Preoperative computed tomography-guided localization for pulmonary nodules: comparison between hook-wire and anchored needle localization.

Introduction: Both hook-wire (HW) and anchored needle (AN) techniques can be used for preoperative computed tomography (CT)-guided localization for pulmonary nodules (PNs). But the outcomes associated with these two materials remain unclear. Aim: To assess the relative safety and efficacy of preoperative CT-guided HW and AN localization for PNs. Material and methods: This was a retrospective analysis of data collected from two institutions. Consecutive patients with PNs between January 2020 and December 2021 who underwent preoperative CT-guided HW or AN localization followed by video-assisted thoracoscopic surgery (VATS) procedures were included in these analyses, which compared the safety and clinical efficiency of these two localization strategies. Results: In total, 98 patients (105 PNs) and 93 patients (107 PNs) underwent CT-guided HW and AN localization procedures, respectively. The HW and AN groups exhibited similar rates of successful PN localization (95.2% vs. 99.1%, p = 0.117), but the dislodgement rate in the HW group was significantly higher than that for the AN group (4.8% vs. 0.0%, p = 0.029). The mean pain score of patients in the HW group was significantly higher than that for the AN group (p = 0.001). HW and AN localization strategies were associated with comparable pneumothorax (21.4% vs. 16.1%, p = 0.349) and pulmonary hemorrhage (29.6% vs. 23.7%, p = 0.354) rates. All patients other than 1 individual in the HW group successfully underwent VATS-guided limited resection. Conclusions: These data suggest that AN represents a safe, well-tolerated, feasible preoperative localization strategy for PNs that may offer value as a replacement for HW localization.

Effect of seasonal variations in sea level on residual saltwater removal upstream of subsurface dam in coastal layered heterogeneity aquifers.

Subsurface dams have been recognized as one of the most effective measures for preventing saltwater intrusion. However, it may result in large amounts of residual saltwater being trapped upstream of the dam and take years to decades to remove, which may limit the utilization of fresh groundwater in coastal areas. In this study, field-scale numerical simulations were used to investigate the mechanisms of residual saltwater removal from a typical stratified aquifer, where an intermediate low-permeability layer (LPL) exists between two high-permeability layers, under the effect of seasonal sea level fluctuations. The study quantifies and compares the time of residual saltwater removal (Tre) for constant sea level (CSL) and seasonally varying sea level (FSL) scenarios. The modelling results indicate that, in most cases, seasonal fluctuations in sea level facilitate the dilution of residual saltwater and thus accelerate residual saltwater removal compared to a static sea level scenario. However, accounting for seasonal sea level variations may increase the required critical dam height (the minimum dam height required to achieve complete residual saltwater removal). Sensitivity analyses show that Tre decreases with increasing height of subsurface dam (Hd) under CSL or weaker sea level fluctuation scenarios; however, when the magnitude of sea level fluctuation is large, Tre changes non-monotonically with Hd. Tre decreases with increasing distance between subsurface dam and ocean for both CSL and FSL scenarios. We also found that stratification model had a significant effect on Tre. The increase in LPL thickness for both CSL and FSL scenarios leads to a decrease in Tre and critical dam height. Tre generally shows a non-monotonically decreasing trend as LPL elevation increases. These quantitative analyses provide valuable insights into the design of subsurface dams in complex situations.

Near Ultraviolet-Excitable Cyan-Emissive Hybrid Copper(I) Halides Nonlinear Optical Crystals with Near-Unity Photoluminescence Quantum Yield and High-Efficiency X-ray Scintillation.

