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Background. Tumor microenvironment (TME) takes a vital effect on the occurrence and development of cancer. Radix Rhei Et Rhizome (RRER, Da-Huang in pinyin), a classical Chinese herb, has been widely used in gastric cancer (GC) for many years in China. However, inadequate systematic studies have focused on the anti-GC effect of RRER in TME. This study intended to uncover the mechanism of it by network pharmacology. Methods. We collected compounds and targets of RRER from traditional Chinese medicine system pharmacology database and analysis platform (TCMSP) and SwissTargetPrediction. GC targets were obtained from GeneCards. Protein-protein interaction (PPI) network and RRER-GC-target network were built by STRING and Cytoscape 3.2.1. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed using Database for Annotation, Visualization, and Integrated Discovery (DAVID). Results. We obtained 92 compounds of RRER. A total of 10 key compounds and 20 key targets were selected by “RRER-GC-target network” topological analysis. GO analysis showed that the biological process mainly involved in response to the tumor necrosis factor, positive regulation of fibroblast proliferation, and DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest. Molecular functions included cyclin-dependent protein serine/threonine kinase activity, RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding, and transmembrane receptor protein tyrosine kinase activity. Cellular components mainly were centrosome, cell surface, and membrane. KEGG pathway enrichment results mainly involved in the p53 signaling pathway, estrogen signaling pathway, and regulation of lipolysis in adipocytes. Conclusion. This study explored the anti-GC mechanism of RRER from the perspective of TME based on network pharmacology, which contributed to the development and application of RRER.

Purpose This study aims to explore the characteristics and related factors of insomnia of patients after operation for gastric cancer. Methods A cross-sectional survey was carried out and finally 115 patients with insomnia after operation for gastric cancer were included. The general information, gastric cancer-related information, sleep quality, and other symptoms were investigated. Results ① The Pittsburgh sleep quality index score of most insomnia patients after gastric cancer surgery was 11-15 points, and the sleep quality rating was “poor”. ② The sleep quality of patients with insomnia after surgery for gastric cancer is related to the number of chemotherapy cycles, fatigue, and depression. ③ The probability of reduced sleep quality with the number of chemotherapy cycles >6 is 3.640 times that of ≤6. The probability of reduced sleep quality during moderate to severe fatigue was 4.390 times that of patients with no or mild fatigue. Conclusion Attention to related factors may be associated with improvement of sleep quality in patients with gastric cancer after surgery.

Background: Idiopathic congenital talipes equinovarus (ICTEV) is one of the most common congenital deformities of children, and dysplasia of the striated muscle may be one of the causes of ICTEV. P...

Background Non-small-cell lung cancer (NSCLC) is usually diagnosed at an advanced stage, and chemotherapy is the main treatment for this disease. Kanglaite injections (KLTi) have been widely used for the treatment of cancer in China. KLTi combined with chemotherapy could improve the short-term efficacy, quality of life, and performance status for NSCLC compared with chemotherapy alone. This trial aims to assess the long-term efficacy and safety of KLTi in combination with chemotherapy for the treatment of advanced NSCLC. Methods This will be an investigator-initiated multicenter open-label randomized controlled trial. We will randomly assign 334 eligible participants with stage IIIA-IV NSCLC to the treatment or control groups in a 1:1 ratio. Patients in both groups will be administered 4–6 cycles of first-line platinum-based double chemotherapy regimens. Patients with complete response, partial response, or stable disease after 4–6 cycles will receive non-platinum single-agent chemotherapy. Patients in the treatment group are to receive intravenous KLTi 200 ml per day continuously for 14 days, commencing on the first day of chemotherapy. The treatment will be discontinued at the time of disease progression or until unacceptable toxicity is noted. The follow-up will be conducted every 2 months until death, loss of follow-up, or 12 months from randomized enrollment. The primary outcome will be progression-free survival (PFS). The secondary outcomes will be the objective response rate, 1-year survival rate, quality of life, living ability, and blood lipids. The safety outcome will be the rate of adverse events. Discussion This study will be the first randomized controlled trial in which PFS is used as the primary outcome to test whether KLTi combined with first-line chemotherapy has superior efficacy and reduced toxicity compared to chemotherapy alone in advanced NSCLC. This will also be the first clinical study to observe the effects of KLTi on blood lipids. Trial registration ClinicalTrials.gov NCT03986528. Prospectively registered on 30 May 2019.

Bone fracture is one of the most common injuries. Despite the high regenerative capacity of bones, failure of healing still occurs to near 10% of the patients. Herein, we aim to investigate the modulatory role of neurofibromatosis type I gene (NF1) to osteogenic differentiation of bone marrow–derived mesenchymal stem cells (BMSCs) and new bone formation after fracture in a rat model. We studied the NF1 gene expression in normal and non‐union bone fracture models. Then, we evaluated how NF1 overexpression modulated osteogenic differentiation of BMSCs, autophagy activity, mTORC1 signalling and osteoclastic bone resorption by qRT‐PCR, Western blot and immunostaining assays. Finally, we injected lentivirus‐NF1 (Lv‐NF1) to rat non‐union bone fracture model and analysed the bone formation process. The NF1 gene expression was significantly down‐regulated in non‐union bone fracture group, indicating NF1 is critical in bone healing process. In the NF1 overexpressing BMSCs, autophagy activity and osteogenic differentiation were significantly enhanced. Meanwhile, the NF1 overexpression inhibited mTORC1 signalling and osteoclastic bone resorption. In rat non‐union bone fracture model, the NF1 overexpression significantly promoted bone formation during fracture healing. In summary, we proved the NF1 gene is critical in non‐union bone healing, and NF1 overexpression promoted new bone formation after fracture by enhancing autophagy and inhibiting mTORC1 signalling. Our results may provide a novel therapeutic clue of promoting bone fracture healing.

