Guideline for the cognitive assessment and follow-up in the Guangdong-Hong Kong-Macao Greater Bay Area (2024 edition).

This practice guideline focuses on the cognitive assessment for mild cognitive impairment in the Guangdong-Hong Kong-Macao Greater Bay Area. To achieve the standardization and normalization of its clinical practice and generate individualized intervention, the National Core Cognitive Center of the Second Affiliated Hospital of Guangzhou Medical University, the Cognitive Disorders Branch of Chinese Geriatic Society, the Dementia Group of Neurology Branch of Guangdong Medical Association and specialists from Hong Kong and Macao developed guidelines based on China's actual conditions and efficiency, economic cost and accuracy. The article addresses the significance, background, and the process of the assessment and follow-up to realize the promotion and dissemination of cognitive assessment.

Different Contributions of embB and ubiA Mutations to Variable Level of Ethambutol Resistance in Mycobacterium tuberculosis Isolates.

Objective: To explore the association between the variant mutations within embB and ubiA, and the degree of ethambutol (EMB) resistance of Mycobacterium tuberculosis (M. tuberculosis) isolates. Methods: A total of 146 M. tuberculosis isolates were used to determine the minimum inhibitory concentrations (MICs) of EMB with a 96-well microplate-based assay. The mutations within embB and ubiA among these isolates were identified with DNA sequencing. Moreover, a multivariate regression model and a computer model were established to assess the effects of mutations on EMB resistance. Results: Our data showed that overall 100 isolates exhibited 28 mutated patterns within the sequenced embB and ubiA. Statistical analysis indicated that embB mutations Met306Val, Met306Ile, Gly406Ala, and Gln497Arg, were strongly associated with EMB resistance. Of these mutations, Met306Val and Gln497Arg were significantly associated with high-level EMB resistance. Almost all multiple mutations occurred in high-level EMB-resistant isolates. Although the mutation within ubiA accompanied with embB mutation presented exclusively in EMB-resistant isolates, four single ubiA mutations (Ala39Glu, Ser173Ala, Trp175Cys, and Val283Leu) leading to protein instability were observed in EMB-susceptible isolates. Conclusion: This study highlighted the complexity of EMB resistance. Some individual mutations and multiple mutations within embB and ubiA contributed to the different levels of EMB resistance.

RPN1: a pan-cancer biomarker and disulfidptosis regulator.

Background: Elevated expression of SLC7A11, in conjunction with glucose deprivation, has revealed disulfidptosis as an emerging cell death modality. However, the prevalence of disulfidptosis across tumor cell lines, irrespective of SLC7A11 levels, remains uncertain. Additionally, deletion of the ribophorin I (RPN1) gene imparts resistance to disulfidptosis, yet the precise mechanism linking RPN1 to disulfidptosis remains elusive. The aim of this study is to determine the mechanism of RPN1-induced disulfidptosis and to determine the possibility of RPN1 as a pan-cancer marker. Methods: We hypothesized the widespread occurrence of disulfidptosis in various tumor cells, and proposed that RPN1-mediated disulfidptosis may be executed through cell skeleton breakdown. Experimental validation was conducted via flow cytometry, immunofluorescence, and western blot techniques. Furthermore, given RPN1's status as an emerging cell death marker, we utilized bioinformatics to analyze its expression in tumor tissues, clinical relevance, mechanisms within the tumor microenvironment, and potential for immunotherapy. Results: Conducting experiments on breast cancer (MDA-MB-231) and lung cancer (A549) cell lines under glucose-starved conditions, we found that RPN1 primarily induces cell skeleton breakdown to facilitate disulfidptosis. RPN1 demonstrated robust messenger RNA (mRNA) expression across 16 solid tumors, validated by data from 12 tumor types in the Gene Expression Omnibus (GEO). Across 12 cancer types, RPN1 exhibited significant diagnostic potential, particularly excelling in accuracy for glioblastoma (GBM). Elevated RPN1 expression in tumor tissues was found to correlate with improved overall survival (OS) in certain cancers [diffuse large B-cell lymphoma (DLBC) and thymoma (THYM)] but poorer prognosis in others [adrenocortical carcinoma (ACC), kidney chromophobe (KICH), brain lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), and pancreatic adenocarcinoma (PAAD)]. RPN1 is enriched in immune-related pathways and correlates with immune scores in tumor tissues. In urothelial carcinoma (UCC), RPN1 demonstrates potential in predicting the efficacy of anti-programmed cell death ligand 1 (PD-L1) immune therapy. Conclusions: This study underscores RPN1's role in facilitating disulfidptosis, its broad relevance as a pan-cancer biomarker, and its association with the efficacy of anti-PD-L1 immune therapy.