Designing and synthesizing multifunctional hybrid copper halides with near ultraviolet (NUV) light-excited high-energy emission (< 500 nm) remains challenging. Here, a pair of broadband-excited high-energy emitting isomers, namely, α-/ß-(MePh3P)2CuI3 (MePh3P = methyltriphenylphosphonium), were synthesized. α-(MePh3P)2CuI3 with blue emission peaking at 475 nm is firstly discovered wherein its structure contains regular [CuI3]2‒ triangles and crystallizes in centrosymmetric space group P21/c. While ß-(MePh3P)2CuI3 featuring distorted [CuI3]2‒ planar triangles shows inversion symmetry breaking and crystallizes in the noncentrosymmetric space group P21, which exhibits cyan emission peaking at 495 nm with prominent near-unity photoluminescence quantum yield and the excitation band ranging from 200 to 450 nm. Intriguingly, ß-(MePh3P)2CuI3 exhibits phase-matchable second-harmonic generation response of 0.54 × KDP and a suitable birefringence of 0.06@1064 nm. Furthermore, ß-(MePh3P)2CuI3 also can be excited by X-ray radioluminescence with a high scintillation light yield of 16193 photon/MeV and an ultra-low detection limit of 47.97 nGy/s, which is only 0.87% of the standard medical diagnosis (5.5 µGy/s). This work not only promotes the development of solid-state lighting, laser frequency conversion and X-ray imaging, but also provides a reference for constructing multifunctional hybrid metal halides.

Deciphering the interplay of gut microbiota and metabolomics in retinal vein occlusion.

This study aims to explore the link between retinal vein occlusion (RVO), a blinding ocular condition, and alterations in gut microbiota composition, to offer insights into the pathogenesis of RVO. Fecal samples from 25 RVO patients and 11 non-RVO individuals were analyzed using 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC-MS). Significant differences in the abundance of gut microbial species were noted between RVO and non-RVO groups. At the phylum level, the RVO group showed an elevation in the ratio of Firmicutes to Bacteroidetes. At the genus level, the RVO group showed higher abundance in Escherichia_Shigella (P < 0.05) and less abundance in Parabacteroides (P < 0.01) than the non-RVO group. Functional predictions indicated reduced folate synthesis, biotin metabolism, and oxidative phosphorylation, with an increase in butyric acid metabolism in the RVO group. LC-MS analysis showed significant differences in purine metabolism, ABC transporters, and naphthalene degradation pathways, especially purine metabolism. Pearson correlation analysis revealed significant associations between bacterial genera and fecal metabolites. Enrichment analysis highlighted connections between specific metabolites and bacterial genera. The findings showed that the dysregulation of gut microbiota was observed in RVO patients, suggesting the gut microbiota as a potential therapeutic target. Modulating the gut microbiota could be a novel strategy for managing RVO and improving patient outcomes. Furthermore, the study findings suggest the involvement of gut microbial dysbiosis in RVO development, underscoring the significance of understanding its pathogenesis for effective treatment development. IMPORTANCE: Retinal vein occlusion (RVO) is a blinding ocular condition, and understanding its pathogenesis is crucial for developing effective treatments. This study demonstrates significant differences in gut microbiota composition between RVO patients and non-RVO individuals, implicating the involvement of gut microbial dysbiosis in RVO development. Functional predictions and metabolic profiling provide insights into the underlying mechanisms, highlighting potential pathways for therapeutic intervention. These findings suggest that modulating the gut microbiota might be a promising strategy for managing RVO and improving patient outcomes.

Advancements in Ultrasound Techniques for Evaluating Intracranial Pressure through Optic Nerve Sheath Diameter Measurement.

Elevated intracranial pressure (ICP) in patients with cerebral lesions has garnered considerable attention in research. It often manifests as a common symptom in conditions such as intracranial tumors, intracerebral hemorrhage (ICH), and cerebral edema. This paper provides an overview of ICP concepts, discusses the advantages and disadvantages of traditional monitoring methods, explores the physiological and anatomical aspects of the optic nerve sheath, examines the utility of ultrasound measurement of optic nerve sheath diameter (ONSD) in both nervous system and non-nervous system disorders, and outlines the cutoff values and normal ranges for assessing elevated ICP using ultrasound measurement of ONSD. The review underscores ultrasound measurement of ONSD as a promising non-invasive, safe, straightforward, and repeatable examination technique for various diseases. Nevertheless, the lack of standardized cutoff values for elevated ICP remains a challenge. Summarizing studies on optic nerve sheaths is crucial for enhancing the efficacy of ultrasound measurement of ONSD in assessing ICP.

SIAH2 is specifically expressed during cervical carcinogenesis, and closely relates to the abnormal proliferation of cervical epithelial cells.