Tuberculosis (TB) is one of the most prevalent infections. However, anti-TB drugs induce adverse liver injury in up to 40% of patients. Studies on candidate genes have suggested that single-nucleotide polymorphisms account for only a small contribution to the occurrence of anti-TB drug-induced liver injury (ATLI). In this study, whole-genome DNA methylation analysis was performed to systematically screen the ATLI-associated factors in a 49 vs. 51 case-control population. Next, 34 identified candidate probes were validated using MassARRAY in 296 cases and 288 controls. Our results indicated that 12 CpG sites on seven probes were positively associated with ATLI risk. Furthermore, we applied a CRISPR/Cas9-mediated methylation modifiable cell model and demonstrated that four CpGs in or near the gene region of AK2, SLC8A2, and PSTPIP2 affected the cellular response to rifampicin treatment. This study provides new biomarkers associated with ATLI occurrence.

Podocytes are essential components of the glomerular basement membrane. Epithelial-mesenchymal-transition (EMT) in podocytes results in proteinuria. Fibroblast growth factor 1 (FGF1) protects renal function against diabetic nephropathy (DN). In the present study, we showed that treatment with an FGF1 variant with decreased mitogenic potency (FGF1ΔHBS) inhibited podocyte EMT, depletion, renal fibrosis, and preserved renal function in two nephropathy models. Mechanistic studies revealed that the inhibitory effects of FGF1ΔHBS podocyte EMT were mediated by decreased expression of transforming growth factor β1 via upregulation of PPARγ. FGF1ΔHBS enhanced the interaction between PPARγ and SMAD3 and suppressed SMAD3 nuclei translocation. We found that the anti-EMT activities of FGF1ΔHBS were independent of glucose-lowering effects. These findings expand the potential uses of FGF1ΔHBS in the treatment of diseases associated with EMT.

As a classically known mitogen, fibroblast growth factor 1 (FGF1) has been found to exert other pleiotropic functions such as metabolic regulation and myocardial protection. Here, we show that serum levels of FGF1 were decreased and positively correlated with fraction shortening in diabetic cardiomyopathy (DCM) patients, indicating that FGF1 is a potential therapeutic target for DCM. We found that treatment with a FGF1 variant (FGF1∆HBS) with reduced proliferative potency prevented diabetes-induced cardiac injury and remodeling and restored cardiac function. RNA-Seq results obtained from the cardiac tissues of db/db mice showed significant increase in the expression levels of anti-oxidative genes and decrease of Nur77 by FGF1∆HBS treatment. Both in vivo and in vitro studies indicate that FGF1∆HBS exerted these beneficial effects by markedly reducing mitochondrial fragmentation, reactive oxygen species (ROS) generation and cytochrome c leakage and enhancing mitochondrial respiration rate and β-oxidation in a 5’ AMP-activated protein kinase (AMPK)/Nur77-dependent manner, all of which were not observed in the AMPK null mice. The favorable metabolic activity and reduced proliferative properties of FGF1∆HBS testify to its promising potential for use in the treatment of DCM and other metabolic disorders.

Speech classification has been widely used in many speech-related applications. However, the complexity of speech classification tasks often exceeds the scope of non-experts, the off-the-shelf speech classification methods are urgently needed. Recently, the automatic speech classification (AutoSpeech) without any human intervention has attracted more and more attention. The practical AutoSpeech solution should be general and can automatically handle classification tasks from different domains. Moreover, AutoSpeech should improve not only the final performance but also the any-time performance especially when the time budget is limited. To address these issues, we propose a three-stage any-time learning algorithm framework called Progressive AutoSpeech for automatic speech classification under a given time budget. Progressive AutoSpeech consists of the fast stage, enhancement stage, and exploration stage. Each stage uses different models and features to ensure generalization. Additionally, we automatically construct ensembles of top-k prediction results to improve the robustness. The experimental results reveal that Progressive AutoSpeech is effective and efficient for a wide range of speech classification tasks and can achieve the best ALC score.

Background: Breast cancer is the most common malignancy in women worldwide. Compared with other malignant tumors, breast cancer patients have a higher incidence of depression and other psychiatric symptoms. The purpose of this meta-analysis was to determine the association between long-term survival and depression in patients with breast cancer. Methods: This review will include cohort studies only. Multiple databases will be searched by 2 independent reviewers, including PubMed, EMBASE, the Cochrane Library, and PsycINFO. The language of studies should be English and Chinese, published from inception to the September 2020. Two independent reviewers will carry out literature screening, research selection and data extraction. Revman5.3 software will be used to generate funnel map, assess heterogeneity, make the subgroup analysis and complete sensitivity analysis. Results: This review will summarize the available evidence to determine the association between depression and survival in breast cancer patients. Conclusion: The results of this study will provide reference for the development of comprehensive treatment for breast cancer, and will promote further research. PROSPERO registration number: CRD42020202200

Prostate cancer shows remarkable clinical heterogeneity, which manifests in spatial and clonal genomic diversity. By contrast, the transcriptomic heterogeneity of prostate tumours is poorly understood. Here we have profiled the transcriptomes of 36,424 single cells from 13 prostate tumours and identified the epithelial cells underlying disease aggressiveness. The tumour microenvironment (TME) showed activation of multiple progression-associated transcriptomic programs. Notably, we observed promiscuous KLK3 expression and validated the ability of cancer cells in altering T-cell transcriptomes. Profiling of a primary tumour and two matched lymph nodes provided evidence that KLK3 ectopic expression is associated with micrometastases. Close cell-cell communication exists among cells. We identified an endothelial subset harbouring active communication (activated endothelial cells, aECs) with tumour cells. Together with sequencing of an additional 11 samples, we showed that aECs are enriched in castration-resistant prostate cancer and promote cancer cell invasion. Finally, we created a user-friendly web interface for users to explore the sequenced data.

