Gastric cancer is one of the most common malignant tumors in the world. Patients with gastric cancer are often treated by surgery, radiotherapy, chemotherapy or immunotherapy, but the clinical efficacy and prognosis are poor. As an important member of ADAMs family, a disintegrin and metalloprotease 17 (ADAM17) is significantly more highly expressed in gastric cancer than in adjacent tissues. It participates in the occurrence and development of gastric cancer by mediating EGFR, TNF-α, TGF-β/Smad, Notch and Wnt, FoxM1-ADAM17 and EGFR/ERK/SP1. The high expression of ADAM17 is also closely related to the poor prognosis of gastric cancer, suggesting that ADAM17 can be used as a biological index to predict the development and prognosis of gastric cancer and has great potential to become a new therapeutic target for gastric cancer. In this paper, the mechanism, treatment and prognosis of ADAM17 in the development of gastric cancer are reviewed, in order to provide new ideas for clinical diagnosis and treatment of gastric cancer.

Attention deficit hyperactivity disorder is a common neurodevelopmental disorder characterized by persistent attention deficit, hyperactivity, and impulsive behaviors that are not consistent with developmental age.Academic and vocational difficulties, social exclusion, and delinquent behaviors are manifested in daily life.It is also commonly accompanied by psychiatric problems.At the same time, mental problems are common, and the overall quality of life is greatly affected, placing a heavy burden on society as well as the family.International attention deficit hyperactivity disorder experts have developed a common and comprehensive International Classification of Functioning, Disability and Health core set of classifications for assessing individual functioning in attention deficit hyperactivity disorder.

Objective To investigate the clinical value of deep learning reconstruction(DLR)for flow sensitive black blood(FSBB)sequence in MRI of lenticulostriate artery(LSA).Methods Thirty robust volunteers were prospectively selected,performed scans with conventional FSBB sequences,and divided into DLR-FSBB group and conventional FSBB group according to whether DLR method was used.The signal-to-noise ratio(SNR),contrast-to-noise ratio(CNR)and number of branches of the two groups of images for bilateral LSA were compared,and the overall image quality was evaluated subjectively using Likert score(5-point scale).A paired t-test was used to compare quantitative indicators,SNR and CNR of image quality between the two groups.The Kappa coefficient was applied to eval-uate the consistency of subjective scores between the two observers.Results The SNR and CNR of DLR-FSBB images of cranial bilateral LSA were considerably higher than those of conventional FSBB images(left SNR 34.45±8.21 vs 16.91±4.67,P＜0.001,and right SNR 31.24±6.35 vs 16.02±3.00,P＜0.001;corresponding CNR 19.38±6.37 vs 9.27±3.12,15.82±4.29 vs 8.01±2.27,P＜0.001).The number of branches of LSA was slightly higher in the DLR-FSBB images[4.00(4.00,5.00)vs 3.00(3.00,4.00)on the left side,P＜0.001;3.00(3.00,4.00)vs 3.00(2.00,3.00)on the right side,P=0.003].The subjective score of overall image quality was higher in DLR-FSBB than that in conventional FSBB[reader 1:4.00(4.00,4.00)points vs 3.00(3.00,3.00)points;reader 2:4.00(4.00,4.00)points vs 3.00(3.00,3.00)points,P＜0.001].Conclusion Compared with conventional FSBB sequences,DLR-FSBB sequences of LSA have lower image noise,and vessel branches are displayed more plainly and slightly more numerous.DLR can improve the overall image quality of LSA in conventional FSBB sequences.

Anti-seizure medications (ASMs) are the main therapy for epilepsy.There are many kinds of ASMs with complex mechanism of action, so it is difficult for pharmacists to examine prescriptions.This paper put forward some suggestions on the indications, dosage forms/routes of administration, appropriateness of usage and dosage, combined medication and drug interaction, long-term prescription review, individual differences in pathophysiology of children, and drug selection when complicated with common epilepsy, for the reference of doctors and pharmacists.

