Safety, tolerance, and pharmacokinetics of salvianolic acid B in healthy Chinese volunteers: A randomized, double-blind, placebo-controlled phase 1 clinical trial.

Background: Salvianolic acid B (Sal B) is one of the main active ingredients of Salvia miltiorrhiza Bunge. In China, many traditional Chinese medicines have been modified into injections for higher bioavailability and better efficacy. Salvianolic acid injection has been widely used in the clinic. Objective: This phase 1, randomized, double-blind, placebo-controlled, single-center study aimed to evaluate the safety, tolerance, and pharmacokinetics of Sal B injection in healthy Chinese volunteers. Methods: For the single-ascending-dose study, forty-seven healthy volunteers were randomly divided into 25, 75, 150, 200, 250, and 300 mg groups. For the multiple-ascending-dose study, sixteen healthy volunteers were randomly divided into 150 and 300 mg groups. In each group, volunteers were treated with Sal B or placebo randomly. Their safety was evaluated by a skin test, physical examination, vital sign, laboratory examination, 12-lead electrocardiogram, Holter, and clinical symptoms and signs. Blood samples were collected in 75, 150, and 300 mg single-ascending-dose study groups and 150 mg multiple-ascending-dose study groups to determine the concentration of salvianolic acid B. Results: In single-ascending-dose study groups, there were 41 adverse events in 24 cases (51.1%, 24/47). In multiple-ascending-dose study groups, there were 13 adverse events in eight cases (50.0%, 8/16). Sixty-six volunteers received the skin test, and three of them were excluded because of the positive result. Adverse events related to the treatment included increased alanine aminotransferase (4.0%), increased bilirubin (2.0%), increased creatinine kinase-MB (2.0%), increased brain natriuretic peptide (8.0%), increased urine N-acetyl-ß-D-glucosidase (4.0%), dizziness (2.0%), and chest discomfort (2.0%). No serious adverse events occurred. No volunteers withdrew from the trial. Peak plasma concentration and the area under the plasma concentration-time curve of salvianolic acid B progressively increased in a dose-dependent manner in 75, 150, and 300 mg single-ascending-dose study groups. There was no accumulation after 5 consecutive days of administration of 150 mg salvianolic acid B. Conclusion: Salvianolic acid B injections administered up to 300 mg in a single dose and 250 mg for 5 consecutive days showed excellent safety and tolerability in healthy Chinese volunteers. Clinical Trial Registration: www.chinadrugtrials.org.cn, identifier CTR20192236.

Drug resistance of hepatoma cells induced by ATP­binding cassette transporter G2 by reducing intracellular drug concentration.

The side effects and drug resistance during chemotherapy seriously affect the outcome of and may lead to the failure of chemotherapy for patients with hepatoma. The aim of the present study was to investigate the association between the expression of ATP-binding cassette transporter G2 (ABCG2) in hepatoma cells and the drug resistance of hepatoma. An MTT assay was used to determine the half-maximal inhibitory concentration (IC50) of Adriamycin (ADM) in hepatoma HepG2 cells after treatment with ADM for 24 h. An ADM-resistant hepatoma cell subline, HepG2/ADM, was generated from the HepG2 hepatoma cell line through a stepwise selection with ADM doses from 0.01 to 0.1 µg/ml. The HepG2/ABCG2 cell line, an ABCG2-overexpressing hepatoma cell line, was established by transfecting the ABCG2 gene into HepG2 cells. The MTT assay was then used to detect the IC50 of ADM in HepG2/ADM and HepG2/ABCG2 cells after treatment with ADM for 24 h and the resistance index was calculated. The apoptosis, cell cycle and ABCG2 protein expression levels in HepG2/ADM, HepG2/ABCG2 cells, HepG2/PCDNA3.1 and their parental HepG2 cells were detected by flow cytometry. In addition, flow cytometry was used to detect the efflux effect of HepG2/ADM and HepG2/ABCG2 cells after ADM treatment. ABCG2 mRNA expression in cells was detected by reverse transcription-quantitative PCR. After 3 months of ADM treatment, HepG2/ADM cells grew stably in the cell culture medium containing 0.1 µg/ml ADM and the cells were named HepG2/ADM cells. ABCG2 was overexpressed in HepG2/ABCG2 cells. The IC50 of ADM in HepG2, HepG2/PCDNA3.1, HepG2/ADM and HepG2/ABCG2 cells was 0.72±0.03, 0.74±0.01, 11.17±0.59 and 12.75±0.47 µg/ml, respectively. The cell apoptotic rate of HepG2/ADM and HepG2/ABCG2 cells was not significantly different compared with that of HepG2 and HepG2/PCDNA3.1 cells (P>0.05), but the G0/G1 phase population of the cell cycle decreased and the proliferation index increased significantly (P<0.05). The expression levels of ABCG2 gene and protein in HepG2/ADM and HepG2/ABCG2 cells were significantly higher than those in HepG2 and HepG2/PCDNA3.1 cells (P<0.01), but there was no significant difference between HepG2 and HepG2/PCDNA3.1 cells (P>0.05). The ADM efflux effect of HepG2/ADM and HepG2/ABCG2 cells was significantly higher than that of parental HepG2 and HepG2/PCDNA3.1 cells (P<0.05). Therefore, the present study demonstrated that ABCG2 expression is highly increased in drug-resistant hepatoma cells and that high expression of ABCG2 is involved in the drug resistance of hepatoma by reducing the intracellular drug concentration.