On account of the acquired drug resistance, the potency of cisplatin-based chemotherapy is far from satisfactory in rectal cancer. Increasing evidence has highlighted the crucial function of aberrantly expressed lncRNAs on the cisplatin resistance in multiple cancers. This research was the first attempt to decipher the underlying function and mechanism of long intergenic non-protein coding RNA 461 (LINC00461) in rectal cancer and also its relation to cisplatin resistance of rectal cancer. Data from this study revealed that LINC00461 expression was upregulated in rectal cancer cells. LINC00461 depletion restrained rectal cancer progression and sensitized rectal cancer cells to cisplatin. Molecular mechanism assays testified that LINC00461 bound with miR-593-5p. Besides, miR-593-5p upregulation improved the sensitivity of rectal cancer cells to cisplatin. Additionally, cyclin D1 (CCND1) was manifested to be a downstream target of miR-593-5p. Furthermore, CCND1 upregulation could reverse the effect of LINC00461 downregulation on rectal cancer progression and cisplatin resistance of rectal cancer. To sum up, LINC00461 mediates cisplatin resistance of rectal cancer by targeting miR-593-5p/CCND1 axis, shedding new light on the treatment of rectal cancer.

Background Re-fracture is the most serious complication in congenital pseudarthrosis of the tibia (CPT). There are reports that children with small cross-sectional areas in the sections of the pseudarthrosis are more prone to re-fracture. Presently, preventing complications is a challenge. Increasing the cross-sectional area in healed segments may reduce the incidence of re-fracture. Purpose To elucidate the indications, surgical technique, and outcomes of combined surgery and 3-in-1 osteosynthesis in CPT with intact fibula. Methods We retrospectively assessed 17 patients with Crawford Type IV CPT with intact fibula (Type A) who were treated with combined surgical technique and 3-in-1 osteosynthesis between March 2014 and August 2015. The average age of the patients at the time of surgery was 3 years. Incidence of re-fracture, ankle valgus, proximal tibial valgus, and limb length discrepancy (LLD) were investigated over an average follow-up time of 47 months. Results Primary union was achieved in all patients. The average time for primary union was 4.9 months. Fifteen (88%) cases showed LLD with an average limb length of 1.6 cm; 6 (35%) cases exhibited tibial valgus with an average tibial valgus deformity of 7.8°; 2 cases had ankle valgus, wherein the ankle valgus deformity was 12° in one and 17° in another; and the cross-sectional area of the bone graft was enlarged to 1.74 times that of the tibia shaft. No case had re-fracture during the follow-up period. Movement of the ankle joint was restored in 16 patients with an average dorsiflexion of 22° and an average plantar flexion of 41°; the function of the ankle joint was normal. One patient had plantar flexion of 20° but did not have dorsiflexion. Conclusion Combined surgical technique with 3-in-1 osteosynthesis, which is primarily considered for bone union with a large cross-sectional area, results in a high primary union rate. This can provide satisfactory results in short-term follow-up when treating CPT with intact fibula (Type A).

Forensic entomology could provide valuable data for the minimum postmortem interval (PMImin) estimation and other relevant information, such as causes and circumstances of death. Some representatives of flesh flies are one of the dominant necrophagous insects during early stages of decomposition, demonstrating unique biological characteristics compared with other necrophagous flies. Moreover, they lead to global health concerns as carriers of various pathogenic micro-organisms, and dominantly result in the traumatic myiasis. Thus, sarcophagid flies are considered important in decomposition processes for PMImin estimation. However, the utility of sarcophagid flies has been seriously hampered by limited ecological, biological and taxonomic knowledge of them. The aim of this paper is to provide a brief review on the species, distribution and biological habit of forensically important sarcophagid flies. In addition, the relation between traumatic myiasis and flesh flies, molecular identification methods and developmental pattern of flesh flies are summarized.

Currently, the timing of surgery for congenital pseudarthrosis of the tibia (CPT) remains controversial. The aim of this study was to investigate the results of treatment of pseudarthrosis of the tibia in children younger than 3 years of age. A retrospective study was carried out to explore the relationship between postoperative complications and the age of surgery in children with CPT. The analysis was carried out on 42 patients with Crawford type IV CPT treated with a combined surgical technique between 2008 and 2012. Patients were divided into two groups according to their age: group A (3 years) and group B (3 years). The incidence rates of refracture, ankle valgus, tibial valgus, and limb-length discrepancy of the two groups were evaluated. Primary bone union was achieved in 28 out of 29 (97%) patients in group A and 12 out of 13 (92%) patients in group B (P0.05). In group A, six (21%) patients developed a refracture; 14 (48%) patients had ankle valgus with a mean degree of 11° (range: 5°-25°); 11 (38%) patients had tibial valgus with a mean tibial valgus deformity of 8.6° (range: 5°-20°); and 12 (41%) patients had limb-length discrepancy with a mean limb length of 2.9 cm (range: 0.5-4 cm). In group B, five (38%) patients developed refracture; seven (54%) patients had ankle valgus with a mean degree of 14° (range: 5°-30°); seven (54%) patients had tibial valgus with a mean tibial valgus deformity of 10.7° (range: 5°-20°); and 10 (77%) patients had limb-length discrepancy with a mean limb length of 2.8 cm (range: 1.5-3 cm). Groups A and B were significantly different in limb-length discrepancy (P=0.033). This study suggests that there is no need to defer surgery for pseudarthrosis of the tibia until the child is older than 3 years of age.

