Cognitive impairment and amygdala subregion volumes in elderly with cerebral small vessel disease: A large prospective cohort study.

Although the amygdala is associated with cognitive impairment resulting from cerebral small vessel disease, the relationship between alterations in amygdala structure and cerebral small vessel disease (CSVD) remains controversial. Given that the amygdala comprises several subregions, detecting subtle regional changes through total amygdala volume measurement is challenging. This study aimed to identify the patterns of amygdala subregion atrophy in cerebral small vessel disease patients and their relationship with cognitive impairment. A total of 114 participants diagnosed with cerebral small vessel disease and 129 healthy participants, aged 40 to 70, underwent 3 T magnetic resonance imaging scans. The amygdala subregions were automatically segmented using FreeSurfer. In the Propensity Score Matching (PSM)-matched cohort, Lasso regression was employed to identify subregions associated with cerebral small vessel disease, and restricted cubic splines (RCS) were used to explore their nonlinear relationship with cognitive abilities. Subsequently, multivariate linear regression models were used to investigate the impact of amygdala subregion volumes on various cognitive abilities. Compared to healthy controls (HC), the volume of the left cortical nucleus was significantly reduced in cerebral small vessel disease patients. The volume of the left cortical nucleus was significantly negatively correlated with cerebral small vessel disease progression, and atrophy in this region was also identified as an independent risk factor for decreased cognitive control and processing ability. Our findings suggest that patients with cerebral small vessel disease exhibit atrophy in specific amygdala subregions compared to healthy controls, which correlates with poorer cognitive control and processing abilities. These insights may advance our understanding of the pathogenesis of cerebral small vessel disease.

Neuromolecular and behavioral effects of cannabidiol on depressive-associated behaviors and neuropathic pain conditions in mice.

BACKGROUND AND AIMS: Neuropathic pain (NP) has a high incidence in the general population, is closely related to anxiety disorders, and has a negative impact on the quality of life. Cannabidiol (CBD), as a natural product, has been extensively studied for its potential therapeutic effects on symptoms such as pain and depression (DP). However, the mechanism of CBD in improving NP with depression is not fully understood. METHODS: First, we used bioinformatics tools to deeply mine the intersection genes associated with NP, DP, and CBD. Secondly, the core targets were screened by Protein-protein interaction network, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, molecular docking and molecular dynamics simulation. Next, the effects of CBD intervention on pain and depressive behaviors in the spinal nerve ligation (SNL) mouse model were evaluated using behavioral tests, and dose-response curves were plotted. After the optimal intervention dose was determined, the core targets were verified by Western blot (WB) and Quantitative Polymerase Chain Reaction (qPCR). Finally, we investigated the potential mechanism of CBD by Nissl staining, Immunofluorescence (IF) and Transmission Electron Microscopy (TEM). RESULTS: A total of five core genes of CBD most associated with NP and DP were screened by bioinformatics analysis, including PTGS2, GPR55, SOD1, CYP1A2 and NQO1. Behavioral test results showed that CBD by intraperitoneal administration 5 mg/kg can significantly improve the pain behavior and depressive state of SNL mice. WB, qPCR, IF, and TEM experiments further confirmed the regulatory effects of CBD on key molecules. CONCLUSION: In this study, we found five targets of CBD in the treatment of NP with DP. These findings provide further theoretical and experimental basis for CBD as a potential therapeutic agent.

DNA Mechanics: From Single Stranded to Self-Assembled.

DNA encodes genetic information and forms various structural conformations with distinct physical, chemical, and biological properties. Over the past 30 years, advancements in force manipulation technology have enabled the precise manipulation of DNA at nanometer and piconewton resolutions. This mini-review discusses these force manipulation techniques for exploring the mechanical properties of DNA at the single-molecule level. We summarize the distinct mechanical features of different DNA forms while considering the impact of the force geometry. We highlight the role of DNA mechanics in origami structures that serve as self-assembled building blocks or mechanically responsive/active nanomachines. Accordingly, we emphasize how DNA mechanics are integral to the functionality of origami structures for achieving mechanical capabilities. Finally, we provide an outlook on the intrinsic mechanical properties of DNA, from single stranded to self-assembled higher-dimensional structures. This understanding is expected to inspire new design strategies in DNA mechanics, paving the way for innovative applications and technologies.

