBil in predicting IVIG resistance. Results ALBI was significantly higher in patients with IVIG resistance and was identified as an independent risk factor for IVIG resistance in KD. The parameter of ALBI ≥ − 2.57 (AUC: 0.705, 95 %CI: 0.672–0.736), ALB ≤ 33.0 g/L (AUC: 0.659, 95 %CI: 0.626–0.692), and TBil ≥ 16.0µmol/L (AUC: 0.626, 95 %CI: 0.592–0.659), produced a sensitivity, specificity, PPV, and NPV of 0.617, 0.657, 0.226 and 0.914; 0.374, 0.850, 0.289 and 0.893; 0.269, 0.941, 0.425 and 0.888, respectively. Conclusions A higher ALBI was an independent risk factor for IVIG resistance in KD. It yielded better predictive ability than ALB and TBil alone for initial IVIG resistance.

Photoprotection is an important strategy adopted by plants to avoid photoinhibition under stress conditions. However, the way in which photoprotection is regulated is not fully understood. Here, we demonstrate that tomato (Solanum lycopersicum) mutants of brassinosteroid (BR) biosynthesis (dwf) and related signaling through BRASSINAZOLE-RESISTANT1 (bzr1) are more sensitive to (PSII and PSI photoinhibition, with decreased cyclic electron flow around PSI and lower nonphotochemical quenching, accumulation of PSII subunit S (PsbS), violaxanthin deepoxidase (VDE) activity, and D1 protein abundance. Chilling induced the accumulation of active BRs and activated BZR1, which directly activates the transcription of RESPIRATORY BURST OXIDASE HOMOLOG1 (RBOH1) and hydrogen peroxide production in the apoplast. While apoplastic hydrogen peroxide is essential for the induction of PROTON GRADIENT REGULATION5 (PGR5)-dependent cyclic electron flow, PGR5 participates in the regulation of chilling- and BR-dependent induction of nonphotochemical quenching, accumulation of D1, VDE, and PsbS proteins, transcription of genes involved in redox signaling, hormone signaling, and activity of several antioxidant enzymes. Mutations in BZR1 and PGR5 or suppressed transcription of RBOH1 compromised chilling- and BR-induced photoprotection, resulting in increased sensitivity to photoinhibition. These results demonstrate that BRs act as a positive regulator of photoprotection in a redox-PGR5-dependent manner in response to chilling stress in tomato.

Context:Garcinia mangostana Linn. (Guttiferae) pericarp is used as a traditional medicine in South Asia to treat inflammatory diseases. Objective: This study investigates therapeutic effects of G. mangostana pericarp ethanol extract (MAN) on collagen-induced arthritis (CIA) and interactions with methotrexate in vivo. Materials and methods: Male Sprague-Dawley rats with CIA were treated with MAN (0.5 g/kg/day), methotrexate (0.5 mg/kg, bw) or combination of both for 36 days, respectively (n = 8/group). Another eight healthy and CIA rats served as normal and model control, respectively. Therapeutic effects were evaluated based on paw edema and arthritis score during the experiment and serological markers at the end of the study period. Histological and radiological examinations were used to assess joint destructions. The immune status was investigated by immunohistochemistry and flow cytometry. Results: All treatments decreased the arthritis score and paw inflammation in CIA rats. Combination regimen significantly reduced anti-cyclic citrullinated peptide antibody in CIA rats to 85.83% (p

Background Electrocardiographic left ventricular hypertrophy (ECG-LVH) is a common manifestation of preclinical cardiovascular disease. The present study aimed to investigate risk factors for ECG-LVH and its prevalence in a cohort of young Chinese individuals. Methods (1) A total of 1515 participants aged 36–45 years old from our previously established cohort who were followed up in 2017 were included. Cross-sectional analysis was used to examine risk factors for ECG-LVH and its prevalence. (2) A total of 235 participants were recruited from the same cohort in 2013 and were followed up in 2017. Longitudinal analysis was used to determine the predictors of LVH occurrence over the 4-year period. We used multivariable logistic regression models to calculate OR and 95% CIs and to analyze risk factors for ECG-LVH. Results In the cross-sectional analysis, the prevalence of LVH diagnosed by the Cornell voltage-duration product in the overall population and the hypertensive population was 4.6% and 8.8%, respectively. The logistic regression results shown that female sex [2.611 (1.591–4.583)], hypertension [2.638 (1.449–4.803)], systolic blood pressure (SBP) [1.021 (1.007–1.035)], serum uric acid (SUA) [1.004 (1.001–1.006)] and carotid intima-media thickness (CIMT) [67.670 (13.352–342.976)] were significantly associated with the risk of LVH (all P Conclusions Our study suggested that female sex, hypertension, SBP, SUA and CIMT were significantly associated with the risk of LVH in young people. In addition, fasting glucose, SBP and female sex are independent predictors of the occurrence of LVH in a young Chinese general population.

During the spring semester of 2020, medical school anatomists in China were forced by the COVID-19 pandemic to transition from face-to-face educators or part-time online educators to full-time online educators. This nationwide survey was conducted to assess online anatomy education during the pandemic for medical students from nonclinical medicine and clinical medicine majors at medical schools in China via WeChat. The total of 356 responders included 293 responders from clinical medicine and 63 respondents from nonclinical medicine majors (i.e., 21 from preventive medicine, 13 from stomatology, and 29 from traditional Chinese medicine). The survey results showed that several aspects of online anatomy education were quite similar in clinical and nonclinical majors’ classes, including theoretical and practical sessions, active learning, assessments and evaluations. However, there were statistically significant differences in class size, implementation of active learning activities prior to the pandemic, and the evaluation of the effectiveness of online learning during the pandemic, between clinical and nonclinical medicine majors. These results indicated that, compared with teachers of anatomy courses in clinical medicine, teachers of nonclinical medicine majors using online learning in medical schools in China had relatively poor preparation for online learning in response to the unforeseen pandemic.

Patients with non-small-cell lung cancer (NSCLC) frequently develop radioresistance, resulting in poor response to radiation and unfavourable prognosis. Early detection of radioresistance hence can guide the adjustment of treatment regimens in time. Exosomes are lipid bilayer-enclosed vesicles with sub-micrometer size that are released by various cells. Exosomes contain a tissue-specific signature wherein a variety of proteins and nucleic acids are selectively packaged. Growing evidence shows exosomes are involved in cancer pathophysiology and exosomes as the latest addition to the liquid biopsy portfolio have been used in cancer diagnosis. Compared to cell free RNA, exosomal lipid envelope can effectively protect RNA cargo against degradation. Therefore, exosomes may hold great promise for the identification of radioresistance. Here, we report six plasma exosomal miRNAs could be used to distinguish radioresistant NSCLC patients from radiosensitive NSCLC patients and to evaluate the prognosis of NSCLC. Samples were obtained from 52 NSCLC patients with or without radioresistance and 45 age-matched healthy volunteers. Exosomes in 1 ml plasma were isolated followed by extraction of small RNA. The expression levels of miRNAs were determined by quantitative real-time PCR. Potential miRNA markers were further evaluated in additional 52 NSCLC patients. We found exosomal miR-1246 and miR-96 are significantly overexpressed in NSCLC patients. Moreover, exosomal miR-96 in patients with radioresistant NSCLC is significantly higher than that of controls. Exosomal miR-96 also demonstrates a significant correlation with vascular invasion and poor overall survival. Altogether, our results indicate that exosomal miR-96 could be a non-invasive diagnostic and prognostic marker of radioresistant NSCLC.

