The AP-2 Family of Transcription Factors-Still Undervalued Regulators in Gastroenterological Disorders.

Activating enhancer-binding protein 2 (AP-2) is a family of transcription factors (TFs) that play crucial roles in regulating embryonic and oncogenic development. In addition to splice isoforms, five major family members encoded by the TFAP2A/B/C/D/E genes have been identified in humans, i.e., AP-2α/ß/γ/δ/ε. In general, the first three TFs have been studied more thoroughly than AP-2δ or AP-2ε. Currently, there is a relatively limited body of literature focusing on the AP-2 family in the context of gastroenterological research, and a comprehensive overview of the existing knowledge and recommendations for further research directions is lacking. Herein, we have collected available gastroenterological data on AP-2 TFs, discussed the latest medical applications of each family member, and proposed potential future directions. Research on AP-2 in gastrointestinal tumors has predominantly been focused on the two best-described family members, AP-2α and AP-2γ. Surprisingly, research in the past decade has highlighted the importance of AP-2ε in the drug resistance of gastric cancer (GC) and colorectal cancer (CRC). While numerous questions about gastroenterological disorders await elucidation, the available data undoubtedly open avenues for anti-cancer targeted therapy and overcoming chemotherapy resistance. In addition to gastrointestinal cancers, AP-2 family members (primarily AP-2ß and marginally AP-2γ) have been associated with other health issues such as obesity, type 2 diabetes, liver dysfunction, and pseudo-obstruction. On the other hand, AP-2δ has been poorly investigated in gastroenterological disorders, necessitating further research to delineate its role. In conclusion, despite the limited attention given to AP-2 in gastroenterology research, pivotal functions of these transcription factors have started to emerge and warrant further exploration in the future.

Helicobacter pylori eradication following endoscopic resection might prevent metachronous gastric cancer: a systematic review and meta-analysis of studies from Japan and Korea.

Objectives: A systematic review and meta-analysis was performed to evaluate the preventive effectiveness of Helicobacter pylori eradication against metachronous gastric cancer (MGC) or dysplasia following endoscopic resection (ER) for early gastric cancer (EGC) or dysplasia. Methods: PubMed, Cochrane Library, MEDLINE, and EMBASE were searched until 31 October 2023, and randomized controlled trials or cohort studies were peer-reviewed. The incidence of metachronous gastric lesions (MGLs) including MGC or dysplasia was compared between Helicobacter pylori persistent and negative groups, eradicated and negative groups, and eradicated and persistent groups. Results: Totally, 21 eligible studies including 82,256 observations were analyzed. Compared to those never infected, Helicobacter pylori persistent group (RR = 1.58, 95% CI = 0.98-2.53) trended to have a higher risk of MGLs and significantly in partial subgroups, while the post-ER eradicated group (RR = 0.79, 95% CI = 0.43-1.45) did not increase the risk of MGLs. Moreover, successful post-ER eradication could significantly decrease the risk of MGLs (RR = 0.54, 95% CI = 0.44-0.65) compared to those persistently infected. Sensitivity analysis obtained generally consistent results, and no significant publication bias was found. Conclusion: The persistent Helicobacter pylori infection trends to increase the post-ER incidence of MGC or dysplasia, but post-ER eradication can decrease the risk correspondingly. Post-ER screening and eradication of Helicobacter pylori have preventive effectiveness on MGC, and the protocol should be recommended to all the post-ER patients.Systematic review registration: The PROSPERO registration identification was CRD42024512101.

Ferroptosis at the nexus of metabolism and metabolic diseases.

Ferroptosis, an iron-dependent form of regulated cell death, is emerging as a crucial regulator of human physiology and pathology. Increasing evidence showcases a reciprocal relationship between ferroptosis and dysregulated metabolism, propagating a pathogenic vicious cycle that exacerbates pathology and human diseases, particularly metabolic disorders. Consequently, there is a rapidly growing interest in developing ferroptosis-based therapeutics. Therefore, a comprehensive understanding of the intricate interplay between ferroptosis and metabolism could provide an invaluable resource for mechanistic insight and therapeutic development. In this review, we summarize the important metabolic substances and associated pathways in ferroptosis initiation and progression, outline the cascade responses of ferroptosis in disease development, overview the roles and mechanisms of ferroptosis in metabolic diseases, introduce the methods for ferroptosis detection, and discuss the therapeutic perspectives of ferroptosis, which collectively aim to illustrate a comprehensive view of ferroptosis in basic, translational, and clinical science.

