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Abstract Tumor necrosis factor receptor‐associated factor 5 (TRAF5) has been implicated in the pathogenesis of human malignancies. This work aimed to clarify the role of TRAF5 in lung adenocarcinoma (LUAD) progression. Herein, we uncovered that TRAF5 level was reduced in LUAD tissues. Low TRAF5 expression correlated with dismal prognosis in LUAD patients. Moreover, upregulated TRAF5 impeded cell viability, migration, and invasion, induced apoptosis in vitro, as well as impaired tumorigenicity in vivo. However, depletion of TRAF5 revealed opposing results. Moreover, TRAF5 was identified as the downstream target of methyltransferase‐like 3 (METTL3)‐elicited N6‐methyladenosine (m6A) modification. METTL3 stabilized TRAF5 mRNA and positively modulated TRAF5 level. Further, TRAF5 depletion relieved the repressive phenotype caused by METTL3 addition. In addition, it was manifested that the METTL3/TRAF5 axis served as an inhibitor in LUAD through the PI3K/AKT/Nuclear Factor‐Kappa B (NF‐κB) signaling. Collectively, we propose that METTL3‐mediated TRAF5 m6A modification exerted as a vital tumor inhibitory function in LUAD development. The METTL3/TRAF5 axis may be a critical effector of LUAD progression.

Abstract Background Knee osteoarthritis (KOA) is the most common chronic degenerative joint disease and places a substantial burden on the public health resources in China. The purpose of this study is to preliminarily evaluate whether infrared laser moxibustion (ILM) is non-inferior to traditional moxibustion (TM) in the treatment of KOA. Materials and methods In the designed Zelen-design randomized controlled non-inferiority clinical trial, a total of 74 patients with KOA will be randomly allocated to one of two interventions: ILM treatment or TM treatment. All participants will receive a 6-week treatment and a follow-up 4 weeks after treatment. The primary outcomes will be the mean change in pain scores on the numeric rating scale (NRS) measured at baseline and the end of last treatment at week 6. The secondary outcomes will be the pain scores on the NRS from weeks 1 to 5 after the start of treatment and the changes from baseline to endpoints (weeks 6 and 10) in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), SF-36, knee circumference, and 6-min walking test. In addition, safety assessment will be performed throughout the trial. Conclusion The results of our study will help determine whether a 6-week treatment with ILM is non-inferior to TM in patients with KOA, therefore providing evidence to verify if ILM can become a safer alternative for TM in clinical applications in the future. Trial registration: Clinical Trial Registration Platform (ChiCTR2200065264); Pre-results. Registered on 1 November 2022.

Stellar and black hole feedback heat and disperse surrounding cold gas clouds, launching gas flows off circumnuclear and galactic disks, producing a dynamic interstellar medium. On large scales bordering the cosmic web, feedback drives enriched gas out of galaxies and groups, seeding the intergalactic medium with heavy elements. In this way, feedback shapes galaxy evolution by shutting down star formation and ultimately curtailing the growth of structure after the peak at redshift 2–3. To understand the complex interplay between gravity and feedback, we must resolve both the key physics within galaxies and map the impact of these processes over large scales, out into the cosmic web. The Advanced X-ray Imaging Satellite (AXIS) is a proposed X-ray probe mission for the 2030s with arcsecond spatial resolution, large effective area, and low background. AXIS will untangle the interactions of winds, radiation, jets, and supernovae with the surrounding interstellar medium across the wide range of mass scales and large volumes driving galaxy evolution and trace the establishment of feedback back to the main event at cosmic noon. This white paper is part of a series commissioned for the AXIS Probe mission concept; additional AXIS white papers can be found at the AXIS website.

CHANG-ES (Continuum Halos in Nearby Galaxies—an EVLA Survey) is an ambitious project to target 35 nearby disk galaxies that are edge-on to the line of sight. The orientation permits both the disk and halo regions to be studied. The observations were initially at 1.5 GHz (L-band) and 6.0 GHz (C-band) in a variety of VLA array configurations, and in all four Stokes parameters, which allowed for spatially resolved images in total intensity plus polarization. The inclusion of polarization is unique to an edge-on galaxy survey and reveals the galaxies’ halo magnetic fields. This paper will summarize the results to date, some of which are new phenomena, never seen prior to CHANG-ES. For example, we see that ‘X-type’ fields, as well as rotation measure reversals, are common features of spiral galaxies. Further observations at 3.0 GHz (S-band) as well as future scientific opportunities will also be described.