Background. To create an animal model for diabetic ulcers with semi-Yin and semi-Yang (SYSY) syndrome and to study the pathological and metabolic features of SYSY syndrome. Methods. Firstly, based on the clinical characteristics of the SYSY syndrome of diabetic ulcer, an animal model of diabetic ulcers with SYSY syndrome being full-thickness skin defects was created by injecting streptozotocin (STZ) intraperitoneally, infecting with Staphylococcus aureus, and gastrically administering senna. Secondly, the content and distribution patterns of collagen fibers, the expression of neutrophils and macrophage markers, angiogenesis, and the expression of IL-1β and IL-10 in the rats with Yang syndrome, Yin syndrome, and SYSY syndrome of diabetic ulcers at different time points were detected. Representative traditional Chinese medicine (TCM) ointment of Yang syndrome, Yin syndrome, and SYSY syndrome was used to treat this animal model. The above indexes in each treatment group were detected. Finally, metabonomics was used to detect and analyze the changes of differential metabolites related to macrophage metabolism in Yang, Yin, and SYSY syndromes at different time points. Results. An animal model of diabetic ulcers with SYSY syndrome was established. The pathological features of the SYSY syndrome group were chronic low-grade inflammatory reactions. On the third day, the SYSY syndrome group displayed lower expression of CD16, CD68, CD163, IL-1β, and metabolites related to M1-type macrophages compared with other groups. On the seventh day, the SYSY syndrome group showed lower expression of CD31, IL-10, myeloperoxidase, and metabolites related to M2-type macrophages. Treatment with Chong He Ointment, a representative TCM ointment for SYSY syndrome, reversed the expression levels of these indexes and promoted wound healing in the SYSY group. Conclusion. SYSY syndrome presents a persistent pathological state of low inflammation, which may be caused by an insufficient activation of the M1-type metabolic pathway in macrophages in the early acute inflammatory stage, resulting in the incomplete clearance of pathogens and debris and continuous stimulation of macrophages to initiate the M1-type metabolic pathway. CD163, CD31, IL-10, and citric acid can be used as potential specific markers for the recovery and progression of SYSY syndrome.

The clustering of TLR1/2 acts as a driver in integrating the spatial cues of ligands into cell-level activation events., The activation of Toll-like receptor heterodimer 1/2 (TLR1/2) by microbial components plays a critical role in host immune responses against pathogens. TLR1/2 signaling is sensitive to the chemical structure of ligands, but its dependence on the spatial distribution of ligands on microbial surfaces remains unexplored. Here, we reveal the quantitative relationship between TLR1/2-triggered immune responses and the spacing of ligand clusters by designing an artificial “phagocytic synapse” nanoarray platform to mimic the cell-microbe interface. The ligand spacing dictates the proximity of receptor clusters on the cell surface and consequently the pro-inflammatory responses of macrophages. However, cell responses reach their maximum at small ligand spacings when the receptor nanoclusters become adjacent to one another. Our study demonstrates the feasibility of using spatially patterned ligands to modulate innate immunity. It shows that the receptor clusters of TLR1/2 act as a driver in integrating the spatial cues of ligands into cell-level activation events.

Rationale: With the development of endoscopic techniques, endoscopic therapy began to play an important role in the management of esophageal hemangiomas. Patients concerns: A large esophageal submucosal tumor (2.5 cm), which was suspected to be an esophageal hemangioma, was diagnosed in a 50-year-old woman. Diagnosis: Esophageal hemangioma Interventions: Endoscopic submucosal dissection was performed for tumor removal. Outcomes: Histopathological results revealed hemangioma. No complication or recurrence was observed in the 17-month follow-up period. Lessons: Our successful experience showed that endoscopic submucosal dissection is an effective and a safe approach to treat large esophageal hemangiomas (2.5 cm).

Summary Cassava bacterial blight (CBB) caused by Xanthomonas axonopodis pv. manihotis (Xam) seriously affects cassava yield. Nitrate reductase (NR) plays an important role in plant nitrogen metabolism in plants. However, the in vivo role of NR and the corresponding signalling pathway remain unclear in cassava. In this study, we isolated MeNR1/2 and revealed their novel upstream transcription factor MeRAV5. We also identified MeCatalase1 (MeCAT1) as the interacting protein of MeRAV5. In addition, we investigated the role of MeCatalase1 and MeRAV5‐MeNR1/2 module in cassava defence response. MeNRs positively regulates cassava disease resistance against CBB through modulation of nitric oxide (NO) and extensive transcriptional reprogramming especially in mitogen‐activated protein kinase (MAPK) signalling. Notably, MeRAV5 positively regulates cassava disease resistance through the coordination of NO and hydrogen peroxide (H2O2) level. On the one hand, MeRAV5 directly activates the transcripts of MeNRs and NO level by binding to CAACA motif in the promoters of MeNRs. On the other hand, MeRAV5 interacts with MeCAT1 to inhibit its activity, so as to negatively regulate endogenous H2O2 level. This study highlights the precise coordination of NR activity and CAT activity by MeRAV5 through directly activating MeNRs and interacting with MeCAT1 in plant immunity.

Intestinal farnesoid X receptor (FXR) signaling is involved in the development of obesity, fatty liver disease, and type 2 diabetes. However, the role of intestinal FXR in atherosclerosis and its potential as a target for clinical treatment have not been explored. The serum levels of fibroblast growth factor 19 (FGF19), which is encoded by an FXR target gene, were much higher in patients with hypercholesterolemia than in control subjects and were positively related to circulating ceramide levels, indicating a link between intestinal FXR, ceramide metabolism, and atherosclerosis. Among ApoE(–/–) mice fed a high-cholesterol diet (HCD), intestinal FXR deficiency (in Fxr(ΔIE) ApoE(–/–) mice) or direct FXR inhibition (via treatment with the FXR antagonist glycoursodeoxycholic acid [GUDCA]) decreased atherosclerosis and reduced the levels of circulating ceramides and cholesterol. Sphingomyelin phosphodiesterase 3 (SMPD3), which is involved in ceramide synthesis in the intestine, was identified as an FXR target gene. SMPD3 overexpression or C16:0 ceramide supplementation eliminated the improvements in atherosclerosis in Fxr(ΔIE) ApoE(–/–) mice. Administration of GUDCA or GW4869, an SMPD3 inhibitor, elicited therapeutic effects on established atherosclerosis in ApoE(–/–) mice by decreasing circulating ceramide levels. This study identified an intestinal FXR/SMPD3 axis that is a potential target for atherosclerosis therapy.

