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Objective The purpose of this study was to compare the efficacy of focused ultrasound (FU) and interferon drug therapy for cervical intraepithelial neoplasia 1 (CIN1) and chronic cervicitis associated with high risk human papillomavirus (HR-HPV) infection, as well as analyze the influencing factors. Methods A retrospective cohort study was performed from January 2017 to December 2019. A total of 592 patients were enrolled, of which 300 patients were treated with FU and 292 patients were treated with interferon drugs. Kaplan-Meier curves and a COX regression model were used to compare the curative effects of the two therapeutic methods using HR-HPV clearance as the main outcome. The relationship between age, HR-HPV infection type, pathological type, preoperative HR-HPV status and HR-HPV clearance were also analyzed. Results The median time for HR-HPV clearance was 6.00 months (95% CI: 5.24-6.76) in the FU group and 26.00 months (95% CI: 22.32-29.68) in the medication group. A significant difference was observed between the two groups (χ2 =198.902, p = 0.000). The HR-HPV clearance rate was 4.927 (95% CI 3.840-6.321; p = 0.000) times higher in the patients treated with FU than those treated with interferon drugs. In the FU group, no significant difference was observed in HR-HPV clearance rate between CIN1 and chronic cervicitis (χ2=0.660, p = 0.416), which was also insignificant between HR-HPV persistent and non-persistent infections (χ2=0.751, p = 0.386). Conclusion FU therapy can eliminate HR-HPV infections in a short period of time. Moreover, the treatment efficacy of FU was significantly superior to that of interferon drugs.

Background Lung adenocarcinoma (LUAD) is the most common type of lung cancer. DNA repair genes (DRGs) is important in lung cancer. The relationship between the immune environment and the expression levels of DRGs in LUAD remains unclear. The purpose of this study is to assess the relationship between DRGs and the immune environment and clinical characteristics of LUAD. Methods Data of 169 LUAD cases were obtained from cbioportal. The RNA-seq data came from the The Cancer Genome Atlas (TCGA) database. We collected DRGs from the Reactom database (KW0037, Reactom.org). The 302 genes expressed in each sample were analyzed by hierarchical clustering and grouped using the Gene Cluster 3.0 program. The Java Treeview program was used to generate heat maps of cluster indications and tumor staging patterns. GraphPad Prism 8 was used to draw survival curves and compare overall survival (OS). For single genes, an OS difference analysis between low and high expression populations was performed in GraphPad Prism 8. Results Matrix clustering showed no difference in the prognosis of the two clusters. The comparison of subgroups showed that Subcluster 1 (SC1) had the best prognosis, and Subcluster 2 (SC2) had the worst. There was a significant difference in tumor grades between Cluster 1 and Cluster 2 (P=0.01). There were significant differences in smoking status, histological grade and adenocarcinoma subtype among subgroups. In Subcluster 3 (SC3), the proportion of poorly differentiated cases was highest. Immunological index analysis showed that there were significant differences between Cluster 1 and Cluster 2 in interferon, macrophages, monocytes, neutrophils, natural killer (NK) cells, and T cells. Tumor purity, interferon, macrophages, monocytes, neutrophils, NK cells, T cells, translation, and proliferation all showed significant differences between subgroups. In SC2, the proliferation index increased (0.082 vs. 0.070); the protein translation index decreased (0.134 vs. 0.137); and the interferon level increased (0.099 vs. 0.097). In SC3, the proliferation index decreased (0.076 vs. 0.071); the protein translation index decreased (0.140 vs. 0.136); and the level of neutrophils increased (0.083 vs. 0.086). Conclusions The differences of DRGs in LUAD are related to tissue differentiation and immune indicators but not to prognosis.

This study aimed to evaluate and compare the accuracy of average faces constructed by different methods. Original three-dimensional facial images of 26 adults in Chinese ethnicity were imported into Di3DView and MorphAnalyser for image processing. Six average faces (Ave_D15, Ave_D24, Ave_MG15, Ave_MG24, Ave_MO15, Ave_MO24) were constructed using “surface-based registration” method with different number of landmarks and template meshes. Topographic analysis was performed, and the accuracy of six average faces was assessed by linear and angular parameters in correspondence with arithmetic means calculated from individual original images. Among the six average faces constructed by the two systems, Ave_MG15 had the highest accuracy in comparison with the conventional method, while Ave_D15 had the least accuracy. Other average faces were comparable regarding the number of discrepant parameters with clinical significance. However, marginal and non-registered areas were the most inaccurate regions using Di3DView. For MorphAnalyser, the type of template mesh had an effect on the accuracy of the final 3D average face, but additional landmarks did not improve the accuracy. This study highlights the importance of validating software packages and determining the degree of accuracy, as well as the variables which may affect the result.

Abdominal drainage, serving as a diagnostic and therapeutic tool, has been widely applied to prevent complications after major abdominal surgical procedures. However, dislocation of intraperitoneal portion of drainage tube and poor drainage after major surgery has never been detailed. In this retrospective study, we determined whether postoperative abdominal infectious complications are attributed to dislocation of intraperitoneal portion of drainage tube. Patients were recruited from the Department of General Surgery at Beijing Shijitan Hospital, Capital Medical University, between June 2015 and June 2018. All of the enrolled patients had undergone different major abdominal surgical procedures with abdominal drainage. According to different fixation methods of the drainage tube, the patients were categorised as follows: group 1 as conventional extra-abdominal fixation where the tubes were fixed on abdominal wall; group 2 as double fixation where the tubes were fixed by both extra-abdominal and intra-abdominal fixation. Among 60 patients (40 in group 1 and 20 in group 2) with suspected postoperative abdominal infection, abdominal computed tomography (CT) was performed to determine the presence of abnormality. Dislocation of drainage tubes, morbidity, treatment, and prognosis were compared between the two groups. None of the patients showed slip knot or drainage tube slipping from the abdomen based on physical examination and CT imaging. Drainage tube was fixed firmly on the abdominal wall. In group 1, 18 (45%) patients developed postoperative complications resulting from abdominal infection where severe dislocation of intraperitoneal portion of drainage tubes was confirmed by CT. Drainage tubes of six cases were significantly dislocated to the anterior abdominal wall from the target area; 7 upper abdominal drainage tubes dislocated to the lower abdomen; and 5 lower abdominal drainage tubes dislocated to the upper abdomen. Common complications included localised peritonitis (n = 4), abdominal abscess (n = 8), and anastomotic leakage (n = 6). Among them, 8 patients were cured by abdominal puncture catheter drainage; 5 underwent secondary operation and 5 were cured by conservative treatment. In group 2, no tube dislocation was identified by CT. Five patients (25%) developed complications, including localised peritonitis (n = 1), abdominal abscess (n = 1), and anastomotic leakage (n = 3). All the five patients were cured by conservative treatment. Postoperative abdominal infection complications can stem from dislocation of intraperitoneal portion of drainage tube and poor drainage after major abdominal surgery. Maintaining the intraperitoneal portion of drainage tube at the proper location, for example, by applying intraabdominal fixation, is paramount to decrease the incidence and severity of postoperative complications.