Advancing cerebral small vessel disease diagnosis: Integrating quantitative susceptibility mapping with MRI-based radiomics.

Cerebral small vessel disease (CSVD) is a neurodegenerative disease with hidden symptoms and difficult to diagnose. The diagnosis mainly depends on clinical symptoms and neuroimaging. Therefore, we explored the potential of combining clinical detection with MRI-based radiomics features for the diagnosis of CSVD in a large cohort. A total of 118 CSVD patients and 127 healthy controls underwent quantitative susceptibility mapping and 3D-T1 scans, and all completed multiple cognitive tests. Lasso regression was used to select features, and the radiomics model was constructed based on the regression coefficients of these features. Clinical cognitive and motor tests were added to the model to construct a hybrid model. All models were cross-validated to analyze the generalization ability of the models. The AUCs of the radiomics and hybrid models in the internal test set were 0.80 and 0.87, respectively. In the validation set, the AUCs were 0.77 and 0.79, respectively. The hybrid model demonstrated higher decision efficiency. The Trail Making Test, which enhances the diagnostic performance of the model, is associated with multiple brain regions, particularly the right cortical nuclei and the right fimbria. The hybrid model based on radiomics features and cognitive tests can achieve quantitative diagnosis of CSVD and improve the diagnostic efficiency. Furthermore, the reduced processing capacity due to atrophy of the right cortical nucleus and right fimbria suggests the importance of these regions in improving the diagnostic accuracy of the model.

Quantitative evaluation of science and technology financial policies based on the PMC-AE index model: A case study of China's science and technology financial policies since the 13th five-year plan.

The formulation of science and technology financial policies directly influences the direction of national economic development. Quantitative evaluation of these policies is an important method to reflect the consistency and strengths and weaknesses of policy interrelations. This paper analyzes 16 science and technology financial policy documents issued by the Chinese central government from 2016 to 2022, using text analysis and content analysis to extract keyword frequencies, and constructs 9 primary variables and 34 secondary variables. For the first time, a PMC-AE index model for science and technology financial policies is established, and a quantitative evaluation is conducted on 5 significant policy documents out of the 16. The results show that, from an overall analysis, Policy 1 and Policy 4 are at a good level, while the other three policies are at an excellent level. From the analysis of individual policy PMC-AE indexes, the rankings in descending order are: P2 > P5 > P3 > P4 > P1. Overall, the policies effectively meet the needs of China's science and technology financial development, with P2, P3, and P5 being at an excellent level, P4 at a good level, and P1 at an acceptable level, mainly reflecting the need for improvement in aspects such as policy synchronization with the current stage, targeted entities, guiding fields, and policy content. It is recommended that Chinese government departments should focus on five aspects in policy formulation: building a talent system for science and technology finance, improving the quality of financial services, coordinating central and local financial policies, protecting intellectual property rights in science and technology finance, and strengthening financial supervision. This will be conducive to the effective implementation of science and technology financial policies.

Histone acetylation regulated by histone deacetylases during spermatogenesis.

BACKGROUND: Physical, chemical, and biological factors in the environment constantly influence in vivo and in vitro biological processes, including diverse histone modifications involved in cancer and metabolism. However, the intricate mechanisms of acetylation regulation remain poorly elucidated. In mammalian spermatogenesis, acetylation plays a crucial role in repairing double-strand DNA breaks, regulating gene transcription, and modulating various signaling pathways. RESULTS: This review summarizes the histone acetylation sites in the mouse testis and provides a comprehensive overview of how histone acetylation is involved in different stages of spermatogenesis under the regulation by histone deacetylases. The regulatory functions of various class histone deacetylases during spermatogenesis and the crossroad between histone acetylation and other histone modifications are highlighted. It is imperative to understand the mechanisms of histone acetylation regulated by histone deacetylases in spermatogenesis, which facilitates to prevent and treat infertility-related diseases.

Amygdala and cognitive impairment in cerebral small vessel disease: structural, functional, and metabolic changes.