Disease comorbidity is the presence of one or more diseases along with a primary disorder, which causes additional pain to patients and leads to the failure of standard treatments compared with single diseases. Therefore, the identification of potential comorbidity can help prevent those comorbid diseases when treating a primary disease. Unfortunately, most of current known disease comorbidities are discovered occasionally in clinic, and our knowledge about comorbidity is far from complete. Despite the fact that many efforts have been made to predict disease comorbidity, the prediction accuracy of existing computational approaches needs to be improved. By investigating the factors underlying disease comorbidity, e.g., mutated genes and rewired protein-protein interactions (PPIs), we here present a novel algorithm to predict disease comorbidity by integrating multi-scale data ranging from genes to phenotypes. Benchmark results on real data show that our approach outperforms existing algorithms, and some of our novel predictions are validated with those reported in literature, indicating the effectiveness and predictive power of our approach. In addition, we identify some pathway and PPI patterns that underlie the co-occurrence between a primary disease and certain disease classes, which can help explain how the comorbidity is initiated from molecular perspectives.

Understanding the metabolic features of myocardial infarction (MI) is critical to its prevention and treatment. Here, we aimed to characterize the metabolic features of early MI using a tissue metabolomics method based on gas chromatography-mass spectrometry (GC-MS). Thirty-four pairs of infarcted myocardia and their matched non-infarcted myocardia were collected from 34 rats that underwent coronary artery ligation (CAL); their metabolic profiles were compared by GC-MS-based tissue metabolomics to characterize the metabolic features of MI. On the basis of differential metabolites, their diagnostic potential for MI was analyzed, and MI-related metabolic pathways were investigated. Serum samples before and post MI were used to validate the results obtained in myocardia. The metabolic profile of the infarcted myocardia was obviously different from that of the non-infarcted myocardia, as indicated by partial least squares discriminate analysis (PLS-DA) plots. Twenty-two metabolites were identified to be different between the infarcted myocardia and non-infarcted myocardia. These metabolic alterations reflect energy deficit, acidosis, oxidative stress, ionic imbalance, and cardiac injury post MI. Glutamine, glutamate, and lactate were confirmed to jointly confer a favorable potential for diagnosing MI, which can be well validated in serum.

Currently, there is a lack of effective therapeutic approaches to the treatment of chronic kidney disease (CKD) with irreversible deterioration of renal function. This study aimed to investigate the ability of mutant FGF1 (FGF1ΔHBS, which has reduced mitogenic activity) to alleviate CKD and to study its associated mechanisms. We found that FGF1ΔHBS exhibited much weaker mitogenic activity than wild-type FGF1 (FGF1WT) in renal tissues. RNA-seq analysis revealed that FGF1ΔHBS inhibited oxidative stress and inflammatory signals in mouse podocytes challenged with high glucose. These antioxidative stress and anti-inflammatory activities of FGF1ΔHBS prevented CKD in two mouse models: a diabetic nephropathy model and an adriamycin-induced nephropathy model. Further mechanistic analyses suggested that the inhibitory effects of FGF1ΔHBS on oxidative stress and inflammation were mediated by activation of the GSK-3β/Nrf2 pathway and inhibition of the ASK1/JNK signaling pathway, respectively. An in-depth study demonstrated that both pathways are under control of PI3K/AKT signaling activated by FGF1ΔHBS. This finding expands the potential uses of FGF1ΔHBS for the treatment of various kinds of CKD associated with oxidative stress and inflammation.

Background Congenital pseudarthrosis of the tibia (CPT) is a rare disease. Some patients present neurofibromatosis type 1 (NF1), while some others do not manifest NF1 (non-NF1). The etiology of CPT, particularly non-NF1 CPT, is not well understood. Here we screened germline variants of 75 CPT cases, including 55 NF1 and 20 non-NF1. Clinical data were classified and analyzed based on NF1 gene variations to investigate the genotype-phenotype relations of the two types of patients. Results Using whole-exome sequencing and Multiplex Ligation-Dependent Probe Amplification, 44 out of 55 NF1 CPT patients (80.0%) were identified as carrying pathogenic variants of the NF1 gene. Twenty-five variants were novel; 53.5% of variants were de novo, and a higher proportion of their carriers presented bone fractures compared to inherited variant carriers. No NF1 pathogenic variants were found in all 20 non-NF1 patients. Clinical features comparing NF1 CPT to non-NF1 CPT did not show significant differences in bowing or fracture onset, lateralization, tissue pathogenical results, abnormality of the proximal tibial epiphysis, and follow-up tibial union after surgery. A considerably higher proportion of non-NF1 patients have cystic lesion (Crawford type III) and used braces after surgery. Conclusions We analyzed a large cohort of non-NF1 and NF1 CPT patients and provided a new perspective for genotype-phenotype features related to germline NF1 variants. Non-NF1 CPT in general had similar clinical features of the tibia as NF1 CPT. Germline NF1 pathogenic variants could differentiate NF1 from non-NF1 CPT but could not explain the CPT heterogeneity of NF1 patients. Our results suggested that non-NF1 CPT was probably not caused by germline NF1 pathogenic variants. In addition to NF1, other genetic variants could also contribute to CPT pathogenesis. Our findings would facilitate the interpretation of NF1 pathogenic variants in CPT genetic counseling.

White spot syndrome virus (WSSV) is one of the major threats to shrimp aquaculture. It has been found that the signal transducer and activator of transcription (STAT) protein plays an important role in the antiviral immunity of shrimp with a WSSV infection. However, the mechanism that underlies the STAT-mediated antiviral responses in shrimp, against WSSV infection, remains unclear. In this work, based on the gene expression profiles of shrimp with an injection of WSSV and STAT double strand RNA (dsRNA), we constructed a gene co-expression network for shrimp and identified the gene modules that are possibly responsible for STAT-mediated antiviral responses. These gene modules are found enriched in the regulation of the viral process, JAK-STAT cascade and the regulation of immune effector process pathways. The gene modules identified here provide insights into the molecular mechanism that underlies the STAT-mediated antiviral response of shrimp, against WSSV.