Background: The outcome of patients with acute myeloid leukemia (AML) aged ⩾65 years is poor. Effective treatment options are limited for patients with AML who cannot tolerate intensive chemotherapy. Objectives: We aimed to evaluate the efficacy of low-dose decitabine in previously untreated patients with AML aged ⩾65 years who were ineligible for intensive chemotherapy based on a comprehensive geriatric assessment. Design: We performed a prospective, multicenter, open-label, and non-randomized study. Methods: Patients were enrolled at four centers in Beijing between 1 January 2017 and 31 December 2020. They were treated with decitabine at a dose of 6 mg/m 2 for 10 days. The treatment was repeated every 28 days for one cycle for a total of six cycles. The primary endpoint of our study was overall survival (OS) at the end of the first year after enrolment. The secondary endpoints included overall response rate, leukemia-free survival, relapse rate, treatment-related mortality (TRM), quality of life, safety, and transfusion dependence. Patients were continuously monitored for toxicity. Results: Overall, 47 patients (30 males and 17 females) participated in this study. The median age of the enrolled patients was 78 (range, 65−90) years. The median follow-up time was 22.2 (range, 4.6−38.8) months. Fifteen (31.9%) patients achieved complete remission (CR), 11 (23.4%) patients achieved partial remission, 3 (6.4%) patients achieved hematological improvement only, and 18 (38.3%) patients did not achieve remission. The median time to obtain CR was 2 months. The median CR was 8.5 months. Of the patients, 36 (76.6%) patients completed six cycles of treatment with low-dose decitabine, and the 1-year OS was 36.1%. According to instrumental activities of daily living scales, age, comorbidities, and albumin (IACA) scores, the median survival was 11.2 months in the unfit group and 6 months in the frail group. The 1-year OS rates in the unfit and frail groups were 49.2% and 23.4%, respectively. Grade ⩾3 non-hematological toxicity was observed in 70.2% (33/47) of the patients. TRM occurred in three patients. No early deaths occurred after treatment. Conclusion: In newly diagnosed older patients with AML whose IACA assessment was unfit or frail for standard chemotherapy, treatment with low-dose decitabine demonstrated clinical activity and good security in our study.

Early-stage detection of lung tumors helps to reduce patient mortality rates. In this work, we propose a method for diagnosing lung tumors in nude mice through combining laser-induced breakdown spectroscopy (LIBS) with the Histogram of Orientation Gradients (HOG) and Support Vector Machine (SVM). Firstly, the elemental spectral lines and elemental imaging maps for lung tissue are respectively obtained by the LIBS system. Secondly, the HOG is used to obtain the gradient direction relationship of multi-dimensional spectral intensity from LIBS images. The optimal spectral features based on HOG for different biological tissue can be extracted. And then, the SVM model is adopted to determine lung tumors. The results show that, compared to classification models based on SVM with full-spectrum emission intensity and SVM with Principal Component Analysis (PCA), the identification accuracy of lung tumors from the nude mice by using the HOG-SVM can be improved by 10.66% and 4.66%, the sensitivity can be improved by 12% and 4%, and the specificity can be improved by 8% and 6%, respectively. In addition, HOG-SVM is also used to differentiate inflammatory lung tissue from normal lung tissue in nude mice, and achieves the ideal classification result. This work shows that the LIBS technique combined with HOG-SVM provides a complementary method for the rapid detection of lung tumors, contributing to the successful treatment of patients.