Cerebral small vessel disease (CSVD) is a prevalent vascular disorder that has been consistently associated with vascular cognitive impairment (VCI). The diagnosis of CSVD continues to rely on magnetic resonance imaging (MRI). Epidemiological data indicate that the characteristic MRI features of CSVD, including white matter hyperintensity (WMH) and lacunar infarction, are very common among individuals over 40 years of age in community studies. This prevalence poses a significant burden on many low- and middle-income families. The amygdala plays a crucial role in integrating sensory and associative information to regulate emotional cognition. Although many previous studies have linked alterations in the amygdala to various diseases, such as depression, there has been little research on CSVD-associated alterations in the amygdala due to the complexity of CSVD. In this paper, we summarize the various imaging features of CSVD and discuss the correlation between amygdala changes and VCI. We also explore how new neuroimaging methods can assess amygdala changes early, laying a foundation for future comprehensive exploration of the pathogenesis of CSVD.

Rat Model of Neuropathic Pain Induced by Spinal Nerve Ligation: A New Approach via an Oblique Lateral Incision.

Purpose: The spinal nerve ligation (SNL) model is a typical peripheral neuropathic pain model. During its construction, the removal of paraspinal muscles and transverse processes typically occurs, resulting in additional trauma that may potentially affect the pathophysiologic process of neuropathic pain. This study aimed to investigate the feasibility of establishing a more reliable SNL model using an oblique lateral approach. Methods: 36 adult male Sprague-Dawley rats were randomly divided into three groups: the traditional SNL (T-SNL) group, the new SNL (N-SNL) group (where the left L5 spinal nerve was ligated with a titanium clip via an oblique lateral approach), and the sham-operated (Sham) group. The operation time, Intraoperative bleeding, the number of rats that died, gait behavior, mechanical and cold pain threshold were recorded and measured. Stereology technology was used to calculate the number of microglia in spinal dorsal horn, and the Enzyme-linked immunosorbent assay (ELISA) technology was used to detect the expression of TNF-α and IL-1ß in spinal cord as well as C-reactive protein (CRP) in serum in order to assess the effect of surgery on animal inflammation. Results: Compared with the T-SNL group, operative time and intraoperative bleeding were significantly decreased in the N-SNL group. Within 14 days postoperation, one rat in the N-SNL group was died, two rats in the T-SNL group were died. Compared with the Sham group, the N-SNL group showed obvious spontaneous pain behavior, decreased the pain thresholds, the number of microglia and the expression of TNF-α and IL-1ß were significantly increased, and there was no significant difference in these indexes compared with T-SNL group. There was no significant difference in serum CRP levels among the three groups. Conclusion: This study suggests that the oblique lateral approach SNL model is a reliable NP model with the advantages of good reproducibility, accessibility, and low trauma.

Efficacy and safety of TACE combined with tyrosine kinase inhibitors and camrelizumab for unresectable hepatocellular carcinoma: A systematic review and meta­analysis.

Transcatheter arterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) and camrelizumab (collectively: T-T-C) is a novel treatment strategy for unresectable hepatocellular carcinoma (HCC). The present systematic review and meta-analysis aimed to evaluate the efficacy and safety of T-T-C compared with TACE combined with TKIs only (T-T) in the treatment of patients with unresectable HCC. A systematic literature search was conducted on T-T and T-T-C using PubMed, Embase and the Cochrane Library. Data regarding the clinical outcome, including overall survival (OS), progression-free survival (PFS), tumor response and adverse events (AEs), were independently extracted and analyzed by two researchers using standardized protocols. In total, 7 cohort studies, including 1,798 patients (T-T-C, 838; T-T, 960), were included in the meta-analysis. The results of the present study demonstrated that the T-T-C group had significantly prolonged OS [hazard ratio (HR), 0.38; 95% confidence interval (CI), 0.29-0.50; I2=61.5%; P=0.016)] and PFS (HR, 0.37; 95% CI, 0.30-0.46; I2=44.5%; P=0.109), and showed significantly higher objective response rates [risk ratio (RR), 0.82; 95% CI, 0.69-0.96; I2=25.1%; P=0.237)] and slightly higher disease control rates without a significant difference (RR, 0.96; 95% CI, 0.89-1.03; I2=0.0%; P=0.969). In addition, grade 3/4 AEs were more common in the T-T group, including hypertension (RR, 1.15; 95% CI, 0.85-1.56), vomiting or nausea (RR, 0.88; 95% CI, 0.44-1.76) and pain (RR, 0.74; 95% CI, 0.45-1.21); however, these results were not statistically significant. In conclusion, compared with T-T combination therapy, T-T-C demonstrated a notable advantage in terms of OS, PFS, ORR and DCR in patients with unresectable HCC. For manageable AEs, although the results were not statistically significant, the incidence of AEs in the T-T group was higher than that in the T-T-C group in terms of event probability.

