Comparative analysis of cortical anatomy in male participants with internet gaming disorder or tobacco use disorder: Insights from normative modeling.

Background: Research on individual differences in brain structural features of internet gaming disorder (IGD) and established addictions such as tobacco use disorder (TUD) is currently limited. This study utilized normative modeling to analyze the cortical thickness (CT) development patterns of male patients with IGD and TUD, aiming to provide further insights into whether IGD qualifies as an addiction. Methods: Surface-based brain morphometry (SBM) was used to calculate CT from T1-weighted magnetic resonance imaging data of 804 male participants (665 healthy individuals, 68 IGD and 71 TUD). Gaussian process regression was employed to generate normative models of CT development. Deviation maps were produced to depict deviations of IGD and TUD participants from the typical developmental patterns. Results: Both addiction groups exhibited widespread cortical thinning, particularly in regions such as the bilateral temporal pole and medial orbitofrontal cortex. The TUD group demonstrated a higher degree of individualization and limited spatial overlap compared to the IGD group. Opposite trends in CT changes were observed between the two groups in the bilateral pericalcarine cortex and pars triangularis. Conclusions: These findings regarding the similarities and differences between IGD and TUD provide support for the idea that IGD shares common features with substance-related addictions and contribute to a deeper understanding of the neural mechanisms underlying IGD.

Artificial intelligence for geoscience: Progress, challenges, and perspectives.

This paper explores the evolution of geoscientific inquiry, tracing the progression from traditional physics-based models to modern data-driven approaches facilitated by significant advancements in artificial intelligence (AI) and data collection techniques. Traditional models, which are grounded in physical and numerical frameworks, provide robust explanations by explicitly reconstructing underlying physical processes. However, their limitations in comprehensively capturing Earth's complexities and uncertainties pose challenges in optimization and real-world applicability. In contrast, contemporary data-driven models, particularly those utilizing machine learning (ML) and deep learning (DL), leverage extensive geoscience data to glean insights without requiring exhaustive theoretical knowledge. ML techniques have shown promise in addressing Earth science-related questions. Nevertheless, challenges such as data scarcity, computational demands, data privacy concerns, and the "black-box" nature of AI models hinder their seamless integration into geoscience. The integration of physics-based and data-driven methodologies into hybrid models presents an alternative paradigm. These models, which incorporate domain knowledge to guide AI methodologies, demonstrate enhanced efficiency and performance with reduced training data requirements. This review provides a comprehensive overview of geoscientific research paradigms, emphasizing untapped opportunities at the intersection of advanced AI techniques and geoscience. It examines major methodologies, showcases advances in large-scale models, and discusses the challenges and prospects that will shape the future landscape of AI in geoscience. The paper outlines a dynamic field ripe with possibilities, poised to unlock new understandings of Earth's complexities and further advance geoscience exploration.

Case report: Successful radical surgery following complete pathological remission of advanced HCC with Tislelizumab/Lenvatinib plus TACE.

The combination therapy of Tislelizumab plus Lenvatinib has recently emerged as the new standard of care for unresectable hepatocellular carcinoma (HCC). This treatment has demonstrated a significant reduction in tumor burden, raising the possibility of conversion therapy. However, the full safety and efficacy of this combination in real-world settings are not yet fully understood. We recently reported the case of a 36-year-old man with initially unresectable massive HCC, for whom radical surgery (RS) was contraindicated. After receiving Tislelizumab/Lenvatinib plus transarterial chemoembolization (TACE), the patient achieved complete pathological remission and subsequently underwent RS. The patient did not experience postoperative severe complications, and there was no recurrence during the follow-up period. Tislelizumab/Lenvatinib plus TACE therapy may lead to a complete pathological response in advanced HCC. Nevertheless, the safety of prolonged treatment needs to be assessed.

Relative Bioavailability of Sotorasib Following Administration as a Water Dispersion to Healthy Subjects and Compatibility With Enteral Administration.