Normal Fermi Surface in the Nodal Superconductor CeCoIn_{5} Revealed via Thermal Conductivity.

The thermal conductivity of heavy-fermion superconductor CeCoIn_{5} was measured with a magnetic field rotating in the tetragonal a-b plane, with the heat current in the antinodal direction, J|| [100]. We observe a sharp resonance in thermal conductivity for the magnetic field at an angle Θ≈12°, measured from the heat current direction [100]. This resonance corresponds to the reported resonance at an angle Θ^{'}≈33° from the direction of the heat current applied along the nodal direction, J||[110]. Both resonances, therefore, occur when the magnetic field is applied in the same crystallographic orientation in the two experiments, regardless of the direction of the heat current, proving conclusively that these resonances are due to the structure of the Fermi surface of CeCoIn_{5}. We argue that the uncondensed Landau quasiparticles, emerging with field, are responsible for the observed resonance. We support our experimental results with density-functional-theory model calculations of the density of states in a rotating magnetic field. Our calculations, using a model Fermi surface of CeCoIn_{5}, reveal several sharp peaks as a function of the field direction. Our study demonstrates that the thermal-conductivity measurement in rotating magnetic field can probe the normal parts of the Fermi surface deep inside the superconducting state.

The alleviatory effects of koumine on MSU-induced gouty arthritis via the TLR4/NF-κB/NLRP3 pathway.

The aim of this study was to validate the preventive effects of koumine (KM), a monoterpene indole alkaloid, on gouty arthritis (GA) and to explore its possible mechanisms. C57BL/6 mice were intraperitoneally administered KM (0.8, 2.4 or 7.2 mg/kg), colchicine (3.0 mg/kg) or sterile saline. One hour later, a monosodium urate (MSU) suspension was injected into the right hind paws of the mice to establish an acute gout model. Inflammation symptoms were evaluated at 0, 3, 6, 12 and 24 h, and the mechanical withdrawal threshold was evaluated at 0, 6 and 24 h. After 24 h, the mice were euthanized, and the joint tissue, kidney and blood were collected for subsequent experiments. Histological examination and antioxidant enzyme, kidney index and serum uric acid (UA) measurements were taken. The expression levels of the signalling pathway components were determined. KM effectively alleviated the symptoms of redness, swelling and pain; counteracted inflammatory cell infiltration; and increased antioxidant enzyme levels, reduced kidney index and serum UA levels through regulating UA excretion in MSU-induced mice. The expression of toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB)/nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) signalling pathway proteins and mRNA were reduced in the KM group. These results suggest that KM may be effective in alleviating GA through the TLR4/NF-κB/NLRP3 pathway.

A Study on the Dilational Modulus Measurement of Polyacrylic Acid Films at Air-Water Interface by Pendant Bubble Tensiometry.

The dilational modulus (E) of polymer films has been commonly measured using the oscillating ring/bubble/drop methods with an external force, and often without specifying the state of the adsorbed film. This study explores an approach where E was determined from the relaxations of surface tension (ST) and surface area (SA) of natural perturbations, in which ST and SA were monitored using a pendant bubble tensiometer. The E of the adsorbed film of PAA (polyacrylic acid) was evaluated for aqueous solutions at CPAA = 5 × 10-4 g/cm3, [MW = 5, 25, and 250 (kDa)]. The E (=dγ/dlnA) was estimated from the surface dilational rate (dlnA/dt) and the rate of ST change (dγ/dt) of the bubble surface from the natural perturbation caused by minute variations in ambient temperature. The data revealed that (i) a considerable time is required to reach the equilibrium-ST (γeq) and to attain the saturated dilational modulus (Esat) of the adsorbed PAA film, (ii) both γeq and Esat of PAA solutions increase with MW of PAA, (iii) a lower MW solution requires a longer time to reach its γeq and Esat, and (iv) this approach is workable for evaluating the E of adsorbed polymer films.