The [C ii ] 158 μ m emission line and the underlying far-infrared (FIR) dust continuum are important tracers for studying star formation and kinematic properties of early galaxies. We present a survey of the [C ii ] emission lines and FIR continua of 31 luminous quasars at z > 6.5 using the Atacama Large Millimeter Array (ALMA) and the NOrthern Extended Millimeter Array at sub-arcsec resolution. This survey more than doubles the number of quasars with [C ii ] and FIR observations at these redshifts and enables statistical studies of quasar host galaxies deep into the epoch of reionization. We detect [C ii ] emission in 27 quasar hosts with a luminosity range of L _[C _II _] = (0.3–5.5) × 10 ^9 L _⊙ and detect the FIR continuum of 28 quasar hosts with a luminosity range of L _FIR = (0.5–13.0) × 10 ^12 L _⊙ . Both L _[C _II _] and L _FIR are correlated ( ρ ≃ 0.4) with the quasar bolometric luminosity, albeit with substantial scatter. The quasar hosts detected by ALMA are clearly resolved with a median diameter of ∼5 kpc. About 40% of the quasar host galaxies show a velocity gradient in [C ii ] emission, while the rest show either dispersion-dominated or disturbed kinematics. Basic estimates of the dynamical masses of the rotation-dominated host galaxies yield M _dyn = (0.1–7.5) × 10 ^11 M _⊙ . Considering our findings alongside those of literature studies, we found that the ratio between M _BH and M _dyn is about 10 times higher than that of local M _BH – M _dyn relation on average but with substantial scatter (the ratio difference ranging from ∼0.6 to 60) and large uncertainties.

The extraplanar diffuse ionized gas (eDIG) represents ionized gases traced by optical/UV lines beyond the stellar extent of galaxies. We herein introduce a novel multislit narrow-band spectroscopy method to conduct spatially resolved spectroscopy of the eDIG around a sample of nearby edge-on disk galaxies (eDIG-CHANGES). In this paper, we introduce the project design and major scientific goals, as well as a pilot study of NGC 3556 (M108). The eDIG is detected to a vertical extent of a few kiloparsecs above the disk, comparable to the X-ray and radio images. We do not see significant vertical variation of the [N ii ]/H α line ratio. A rough examination of the pressure balance between different circumgalactic medium phases indicates the magnetic field is in a rough pressure balance with the X-ray emitting hot gas and may play an important role in the global motion of both the eDIG and the hot gas in the lower halo. At the location of an Hubble Space Telescope/Cosmic Origins Spectrograph observed UV bright background active galactic nucleus ∼29 kpc from the center of NGC 3556, the magnetic pressure is much lower than that of the hot gas and the ionized gas traced by UV absorption lines, although the extrapolation of the pressure profiles may cause some biases in this comparison. By comparing the position–velocity diagrams of the optical and CO lines, we also find the dynamics of the two gas phases are consistent with each other, with no evidence of a global inflow/outflow and a maximum rotation velocity of ∼150 km s ^−1 .

Superbubbles in the nuclear region of galaxies could be produced by active galactic nuclei (AGN) or nuclear starburst via different driving forces. We report analysis of the multiwavelength data of the kiloparsec-scale nuclear superbubble in NGC 3079 in order to probe the mechanisms driving the expansion of the superbubble. Based on the Chandra X-ray observations, we derive the hot-gas thermal pressure inside the bubble, which is about 1 order of magnitude higher than that of the warm ionized gas traced by optical lines. We derive a [C ii ]-based star formation rate (SFR) of SFR ∼ 1.3 M _⊙ yr ^−1 from the nuclear region using the SOFIA/FIFI-LS observation. This SFR infers a radiation pressure toward the bubble shells much lower than the thermal pressure of the gases. The Very Large Array radio image infers that magnetic pressure at the northeast cap above the superbubble is less than the thermal pressure of the hot gas enclosed in the bubble but has a clearly larger extension. The magnetic field may thus still help to reconcile the expansion of the bubble. The observed thermal energy of the hot gas enclosed in the bubble requires an energy injection rate of ≳10 ^42 erg s ^−1 within the bubble’s dynamical age, which is probably larger than the power provided by the current nuclear starburst and the parsec-scale jet. If this is true, stronger past AGN activity may provide an alternative energy source to drive the observed bubble expansion.

We report the discovery of the 10 kpc scale radio lobes in the Sombrero galaxy (NGC 4594), using data from the Continuum Halos in Nearby Galaxies—an Expanded Very Large Array Survey project. We further examine the balance between the magnetic pressure inside the lobes and the thermal pressure of the ambient hot gas. At the radii r of ∼(1–10) kpc, the magnetic pressure inside the lobes and the thermal pressure of the ambient hot gas are generally in balance. This implies that the jets could expand into the surroundings to at least r ∼ 10 kpc. The feedback from the active galactic nucleus jet responsible for the large-scale lobes may help to explain the unusually high X-ray luminosity of this massive quiescent isolated disk galaxy, although more theoretical work is needed to further examine this possibility.

