Single session of interpretation bias modification helped to improve fear of COVID-19 and COVID-19-related post-traumatic stress symptoms.

BACKGROUND: Post-traumatic stress symptoms (PTSS) are frequently observed in those who have experienced trauma events like the COVID-19 outbreak. The cognitive model of PTSS highlights the relationship between PTSS and negative interpretation bias. OBJECTIVE: The present study aimed to modify interpretation bias and to improve PTSS as well as PTSS-related fear. METHODS: 59 participants with high PTSS levels were recruited and randomly allocated to either the interpretation modification programme (IMP) intervention group or the interpretation control condition (ICC) control group. PTSS, negative interpretation bias, fear of COVID-19, and depression and anxiety symptoms were assessed before and after training. FINDINGS: Intention-to-treat analyses showed that compared with ICC, participants receiving IMP generated fewer negative interpretations for ambiguous scenarios, and the group-by-time interaction effect was significant. IMP also illustrated a more significant change in fear after training compared with ICC. Although no effects of training conditions were found on PTSS, the interaction of training conditions with fear reduction could predict PTSS improvement. CONCLUSIONS: IMP could improve negative interpretations and fear related to COVID-19 and might help to ameliorate PTSS. CLINICAL IMPLICATIONS: The role of PTSS-related emotion should be considered when exploring the effectiveness of IMP. IMP is a flexible approach that can be tailored to the specific characteristics of the traumatic event, which makes it suitable for a broader range of traumatised individuals.

Real-Time Evaluation of Helicobacter pylori Infection by Convolution Neural Network During White-Light Endoscopy: A Prospective, Multicenter Study (With Video).

INTRODUCTION: Convolutional neural network during endoscopy may facilitate evaluation of Helicobacter pylori infection without obtaining gastric biopsies. The aim of the study was to evaluate the diagnosis accuracy of a computer-aided decision support system for H. pylori infection (CADSS-HP) based on convolutional neural network under white-light endoscopy. METHODS: Archived video recordings of upper endoscopy with white-light examinations performed at Sir Run Run Shaw Hospital (January 2019-September 2020) were used to develop CADSS-HP. Patients receiving endoscopy were prospectively enrolled (August 2021-August 2022) from 3 centers to calculate the diagnostic property. Accuracy of CADSS-HP for H. pylori infection was also compared with endoscopic impression, urea breath test (URT), and histopathology. H. pylori infection was defined by positive test on histopathology and/or URT. RESULTS: Video recordings of 599 patients who received endoscopy were used to develop CADSS-HP. Subsequently, 456 patients participated in the prospective evaluation including 189 (41.4%) with H. pylori infection. With a threshold of 0.5, CADSS-HP achieved an area under the curve of 0.95 (95% confidence interval [CI], 0.93-0.97) with sensitivity and specificity of 91.5% (95% CI 86.4%-94.9%) and 88.8% (95% CI 84.2%-92.2%), respectively. CADSS-HP demonstrated higher sensitivity (91.5% vs 78.3%; mean difference = 13.2%, 95% CI 5.7%-20.7%) and accuracy (89.9% vs 83.8%, mean difference = 6.1%, 95% CI 1.6%-10.7%) compared with endoscopic diagnosis by endoscopists. Sensitivity of CADSS-HP in diagnosing H. pylori was comparable with URT (91.5% vs 95.2%; mean difference = 3.7%, 95% CI -1.8% to 9.4%), better than histopathology (91.5% vs 82.0%; mean difference = 9.5%, 95% CI 2.3%-16.8%). DISCUSSION: CADSS-HP achieved high sensitivity in the diagnosis of H. pylori infection in the real-time test, outperforming endoscopic diagnosis by endoscopists and comparable with URT. Clinicaltrials.gov ; ChiCTR2000030724.

Efficacy and safety of modified tetracycline dosing in a quadruple therapy for Helicobacter pylori: A retrospective single center study.