Relationship between thrombus vWF and NETs with clinical severity and peripheral blood immunocytes' indicators in patients with acute ischemic stroke.

OBJECTIVE: To investigate the association between von Willebrand factor (vWF) and neutrophil extracellular traps (NETs) in thrombus with clinical severity and peripheral blood immunocytes' indicators in patients with early-stage acute ischemic stroke (AIS). METHODS: A retrospective study was conducted using the clinical data of 66 patients with AIS who underwent endovascular mechanical thrombectomy and had their thrombus samples collected. The concentrations of vWF and NETs in the thrombus samples were quantitatively assessed. Peripheral blood samples taken in the early stages of the disease were analyzed for total white blood cell counts (WBC), ratios of neutrophils (NEU%), lymphocytes (LYM%), eosinophils (EOS%), and monocytes (MONO%). The severity of clinical symptoms in these patients was evaluated using the modified Rankin Scale (mRS), Essen Stroke Risk Score (ESRS), Barthel Index (BI), and National Institute of Health Stroke Scale (NIHSS). RESULTS: Higher vWF levels in thrombus were associated with lower NIHSS scores, while higher NETs levels were associated with higher initial NIHSS scores. In the early stages of AIS, WBC count and vWF levels were negatively correlated, as well as NEU%. LYM% was positively correlated with vWF level; however, it was negatively correlated with NETs. EOS% was positively correlated with vWF levels. CONCLUSION: In the early stages of AIS, a higher peripheral WBC count and NEU%, combined with decreased EOS% and LYM%, were significantly correlated with a lower vWF level in the thrombus, potentially indicating more severe symptoms. Consequently, the timely administration of vWF-targeted medications is recommended for such patients. Reduced LYM% is indicative of elevated NETs levels and correlated with more severe clinical symptoms. Therefore, the prompt initiation of NETs-targeted medication is warranted for these patients.

Early-onset and later-onset cancer: trends, risk factors, and prevention in Northern China.

The characteristics of early-onset (onset age <50 years) and later-onset (onset age ≽ 50 years) cancers differ significantly. Identifying novel risk factors for both types of cancer is crucial for increasing awareness of cancer prevention and for reducing its burden. This study aimed to analyze the trends in incidence and risk factors for early-onset and late-onset cancers. We conducted a prospective study by drawing data from the Kailuan Study. This study included 6,741 participants with cancer (624 with early-onset cancer and 6,117 with later-onset cancer) and 6,780 matched controls among the 186,249 participants who underwent Kailuan health examinations from 2006 to 2019. The primary outcomes were cancer incidence rates, and associated risk factors for early- and later-onset cancer. Weighted Cox regression was used to calculate hazard ratios and 95% confidence intervals of each exposure factor for early- and later-onset cancer by cancer type. Population-attributable risk proportions were used to estimate the number of cases that could be prevented by eliminating a risk factor from the population. Except for liver cancer, incidence rates for nearly all types of cancer increased during the study period. Smoking, alcohol consumption, lipid metabolism disorders, hypertension, diabetes mellitus, fatty liver, and inflammation were associated with a significantly increased risk of cancer at multiple sites, but risk factors for cancer incidence differed by site. Smoking, alcohol consumption, inflammation, and hypertension were the major contributors to preventable cancer. The incidence of several different types of cancer, including early-onset cancer, is increasing in northeastern China. Differences in risk factors between early-onset and later-onset malignancies may contribute to the divergence in the observed changes in incidence trends between these two specific types of cancer.

Quantum Dynamics of O(3P)+HBr→OH+Br Reaction: Integral Cross Sections and Rate Constants and their Initial State Dependence.