Our goal was to assess the enrichment utility of hippocampal volume (HV) as an enrichment biomarker in amnestic mild cognitive impairment (aMCI) clinical trials, and, hence, develop an HV neuroimaging-informed clinical trial enrichment tool. Modeling of integrated longitudinal patient-level data came from open-access natural history studies in patients diagnosed with aMCI-the Alzheimer's Disease Neuroimaging Initiative (ADNI)-1 and ADNI-2-and indicated that a decrease of 1 cm3 with respect to the analysis dataset median baseline intracranial volume-adjusted HV (ICV-HV; ~ 5 cm3 ) is associated with > 50% increase in disease progression rate as measured by the Clinical Dementia Rating Scale-Sum of Boxes. Clinical trial simulations showed that the inclusion of aMCI subjects with baseline ICV-HV below the 84th or 50th percentile allowed an approximate reduction in trial size of at least 26% and 55%, respectively. This clinical trial enrichment tool can help design more efficient and informative clinical trials.

Background Biomarkers of clinical efficacy for subcutaneous immunotherapy (SCIT) on allergic rhinitis (AR) have not been identified yet. This study aims to assess the clinical relevance of serum inhibitory activity for IgE by the method of enzyme-linked immunosorbent facilitated antigen binding (ELIFAB) during SCIT for Artemisia-sensitized AR patients. Methods 19 AR patients were studied who had undergone Artemisia-specific SCIT for more than 8 months (19.68 months on average, ranging from 9 to 33 months). Peripheral bloods were collected before and after treatment. The serum inhibitory activity for IgE was tested by ELIFAB and the level of Artemisia-specific IgG4 (Artemisia-sIgG4) was determined by ELISA. Clinical improvement was evaluated based on the symptom scores and rescue medication use (SMS). The 2-tailed Wilcoxon signed-rank test and the Spearman rank test (two-tailed) were used to analyze data by using SPSS 20.0, with P values of less than 0.05 considered as significant. Results The SMS decreased significantly after SCIT (before: 12.79 ± 4.250, after: 6.11 ± 3.828, P = 0.000 Conclusions The serum inhibitory activity for IgE increased significantly after SCIT, however, there was no correlation between it and clinical improvements by statistics analysis. So whether the serum inhibitory activity for IgE can act as biomarker of efficacy for SCIT or not needs to be studied further.

Background The results of genetic association studies regarding cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) polymorphisms and digestive system malignancies were controversial. The authors designed this meta-analysis to more precisely estimate relationships between CTLA-4 polymorphisms and digestive system malignancies by pooling the results of related studies. Methods The authors searched PubMed, Embase, Web of Science, and CNKI for eligible studies. Thirty-one eligible studies were pooled analyzed in this meta-analysis. Results The pooled meta-analysis results showed that genetic distributions of rs231775, rs4553808, and rs733618 polymorphisms among patients with digestive system malignancies and controls differed significantly. Moreover, genotypic distribution differences were also observed for rs231775 polymorphism among patients with colorectal cancer/pancreatic cancer and controls, for rs4553808 and rs5742909 polymorphisms among patients with gastric cancer and controls, for rs3087243 polymorphism among patients with liver cancer and controls, and for rs733618 polymorphism among patients with colorectal cancer and controls in pooled meta-analyses. Conclusions This meta-analysis suggested that rs231775 polymorphism was associated with predisposition to colorectal cancer and pancreatic cancer, rs4553808 and rs5742909 polymorphisms were associated with predisposition to gastric cancer, rs3087243 polymorphism was associated with predisposition to liver cancer, and rs733618 polymorphism was associated with predisposition to colorectal cancer.

Objective To compare the effectiveness and safety of high-intensity focused ultrasound (HIFU) versus uterine artery chemoembolization with methotrexate for the management of cesarean scar pregnancy (CSP). Methods A total of 170 women with CSP were enrolled in the retrospective cohort study from April 2016 to September 2020. One hundred women received HIFU followed by suction curettage, and 70 women were treated with uterine artery chemoembolization followed by suction curettage. Results The median blood loss during suction curettage was 20 (range 2-800) ml in the HIFU group versus 20 (range 5-200) ml in the chemoembolization group (P=0.837). The mean time for β-human chorionic gonadotropin (β-HCG) normalization was 28.52 ± 10.82 days versus 26.69 ± 8.97 days (P=0.246), respectively. The mean time of menstruation recovery was 34.36 ± 10.63 days versus 31.93 ± 8.53 days (P=0.114), respectively. The incidence of adverse effects in the HIFU group was lower than that in the chemoembolization group (P=0.028). The median hospitalization time in the HIFU group was longer than that in the chemoembolization group (P=0.000). Conclusion HIFU was as effective and safe as uterine artery chemoembolization in the management of CSP, and the incidence of adverse effects was lower.