Background. Hyperuricemia has long been associated with increased cardiovascular risk, and arterial stiffness is proposed as a mediator. The present study is aimed at examining the associations of uric acid (UA) in blood and urine with arterial stiffness in a Chinese cohort. Methods. A total of 2296 participants (mean age: 43.0 years) from our previously established cohort of Hanzhong Adolescent Hypertension Study were included. The participants were classified as subjects with or without arterial stiffness, which was defined as brachial-ankle pulse wave velocity baPWV≥1400 cm/s and/or carotid intima-media thickness CIMT≥0.9 mm. Multivariate regression analyses were used to examine the relationship between serum and urinary UA and the risk of arterial stiffness after adjusting for age, gender, systolic blood pressure, fasting glucose, BMI, heart rate, total cholesterol, and triglycerides. Results. baPWV was positively correlated with urinary uric acid/creatinine ratio (uUA/Cre) (β=0.061, P<0.001), while CIMT was correlated with uUA/Cre (β=0.085, P<0.001) and fractional excretion of uric acid (FEUA) (β=0.044, P=0.033) in all subjects. In addition, uUA/Cre was significantly associated with the risk of high baPWV [1.032 (1.019-1.045)] and arterial stiffness [1.028 (1.016-1.040)]. Conclusion. Our study showed that urinary UA excretion was significantly associated with the risk of arterial stiffness in Chinese adults. These findings suggest that UA, especially urinary UA, may be used as a simple, noninvasive marker for early detection of arterial stiffness in otherwise healthy subjects.

Background Progressive supranuclear palsy (PSP) is a rare movement disorder with poor prognosis. This retrospective study aimed to characterize the natural history of PSP and to find predictors of shorter survival and faster decline of activity of daily living. Method All patients recruited fulfilled the movement disorder society (MDS) clinical diagnostic criteria for PSP (MDS-PSP criteria) for probable and possible PSP with median 12 years. Data were obtained including age, sex, date of onset, age at onset (AAO), symptoms reported at first visit and follow-up, date of death and date of institutionalization. Magnetic resonance imaging was collected at the first visit. Endpoints were death and institutionalization. Kaplan-Meier method and Cox proportional hazard model were used to explore factors associated with early death and institutionalization. Results Fifty-nine patients fulfilling MDS-PSP criteria were enrolled in our study. Nineteen patients (32.2%) had died and 31 patients (52.5%) were institutionalized by the end of the follow-up. Predictors associated with poorer survival were late-onset PSP and decreased M/P area ratio. Predictors associated with earlier institutionalization were older AAO and decreased M/P area ratio. Conclusion Older AAO and decreased M/P area ratio were predictors for earlier dearth and institutionalization in PSP. The neuroimaging biomarker M/P area ratio was a predictor for prognosis in PSP.

The osteoporosis was common complication of ankylosing spondylitis (AS), but it was frequently unrecognized in the initial stage of the disease. This study was to compare areal bone mineral density (BMD) of hip joints in early AS patients with that in healthy controls, to explore the progress of bone loss in cortex and spongiosa in early AS. Quantitative computed tomography (QCT) of hip was performed in 60 AS patients (modified New York criteria for AS, with grade 2 sacroiliitis in computed tomography) and 57 healthy controls. The QCT measurements of AS patients were compared with the measurements of healthy controls. The AS patients had lower areal BMD in cortical bone and total bone of proximal femur in early AS patients (P

Disruption of mitochondrial dynamics is an important pathogenic event in both acute and chronic kidney diseases, but the underlying mechanism remains poorly understood. Here, we report the regulation of mitofusin-2 (Mfn2; a key mitochondrial fusion protein) by microRNA-214 (miR-214) in renal ischemia-reperfusion that contributes to mitochondrial fragmentation, renal tubular cell death, and ischemic acute kidney injury (AKI). miR-214 was induced, whereas Mfn2 expression was decreased, in mouse ischemic AKI and cultured rat kidney proximal tubular cells (RPTCs) following ATP depletion treatment. Overexpression of miR-214 decreased Mfn2. Conversely, inhibition of miR-214 with anti-miR-214 prevented Mfn2 downregulation in RPTCs following ATP depletion. Anti-miR-214 further ameliorated mitochondrial fragmentation and apoptosis, whereas overexpression of miR-214 increased apoptosis, in ATP-depleted RPTCs. To test regulation in vivo, we established a mouse model with miR-214 specifically deleted from kidney proximal tubular cells (PT- miR-214−/−). Compared with wild-type mice, PT- miR-214−/− mice had less severe tissue damage, fewer apoptotic cells, and better renal function after ischemic AKI. miR-214 induction in ischemic AKI was suppressed in PT- miR-214−/− mice, accompanied by partial preservation of Mfn2 in kidneys. These results unveil the miR-214/Mfn2 axis that contributes to the disruption of mitochondrial dynamics and tubular cell death in ischemic AKI, offering new therapeutic targets.

Background This study aimed to devise a Cancer symptoms Discrimination Scale (CSDS) suitable for China based on a cross-sectional survey. Methods The CSDS was developed using the classical measurement theory. A total of 3610 students from Yunnan province, China, participated in the cross-sectional survey. The test version of the scale was modified by the item analysis method, and after the official version of CSDS was developed, its reliability and validity were verified. A univariate analysis of variance and a multiple linear regression model were used to analyze the influencing factors of cancer symptoms discrimination among the university/college students. Results There were 21 items in total for the CSDS, including 3 subscales --- common clinical manifestations (11 items), physical appearance defects (6 items), and drainage tube(s) wearing (4 items). This CSDS had good validity (GFI = 0.930, AGFI = 0.905, RMR = 0.013, I-CVIs> 0.80, and the Pearson correlation coefficient was satisfactory.) and reliability (Cronbach’s alpha = 0.862, spearman-brown coefficient = 0.875). The multiple linear regression showed that certain factors may affect the students’ discrimination level against cancer symptoms (P Conclusion This CSDS, with good reliability and validity, can be used for the evaluation of the discrimination risk and levels against cancer symptoms among healthy students.