The integral cross sections (ICSs) and rate constants (RCs) for the title reaction are calculated by means of accurate quantum wave packet method employing the recent ab initio potential energy surface developed by Peterson and co-workers. Hundreds of partial wave contributions (up to J=150) are calculated explicitly taking Coriolis coupling into account. The ICSs are found to increase monotonically with energy and their energy dependences are smooth except in the energy range below the potential energy barrier, where several resonance peaks are observed. The temperature dependences of the RCs obey in general the Arrhenius law. These behaviors manifest the dominance of abstract mechanism. Initial rotational state (ji) excitations are found to greatly enhance the reactivity starting from ji=4, while exhibiting a complicated dependence for ji<4. From Boltzmann average of the initial state specified RCs (for ji=0-15) we obtained thermal RCs which are in reasonable agreement with available experimental results.

Identifying the risk factors of ICU-acquired fungal infections: clinical evidence from using machine learning.

Background: Fungal infections are associated with high morbidity and mortality in the intensive care unit (ICU), but their diagnosis is difficult. In this study, machine learning was applied to design and define the predictive model of ICU-acquired fungi (ICU-AF) in the early stage of fungal infections using Random Forest. Objectives: This study aimed to provide evidence for the early warning and management of fungal infections. Methods: We analyzed the data of patients with culture-positive fungi during their admission to seven ICUs of the First Affiliated Hospital of Chongqing Medical University from January 1, 2015, to December 31, 2019. Patients whose first culture was positive for fungi longer than 48 h after ICU admission were included in the ICU-AF cohort. A predictive model of ICU-AF was obtained using the Least Absolute Shrinkage and Selection Operator and machine learning, and the relationship between the features within the model and the disease severity and mortality of patients was analyzed. Finally, the relationships between the ICU-AF model, antifungal therapy and empirical antifungal therapy were analyzed. Results: A total of 1,434 cases were included finally. We used lasso dimensionality reduction for all features and selected six features with importance ≥0.05 in the optimal model, namely, times of arterial catheter, enteral nutrition, corticosteroids, broadspectrum antibiotics, urinary catheter, and invasive mechanical ventilation. The area under the curve of the model for predicting ICU-AF was 0.981 in the test set, with a sensitivity of 0.960 and specificity of 0.990. The times of arterial catheter (p = 0.011, OR = 1.057, 95% CI = 1.053-1.104) and invasive mechanical ventilation (p = 0.007, OR = 1.056, 95%CI = 1.015-1.098) were independent risk factors for antifungal therapy in ICU-AF. The times of arterial catheter (p = 0.004, OR = 1.098, 95%CI = 0.855-0.970) were an independent risk factor for empirical antifungal therapy. Conclusion: The most important risk factors for ICU-AF are the six time-related features of clinical parameters (arterial catheter, enteral nutrition, corticosteroids, broadspectrum antibiotics, urinary catheter, and invasive mechanical ventilation), which provide early warning for the occurrence of fungal infection. Furthermore, this model can help ICU physicians to assess whether empiric antifungal therapy should be administered to ICU patients who are susceptible to fungal infections.

Tracking Chinese Online Activity and Interest in Osteoporosis Using the Baidu Index.

Introduction China's most widely used online search engine, Baidu (Baidu, Inc., Beijing, China), has developed a data collection and analysis tool called the Baidu Index for tracking Internet search trends. The purpose of this study was to examine the utility of the Baidu Index in tracking online osteoporosis information-seeking behavior and comprehending the traits and concerns of the Chinese population. Methods We used the search term "osteoporosis" for the Baidu Index for the years 2018-2022. The geographic and demographic distributions, search volumes, and demand maps were recorded. Results The popularity of the search term "osteoporosis" has increased over time. The search was mostly conducted among women aged 20-39 in northern China. The demand map revealed that the most significant concerns are related to the diagnosis, treatment, and etiology of osteoporosis. Conclusion The Baidu Index is a valuable tool for tracking online health information-seeking behavior among Chinese netizens. Online search trend data appears to reflect the geographic and demographic aspects of osteoporosis to a certain extent.

Causal relationship of interleukin-6 and its receptor on sarcopenia traits using mendelian randomization.