Sotorasib is approved to be taken as 960 mg orally once daily (8 × 120-mg tablets) for the treatment of KRAS G12C-mutated nonsmall cell lung cancer. Dispersion of tablets in water could be an alternative method for patients who require a liquid formulation due to dysphagia and enteral administration. A clinical study was conducted to assess the pharmacokinetics of 960 mg of sotorasib administered as tablets and as tablets dispersed in water in healthy volunteers. Each subject received 960 mg of sotorasib by mouth, as tablets and as tablets dispersed in water on Days 1 and 4. Sotorasib median time to maximum observed plasma concentration was similar when administered as tablets and as tablets predispersed in water. The geometric least squares mean ratios (water dispersion/tablets) for area under the concentration-time curve from time 0 extrapolated to infinity and maximum observed plasma concentration were 1.049 and 1.080, respectively. Sotorasib 960 mg was well tolerated. Administration of 960 mg of sotorasib as tablets predispersed in water achieved similar systemic exposures to that of sotorasib administered as oral tablets. In vitro evaluations were performed to assess the feasibility of administering sotorasib through an enteral feeding tube. Approximately 98% of sotorasib was recovered, with no new impurities, from enteral feeding tubes. Collectively, these results support that sotorasib can be administered by mouth and via enteral feeding tubes as tablets predispersed in water.

Biostimulation accelerates landfill stabilization and resource utilization efficiency, providing feasible technical support for the overall lifecycle management of landfills.

Although sanitary landfill is one of the principal municipal solid waste (MSW) treatment and disposal methods, its limitations, such as insufficient use of resources, long stability time, and high risk of environmental pollution, must be urgently resolved. The effect of multifunctional microbial community (MMC) inoculation on MSW landfill process was investigated using simulated anaerobic bioreactor landfill (ABL), and composition and microbial community structure of waste, leachate water quality, and gas production were monitored. MMC inoculation significantly accelerated lignocellulose degradation, and the (Hemicellulose content + Cellulose content)/Lignin content ((C + H)/L) of MMC inoculation treatment was 0.89 ± 0.04 on day 44, which was significantly lower than that of the control group (1.14 ± 0.02). At the end of the landfill process, the reductive organic matter, ammonia nitrogen, and volatile fatty acids in the leachate of the MMC group decreased to 9400.00 ± 288.68, 332.78 ± 5.77, and 79.33 ± 6.44 mg L-1, respectively, significantly lower than those of the control group (24,167.00 ± 208.17, 551.14 ± 5.60, and 156.33 ± 8.22 mg L-1). Meanwhile, MMC inoculation increased the methane production to 118.12 ± 5.42 L kg-1 of dry matter, significantly higher than the output of the control group (60.60 ± 2.24 L kg-1). MMC inoculation optimized the microbial community structure in ABL and increased lignocellulose-degrading microorganisms (Brevundimonas, Cellvibrio, Leifsonia, and Devosia) and methanogen (Methanosaeta and Methanoculleus) abundance in the middle stage of landfill. Moreover, MMC introduction improved the abundance of carbon metabolism enzymes and increased saprophytic fungal abundance by 30.09% in the middle stage of landfill. Overall, these findings may help in developing an effective method to increase the lifespan of landfills and enhance their post-closure management.

The recovery of endoscopic activity and cancer detection after the COVID-19 pandemic.

Background: The COVID-19 pandemic had a substantial impact on cancer services. The aim of our study was to evaluate the recovery of endoscopic activity and cancer detection after the COVID-19 pandemic. Methods: Endoscopic data from January 2019 to December 2020 were retrospectively collected to assess the endoscopic activity and cancer detection during the COVID-19 peak period (February 2020) and the post-COVID-19 peak period (March to July 2020). Results: The COVID-19 pandemic almost brought endoscopic activity and cancer detection to a standstill. Diagnostic procedure and endoscopic resection showed the greatest reduction. With the decline in COVID-19 infections, endoscopic activity gradually returned to previous level in July. However, the detection rate of gastric cancer resumed in September, whereas colorectal cancer resumed in August. The monthly detection rates of gastric and colorectal cancers decreased from their initial peaks of 2.98 % and 6.45 %, respectively, and finally were even lower than the average in 2019. Similarly, the mean age of patients who received endoscopy also declined as the detection rates resumed. The increasing colonoscopies allowed the missing colorectal cancer patients to be caught up. In contrast, it was expected that 6.69 % of gastric cancer patients were missed and did not receive needed endoscopy. Conclusions: The recovery of cancer detection occurred later than that of endoscopic activity, especially for gastric cancer. Older people were vulnerable to the continuous impact of COVID-19 pandemic than young people for seeking medical services. Urgent efforts are required to recover and maintain cancer services before subsequent waves of the COVID-19 pandemic.