There is a high prevalence of mild cognitive impairment (MCI) and dementia in Parkinson’s disease (PD) patients, but a Chinese version of cognitive rating scale that is specific and sensitive to PD patients is still lacking. The aims of this study are to test the reliability and validity of a Chinese version of Parkinson’s disease-cognitive rating scale (PD-CRS), establish cutoff scores for diagnosis of Parkinson’s disease dementia (PDD) and PD with mild cognitive impairment (PD-MCI), explore cognitive profiles of PD-MCI and PDD, and find cognitive deficits suggesting a transition from PD-MCI to PDD. PD-CRS was revised based on the culture background of Chinese people. Ninety-two PD patients were recruited in three PD centers and were classified into PD with normal cognitive function (PD-NC), PD-MCI, and PDD subgroups according to the cognitive rating scale (CDR). Those PD patients underwent PD-CRS blind assessment by a separate neurologist. The PD-CRS showed a high internal consistency (Cronbach’s Alpha = 0.840). Intraclass Correlation coefficient (ICC) of test-retest reliability reached 0.906 (95% CI 0.860–0.935, p<0.001). ICC of inter-rater reliability was 0.899 (95% CI 0.848–0.933, p<0.001). PD-CRS had fair concurrent validity with MDRS (ICC = 0.731, 95% CI 0.602–0.816). All the frontal-subcortical items showed significant decrease in PD-MCI compared with the PD-NC group (p≤0.001), but the instrument cortical items did not (confrontation naming p=0.717, copying a clock p=0.620). All the frontal-subcortical and instrumental-cortical functions showed significant decline in PDD compared with the PD-NC group (p≤0.001). The cutoff value for diagnosis of PD-MCI is 80.5 with the sensitivity of 75.7% and the specificity of 75.0%, and for diagnosis of PDD is 73.5 with the sensitivity of 89.2% and the specificity of 98.9%. Revised Chinese version of PD-CRS is a reliable, acceptable, valid, and useful neuropsychological battery for assessing cognition in PD patients.

The Coronavirus Disease 2019 (COVID-19) has fast spread to over 200 countries and regions worldwide since its outbreak, while in March, Europe became the emerging epicentre. In this study, we aimed to model the epidemic trends and estimate the essential epidemic features of COVID-19 in Italy, Spain, Germany, and France at the initial stage. The numbers of daily confirmed cases and total confirmed cases were extracted from the Coronavirus disease (COVID-19) situation reports of WHO. We applied an extended Susceptible-Exposed-Infectious-Removed (SEIR) model to fit the epidemic trend and estimated corresponding epidemic features. The transmission rate estimates were 1.67 (95% credible interval (CrI), 1.64–1.71), 2.83 (2.72–2.85), 1.91 (1.84–1.98), and 1.89 (1.82–1.96) for Italy, Spain, Germany, and France, corresponding to the basic reproduction numbers (R0) 3.44 (3.35–3.54), 6.25 (5.97–6.55), 4.03 (3.84–4.23), and 4.00 (3.82–4.19), respectively. We found Spain had the lowest ascertainment rate of 0.22 (0.19–0.25), followed by France, Germany, and Italy of 0.45 (0.40–0.50), 0.46 (0.40–0.52), and 0.59 (0.55–0.64). The peaks of daily new confirmed cases would reach on April 16, April 5, April 21, and April 19 for Italy, Spain, Germany, and France if no action was taken by the authorities. Given the high transmissibility and high covertness of COVID-19, strict countermeasures, such as national lockdown and social distancing, were essential to be implemented to reduce the spread of the disease.

Background Qishen (QS) capsules, a Traditional Chinese Medicine, has been widely used to treat coronary heart disease in China. However, evidence of its effectiveness remains unclear. Methods To explore whether QS has cardioprotective efficacy and/or promotes angiogenesis after myocardial infarction (MI), we performed experiments in a preclinical rat MI model. One month after left anterior descending coronary artery ligation, the rats received either QS solution (0.4 g/kg/day) or the same volume of saline by intragastric injection for four weeks. Results Echocardiographic and hemodynamic analyses demonstrated relatively preserved cardiac function in MI rats administered QS. Indeed, QS treatment was associated with reduced infarct scar size and heart weight index, and these beneficial effects were responsible for enhancing angiogenesis. Mechanistically, QS treatment increased phosphorylation of protein kinase B (Akt) and downregulated phosphorylation of mitogen-activated protein kinase/extracellular-regulated kinase (MEK/ERK). Conclusions QS therapy can improve the cardiac function of rats after MI by an underlying mechanism involving increased angiogenesis, at least partially via activation of the Akt signaling pathway and inhibition of MEK/ERK phosphorylation.

The objective of the present study is to develop an age-specific lower extremity finite element model for pedestrian accident simulation. Finite element (FE) models have been used as a versatile tool to simulate and understand the pedestrian injury mechanisms and assess injury risk during crashes. However, current computational models only represent certain ages in the population, the age spectrum of the pedestrian victims is very large, and the geometry of anatomical structures and material property of the lower extremities changes with age for adults, which could affect the injury tolerance, especially in at-risk populations such as the elderly. The effects of age on the material mechanical property of bone and soft tissues of the lower extremities as well as the geometry of the long bone were studied. Then an existing 50th percentile male pedestrian lower extremity model was rebuilt to depict lower extremity morphology for 30- to 70-year-old (YO) individuals. A series of PMHS tests were simulated to validate the biofidelity and stability of the created age-specific models and evaluate the lower extremity response. The development of age-specific lower extremity models will lead to an improved understanding of the pedestrian lower extremity injury mechanisms and injury risk prediction for the whole population in vehicle-pedestrian collision accidents.

The present study was performed to evaluate the effects of seed priming. This was done by soaking the seeds of two rapeseed cultivars, namely, ZY15 (tolerant to low temperature and drought) and HY49 (sensitive to low temperature and drought), for 12 h in varying solutions: distilled water, 138 mg/L salicylic acid (SA), 300 mg/L gibberellic acid (GA), 89.4 mg/L sodium nitroprusside (SNP), 3000 mg/L calcium chloride (CaCl2), and 30 mg/L abscisic acid (ABA). Primed and non-primed seeds were left to germinate at 15°C and -0.15 MPa (T15W15) and at 25°C and 0 MPa (T25W0), respectively. The results showed that SA, GA, SNP, CaCl2, and ABA significantly improved the germination potential (GP), germination rate (GR), germination index (GI), stem fresh weight (SFW), stem dry weight (SDW), root length (RL), stem length (SL), and seed vigor index (SVI) under T15W15. For ZY15 seeds under T25W0, GA, SNP, CaCl2, and ABA priming reduced the average germination time (96% after 5 days) compared to that of the control (88% after 5 days). For ZY15 seeds under T15W15, SA, SNP, CaCl2, and ABA priming, with respect to the control and water-treated groups, shortened the average germination time (92% after 5 days) compared to that of the control (80% after 5 days). For HY49 seeds under T25W0, GA, SNP, CaCl2, and ABA priming reduced the average germination time (92% after 5 days) compared to that of the control (85% after 5 days). Similarly, for HY49 seeds under T15W15, GA priming shortened the average germination time (89% after 5 days) compared to that of the control (83% after 5 days). These priming agents increased the net photosynthesis, stomatal conductivity, and transpiration rate of rape seedlings under conditions of low temperature and drought stress, while also decreasing intercellular carbon dioxide (CO2) concentrations. Additionally, SA, GA, SNP, CaCl2, and ABA increased superoxide dismutase concentrations (SOD) and ascorbic peroxidase (APX) activities of rape seedlings under stress conditions, while decreasing catalase (CAT) and peroxidase (POD) activities in ZY15 seedlings. In HY49, which is sensitive to low temperature and drought, all priming solutions, except for SNP, led to an increase in SOD activity levels and a decrease in CAT activity levels. Overall, SA, GA, SNP, and CaCl2 increased the concentrations of indoleacetic acid (IAA), GA, ABA, and cytokinin (CTK) in seedlings under stress conditions. Moreover, compared to SA, CaCl2, and ABA, GA (300 mg/L) and SNP (300 mol/L) showed improved priming effects for ZY15 and HY49 under stress conditions.