Lenvatinib in combination with transarterial chemoembolization vs. sorafenib in combination with transarterial chemoembolization for unresectable hepatocellular carcinoma: A network meta­analysis.

The use of tyrosine kinase inhibitors combined with transarterial chemoembolization (TACE) is considered the standard therapy for patients with unresectable hepatocellular carcinoma (uHCC). However, information regarding the efficacy of lenvatinib or sorafenib in combination with TACE for patients with uHCC is limited. The present study involved a systematic search for randomized controlled trials on the PubMed, Embase, Web of Science and the Cochrane Library online databases to compare the use of TACE combined with either lenvatinib or sorafenib, and monotherapy using either lenvatinib or sorafenib for patients with uHCC. The network meta-analysis of the present study included eight randomized controlled trials involving 2,929 patients. The random-effects model was used, and hazard ratios and risk ratios with 95% CIs were calculated. Lenvatinib in combination with TACE provided the maximal overall survival (97.92%), progression-free survival (87.8%), objective response (96.68%) and disease control (96.27%) rates. The results of the present study indicated that, in the treatment of patients with uHCC, lenvatinib in combination with TACE showed a significantly improved efficacy when compared with sorafenib and TACE. Therefore, in the future, combination therapy of lenvatinib with TACE could be potentially prioritized over sorafenib with TACE for the treatment of patients with uHCC.

Green processing via surface diffuse atmospheric plasma to enhance the dyeing performance on polylactic acid fabric.

Poor dyeing performance has been a major defect of polylactic acid (PLA) fibers, which is caused by the lack of active chemical groups in PLA, and hinders the widespread use of this biodegradable material. Most of the existing chemical modification methods are not environmentally friendly and produce effluents. Herein, we report a green, efficient and continuous method to process PLA fibers via surface diffuse atmospheric plasma for the improvement of its hydrophilicity and dyeing performance. PLA fibers were processed via atmospheric plasma for grafting oxygen-containing functional groups, such as carboxyl, to achieve hydrophilicity and, meanwhile, strengthen the binding interactions with various dye molecules via covalent bonds, ionic bonds, or hydrogen bonds. In addition, different mechanisms of improving the dyeing performance on plasma-modified PLA fibers with different kinds of dyes have been discussed. This approach of material modification involves no chemical additives and has high processing efficiency, showing the potential applicability of green treatment to products in various fields.

Salvage liver transplantation versus curative treatment for patients with recurrent hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND: Salvage liver transplantation (SLT) is an effective treatment option for recurrent hepatocellular carcinoma (rHCC) following primary curative treatment (CUR). However, its efficacy remains controversial compared to that of CURs, including repeat liver resection (RLR) and local ablation. This meta-analysis compared the efficacy and safety of these procedures. METHODS: A systematic literature search of the PubMed, Embase, Web of Science, and Cochrane Library databases for studies investigating SLT and CUR was performed. Outcome data, including overall and disease-free survival, tumor response, and operative and postoperative outcomes, were independently extracted and analyzed by two authors using a standardized protocol. RESULTS: Fifteen cohort studies comprising 508 and 2050 patients with rHCC, who underwent SLT or CUR, respectively, were included. SLT achieved significantly longer overall survival than both CUR (hazard ratio [HR]: 0.56, 95 % confidence interval [CI]: 0.45-0.68; I2 = 34.6 %, p = 0.105) and RLR (HR: 0.64, 95 % CI: 0.49-0.84; I2 = 0.0 %, p = 0.639). Similar significantly better survival benefits were observed compared with CUR (HR: 0.30, 95 % CI: 0.20-0.45; I2 = 51.1 %, p = 0.038) or RLR (HR: 0.31, 95 % CI: 0.18-0.56; I2 = 65.7 %, p = 0.005) regarding disease-free survival. However, SLT resulted in a longer operative duration and hospital stay, larger amount of blood loss, higher rate of transfusion and postoperative morbidity, and slightly higher postoperative mortality than CUR. CONCLUSION: SLT was associated with better long-term survival than CUR or RLR in patients with rHCC after primary curative treatment.