The COVID-19 pandemic caused by the novel SARS-CoV-2 virus has caused havoc across the entire world. Even though several COVID-19 vaccines are currently in distribution worldwide, with others in the pipeline, treatment modalities lag behind. Accordingly, researchers have been working hard to understand the nature of the virus, its mutant strains, and the pathogenesis of the disease in order to uncover possible drug targets and effective therapeutic agents. As the research continues, we now know the genome structure, epidemiological and clinical features, and pathogenic mechanism of SARS-CoV-2. Here, we summarized the potential therapeutic targets involved in the life cycle of the virus. On the basis of these targets, small-molecule prophylactic and therapeutic agents have been or are being developed for prevention and treatment of SARS-CoV-2 infection.

Objective:To investigate the effect of albumin to fibrinogen ratio on the prognosis of patients undergoing radical resection for colorectal cancer.Methods:Clinical and pathological data of 216 patients who underwent laparoscopic radical resection of colorectal cancer at the General Surgery Department of Taizhou People's Hospital from Aug 2015 to Jul 2017 were retrospectively analyzed. Albumin and fibrinogen results within 7 days before surgery was collected. The optimal cut-off point of AFR was determined by Youden index of ROC curve. Kaplan-Meier analysis, univariate and multivariate COX regression models were used to analyze the prognostic factors of OS and DFS.Results:The best postoperative OS threshold of AFR for patients undergoing laparoscopic radical resection of colorectal cancer was 9.43. Univariate analysis and multivariate COX regression analysis showed that age ≤65 years, TNM stage Ⅰ-Ⅱ, and AFR≥9.43 had better OS and DFS (all P<0.05). Conclusions:Preoperative AFR level had a good predictive value on postoperative survival of patients undergoing laparoscopic radical resection of colorectal cancer, and AFR<9.43 was an independent risk factor for postoperative OS and DFS.

Reflux Esophagitis (RE) is a gastroesophageal motility disorder mainly caused by lower esophageal sphincter disorder caused by a variety of injury factors, acid-suppressing drugs such as Proton Pump Inhibitors (PPIs) are often used clinically. With the increase of PPIs-resistant reflux esophagitis cases, the demand for the pharmacokinetics and pharmacodynamics of acid-suppressing drugs is higher. In recent years, the emergence of a new class of acid-suppressing drugs, potassium-competitive acid blockers (P-CABs), has solved some clinical deficiencies of traditional proton pump inhibitors. It has the characteristics of effective, longer-lasting acid suppression, the inhibitory effect on gastric acid secretion is not affected by the state of gastric acid secretion, the individual differences in drug metabolism and efficacy are smaller, and the drug efficacy is not affected by food intake or not. It has obvious advantages in the efficacy of severe erosive esophagitis and PPIs-resistant severe erosive esophagitis, and is more cost-effective, and is expected to replace PPI as the first-line treatment for reflux esophagitis.

As an important component of the tumor microenvironment, cancer-associated fibroblasts (CAFs) secrete energy metabolites to supply energy for tumor progression. Abnormal regulation of long noncoding RNAs (lncRNAs) is thought to contribute to glucose metabolism, but the role of lncRNAs in glycolysis in oral CAFs has not been systematically examined. In the present study, by using RNA sequencing and bioinformatics analysis, we analyzed the lncRNA/mRNA profiles of normal fibroblasts (NFs) derived from normal tissues and CAFs derived from patients with oral squamous cell carcinoma (OSCC). LncRNA H19 was identified as a key lncRNA in oral CAFs and was synchronously upregulated in both oral cancer cell lines and CAFs. Using small interfering RNA (siRNA) strategies, we determined that lncRNA H19 knockdown affected proliferation, migration, and glycolysis in oral CAFs. We found that knockdown of lncRNA H19 by siRNA suppressed the MAPK signaling pathway, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and miR-675-5p. Furthermore, the lncRNA H19/miR-675-5p/PFKFB3 axis was involved in promoting the glycolysis pathway in oral CAFs, as demonstrated by a luciferase reporter system assay and treatment with a miRNA-specific inhibitor. Our study presents a new way to understand glucose metabolism in oral CAFs, theoretically providing a novel biomarker for OSCC molecular diagnosis and a new target for antitumor therapy.
Cancer-Associated Fibroblasts/metabolism* ; Carcinoma, Squamous Cell/genetics* ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glycolysis ; Head and Neck Neoplasms ; Humans ; MicroRNAs/metabolism* ; Mouth Neoplasms/genetics* ; Phosphofructokinase-2/genetics* ; RNA, Long Noncoding/genetics* ; Signal Transduction ; Tumor Microenvironment