Network Pharmacological Study of Compound Kushen Injection in Esophageal Cancer.

AIM: To provide new methods and ideas for the clinical application of integrated traditional Chinese and Western medicine in the treatment of esophageal cancer. BACKGROUND: Traditional Chinese medicine compound Kushen injection (CKI) has been widely used in the clinic with adjuvant radiotherapy and chemotherapy. However, the mechanism of action of CKI as adjuvant therapy for esophageal cancer has not yet been described. METHODS: This study is based on network pharmacology, data mining, and molecular docking technology to explore the mechanism of action of CKI in the treatment of esophageal cancer. We obtained the effective ingredients and targets of CKI from the traditional Chinese medicine system pharmacology database and analysis platform (TCMSP) and esophageal cancer-related genes from the Online Mendelian Inheritance in Man (OMIM) and GeneCards databases. RESULTS: CKI mainly contains 58 active components. Among them, the top 5 active ingredients are quercetin, luteolin, naringenin, formononetin, and beta-sitostero. The target protein of the active ingredient was matched with the genes associated with esophageal cancer. The active ingredients targeted 187 esophageal cancer target proteins, including AKT1, MAPK1, MAPK3, TP53, HSP90AA1, and other proteins. Then, we enriched and analyzed the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) and used AutoDockVina to dock the core targets and compounds. Finally, PyMOL and Ligplot were used for data visualization. CONCLUSION: This study provides a new method and ideas for the clinical application of integrated traditional Chinese and Western medicine in the treatment of esophageal cancer.

Insights into the degradation of diphenhydramine - An emerging SARS-CoV-2 medicine by UV/Sulfite.

As Diphenhydramine (DPH) has been considered as a drug to treat SARS-CoV-2, the degradation of DPH from water was investigated and evaluated in this study by adopting an advanced oxidation/advanced reduction process - the UV/sulfite process. The UV/sulfite system was able to eliminate DPH within 6 mins under UV254nm and 1.0 mM sulfite. It was observed that the presence of N O 3 - , N O 2 - , C l - , H C O 3 - , and S O 4 2 - anions in water can affect the performance of UV/Sulfite degradation system. The mechanism of UV/sulfite/anions was evaluated which the presence of N O 3 - in UV/sulfite process has revealed faster initial decay rate but lower final DPH removal. It was observed that the UV/Sulfite process was extremely sensitive to pH as the dissociation of ion species varied among pH. The reaction became sluggish in acidic solution due to the dissociation of less reactive species such as HSO3 -. In alkaline solution, SO3 2- was the dominant species, producing powerful SO 3 ∙ - and e aq - when activated by UV at 254 nm. By conducting LC/MS analysis, the degradation pathway was proposed and can be summarized into four main pathways: hydroxylation, side chain cleavage, losing aromatic ring or ring opening. Scavenging tests were also carried out and validated the presence of various radicals contributing to the reaction, including e aq - , H˙, OH˙, SO3 ˙-, O2 •- and SO4 ˙-.