The tumor mutational burden (TMB) calculated by whole-exome sequencing (WES) is a promising biomarker for the response to immune checkpoint inhibition (ICIs) in solid tumors. However, WES is not feasible in the routine clinical setting. In addition, the characteristics of the TMB in Chinese urothelial carcinoma (UC) are unclear. The aim of this study was to demonstrate the reliability of an Acornmed 808 panel and analyze the characteristics of the TMB in Chinese UC. An Acornmed 808 panel was designed and virtually validated using UC data from the cancer genome atlas (TCGA). Comprehensive analysis of sequencing and clinical data was performed to explore the characteristics of the TMB for 143 Chinese UC patients. Compared to the TMB calculated with random 808-, 500-, and 250-gene panels, the TMB calculated with the Acornmed 808 panel was closer to that calculated by WES. There were marked disparities in the mutational landscape and TMB between Chinese and TCGA UC data. The TMB was negatively associated with copy number variation (CNV). In contrast, the TMB was positive correlation with numbers of mutated DDR genes. Exposure to aristolochic acid signature was observed only in the TMB-high groups. The Acornmed 808 panel is a clinically practical method to assess the TMB. The TMB was associated with the DDR gene status and CNV counts and might be a biomarker for further stratification of UC patients. The study suggested that patients with high TMB may have a unique carcinogenic mechanism.

Neurotransmitter catecholamines (dopamine, epinephrine, and norepinephrine) are liable to undergo oxidation, which copper is deeply involved in. Catecholamine oxidation-derived neurotoxicity is recognized as a pivotal pathological mechanism in neurodegenerative diseases. Glutamate, as an excitatory neurotransmitter, is enriched in the brain at extremely high concentrations. However, the chemical biology relationship of these two classes of neurotransmitters remains largely unknown. In the present study, we assessed the influences of glutamate on the autoxidation of catecholamines, the copper- and copper-containing ceruloplasmin-mediated oxidation of catecholamines, the catecholamine-induced formation of quinoprotein, catecholamine/copper-induced hydroxyl radicals, and DNA damage in vitro. The results demonstrate that glutamate, at a physiologically achievable molar ratio of glutamate/catecholamines, has a pronounced inhibitory effect on catecholamine oxidation, catecholamine oxidation-evoked hydroxyl radicals, quinoprotein, and DNA damage. The protective mechanism of glutamate against catecholamine oxidation could be attributed to its restriction of the redox activity of copper via chelation. This previously unrecognized link between glutamate, catecholamines, and copper suggests that neurodegenerative disorders may occur and develop once the built-in equilibrium is disrupted and brings new insight into developing more effective prevention and treatment strategies for neurodegenerative diseases.

The dysregulated expression of long non-coding RNA FTX transcript X inactive specific transcript regulator (FTX) has been reported to be involved in the tumorigenesis of multiple cancer types. However, to the best our knowledge, its function and clinical value in thyroid cancer remain unclear. The present study aimed to determine the potential role of FTX in the development and progression of thyroid cancer. Reverse transcription-quantitative PCR analysis revealed that the expression levels of FTX were upregulated in thyroid cancer tissues and cell lines compared with those in normal tissues and cell lines, respectively. Survival analysis demonstrated that patients with upregulated FTX expression had a lower survival rate. Functional experiments revealed that the knockdown of FTX inhibited proliferation, cell cycle progression, migration and invasion, and induced apoptosis in thyroid cancer cells, while FTX overexpression accelerated proliferation, migration and invasion, and alleviated apoptosis in thyroid cancer cells. In addition, FTX knockdown significantly inhibited tumor growth in vivo. Furthermore, in thyroid cancer cells, FTX was identified to positively regulate the expression levels of TGF-β1, which is known to play an important regulatory role in tumor metastasis. In conclusion, the findings of the present study suggested that FTX may accelerate thyroid cancer progression via regulation of cellular activities, including cell proliferation, migration, invasion and apoptosis. Thus, FTX may represent a potential biomarker for the diagnosis, treatment and prognosis of thyroid cancer.

Exogenous application of CLAVATA3 (CLV3)/EMBRYO SURROUNDING REGION (CLE) peptides suppresses protophloem differentiation and leads to the consumption of the proximal root meristem. However, the exact CLE peptides and the corresponding receptor complex regulating protophloem differentiation have not been clarified yet. Through expression pattern and phylogenetic analyses, CLE25/26/45 were identified as candidate peptides. Further genetic analyses, physiological assays, and specific protophloem marker observations indicated that CLE25/26/45, BARELY ANY MERISTEM1/3 (BAM1/3), and CLV3 INSENSITIVE KINASES (CIKs) are involved in regulating protophloem differentiation. The cle25 26 45 and cik2 3 4 5 6 mutation can greatly rescue the root defects of brevis radix (brx) and octopus (ops) mutants. The protophloem differentiation and proximal root meristem consumption of clv1 bam1 3 and cik2 3 4 5 6 were insensitive to CLE25/26/45 treatments. cle25 26 45, clv1 bam1 3, and cik2 3 4 5 6 displayed similar premature protophloem. In addition, CLE25/26/45 induced the interactions between BAMs and CIKs in vivo. Furthermore, CLE25/26/45 enhanced the phosphorylation levels of CIKs, which were greatly impaired in clv1 bam1 3 mutant. Our work clarifies that the CLE25/26/45-BAM1/3-CIK2/3/4/5/6 signaling module genetically acts downstream of BRX and OPS to suppress protophloem differentiation.

A functional piezoelectric kirigami monitors the joint motions for the prevention of musculoskeletal disorders., The prevention of work-related upper extremity musculoskeletal disorders (MSDs; e.g., neck pain and shoulder fatigue) requires frequent exercises of neck and shoulder that primarily rely on the assistance of joint motion monitoring devices. However, most available wearable healthcare sensors are rigid, bulky, and incapable of recognizing the full range of human motions. Here, we propose a kirigami-structured highly anisotropic piezoelectric network composite sensor that is able to monitor multiple information of joint motions, including bending direction, bending radius, and motion modes, and to distinguish them simultaneously within one sensor unit. On the basis of the modified template-assisted processing method, we design a functional piezoceramic kirigami with a honeycomb network structure that is stretchable (~100% strain), highly sensitive (15.4 mV kPa−1), and highly anisotropic to bending directions (17.3 times from 90° to 0°). An integrated monitoring system is further established to alarm the prolonged sedentary behaviors, facilitating the prevention of upper extremity MSDs.