During 6–10 January 2021, a recorded strong cold surge took place in China, with over 800 observational stations reaching their historical extremes. Unlike previous studies that focused on the response of either the power load or generation separately, this study quantitatively revealed the impacts on the balance between the demand and supply sides of the grid. On the demand side, the sensitivity of power load was found to increase substantially higher in southern China (0.533 GW °C−1) than in the northern region (0.139 GW °C−1) due to the limited municipal heating system. On the supply side, the hourly wind power generation dropped from the highest of 110 GW on 6 January to the lowest of 54 GW on 9 January due to the reduction in wind speed. In addition, a reduction in solar power generation was observed during 8–10 January. Thus, the balance of the power system was influenced by this cold event. As an effective adaptation measure, results further showed that early warning by three weeks ahead can be obtained by an operational climate model. The sensitivity of China's power system to such cold surge events may increase remarkably due to the expected increase in the proportion of wind and solar power generation in future new-type power systems. Thus, close cooperation between climate scientists and power engineers is needed to build the resilience of the power system to the cold extremes.

Abstract Background Hepatectomy is currently the most effective modality for the treatment of intrahepatic cholangiocarcinoma (ICC). The status of the lymph nodes directly affects the choice of surgical method and the formulation of postoperative treatment plans. Therefore, a preoperative judgment of lymph node status is of great significance for patients diagnosed with this condition. Previous prediction models mostly adopted logistic regression modeling, and few relevant studies applied random forests in the prediction of ICC lymph node metastasis (LNM). Methods A total of 149 ICC patients who met clinical conditions were enrolled in the training group. Taking into account preoperative clinical data and imaging features, 21 indicators were included for analysis and modeling. Logistic regression was used to filter variables through multivariate analysis, and random forest regression was used to rank the importance of these variables through the use of algorithms. The model’s prediction accuracy was assessed by the concordance index (C-index) and calibration curve and validated with external data. Result Multivariate analysis shows that Carcinoembryonic antigen (CEA), Carbohydrate antigen19-9 (CA19-9), and lymphadenopathy on imaging are independent risk factors for lymph node metastasis. The random forest algorithm identifies the top four risk factors as CEA, CA19-9, and lymphadenopathy on imaging and Aspartate Transaminase (AST). The predictive power of random forest is significantly better than the nomogram established by logistic regression in both the validation group and the training group (Area Under Curve reached 0.758 in the validation group). Conclusions We constructed a random forest model for predicting lymph node metastasis that, compared with the traditional nomogram, has higher prediction accuracy and simultaneously plays an auxiliary role in imaging examinations.

Photocatalytic radical cascade reactions enable the facile construction of diverse cyclic compounds, though they rely on templated precursors. In this paper, the authors report on stereoselective intermolecular radical cascade reaction between tryptophan or ɤ-alkenyl substituted amino acids and acrylamides to synthesise multi-substituted trans-fused hexahydrocarbazoles or 1,3,5-trisubstituted cyclohexanes.

As a rare disease, intrahepatic sarcomatoid cholangiocarcinoma (s-CCC) represents less than 1% of malignancies of the hepatobiliary system and its main clinical symptoms include abdominal pain and fever. Results of pathological examinations, despite being the “gold standard”, can easily be confused with hepatocellular carcinoma (HCC). This report is about a 32-year-old male patient who was hospitalized due to occupancy of segment V of the liver for three days and had a history of chronic hepatitis B (CHB) over a 20-year span. Magnetic resonance imaging (MRI) showed a 43 mm × 52 mm-sized liver mass in the V segment, with patchy peripheral enhancement during the arterial phase and rapid wash-out during the portal and late phases. A laparoscopic hepatectomy of segment V, along with cholecystectomy, was performed. Histopathological and immunohistochemical examinations indicated a malignant neoplasm that was positive for vimentin and cytokeratin, with these features providing a positive diagnosis for intrahepatic sarcomatoid cholangiocarcinoma. After surgery, an adjuvant therapy of albumin-paclitaxel combined with gemcitabine regimen was given. No recurrence was found six months after the surgery, with follow-up still ongoing. This report aims to improve the awareness, diagnosis, and treatment of s-CCC.