BACKGROUND: Although highly effective as a component of Helicobacter pylori (H. pylori) treatment regimen, tetracycline is associated with a high incidence of medication-related adverse events. Modified dosing of tetracycline as part of quadruple therapy may improve safety while providing comparable eradication rates. AIM: To evaluate the efficacy and safety of modified dosing of tetracycline in patients receiving tetracycline and furazolidone-containing quadruple therapy in patients with H. pylori infection. METHODS: Consecutive patients (10/2020-12/2021) who received tetracycline and furazolidone quadruple therapy for H. pylori infection at Sir Run Run Shaw Hospital were identified. All patients received tetracycline, furazolidone, proton pump inhibitor, and bismuth for 14 d as primary or rescue therapy. Modified tetracycline dose group received tetracycline 500 mg twice daily while standard group received 750 mg twice daily or 500 mg three times daily. RESULTS: Three hundred and ninety-four patients [mean age = 46.3 ± 13.9, male = 137 (34.8%), and 309 (78.4%) primary therapy] completed tetracycline and furazolidone quadruple therapy for H. pylori infection including those who received modified tetracycline dose in 157 and standard doses in 118 (750 mg twice daily) and 119 (500 mg three times daily). Eradication rates in the modified tetracycline dose group were 92.40% and in the standard groups, eradication rates were 93.20% for 750 mg twice daily group and 92.43% for 500 mg three times daily group, respectively, without statistical difference (P = 0.959). The incidence of adverse events was lower in the modified tetracycline dose (15.3% vs 32.3% and 29.4%; P = 0.002) compared to the standard dose group. CONCLUSION: In a real-world experience, modified tetracycline dosing as part of tetracycline and furazolidone quadruple therapy for 14 d demonstrated high efficacy, comparable to standard tetracycline dose regimens, with a favorable safety profile.

Advances of endoscopic and surgical management in gastrointestinal stromal tumors.

As one of the most common mesenchymal malignancies in the digestive system, gastrointestinal stromal tumors (GISTs) occur throughout the alimentary tract with diversified oncological characteristics. With the advent of the tyrosine kinase inhibitor era, the treatment regimens of patients with GISTs have been revolutionized and GISTs have become the paradigm of multidisciplinary therapy. However, surgery resection remains recognized as the potentially curative management for the radical resection and provided with favorable oncological outcomes. The existing available surgery algorithms in clinical practice primarily incorporate open procedure, and endoscopic and laparoscopic surgery together with combined operation techniques. The performance of various surgery methods often refers to the consideration of risk evaluation of recurrence and metastases; the degree of disease progression; size, location, and growth pattern of tumor; general conditions of selected patients; and indications and safety profile of various techniques. In the present review, we summarize the fundamental principle of surgery of GISTs based on risk assessment as well as tumor size, location, and degree of progress with an emphasis on the indications, strengths, and limitations of current surgery techniques.

A Leucine-Rich Repeat Receptor-like Kinase TaBIR1 Contributes to Wheat Resistance against Puccinia striiformis f. sp. tritici.

Plant cell surface-localized receptor-like kinases (RLKs) recognize invading pathogens and transduce the immune signals inside host cells, subsequently triggering immune responses to fight off pathogen invasion. Nonetheless, our understanding of the role of RLKs in wheat resistance to the biotrophic fungus Puccinia striiformis f. sp. tritici (Pst) remains limited. During the differentially expressed genes in Pst infected wheat leaves, a Leucine-repeat receptor-like kinase (LRR-RLK) gene TaBIR1 was significantly upregulated in the incompatible wheat-Pst interaction. qRT-PCR verified that TaBIR1 is induced at the early infection stage of Pst. The transient expression of TaBIR1-GFP protein in N. bentamiana cells and wheat mesophyll protoplasts revealed its plasma membrane location. The knockdown of TaBIR1 expression by VIGS (virus induced gene silencing) declined wheat resistance to stripe rust, resulting in reduced reactive oxygen species (ROS) production, callose deposition, and transcripts of pathogenesis-related genes TaPR1 and TaPR2, along with increased Pst infection area. Ectopic overexpression of TaBIR1 in N. benthamiana triggered constitutive immune responses with significant cell death, callose accumulation, and ROS production. Moreover, TaBIR1 triggered immunity is dependent on NbBAK1, the silencing of which significantly attenuated the defense response triggered by TaBIR1. TaBIR1 interacted with the NbBAK1 homologues in wheat, co-receptor TaSERK2 and TaSERK5, the transient expression of which could restore the impaired defense due to NbBAK1 silencing. Taken together, TaBIR1 is a cell surface RLK that contributes to wheat stripe rust resistance, probably as a positive regulator of plant immunity in a BAK1-dependent manner.