Baicalein Inhibits the Progression and Promotes Radiosensitivity of Esophageal Squamous Cell Carcinoma by Targeting HIF-1A.

Purpose: To explore the mechanism of the effect of baicalein on radioresistance of esophageal cancer, and to provide ideas for the treatment of patients with poor radiotherapy effect of esophageal cancer. Methods: The glycolytic rate assay kit was used to detect the changes in glycolytic metabolism in esophageal cancer cells after treatment with baicalein, and mass spectrometry was used to detect whether baicalein could affect the level of glycolysis-related metabolites in esophageal cancer cells. The binding of baicalein to the target protein was simulated by molecular docking technique, the protein expression level was detected by Western Blot, and the changes in the cell cycle were detected by flow cytometry. Results: Radiation combined with baicalein could significantly inhibit the proliferation and migration of esophageal cancer cells compared with that of 6 Gy rays alone. The results of the glycolytic rate assay showed that baicalein could inhibit the glycolysis of esophageal cancer cells. Metabonomic studies showed that baicalein could affect the expression levels of glycolysis-related metabolites. The results of network pharmacology showed that baicalein could target several key glycolysis enzymes and glycolysis-related proteins, such as HIF-1A. The results of the WB experiment showed that glycolysis-related proteins and cycle-related proteins were down-regulated after baicalein treatment. Conclusion: The main mechanism of baicalein inhibiting radiation resistance of esophageal cancer cells is that targeting HIF-1A protein regulates glucose metabolism and then regulates Cyclin D1/CDK4 axis to change the cell cycle.

Online Learning for DNN Training: A Stochastic Block Adaptive Gradient Algorithm.

Adaptive algorithms are widely used because of their fast convergence rate for training deep neural networks (DNNs). However, the training cost becomes prohibitively expensive due to the computation of the full gradient when training complicated DNN. To reduce the computational cost, we present a stochastic block adaptive gradient online training algorithm in this study, called SBAG. In this algorithm, stochastic block coordinate descent and the adaptive learning rate are utilized at each iteration. We also prove that the regret bound of O T can be achieved via SBAG, in which T is a time horizon. In addition, we use SBAG to train ResNet-34 and DenseNet-121 on CIFAR-10, respectively. The results demonstrate that SBAG has better training speed and generalized ability than other existing training methods.

Service Migration Policy Optimization considering User Mobility for E-Healthcare Applications.

Mobile edge computing (MEC) is an emerging technology that provides cloud services at the edge of network to enable latency-critical and resource-intensive E-healthcare applications. User mobility is common in MEC. User mobility can result in an interruption of ongoing edge services and a dramatic drop in quality of service. Service migration has a great potential to address the issues and brings inevitable cost for the system. In this paper, we propose a service migration solution based on migration zone and formulate service migration cost with a comprehensive model that captures the key challenges. Then, we formulate service migration problem into Markov decision process to obtain optimal service migration policies that decide where to migrate in a limited area. We propose three algorithms to resolve the optimization problem given by the formulated model. Finally, we demonstrate the performance of our proposed algorithms by carrying out extensive experiments. We show that the proposed service migration approach reduces the total cost by up to 3 times compared to no migration and outperforms the general solution in terms of the total expected reward.

MicroRNA-29b regulates the radiosensitivity of esophageal squamous cell carcinoma by regulating the BTG2-mediated cell cycle.