An Imine-Functionalized Silicone-Based Epoxy Coating with Stable Adhesion and Controllable Degradation for Enhanced Marine Antifouling and Anticorrosion Properties.

Biofouling and corrosion of submerged equipment caused by marine organisms severely restrict the rapid development of the marine industry. Traditional antifouling or anticorrosion coatings typically serve a sole purpose and exhibit limited degradability upon failure, rendering them inadequate for current demands. Herein, a novel imine-functionalized command-degradable bio-based epoxy coating (SAHPEP-DDM) with enhanced integrated antifouling and anticorrosion performances was synthesized utilizing 1,3-bis (3-aminopropyl)-1,1,3,3-tetramethyldisiloxane and syringaldehyde. Compared with commercial epoxy resins (E51-DDM) and polydimethylsiloxanes (PDMS), the SAHPEP-DDM coating exhibits superior antifouling and anticorrosion properties due to the existence of -C=N- and Si-O-Si chain segments in the cross-linking network. The coating achieves resistance rates of 99.59 % and 99.20 % against E. coli and S. aureus, respectively, and shows promising resistance against algae and proteins, as well as excellent corrosion resistance in artificial seawater (with |Z|0.01 Hz and arc radius of about 1011â€…Ω and exceeding 1010â€…Ω respectively). The coating also exhibits excellent chemical resistance in organic solvents as well as neutral and alkaline environments. Moreover, its controlled degradation after coating failure can be achieved in acid aqueous solutions through temperature and acidity adjustments, facilitated by the presence of -C=N-. This work presents a novel degradable coating successfully coupled the dual functions of antifouling and anticorrosion coatings, avoiding the employment of intermediate coat, indicating vast potential for application in various marine engineering fields.

Clinicopathological features of hepatoid adenocarcinoma and non-hepatoid adenocarcinoma of the stomach: A systematic review and meta-analysis.

BACKGROUND: Hepatoid adenocarcinoma of the stomach (HAS) is an extremely rare and unique malignant gastric tumor with a significantly worse prognosis than non-hepatoid adenocarcinoma of the stomach (non-HAS). The present study explored the clinicopathological features of HAS and non-HAS patients to provide insights into HAS treatment strategies. METHODS: From December 26, 2023, we performed a comprehensive search of the PubMed, Web of Science, Cochrane Library, and Embase.com databases for relevant studies. Two authors independently screened the studies, evaluated their quality, extracted data, and performed the analyses. This study was registered with PROSPERO on January 2, 2024. RESULTS: Nine retrospective studies were included for analysis after screening 833 articles. A total of 350 and 924 patients were enrolled in the HAS and non-HAS groups, respectively. While no significant differences were observed in age, sex, tumor size, T3 or T4 stage, and N2 or N3 stage between the two groups, the HAS group exhibited higher rates of lymph node metastasis (OR = 1.93, 95% CI: 1.19-3.13, p = 0.007), liver metastasis (OR = 3.45, 95% CI: 2.26-5.28, p < 0.001), and vascular invasion (OR = 2.76, 95% CI: 2.05-3.71, p < 0.001). Additionally, the HAS group had lower 3-year survival rates (HR = 2.35, 95% CI: 1.70-3.25, p < 0.001) and 5-year survival rates (HR = 3.63, 95% CI: 1.49-8.88, p = 0.005), but lower rates of lymphatic permeation (OR = 0.68, 95% CI: 0.47-0.99, p = 0.040). CONCLUSION: Based on the current clinical evidence, patients with HAS present distinct clinicopathological features, greater invasiveness, and poorer prognosis than non-HAS patients. Further research is warranted to develop optimal treatment strategies for HAS.

Distinct oral-associated gastric microbiota and Helicobacter pylori communities for spatial microbial heterogeneity in gastric cancer.