Accurate localization and identification of vertebrae from CT images is a fundamental step in clinical spine diagnosis and treatment. Previous methods have made various attempts in this task; however, they fail to robustly localize the vertebrae with challenging appearance or identify vertebra labels from CT images with a limited field of view. In this paper, we propose a novel two-stage framework, VertNet, for accurate and robust vertebra localization and identification from CT images. Our method first detects all vertebra centers by a weighted voting-based localization network. Then, an identification network is designed to identify the label of each detected vertebra in leveraging the synergy of global and local information. Specifically, a bidirectional relation module is designed to learn the global correlation among vertebrae along the upward and downward directions, and a continuous label map with dense annotation is employed to enhance the feature learning in local vertebra patches. Extensive experiments on a large dataset collected from real-world clinics show that our framework can accurately localize and identify vertebrae in various challenging cases and outperforms the state-of-the-art methods.

Background: Primary liver cancer, around 90% are hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. Summary: Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer (2017 Edition) in 2018, additional high-quality evidence has emerged with relevance to the diagnosis, staging, and treatment of liver cancer in and outside China that requires the guidelines to be updated. The new edition (2019 Edition) was written by more than 70 experts in the field of liver cancer in China. They reflect the real-world situation in China regarding diagnosing and treating liver cancer in recent years. Key Messages: Most importantly, the new guidelines were endorsed and promulgated by the Bureau of Medical Administration of the National Health Commission of the People’s Republic of China in December 2019.

Hepatocellular carcinoma (HCC) is one of the most common cancers with the highest morbidity and mortality. It is necessary to develop new anti-liver cancer drugs. Itraconazole is a popular systemic anti-fungal drug with a strong anti-tumor effect. However, so far, it is not clear whether itraconazole has specific anti-tumor effect on liver cancer. The purpose of this study was to investigate itraconazole resistant effect of liver cancer and to explore its potential anti-cancer mechanism. The effect of itraconazole on the proliferation of liver cancer cells was studied with MTT assay. Flow cytometry was used to determine the effect of itraconazole on apoptosis, cell cycle distribution, changes in intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP). In addition, after DAPI staining, nuclear morphological changes were observed under the fluorescent microscope, and the release of lactate dehydrogenase (LDH) was measured using the microplate reader. Finally, the expressions of proteins related to the anti-tumor signaling pathway were determined by Western blotting. The results showed that itraconazole significantly inhibited the proliferation of HepG2 and Bel-7405 cells. In addition, the data showed that itraconazole induced apoptosis in HepG2 cells, increased the production of ROS, blocked cell cycle, and decreased MMP. Furthermore, itraconazole inhibited HCC cell growth and promoted apoptosis through the Hh, Wnt/catenin, AKT/mTOR/S6K, ROS and death receptor pathways. Finally, we come to the conclusion that itraconazole exerts anti-liver cancer effect, and has potential for use as a new drug for liver cancer in clinic.

Matrine (MT) is a naturally occurring alkaloid and an bioactive component of Chinese herbs, such as Sophora flavescens and Radix Sophorae tonkinensis. Emerging evidence suggests that MT possesses anti-cancer, anti-inflammatory, anti-oxidant, antiviral, antimicrobial, anti-fibrotic, anti-allergic, antinociceptive, hepatoprotective, cardioprotective, and neuroprotective properties. These pharmacological properties form the foundation for its application in the treatment of various diseases, such as multiple types of cancers, hepatitis, skin diseases, allergic asthma, diabetic cardiomyopathy, pain, Alzheimer’s disease (AD), Parkinson’s disease (PD), and central nervous system (CNS) inflammation. However, an increasing number of published studies indicate that MT has serious adverse effects, the most obvious being liver toxicity and neurotoxicity, which are major factors limiting its clinical use. Pharmacokinetic studies have shown that MT has low oral bioavailability and short half-life in vivo. This review summarizes the latest advances in research on the pharmacology, toxicology, and pharmacokinetics of MT, with a focus on its biological properties and mechanism of action. The review provides insight into the future of research on traditional Chinese medicine.

Oxidative stress-induced dysfunction or apoptosis in retinal pigment epithelial (RPE) cells is an important cause of dry age-related macular degeneration (AMD). Although phillyrin has been shown to exert significant antioxidant effects, the underlying mechanism of action remains unclear. The purpose of this study was to investigate the protective effect of phillyrin on hydrogen peroxide- (H2O2-) induced oxidative stress damage in RPE cells and the potential mechanism involved. It was found that phillyrin significantly protected RPE cells from H2O2 cytotoxicity. Furthermore, phillyrin alleviated oxidative stress-induced apoptosis via inhibition of endogenous and exogenous apoptotic pathways. Compared with the H2O2-treated group, the expressions of cleaved caspase-3, cleaved caspase-9, cleaved polymerase (PARP), death receptor Fas, and cleaved caspase-8, as well as Bax/Bcl-2 ratio were decreased in RPE cells after the phillyrin intervention. In addition, phillyrin reversed the oxidative stress-induced reductions in superoxide dismutase (SOD) and glutathione (GSH) levels and annulled the elevations in reactive oxygen species (ROS) and malondialdehyde (MDA), thereby restoring oxidant-antioxidant homeostasis. Phillyrin treatment upregulated the expressions of cyclin E, cyclin-dependent kinase 2 (CDK2), and cyclin A and downregulated the expressions of p21 and p-p53, thereby reversing the G0/G1 cell cycle arrest in H2O2-treated RPE cells. Pretreatment with phillyrin also increased the expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2), total Nrf2, heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductases-1 (NQO-1) in RPE cells and inhibited the formation of Kelch-like ECH-associated protein 1 (Keap1)/Nrf2 protein complex. Thus, phillyrin effectively protected RPE cells from oxidative stress through activation of the Nrf2 signaling pathway and inhibition of the mitochondria-dependent apoptosis pathway.