Background: Cervical cancer is one of the most common malignancies in women worldwide. As a RING type ubiquitin ligase, SIAH2 has been reported to promote the progression of a variety of tumors by interacting with and targeting multiple chaperones and substrates. The aim of this study was to further identify the role and the related molecular mechanisms involved of SIAH2 in cervical carcinogenesis. Methods and results: Cellular assays in vitro showed that knockdown of SIAH2 inhibited the proliferation, migration and invasion of human cervical cancer cells C33A and SiHa, induced apoptosis, and increased the sensitivity to cisplatin treatment. Knockdown of SIAH2 also inhibited the epithelial-mesenchymal transition and activation of the Akt/mTOR signaling pathway in cervical cancer cells, which were detected by Western blot. Mechanistically, SIAH2, as a ubiquitin ligase, induced the ubiquitination degradation of GSK3ß degradation by using coIP. The results of complementation experiments further demonstrated that GSK3ß overexpression rescued the increase of cell proliferation and invasion caused by SIAH2 overexpression. Specific expression of SIAH2 appeared in precancerous and cervical cancer tissues compared to inflammatory cervical lesions tissues using immunohistochemical staining. The more SIAH2 was expressed as the degree of cancer progressed. SIAH2 was significantly highly expressed in cervical cancer tissues (44/55, 80 %) compared with precancerous tissues (18/69, 26.1 %). Moreover, the expression level of SIAH2 in cervical cancer tissues was significantly correlated with the degree of cancer differentiation, and cervical cancer tissues with higher SIAH2 expression levels were less differentiated. Conclusion: Targeting SIAH2 may be beneficial to the treatment of cervical cancer.

The effect of systematic couple group therapy on families with depressed juveniles: a pilot trial.

Background: Depression is a primary cause of illness and disability among teenagers, and the incidence of depression and the number of untreated young people have increased in recent years. Effective intervention for those youths could decrease the disease burden and suicide or self-harm risk during preadolescence and adolescence. Objective: To verify the short efficacy of the systemic couple group therapy (SCGT) on youths' depression changes and families with depressed adolescents. Methods: The study was a self-control trial; only within-group changes were evaluated. Participants were couples with a depressed child who was resistant to psychotherapy; they were recruited non-randomly through convenient sampling. The paired-sample t-test and Wilcoxon signed-rank test were used to compare differences before and after interventions. The effect sizes were also estimated using Cohen's d. Spearman's correlation analysis was used to examine associations between changes. Results: A downward trend was seen in depressive symptoms after treatment, and Cohen's d was 0.33 (p = 0.258). The adolescents perceived fewer interparental conflicts, and the effect sizes were medium for perceived conflict frequency (0.66, p = 0.043), conflict intensity (0.73, p = 0.028), conflict solutions (0.75, p = 0.025), coping efficacy (0.68, p = 0.038), and perceived threat (0.57, p = 0.072). For parents, global communication quality, constructive communication patterns, and subjective marital satisfaction significantly improved after interventions, with large effect sizes (1.11, 0.85, and 1.03, respectively; all p < 0.001). Other destructive communication patterns such as demand/withdraw (p = 0.003) and mutual avoidance (p = 0.018) and communication strategies like verbal aggression (p = 0.012), stonewalling (p = 0.002), avoidance-capitulation (p = 0.036), and child involvement (p = 0.001) also reduced, with medium effect sizes (0.69, 0.52, 0.55, 0.71, 0.46, and 0.79, respectively). Meanwhile, the associations between depression changes and changes in interparental conflicts (p < 0.001) and marital satisfaction (p = 0.001) were significant. Conclusions and clinical relevance: The SCGT offers the possibility for the treatment of families with depressed children who are unwilling to seek treatment. Helping parents improve communication and marital quality may have benefits on children's depressive symptoms.

Lipiodol combined with drug-eluting beads versus drug-eluting beads alone for transarterial chemoembolization of hepatocellular carcinoma: a multicenter study.