BACKGROUND: Many patients with esophageal squamous cell carcinoma (ESCC) are inoperable due to old age or advanced stage; thus, radio- and chemotherapy are considered the standard treatments for these patients. However, due to the radiation resistance of tumor cells that may arise during radiotherapy, results are still not satisfactory. The authors' previous studies found that microRNA can affect radiosensitivity, and further microRNA research was conducted to improve the radiosensitivity of ESCC. METHODS: Cells were treated with silent miR-29b (si-miR-29b). Thereafter,proliferation, colony formation, cell cycle, and apoptosis were determined. The luciferase reporting assay was used to confirm the direct interaction between miR-29b and BTG2. Serum samples and clinical follow-up data of 75 elderly or advanced ESCC patients who could not tolerate surgery were collected. RESULTS: The expression level of miR-29 in ESCC serum was closely correlated to radiosensitivity (χ2 =8.36, p < 0.05) and correlated with overall survival (OS; hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.24-0.90). Function assays demonstrated that the number of cell clones increased after radiometry radiation, and the cell cycle was blocked in the G0/G1 phase (from 37.2 to 56.9%) in the si-miR-29b transfection group. Expression of BTG2 was upregulated and expression of cyclin D1 was downregulated (p < 0.05). Transfection of si-BTG2 can reverse this result and restore the expression level of cyclin D1 (p < 0.05). The target gene BTG2 of miR-29b was predicted using a bioinformatics tool and confirmed by dual-luciferase reporter assay. CONCLUSION: Silencing of miR-29b in ESCC cells can increase expression of BTG2 and decrease the level of intracellular cyclin D1, resulting in cell cycle arrest and accumulation in the G0/G1 phase. Because G0/G1-phase cells are insensitive to radiotherapy, the sensitivity of radiotherapy is reduced.

Metabolic Reprogramming of Myeloid-derived Suppressor Cells in the Tumor Microenvironment.

A large number of studies on the metabolism of immune cells in anti-tumor response have been carried out in recent years. It is proved that metabolic reprogramming can determine the differentiation and functions of immune cells. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immunosuppressive cells in the tumor microenvironment (TME). They can significantly inhibit the anti-tumor response of T cells and play an important role in promoting tumor growth, metastasis, and invasion. This review summarizes the energy metabolic pathways of MDSCs in the TME, such as fatty acid oxidation (FAO), glycolysis, and amino acids (AAs) metabolism, and highlights the importance of metabolic reprogramming of MDSCs for its immunosuppressive functions.

Inhibition of proliferation and migration and induction of apoptosis in glioma cells by silencing TLR4 expression levels via RNA interference.

The objective of the present study was to investigate the expression levels of toll-like receptor 4 (TLR4) in glioma cells and the mechanisms underlying its regulatory effects on proliferation, migration and apoptosis of glioma cells. A total of three TLR4 silencing short hairpin (sh)RNA plasmids were established, and Lipofectamine® was used to the transfect the human glioma cell line U-87MG. Transfection efficiency was measured via flow cytometry. The interference plasmid exhibiting the largest silencing effect on TLR4 was screened for subsequent experiments using puromycin. Reverse transcription-quantitative PCR and western blot analysis were used to detect the TLR4 gene and protein expression levels, respectively, in stably transfected cells. Flow cytometry measured cell cycle and apoptosis and a wound healing assay was employed to assess the migration ability of transfected cells. The proliferation of transfected cells was detected using Cell Counting Kit-8 assay. TLR4-sh2 exhibited the highest transfection efficiency. Following transfection of U-87MG cells with TLR4-sh2 and negative control (NC) plasmids for 48 h and screening by puromycin, stable transfected cells were named U-87MG-Sh and U-87MG-NC cells respectively. The TLR4 gene and protein expression levels in the U-87MG-Sh cells were significantly lower than in U-87MG and U-87MG-NC cells. The apoptosis rate and the percentage of G0/1 cells were significantly higher, whereas the cell proliferation rate was notably lower, in U-87MG-Sh cells than in the U-87MG-NC and U-87MG cells. The proliferation rate and the cell migration ability of U-87MG-Sh cells were significantly lower than those of U-87MG-NC and U-87MG cells. TLR4 is associated with the proliferation of glioma cells. Inhibition of TLR4 expression levels significantly inhibited proliferation of glioma cells and induced apoptosis. The present study provided insights into the mechanisms associated with the development, progression and invasion ability of glioma cells.

Screening potential topological insulators in half-Heusler compounds via compressed-sensing.

Ternary half-Heusler compounds with widely tunable electronic structures, present a new platform to discover topological insulators (TIs). Due to time-consuming computations and synthesis procedures, the identification of new TIs is however a rough task. Here, we adopt a compressed-sensing approach to rapidly screen potential TIs in half-Heusler family, which is realized via a two-dimensional descriptor that only depends on the fundamental properties of the constituent atoms. Beyond the finite training data, the proposed descriptor is employed to screen many new half-Heusler compounds, including those with integer and fractional stoichiometry, and a larger number of possible TIs are predicted.

Artesunate inhibits lung cancer cells via regulation of mitochondrial membrane potential and induction of apoptosis.