The gastric microbial community plays a fundamental role in gastric cancer (GC), and the two main anatomical subtypes of GC, non-cardia and cardia GC, are associated with different risk factors (Helicobacter pylori for non-cardia GC). To decipher the different microbial spatial communities of GC, we performed a multicenter retrospective analysis to characterize the gastric microbiota in 223 GC patients, including H. pylori-positive or -negative patients, with tumors and paired adjacent normal tissues, using third-generation sequencing. In the independent validation cohort, both dental plaque and GC tumoral tissue samples were collected and sequenced. The prevalence of H. pylori and oral-associated bacteria was verified using fluorescence in situ hybridization (FISH) assays in GC tumoral tissues and matched nontumoral tissues. We found that the vertical distribution of the gastric microbiota, at the upper, middle, and lower third sites of GC, was likely an important factor causing microbial diversity in GC tumor tissues. The oral-associated microbiota cluster, which included Veillonella parvula, Streptococcus oralis, and Prevotella intermedia, was more abundant in the upper third of the GC. However, H. pylori was more abundant in the lower third of the GC and exhibited a significantly high degree of microbial correlation. The oral-associated microbiota module was co-exclusive with H. pylori in the lower third site of the GC tumoral tissue. Importantly, H. pylori-negative GC patients with oral-associated gastric microbiota showed worse overall survival, while the increase in microbial abundance in H. pylori-positive GC patients showed no difference in overall survival. The prevalence of V. parvula in both the dental plaque and GC tissue samples was concordant in the independent validation phase. We showed that the oral-associated species V. parvula and S. oralis were correlated with overall survival. Our study highlights the roles of the oral-associated microbiota in the upper third of the GC. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for H. pylori-negative GCs. IMPORTANCE: Our study highlights the roles of the oral-associated microbiota in the upper third of gastric cancer (GC).We showed that the oral-associated species Veillonella parvula and Streptococcus oralis were correlated with overall survival. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for Helicobacter pylori-negative GCs.

Dissecting positive selection events and immunological drives during the evolution of adeno-associated virus lineages.

Adeno-associated virus (AAV) serotypes from primates are being developed and clinically used as vectors for human gene therapy. However, the evolutionary mechanism of AAV variants is far from being understood, except that genetic recombination plays an important role. Furthermore, little is known about the interaction between AAV and its natural hosts, human and nonhuman primates. In this study, natural AAV capsid genes were subjected to systemic evolutionary analysis with a focus on selection drives during the diversification of AAV lineages. A number of positively selected sites were identified from these AAV lineages with functional relevance implied by their localization on the AAV structures. The selection drives of the two AAV2 capsid sites were further investigated in a series of biological experiments. These observations did not support the evolution of the site 410 of the AAV2 capsid driven by selection pressure from the human CD4+ T-cell response. However, positive selection on site 548 of the AAV2 capsid was directly related to host humoral immunity because of the profound effects of mutations at this site on the immune evasion of AAV variants from human neutralizing antibodies at both the individual and population levels. Overall, this work provides a novel interpretation of the genetic diversity and evolution of AAV lineages in their natural hosts, which may contribute to their further engineering and application in human gene therapy.

Sea Anemone-Inspired Slippery Liquid-Infused Porous Surface (SLIPS) with Bionic Cilia for Responsive 4D Antifouling.

The formation process of biofouling is actually a 4D process with both spatial and temporal dimensions. However, most traditional antifouling coatings, including slippery liquid-infused porous surface (SLIPS), are limited to performing antifouling process in the 2D coating plane. Herein, inspired by the defensive behavior of sea anemones' wielding toxic tentacles, a "4D SLIPS" (FSLIPS) is constructed with biomimetic cilia via a magnetic field self-assembly method for antifouling. The bionic cilia move in 3D space driven by an external magnetic field, thereby preventing the attachment of microorganisms. The FSLIPS releases the gaseous antifoulant (nitric oxide) at 1D time in response to light, thereby achieving a controllable biocide effect on microorganisms. The FSLIPS regulates the movement of cilia via the external magnetic field, and controls the release of NO overtime via the light response, so as to adjust the antifouling modes on demand during the day or night. The light/magnetic response mechanism endow the FSLIPS with the ability to adjust the antifouling effect in the 4D dimension of 1D time and 3D space, effectively realizing the intelligence, multi-dimensionality and precision of the antifouling process.