RATIONALE AND OBJECTIVES: This study aimed to propose a novel approach of lipiodol combined with drug-eluting beads transarterial chemoembolization (Lipiodol-DEB TACE) and to compare the safety and efficacy with DEB-TACE alone for patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From the database of four centers, the records of patients with HCC who received DEB-TACE or Lipiodol-DEB TACE as initial treatment were retrospectively evaluated. The tumor response was measured based on the Modified Response Evaluation Criteria in Solid Tumors. Overall survival (OS), progression-free survival (PFS) and adverse events (AEs) were compared between two groups. RESULTS: A total of 244 patients were included with 160 patients receiving DEB-TACE and 84 patients receiving Lipiodol-DEB TACE. Lipiodol-DEB TACE group had higher objective response rate (86.9 % vs. 76.3 %), higher disease control rate (97.6 % vs. 88.8 %), longer median OS (42.6 vs. 25.8 months) and longer median PFS (34.0 vs. 17.0 months) than DEB-TACE group (P < 0.05). There was no significant difference observed in the incidence of AEs between two groups. Cox analysis identified total bilirubin level, maximum tumor diameter, TACE method and portal vein invasion as independent prognostic factors. CONCLUSION: Lipiodol-DEB TACE was a safe option and associated with improved tumor response and survival outcome compared to DEB-TACE alone for selected patients with HCC.

Highly Selective Protic-Solvent-Mediated Organic-Inorganic Hybrid Cuprous Bromides Achieving Structural Transformation.

The potential application of stimuli-responsive hybrid copper halides in information storage and switch devices has generated significant interest. However, their transformation mechanism needs to be further studied deeply. Herein, two zero-dimensional (0D) organic-inorganic hybrids, namely, (TBA)CuBr2 (1) with linear [CuBr2]- units and (TBA)2Cu4Br6 (2) with [Cu4Br6]2- clusters (TBA+ = (C4H9)4N+), are synthesized using simple solvent evaporation approaches. Interestingly, upon exposure to distinct protic solvents, such as methanol, ethanol, ethylene glycol, or hot water, 1 undergoes a transformation into 2 with varying degrees of transition, accompanied by a change in luminescence color from cyan to orange (or mixed color) under high-energy emission (e.g., 254 nm) excitation. Hot water can trigger 1 to completely transform into 2 because of its large contact angle difference in the solvents. Furthermore, 2 can be converted back to 1 through a simple solid-state mechanochemical reaction. Additionally, the structure of 2 remains unchanged even after immersion in 80 °C H2O for 168 h due to the dense organic framework. This study provides valuable insights for exploring reversible structural transformation materials in the 0D metal halide system.

Computer-assisted three-dimensional individualized extreme liver resection for hepatoblastoma in proximity to the major liver vasculature.

BACKGROUND: The management of hepatoblastoma (HB) becomes challenging when the tumor remains in close proximity to the major liver vasculature (PMV) even after a full course of neoadjuvant chemotherapy (NAC). In such cases, extreme liver resection can be considered a potential option. AIM: To explore whether computer-assisted three-dimensional individualized extreme liver resection is safe and feasible for children with HB who still have PMV after a full course of NAC. METHODS: We retrospectively collected data from children with HB who underwent surgical resection at our center from June 2013 to June 2023. We then analyzed the detailed clinical and three-dimensional characteristics of children with HB who still had PMV after a full course of NAC. RESULTS: Sixty-seven children diagnosed with HB underwent surgical resection. The age at diagnosis was 21.4 ± 18.8 months, and 40 boys and 27 girls were included. Fifty-nine (88.1%) patients had a single tumor, 39 (58.2%) of which was located in the right lobe of the liver. A total of 47 patients (70.1%) had PRE-TEXT III or IV. Thirty-nine patients (58.2%) underwent delayed resection. After a full course of NAC, 16 patients still had close PMV (within 1 cm in two patients, touching in 11 patients, compressing in four patients, and showing tumor thrombus in three patients). There were 6 patients of tumors in the middle lobe of the liver, and four of those patients exhibited liver anatomy variations. These 16 children underwent extreme liver resection after comprehensive preoperative evaluation. Intraoperative procedures were performed according to the preoperative plan, and the operations were successfully performed. Currently, the 3-year event-free survival of 67 children with HB is 88%. Among the 16 children who underwent extreme liver resection, three experienced recurrence, and one died due to multiple metastases. CONCLUSION: Extreme liver resection for HB that is still in close PMV after a full course of NAC is both safe and feasible. This approach not only reduces the necessity for liver transplantation but also results in a favorable prognosis. Individualized three-dimensional surgical planning is beneficial for accurate and complete resection of HB, particularly for assessing vascular involvement, remnant liver volume and anatomical variations.

