Comparison of thoracoabdominal versus abdominal-transhiatal surgical approaches in Siewert type II adenocarcinoma at the esophagogastric junction: Protocol for a prospective multicenter randomized controlled trial

BackgroundSiewert type II adenocarcinoma of the esophagogastric junction (Siewert II AEG) can be resected by the right thoracoabdominal surgical approach (RTA) or abdominal-transhiatal surgical approach (TH) under minimally invasive conditions. Although both surgical methods achieve complete tumor resection, there is a debate as to whether the former method is superior to or at least noninferior to the latter in terms of surgical safety. Currently, a small number of retrospective studies have compared the two surgical approaches, with inconclusive results. As such, a prospective multicenter randomized controlled trial is necessary to validate the value of RTA (Ivor-Lewis) compared to TH.MethodsThe planned study is a prospective, multicenter, randomized clinical trial. Patients (n=212) with Siewert II AEG that could be resected by either of the above two surgical approaches will be included in this trial and randomized to the RTA group (n=106) or the TH group (n=106). The primary outcome will be 3-year disease-free survival (DFS). The secondary outcomes will include 5-year overall survival (OS), incidence of postoperative complications, postoperative mortality, local recurrence rate, number and location of removed lymph nodes, quality of life (QOL), surgical Apgar score, and duration of the operation. Follow-ups are scheduled every three months for the first 3 years after the surgery and every six months for the next 2 years.DiscussionAmong Siewert II AEG patients with resectable tumors, this is the first prospective, randomized clinical trial comparing the surgical safety of minimally invasive RTA and TH. RTA is hypothesized to provide better digestive tract reconstruction and dissection of mediastinal lymph nodes while maintaining a high quality of life and good postoperative outcome. Moreover, this trial will provide a high level of evidence for the choice of surgical procedures for Siewert II AEG.Clinical trial registrationChinese Ethics Committee of Registering Clinical Trials, identifier (ChiECRCT20210635); Clinical Trial.gov, identifier (NCT05356520)

Consumer responses to price promotion of organic products in virtue and vice food categories

A substantial body of literature has examined price premiums, willingness-to-pay (WTP), and demand elasticities for organic products, but they have yielded conflicting results regarding how consumers respond to price changes of organic products. These mixed results may be attributed to a number of factors, including frequency of buying organic products, product categories, and consumers’ adaptation to prices of organic products over time. This study investigates the effects of price promotions on purchases of organic products in relative virtue and vice food categories. Consistent with prior research, we consider healthy and unhealthy foods as relative virtue and vice foods, respectively. Using data from the 2015 Nielsen Consumer Panel, our preliminary analyses focus on 57 food categories. Building on the standard log–log model of assessing the effect of price promotions on sales, we consider possible differential responses between organic and nonorganic food within each product category. The estimated demand elasticities suggest that consumers are less sensitive to price changes in organic foods than in conventional foods in certain categories but more sensitive in other categories. We use a logit model to investigate how differential responses depend on food category features, especially the virtue/vice classification. The virtue feature increases the probability that consumers are more sensitive to price changes of organic foods compared to conventional counterparts. This is consistent with past findings that the own-price elasticities of organic fruits and vegetables (virtue foods) are higher than those of their conventional counterparts using data from both the United Kingdom and United States. Consumer WTP for organic products is higher among virtue products, which translates to higher price premiums for organic virtue foods, making a price discount enticing. A price discount on organic virtue foods is more likely to trigger indulgent consumption, as consumers don’t need to find justifications for consuming larger quantities of healthy products. In contrast, to mitigate the guilty feeling from consuming vice foods, consumers may impose quantity constraints on the consumption of these foods, making them less price elastic. We conclude that price promotion effects of organic foods are stronger in virtue categories. Understanding these differential effects has important implications for both manufacturers and retailers in terms of distinctive promotion strategies for organic virtue and vice foods