The deep-sea hydrothermal vents (DSHVs) in the Southwest Indian Ridge (SWIR) are formed by specific geological settings. However, the community structure and ecological function of the microbial inhabitants on the sulfide chimneys of active hydrothermal vents remain largely unknown. In this study, our analyses of 16S rRNA gene amplicons and 16S rRNA metagenomic reads showed the dominance of sulfur-oxidizing Ectothiorhodospiraceae, Thiomicrorhabdus, Sulfurimonas, and Sulfurovum on the wall of two active hydrothermal chimneys. Compared with the inactive hydrothermal sediments of SWIR, the active hydrothermal chimneys lacked sulfur-reducing bacteria. The metabolic potentials of the retrieved 82 metagenome-assembled genomes (MAGs) suggest that sulfur oxidation might be conducted by Thiohalomonadales (classified as Ectothiorhodospiraceae based on 16S rRNA gene amplicons), Sulfurovaceae, Hyphomicrobiaceae, Thiotrichaceae, Thiomicrospiraceae, and Rhodobacteraceae. For CO2 fixation, the Calvin-Benson-Bassham and reductive TCA pathways were employed by these bacteria. In Thiohalomonadales MAGs, we revealed putative phytochrome, carotenoid precursor, and squalene synthesis pathways, indicating a possible capacity of Thiohalomonadales in adaptation to dynamics redox conditions and the utilization of red light from the hot hydrothermal chimneys for photolithotrophic growth. This study, therefore, reveals unique microbiomes and their genomic features in the active hydrothermal chimneys of SWIR, which casts light on ecosystem establishment and development in hydrothermal fields and the deep biosphere.

We introduce the New-ANGELS program, an XMM-Newton survey of a ∼7.2 deg ^2 area around M31, which aims to study the X-ray populations in the M31 disk and the X-ray-emitting hot gas in the inner halo of M31 up to 30 kpc. In this first paper, we report the catalog of 4506 detected X-ray sources and attempt to cross-identify or roughly classify them. We identify 352 single stars in the foreground, 35 globular clusters, and 27 supernova remnants associated with M31, as well as 62 active galactic nuclei, 59 galaxies, and one galaxy cluster in the background. We uniquely classify 236 foreground stars and 17 supersoft sources based on their X-ray colors. X-ray binaries (83 low-mass and one high-mass) are classified based on their X-ray colors and X-ray variabilities. The remaining X-ray sources either have too low signal-to-noise ratios to calculate their X-ray colors or do not have a unique classification, so are regarded as unclassified. The X-ray source catalog is published online. Studies of the X-ray source populations and the contribution of X-ray sources in the unresolved X-ray emissions based on this catalog will be published in companion papers.

Abstract. Background:. Acute myeloid leukemia (AML) is a common type of hematological malignancy in elderly people. Geriatricians have developed comprehensive geriatric assessment (CGA) methods for elderly patients; however, the tools used for CGA in AML are not uniform. Thus, we aimed to validate the instrumental activities of daily living (IADL) scales, age, comorbidities (Charlson Comorbidity Index), and albumin (IACA) index, which is a new tool for CGA, in elderly patients with AML. Methods:. Patients aged ≥60 years who had been diagnosed with AML were screened for eligibility. Among the IACA low-, intermediate-, and high-risk groups, continuous variables were compared using the Mann-Whitney U test, and categorical variables were compared using χ2 and Fisher exact tests. In addition, probabilities of overall survival (OS) were estimated using the Kaplan-Meier method. Results:. A total of 21, 34, and 6 patients were categorized into IACA low-risk (0 point), intermediate-risk (1–2 points), and high-risk (≥3 points) groups, respectively. The rates of relapse/progression-related mortality were 23.8%, 58.8%, and 100.0% in the IACA low-, intermediate-, and high-risk groups, respectively (χ2 = 12.81, P