Rich oxygen vacancy and amorphous/crystalline ruthenium-doped CoCu -layered double hydroxide electrocatalysts for enhanced oxygen evolution reactions.

Reinforcing the development of efficient and robust electrocatalysts is pivotal in addressing the challenges associated with oxygen evolution reactions (OER) in water splitting technology. Here, an amorphous/crystalline low-ruthenium-doped bimetallic layered double hydroxide (LDH) electrocatalyst (a/c-CoCu + Rux-LDH/NF) with massive oxygen vacancy on nickel foam was fabricated via ion-exchange and chemical etching, facilitating efficient OER. Among the various catalyst materials tested, the a/c-CoCu + Ru10-LDH/NF exhibits remarkable performance in the OER when employed in an alkaline electrolyte containing 1 M KOH. Achieving a minimal overpotential at 10 mA cm-2 of 214 mV, exhibiting a low Tafel slope value of 64.3 mV dec-1 and exceptional durability lasting for over 100 h. Theoretical calculations demonstrate that the electron structure and d-band center of CoCu-LDH can be effectively regulated through the utilization of a strategy possessing abundant oxygen vacancies and a Ru-doped crystalline/amorphous heterostructure. It will lead to optimized adsorption free energy of reactants and reduced energy barriers for OER. The construction strategy proposed in this paper for catalysts with amorphous/crystalline heterointerfaces offer a novel opportunity to achieve highly efficient OER.

Therapeutic effect and psychological impact of aspirin plus edaravone on patients with cerebral infarction.

BACKGROUND: Cerebral infarction (CI) is characterized by a high prevalence, disability, and mortality. Timely or improper treatment greatly affects patient prognosis. AIM: To explore the drug efficacy of aspirin plus edaravone and to explore their effect on quality of life (QOL), anxiety and depression in CI patients. METHODS: We retrospectively analyzed the records of 124 CI patients treated between June 2019 and February 2021 who were assigned to an observation group (OG) (combination therapy of aspirin and edaravone, 65 patients) or a control group (CG) (aspirin monotherapy, 59 patients). The therapeutic effects, pre- and posttreatment National Institutes of Health Stroke Scale (NIHSS) scores, activities of daily living, degree of cognitive impairment, protein levels of glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE) and S-100B, occurrence of adverse reactions, and serum high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6 and tumor necrosis factor (TNF)-α were evaluated, detected and compared between the two groups. Finally, posttreatment QOL, anxiety, and depression were assessed by the Medical Outcomes Study 36- Item Short Form Health Survey Scale, Self-rating Depression Scale (SDS), and Self-rating Anxiety Scale (SAS), respectively. RESULTS: Compared with the CG, the OG had markedly better therapeutic effects, greater improvements in activities of daily living, and better alleviation in cognitive dysfunction after treatment, as well as lower posttreatment NIHSS scores and serum NSE, GFAP, S-100B, hs-CRP, IL-6, and TNF-α levels; the OG was similar to the CG in terms of adverse reactions but was better than the CG in terms of posttreatment QOL; and the OG also had lower SDS and SAS scores than the CG after treatment. CONCLUSION: Aspirin plus edaravone had a good curative effect on CI. It can reverse cranial nerve damage in patients, improve neurological function and prognosis, and alleviate inflammation, anxiety, and depression; thus, it is considered safe and worthy of clinical application.

Gender and race disparities in the prevalence of chronic kidney disease among individuals with hypertension in the United States, 2001-2016.

Background: Chronic kidney disease (CKD) is a common complication among individuals with hypertension. We aimed to identify the prevalence of CKD and the sex and race disparities within the hypertensive population in the United States from 2001-2016. Methods: A total of 16,148 participants with hypertension were included, representing 561,909,480 individuals from the U.S. population between 2001 and 2016, as documented in the National Health and Nutrition Examination Survey. The prevalence of albuminuria and CKD stage were assessed using survey-weighted general linear regression analysis. Heterogeneity in the CKD stage among the hypertensive population, stratified by sex and race, was identified through survey-weighted logistic regression analysis. Results: Overall, the prevalence of albuminuria remained stable (p for trend = 0.3196), and changes in the CKD stage were minimal (p for trend > 0.05) from 2001-2016. In the analysis of CKD stage heterogeneity by sex and race, the prevalence of CKD was higher among women than men and higher among individuals of other races combined than non-Hispanic Whites, but the differences were not statistically significant. Conclusion: The overall CKD stage within the hypertensive population plateaued between 2001 and 2016. Our findings highlight the importance of continuous monitoring and potential refinement of renoprotection strategies in individuals with hypertension to mitigate the persistent burden of CKD and address health disparities among different demographic groups.