Scope Tea, made from the plant Camellia sinensis, is known to have anti-diabetes effects and different mechanisms of action are proposed. Kidney is a vital organ in managing water reabsorption and glucose metabolism, and is greatly influenced by diabetes. The present study investigates the effects of tea administration on water reabsorption and gluconeogenesis in the kidney of diabetic mice. Methods and results Db/db mice are given tea infusion as drinking fluid when they begin to exhibit hyperglycemia. It is found that green tea or black tea infusion potently elevates renal proteins vital for water reabsorption, including protein kinase C-α, aquaporin 2, and urea transporter-A1, as well as increases trafficking of these proteins to apical plasma membrane where they exert water reabsorption function. The treatment also downregulates renal gluconeogenic enzymes, including glucose-6-phosphatase-α and phosphoenolpyruvate carboxykinase. Associated with these biochemical changes are the rectified polyuria, polydipsia, polyphagia, and hyperglycemia, all symptoms of diabetes. Conclusions For the first time, the present study demonstrates that tea has robust effects in enhancing kidney water reabsorption proteins and downregulating gluconeogenic enzymes in db/db mice. It remains to be investigated whether such beneficial effects of tea occur in humans.

Testate amoebae are widely distributed in natural ecosystems and play an important role in the material cycle and energy flow. However, community assembly of testate amoebae is not well understood, especially with regard to the relative importance of the stochastic and deterministic processes over time. In this study, we used Illumina high-throughput sequencing to explore the community assembly of testate amoebae from surface waters in two reservoirs of subtropical China over a seven-year period. Majority of testate amoebae belonged to the rare taxa because their relative abundances were typically lower than 0.01% of the total eukaryotic plankton community. The testate amoeba community dynamics exhibited a stronger interannual than seasonal variation in both reservoirs. Further, species richness, rather than species turnover, accounted for the majority of community variation. Environmental variables explained less than 20% of the variation in community composition of testate amoebae, and the community assembly appeared to be strongly driven by stochastic processes. Based on the Sloan neutral community model, it was found that neutral processes explained more than 65% of community variation. More importantly, the Stegen null model analysis showed that the stochastic processes (e.g., ecological drift) explained a significantly higher percentage of community assembly than deterministic processes over seven years, although deterministic processes were more influential in certain years. Our results provide new perspectives for understanding the ecological patterns, processes and mechanisms of testate amoeba communities in freshwater ecosystems at temporal scale, and have important implications for monitoring plankton diversity and protecting drinking-water resources.

Objectives: To establish a radiomic algorithm based on grayscale ultrasound images and to make preoperative predictions of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients. Methods: In this retrospective study, 322 cases of histopathologically confirmed HCC lesions were included. The classifications based on preoperative grayscale ultrasound images were performed in two stages: (1) classifier #1, MVI-negative and MVI-positive cases; (2) classifier #2, MVI-positive cases were further classified as M1 or M2 cases. The gross-tumoral region (GTR) and peri-tumoral region (PTR) signatures were combined to generate gross- and peri-tumoral region (GPTR) radiomic signatures. The optimal radiomic signatures were further incorporated with vital clinical information. Multivariable logistic regression was used to build radiomic models. Results: Finally, 1,595 radiomic features were extracted from each HCC lesion. At the classifier #1 stage, the radiomic signatures based on features of GTR, PTR, and GPTR showed area under the curve (AUC) values of 0.708 (95% CI, 0.603–0.812), 0.710 (95% CI, 0.609–0.811), and 0.726 (95% CI, 0.625–0.827), respectively. Upon incorporation of vital clinical information, the AUC of the GPTR radiomic algorithm was 0.744 (95% CI, 0.646–0.841). At the classifier #2 stage, the AUC of the GTR radiomic signature was 0.806 (95% CI, 0.667–0.944). Conclusions: Our radiomic algorithm based on grayscale ultrasound images has potential value to facilitate preoperative prediction of MVI in HCC patients. The GTR radiomic signature may be helpful for further discriminating between M1 and M2 levels among MVI-positive patients.

Polygonum multiflorum Thunb. (PM), called Heshouwu in China, is a popular Chinese medicine in clinical practice. Several clinical studies have been conducted to evaluate the traditional therapeutic claims and to study the potential therapeutic activity of PM in dyslipidemia and neurodegenerative diseases, highlighting available clinical evidence. In recent years, reports on clinical adverse reactions of Raw Radix P. multiflorum (RPM) and P. multiflorum Praeparata (PMP) have been on the increase, especially with respect to liver injury. Most liver injury cases had been assessed for causality using RUCAM (Roussel Uclaf Causality Assessment Method) in this paper. However, the components of PM responsible for the reported hepatotoxic effects have not yet been identified. Moreover, many of the reports are contradictory, while studies on the mechanism involved in PM-induced liver damage are not comprehensive. This study was aimed at reviewing the status of research on liver injury due to PM, including clinical characteristics, risk factors, material basis research and mechanism of action, with a view to understanding PM-induced hepatotoxicity, and taking reasonable and effective measures to prevent it. In short, quality control is still one of the major safety problems in TCM drug safety concerns. The model of safety monitoring and risk management of PM drugs is not yet developed. Indeed, the characteristics and risk factors associated with PM require both proper understanding and control of the risk by strengthening standardization of clinical applications, basic science research, quality control in manufacturing, active monitoring methodology and enhancement of international communication and cooperation. Measures should also be encouraged and implemented to promote healthy development of the TCM industry.