Objective: To observe the effect of transforming growth factor-β1 (TGF-β1) on the migration of oral carcinoma associated fibroblasts (CAFs) with two-dimensional culture model and three-dimensional model. Methods : Under two-dimensional culture conditions, CAFs stimulated by TGF-β1 with the addition of 10 ng/mL medium were used as the experimental group, and untreated CAFs were used as the control group. The migration of CAFs with the stimulation of TGF-β1 was measured by cell scratch assay and transwell assay. CAFs positive for green fluorescent protein (GFP) were cultured by retrovirus transfection. Human tongue squamous cell carcinoma cells SCC25, GFP(+) CAFs and CAFs with three-dimensional cell co-culture models were established. The three-dimensional model cultured under the stimulation of TGF-β1 with 10 ng/mL medium was used as the experimental group, and the three-dimensional model without TGF-β1 was used as the control group. The migration of CAFs with the stimulation of TGF-β1 was also measured by the three-dimensional models. Results: It was verified that 10 ng/mL TGF-β1 promoted the migration of CAFs in the two-dimensional culture model. The three-dimensional co-culture models of SCC25, GFP(+) CAFs and CAFs were successfully established. The migration of SCC25 and CAFs was detected in the three-dimensional model. However, 10 ng/mL TGF-β1 had little effect on their migration. Conclusion The effect of TGF-β1 in vitro on the migration of oral CAFs was associated with different culture models in two and three dimensions.

Objective:To investigate the effect of esculin on the proliferation of triple negative breast cancer cells and its molecular mechanism.Methods:MDA-MB-231 cells were treated with 28, 56, 112, 225, 450 and 900 μmol/L of esculin for 24, 48 and 72 h, respectively, and the cell viability was detected by cell counting kit 8 (CCK-8) assay. In addition, MDA-MB-231 cells were treated with 0, 225, 450 and 900 μmol/L of esculin for 48 h. And then the changes in cell morphology were observed by inverted microscope. The clone-forming ability was detected by colony formation assay. The mRNA expression levels of FBI-1, p53 and p21 were detected using real-time fluorescence quantitative polymerase chain reaction. The protein expression levels of FBI-1, p53, p21 and Ki67 were detected by western blot.Results:Compared with the blank control group, the cell viability of MDA-MB-231 cells that treated with esculin significantly decreased in a dose-dependent and time-dependent manners. After treatment with esculin, MDA-MB-231 cells shrunk, flattened, adhered poorly to the culture dish and the cell spacing became larger. Meanwhile, shedding and incomplete cells appeared, of which 900 μmol/L of esculin treatment group showed the most dramatic changes. In addition, the colony formation ratios were decreased to (77.18±5.13)%, (65.94±4.98)% and (45.92±3.70)% in the 225, 450 and 900 μmol/L of esculin treatment groups compared with blank control, respectively ( P<0.01). Furthermore, the mRNA and protein expressions of FBI-1 increased, while the levels of p53 and p21 mRNA and protein, as well as the protein expression of Ki67 decreased in a concentration-dependent manner ( P<0.01). Conclusion:Esculin may regulate cell cycle-related p53-p21 pathway via FBI-1 mediated DNA replication, thus inhibit the proliferation of triple negative breast cancer cells.