Toward Verification of DAG-Based Distributed Ledger Technologies through Discrete-Event Simulation.

As the potential of directed acyclic graph (DAG)-based distributed ledgers in IoT systems unfolds, a need arises to understand their intricate dynamics in real-world scenarios. It is well known that discrete event simulations can provide high-fidelity evaluations of protocols. However, there is a lack of public discrete event simulators capable of assessing DAG-based distributed ledgers. In this paper, a discrete-event-based distributed ledger simulator is introduced, with which we investigate a custom Python-based implementation of IOTA's Tangle DAG protocol. The study reveals the dynamics of Tangle (particularly Poisson processes in transaction dynamics), the efficiency and intricacies of the random walk in Tangle, and the quantitative assessment of node convergence. Furthermore, the research underscores the significance of weight updates without depth limitations and provides insights into the role, challenges, and implications of the coordinator/validator in DAG architectures. The results are striking, and although the findings are reported only for Tangle, they demonstrate the need for adaptable and versatile discrete event simulators for DAG architectures and tip selection methodologies in general.

Development and validation of a nomogram for Siewert II esophagogastric junction adenocarcinoma: a retrospective analysis.

Background: Due to the complex histological type and anatomical structures, there has been considerable debate on the classification of adenocarcinoma of the esophagogastric junction (AEG), especially Siewert II AEG. Furthermore, neither the American Joint Committee on Cancer (AJCC) 7th tumor-node-metastasis (TNM) [esophageal adenocarcinoma (E) or gastric cancer (G)] nor the AJCC 8th TNM (E or G) accurately predicted the prognosis of patients with Siewert II AEG. Objective: This study aimed to investigate the factors influencing the survival and prognosis of patients with Siewert II AEG and establish a new and better prognostic predictive model. Design: A retrospective study. Methods: Patients with Siewert II AEG, retrieved from the Surveillance, Epidemiology, and End Results (SEER) databases, were assigned to the training set. Patients retrieved from a single tertiary medical center were assigned to the external validation set. Significant variables were selected using univariate and multivariate Cox regression analyses to construct the nomogram. Nomogram models were assessed using the concordance index (C-index), a calibration plot, decision curve analysis (DCA), and external validation. Results: Age, tumor grade, and size, as well as the T, N, and M stages, were included in the nomograms. For the SEER training set, the C-index of the nomogram was 0.683 (0.665-0.701). The C-index of the nomogram for the external validation set was 0.690 (0.653-0.727). The calibration curve showed good agreement between the nomogram estimations and actual observations in both the training and external validation sets. The DCA showed that the nomogram was clinically useful. Conclusion: The new predictive model showed significant accuracy in predicting the prognosis of Siewert II AEG.

Long-term oncological outcomes of robotic versus laparoscopic gastrectomy for gastric cancer: multicentre cohort study.

BACKGROUND: The aim of this multicentre cohort study was to compare the long-term oncological outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for patients with gastric cancer. METHODS: Patients with gastric cancer who underwent radical gastrectomy by robotic or laparoscopic approaches from 1 March 2010 to 31 December 2018 at 10 high-volume centres in China were selected from institutional databases. Patients receiving RG were matched 1 : 1 by propensity score with patients undergoing LG. The primary outcome was 3-year disease-free survival. Secondary outcomes were overall survival and disease recurrence. RESULTS: Some 2055 patients who underwent RG and 4309 patients who had LG were included. The propensity score-matched cohort comprised 2026 RGs and 2026 LGs. Median follow-up was 41 (i.q.r. 39-58) months for the RG group and 39 (38-56) months for the LG group. The 3-year disease-free survival rates were 80.8% in the RG group and 79.5% in the LG group (log rank P = 0.240; HR 0.92, 95% c.i. 0.80 to 1.06; P = 0.242). Three-year OS rates were 83.9 and 81.8% respectively (log rank P = 0.068; HR 0.87, 0.75 to 1.01; P = 0.068) and the cumulative incidence of recurrence over 3 years was 19.3% versus 20.8% (HR 0.95, 0.88 to 1.03; P = 0.219), with no difference between groups. CONCLUSION: RG and LG in patients with gastric cancer are associated with comparable disease-free and overall survival.