This study aimed to investigate the relationship between postoperative complications and fibular integrity in congenital pseudarthrosis of the tibia (CPT) in children.A retrospective study was performed in 59 patients with Crawford type IV CPT who were treated with combined surgical technique from 2007 to 2011. The patients were divided into two groups, the CPT with fibular pseudarthrosis (group A) and CPT with intact fibula groups (group B), on the basis of fibula status after the union of CPT. The incidence rates of refracture, ankle valgus, tibial valgus, and limb length discrepancy in the two groups were investigated.In group A, 14 (36.8%) cases had refracture, 30 (78.9%) had ankle valgus; 27 (71%) exhibited tibial valgus with an average tibial valgus of 7° (6°-20°), and 24 (63.2%) had limb length discrepancy with an average limb length of 1.26 cm (0.6-4.4 cm). In group B, 2 (9.5%) cases had refracture, 11 (52.4%) had ankle valgus, 8 (42.9%) had tibial valgus with an average tibial valgus deformity of 2.9° (6°-13°), and 13 (61.9%) had limb length discrepancy with an average limb length of 1.48 cm (0.5-5 cm). Significant difference in refracture and ankle valgus was found between groups A and B (P0.05).After the union of CPT, patients with fibular pseudarthrosis showed higher incidence of refracture and ankle valgus than those with intact fibula. Attention should be paid to the presence of fibular pseudarthrosis when managing CPT.

Identifying biomarkers for accurate diagnosis and prognosis of diseases is important for the prevention of disease development. The molecular networks that describe the functional relationships among molecules provide a global view of the complex biological systems. With the molecular networks, the molecular mechanisms underlying diseases can be unveiled, which helps identify biomarkers in a systematic way. In this survey, we report the recent progress on identifying biomarkers based on the topology of molecular networks, and we categorize those biomarkers into three groups, including node biomarkers, edge biomarkers and network biomarkers. These distinct types of biomarkers can be detected under different conditions depending on the data available. The biomarkers identified based on molecular networks can provide more accurate diagnosis and prognosis. The pros and cons of different types of biomarkers as well as future directions to improve the methods for identifying biomarkers are also discussed.

Over the past decade, there has been a global trend toward a minimally invasive approach for thyroidectomy. Since endoscopic parathyroidectomy was first introduced in 1996,1 various endoscopic surgical procedures for the thyroid have been devised, including cervical, axillary, breast, and anterior chest approaches. In particular, a higher level of surgical technique is necessary in minimally invasive thyroidectomy because of no natural cavity that is an unfavorable circumstance to carry the surgery. The concept of a learning curve for an operation refers to the number of cases a surgeon needs to perform before the operative time and complication rate become reproducibly minimized.2 Few have addressed a learning curve for transareola single-site laparoendoscopic thyroidectomy (TASSET). We have documented the use of a TASSET technique.3–5 This study focused on the analysis of a learning curve in an attempt to determine how many surgeries must be performed before a surgeon feels confident and efficient in performing a TASSET. We evaluated the learning curve for TASSET based on a cumulative summation technique.

Anti-inflammation strategy is one of the proposed therapeutic approaches to hepatic fibrosis. IL-17 is critical in inflammation, but the role of IL-17 in liver fibrosis has not yet been elucidated. In this study, we investigate the role of IL-17 on bile duct ligation-induced liver injury and fibrosis in C57BL/6 mice. Animals were sacrificed at designated times, and serum and liver tissues were collected for analysis of liver function and serum IL-6, IL-1β, tumour necrosis factor-alpha (TNF-α) and transforming growth factor-β (TGF-β) levels. IL-17 blockade with anti-IL-17A mAb significantly improved liver function and decreased hepatocellular necrosis, pro-inflammatory cytokines, neutrophils and macrophages influx. Furthermore, CD3 + and CD8 + lymphocytes, neutrophils and macrophages were found to express IL-17, and neutrophils are the principal IL-17-producing cells after BDL-induced liver injury. These data indicated that IL-17 signal contributes to the pathogenesis of cholestatic liver injury and blocked of IL-17 could potentially benefit patients with cholestatic liver disease.

BACKGROUND Piperine has been reported to inhibit proliferation and induce apoptosis in various cancer cells. This study aimed to explore the efficacy and underlying mechanism of piperine in human gastric cancer. MATERIAL AND METHODS MTT assay was performed to examine the effect of piperine (concentrations of 0-300 μM) on the proliferation of human gastric cancer SNU-16 cells and normal human gastric epithelial GES-1 cells. Flow cytometry and Western blot were used to determine cell apoptosis and the expression level of protein (Cyto C, cleaved PARP, cleaved caspase-3, Bax, Bcl-2, Bad, Bcl-xl, PI3K, pPI3K, Akt, and pAkt), respectively. To further investigate the anti-tumor mechanism of piperine in SNU-16 cells, we used a small-molecule Akt activator SC79 in this study. The in vivo mechanism of piperine against gastric cancer was evaluated using a xenograft tumor model. RESULTS The results showed that piperine inhibited proliferation and induced apoptosis of SNU-16 cells. Piperine upregulated the protein expression of Bax, Bad, Cyto C, cleaved PARP, and cleaved caspase-3, but downregulated the protein expression of Bcl-2, Bcl-xl, pPI3k, and pAkt. However, SC79 reversed the function of piperine on the apoptosis-related proteins. An in vivo study revealed that, compared with the control group, the tumor volume of mice treated with piperine was significantly reduced. Piperine enhanced cleaved caspase-3 expression but decreased Ki-67 expression in a dose-dependent manner. Moreover, the nontoxicity effect of piperine was confirmed by H&E staining analysis in kidney and heart tissues of mice. CONCLUSIONS Our findings suggest that piperine inhibits proliferation and induces apoptosis of human gastric cancer cells through inhibition of the PI3K/Akt signaling pathway.

