摘要：The dysregulation of pathways regulat-ing cellular function is a frequent hall-mark of cancer and the development of specific pathway inhibitors that alter tumor growth and progression are the focus of multiple recent studies. E3 ubiquitin ligases are a large group of diverse protein enzymes that specifically target proteins for dear- ance, and their importance to normal cel-lular function is illustrated in the many diseases associated with their loss of func- tion or inappropriate targeting. S-phase kinase-associated protein 2 （Skp2） is an F box protein that plays critical roles in cell-cycle progression, senescence, metabolism, and acts as an Skpl-Cullin-l-F box （SCF） ubiquitin ligase substrate recognition fac-tor. Overexpression of Skp2 is associated with poor prognosis and metastasis in many cancers and is a well validated drug target. In a recent report, Chart et al. have iden-tified an Skp2 inhibitor that selectively impairs Skp2 E3 ligase activity using an integrated virtual high-throughput drug screening and experimental validation approach. This Skp2 inhibitor restricts cancer stemness and potentiates sensitivity to chemotherapeutic agents in multiple ani-mal tumor models. These findings identify a new novel small molecule that targets the Skp2 and reduces tumor growth by attenu-ating aerobic glycolysis and inducing cel-lular senescence.

摘要：Chronic hepatitis B(CHB)is a global health issue that increases the risk of liver cirrhosis and hepatocellular carcinoma in infected *** syndrome(Met S)is a disease endemic mostly to the developed *** is associated with high cardiovascular mortality and morbidity,diabetes mellitus as well as *** this manuscript,we systematically review the published data on the relationship between Met S and CHB *** studies have described highly variable correlations between CHB on one hand and Met S,non-alcoholic fatty liver disease and dyslipidemia on the *** association between CHB and diabetes mellitus or atherosclerosis has been described as of *** presence of Met S in patients infected with hepatitis B virus increases the risk of fibrosis,cirrhosis and hepatocellular *** lifestyle,but also pharmacological interventions are needed to prevent the development of these complications.

摘要：The immune response after implantation of a biomaterial may shorten the functional life of the implant,depending on the degree of the *** this study,we used a polyacrylamide-alginate(PAAm-Alg)hydrogel,which has been previously characterized as a biocompatible material and shown to enhance regeneration of cartilage in vivo,along with a graphiteenhanced hydrogel(PAAm-Alg-G)as a non-biocompatible counterpart,to evaluate macrophage attachment and polarization to pro-or anti-inflammatory *** performance of each biomaterial in the presence of fibroblasts and chondrocytes was validated by an in vitro model which demonstrated modulation of the foreign-body response.A blend of 5%gelatin methacryloyl and 0.1%methacrylated hyaluronic acid was optimized to mimic the extracellular matrix(ECM)and support cell viability,proliferation,migration,and functionality at an initial concentration of 3.25×10^(5) cells/*** PAAm-Alg-G hydrogel localized in the simulated ECM showed cytotoxic and genotoxic effects for both fibroblasts and chondrocytes,while exhibiting a proliferative effect on macrophages with elevated immune *** M1/M2 ratio was 0.73 for PAAm-Alg hydrogel but 2.64 for PAAm-Alg-G,leading to significant M1 dominance(p0.05).The interleukin-6(IL-6)concentration secreted in the presence of PAAm-Alg hydrogel(4.58 pg/mL)significantly decreased(p<0.0001)on day 13,while the increase(p<0.0001)in interleukin-10(IL-10)concentration(120.73 pg/mL)confirmed the switch from a pro-inflammatory to an anti-inflammatory *** immune responses by developing a simplistic yet powerful three-dimensional in vitro model provides advantages in preparing for clinical use of biomaterials.

摘要：Many epidemiological reports indicate that Helicobacter pylori （H pylori） infection plays an important role in gastric carcinogenesis. Several genetic and epigenetic alterations contribute to the initiation, promotion, and progression of the cancer cells in a multi-step manner. H pylori is known to induce chronic inflammation in the gastric mucosa. Its products, including superoxides, participate in the DNA damage followed by initiation, and the inflammation-derived cytokines and growth factors contribute to the promotion of gastric carcinogenesis. By eradicating H pylori, gastric inflammation can be cured; the therapy diminishes the levels not only of inflammatory cell infiltration, but also atrophy/ intestinal metaplasia in part. A randomized controlled trial revealed that the eradication therapy diminished the gastric cancer prevalence in cases without precancerous conditions. In addition, recent epidemiological studies from Japanese groups demonstrated that the development of gastric cancer, especially of the intestinal type, was decreased by successful eradication therapy, although these were designed in a non- randomized manner. However, it should be mentioned that endoscopic detection is the only way to evaluate the degree of gastric carcinogenesis. We have reported that the endoscopic and histological morphologies could be modified by eradication therapy and it might contribute to the prevalence of gastric cancer development. Considering the biological nature of cancer cell proliferation, it is considered that a sufficiently long-term follow-up would be essential to discuss the anticancer effect of eradication therapy.