[Carbon Emission Characteristics and Influencing Factors of Typical Processes in Drinking Water Treatment Plant].

Based on the actual operating conditions and data monitoring, the carbon emission characteristics of typical processes of a drinking water treatment plant (DWTP) in Tianjin were studied. The total carbon emission intensity measured by CO2-eq was 0.254 kg·m-3, and the proportion of carbon emissions from electricity consumption and reagent consumption was 81.76% and 9.15%, respectively. The key carbon emission sectors of electricity consumption were the water supply pump house, ultrafiltration membrane process, and inlet pump house, which accounted for 50.99%-73.51%, 17.64%-20.70%, and 17.97%-22.40% of the total carbon emission from electricity consumption in the DWTP, respectively. The contribution of sodium hypochlorite to the carbon emission of reagent consumption was 89.12%-90.30%, followed by ferric chloride, PAC, and ammonium sulfate. In the traditional water purification process, the carbon emission intensity of the process unit was in the order of inlet pump house > rapid filter > sedimentation tank. The order in the ultrafiltration membrane advanced treatment process was inlet pump house > ultrafiltration membrane > mechanical coagulation > clarification tank. The carbon emission intensity of the rapid filter process and the ultrafiltration membrane process were 0.070 9 kg·m-3 and 0.109 0 kg·m-3, respectively. The ultrafiltration membrane process could save 23% of the reagent consumption, and its carbon emission of electricity consumption was twice that of the traditional treatment process. The analysis of factors affecting carbon emission in key sectors showed that the raw water quality parameters such as turbidity, pH, ammonia nitrogen, temperature, etc., were significantly correlated with the carbon emission intensity of sodium hypochlorite. There was a significant linear regression relationship between ex-factory water pressure, daily water supply, and carbon emission intensity of the water supply pump house. The control measures of water quality and water pressure can effectively reduce the carbon emissions of the DWTP.

Enzyme-Responsive Branched Glycopolymer-Based Nanoassembly for Co-Delivery of Paclitaxel and Akt Inhibitor toward Synergistic Therapy of Gastric Cancer.

Combined chemotherapy and targeted therapy holds immense potential in the management of advanced gastric cancer (GC). GC tissues exhibit an elevated expression level of protein kinase B (AKT), which contributes to disease progression and poor chemotherapeutic responsiveness. Inhibition of AKT expression through an AKT inhibitor, capivasertib (CAP), to enhance cytotoxicity of paclitaxel (PTX) toward GC cells is demonstrated in this study. A cathepsin B-responsive polymeric nanoparticle prodrug system is employed for co-delivery of PTX and CAP, resulting in a polymeric nano-drug BPGP@CAP. The release of PTX and CAP is triggered in an environment with overexpressed cathepsin B upon lysosomal uptake of BPGP@CAP. A synergistic therapeutic effect of PTX and CAP on killing GC cells is confirmed by in vitro and in vivo experiments. Mechanistic investigations suggested that CAP may inhibit AKT expression, leading to suppression of the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. Encouragingly, CAP can synergize with PTX to exert potent antitumor effects against GC after they are co-delivered via a polymeric drug delivery system, and this delivery system helped reduce their toxic side effects, which provides an effective therapeutic strategy for treating GC.

Slippery Porous-Liquid-Infused Porous Surface (SPIPS) with On-Demand Responsive Switching between "Defensive" and "Offensive" Antifouling Modes.

Slippery liquid-infused porous surfaces (SLIPS) have received widespread attention in the antifouling field. However, the reduction in antifouling performance caused by lubricant loss limits their application in marine antifouling. Herein, inspired by the skin of a poison dart frog which contains venom glands and mucus, a porous liquid (PL) based on ZIF-8 is prepared as a lubricant and injected into a silicone polyurethane (SPU) matrix to construct a new type of SLIPS for marine antifouling applications: the slippery porous-liquid-infused porous surface (SPIPS). The SPIPS consists of a responsive antifoulant-releasing switch between "defensive" and "offensive" antifouling modes to intelligently enhance the antifouling effect after lubricant loss. The SPIPS can adjust antifouling performance to meet the antifouling requirements under different light conditions. The wastage of antifoulants is reduced, thereby effectively maintaining the durability and service life of SLIPS materials. The SPIPS exhibits efficient lubricant self-replenishment, self-cleaning, anti-protein, anti-bacterial, anti-algal, and self-healing (97.48%) properties. Furthermore, it shows satisfactory 360-day antifouling performance in actual marine fields during boom seasons, demonstrating the longest antifouling lifespan in the field tests of reported SLIPS coatings. Hence, the SPIPS can effectively promote the development of SLIPS for neritic antifouling.