Lung cancer is a common malignant disease with a high incidence rate worldwide, posing a great threat to human health. To date, only a small number of studies have assessed the potential anti­cancer effect of artesunate (Art) and the associated mechanisms in lung cancer. The present study aimed to investigate the inhibitory effects of Art in human lung cancer cells and investigated the underlying molecular mechanisms. The inhibitory effect of Art on the growth of A549 lung cancer cells was detected by the MTT assay, and flow cytometry was utilized to determine cell cycle progression, apoptosis, mitochondrial membrane potential, as well as the expression of Bcl­2 and Bax proteins in A549 cells after Art treatment for 24 h. Art inhibited the growth of A549 cells in a dose­dependent manner, induced cell apoptosis and cell cycle arrest, decreased the expression of Bcl­2 protein and mitochondrial membrane potential, and increased the expression of Bax protein. In conclusion, Art significantly inhibited the growth of lung cancer cells by preventing cell cycle progression. This phenomenon indicated its promising therapeutic potential in the treatment of lung cancer.

Small cell lung cancer (SCLC) incidence and trends vary by gender, geography, age, and subcategory based on population and hospital cancer registries in Hebei, China (2008-2017).

BACKGROUND: Lung cancer is the leading cause of morbidity and mortality worldwide. Small cell lung cancer (SCLC) has been determined to be the most lethal lung malignancy. Few studies have previously analyzed the epidemiological characteristics of SCLC in China. This study analyzed the epidemiological characteristics of SCLC aiming to provide a reference for the prevention of SCLC in Hebei Province. METHODS: The epidemiological characteristics of SCLC using lung cancer data based on population and hospital cancer registries in Hebei Province between 2008 and 2017 were analyzed. RESULTS: The proportion of both population- and hospital-based SCLC cases displayed a significant increasing trend. Moreover, the proportion of males was higher than that for female based on population- and hospital-based cases. The proportion of hospital-based SCLC cases in counties was higher than that in cities, whereas there were no significant regional differences between cities and counties based on population. The proportion of both population- and hospital-based SCLC cases decreased consistently with increasing age. There was a difference between population- and hospital-based distribution of subcategories of SCLC. CONCLUSIONS: Significant increases in the proportion of both population- and hospital-based SCLC cases over recent years, particularly in males and in patients aged over 55 years, were observed. Research on the pathogenesis of SCLC in these patients and prevention is urgently required.

Methylation-associated silencing of miR-193b improves the radiotherapy sensitivity of esophageal cancer cells by targeting cyclin D1 in areas with zinc deficiency.

BACKGROUND: Although radiotherapy is an important treatment mode for esophageal cancer (EC), the outcome remains unsatisfactory due to radioresistance, and the key cause of radiotherapy resistance is a change in the cell cycle. Zinc deficiency (ZD) has a significant influence on the cell cycle, and this effect is a common phenomenon in areas with a high incidence of esophageal cancer. METHODS: Radioresistant sub-cell lines were established by exposing esophageal cancer cells to nine rounds of X-ray irradiation at a dose of 2 Gy. The cells were treated with a range of different concentrations of zinc and overexpression of miR-193b. And proliferation, colony formation, cell cycle and apoptosis assays were then conducted. Luciferase reporter assays were performed to confirm direct interactions between miR-193b and ZRT/IRT-like protein 5 (ZIP5) and between miR-193b and Cyclin D1. Analysis of clinical and follow-up data was performed using data obtained from 75 patients from Cixian, a well-known high incidence area of esophageal cancer. All these patients are unable to tolerate surgery due to their advanced age or advanced stage, and serum specimens were obtained before the patients received therapy. RESULTS: The cell cycle of radioresistant cells is blocked in G0/G1 phase (from 50% to 68%). The expression level of Cyclin D1 was decreased and miR-193b was increased in radioresistant cells (P < 0.001). ZD decreased the proportion of cells in G0/G1 phase both in EC (from 50% to 32%) and radioresistant (from 68% to 47%) cells. And the radioresistance of these two cells were decreased. ZD increased the expression of Cyclin D1 (P < 0.001) and inhibited the level of miR-193b (P < 0.001). Up-regulation of miR-193b recovered the proportion of cells in G0/G1 phase and the radioresistance, meanwhile, recovered the altered expression levels of Cyclin D1 and miR-193b of these two cells by ZD. ZD enhanced DNMT activity both in EC (32%) and radioresistant (26%). And miR-193b was hypermethylated both in EC and radioresistant cells. MiR-193b supp ressed Cyclin D1 expression by targeting the 3'UTR of Cyclin D1 mRNA. The expression level of miR-193b in the serum of patients was correlated with the disease control rate (DCR) and had a good diagnostic value for distinguishing DCR of EC patients (AUC = 0.710, 95%CI: 0.580-0.839, P = 0.003). And the level of miR-193b was correlated with overall survival (OS) (HR = 0.208, 95%CI: 0.094-0.464). CONCLUSIONS: The methylation-mediated silencing of miR-193b in EC cells due to ZD increased the expression of ZIP5, and the overexpression of ZIP5 increased the intracellular zinc levels to maintain zinc homeostasis. Meanwhile, the silencing of miR-193b increased the sensitivity of radiotherapy by promoting the expression of Cyclin D1.