Tubular adenoma of common bile duct (CBD) is an extremely rare benign extrahepatic bile duct adenoma. We report a case of surgery and histopathological proved CBD tubular adenoma. A 69-year-old man was admitted to the hospital for yellow urine for one month. Clinical, radiological and laboratory results were analyzed. Medical literature in PubMed pertaining to similar cases was reviewed. A solid mass was detected in the distant part of CBD, with dilation of the extrahepatic and intrahepatic bile duct by ultrasound, contrast enhanced ultrasound (CEUS), computer tomography (CT) and magnetic resonance imaging (MRI). It showed heterogeneous enhancement both in contrast-enhanced CT, MRI and CEUS. After operation, pathological findings indicated a tubular adenoma of CBD. Our case highlighted the fact that tubular adenoma of CBD was demonstrated as a homogeneous mass in the distant part of CBD.

Full-thickness skin damage is a server issue and sometimes even dangerous to life. Many researches have been done toward full-thickness wound dressing. In this study, we demonstrated a facile and one-step procedure of SIS bilayer wound dressing. The top layer could protect the wound from bacterial infection and provide a moist environment suitable for wound healing, while the cryogel layer could promote cell proliferation. The SIS bilayer wound dressing has sufficient mechanical properties to protect wound from second damage and can maintain a moist environment for cell proliferation and migration at wound site. Bacterial permeation testing demonstrated that the bilayer scaffold had high efficiency in blocking bacteria at the wound site. In vivo tests and qRT-PCR results revealed that the bilayer group possessed a higher tendency toward keratinocyte proliferation and migration. The SIS bilayer has a high potential to use as full-thickness wound dressing.

Low aqueous solubility and intestinal permeability limit the oral chemotherapy efficacy of paclitaxel (PTX). Traditional nanodrug delivery systems show excellent aqueous solubility improved ability of PTX. However, gastrointestinal (GI) mucus limits the improvement of intestinal permeability in traditional nanodrug delivery systems. A novel mucus adhesion- and penetration-functionalized chitosan-thioglycolic acid-Pluronic F127 (CS-TGA-PF) liposome system was developed for PTX oral delivery. The optimized formulation of PTX-loaded CS-TGA-PF liposomes showed particle size of 121.4 nm and zeta potential of 50.2 mV. CS-TGA-PF liposomes were more stable than unmodified liposomes and demonstrated a sustained-release manner of PTX incubated in simulated gastric fluid and intestinal fluid. CS-TGA-PF liposomes absorbed a three-fold amount of mucin compared with that of unmodified liposomes, which would prolong the residence time of liposomes on the mucosal surface in the intestinal tract. The intestinal mucus adhesion- and penetration-enhanced efficacy of CS-TGA-PF liposomes for intestinal PTX delivery was studied by observing the intestinal absorption and distribution. Results exhibited increased liposome uptake by the GI mucosa and improved drug intestinal absorption. In conclusion, the dual functional CS-TGA-PF liposomes with mucus adhesion- and permeation-enhanced properties could be used as a promising nanodrug delivery system for PTX oral delivery.

This paper aims to build an artificial intelligence (AI) architecture for automated extraction of learned-from-data image features from contrast-enhanced ultrasound (CEUS) videos and to evaluate the AI architecture for classification between benign and malignant cervical lymph nodes. An AI architecture for CEUS feature extraction and classification was constructed by using the point-wise gated Boltzmann machine (PGBM). The PGBM consisted of task-relevant and task-irrelevant hidden units for both feature learning and feature selection, and the task-relevant units were connected to the support vector machine (SVM) to yield the likelihood for classification. The synthetic minority over-sampling technique was used to improve the classification ability for an unbalanced data set. Experimental evaluation was performed with the five-fold cross validation on a database of 127 lymph nodes (39 benign and 88 malignant) from 88 patients. The SVM likelihood exhibited a significant difference between benign and malignant cervical lymph nodes (0.74±0.21 versus 0.33±0.28, p

BACKGROUND Previous research showed that Jin-Fu-An decoction has a significant effect on lung cancer. However, it remains unclear whether p120ctn and its transcription factor Kaiso play a role in lung cancer cell proliferation, adhesion, migration, and metastasis. MATERIAL AND METHODS Proliferation inhibition was detected by CCK-8 assay. The migration and invasion were detected using Transwell assay. The location and expression of p120ctn and Kaiso were monitored by immunofluorescence staining. The expression changes of p120ctn, its isoform 1A, its S288 phosphorylation, and Kaiso were measured by Western blot assay. RESULTS The lung cancer cell line H1650 administered Jin-Fu-An decoction had significantly reduced the growth in dose-dependent and time-dependent manners. Migration and metastasis were significantly inhibited by application of Jin-Fu-An decoction in a dose-dependent manner. Additionally, Jin-Fu-An decoction decreased the expressions of p120ctn, its isoform 1A, and its S288 phosphorylation, but the protein level of Kaiso was elevated. CONCLUSIONS Jin-Fu-An decoction inhibits the proliferation, adhesion, migration, and metastasis though down-regulation of p120ctn or its isoform 1A expression, mediating the up-regulation of Kaiso. The underlying mechanism of Jin-Fu-An decoction might involve targeting the lower expression of p120ctn S288 phosphorylation, which suggests that Jin-Fu-An decoction may be a potential therapeutic measure as prevention and control of recurrence and metastasis of lung cancer.

The present study evaluated the changes of taste profiles, taste active indicators, and antioxidant activity in Monascus rice vinegar during the solid-state fermentation process, as well as their potential relationships. The results showed that the contents of antioxidant components and antioxidant activity increased with fermentation time. According to the taste active value (TAV) evaluation, seven organic acids and four free amino acids (FAAs) with high TAVs were considered as taste active indicators. The correlation analysis between antioxidant activity and major antioxidant compounds in Monascus rice vinegar followed the order: FAAs＞total phenols＞total flavonoids＞organic acids. Further analysis revealed that seven key components including acetic acid, lactic acid, tartaric acid, succinic acid, Glu, Ala, and Val were taste active indicators of antioxidant activity, which had significant effects on the taste characteristic and antioxidant activity in Monascus rice vinegar. Thus, our findings would provide references to regulate the antioxidant characteristic of Monascus rice vinegar through the key taste active indicators, and would provide new insights to further explore the development of new vinegar-based functional foods.