The diagnostic efficiency of artificial intelligence based 2 hours Holter monitoring in premature ventricular and supraventricular contractions detection.

BACKGROUND: Electrocardiography (ECG) and 24 hours Holter monitoring (24 h-Holter) provided valuable information for premature ventricular and supraventricular contractions (PVC and PSVC). Currently, artificial intelligence (AI) based 2 hours single-lead Holter (2 h-Holter) monitoring may provide an improved strategy for PSVC/PVC diagnosis. HYPOTHESIS: AI combined with single-lead Holter monitoring improves PSVC/PVC detection. METHODS: In total, 170 patients were enrolled between August 2022 and 2023. All patients wore both devices simultaneously; then, we compared diagnostic efficiency, including the sensitivity/specificity/positive predictive-value (PPV) and negative predictive-value (NPV) in detecting PSVC/PVC by 24 h-Holter and 2 h-Holter. RESULTS: The PPV and NPV in patients underwent 2 h-Holter were 76.00%/87.50% and 96.35%/98.55, respectively, and the sensitivity and specificity were 79.17%/91.30%, and 95.65%/97.84% in PSVC/PVC detection compared with 24 h-Holter. The areas under the ROC curves (AUCs) for PSVC and PVC were 0.885 and 0.741, respectively (p < .0001). CONCLUSIONS: The potential advantages of the 2 h-Holter were shortened wearing period, improved convenience, and excellent consistency of diagnosis.

Microemulsion-Assisted Self-Assembly of Indium Porphyrin Photosensitizers with Enhanced Photodynamic Therapy.

Designing and constructing supramolecular photosensitizer nanosystems with highly efficient photodynamic therapy (PDT) is vital in the nanomedical field. Despite recent advances in forming well-defined superstructures, the relationship between molecular arrangement in nanostructures and photodynamic properties has rarely been involved, which is crucial for developing stable photosensitizers for highly efficient PDT. In this work, through a microemulsion-assisted self-assembly approach, indium porphyrin (InTPP) was used to fabricate a series of morphology-controlled self-assemblies, including nanorods, nanospheres, nanoplates, and nanoparticles. They possessed structure-dependent 1O2 generation efficiency. Compared with the other three nanostructures, InTPP nanorods featuring strong π-π stacking, J-aggregation, and high crystallinity proved to be much more efficient at singlet oxygen (1O2) production. Also, theoretical modeling and photophysical experiments verified that the intermolecular π-π stacking in the nanorods could cause a decreased singlet-triplet energy gap (ΔEST) compared with the monomer. This played a key role in enhancing intersystem crossing and facilitating 1O2 generation. Both in vitro and in vivo experiments demonstrated that the InTPP nanorods could trigger cell apoptosis and tumor ablation upon laser irradiation (635 nm, 0.1 W/cm2) and exhibited negligible dark toxicity and high phototoxicity. Thus, the supramolecular self-assembly strategy provides an avenue for designing high-performance photosensitizer nanosystems for photodynamic therapy and beyond.

A retrospective study of transarterial chemoembolization (TACE) combined with lenvatinib compared with TACE monotherapy for BCLC B2 stage hepatocellular carcinoma.

The present study aimed to compare the efficacy and safety of combination therapy with lenvatinib (Len) plus transarterial chemoembolization (TACE) and TACE alone in patients with Barcelona Clinic Liver Cancer (BCLC) B2 stage hepatocellular carcinoma (HCC). A total of 66 patients with BCLC B2 stage HCC were retrospectively reviewed in the present study, of which 34 patients received Len + TACE, while 32 patients received TACE alone between May 2018 and May 2020. Survival outcome, tumor response and adverse events (AEs) were compared between the two treatment groups. The 6-month, 1- and 2-year overall survival (OS) rates were significantly higher in the Len + TACE group (97.1, 85.3 and 76.3%, respectively) compared with those in the TACE group [(93.8, 81.1 and 45.4%, respectively); hazard ratio (HR), 0.395; 95% confidence interval (CI), 0.180-0.867; P=0.023], but no significant difference in progression-free survival rate was observed between the two groups (HR, 0.815; 95% CI, 0.437-1.520; P=0.510). Patients receiving Len + TACE demonstrated a higher objective response rate compared with those receiving TACE alone (64.7 vs. 34.4%; P=0.014). Therefore, Len + TACE combination therapy was associated with increased OS and tumor response compared with that of TACE monotherapy in patients with BCLC B2 stage HCC. However, large-scale, multicenter, prospective studies are needed to further confirm these results.