Lactiplantibacillus plantarum P9 for chronic diarrhea in young adults: a large double-blind, randomized, placebo-controlled trial.

Current treatments for chronic diarrhea have limited efficacy and several side effects. Probiotics have the potential to alleviate symptoms of diarrhea. This randomized, double-blind, placebo-controlled trial evaluates the effects of administering the probiotic Lactiplantibacillus plantarum P9 (P9) strain in young adults with chronic diarrhea (Clinical Trial Registration Number: ChiCTR2000038410). The intervention period lasts for 28 days, followed by a 14-day post-intervention period. Participants are randomized into the P9 (n = 93) and placebo (n = 96) groups, with 170 individuals completing the double-blind intervention phase (n = 85 per group). The primary endpoint is the diarrhea symptom severity score. Both intention-to-treat (n = 189) and per-protocol (n = 170) analyses reveal a modest yet statistically significant reduction in diarrhea severity compared to the placebo group (20.0%, P = 0.050; 21.4%, P = 0.048, respectively). In conclusion, the results of this study support the use of probiotics in managing chronic diarrhea in young adults. However, the lack of blood parameter assessment and the short intervention period represent limitations of this study.

Design, synthesis and anti-HBV activity study of novel HBV capsid assembly modulators.

Capsid assembly modulators (CAMs) have the potential to cure chronic hepatitis B, as demonstrated in clinical trials. Lead compounds NVR3-778 and 5a were found to exist in normal and flipped conformations through induced fit docking. Therefore, we designed and synthesized series I and II compounds by interchanging the amide and sulfonamide bonds of 5a to modify both the tolerance region and solvent-opening region. Among them, compound 4a (EC50 = 0.24 ± 0.10 µM, CC50 > 100 µM) exhibited potent anti-HBV activity with low toxicity, surpassing the lead compounds NVR3-778 (EC50 = 0.29 ± 0.03 µM, CC50 = 20.78 ± 2.29 µM) and 5a (EC50 = 0.50 ± 0.07 µM, CC50 = 48.16 ± 9.15 µM) in HepAD38 cells. Additionally, compared with the lead compound, 4a displayed a stronger inhibitory effect on HBV capsid protein assembly. Molecular dynamics (MD) simulations confirmed that the normal conformation of 4a had relatively stable conformation at different frames of binding modes. Furthermore, 4a showed better metabolic stability in human plasma than positive control drugs. Therefore, compound 4a could be further structurally modified as a potent lead compound.

The clinical characteristics analysis of serum markers for the cardiovascular system in early-stage COVID-19 patients.

Background: This study aimed to investigate alterations in serum markers [creatine kinase-MB (CKMB), cardiac troponin T (cTnT), myoglobin (Myo), B-type natriuretic peptide (BNP), D-dimer (DD), procalcitonin (PCT) and interleukin-6 (IL6)] in early Omicron variant infection and analyzed their correlation with clinical parameters. Methods: Retrospective analysis of 1,138 mild/asymptomatic cases at Tianjin First Central Hospital, including age, gender, serum markers and nucleic acid test results. Statistical analysis used SPSS software, version 24.0. Results: Elevated cTnT, BNP (125-400), and DD (0.55-1.10) levels were prevalent at 12.92%, 15.64%, and 14.50%, respectively. Females had significantly higher proportions with slightly elevated BNP (19.34%) and DD (19.69%) levels. Patients over 35 had a higher proportion of slight elevation in BNP (20.00%). Abnormal levels of serum markers were significantly associated with older age, increased PCT and IL6 levels, as well as delayed nucleic acid clearance. Additionally, levels of immunoglobulin G (IgG) were notably reduced in these cases. Patients with prolonged nucleic acid clearance (>14 days) had higher BNP and DD levels upon admission. Logistic regression identified PCT (OR = 237.95) as the most significant risk factor for abnormal serum markers for cardiovascular system injury. Conclusion: Early Omicron infection might do subclinical damage to the cardiovascular system. Elevated cTnT, BNP and DD levels were correlated with age, gender, inflammatory factors, and IgG. Notably, high PCT level emerged as the most robust predictor of abnormal serum biomarkers.