While complete dental models are crucial for digital dentistry, current technologies mostly focus on the 3D dental crown but overlook the dental gum that is important for applications in orthodontics and prosthodontics. To reconstruct the complete dental models with visually realistic geometry from the given crown data, we propose to combine the implicit function representation with the self-attention mechanism. Recent studies have shown that the implicit function is an effective 3D representation for shape completion. However, existing methods fail in dealing with dental models with complex shapes and details, because the convolution and linear operations adopted in their networks are inefficient for modeling long-range dependencies or hard to maintain detailed geometry of the shapes. Therefore, we propose to introduce self-attention to the implicit function network for the first time and use it to effectively capture non-local features at different levels. Extensive ablation studies were conducted to validate the efficiency of our method. Quantitative and qualitative comparisons demonstrate that the feature extracted by our network is more expressive and thus leads to better dental model completion and reconstruction results.

Background Exercise can reduce the coronary artery disease (CAD) incidence. MiRNA-20a has been reported to distinctly expressed after sustain physical activity. However, its expression and regulation pattern in CAD model with or without exercise has not been reported. Objective In present study, we aim to investigate regulatory mechanism of miR-20a in exercise-associated reduced-CAD incidence and miR-20a-dependent signaling pathways. Methods Eight weeks old male ApoE/LDLR double knock out mice were recruited for this study. CAD model was established in mice fed with or without western diet and cholesterol levels were measured using detection kit as well as fast protein liquid chromatography. Relative mRNA levels were determined using quantitative RT-PCR while the protein levels were analyzed using western blotting. Luciferase assay was used to determine the miRNA binding site on target genes. CCK-8 assay and flow cytometry (FCM) were used for assessing the proliferative and apoptotic rate. Results Overall cholesterol level was significantly increased in CAD model group, compared to normal control group. Expression of miR-20 was significantly lower in CAD group where the VEGF and PTEN were upregulated, compared to non-CAD group. Increased miR-20a was induced after exercise in CAD model group, and miR-20a agomir group. Overexpression of miR-20a decreased the expression level of ET-1, TxA2, ANGII, PTEN and increased the eNOS, PGI2, and VEGF, at both transcriptional and translational levels. In vitro examination further confirmed these findings in human umbilical vein endothelial cells (HUVEC). MiR-20a specifically binds to the 3′UTR of PTEN and mediated the cell survival and proliferation through activating the PI3K/Akt signaling pathways. Conclusion MiRNA-20a may have great potential as therapeutic target for CAD, since its participation can induce alteration of functional genes as well as PTEN, which is specifically targeted by miR-20a, and promote the survival and proliferation of vein endothelial cells.

In this study, lentivirus-mediated RNA interference (RNAi) was applied to inhibit latent membrane protein 2A (LMP2A) gene expression, in order to explore the effects of LMP2A silencing on the growth of an Epstein-Barr virus-associated gastric carcinoma (EBVaGC) cell line in vitro. Lentivirus-mediated RNAi technology was employed to specifically knock down the LMP2A gene in the EBV-positive gastric carcinoma cell line GT38. After infection, reverse transcription-quantitative polymerase chain reaction, western blotting, flow cytometry and colony formation assays were conducted to evaluate the expression of LMP2A and the biological behavior of the GT38 cell line in vitro. The results showed that the expression of the LMP2A gene was clearly downregulated in the infected cells, which indicated that a highly efficient and stable lentivirus vector was successfully constructed. In the GT38 cells in which the expression of LMP2A was downregulated, the proliferation and colony formation of the cells was significantly inhibited. In addition, it was found that the cell cycle of the GT38 cells was arrested in the G0/G1 phase and the apoptosis rate was increased. These results indicate that lentivirus-mediated RNAi knockdown of LMP2A inhibits the growth of the EBVaGC cell line GT38 in vitro, and suggests that LMP2A is a potential target for gene therapy in the treatment of EBVaGC.

Background: To evaluate the accuracy of radiomics algorithm based on original radio frequency (ORF) signals for prospective prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) lesions. Methods: In this prospective study, we enrolled 42 inpatients diagnosed with HCC from January 2018 to December 2018. All HCC lesions were proved by surgical resection and histopathology results, including 21 lesions with MVI. Ultrasound ORF data and grayscale ultrasound images of HCC lesions were collected before operation for further radiomics analysis. Three ultrasound feature maps were calculated using signal analysis and processing (SAP) technology in first feature extraction. The diagnostic accuracy of model based on ORF signals was compared with the model based on grayscale ultrasound images. Results: A total of 1,050 radiomics features were extracted from ORF signals of each HCC lesion. The performance of MVI prediction model based on ORF was better than those based on grayscale ultrasound images. The best area under curve, accuracy, sensitivity, and specificity of ultrasound radiomics in prediction of MVI were 95.01, 92.86, 85.71, and 100%, respectively. Conclusions: Radiomics algorithm based on ultrasound ORF data combined with SAP technology can effectively predict MVI, which has potential clinical application value for non-invasively preoperative prediction of MVI in HCC patients.