Abstract Background In the era of primary percutaneous coronary intervention (PPCI), the incidence of post-cardiac injury syndrome (PCIS) in patients with acute myocardial infarction (AMI) following PPCI has become less common. However, the intrinsic pathogenesis of this medical condition remains largely uncertain. Unlike the prior reports, the present paper provides new mechanistic clues concerning the pathogenesis of PCI-related PCIS. Case presentation A 45-year-old male with AMI had developed an early onset of PCIS at 3 h after PPCI. A significantly slower TIMI flow (grade ≤ 2) for the culprit arteries was observed through follow-up coronary angiography (CAG); no stent thrombosis or any significant evidence of iatrogenic trauma due the intervention procedures was found. Nevertheless, the the serum level of HsCRP showed similar variation trend as the neutrophil count and troponin T in continuous blood monitoring, which suggested a potential association between PPCI-related coronary microvascular dysfunction (CMD) and pathogenesis of PCIS. Conclusions The reported case had excessive inflammatory reaction and CMD resulting from cardiac ischemia-reperfusion injury in an AMI patient with risk factors of endothelial dysfunction. There exists a potential reciprocal causation between PCIS and performance of PPCI in the AMI patient who was susceptible to endothelial damage.

Abstract Recent research has shown that the triggering receptor expressed on myeloid cells 2 (TREM2) in microglia is closely related to the pathogenesis of Alzheimer’s disease (AD). The mechanism of this relationship, however, remains unclear. TREM2 is part of the TREM family of receptors, which are expressed primarily in myeloid cells, including monocytes, dendritic cells, and microglia. The TREM family members are cell surface glycoproteins with an immunoglobulin-like extracellular domain, a transmembrane region and a short cytoplasmic tail region. The present article reviews the following: (1) the structure, function, and variant site analysis of the Trem2 gene; (2) the metabolism of TREM2 in peripheral blood and cerebrospinal fluid; and (3) the possible underlying mechanism by which TREM2 regulates innate immunity and participates in AD.

Background: Much evidence has demonstrated that interleukin (IL)-33 plays an important role in rheumatoid arthritis (RA). However, there have been limited studies about soluble ST2, a receptor for IL-33, in RA. The aims of this study were to detect the levels of ST2 in the serum and synovial fluid of RA patients and to reveal the association of these levels with disease activity and the function of ST2 in RA. Methods: A total of 56 RA patients and 38 age-matched healthy controls were enrolled in this study. Synovial fluid samples were collected from another 30 RA patients and 20 osteoarthritis patients. Serum and synovial fluid levels of ST2 were measured by ELISA. In addition, the levels of ST2 in the serum of RA patients before and after therapy were detected. The function of ST2 in RA was revealed by the results of an in vitro cell assay, where recombinant ST2 proteins were used to treat peripheral blood mononuclear cells (PBMCs) and RA synovial fibroblasts (RASFs). Results: Serum-soluble ST2 levels were significantly higher in RA patients (127.14 ± 61.43 pg/ml) than those in healthy controls (78.37 ± 41.93 pg/ml, P < 0.01). Synovial fluid-soluble ST2 levels (41.90 ± 33.58 pg/ml) were much higher in RA patients than those in osteoarthritis patients (19.71 ± 16.72 pg/ml, P < 0.05). RA patients who received effective therapy for 6 months showed decreased serum-soluble ST2 levels (113.01 ± 53.90 pg/ml) compared to baseline (139.59 ± 68.36 pg/ml) (P = 0.01). RA patients with high disease activity had higher serum-soluble ST2 levels (162.02 ± 56.78 pg/ml) than those with low disease activity (94.67 ± 40.27 pg/ml, P = 0.001). Soluble ST2 did not affect IL-1β, IL-6, IL-8, or tumor necrosis factor-α (TNF-α) expression in PBMCs from RA patients. However, soluble ST2 ameliorated the expressions of IL-33 and IL-1β but not that of IL-6, IL-8, or TNF-α in resting RASFs. Interestingly, in the RASFs stimulated by TNF-α plus IL-1β, soluble ST2 showed extensive suppressive effects on the expression of IL-6, IL-8, and TNF-α. Conclusion: Elevated levels of ST2 in the serum and synovial fluid were associated with disease activity and ameliorated IL-33 expression and IL-33-induced inflammation in RASFs, suggesting that soluble ST2 might be a potential therapeutic candidate for RA.