Effectiveness and safety of vonoprazan-based regimens compared with those of proton pump inhibitor (PPI)-based regimens as first-line agents for Helicobacter pylori: a meta-analysis of randomized clinical trials.

PURPOSE: Vonoprazan (VPZ), a reversible H+-K+ ATPase inhibitor, has a relatively fast and sustained acid-suppression action that is unaffected by diet or gene polymorphisms. Several randomized controlled trials have evaluated the difference in the eradication rate of Helicobacter pylori (HP) between VPZ-based and proton pump inhibitor (PPI)-based regimens. The present review aimed to (1) evaluate the efficacy, safety, and compliance of VPZ-based regimens compared with those of PPI-based regimens as first-line treatments for HP infection and (2) perform a subgroup analysis to examine the influence of differences in clarithromycin-resistance status, treatment duration, treatment regimens, and research region on treatment outcomes. METHODS: We conducted a systematic literature search on PubMed, Embase, Cochrane Library, Web of Science, and ChiCTR Register. Systematic searches, study selection, data extraction, risk of bias assessment, and statistical analysis were performed according to pre-registered protocol on the PROSPERO (CRD42022336608). RESULTS: Eight studies and 2956 HP-infected patients were enrolled. Only first-line therapy and RCT study were considered. VPZ-based group had a superior eradication efficacy compared to PPI-based group by intention-to-treat (ITT) (pooled risk ratio (RR): 1.14, 95% CI: 1.08-1.21, p < 0.00001) and per-protocol analysis (pooled RR: 1.13, 95% CI: 1.07-1.20, p < 0.00001). This finding was further validated by subgroup analysis depending on treatment regimens, duration, region, and clarithromycin resistance. In addition, there was no significant difference in adverse events (p = 0.33) and compliances (p = 0.30) between the regimens. CONCLUSION: The VPZ-based regimens showed a superior eradication efficacy compared to the already frequently used PPI-based regimens. Furthermore, VPZ-based therapy showed comparable tolerability and incidence of adverse events.

SHP2 inhibition mitigates adaptive resistance to MEK inhibitors in KRAS-mutant gastric cancer through the suppression of KSR1 activity.

Despite the promising antitumor activity of RAF/MEK inhibitors for RAS-driven cancers, not all patients respond to these therapies. Adaptive resistance has been reported as a major culprit in non-responders, which can be reversed by SHP2 inhibitors (SHP2is) in multiple cancer cells; however, the underlying mechanisms remain unknown. In this study, we found that KRAS-mutant gastric cancer cells respond to MEK inhibitors (MEKis) with adaptive resistance. Markedly, SHP2 activation accompanied by ERK signaling restoration in MEKi-treated cells, and a MEKi and SHP2i combination had a synergistic effect on downstream signaling blockade. In vivo, SHP099 combined with AZD6244 (selumetinib) was highly efficacious for the treatment of xenografts. Mechanistically, SHP2 was found to interact with the scaffold protein KSR1 through its protein tyrosine phosphatase domain. KSR1 knockdown sensitized cells to AZD6244, whereas a KSR1 activating mutation (S269A) diminished the synergistic anti-proliferative effect of SHP2i and MEKi. Interestingly, activated SHP2, during adaptive resistance to MEKis, impaired the interaction with KSR1, activating KSR1 to promote MAPK signaling. In conclusion, SHP2 promotes adaptive resistance to MEKis by activating KSR1; selumetinib combined with SHP099 might be an available therapeutic strategy for KRAS-mutant gastric cancers.

Multiple Bismuth Quadruple Therapy Containing Tetracyclines Combined with Other Antibiotics and Helicobacter pylori Eradication Therapy.