Rhizoma paridis is a popularly-used Chinese medicine in clinics, based on the pharmacodynamic properties of its saponin components. The four main saponins in Rhizoma paridis are designated saponins I, II, VI, and VII. At present, much attention is focused on the anticancer effect of Rhizoma paridis which is manifested in its cytotoxicity to various cancer cells. The purpose of this study was to investigate the hepatocellular toxicities of the four saponins in Rhizoma paridis and the relative intensities of their cytotoxic effects. It was found that the four saponins were cytotoxic to two types of hepatocytes-HL-7702 and HepaRG cells. The cytotoxicities of the four saponins to the two cell models were compared. One of the most cytotoxic saponins was Rhizoma paridis saponin I (PSI). This was used to determine the mechanism of hepatocellular toxicity. Results from MTT assays demonstrated that the four saponins induced apoptosis of the two hepatocyte models in a dose-dependent and time-dependent manner. In addition, fluorescent 4&prime, 6-diamidino-2-phenylindole (DAPI) staining was used to observe the morphological changes of HepaRG cells after saponin administration. Further, as the concentration increased, PSI-induced lactate dehydrogenase (LDH) release from HepaRG cells increased gradually. In addition, PSI enhanced the levels of reactive oxygen species (ROS) and blocked the S and G2 phases of the cell cycle in HepaRG cells. A western blot indicated that PSI upregulated the protein expression levels of p53, p21, and Fas. Furthermore, the PSI-induced changes in the p53 protein increased the Bax/bcl-2 ratio, resulting in enhancement of the release of mitochondrial cytochrome c, activation of caspases-3, -8, and -9, poly-ADP ribose polymerase (PARP), and ultimately apoptosis. Increased Fas protein activated caspase-8, which led to the activation of caspase-3 and its downstream PARP protein, resulting in cell apoptosis. These results indicate that PSI induced apoptosis in HepaRG cells through activation of ROS and death receptor pathways. The results obtained in this study suggest that the hepatocellular toxicity of saponins in Rhizoma paridis should be considered during the clinical application of this drug. In addition, they provide a reference for future anti-cancer studies on Rhizoma paridis.

Nowadays, people pay more attention to biomarkers that can predict clinical efficacy of immunotherapy for allergic rhinitis. As the only recognized aetiological treatment, the efficacy of allergen immunotherapy (AIT) has been proved by many studies. However, treatment success depends on compliance and persistence greatly, which can be impaired by the lengthy duration of AIT and socioeconomic status of patients. Besides, ineffectiveness is another factor that accounts for non-adherence. If the clinical efficacy can be predicted in the early stage of immunotherapy, it can help patients choose appropriate treatment plans, increase patient compliance and optimize the allocation of medical resources. This paper mainly focuses on five candidate biomarkers, the sIgE/tIgE ratio before treatment, serum inhibitory activity for IgE, decreased basophil activation, upregulation of Tregs and tolerogenic DCs, reviews the time when potential biomarkers can predict or monitor the efficacy of AIT, discusses the reason why these indicators could serve as efficacy biomarkers and interactions among potential biomarkers.

Peritoneal carcinomatosis has an extremely poor overall prognosis and remains one of the greatest oncologic challenges. Prior studies in mice show that sodium selenite administered intraperitoneally is highly effective in inhibiting cancer cells implanted in the peritoneal cavity. However, the pharmacological mechanism remains unclear. The present study revisited the therapeutic effect of selenite and elucidated its mechanism of action. We found that intraperitoneal delivery of selenite to cancer cells in the peritoneal cavity of mice rapidly and robustly killed the cancer cells, with a therapeutic efficacy higher than that of cisplatin. The action of selenite was associated with the following pharmacological mechanisms. 1) Favorable drug distribution: selenite increased selenium levels in the cancer cells by 250-fold, while in normal tissues only by 7-fold. 2) Optimal selenium form: selenite was converted in the cancer cells mainly into selenium nanoparticles (SeNPs), which are more efficient than selenite in producing reactive oxygen species (ROS). 3) Persistent hijacking of two pro-survival systems to generate ROS: selenite did not impair thioredoxin- and glutaredoxin-coupled glutathione systems, which facilitate SeNPs to generate ROS and caused severe organelle injury and apoptotic response in the cancer cells. Overall, these mechanisms tend to maximize the potential of selenite in producing ROS in cancer cells and underlie selenite as a candidate therapeutic agent for peritoneal carcinomatosis.

Lung-targeting sophoridine-loaded poly(lactide-co-glycolide) (PLGA) microspheres were constructed by a simple oil-in-oil emulsion-solvent evaporation method. The obtained microspheres were systematically studied on their morphology, size distribution, drug loading, encapsulation efficiency, in vitro release profile, and biodistribution in rats. The drug-loaded microparticles showed as tiny spheres under SEM and had an average size of 17 μm with 90% of the microspheres ranging from 12 to 24 μm. The drug loading and encapsulation efficiency were 65% and 6.5%, respectively. The in vitro drug release behavior of microspheres exhibited an initial burst of 16.6% at 4 h and a sustained-release period of 14 days. Drug concentration in lung tissue of rats was 220.10 μg/g for microspheres and 6.77 μg/g for solution after intraveneous injection for 30 min, respectively. And the microsphere formulation showed a significantly higher drug level in lung tissue than in other major organs and blood samples for 12 days. These results demonstrated that the obtained PLGA microspheres could potentially improve the treatment efficacy of sophoridine against lung cancer.

Keloids are fibroproliferative disorders characterized by the overabundant deposition of extracellular matrix (ECM), especially collagen and overgrowth of scar tissue in response to cutaneous injury. In this study, we isolated a selenium (Se)-containing polysaccharide (Se-ZGTP-I) from Ziyang green tea and explored its potential therapeutic effects on keloid fibroblasts formation. 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and annexin V/propidium iodide (PI) staining assays demonstrated that Se-ZGTP-I or neuron-glia 2 (NG2) short hairpin RNA (shRNA) significantly inhibited proliferation of human keloid fibroblasts via induction of apoptosis. Besides, the activation of caspase-3 and the subsequent cleavage of poly (ADP-ribose) polymerase (PARP) were observed in keloid fibroblasts following Se-ZGTP-I (200 and 400 μg/ml) or NG2 shRNA treatment. Moreover, Western blotting analysis showed that treatment of keloid fibroblasts with Se-ZGTP-I (200 and 400 μg/ml) or NG2 shRNA resulted in an increase of pro-apoptotic protein Bax expression and a decrease in expression levels of anti-apoptotic protein Bcl-2 and NG2. In addition, type I collagen biosynthesis and protein expression in keloid fibroblasts following TGF-β1 stimulation were decreased by Se-ZGTP-I (200 and 400 μg/ml) or NG2 shRNA management. Current findings imply that Se-ZGTP-I has a therapeutic potential to intervene and prevent keloid formation and other fibrotic diseases.