Hepatocellular carcinoma (HCC) is the fourth most common driver of cancer-related death globally, with an estimated 72% of cases in Asia. For more than a decade, first-line systemic treatments for advanced or unresectable HCC were limited to the multi-targeted kinase inhibitors sorafenib and, more recently, lenvatinib. Now, treatment options have expanded to include immunotherapy, as exemplified by the immune checkpoint inhibitor (ICI) atezolizumab combined with the antiangiogenic agent bevacizumab. Additional combinations of ICIs with kinase inhibitors, other ICIs, or antiangiogenic agents are under investigation, further supporting the new era of immunotherapy for first-line treatment of advanced or unresectable HCC. We describe this evolving landscape and provide expert opinion on therapeutic best practices in the Asia–Pacific region, where different costs of, and patient access to, treatment are a challenge. With the combination of atezolizumab plus bevacizumab likely to become the clinical standard of care, optimising treatment sequence and ensuring patient access to newer therapies remain priorities. Cost containment and treatment sequencing may be facilitated by characterisation of predictive positive and negative biomarkers. With these considerations in mind, this review and expert opinion focused on advanced HCC in the Asia–Pacific region offers perspectives of multiple stakeholders, including physicians, payer systems, and patients.

Amorphous Y2O3–Al2O3–SiO2 beads were directly melted by a Nd:YAG laser. The structural features in multi-scale of the samples after solidification were investigated. The results showed that the cooling speed in the applied processing conditions was not high enough to retain the amorphous nature of ceramic beads into the consolidated bulks. In addition to an amorphous phase two crystalline phases, YAG and α-Al2O3, were formed yielding the formation of complex structural hierarchies.

Mucoepidermoid carcinoma of the pancreas is rare. Here, a 63-year-old woman with left upper abdominal pain and abdominal distension is presented. Her mucoepidermoid carcinoma was located at the left upper abdomen, arising from the pancreatic body and tail without invasion of pancreatic capsule. On pathologic examination, the tumor consisted of three types of cells, the majority being poorly differentiated adenocarcinoma cells with mucin products in their cytoplasm, and some moderately differentiated adenocarcinoma with a tendency to form ducts. In addition, there were epidermoid cells and intermediate undifferentiated cells. She survived for 12 months after surgery.

BACKGROUND Hypertension usually clusters with multiple comorbidities. However, the association between cardiometabolic multimorbidity (CMM) and mortality in hypertensive patients is unclear. This study aimed to investigate the association between CMM and all-cause and cardiovascular disease (CVD) mortality in Chinese patients with hypertension. METHODS The data used in this study were from the China National Survey for Determinants of Detection and Treatment Status of Hypertensive Patients with Multiple Risk Factors (CONSIDER), which comprised 5006 participants aged 19-91 years. CMM was defined as the presence of one or more of the following morbidities: diabetes mellitus, dyslipidemia, chronic kidney disease, coronary heart disease, and stroke. Cox proportional hazard models were used to calculate the hazard ratios (HR) with 95% CI to determine the association between the number of CMMs and both all-cause and CVD mortality. RESULTS Among 5006 participants [mean age: 58.6 ± 10.4 years, 50% women (2509 participants)], 76.4% of participants had at least one comorbidity. The mortality rate was 4.57, 4.76, 8.48, and 16.04 deaths per 1000 person-years in hypertensive patients without any comorbidity and with one, two, and three or more morbidities, respectively. In the fully adjusted model, hypertensive participants with two cardiometabolic diseases (HR = 1.52, 95% CI: 1.09-2.13) and those with three or more cardiometabolic diseases (HR = 2.44, 95% CI: 1.71-3.48) had a significantly elevated risk of all-cause mortality. The findings were similar for CVD mortality but with a greater increase in risk magnitude. CONCLUSIONS In this study, three-fourths of hypertensive patients had CMM. Clustering with two or more comorbidities was associated with a significant increase in the risk of all-cause and cardiovascular mortality among hypertensive patients, suggesting more intensive treatment and control in this high-risk patient group. [ABSTRACT FROM AUTHOR]