BACKGROUND: Previous research has extensively examined the role of interleukin 6 (IL-6) in sarcopenia. However, the presence of a causal relationship between IL-6, its receptor (IL-6R), and sarcopenia remains unclear. METHOD: In this study, we utilized summary-level data from genome-wide association studies (GWAS) focused on appendicular lean mass (ALM), hand grip strength, and walking pace. Single nucleotide polymorphisms (SNPs) were employed as genetic instruments for IL-6 and IL-6R to estimate the causal effect of sarcopenia traits. We adopted the Mendelian randomization (MR) approach to investigate these associations using the inverse variance weighted (IVW) method as the primary analytical approach. Additionally, we performed sensitivity analyses to validate the reliability of the MR results. RESULT: This study revealed a significant negative association between main IL-6R and eQTL IL-6R on the left grip strength were - 0.013 (SE = 0.004, p < 0.001) and -0.029 (SE = 0.007, p < 0.001), respectively. While for the right grip strength, the estimates were - 0.011 (SE = 0.001, p < 0.001) and - 0.021 (SE = 0.008, p = 0.005). However, no evidence of an association for IL-6R with ALM and walking pace. In addition, IL-6 did not affect sarcopenia traits. CONCLUSION: Our study findings suggest a negative association between IL-6R and hand grip strength. Additionally, targeting IL-6R may hold potential value as a therapeutic approach for the treatment of hand grip-related issues.

Type 2 diabetic mellitus related osteoporosis: focusing on ferroptosis.

With the aging global population, type 2 diabetes mellitus (T2DM) and osteoporosis(OP) are becoming increasingly prevalent. Diabetic osteoporosis (DOP) is a metabolic bone disorder characterized by abnormal bone tissue structure and reduced bone strength in patients with diabetes. Studies have revealed a close association among diabetes, increased fracture risk, and disturbances in iron metabolism. This review explores the concept of ferroptosis, a non-apoptotic cell death process dependent on intracellular iron, focusing on its role in DOP. Iron-dependent lipid peroxidation, particularly impacting pancreatic ß-cells, osteoblasts (OBs) and osteoclasts (OCs), contributes to DOP. The intricate interplay between iron dysregulation, which comprises deficiency and overload, and DOP has been discussed, emphasizing how excessive iron accumulation triggers ferroptosis in DOP. This concise overview highlights the need to understand the complex relationship between T2DM and OP, particularly ferroptosis. This review aimed to elucidate the pathogenesis of ferroptosis in DOP and provide a prospective for future research targeting interventions in the field of ferroptosis.

Mild hyperthermia enhanced synergistic uric acid degradation and multiple ROS elimination for an effective acute gout therapy.

BACKGROUND: Acute gouty is caused by the excessive accumulation of Monosodium Urate (MSU) crystals within various parts of the body, which leads to a deterioration of the local microenvironment. This degradation is marked by elevated levels of uric acid (UA), increased reactive oxygen species (ROS) production, hypoxic conditions, an upsurge in pro-inflammatory mediators, and mitochondrial dysfunction. RESULTS: In this study, we developed a multifunctional nanoparticle of polydopamine-platinum (PDA@Pt) to combat acute gout by leveraging mild hyperthermia to synergistically enhance UA degradation and anti-inflammatory effect. Herein, PDA acts as a foundational template that facilitates the growth of a Pt shell on the surface of its nanospheres, leading to the formation of the PDA@Pt nanomedicine. Within this therapeutic agent, the Pt nanoparticle catalyzes the decomposition of UA and actively breaks down endogenous hydrogen peroxide (H2O2) to produce O2, which helps to alleviate hypoxic conditions. Concurrently, the PDA component possesses exceptional capacity for ROS scavenging. Most significantly, Both PDA and Pt shell exhibit absorption in the Near-Infrared-II (NIR-II) region, which not only endow PDA@Pt with superior photothermal conversion efficiency for effective photothermal therapy (PTT) but also substantially enhances the nanomedicine's capacity for UA degradation, O2 production and ROS scavenging enzymatic activities. This photothermally-enhanced approach effectively facilitates the repair of mitochondrial damage and downregulates the NF-κB signaling pathway to inhibit the expression of pro-inflammatory cytokines. CONCLUSIONS: The multifunctional nanomedicine PDA@Pt exhibits exceptional efficacy in UA reduction and anti-inflammatory effects, presenting a promising potential therapeutic strategy for the management of acute gout.