Analysis of the characteristics of intestinal microbiota after oral tolerance in infants with food protein-induced proctocolitis.

Objective: To understand the characteristics of the intestinal microbiota after oral tolerance in infants with food protein-induced proctocolitis (FPIAP) treated with amino acid formula and their differences from healthy children, aiming to provide a scientific basis for guiding the application of probiotics during treatment. Methods: FPIAP infants were prospectively enrolled, fecal specimens were obtained, and DNA was extracted for PCR amplification of the bacterial 16S rRNA gene V4 region. Library construction and sequencing were performed, and bioinformatic analysis was performed after obtaining valid data. Results: There were 36 patients in the FPIAP group: 20 males and 16 females, age 21.944 ± 13.277 months. Diarrhea with blood in the stool were the main symptom, with an average course of 14.83 ± 9.33 days. Thirty infants (83.33%) had mucus stool, 11.11% (4/36) of them experiencing vomiting, and 55.56% (20/36) of the infants displaying poor intake and weight gain, 28 (77.78%) patients with moderate eczema, 2 (5.6%) patients with chronic respiratory symptoms. The treatment time with amino acid formula was 5.51 ± 2.88 months. A control group comprising of 25 healthy infants who were full-term, natural delivery, bottle fed, and matched in terms of age (24.840 ± 12.680 months) and gender (15 males and 10 females) was selected. Anaerobic bacteria were less abundant in FPIAP infants than healthy infants (P = 4.811 × 10-5), but potentially pathogenic bacteria were more abundant (P = 0.000). The abundance of Actinobacteria was low in FPIAP infants, the abundance of Proteobacteria was high, and the abundance of Firmicutes was reduced. Bifidobacterium could be used as a bacterial genus to differentiate healthy and FPIAP infants. Both α-and ß-diversity indicators of intestinal microbiota were lower in FPIAP infants. In FPIAP infants, glucose and energy metabolism and amino acid anabolism were decreased, and inflammation-related lipopolysaccharide synthesis pathways were increased. Conclusion: Compared with healthy infants, FPIAP infants with oral tolerance after amino acid formula treatment had differences in the structure and diversity of intestinal microbiota, among which Bifidobacterium was significantly reduced. Trial Registration: This trial was registered on https://register.clinicaltrials.gov/.

Visualizing Electrochemical CO2 Conversion via the Emerging Scanning Electrochemical Microscope: Fundamentals, Applications and Perspectives.

With the rapid development and maturity of electrochemical CO2 conversion involving cathodic CO2 reduction reaction (CO2RR) and anodic oxygen evolution reaction (OER), conventional ex situ characterizations gradually fall behind in detecting real-time products distribution, tracking intermediates, and monitoring structural evolution, etc. Nevertheless, advanced in situ techniques, with intriguing merits like good reproducibility, facile operability, high sensitivity, and short response time, can realize in situ detection and recording of dynamic data, and observe materials structural evolution in real time. As an emerging visual technique, scanning electrochemical microscope (SECM) presents local electrochemical signals on various materials surface through capturing micro-current caused by reactants oxidation and reduction. Importantly, SECM holds particular potentials in visualizing reactive intermediates at active sites and obtaining instantaneous morphology evolution images to reveal the intrinsic reactivity of active sites. Therefore, this review focuses on SECM fundamentals and its specific applications toward CO2RR and OER, mainly including electrochemical behavior observation on local regions of various materials, target products and onset potentials identification in real-time, reaction pathways clarification, reaction kinetics exploration under steady-state conditions, electroactive materials screening and multi-techniques coupling for a joint utilization. This review undoubtedly provides a leading guidance to extend various SECM applications to other energy-related fields.