Nanomedicine Combats Drug Resistance in Lung Cancer.

Lung cancer is the second most prevalent cancer and the leading cause of cancer-related death worldwide. Surgery, chemotherapy, molecular targeted therapy, immunotherapy, and radiotherapy are currently available as treatment methods. However, drug resistance is a significant factor in the failure of lung cancer treatments. Novel therapeutics have been exploited to address complicated resistance mechanisms of lung cancer and the advancement of nanomedicine is extremely promising in terms of overcoming drug resistance. Nanomedicine equipped with multifunctional and tunable physiochemical properties in alignment with tumor genetic profiles can achieve precise, safe, and effective treatment while minimizing or eradicating drug resistance in cancer. Here, this work reviews the discovered resistance mechanisms for lung cancer chemotherapy, molecular targeted therapy, immunotherapy, and radiotherapy, and outlines novel strategies for the development of nanomedicine against drug resistance. This work focuses on engineering design, customized delivery, current challenges, and clinical translation of nanomedicine in the application of resistant lung cancer.

Weakly Supervised Solar Panel Mapping via Uncertainty Adjusted Label Transition in Aerial Images.

This paper proposes a novel uncertainty-adjusted label transition (UALT) method for weakly supervised solar panel mapping (WS-SPM) in aerial Images. In weakly supervised learning (WSL), the noisy nature of pseudo labels (PLs) often leads to poor model performance. To address this problem, we formulate the task as a label-noise learning problem and build a statistically consistent mapping model by estimating the instance-dependent transition matrix (IDTM). We propose to estimate the IDTM with a parameterized label transition network describing the relationship between the latent clean labels and noisy PLs. A trace regularizer is employed to impose constraints on the form of IDTM for its stability. To further reduce the estimation difficulty of IDTM, we incorporate uncertainty estimation to first improve the accuracy of noisy dataset distillation and then mitigate the negative impacts of falsely distilled examples with an uncertainty-adjusted re-weighting strategy. Extensive experiments and ablation studies on two challenging aerial data sets support the validity of the proposed UALT.

Incidence of cancer for patients after bariatric surgery: evidence from 33 cohort studies.

BACKGROUND: With the rising prevalence of severe obesity, bariatric surgery has emerged as a crucial treatment option. As the number of surgeries performed worldwide increases, there has been growing interest in the impact of bariatric surgery on cancer incidence. While several studies have examined this relationship, the topic remains controversial. OBJECTIVES: We conducted this systematic review of cohort studies with meta-analysis to evaluate the effect of bariatric surgery versus nonsurgical treatment on overall cancer incidence. However, the effects may vary when focusing on specific cancer types, surgical procedures, or gender, so we conducted additional subgroup analyses. SETTING: A meta-analysis. University hospital. METHODS: The Cochrane, Embase, PubMed, and Web of Science databases were searched for studies from 1 January 2000 to 1 December 2022. Meta-analysis was conducted to evaluate the pooled effect and further implemented subgroup analysis stratified by cancer type, operation type, and sex. RESULTS: All cohort studies were included in this meta-analysis from 18,216 studies. The overall cancer incidence demonstrated a significant decrease in the group with bariatric surgery (odds ratios [OR] = .56, P = .000, 95% CI .46 to .68). In subgroup analysis, similar decrease effect was found in 9 cancers. Furthermore, the incidence of cancer decreased significantly in male (OR = .66, P = .001, 95% CI .51 to .85) and female patients (OR = .63, P = .000, 95% CI .57 to .69) and patients undergoing gastric bypass (OR = .46, P = .000, 95% CI .33 to .63) or sleeve gastrectomy (OR = .44, P = .001, 95% CI .27 to .70). CONCLUSIONS: In the overall analysis, bariatric surgery could reduce the incidence of cancer significantly. Further large-scale well-matched studies are needed to verify the protective effect of bariatric surgery on cancer incidence.