Experimental observation of current-driven antiskyrmion sliding in stripe domains.

Magnetic skyrmions are promising as next-generation information units. Their antiparticle-the antiskyrmion-has also been discovered in chiral magnets. Here we experimentally demonstrate antiskyrmion sliding in response to a pulsed electric current at room temperature without the requirement of an external magnetic field. This is realized by embedding antiskyrmions in helical stripe domains, which naturally provide one-dimensional straight tracks along which antiskyrmion sliding can be easily launched with low current density and without transverse deflection from the antiskyrmion Hall effect. The higher mobility of the antiskyrmions in the background of helical stripes in contrast to the typical ferromagnetic state is a result of intrinsic material parameters and elastic energy of the stripe domain, thereby smearing out the random pinning potential, as supported by micromagnetic simulations. The demonstration and comprehensive understanding of antiskyrmion movement along naturally straight tracks offers a new perspective for (anti)skyrmion application in spintronics.

Locoregional treatment improves overall survival for liver cancer during second-line regorafenib or immune checkpoint inhibitor.

For advanced hepatocellular carcinoma (HCC), the best second-line treatment after first-line treatment with sorafenib is unclear. This study aimed to compared the efficacy of second-line regorafenib (a tyrosine kinase inhibitor) and immune checkpoint inhibitors (ICIs) in patients with advanced HCC after sorafenib therapy. This retrospective study included 89 patients with HCC treated with sorafenib, and then regorafenib (n = 58) or an ICI (n = 31). Treatment response, overall survival (OS) and progression-free survival (PFS) of the 2 groups were compared, and factors associated with post-treatment mortality or disease progression were evaluated. During follow-up period, compared to regorafenib, treatment with an ICI results in a slight increase in a 20% decrease of AFP (35.7% vs. 31.8%), complete response rate (6.5% vs. 0%), objective response rate (16.1% vs. 6.9%), median overall survival (13.3 vs. 5 months), and median PFS (3.0 vs. 2.6 months). Combined locoregional treatment (LRT) (hazard ratio [HR] = 0.40, 95% confidence interval [CI]: 0.15-0.99) during second-line treatment was associated with a decreased risk of post-treatment mortality. After propensity scoring matching, combined LRT during second-line treatment had longer post-treatment OS than patients without combined LRT. A 20% decrease of AFP (HR = 0.54, 95% CI: 0.31-0.94) was associated with a decreased risk of post-treatment disease progression. In conclusions, second-line treatment with regorafenib or ICI prolongs OS in patients with advanced HCC treated with sorafenib. Combined LRT during second-line treatment is associated with decreased post-treatment mortality. A 20% decrease of AFP level may be predictive of a lower rate of disease progression.

The relationship between different fatty acids intake and the depressive symptoms: A population-based study.

BACKGROUND: Depression is a common psychological disorder worldwide, affecting mental and physical health. Previous studies have explored the benefits of polyunsaturated fatty acids (PUFAs) intake in depressive symptoms; however, few studies have focused on the association between all types of fatty acids intake and depressive symptoms. Therefore, we explored the relationship between the intake of different fatty acids intake and the risk of depressive symptoms. METHODS: The study was based on the data from the 2005-2018 National Health and Nutrition Examination Survey (NHANES), a large US-based database. We used a nutrient residual model and multi-nutrient density model for the analysis. We calculated the nutrient density and residual in men and women separately, and the fatty acids intake was divided into quartiles based on the sex distribution. The relationship between the depressive symptoms and the intake of different fatty acids was examined using logistic regression; furthermore, we explored the relationships separately in men and women. RESULTS: The intake of monounsaturated fatty acids (MUFAs) and PUFAs, particularly n-3 and n-6 PUFAs, were associated with reduced odds ratios for depressive symptoms. The inverse relationship between the intake of MUFAs, PUFAs, n-3, and n-6 PUFAs and depressive symptoms was stronger in women. The inverse relationship between total fatty acid (TFAs) intake and depressive symptoms existed only in a single model. In contrast, saturated fatty acid (SFAs) intake was not related to depressive symptoms. CONCLUSION: Consuming MUFAs and PUFAs can counteract the depressive symptoms, especially in women.