Comparison of drug-eluting bead with conventional transcatheter arterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombus: A randomized clinical trial.

BACKGROUND: Drug-eluting bead transarterial chemoembolization (DEB-TACE) has shown efficacy for treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). However, whether DEB-TACE is superior to conventional TACE (cTACE) remains unclear. OBJECTIVE: This randomized controlled trial aimed to compare the efficacy and safety of DEB-TACE versus cTACE in treating HCC with PVTT. METHODS: The study was conducted in a tertiary care center in Southeast China. HCC patients with PVTT were randomized at a 1:1 ratio to the DEB-TACE or cTACE groups. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS) and incidence of adverse events (AEs). An independent review committee assessed the radiologic response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). AEs were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Systemic therapies were not limited. RESULTS: Between September 2018, and July 2020, 163 patients were randomized to undergo DEB-TACE (n=82) or cTACE (n=81). Nine patients were excluded, and 154 patients were included in the final analysis; the median age was 55 years (range, 24-78 y), and 140 (90.9%) were male. The median PFS in the DEB-TACE group was 6.0 months (95% CI, 5.0 to 10.0) versus 4.0 months (95% CI, 3.0 to 5.0) in the cTACE group (hazard ratio, 0.63; 95% CI, 0.42 to 0.95; P=0.027). The DEB-TACE group showed a higher response rate (51[66.2%] vs. 36 [46.8%]; P=0.0015) and a longer median OS (12.0 months [95% CI, 9.0 to 16.0] vs. 8.0 months [95% CI, 7.0 to 11.0], P=0.039) than the cTACE group. Multivariate analysis showed that the treatment group, ALBI score, distant metastasis and additional TKIs were the four independent prognostic factors correlated with PFS. In addition, the treatment group, PVTT group and combined with surgery were independently correlated with OS. AEs were similar in the two groups, and postembolization syndrome was the most frequent AEs. CONCLUSION: DEB-TACE is superior to cTACE in treating HCC patients with PVTT due to the improved PFS and OS with an acceptable safety profile and may become a promising treatment strategy for HCC patients with PVTT. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800018035.

Ecoclimate drivers shape virome diversity in a globally invasive tick species.

Spillovers of viruses from animals to humans occur more frequently under warmer conditions, particularly arboviruses. The invasive tick species Haemaphysalis longicornis, the Asian longhorned tick, poses a significant public health threat due to its global expansion and its potential to carry a wide range of pathogens. We analyzed meta-transcriptomic data from 3595 adult H. longicornis ticks collected between 2016 and 2019 in 22 provinces across China encompassing diverse ecological conditions. Generalized additive modeling revealed that climate factors exerted a stronger influence on the virome of H. longicornis than other ecological factors, such as ecotypes, distance to coastline, animal host, tick gender, and antiviral immunity. To understand how climate changes drive the tick virome, we performed a mechanistic investigation using causality inference with emphasis on the significance of this process for public health. Our findings demonstrated that higher temperatures and lower relative humidity/precipitation contribute to variations in animal host diversity, leading to increased diversity of the tick virome, particularly the evenness of vertebrate-associated viruses. These findings may explain the evolution of tick-borne viruses into generalists across multiple hosts, thereby increasing the probability of spillover events involving tick-borne pathogens. Deep learning projections have indicated that the diversity of the H. longicornis virome is expected to increase in 81.9% of regions under the SSP8.5 scenario from 2019 to 2030. Extension of surveillance should be implemented to avert the spread of tick-borne diseases.

Identification of metabolism-related key genes as potential biomarkers for pathogenesis of immune thrombocytopenia.