Background: Tenofovir disoproxil fumarate (TDF) has been widely recommended as a first-line antiviral agent to treat chronic hepatitis B (CHB). Qingzhong and Viread, formulations of TDF commercialized by Jiangsu Chia-tai Tianqing Pharmaceutical Co Ltd and GlaxoSmithKline, respectively, have both been approved by the State Food and Drug Administration, China. This study analyzed the efficacy and safety of these 2 TDF agents in Chinese patients with CHB. Methods: In this multicenter, randomized, double-blind, double-dummy, noninferiority phase 3 clinical trial (ClinicalTrials.gov identifier: NCT02287857), 330 Chinese patients with CHB [hepatitis B envelope antigen-positive (HBeAg) (+): 232] were randomly assigned to receive Qingzhong (group A: 161 patients) or Viread (group B: 169 patients) 300 mg once daily for 48 weeks. Subsequently, all patients were administered Qingzhong 300 mg once daily from week 49 to week 240. The primary end point was the degree of decline of plasma hepatitis B virus (HBV) DNA levels at week 48 and the secondary endpoints were viral suppression, normalization of alanine aminotransferase (ALT) levels, hepatitis B surface antigen (HBsAg)/HBeAg loss or seroconversion, and virological breakthrough. Results: Among patients with CHB who were HBeAg (+), the mean HBV DNA titer decreased similarly between the groups at week 48. The percentages of patients who achieved undetectable HBV DNA were similar between the groups (85.11% and 82.35% in groups A and B, respectively) and similar losses of HBeAg and HBeAg seroconversion rates were achieved. Moreover, for patients with CHB who were HBeAg (−), reductions in HBV DNA were similar. Among all patients with CHB, the rates of normalization of ALT and the loss of HBsAg were similar. The overall incidence of adverse events was comparable between the groups. Conclusion: In conclusion, the 48-week administration of Qingzhong showed noninferior efficacy and safety profiles compared to Viread in Chinese patients with CHB.

Background Speciation with gene flow is an alternative to the nascence of new taxa in strict allopatric separation. Indeed, many taxa have parapatric distributions at present. It is often unclear if these are secondary contacts, e.g. caused by past glaciation cycles or the manifestation of speciation with gene flow, which hampers our understanding of how different forces drive diversification. Here we studied genetic, phenotypic and ecological aspects of divergence in a pair of incipient shorebird species, the Kentish (Charadrius alexandrinus) and the White-faced Plovers (C. dealbatus), shorebirds with parapatric breeding ranges along the Chinese coast. We assessed divergence based on molecular markers with different modes of inheritance and quantified phenotypic and ecological divergence in aspects of morphometric, dietary and climatic niches. Results Our integrative analyses revealed small to moderate levels of genetic and phenotypic distinctiveness with symmetric gene flow across the contact area at the Chinese coast. The two species diverged approximately half a million years ago in dynamic isolation with secondary contact occurring due to cycling sea level changes between the Eastern and Southern China Sea in the mid-late Pleistocene. We found evidence of character displacement and ecological niche differentiation between the two species, invoking the role of selection in facilitating divergence despite gene flow. Conclusion These findings imply that ecology can indeed counter gene flow through divergent selection and thus contributes to incipient speciation in these plovers. Furthermore, our study highlights the importance of using integrative datasets to reveal the evolutionary history and assist the inference of mechanisms of speciation. Electronic supplementary material The online version of this article (10.1186/s12862-019-1449-5) contains supplementary material, which is available to authorized users.

Objectives High dependency on pesticides could cause selection pressure leading to the development of resistance. This study was conducted to assess the resistance of the house fly, Musca domestica, to five insecticides, namely, permethrin, deltamethrin, beta-cypermethrin, propoxur, and dichlorvos, in Zhejiang Province. Methods Field strains of house flies were collected from the 12 administrative districts in Zhejiang Province in 2011, 2014, and 2017, respectively. Topical application method was adopted for the bioassays. The probit analysis was used to determine the median lethal doses with the 95% confidence interval, and then the resistance ratio (RR) was calculated. The insecticides resistance in different years and the correlations of the resistance between different insecticides were also analyzed. Results The resistance of field strains house flies to insecticides in Zhejiang Province was relatively common, especially for permethrin, deltamethrin, and beta-cypermethrin. The reversion of the resistance to dichlorvos was found, and most of the field strains in Zhejiang Province became sensitive to dichlorvos in 2017. Propoxur was much easier to cause very high level of resistance; the Hangzhou strain had the highest RR value more than 1000 in 2014, and five field strains had the RR value more than 100 in 2017. Compared to 2011 and 2014, the resistance of the house flies to propoxur and deltamethrin increased significantly in 2017. The resistance of permethrin, deltamethrin, beta-cypermethrin, and propoxur was significantly correlated with each other, and the resistance of dichlorvos was significantly correlated with beta-cypermethrin. Conclusions Our results suggested that resistance was existed in permethrin, deltamethrin, beta-cypermethrin, and propoxur in the house flies of Zhejiang Province, while the resistance reversion to dichlorvos was found.

Background and objectivesThe aim of the study was to examine the associations of uric acid (UA) in blood and urine with subclinical renal damage (SRD) and its progression in a Chinese cohort.Methods1) 2342 participants from our previously established cohort who were followed up in 2017 were included. Cross-sectional analysis was used to examine the relationships between serum and urinary UA and the risk of SRD. 2) A total of 266 participants were recruited from the same cohort in 2013, and followed up in 2017. Longitudinal analysis was used to determine the relationships of serum and urinary UA with progression of SRD, which was defined as urinary albumin-to-creatinine ratio (uACR) progression or estimated glomerular filtration rate (eGFR) decline.ResultsIn cross-sectional analysis, higher levels of uACR were associated with higher levels of serum uric acid (SUA) and urinary uric acid/creatinine ratio (uUA/Cre). Lower eGFR was associated with higher levels of SUA and fractional excretion of uric acid (FEUA) but lower uUA/Cre levels in all subjects. In addition, the multivariate-adjusted odds ratios for SRD compared with non-SRD were 3.574 (2.255-5.664) for uUA/Cre. Increasing uUA/Cre levels were associated with higher risk of SRD. In longitudinal analysis, 4-year changes of uUA/Cre and SUA were significantly associated with eGFR decline.ConclusionsThis study suggested that urinary UA excretion was significantly associated with the risk of SRD in Chinese adults. Furthermore, 4-year changes of serum and urinary UA were associated with SRD progression. These findings suggest that UA, especially urinary UA, may be used as a simple, noninvasive marker for early detection of decreased renal function in otherwise healthy subjects.