Pharmacokinetics and Bioequivalence of 2 Olanzapine Orally Disintegrating Tablet Products in Healthy Chinese Subjects Under Fed and Fasting Conditions.

To assess the bioequivalence of two 5-mg olanzapine orally disintegrating tablet (ODT) products, 2 randomized, open-label, single-dose, 2-way crossover studies were carried out under fasting or fed conditions. Blood samples were collected at scheduled times according to the study protocol. Statistical analysis of area under the concentration-time curve from time 0 to 168 hours (AUC0-t ), area under the curve from time zero to infinity (AUC0-∞ ), and peak plasma concentration (Cmax ) was conducted. Two formulations were considered bioequivalent if the 90% confidence intervals (CIs) of the geometric mean ratios for AUC0-t, AUC0-∞ , and Cmax were within the range of 0.80-1.25. Adverse events were recorded and evaluated throughout the studies. A total of 48 subjects with 24 in each study completed the 2 studies. In fasted subjects, the 90%CIs for the test product versus the reference product were 97.28%-105.13% for AUC0-t , 97.57%-105.54% for AUC0-∞ , and 90.94%-103.97% for Cmax . In fed subjects, the 90%CIs for AUC0-t , AUC0-∞ and Cmax were 99.73%-122.63%, 99.56%-121.75%, and 99.46%-120.46%, respectively. No serious adverse events were reported in the studies. The reference and the test product of 5-mg olanzapine ODT show comparable pharmacokinetic profiles under both fed and fasted conditions and were considered bioequivalent.

Intensity modulation based optical proximity optimization for the maskless lithography.

The undesirable optical proximity effect (OPE) that appeared in the digital micro-mirrors device (DMD) based maskless lithography directly influences the final exposure pattern and decreases the lithography quality. In this manuscript, a convenient method of intensity modulation applied for the maskless lithography is proposed to optimize such an effect. According to the pulse width modulation based image recognition of DMD, we replaced the digital binary mask with a special digital grayscale mask to modulate the UV intensity distribution to be closer to the expectation in a way of point-by-point modification. The exposure result applying the grayscale mask has a better consistency with the design pattern than that for the case in which the original binary mask is used. The effectiveness of this method was analyzed by the image subtraction technique. Experimental data revealed that the matching rate between the exposure pattern and the mask pattern has been improved from 78% to 91%. Besides, more experiments have been conducted to verify the validity of this method for the optical proximity optimization and its potential in the high-fidelity DMD based maskless lithography.

Anatomical and Clinical Comparison of Small Free Flaps for Repairing Finger Skin Defects.