Immune thrombocytopenia (ITP), an acquired autoimmune disease, is characterized by immune-mediated platelet destruction. A biomarker is a biological entity that contributes to disease pathogenesis and reflects disease activity. Metabolic alterations are reported to be associated with the occurrence of various diseases. As metabolic biomarkers for ITP have not been identified. This study aimed to identify metabolism-related differentially expressed genes as potential biomarkers for pathogenesis of ITP using bioinformatic analyses.The microarray expression data of the peripheral blood mononuclear cells were downloaded from the Gene Expression Omnibus database (GSE112278 download link: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE112278 ). Key module genes were intersected with metabolism-related genes to obtain the metabolism-related key candidate genes. The hub genes were screened based on the degree function in the coytoscape sofware. The key ITP-related genes were subjected to functional enrichment analysis. Immune infiltration analysis was performed using a single-sample gene set enrichment analysis algorithm to evaluate the differential infiltration levels of immune cell types between ITP patient and control. Molecular subtypes were identified based on the expression of hub genes. The expression of hub genes in the ITP patients was validated using quantitative real-time polymerase chain reaction analysis. This study identified five hub genes (ADH4, CYP7A1, CYP1A2, CYP8B1, and NR1H4), which were be associated with the pathogenesis of ITP, and two molecular subtypes of ITP. Among these hub genes, CYP7A1 and CYP8B1 involved in cholesterol metabolism,were further verified in clinical samples.

CD133 expression is associated with less DNA repair, better response to chemotherapy and survival in ER-positive/HER2-negative breast cancer.

Purpose: CD133, a cancer stem cells (CSC) marker, has been reported to be associated with treatment resistance and worse survival in triple-negative breast cancer (BC). However, the clinical relevance of CD133 expression in ER-positive/HER2-negative (ER+/HER2-) BC, the most abundant subtype, remains unknown. Methods: The BC cohorts from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC, n = 1904) and The Cancer Genome Atlas (TCGA, n = 1065) were used to obtain biological variables and gene expression data. Results: Epithelial cells were the exclusive source of CD133 gene expression in a bulk BC. CD133-high ER+/HER2- BC was associated with CD24, NOTCH1, DLL1, and ALDH1A1 gene expressions, as well as with WNT/ß-Catenin, Hedgehog, and Notchsignaling pathways, all characteristic for CSC. Consistent with a CSC phenotype, CD133-low BC was enriched with gene sets related to cell proliferation, such as G2M Checkpoint, MYC Targets V1, E2F Targets, and Ki67 gene expression. CD133-low BC was also linked with enrichment of genes related to DNA repair, such as BRCA1, E2F1, E2F4, CDK1/2. On the other hand, CD133-high tumors had proinflammatory microenvironment, higher activity of immune cells, and higher expression of genes related to inflammation and immune response. Finally, CD133-high tumors had better pathological complete response after neoadjuvant chemotherapy in GSE25066 cohort and better disease-free survival and overall survival in both TCGA and METABRIC cohorts. Conclusion: CD133-high ER+/HER2- BC was associated with CSC phenotype such as less cell proliferation and DNA repair, but also with enhanced inflammation, better response to neoadjuvant chemotherapy and better prognosis.

Perovskite Oxides Toward Oxygen Evolution Reaction: Intellectual Design Strategies, Properties and Perspectives.

Developing electrochemical energy storage and conversion devices (e.g., water splitting, regenerative fuel cells and rechargeable metal-air batteries) driven by intermittent renewable energy sources holds a great potential to facilitate global energy transition and alleviate the associated environmental issues. However, the involved kinetically sluggish oxygen evolution reaction (OER) severely limits the entire reaction efficiency, thus designing high-performance materials toward efficient OER is of prime significance to remove this obstacle. Among various materials, cost-effective perovskite oxides have drawn particular attention due to their desirable catalytic activity, excellent stability and large reserves. To date, substantial efforts have been dedicated with varying degrees of success to promoting OER on perovskite oxides, which have generated multiple reviews from various perspectives, e.g., electronic structure modulation and heteroatom doping and various applications. Nonetheless, the reviews that comprehensively and systematically focus on the latest intellectual design strategies of perovskite oxides toward efficient OER are quite limited. To bridge the gap, this review thus emphatically concentrates on this very topic with broader coverages, more comparative discussions and deeper insights into the synthetic modulation, doping, surface engineering, structure mutation and hybrids. More specifically, this review elucidates, in details, the underlying causality between the being-tuned physiochemical properties [e.g., electronic structure, metal-oxygen (M-O) bonding configuration, adsorption capacity of oxygenated species and electrical conductivity] of the intellectually designed perovskite oxides and the resulting OER performances, coupled with perspectives and potential challenges on future research. It is our sincere hope for this review to provide the scientific community with more insights for developing advanced perovskite oxides with high OER catalytic efficiency and further stimulate more exciting applications.