EpCAM-targeting CAR-T cell immunotherapy is safe and efficacious for epithelial tumors.

The efficacy of CAR-T cells for solid tumors is unsatisfactory. EpCAM is a biomarker of epithelial tumors, but the clinical feasibility of CAR-T therapy targeting EpCAM is lacking. Here, we report pre- and clinical investigations of EpCAM-CAR-T cells for solid tumors. We demonstrated that EpCAM-CAR-T cells costimulated by Dectin-1 exhibited robust antitumor activity without adverse effects in xenograft mouse models and EpCAM-humanized mice. Notably, in clinical trials for epithelial tumors (NCT02915445), 6 (50%) of the 12 enrolled patients experienced self-remitted grade 1/2 toxicities, 1 patient (8.3%) experienced reversible grade 3 leukopenia, and no higher-grade toxicity reported. Efficacy analysis determined two patients as partial response. Three patients showed >23 months of progression-free survival, among whom one patient experienced 2-year progress-free survival with detectable CAR-T cells 200 days after infusion. These data demonstrate the feasibility and tolerability of EpCAM-CAR-T therapy.

Helicobacter pylori infection prevalence declined among an urban health check-up population in Chengdu, China: a longitudinal analysis of multiple cross-sectional studies.

Objectives: The efficacy of updated health policy in improving the generalization of Helicobacter pylori screening and eradication in southwest China was assessed in a longitudinal analysis of multiple cross-sectional studies from an institution. Methods: In the periods 2009-2010, 2013-2014, and 2019-2021, 8,365, 16,914, and 18,281 urban observations from health check-ups at West China Hospital were analyzed, respectively. The 14C-urea or 13C-urea breath test was consistently used for H. pylori detection. The protocol has been reported elsewhere (PROSPERO Registration number: CRD42019120764). Results: The overall prevalence of H. pylori dramatically decreased from 53.1% to 30.7% over the past decade (OR = 0.39, 95% CI 0.37-0.41), with a similar decline in all sex-specific and age-specific subgroups. The age-specific prevalence consistently increased before 40 years of age and always peaked at 50-59 years. Longitudinal clearance increased along with aging, and prevalence dropped to 22.6%, 25.1%, and 23.6% in the 40-49, 50-59, and 60-69 years initial age groups, respectively. Conclusion: The generalization of H. pylori screening and eradication could greatly contribute to the control of H. pylori infection among urban health check-up populations and lower gastric cancer incidence.

Optimal timing of surgery for gastric cancer after neoadjuvant chemotherapy: a systematic review and meta-analysis.

BACKGROUND: Following neoadjuvant chemotherapy, surgical resection is one of the most preferred treatment options for locally advanced gastric cancer patients. However, the optimal time interval between chemotherapy and surgery is unclear. This review aimed to identify the optimal time interval between neoadjuvant chemotherapy and surgery for advanced gastric cancer. METHODS: Beginning on November 12, 2022, we searched the PubMed, Cochrane Library, Web of Science databases, and Embase.com databases for relevant English-language research. Two authors independently screened the studies, assessed their quality, extracted the data, and analyzed the results. The primary goal was to investigate the relationship between the time interval to surgery (TTS) and long-term survival outcomes for patients. This study has been registered with PROSPERO (CRD42022365196). RESULTS: After an initial search of 4880 articles, the meta-analysis review ultimately included only five retrospective studies. Ultimately, this meta-analysis included 1171 patients, of which 411 patients had TTS of < 4 weeks, 507 patients had TTS of 4-6 weeks, and 253 patients had TTS of > 6 weeks. In survival analysis, patients with TTS of > 6 weeks had poorer overall survival outcomes than patients with TTS of 4-6 weeks (HR = 1.34, 95% CI: 1.03-1.75, P = 0.03). No significant differences were found in terms of disease-free survival the groups. CONCLUSION: Based on the current clinical evidence, patients with locally advanced gastric cancer may benefit better with a TTS of 4-6 weeks; however, this option still needs additional study.