Satellite-ground synchronous in-situ dataset of water optical parameters and surface temperature for typical lakes in China.

Remote sensing technology has the potential to enhance the lake's large-scale and long-term dynamic monitoring capabilities significantly. High-quality in-situ datasets are essential for improving the accuracy and reliability of remote sensing retrieval of lake ecosystems. This dataset provides satellite-ground synchronized in-situ data on water multi-parameters for typical lakes in China spanning the period between 2020 and 2023. It includes quality-checked water optical parameters (remote sensing reflectance (Rrs), chlorophyll-a (Chl-a), total suspended matter (TSM) and Secchi disk depth (SDD)), and water surface temperature (WST) data. It encompasses 586 sampling points across 18 lakes. The dataset exhibits two significant highlights: Firstly, synchronous observations from multiple satellites are coordinated during the data collection effectively supporting the retrieval and validation of water remote sensing products. Secondly, it encompasses diverse data types, collecting synchronous measurements of Rrs and various parameters. This dataset will continuously update, substantially enhancing regional and global lake monitoring capabilities through satellite remote sensing data.

New findings on post-mortem chicken quality changes: The ROS-influenced MAPK-JNK signaling pathway affects chicken quality by regulating muscle cell apoptosis.

Research conducted previously has demonstrated that apoptosis significantly influences the chicken quality. While ROS are acknowledged as significant activators of apoptosis, the precise mechanism by which they influence muscle cell apoptosis in the post-mortem remains unclear. In this study, chicken samples were treated with rosemarinic acid and H2O2 to induce varying ROS levels, and the ROS-triggered apoptosis mechanism in chicken muscle cells in post-mortem was analyzed. The TUNEL results revealed that elevated ROS levels in chicken were associated with a greater degree of muscle cell apoptosis. Western-blot results suggested that sarcoplasmic ROS could initiate apoptosis through the mitochondrial pathway by activating the MAPK-JNK signaling pathway. Moreover, TEM and shear force results demonstrated that muscle cell apoptosis initiates myofiber fragmentation and structural damage to sarcomeres, ultimately reducing chicken tenderness. This study enhances our understanding of post-mortem muscle cell apoptosis, providing valuable insights for regulating chicken quality.

Imbalance of mitochondrial quality control regulated by STING and PINK1 affects cyfluthrin-induced neuroinflammation.

Nervous system diseases are a global health problem, and with the increase in the elderly population around the world, their incidence will also increase. Harmful substances in the environment are closely related to the occurrence of nervous system diseases. China is a large agricultural country, and thus the insecticide cyfluthrin has been widely used. Cyfluthrin is neurotoxic, but the mechanism of this injury is not clear. Inflammation is an important mechanism for the occurrence of nervous system diseases. Mitochondria are the main regulators of the inflammatory response, and various cellular responses, including autophagy, directly affect the regulation of inflammatory processes. Mitochondrial damage is related to mitochondrial quality control (MQC) and PTEN-induced kinase 1 (PINK1). As an anti-inflammatory factor, stimulator of interferon genes (STING) participates in the regulation of inflammation. However, the relationship between STING and mitochondria in the process of cyfluthrin-induced nerve injury is unclear. This study established in vivo and in vitro models of cyfluthrin exposure to explore the role of MQC and to clarify the mechanism of action of STING and PINK1. Our results showed that cyfluthrin can increase the reactive oxygen species (ROS) level, resulting in mitochondrial damage and inflammation. In this process, an imbalance in MQC leads to the aggravation of mitochondrial damage, and high STING expression drives the occurrence of inflammation. We established a differential expression model of STING and PINK1 to further determine the underlying mechanism and found that the interaction between STING and PINK1 regulates MQC to affect the levels of mitochondrial damage and inflammation. When STING and PINK1 expression are downregulated, mitochondrial damage and STING-induced inflammation are significantly alleviated. In summary, a synergistic effect between STING and PINK1 on cyfluthrin-induced neuroinflammation may exist, which leads to an imbalance in MQC by inhibiting mitochondrial biogenesis and division/fusion, and PINK1 can reduce STING-driven inflammation.