Concurrent Atezolizumab Plus Bevacizumab and High-Dose External Beam Radiotherapy for Highly Advanced Hepatocellular Carcinoma.

BACKGROUND: Atezolizumab plus bevacizumab (atezo-bev) has been recommended for advanced hepatocellular carcinoma (HCC). High-dose external beam radiotherapy (RT) is recognized for its excellent local tumor control. The efficacy and safety of concurrent atezo-bev with RT for highly advanced HCC has been minimally explored. METHODS: In this preliminary retrospective study, we assessed patients with highly advanced HCC, characterized by Vp4 portal vein thrombosis or tumors exceeding 50% of liver volume, who received concurrent atezo-bev and RT (group A). Group A included 13 patients who received proton radiation at a dose of 72.6 GyE in 22 fractions, and one patient who received photon radiation at a dose of 54 Gy in 18 fractions. This group was compared with 34 similar patients treated atezo-bev alone as a control (group B). The primary objectives were to evaluate the objective response rate (ORR), overall survival (OS), and safety. RESULTS: Baseline characteristics were similar between groups, except for a higher incidence of Vp4 portal vein thrombosis in group A (78.6% vs. 21.4%, P = .05). Group A achieved a higher ORR (50.0% vs. 11.8%, P < .01) and a longer OS (not reached vs. 5.5 months, P = .01) after a median follow-up of 5.2 months. Multivariate analysis indicated that concurrent RT independently favored longer OS (hazard ratio: 0.18; 95% CI, 0.05-0.63, P < .01). Group A did not increase any grade adverse events (78.6% vs. 58.8%, P = .19) or severe adverse events of grade ≥ 3 (14.3% vs. 14.7%, P = .97) compared to group B. CONCLUSIONS: The concurrent high-dose external beam radiotherapy appears to safely enhance the effectiveness of atezolizumab plus bevacizumab for highly advanced patients with HCC. Further studies are warranted to confirm these findings.

The association of metabolic syndrome score trajectory patterns with risk of all cancer types.

BACKGROUND: Metabolic syndrome (MetS) elevates cancer risk. However, a single MetS assessment does not fully reveal the long-term association with cancer. Inflammation, alongside MetS, could synergistically expedite both the onset and advancement of cancer. This study aims to investigate MetS score trajectories and cancer risk in a large, prospective cohort study. METHODS: The authors prospectively examined the relationship between MetS score trajectory patterns and new-onset cancer in 44,115 participants. Latent mixture modeling was used to identify the MetS score trajectories. Cox proportional hazards regression models were used to evaluate the association between MetS score trajectory patterns and the risk of overall and site-specific cancers. RESULTS: Four MetS score trajectory patterns were identified: low-stable (n = 4657), moderate-low (n = 18,018), moderate-high (n = 18,288), and elevated-increasing (n = 3152). Compared to participants with a low-stable trajectory pattern, the elevated-increasing trajectory pattern was associated with an elevated risk of overall (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.04-1.55), breast (HR, 2.11; 95% CI, 1.04-4.34), endometrial (HR, 3.33; 95% CI, 1.16-6.77), kidney (HR, 4.52; 95% CI, 1.17-10.48), colorectal (HR, 2.54; 95% CI, 1.27-5.09), and liver (HR, 1.61; 95% CI, 1.09-4.57) cancers. Among participants with chronic inflammation (C-reactive protein levels ≥3 mg/L), the elevated-increasing trajectory pattern was significantly associated with subsequent breast, endometrial, colorectal, and liver cancers. CONCLUSIONS: Trajectories of MetS scores are associated with the occurrence of cancers, especially breast, endometrial, kidney, colorectal, and liver cancers, emphasizing the importance of long-term monitoring and evaluation of MetS. PLAIN LANGUAGE SUMMARY: The association between long-term elevated metabolic syndrome (MetS) scores and a heightened risk of various cancers is a pivotal finding of our study. Our research further indicates that individuals with MetS, particularly when coupled with chronic inflammation, are at an increased risk of cancer. We propose that sustained monitoring and management of MetS could be beneficial in reducing cancer risk.