Introduction: With the rapid development of social economy, peoples dependence on computers and mobile phones is increasing day by day. This causes people to often overuse. Therefore, the incidence of Ocular muscle spasm has been increasing year by year in recent years. The disease usually starts and hides, which seriously affects the patients social image, daily life, and work. Methods/design: We will compare the clinical efficacy of thunder-fire moxibustion combined with acupressure with pure thunder-fire moxibustion on Ocular muscle spasm using random control method. Discussion: We aim to find a simple, safe, simple and effective Chinese medicine nursing technology that relieves Ocular muscle spasm. Trial registration: ClinicalTrials.gov,ChiCTR2000034187, Registered on 27 June 2020.

Background Sotetsuflavone is isolated from Cycas revoluta Thunb., which has biological activity against tumors. However, the anti-proliferative effects of sotetsuflavone on A549 cells and its mechanism are not fully elucidated. Methods This study investigated the mechanisms of growth inhibition, cell cycle arrest and apoptosis in non-small cell lung cancer A549 cells induced by sotetsuflavone and evaluated whether sotetsuflavone can be safely utilized by humans as therapeutic agent. Results We found that sotetsuflavone had significant antiproliferative activity against A549 cells. At the same time, the reactive oxygen species (ROS) content increased while the mitochondrial membrane potential and the ratio of Bcl-2/Bax decreased. Cleaved caspase-3, cleaved caspase-9, cytochrome C and Bax expression increased, and Cyclin D1, CDK4, cleaved caspase-8 and Bcl-2 expression decreased. Interestingly, we demonstrated that sotetsuflavone could effectively inhibit the G0/G1 cycle progression, and then induce the endogenous apoptosis pathway. Our results show that sotetsuflavone could inhibit the growth of A549 cells by up-regulating intracellular ROS levels and causing the mitochondrial membrane potential to collapse, inducing G0/G1 phase arrest and endogenous apoptosis. Conclusions In short, we confirm that sotetsuflavone had an inhibitory effect on A549 cells and discovered that it causes apoptosis of A549 lung cancer cells. Sotetsuflavone may be used as a novel candidate for anti-tumor therapy in patients with lung cancer.

It is not rare to find Immunoglobulin A (IgA) nephropathy (IgAN) combined with other glomerular diseases, which can be called compound IgAN (cIgAN). Till now, clinical-pathological investigation of cIgAN was lacking, especially the severity of “background IgAN lesions.” This research aimed to investigate the incidence, clinical and pathological characteristics of cIgAN, and thus improve the understanding of the clinical significance of this combination. Patients with cIgAN diagnosed in Peking University People's Hospital from November 2012 to April 2018 were retrospectively analyzed. Patients with IgAN without compound glomerular diseases (sIgAN) were enrolled as a control group. Among 1407 patients diagnosed with IgAN, 80 (5.69%) were cIgAN patients. Compared with sIgAN, cIgAN patients had a significantly lower prevalence of microscopic hematuria and more urine protein. There were 10 pathological types of glomerular diseases combined with IgAN, led by diabetic nephropathy 37 (46.25%) and membranous nephropathy 14 (17.5%). Histologically, although the mesangial hypercellularity was comparable in 2 groups, cIgAN patients had a lower prevalence of endocapillary proliferation, segmental glomerulosclerosis, and cellular or fibrocellular crescents formation, as well as weaker immunofluorescence intensity for IgA and C3 (all P

Background The involvement of inflammasome activation and macrophage polarization during the process of syphilis infection remains unknown. In this study, A series of experiments were performed using human macrophages to research the role of NLRP3 inflammasome regulation in interleukin (IL)-1β production and its influence on macrophage polarization triggered by T. pallidum. Results The results showed that in M0 macrophages treated with T. pallidum, the M1-associated markers inducible nitric oxide synthase (iNOS), IL-1β and TNF-α were upregulated, and the M2-associated markers CD206 and IL-10 were downregulated. In addition, we observed NLRP3 inflammasome activation and IL-1β secretion in T. pallidum-treated macrophages, and the observed production of IL-1β occurred in a dose- and time-dependent manner. Moreover, the secretion of IL-1β by macrophages after T. pallidum treatment was notably reduced by anti-NLRP3 siRNA and caspase-1 inhibitor treatment. NAC, KCl, and CA074-ME treatment also suppressed IL-1β release from T. pallidum-treated macrophages. Conclusions These findings showed that T. pallidum induces M0 macrophages to undergo M1 macrophage polarization and elevate IL-1β secretion through NLRP3. Moreover, the process of NLRP3 inflammasome activation and IL-1β production in macrophages in response to T. pallidum infection involves K+ efflux, mitochondrial ROS production and cathepsin release. This study provides a new insight into the innate immune response to T. pallidum infection.

Damaged cartilage has very low regenerative potential which has led to the search for novel tissue-engineering approaches to help treat cartilage defects. While various approaches have been reported, there is no perfect treatment currently. In this study we evaluated the effects of a plant extract, chlorogenic acid (CGA), as part of chondrocyte transplantation on a model of knee joint injury in chicks. First, primary cultured chondrocytes used to evaluate the effects of CGA on chondrogenesis. Then using an articular cartilage injury model of chick knee we assessed the functional recovery after transplantation of the complexes containing chondrocytes and CGA in an alginate scaffold. Histological analysis, PCR, and western blot were further used to understand the underlying mechanisms. We showed that 60 μM CGA in alginate exhibited notable effects on stimulating chondrogenesis in vitro. Secondly, it was shown that the application of these complexes accelerated the recovery of injury-induced dysfunction by gait analysis when followed for 21 days. Histochemical analysis demonstrated that there was less abnormal vasculature formation, more chondrocyte proliferation and cartilage matrix synthesis in the presence of the complexes containing CGA. We discovered CGA treated transplantation up-regulated the expressions of Sox9 and Col2a1 which were responsible for the stimulation of chondrogenesis. Furthermore, the application of these complexes could suppress the abnormal angiogenesis and fibrosis at the injury site. Lastly, the elevated levels of inflammatory cytokines IL-1β, TNF-α, p-p65, and MMPs expression were decreased in the presence of CGA. This may be caused through adjusting cellular redox homeostasis associated with Nrf2. This study suggests that combining chondrocytes and CGA on an alginate scaffold can improve the recovery of damaged articular cartilage.