Revealing the spoilage characteristics of refrigerated prepared beef steak by advanced bioinformatics tools.

BACKGROUND: Although microorganisms are the main cause of spoilage in prepared beef steaks, very few deep spoilage mechanisms have been reported so far. Aiming to unravel the mechanisms during 12 days of storage at 4 °C affecting the quality of prepared beef steak, the present study investigated the changes in microbial dynamic community using a combined high-throughput sequencing combined and bioinformatics. In addition, gas chromatography-mass spectrometry combined with multivariate statistical analysis was utilized to identify marker candidates for prepared steaks. Furthermore, cloud platform analysis was applied to determine prepared beef steak spoilage, including the relationship between microbiological and physicochemical indicators and volatile compounds. RESULTS: The results showed that the dominant groups of Pseudomonas, Brochothrix thermosphacta, Lactobacillus and Lactococcus caused the spoilage of prepared beef steak, which are strongly associated with significant changes in physicochemical properties and volatile organic compounds (furan-2-pentyl-, pentanal, 1-octanol, 1-nonanol and dimethyl sulfide). Metabolic pathways were proposed, among which lipid metabolism and amino acid metabolism were most abundant. CONCLUSION: The present study is helpful with respect to further understanding the relationship between spoilage microorganisms and the quality of prepared beef steak, and provides a reference for investigating the spoilage mechanism of dominant spoilage bacteria and how to extend the shelf life of meat products. © 2024 Society of Chemical Industry.

Association between gut microbiota and acute pancreatitis: a bidirectional Mendelian randomization study.

BACKGROUND AND AIM: The dysbiosis of gut microbiota has been reported in acute pancreatitis. However, the direction and magnitude between host microbiota and pancreas remains to be established. This study investigated the association between gut microbiota and acute pancreatitis using Mendelian randomization (MR) methods. METHODS: Summary statistics of gut microbiota abundance and acute pancreatitis were extracted from genome-wide association studies (GWAS). The two-sample bidirectional MR design was employed to assess genetic association between the microbiota and pancreatitis, followed by a comprehensive sensitivity analysis to verify the robustness of the results. RESULTS: Seven microbiota taxa have been identified as significantly associated with the development of pancreatitis. Host genetic-driven order Bacteroidales and class Bacteroidia are associated with an increased risk of pancreatitis. The genera Coprococcus and Eubacterium fissicatena group also exhibit a positive effect on the development of pancreatitis, while the genera Prevotella, Ruminiclostridium, and Ruminococcaceae act as protective factors against pancreatitis. In contrast, acute pancreatitis was positively correlated with phylum Proteobacteria and genus Lachnospiraceae and negatively correlated with genus Holdemania. CONCLUSIONS: The bidirectional relationship between gut microbiota and acute pancreatitis suggests a critical role for host-microbiota crosstalk in the development of the disease. Targeted modulation of specific gut microbiota enables the prevention and treatment of acute pancreatitis.

Inflammation and endothelial function relevant genetic polymorphisms, carotid atherosclerosis, and vascular events in high-risk stroke population.