Populational pan-ethnic screening panel enabled by deep whole genome sequencing.

Birth defect is a global threat to the public health systems. Mitigating neonatal anomalies is hampered by elusive molecular mechanisms of pathogenic mutations and poor subsequent translation into preventative measures. Applying appropriate strategies in China to promote reproductive health is particularly challenging, as the Chinese population compromises complex genomic diversity due to the inclusion of many ethnic groups with distinct genetic backgrounds. To investigate and evaluate the feasibility of implementing a pan-ethnic screening strategy, and guide future reproductive counselling, high-quality variants associated with autosome recessive (AR) diseases derived from the largest publicly available cohort of the Chinese population were re-analysed using a bottom-up approach. The analyses of gene carrier rates (GCRs) across distinct ethnic groups revealed that substantial heterogeneity existed potentially due to diverse evolutionary selection. The sampling population, sequencing coverage and underlying population structure contributed to the differential variants observed between ChinaMAP and the East Asian group in gnomAD. Beyond characteristics of GCR, potential druggable targets were additionally explored according to genomic features and functional roles of investigated genes, demonstrating that phase separation could be a therapeutic target for autosomal recessive diseases. A further examination of estimated GCR across ethnic groups indicated that most genes shared by at least two populations could be utilised to direct the design of a pan-ethnic screening application once sequencing and interpreting costs become negligible. To this end, a list of autosomal recessive disease genes is proposed based on the prioritised rank of GCR to formulate a tiered screening strategy.

Response of preosteoblasts on micromachined Ti-6Al-4V surface to microstructure dimension.

The cell incubation depends on the cultured surface, but various machining methods produce different surface topographies, but it has not been clear how it is related to the topographic feature until now. Hence, the machined Ti-6Al-4V surface is characterized for preosteoblasts incubation via different mechanical fabrication. The relationship between surface topography created by various machining methods and cell incubation behaviour was explored. The objective is to control the surface preosteoblasts growth in machining of biological titanium alloy. According to the cell growth kinetic, the cell incubation behaviour was first proposed and modelled in relation to microstructural dimension and culture duration. Then, the topological cultured microstructure surface was fabricated via mechanical fabrication. Finally, the cell initial adhesion and incubation behaviour on microstructured surface was investigated. It is shown that the surface undulation on machined microstructure is conducive to controlling the direction and distribution of cell incubation from cell growth kinetic model. The cell culture can be controlled on the peak with a small undulation, while it is concentred on the sidewall with a high aspect ratio. Increasing the aspect ratio extends cell growth, while low aspect ratio promotes initial cell adhesion and growth rate. Within the optimal cultured duration, the microstructured surface is more favourable for cell survival, and the cell growth keep positive beyond critical aspect ratio. As a result, the cell adhesion ability is topologically controlled to 5.4 times higher and the growth rate can be improved by 101.7% on milled microgrooved surface. It may be applied to the rapid production of biomedical Ti-6Al-4V implant.

Efficacy and safety of atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: Atezolizumab plus bevacizumab and lenvatinib are the current first-line systematic therapy for unresectable hepatocellular carcinoma (uHCC). However, the selection of initial treatment among the two therapies are controversial. This meta-analysis aims to compare efficacy and safety between atezolizumab plus bevacizumab and lenvatinib. METHODS: We systematically searched for studies on atezolizumab plus bevacizumab and lenvatinib in the online databases PubMed, Embase, Web of Science and Cochrane Library. The outcome data including overall survival (OS), progression free survival (PFS), tumor response and adverse events (AEs), were independently extracted by two authors in a standardized way. RESULTS: Eight retrospective cohort studies with 3690 patients (atezolizumab plus bevacizumab: 1680, lenvatinib: 2010) were included in the meta-analysis. The atezolizumab plus bevacizumab group had significant longer PFS [hazard ratio (HR) 0.76, 95% confidence intervals (CI) 0.65-0.88; I squared statistic (I2) = 0.0%, p = 0.590], compared with lenvatinib group but no significant difference in OS (HR 0.87, 95% CI 0.75-1.01; I2 = 0.0%, p = 0.597), objective response rate (ORR) [risk ratio (RR) 0.89, 95% CI 0.79-1.02; I2 = 19.3%, p = 0.283] and disease control rate (DCR) (RR 1.03, 95% CI 0.98-1.09; I2 = 0.0%, p = 0.467) among them. Moreover, patients receiving atezolizumab plus bevacizumab exhibited lower incidences of grade 3/4 AEs than those receiving lenvatinib (RR 0.65, 95% CI 0.51-0.83; I2 = 69.3%, p = 0.003). However, in non-viral patients group, lenvatinib delivered favorable outcomes in OS (HR 1.32, 95% CI 1.04-1.67; I2 = 0.0%, p = 0.380) compared with atezolizumab plus bevacizumab. CONCLUSION: Atezolizumab plus bevacizumab provides potential advantage in efficacy and better safety than lenvatinib in the treatment of uHCC. Lenvatinib is an appropriate effective alternative to atezolizumab plus bevacizumab in patients without viral infecting.