Pharmacological Targeting of the Mitochondrial Phosphatase PTPMT1S⃞

The dual-specificity protein tyrosine phosphatases (PTPs) play integral roles in the regulation of cell signaling. There is a need for new tools to study these phosphatases, and the identification of inhibitors potentially affords not only new means for their study, but also possible therapeutics for the treatment of diseases caused by their dysregulation. However, the identification of selective inhibitors of the protein phosphatases has proven somewhat difficult. PTP localized to mitochondrion 1 (PTPMT1) is a recently discovered dual-specificity phosphatase that has been implicated in the regulation of insulin secretion. Screening of a commercially available small-molecule library yielded alexidine dihydrochloride, a dibiguanide compound, as an effective and selective inhibitor of PTPMT1 with an in vitro concentration that inhibits response by 50% of 1.08 μM. A related dibiguanide analog, chlorhexidine dihydrochloride, also significantly inhibited PTPMT1, albeit with lower potency, while a monobiguanide analog showed very weak inhibition. Treatment of isolated rat pancreatic islets with alexidine dihydrochloride resulted in a dose-dependent increase in insulin secretion, whereas treatment of a pancreatic β-cell line with the drug affected the phosphorylation of mitochondrial proteins in a manner similar to genetic inhibition of PTPMT1. Furthermore, knockdown of PTPMT1 in rat islets rendered them insensitive to alexidine dihydrochloride treatment, providing evidence for mechanism-based activity of the inhibitor. Taken together, these studies establish alexidine dihydrochloride as an effective inhibitor of PTPMT1, both in vitro and in cells, and support the notion that PTPMT1 could serve as a pharmacological target in the treatment of type II diabetes

Prevalence of Antibiotic Resistance and Virulence Genes in <i>Escherichia coli</i> Carried by Migratory Birds on the Inner Mongolia Plateau of Northern China from 2018 to 2023

(1) Background: Antibiotic resistance in bacteria is an urgent global threat to public health. Migratory birds can acquire antibiotic-resistant and pathogenic bacteria from the environment or through contact with each other and spread them over long distances. The objectives of this study were to explore the relationship between migratory birds and the transmission of drug-resistant pathogenic Escherichia coli. (2) Methods: Faeces and swab samples from migratory birds were collected for isolating E. coli on the Inner Mongolia Plateau of northern China from 2018 to 2023. The resistant phenotypes and spectra of isolates were determined using a BD Phoenix 100 System. Conjugation assays were performed on extended-spectrum β-lactamase (ESBL)-producing strains, and the genomes of multidrug-resistant (MDR) and ESBL-producing isolates were sequenced and analysed. (3) Results: Overall, 179 isolates were antibiotic-resistant, with 49.7% MDR and 14.0% ESBL. Plasmids were successfully transferred from 32% of ESBL-producing strains. Genome sequencing analysis of 91 MDR E. coli strains identified 57 acquired resistance genes of 13 classes, and extraintestinal pathogenic E. coli and avian pathogenic E. coli accounted for 26.4% and 9.9%, respectively. There were 52 serotypes and 54 sequence types (STs), including ST48 (4.4%), ST69 (4.4%), ST131 (2.2%) and ST10 (2.2%). The international high-risk clonal strains ST131 and ST10 primarily carried blaCTX-M-27 and blaTEM-176. (4) Conclusions: There is a high prevalence of multidrug-resistant virulent E. coli in migratory birds on the Inner Mongolian Plateau. This indicates a risk of intercontinental transmission from migratory birds to livestock and humans

Efficacy and safety of olmesartan medoxomil‐amlodipine besylate tablet in Chinese patients with essential hypertension: A prospective, single‐arm, multi‐center, real‐world study

Abstract There lacks real‐world study with a large sample size assessing olmesartan medoxomil‐amlodipine besylate (OM‐AML) tablet. Therefore, this study aimed to evaluate the efficacy and safety of OM‐AML tablet in patients with essential hypertension. Totally, 1341 patients from 36 medical centers with essential hypertension who took OM‐AML (20/5 mg) tablet were analyzed in the current prospective, single‐arm, multi‐center, real‐world study (SVK study). Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, week (W)4 and W8 were measured. The mean (±SE) change of SeSBP/SeDBP was ‐10.8 ± 0.4/‐6.6 ± 0.3 mmHg at W4 and ‐12.7 ± 0.5/‐7.6 ± 0.3 mmHg at W8, respectively. At W4, 78.8% and 29.0% patients achieved BP target by China and American Heart Association (AHA) criteria; at W8, 84.7% and 36.5% patients reached blood pressure (BP) target by China and AHA criteria, accordingly. Meanwhile, 80.2% and 86.4% patients achieved BP response at W4 and W8, respectively. Home‐measured SeSBP and SeDBP decreased from W1 to W8 (both p < .001). Besides, patients’ and physicians’ satisfaction were elevated at W8 compared with W0 (both p < .001). The medication possession rate was 94.8% from baseline to W4 and 91.3% from baseline to W8. The most common drug‐related adverse events were nervous system disorders (4.6%), vascular disorders (2.6%), and general disorders and administration site conditions (2.3%) by system organ class, which were generally mild and manageable. In conclusion, OM‐AML tablet is one of the best antihypertensive agents in patients with essential hypertension