Aim: To identify the associations of 19 single nucleotide polymorphisms (SNPs) in genes involved in inflammation and endothelial function and carotid atherosclerosis with subsequent ischemic stroke and other vascular events in the high-risk stroke population. Methods: This was a multicenter community-based sectional survey and prospective cohort study in Sichuan, southwestern China. Eight communities were randomly selected, and the residents in each community were surveyed using a structured face-to-face questionnaire. Carotid ultrasonography and DNA information were obtained from 2,377 out of 2,893 individuals belonging to a high-risk stroke population. Genotypes of the 19 SNPs in genes involved in inflammation and endothelial function were measured. All the 2,377 subjects were followed up for 4.7 years after the face-to-face survey. The primary outcome was ischemic stroke, and the secondary outcome was a composite of vascular events. Results: Among the 2,377 subjects, 2,205 (92.8%) completed a 4.7-year follow-up, 947 (42.9%) had carotid atherosclerosis [372 (16.9%) carotid vulnerable plaque, 405 (18.4%) mean IMT > 0.9 mm, 285 (12.0%) carotid stenosis ≥15%]. Outcomes occurred in 158 (7.2%) subjects [92 (4.2%) ischemic stroke, 17 (0.8%) hemorrhagic stroke, 48 (2.2%) myocardial infarction, and 26 (1.2%) death] during follow-up. There was a significant gene-gene interaction among ITGA2 rs1991013, IL1A rs1609682, and HABP2 rs7923349 in the 19 SNPs. The multivariate logistic regression model revealed that carotid atherosclerosis and the high-risk interactive genotypes among the three SNPs were independent with a higher risk for ischemic stroke (OR = 2.67, 95% CI: 1.52-6.78, p = 0.004; and OR = 3.11, 95% CI: 2.12-9.27, p < 0.001, respectively) and composite vascular events (OR = 3.04, 95% CI: 1.46-6.35, p < 0.001; and OR = 3.23, 95% CI: 1.97-8.52, p < 0.001, respectively). Conclusion: The prevalence of carotid atherosclerosis was shown to be very high in the high-risk stroke population. Specific SNPs, interactions among them, and carotid atherosclerosis were independently associated with a higher risk of ischemic stroke and other vascular events.

A Self-Delivery Nanodrug Simultaneously Inhibits COX-2/PGE2 Mediated Inflammation and Downregulates PD-L1 to Boost Photoimmunotherapy.

Phototherapy promotes anti-tumor immunity by inducing immunogenic cell death (ICD), However, the accompanying inflammatory responses also trigger immunosuppression, attenuating the efficacy of photo-immunotherapy. Herein, they co-assembled a cell-membrane targeting chimeric peptide C16-Cypate-RRKK-PEG8-COOH (CCP) and anti-inflammatory diclofenac (DA) to develop a nanodrug (CCP@DA) that both enhances the immune effect of phototherapy and weakens the inflammation-mediated immunosuppression. CCP@DA achieves cell membrane-targeting photodynamic and photothermal synergistic therapies to damage programmed death ligand 1 (PD-L1) and induce a strong ICD to activate anti-tumor response. Simultaneously, the released DA inhibits the cycoperoxidase-2 (COX-2)/prostaglandin E2 (PGE2) pathway in tumor cells to inhibit pro-tumor inflammation and further down-regulate PD-L1 expression to relieve the immunosuppressive microenvironment. CCP@DA significantly inhibited tumor growth and inflammation both in vitro and in vivo, while maintaining a potent anti-tumor immune response. Additionally, it exhibits excellent anti-metastatic capabilities and prolongs mouse survival time with a single dose and low levels of near-infrared (NIR) light exposure. This work provides a valuable strategy to control the therapy-induced inflammation for high-efficiency photoimmunotherapy.

Insight into the evolution of textural properties and juiciness of ready-to-eat chicken breasts upon different thermal sterilization: From the perspective of protein degradation.

Texture deterioration of meat products upon high-temperature sterilization is a pressing issue in the meat industry. This study evaluated the effect of different thermal sterilization temperatures on the textural and juiciness of ready-to-eat (RTE) chicken breast. In this study, by dynamically monitoring the texture and juiciness of chicken meat products during the process of thermal sterilization, it has been observed that excessively high sterilization temperatures (above 100°C) significantly diminish the shear force, springiness and water-holding capacity of the products. Furthermore, from the perspective of myofibrillar protein degradation, molecular mechanisms have been elucidated, unveiling that the thermal sterilization treatment at 121°C/10 min triggers the degradation of myosin heavy chains and F-actin, disrupting the lattice arrangement of myofilaments, compromising the integrity of sarcomeres, and resulting in an increase of approximately 40.66% in the myofibrillar fragmentation index, thus diminishing the quality characteristics of the products. This study unravels the underlying mechanisms governing the dynamic changes in quality of chicken meat products during the process of thermal sterilization, thereby providing theoretical guidance for the development of high-quality chicken products.