Helicobacter pylori (HP) infection is closely associated with the development of chronic gastritis, peptic ulcer, and gastric cancer. However, the resistance rate of H. pylori strains to antibiotics such as clarithromycin, metronidazole, and levofloxacin has increased significantly, resulting in a significant decrease in the eradication efficacy of commonly used regimens. Tetracycline has received the attention of domestic and foreign scholars because of its low resistance. The purpose of this review is to provide an update on the tetracycline-containing bismuth quadruple eradication therapy for H. pylori infection and review the efficacy and safety of the regimens, hoping to provide guidance for clinical practice.

An overview of agents and treatments for PDGFRA-mutated gastrointestinal stromal tumors.

Platelet-derived growth factor receptor A (PDGFRA) mutations occur in approximately 10-15% of gastrointestinal stromal tumors (GISTs). These tumors with PDGFRA mutations have a different pathogenesis, clinical characteristics, and treatment response compared to tumors with receptor tyrosine kinase protein (KIT) mutations (60-70%). Many clinical studies have investigated the use of tyrosine kinase inhibitors mainly in patients with KIT mutations; however, there is a lack of attention to the PDGFRA-mutated molecular subtype. The main effective inhibitors of PDGFRA are ripretinib, avapritinib, and crenolanib, and their mechanisms and efficacy in GIST (as confirmed in clinical trials) are described in this review. Some multi-targeted tyrosine kinase inhibitors with inhibitory effects on this molecular subtype are also introduced and summarized in this paper. This review focuses on PDGFRA-mutated GISTs, introduces their clinical characteristics, downstream molecular signaling pathways, and existing resistance mechanisms. We focus on the most recent literature that describes the development of PDGFRA inhibitors and their use in clinical trials, as well as the potential benefits from different combination therapy strategies.

Might Patients with Metastatic Gastrointestinal Stromal Tumors Benefit from Operative Management? A Population-Based Retrospective Study.

Background: With respect to effect of surgery on the therapy of patients with metastatic gastrointestinal stromal tumors (mGISTs), still no consensus has been reached. This research designed to investigate the effect of surgical treatment on prognosis in patients with mGISTs. Methods: The population-based study consisted of 6282 GIST patients diagnosed between 2001 and 2016, from the Surveillance, Epidemiology, and End Results (SEER) database registry. The Kaplan-Meier method and Cox model were employed for the exploration of the effect of surgery on overall survival (OS) and GIST-specific survival (GSS). Results: In total, 6282 patients were diagnosed with GISTs, including 1238 (19.7%) mGIST patients and 5044 (80.3%) non-mGIST patients. Compared with the patients with non-mGISTs, metastatic patients assumed relatively lower proportion of surgical management (756 [61.1%] vs. 4666 [92.5%], P < 0.001). Based on unadjusted analysis, mGIST patients with operative management presented higher five years OS together with GSS in comparison with those without operative management (OS: 58.3% vs. 33.1%, P < 0.001; GSS: 61.6% vs. 36.7%, P < 0.001). Multivariable analysis found that no surgery was correlated to more than 2-fold increased death risk (OS, adjusted HR = 2.27, 95% CI: 1.90-2.71; GSS, adjusted HR = 2.42, 95% CI: 2.00-2.93). Conclusion: Metastatic GIST patients could potentially benefit from operative management with improved GSS and OS.

[Preliminary study of dihydroartemisin in inhibiting invasion and metastasis of hepatoma cells].