Background: Many research has indicated that some Chinese herb injections (CHIs) might be beneficial in combination with chemotherapy, however, with inconsistent results. Hence, the purpose of this network meta-analysis is to evaluate different CHIs plus cisplatin and gemcitabine (GP) with GP alone in terms of clinical efficacy and safety for treating patients with advanced NSCLC. Methods: A comprehensive systematic search of clinical randomized controlled trials (RCTs) published in the PubMed, Embase, Web of Science (ISI), Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure Database (CNKI), Chinese Scientific Journals Full-Text Database (VIP), Wanfang Database and China Biological Medicine Database (CBM) databases will be conducted to identify eligible studies up to the date of May 2020. The primary outcome measures objective response rate and adverse reactions (nausea and vomiting, leukopenia). The secondary outcome measures median survival time (MST), disease control rate, and quality of life. The methodological qualities, including the risk of bias, will be evaluated using the Cochrane risk of bias assessment tool, while confidence in the cumulative evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The network meta-analysis will be performed using WinBUGS 14 and Stata 15.1 software. Results: Based on the current evidence, the potential rank of the efficacy and safety of CHIs plus GP chemotherapy for advanced NSCLC will be assessed, and a prioritization regimen will be summarized. Conclusion: Evidence from this systematic review could be useful for patients, clinical practitioners, and guideline-makers to select an optimum proposal of CHIs plus GP for advanced NSCLC. Ethics and dissemination: It is not necessary for ethical approval because it is based on published studies. The protocol will be disseminated in a peer-reviewed journal or presented at a topic-related conference. PROSPERO registration number: CRD42020167142

Early effective identification of high-risk patients for acute pulmonary embolism (APE) contributes to timely treatment. The pulmonary artery obstruction index (PAOI) in computed tomography angiography (CTA) is a semi-quantitative observation index, commonly used to evaluate the severity of a patient’s condition. This study explores the ability of PAOI to assess the risk stratification of APE. Thirty patients with APE were analysed. They were classified according to the guidelines, and the PAOI and cardiovascular parameters were measured in CTA. The difference of PAOI between different risk stratification patients was compared, and the predictive value of the PAOI for high-risk stratification was evaluated by the receiver operating characteristic curve. The correlation between PAOI and cardiovascular parameters was also analysed by Spearman correlation analysis. The PAOI in low- and high-risk patients was (33.2 ± 18.6)% and (68.1 ± 11.8)% respectively, and the difference was statistically significant. The PAOI was strongly predictive for high-risk patients. The cut-off value was 52.5%, with a sensitivity of 100% and specificity of 81.0%. The PAOI was correlated with the main cardiovascular parameters. We conclude that the PAOI in CTA is helpful for assessing risk stratification in patients with APE, which contributes to the selection of both the treatment plan and prognostic evaluation.

Severe trauma can cause secondary multiple organ dysfunction syndrome and death. The absolute and relative concentrations of trace elements in both critical care and conventional treatment, which can lead to acute trace element deficiency, constitute an important mechanism of multiple organ dysfunction syndrome (MODS)/multiple organ failure (MOF).We investigated the changes in serum Cu, Zn, and Fe in early stage trauma of patients with the high injury severity score (ISS) and correlated the change in trace elements with ISS. Blood samples were collected within an hour of admittance and the patients were scored according to ISS. We collected clinical data records and ISS score values, and determined serum Fe, Zn, and Cu by inductively coupled plasma mass spectrometry.Compared with the control group, the serum Zn and Fe values of trauma patients were decreased. There was no significant difference in serum Cu between the patients and the control group. In the trauma group, the serum Zn and Fe were lower than that of the minor injury group, and the difference of Cu concentration was not statistically significant.Serum Zn and Fe levels in patients with multiple trauma fractures were significantly different than those in the normal group, suggesting that Zn and Fe need to be monitored in the early stage of trauma.

The current therapies for endometriosis are restricted by various side effects and treatment outcome has been less than satisfactory. Shaofu Zhuyu Decoction (SZD), a classic traditional Chinese medicinal (TCM) prescription for dysmenorrhea, has been widely used in clinical practice by TCM doctors to relieve symptoms of endometriosis. The present study aimed to investigate the effects of SZD on a rat model of endometriosis. Forty-eight female Sprague-Dawley rats with regular estrous cycles went through autotransplantation operation to establish endometriosis model. Then 38 rats with successful ectopic implants were randomized into two groups: vehicle- and SZD-treated groups. The latter were administered SZD through oral gavage for 4 weeks. By the end of the treatment period, the volume of the endometriotic lesions was measured, the histopathological properties of the ectopic endometrium were evaluated, and levels of proliferating cell nuclear antigen (PCNA), CD34, and hypoxia inducible factor- (HIF-) 1α in the ectopic endometrium were detected with immunohistochemistry. Furthermore, apoptosis was assessed using the terminal deoxynucleotidyl transferase (TdT) deoxyuridine 5′-triphosphate (dUTP) nick-end labeling (TUNEL) assay. In this study, SZD significantly reduced the size of ectopic lesions in rats with endometriosis, inhibited cell proliferation, increased cell apoptosis, and reduced microvessel density and HIF-1α expression. It suggested that SZD could be an effective therapy for the treatment and prevention of endometriosis recurrence.

Chrysomya nigripes (Diptera: Calliphoridae) is a blow fly species of forensic importance. Here we demonstrated the complete mitochondrial genome of this species for the first time. Phylogenetic analyses indicated that entire mitochondrial genome sequences can provide more useful information for distinguishing C. nigripes from the other species.