Treatment failure is a key factor in the development of Helicobacter pylori resistance.

BACKGROUND: Helicobacter pylori eradication failure influences its antibiotic resistance. AIMS: This study aimed to evaluate the effect of previous treatment failures on it, including the changes in the antibiotic resistance rates, minimal inhibitory concentration (MIC) distributions, and resistance patterns. MATERIALS AND METHODS: This single-center retrospective study included 860 primary isolates and 247 secondary isolates. Antibiotic susceptibility testing was performed for amoxicillin, metronidazole, clarithromycin, levofloxacin, furazolidone, tetracycline, and rifampicin. The demographic data and detailed regimens were collected. RESULTS: The primary resistance rates to amoxicillin, metronidazole, clarithromycin, levofloxacin, tetracycline, rifampin, and furazolidone were 5.93%, 83.84%, 28.82%, 26.28%, 0.35%, 1.16%, and 0%, while secondary were 25.10%, 92.31%, 79.76%, 63.16%, 1.06%, 3.19%, and 0%, respectively. The resistance rates to amoxicillin, metronidazole, clarithromycin, and levofloxacin increased significantly with the number of treatment failures accumulated, and showed a linear trend. The proportion of primary and secondary multidrug-resistant (MDR) isolates were 17.79% and 63.16%, respectively. The MIC values of amoxicillin, clarithromycin, and levofloxacin were elevated significantly with medication courses increased. CONCLUSION: The prevalence of amoxicillin, clarithromycin, levofloxacin, and metronidazole resistance would increase rapidly following first-line treatment failure, as well as the MIC values of them. Clinicians should pay great attention to the first-line treatment to cure H. pylori infection successfully.

Radiofrequency ablation with or without transarterial chemoembolization for hepatocellular carcinoma meeting Milan criteria: a focus on tumor progression and recurrence patterns.

Background/objective: The aim of this study was to evaluate tumor progression and recurrence patterns of radiofrequency ablation (RFA) with or without transarterial chemoembolization (TACE) for treating hepatocellular carcinoma (HCC) that meets Milan criteria. Methods: This retrospective study included consecutive HCC patients meeting Milan criteria who underwent percutaneous RFA with or without TACE as initial treatment at a tertiary academic center between December 2017 and 2022. Technical success rate, local recurrence-free survival (LRFS), progression-free survival (PFS) and recurrence patterns were recorded. Results: A total of 135 HCC patients (109 male [80.7%]) with a mean age of 62 years and 147 target lesions were retrospectively enrolled. The technical success rate was 99.3%. The median LRFS was 60 months, and the cumulative 1-, 3-, and 5-year LRFS were 88.9%, 70.1%, and 30.0%, respectively. Additionally, the median PFS was 23 months, with cumulative 1-, 3-, and 5-year PFS of 74%, 30%, and 0%, respectively. Multivariate analysis confirmed that age > 60, alpha-fetoprotein (AFP) (> 10), and albumin were associated with PFS (2.34, p = 0.004; 1.96, p = 0.021; 0.94, p = 0.007, respectively). Six recurrence patterns were identified: local tumor progression (LTP) alone (n = 15, 25.0%), intrahepatic distant recurrence (IDR) alone (n = 34, 56.7%), extrahepatic recurrence (ER) alone (n = 2, 3.3%), IDR + ER (n = 2, 3.3%), LTP + IDR (n = 5, 8.8%), and LTP + IDR + ER (n = 2, 3.3%). IDR occurred most frequently as a sign of good local treatment. Conclusions: RFA in combination with TACE does not appear to provide an advantage over RFA alone in improving tumor progression in patients with HCC meeting the Milan criteria. However, further prospective studies are needed to confirm these findings and to determine the optimal treatment approach for this patient population.