Background The inflammasome responses in Treponema pallidum infection have been poorly understood to date. This study aimed to investigate the expression of the nucleotide-binding leucine-rich receptor protein 3 (NLRP3) inflammasome in the development of tissue inflammation in rabbits infected with T. pallidum. Methods Forty-five rabbits were randomly assigned to a blank group or an infection group, and the latter was divided into no benzathine penicillin G (BPG) and BPG treatment subgroups. Rabbits in the infection group were injected intradermally with 0.1 mL of a 107/mL T. pallidum suspension at 10 marked sites along the back, and the blank group was treated with normal saline. The BPG treatment subgroup received 200,000 U of BPG administered intramuscularly twice, at 14 d and 21 d post-infection. The development of lesions was observed, and biopsies of the injection site and various organs, including the kidney, liver, spleen, lung, and testis, were obtained for NLRP3, caspase-1, and interleukin-1β (IL-1β) mRNA analysis during infection. Blood was also collected for the determination of IL-1β concentration. Results Rabbits infected with T. pallidum (both the BPG treatment and no BPG treatment subgroups), exhibited NLRP3 inflammasome activation and IL-1β secretion in cutaneous lesions, showing a trend in elevation to decline; NLRP3 mRNA expression reached a peak at 18 d in the BPG treatment subgroup and 21 d in the no BPG treatment subgroup and returned to “normal” levels [vs. the blank group (P > 0.05)] at 42 d post-infection. The trend was similar to the change in cutaneous lesions in the infected rabbits, which reached a peak at 16 d in the BPG treatment subgroup and 18 d in the no BPG treatment subgroup. NLRP3, caspase-1, and IL-1β mRNA expression levels were slightly different in different organs. NLRP3 inflammasome activation was also observed in the kidney, liver, lung, spleen and testis. IL-1β expression was observed in the kidney, liver, lung and spleen; however, there was no detectable level of IL-1β in the testes of the infected rabbits. Conclusions This study established a clear link between NLRP3 inflammasome activation and the development of tissue inflammation in rabbits infected with T. pallidum. BPG therapy imperceptibly adjusted syphilitic inflammation.

Brain plasticity, including anatomical changes and functional reorganization, is the physiological basis of functional recovery after spinal cord injury (SCI). The correlation between brain anatomical changes and functional reorganization after SCI is unclear. This study aimed to explore whether alterations of cortical structure and network function are concomitant in sensorimotor areas after incomplete SCI. Eighteen patients with incomplete SCI (mean age 40.94 ± 14.10 years old; male:female, 7:11) and 18 healthy subjects (37.33 ± 11.79 years old; male:female, 7:11) were studied by resting state functional magnetic resonance imaging. Gray matter volume (GMV) and functional connectivity were used to evaluate cortical structure and network function, respectively. There was no significant alteration of GMV in sensorimotor areas in patients with incomplete SCI compared with healthy subjects. Intra-hemispheric functional connectivity between left primary somatosensory cortex (BA1) and left primary motor cortex (BA4), and left BA1 and left somatosensory association cortex (BA5) was decreased, as well as inter-hemispheric functional connectivity between left BA1 and right BA4, left BA1 and right BA5, and left BA4 and right BA5 in patients with SCI. Functional connectivity between both BA4 areas was also decreased. The decreased functional connectivity between the left BA1 and the right BA4 positively correlated with American Spinal Injury Association sensory score in SCI patients. The results indicate that alterations of cortical anatomical structure and network functional connectivity in sensorimotor areas were non-concomitant in patients with incomplete SCI, indicating the network functional changes in sensorimotor areas may not be dependent on anatomic structure. The strength of functional connectivity within sensorimotor areas could serve as a potential imaging biomarker for assessment and prediction of sensory function in patients with incomplete SCI. This trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-ROC-17013566).

The objective of the present study is to investigate the influence of neck muscle activation on whiplash neck injury of the occupants of a passenger vehicle under different severities of frontal and rear-end impact collisions. The finite element (FE) model has been used as a versatile tool to simulate and understand the whiplash injury mechanism for occupant injury prevention. However, whiplash injuries and injury mechanisms have rarely been investigated in connection with neck active muscle forces, which restricts the complete reappearance and understanding of the injury mechanism. In this manuscript, a mixed FE human model in a sitting posture with an active head-neck was developed. The response of the cervical spine under frontal and rear-end collision conditions was then studied using the FE model with and without neck muscle activation. The effect of the neck muscle activation on the whiplash injury was studied based on the results of the FE simulations. The results indicated that the neck active force influenced the head-neck dynamic response and whiplash injury during a collision, especially in a low-speed collision.

Background Prostatic artery embolization (PAE) has been proved effective in the treatment of lower urinary tracts (LUTS) secondary to benign prostatic hyperplasia (BPH) with low complications, and most of the them are due to non-target embolization of adjacent organs, such as bladder, rectum, seminal vesicles and penis. Aim of this study was to present seminal vesicle (SV) abnormalities following prostatic artery embolization (PAE) for the treatment of symptomatic benign prostatic hyperplasia. Methods We reviewed 139 BPH patients who received PAE during the period of February 2009 and January 2015 at a single institution, highlighting seminal vesicle abnormalities and their clinical relevance after PAE. PAE was performed using 90~ 180-μm (mean 100-μm) polyvinyl alcohol foam particles. Results Nine of 139 patients with SV abnormalities (6.5%) were identified by magnetic resonance imaging (MRI), including subacute haemorrhage in 3 patients and ischaemia in 6 patients. Using cone-beam computed tomography (CB-CT), the seminal vesicle arteries were identified 8 of the 9 patients. All 9 patients complained of a few episodes of mild haematospermia during the 1–4 weeks after PAE; the haematospermia disappeared spontaneously without any treatment. Conclusion SV haemorrhage and ischaemia may occur after PAE, and these patients may present with transient and self-limited haematospermia.

Background. Facet joint violation (FV) was reported as variable iatrogenic damage that can be a crucial risk factor leading to the adjacent segment degeneration (ASD). “Blind” screw placement technique in minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) contributes to the increasing incidence of FV that can be influenced by several potential factors. Many controversies about these factors and clinical outcomes of different types of FV patients exist, yet they have not been analyzed. Methods. 99 cases undergoing single-segment MIS-TLIF from July 2013 to December 2015 were retrospectively analyzed. Computed tomography (CT) was applied to determine the incidence of FV, and then the correlation between FV and relevant factors, including gender, age, body mass index (BMI), top-screw level, and decompression, was analyzed. A total of 53 cases were followed up after one year, 31 cases in noninjury (A group) and 22 patients in FV injury (B group). Results. The incidence of FV was 39. 39% (39/99) in the patients and 23.23% (46/198) in the screws. Logistic regression analysis showed that screw at L5 in patients with BMI > 30 kg/m2 was vulnerable to FV (P<0.05). Moreover, postoperative average intervertebral disc height (AIDH) of fusion segment, visual analog scale (VAS), and Oswestry disability index (ODI) scores improved significantly in group A and B when compared with preoperative data (P<0.05). Adjacent superior average intervertebral disc height (ASAIDH) presented decrease, but adjacent superior intervertebral disc Cobb angle (ASIDCA) appeared to increase in the two groups at the final follow-up compared with postoperative 3 days (P<0.05). Low back VAS and ODI scores in group A (31 cases) were lower than those in group B (22 cases) in the final follow-up (P<0.05). Conclusion. MIS-TLIF is an effective treatment for lumbar degenerative disease, but FV occurred at a higher incidence. Facet joints should be protected in MIS-TLIF to avoid FV.