Main conclusion High-throughput sequencing and degradome analysis forCercis giganteaidentified 194 known miRNAs and 23 novel miRNAs with 61 targets. The comparison results of highly conserved miRNAs and non-conserved miRNAs implied thatC. giganteamiRNAs were subjected to the neutral evolution. MicroRNAs play a key role in post-transcriptionally regulating gene expression during plant growth, development and other various biological processes. Although numerous miRNAs have been identified and documented, to date, there are no reports on Cercis gigantea (C. gigantea) miRNAs. In this study, C. gigantea miRNAs and their target genes were investigated by extracting RNA from young roots, tender stems, young leaves, and flower buds of C. gigantea to establish a small RNA and a degradome library to further sequence. This study identified 194 known miRNAs belonging to 52 miRNA families and 23 novel miRNAs. Among these, 158 miRNAs from 27 miRNA families were highly conserved and existed in a plurality of plants. In addition, 60 different targets for 30 known families and one target for novel miRNA were identified by high-throughput sequencing and degradome analysis in C. gigantea. The comparison results revealed that highly conserved miRNAs have higher expression levels, more family members and more targets than non-conserved miRNAs, indicating that C. gigantea miRNAs were subjected to the neutral evolution. Meanwhile, these conserved miRNAs were also found to be involved in auxin signal transduction, regulation of transcription, and other developmental processes, which will help further understanding regulatory mechanisms of C. gigantea miRNAs. Electronic supplementary material The online version of this article (doi:10.1007/s00425-015-2389-y) contains supplementary material, which is available to authorized users.

Naked2 (NKD2), one member of Naked family, has been shown to negatively regulate Wnt/β-catenin signaling pathway. It has been recognized that NKD2 plays a vital role in cell homeostasis and prevention of tumorigenesis. However, NKD2 expression and its functional role in the brain in neuroinflammatory processes remain unclear. In our study, we investigated NKD2 distribution and role in lipopolysaccharide (LPS)-induced neuroinflammation rat model. The data indicated that NKD2 was up-regulated in LPS-injected brain, and the cellular localization of NKD2 was predominantly in cerebral cortical neurons. Furthermore, we treated primary neurons with conditioned media (CM) collected from LPS-stimulated mixed glial cultures (MGC). We detected that the up-regulation of NKD2 might be associated with the subsequent apoptosis in neurons. We also found knockdown NKD2 partially depressed the increase of cleaved caspase-3 and increased the reduction of β-catenin stimulated by MGC-CM. Taken together, these results suggested that NKD2 might be involved in neuronal apoptosis via the Wnt/β-catenin pathway during neuroinflammation in CNS. Our findings might provide a new therapeutic target for the prevention of neuroinflammation-involved neurological disorders.

Background/Aims: MicroRNAs (miRNAs) have been shown to participate in the development of pancreatic ductal adenocarcinoma (PDAC) by modulating multiple cellular processes. Increased miR-224 expression enhances proliferation and metastasis in human cancers. This study aimed to investigate the role of miR-224 and its underlying mechanism of action in PDAC. Methods: BrdU, MTT, and cell migration assays were performed to determine cell proliferation, viability, and migration, respectively. The binding sites of miR-224 were identified using a luciferase reporter system, whereas protein expression of target genes was determined by immunoblotting and immunofluorescence analyses. A BALB/c nude mouse xenograft model was used to evaluate the role of miR-224 in vivo. Results: We demonstrated that miR-224 expression was enhanced in PDAC cells and tissues, and was related to migration and proliferation. Noticeably, miR-224 overexpression promoted the proliferation, migration, and metastasis of Panc1 cells, while miR-224 inhibition had the reverse effect on PDAC cells. Moreover, we found that thioredoxin-interacting protein (TXNIP) is a target of miR-224. The results also indicated that miR-224 inversely regulated TXNIP by binding directly to its 3′-untranslated region, which resulted in the activation of hypoxia-inducible factor 1α (HIF1α). Further, either TXNIP re-expression or HIF1α depletion abolished the effects of miR-224 on the proliferation and migration of PDAC cells in vitro and in vivo. Regarding the relationship of TXNIP and HIF1α, we found that TXNIP mediated the nuclear export of HIF1α and its degradation by forming a complex with HIF1α. Conclusion: The miR-224-TXNIP-HIF1α axis may be useful in developing novel therapies for PDAC.

Cell state transition is one of the fundamental events in the development of multicellular organisms, and the transition trajectory path has recently attracted much attention. With the accumulation of large amounts of “-omics” data, it is becoming possible to get insights into the molecule mechanisms underlying the transitions between cell states. Here, we present CSTEA (Cell State Transition Expression Atlas), a webserver that organizes, analyzes and visualizes the time-course gene expression data during cell differentiation, cellular reprogramming and trans-differentiation in human and mouse. In particular, CSTEA defines gene signatures for uncharacterized stages during cell state transitions, thereby enabling both experimental and computational biologists to better understand the mechanisms of cell fate determination in mammals. To our best knowledge, CSTEA is the first webserver dedicated to the analysis of time-series gene expression data during cell state transitions. CSTEA is freely available at http://comp-sysbio.org/cstea/.

PURPOSE:Pedicle screw fixation in the upper cervical spine is a difficult and high-risk procedure. The screw is difficult to place rapidly and accurately, and can lead to serious injury of spinal cord or vertebral artery. The aim of this study was to design an individualized 3D printing navigation template for pedicle screw fixation in the upper cervical spine. METHODS:Using CT thin slices data, we employed computer software to design the navigation template for pedicle screw fixation in the upper cervical spine (atlas and axis). The upper cervical spine models and navigation templates were produced by 3D printer with equal proportion, two sets for each case. In one set (Test group), pedicle screws fixation were guided by the navigation template; in the second set (Control group), the screws were fixed under fluoroscopy. According to the degree of pedicle cortex perforation and whether the screw needed to be refitted, the fixation effects were divided into 3 types: Type I, screw is fully located within the vertebral pedicle; Type II, degree of pedicle cortex perforation is 1 mm or with the poor internal fixation stability and in need of renovation. Type I and Type II were acceptable placements; Type III placements were unacceptable. RESULTS:A total of 19 upper cervical spine and 19 navigation templates were printed, and 37 pedicle screws were fixed in each group. Type I screw-placements in the test group totaled 32; Type II totaled 3; and Type III totaled 2; with an acceptable rate of 94.60%. Type I screw placements in the control group totaled 23; Type II totaled 3; and Type III totaled 11, with an acceptable rate of 70.27%. The acceptability rate in test group was higher than the rate in control group. The operation time and fluoroscopic frequency for each screw were decreased, compared with control group. CONCLUSION:The individualized 3D printing navigation template for pedicle screw fixation is easy and safe, with a high success rate in the upper cervical spine surgery.