Efficacy and safety of transarterial chemoembolization plus lenvatinib with or without programmed death-1 inhibitors in the treatment of unresectable hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: Programmed death-1 inhibitors plus lenvatinib and transarterial chemoembolization (TACE) (P-L-T) is a novel combination strategy. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of P-L-T compared with lenvatinib and TACE (L-T) therapy in patients with unresectable hepatocellular carcinoma. METHODS: A systematic literature search of the PubMed, Embase, Web of Science and Cochrane Library databases for studies investigating P-L-T therapy was performed. Data regarding outcome data, including overall survival (OS), progression-free survival (PFS), tumor response, and adverse events (AEs), were independently extracted by two authors using a standardized protocol. RESULTS: Eight cohort studies comprising 847 patients (P-L-T: 416, L-T: 431) were included in the meta-analysis. The P-L-T group exhibited significantly longer OS (hazard ratio (Page et al.) 0.51 [95% confidence interval (CI) 0.42-0.62]; I2 = 9.8%; p = 0.354] and PFS (HR 0.51 [95% CI 0.43-0.61]; I2 = 0%; p = 0.824), and higher objective response rate (risk ratio [RR] 1.54 [95% CI 1.33-1.78]; I2 = 0%, p = 0.858]) and disease control rate (RR 1.27 [95% CI 1.17-1.38]; I2 = 17.3%; p = 0.467). Grade 3/4 AEs were more prevalent in the P-L-T group, including hypertension (RR 1.91 [95% CI 1.16-3.15]), vomiting or nausea (RR 2.29 [95% CI 1.01-5.19]), and hypothyroidism (RR 12.21 [95% CI 1.63-91.23]). CONCLUSION: Compared with L-T combination therapy, P-L-T demonstrated a significant advantage in terms of OS, PFS, objective response rate, disease control rate, and manageable AEs.

Design of OMC-Sagnac Loop Using PDMS and Different Package Structures to Improve Sensing Performance and Optimize the Ill-Conditioned Matrix.

In the process of ocean exploration, highly accurate and sensitive measurements of seawater temperature and pressure significantly impact the study of seawater's physical, chemical, and biological processes. In this paper, three different package structures, V-shape, square-shape, and semicircle-shape, are designed and fabricated, and an optical microfiber coupler combined Sagnac loop (OMCSL) is encapsulated in these structures with polydimethylsiloxane (PDMS). Then, the temperature and pressure response characteristics of the OMCSL, under different package structures, are analyzed by simulation and experiment. The experimental results show that structural change hardly affects temperature sensitivity, and square-shape has the highest pressure sensitivity. In addition, with an input error of 1% F.S., temperature and pressure errors were calculated, which shows that a semicircle-shape structure can increase the angle between lines in the sensitivity matrix method (SMM), and reduce the effect of the input error, thus optimizing the ill-conditioned matrix. Finally, this paper shows that using the machine learning method (MLM) effectively improves demodulation accuracy. In conclusion, this paper proposes to optimize the ill-conditioned matrix problem in SMM demodulation by improving sensitivity with structural optimization, which essentially explains the cause of the large errors for multiparameter cross-sensitivity. In addition, this paper proposes to use the MLM to solve the problem of large errors in the SMM, which provides a new method to solve the problem of the ill-conditioned matrix in SMM demodulation. These have practical implications for engineering an all-optical sensor that can be used for detection in the ocean environment.