The reconstruction of finger defects requires improved functional outcomes and acceptable esthetic outcomes, and small free flaps present a good alternative technique for repairing finger skin defects. From January 2006 to December 2018, we investigated the number and diameter of proximal digital artery perforators, medial plantar artery perforators, and peroneal proper plantar digital arteries of the hallux by dissection and then transplanted free digital arterial perforator flaps, free medial plantar flaps, and free peroneal flaps from the hallux to repair small finger skin defects. The number (SD) of perforators from the medial plantar artery was approximately 2.2 (0.5), and these perforators measured 0.53 (0.20) mm in diameter. The diameter (SD) of the first metatarsal dorsal artery was approximately 1.16 (0.30) mm. A total of 25 patients were included in this study. The transplantation times (SD) for free digital arterial perforator flaps, free medial plantar flaps, and free peroneal flaps from the hallux were 3.5 (0.5) hours, 3.2 (0.7) hours, and 2.0 (0.4) hours, respectively. The follow-up period ranged from 8 to 15 months. All flaps survived and were appropriately shaped. The donor site was either covered with a free flap or directly sutured. Among these 3 types of small flaps, the free peroneal flap from the hallux can be recommended for clinical use because of the large diameter of the contributing vessels, the short operative time, the ease of access, and the improved appearance of the donor site.

miR-1-3p suppresses the epithelial-mesenchymal transition property in renal cell cancer by downregulating Fibronectin 1.

PURPOSE: Renal cell cancer (RCC) is one of the primary causes of malignancy deaths all over the world. The most important cause of RCC-related mortality is metastasis. Epithelial-mesenchymal transition (EMT) plays an important role in metastasis of malignant tumors including RCC. miR-1-3p is confirmed to be decreased in many types of cancer. Nevertheless, the function of miR-1-3p in RCC metastasis and EMT process was still unclear. MATERIALS AND METHODS: In this study, information from clinical investigation, in vitro study, and in vivo study discovered miR-1-3p expression character and its status in RCC. The character of miR-1-3p in invasive and metastatic properties in vitro and in vivo was also inspected in RCC cells and xenograft tumor model, and expression levels of EMT markers were evaluated in RCC cells and tissues. RESULTS: miR-1-3p was proved to be decreased in RCC cell lines and tissues compared with normal renal cells and tissues. miR-1-3p expression level in RCC tissues was closely related with capsulation, lymph node metastasis, and vascular invasion. miR-1-3p was found to be able to block the EMT process in A498 and CAKI-1 RCC cells and tumors. Luciferase reporter assay and expression level rescue assays were employed to reveal that miR-1-3p inhibited the invasion and migration property of RCC cells by directly targeting Fibronectin 1. Upregulation of Fibronectin 1 partially reversed the suppressive effect of miR-1-3p on EMT process. CONCLUSION: In brief, this study has verified that miR-1-3p blocked the EMT process of RCC cells by reducing Fibronectin 1 expression. miR-1-3p/Fibronectin 1 axis may be considered as a new target for drug development of RCC.

LPI-IBNRA: Long Non-coding RNA-Protein Interaction Prediction Based on Improved Bipartite Network Recommender Algorithm.

According to the latest research, lncRNAs (long non-coding RNAs) play a broad and important role in various biological processes by interacting with proteins. However, identifying whether proteins interact with a specific lncRNA through biological experimental methods is difficult, costly, and time-consuming. Thus, many bioinformatics computational methods have been proposed to predict lncRNA-protein interactions. In this paper, we proposed a novel approach called Long non-coding RNA-Protein Interaction Prediction based on Improved Bipartite Network Recommender Algorithm (LPI-IBNRA). In the proposed method, we implemented a two-round resource allocation and eliminated the second-order correlations appropriately on the bipartite network. Experimental results illustrate that LPI-IBNRA outperforms five previous methods, with the AUC values of 0.8932 in leave-one-out cross validation (LOOCV) and 0.8819 ± 0.0052 in 10-fold cross validation, respectively. In addition, case studies on four lncRNAs were carried out to show the predictive power of LPI-IBNRA.

Modulation of cancer immunotherapy efficacy by gut microbiota.

The microbial community is present abundantly in mucosal organs including the intestine, the oral cavity, and the vagina, and is referred to as the microbiota. The microbiota is composed of commensal bacteria and other microorganisms. Intestinal colonization by commensal microorganisms is essential for host physiological functions from the maintenance of barrier homeostasis locally to the regulation of metabolism, hematopoiesis, inflammation, immune development, and other functions systemically. Evidence is growing that the gut microbiota can modulate the host response to cancer immunotherapy. In this review, we discuss the evidence for the ability of the microbiota to modulate immunotherapy, their mechanisms of action, and the possibility of altering the microbiota to improve immunotherapy efficacy.