Inflammation plays a central role in the etiology of diabetic nephropathy, a global health issue. We observed a significant reduction in the renal expression of fibroblast growth factor 1, a known mitogen and insulin sensitizer, in patients with diabetic nephropathy and in mouse models implying that fibroblast growth factor 1 possesses beneficial anti-inflammatory and renoprotective activities in vivo. To test this possibility, we investigated the effects of chronic intraperitoneal administration of fibroblast growth factor 1 into both the streptozotocin-induced type 1 diabetes and db/db type 2 diabetes models. Indeed, recombinant fibroblast growth factor 1 significantly suppressed renal inflammation (i.e., cytokines, macrophage infiltration), glomerular and tubular damage, and renal dysfunction in both type 1 and type 2 diabetes mice. Fibroblast growth factor 1 was able to correct the elevated blood glucose levels in type 2 but not in type 1 diabetic mice, suggesting that the anti-inflammatory effect of fibroblast growth factor 1 was independent of its glucose-lowering activity. The mechanistic study demonstrated that fibroblast growth factor 1–mediated inhibition of the renal inflammation in vivo was accompanied by attenuation of the nuclear factor κB and c-Jun N-terminal kinase signaling pathways, further validated in vitro using cultured glomerular mesangial cells and podocytes. Thus, fibroblast growth factor 1 holds great promise for developing new treatments for diabetic nephropathy through countering inflammatory signaling cascades in injured renal tissue.

To investigate the characteristics of magnetic resonance image (MRI) in solitary fibrous tumor (SFT) of the kidney.MRI findings and clinical features of SFT of the kidney in 4 patients (2 men and 2 women with a mean age of 37.8 ± 8.7 years) were reviewed retrospectively. All patients were scanned by a 3.0-T magnetic resonance (MR) imaging system and the lesions were detected with emphasis on size, shape, location, margin, presence of pseudocapsule, signal intensity, degree of MR enhancement, and apparent diffusion coefficient (ADC).The 5 tumors from 4 patients were located in renal parenchyma (n = 1), renal pelvis (n = 3), and renal capsule (n = 1). On MRIs, the tumors were round (n = 1) or oval-shaped (n = 4), and presented pseudocapsule (n = 2) and well-circumscribed margins (n = 3) can be found. On T2-weighted images (T2WIs), solid components of the tumor presented homogeneously mild hypointensity or isointensity (n = 4) compared with the renal cortex. On diffusion-weighted images (DWIs), the lesions showed normal or mild hyperintensity (n = 4) with mean ADC of 1.687 × 10 mm/s. On dynamic contrast-enhanced MRIs, all lesions showed progressively mild enhancement. In the follow-up of 24 to 36 months after the surgery, 3 patients survived and 1 deceased.The SFT of the kidney appeared as a circle or oval and presented homogeneously mild hypointensity or isointensity on T2WIs, hyperintensity on DWIs, and progressively mild enhancement on DCE MRIs.

Maize (Zea mays) is one of the most important crops worldwide. To understand the biological processes underlying various traits of the crop (e.g. yield and response to stress), a detailed protein-protein interaction (PPI) network is highly demanded. Unfortunately, there are very few such PPIs available in the literature. Therefore, in this work, we present the Protein-Protein Interaction Database for Maize (PPIM), which covers 2,762,560 interactions among 14,000 proteins. The PPIM contains not only accurately predicted PPIs but also those molecular interactions collected from the literature. The database is freely available at http://comp-sysbio.org/ppim with a user-friendly powerful interface. We believe that the PPIM resource can help biologists better understand the maize crop.

OBJECTIVE Treatment of congenital pseudarthrosis of the tibia (CPT) remains a challenge. The autogenic iliac bone graft is important consistent of treatment for CPT. The purpose of this study was to investigate the role of wrapping autogenic iliac bone graft in improvement of the curing opportunities of CPT. METHODS We combined Ilizarov fixator with intramedullary rodding of the tibia and wrapping autogenic iliac bone graft for treatment 51 cases of CPT between 2007 and 2010. The mean age is 3.2 years at index operation, of which 31 patients (61%) were below 3 years old. According to Crawford classification, 5 tibia had type-II morphology; 3, type-III; 43, type-IV. RESULTS In the postoperative follow-up of 3.5 months (range from 3 to 4.5 months), all cases were found that the bone graft sites of pseudarthrosis of the tibia showed a significant augmentation and spindle-shaped expansion as obvious change. All cases of this series have been followed-up, average followed-up time were 1.6 years (range from 7 to 3.1 years), of which 19 cases were more than 2 years. The average time of removed the Ilizarov ring fixator was 3.5 months (range from 3 to 4.5 months). According to Johnston Clinical evaluation system, 26 cases had grade I, 21 cases, grade II, 4 cases, grade III. Following the Ohnishi X-ray evaluation criteria, union of pseudarthrosis of the tibia were 42 cases, delayed union 5 cases, nonunion 4 cases. CONCLUSION Autogenic iliac bone graft is able to offer the activity of osteoblasts and osteogenesis induced by bone morphogenetic protein (BMP) and glycoprotein, meanwhile enclosing bone graft could help keep cancellous bone fragments in close contact around pseudarthrosis of the tibia, allowing the formation of high concentration of glycoprotein and BMP induced by chemical factors because of established the sealing environment in location, all of which could enhance the healing of pseudarthrosis of the tibia.