摘要：For much of the twentieth century, surgery was frequently the solution for peptic ulcer disease. Our understanding of the pathophysiology of ulcers paralleled the development of potent pharmaceutical therapy. As the surgical world developed parietal cell vagotomy which would minimize the complications of surgery, patients failing medical therapy became rare. Emergent surgery for complicated peptic ulcers has not declined however. The development of proton pump inhibitors and the full understanding of the impact of H pylori has led to a trend towards minimalism in surgical therapy for complicated peptic ulcer disease. In addition to the changes in patient care, these developments have had an impact on the training of surgeons. This article outlines these trends and developments.

摘要：AIM:To design and validate broad-range 16S rRNA primers for use in high throughput sequencing to classify bacteria isolated from the human foregut ***:A foregut microbiome dataset was constructed using 16S rRNA gene sequences obtained from oral,esophageal,and gastric microbiomes produced by Sanger sequencing in previous studies represented by 219 bacterial *** primers evaluated were from the European rRNA *** assess the effect of sequence length on accuracy of classification,16S rRNA genes of various lengths were created by trimming the full length *** spanning various hypervariable regions were selected to simulate the amplicons that would be obtained using possible primer *** sequences were compared with full length 16S rRNA genes for accuracy in taxonomic classification using online software at the Ribosomal Database Project (RDP).The universality of the primer set was evaluated using the RDP 16S rRNA database which is comprised of 433 306 16S rRNA genes,represented by 36 ***:Truncation to 100 nucleotides(nt)downstream from the position corresponding to base 28 in the Escherichia coli 16S rRNA gene caused misclassification of 87(39.7%)of the 219 sequences,compared with misclassification of only 29(13.2%)sequences with truncation to 350 *** 350-nt sequence reads within various regions of the 16S rRNA gene,the reverse read of an amplicon generated using the 343F/798R primers had the least(8.2%)effect on *** comparison,truncation to 900 nt mimicking single pass Sanger reads misclassified 5.0%of the 219 *** 343F/798R amplicon accurately assigned 91.8%of the 219 sequences at the species *** by abundance of the species in the esophageal dataset,the 343F/798R amplicon yielded similar classification accuracy without a significant loss in species coverage(92%).Modification of the 343F/798R primers to 347F/803R increased their universality among foregut ***

摘要：The lateral hypothalamic area(LHA)plays a pivotal role in regulating consciousness transition,in which orexinergic neurons,GABAergic neurons,and melanin-concentrating hormone neurons are *** neurons have a large population in the LHA,but their anesthesia-related effect has not been ***,we found that genetic ablation of LHA glutamatergic neurons shortened the induction time and prolonged the recovery time of isoflurane anesthesia in *** contrast,chemogenetic activation of LHA glutamatergic neurons increased the time to anesthesia and decreased the time to *** activation of LHA glutamatergic neurons during the maintenance of anesthesia reduced the burst suppression pattern of the electroencephalogram(EEG)and shifted EEG features to an arousal *** of LHA glutamatergic projections to the lateral habenula(LHb)also facilitated the emergence from anesthesia and the transition of anesthesia depth to a lighter ***,LHA glutamatergic neurons and their projections to the LHb regulate anesthetic potency and EEG features.

摘要：Interstitial cells of Cajal (ICC) are important players in the symphony of gut motility. They have a very signif icant physiological role orchestrating the normal peristaltic activity of the digestive system. They are the pacemaker cells in gastrointestinal (GI) muscles. Absence, reduction in number or altered integrity of the ICC network may have a dramatic effect on GI system motility. More understanding of ICC physiology will foster advances in physiology of gut motility which will help in a future breakthrough in the pharmacological interventions to restore normal motor function of GI tract. This mini review describes what is known about the physiologic function and role of ICCs in GI system motility and in a variety of GI system motility disorders.

摘要：In the era of burgeoning breakthroughs around medical and biomedical technologies,personalizing our medicine still sounds like a dream yet to be *** cancer as an example,while the pool of anti-cancer therapeutic agents is tremendously large,pinpointing a drug or a combination of drugs that would always work out well for a given patient,remains quite impossible—in fact,we are not even close to this ideal *** an incapability,of course,originates primarily from the overly complex,volumetrically structured and dynamic microenvironments in a patient’s tumor,meaning that the same tumor as seen on Day 1 might be entirely different than when seen again a month later.

摘要：With the aid of advanced surgical techniques and instruments, single-port laparoscopic surgery(SPLS) can be accomplished with just two surgical members: an operator and a camera assistant. Under these circumstances, the reasonable replacement of a human camera assistant by a mechanical camera holder has resulted in a new surgical procedure termed singleport solo surgery(SPSS). In SPSS, the fixation and coordinated movement of a camera held by mechanicaldevices provides fixed and stable operative images that are under the control of the operator. Therefore, SPSS primarily benefits from the provision of the operator's eye-to-hand coordination. Because SPSS is an intuitive modification of SPLS, the indications for SPSS are the same as those for SPLS. Though SPSS necessitates more actions than the surgery with a human assistant, these difficulties seem to be easily overcome by the greater provision of static operative images and the need for less lens cleaning and repositioning of the camera. When the operation is expected to be difficult and demanding, the SPSS process could be assisted by the addition of another instrument holder besides the camera holder.