Caulophyllum robustum Maxim (C. robustum) has commonly been used as traditional Chinese medicine for the treatment of rheumatic pain and rheumatoid arthritis (RA) in China. This paper first investigated the anti-inflammation effect of C. robustum extraction (CRME) on RAW264.7 cells stimulated by lipopolysaccharide (LPS) and gene expression levels of inflammatory factors. Moreover, we first evaluated the anti-RA effects of CRME using collagen-induced arthritis (CIA) in DBA/1J mice, and the incidence, clinical score, and joint histopathology were evaluated. The levels of IL-1, IL-6, TNF-α, and PGE2 inflammatory factors in sera of mice were detected by enzyme-linked immunosorbent assay. The expression of NF-κB p65 in the joint was tested by immune histochemical technique. The results showed that, compared with the model group, CRME significantly improved symptoms of the arthritis index, limb swelling, and histological findings by decreasing synovial membrane damage, the extent of inflammatory cell infiltration, and the expansion of capillaries in CIA mice. The results also showed that CRME can reduce the levels of IL-1, IL-6, TNF-α, and PGE2 and inhibit the expression of NF-κB p65. All these results indicated the anti-inflammatory efficacy of CRME as a novel botanical extraction for the treatment of RA.

Sinogastromyzon szechuanensis is endemic to the Upper Yangtze River in China. In this study, we first determined the complete mitochondrial genome of S. szechuanensis. The circular mitogenome was 16,565 bp in length, including 13 protein-coding genes (PCGs), 2 rRNA genes, 22 tRNA genes, and 2 main noncoding regions. Most mitochondrial genes were encoded on the H-strand, except for ND6 and eight tRNA genes. The overall nucleotides composition was 30.38% A, 25.26% T, 27.74% C, and 16.62% G, with AT bias of 55.64%, respectively. Phylogenetic analysis using concatenated nucleotide sequences of the 13 PCGs with two different methods (ML and NJ) both highly supported that S. szechuanensis showed a close relationship with S. puliensis and S. sichangensis. These data would be useful for further studies on genetic diversity and molecular phylogenetic relationship of the family Homalopteridae.

Rationale: POEMS syndrome is a rare multi-system disorder, which sometimes involves the kidney. Immunotactoid glomerulopathy (ITG) is an uncommon glomerular disease resulted from deposits of immunoglobulins and its derivatives. ITG caused by POEMS syndrome is rarely reported. Patient concerns: A 63-year-old man was presented with acute kidney injury. In addition, it's found that he had abnormal serum free κ /λ ratio, polyneuropathy, Castleman's disease, organomegaly, endocrinopathy and skin changes. Diagnoses: POEMS syndrome was diagnosed, Renal biopsy revealed an ITG. Interventions: Dexamethasone and thalidomide were given, as well as hemodialysis and other supportive treatments. Outcomes: The patient's extrarenal manifestations improved gradually and his renal function also showed slight improvement. Lessons: ITG caused by POEMS syndrome is rare, however, it makes sense that the monoclonal proteins produced by the plasma cells could cause ITG. Chemotherapy similar to that employed in multiple myeloma may be beneficial for these patients.

The relationship between hepatitis B virus (HBV) and the prognosis of hepatocellular carcinoma (HCC) after surgery remains uncertain. A retrospective cohort study was performed to evaluate the impact of pre-S deletions, T1762/A1764, and A1896 mutations on prognosis of HCC after curative resection. A total of 113 patients with positive serum HBV DNA (>200 IU/mL) who had underwent curative resection of pathologically proven HCC were recruited to determine the risk factors affecting the prognosis. The median follow-up time was 36.5 months and recurrence was detected in 67 patients (59.3%). The cumulative recurrence rates and overall survival rates at 1-, 3-, and 5-year after curative resection were 18.0%, 49.7%, 70.3%, and 93.7%, 61.0%, 42.5%, respectively. Patients with pre-S deletions showed significantly higher recurrence rates compared with those with wild type infection (HR: 1.822, P = .018), but not related with a significantly poor survival (HR: 1.388, P = .235). Subgroup analysis indicated that the patients with type III deletion had significant higher tumor recurrence rates than other deletion types (HR: 2.211, 95% confidence intervals [CI]: 1.008–4.846, P = .048). Multivariate analysis revealed that pre-S deletion, tumor size >3 cm in diameter, and the presence of microvascular invasion were independent risk factors for tumor recurrence. HBV pre-S deletions were found to be clustered primarily in the 5′ end of pre-S2 region and were more often found between amino acids 120 and 142 of the pre-S2 domain. The domains most frequently potentially involved were the transactivator domain in pre-S2 and polymerized human serum albumin binding site. Our cohort showed that pre-S deletions at the time of resection could predict tumor recurrence in HCC patients after curative resection.

Background Currently, large prostate size (>80 mL) of benign prostatic hyperplasia (BPH) still pose technical challenges for surgical treatment. This prospective study was designed to explore the safety and efficacy of prostatic arterial embolization (PAE) as an alternative treatment for patients with lower urinary tract symptoms (LUTS) due to largeBPH. Methods A total of 117 patients with prostates >80 mL were included in the study; all were failure of medical treatment and unsuited for surgery. PAE was performed using combination of 50-μm and 100-μm particles in size, under local anaesthesia by a unilateral femoral approach. Clinical follow-up was performed using the international prostate symptoms score (IPSS), quality of life (QoL), peak urinary flow (Qmax), post-void residual volume (PVR), international index of erectile function short form (IIEF-5), prostatic specific antigen (PSA) and prostatic volume (PV) measured by magnetic resonance (MR) imaging, at 1, 3, 6 and every 6 months thereafter. Results The prostatic artery origins in this study population were different from previously published results. PAE was technically successful in 109 of 117 patients (93.2%). Follow-up data were available for the 105 patients with a mean follow-up of 24 months. The clinical improvements in IPSS, QoL, Qmax, PVR, and PV at 1, 3, 6, 12, and 24 months was 94.3%, 94.3%, 93.3%, 92.6%, and 91.7%, respectively. The mean IPSS (pre-PAE vs post-PAE 26.0 vs 9.0; P