It is reported that dihydroartemisinin could reduce the expression of phosphorylated adhesion kinase and matrix metalloproteinase-2, inhibit the growth, migration and invasion of ovarian cancer cells, promote the formation of Treg cells through TGF-beta/Smad signaling pathway, and play an immunosuppressive role; dihydroartemisinin could also inhibit the growth of lung cancer cells by inhibiting the expression of vascular endothelial growth factor(VEGF) receptor KDR. However, there are few studies on dihydroartemisinin in hepatocellular carcinoma cells. In order to preliminarily explore the effect of dihydroartemisinin on invasion and metastasis of hepatocellular carcinoma cells, CCK-8 method and crystal violet staining were used to detect the effect of dihydroartemisinin on the growth of hepatocellular carcinoma cell 7402 and highly metastatic hepatocellular carcinoma cell MHCC97 H. The effects of dihydroartemisinin on the invasion and metastasis of hepatocellular carcinoma cell 7402 and highly metastatic hepatocellular carcinoma cell MHCC97 H were studied by using cell wound healing and Transwell. Western blot was used to detect the protein expression of epidermal growth factor receptor(EGFR) and its downstream signaling pathway in cells treated with dihydroartemisinin for 48 hours. The results showed that dihydroartemisinin could inhibit the growth of hepatocellular carcinoma cell 7402 and highly metastatic hepatocellular carcinoma cell MHCC97 H at 25 µmol·L~(-1). As compared with the control group, the number of cell clones was significantly reduced, and the ability of cell migration and invasion was weakened. Western blot results showed that as compared with the control group, dihydroartemisinin group could down-regulate the protein expression of EGFR and its downstream signaling pathways p-AKT, p-ERK, N-cadherin, Snail and Slug, and up-regulate the expression of E-cadherin protein, thus affecting the migration, invasion and metastasis of hepatocellular carcinoma cells 7402 and MHCC97 H.

Effects of dietary-fiber levels on RANK/RANKL/OPG expression in the appendix of weanling rabbits.

BACKGROUND/PURPOSE: The dietary fiber can regulate the intestinal mucosal immunity, and the M cell is the portal for initiating mucosal immunity. We investigated the effects of dietary fiber on the transport of Escherichia coli to assess the function of microfold (M) cells in the appendix. METHOD: A total of 150 New Zealand rabbits were fed three diets (high fiber (HF): 31.72%; control: 37.36%; low dietary fiber (LF): 41.84%; neutral detergent fiber (NDF). An infection model was established in vivo using E. coli containing green fluorescent protein as the indicator in appendix loops. Samples were collected before and after inoculation with indicator for 10, 30, or 60 min. The M cells number, differentiation-related genes and proteins were monitored by respectively using immunofluorescence, Q-PCR and Western-blot. RESULTS: The number of M cells in HF group was significantly higher than that of LF group before and at 10 min, 30 min post injection with E.coli (P < 0.01), which has an opposite at 60 min. The number of fluorescent E. coli transported across the appendix was significantly increased in the HF group (P < 0.01) compared with the LF group at 30 min (P < 0.001); expression of RANKL gene and protein levels were no difference between HF and LF group. The variation tendency of RANK, OPG genes and proteins were consistent with the change of M cell transport indicator number in different time points. CONCLUSION: Our study showed that a high-fiber diet can increase number of M cells and speed up antigen transfer under regulation of ANKL/OPG/RANK system.

Wheat Gene TaATG8j Contributes to Stripe Rust Resistance.

Autophagy-related 8 (ATG8) protein has been reported to be involved in plant's innate immune response, but it is not clear whether such genes play a similar role in cereal crops against obligate biotrophic fungal pathogens. Here, we reported an ATG8 gene from wheat (Triticum aestivum), designated TaATG8j. This gene has three copies located in chromosomes 2AS, 2BS, and 2DS. The transcriptions of all three copies were upregulated in plants of the wheat cultivar Suwon 11, inoculated with an avirulent race (CYR23) of Puccinia striiformis f. sp. tritici (Pst), the causal fungal pathogen of stripe rust. The transient expression of TaATG8j in Nicotiana benthamiana showed that TaATG8j proteins were distributed throughout the cytoplasm, but mainly in the nucleus and plasma membrane. The overexpression of TaATG8j in N. benthamiana slightly delayed the cell death caused by the mouse apoptotic protein BAX (BCL2-associated X protein). However, the expression of TaATG8j in yeast (Schizosaccharomyces pombe) induced cell death. The virus-induced gene silencing of all TaATG8j copies rendered Suwon 11 susceptible to the avirulent Pst race CYR23, accompanied by an increased fungal biomass and a decreased necrotic area per infection site. These results indicate that TaATG8j contributes to wheat resistance against stripe rust fungus by regulating cell death, providing information for the understanding of the mechanisms of wheat resistance to the stripe rust pathogen.