Chemoimmunotherapeutic Nanogel for Pre- and Postsurgical Treatment of Malignant Melanoma by Reprogramming Tumor-Associated Macrophages.

Surgery is the primary method to treat malignant melanoma; however, the residual microtumors that cannot be resected completely often trigger tumor recurrence, causing tumor-related mortality following melanoma resection. Herein, we developed a feasible strategy based on the combinational chemoimmunotherapy by cross-linking carboxymethyl chitosan (CMCS)-originated polymetformin (PolyMetCMCS) with cystamine to prepare stimuli-responsive nanogel (PMNG) owing to the disulfide bond in cystamine that can be cleaved by the massive glutathione (GSH) in tumor sites. Then, chemotherapeutic agent doxorubicin (DOX) was loaded in PMNG, which was followed by a hyaluronic acid coating to improve the overall biocompatibility and targeting ability of the prepared nanogel (D@HPMNG). Notably, PMNG effectively reshaped the tumor immune microenvironment by reprogramming tumor-associated macrophage phenotypes and recruiting intratumoral CD8+ T cells owing to the inherited immunomodulatory capability of metformin. Consequently, D@HPMNG treatment remarkably suppressed melanoma growth and inhibited its recurrence after surgical resection, proposing a promising solution for overcoming lethal melanoma recurrence.

Black Phosphorus Quantum Dot Loaded Bioinspired Nanoplatform Synergized with aPD-L1 for Multimode Cancer Immunotherapy.

Efforts to prolong the blood circulation time and bypass immune clearance play vital roles in improving the therapeutic efficacy of nanoparticles (NPs). Herein, a multifunctional nanoplatform (BPP@RTL) that precisely targets tumor cells is fabricated by encapsulating ultrasmall phototherapeutic agent black phosphorus quantum dot (BPQD), chemotherapeutic drug paclitaxel (PTX), and immunomodulator PolyMetformin (PM) in hybrid membrane-camouflaged liposomes. Specifically, the hybrid cell membrane coating derived from the fusion of cancer cell membrane and red blood cell membrane displays excellent tumor targeting efficiency and long blood circulation property due to the innate features of both membranes. After collaboration with aPD-L1-based immune checkpoint blockade therapy, a boosted immunotherapeutic effect is obtained due to elevated dendritic cell maturation and T cell activation. Significantly, laser-irradiated BPP@RTL combined with aPD-L1 effectively eliminates primary tumors and inhibits lung metastasis in 4T1 breast tumor model, offering a promising treatment plan to develop personalized antitumor strategy.

Structural basis of main proteases of HCoV-229E bound to inhibitor PF-07304814 and PF-07321332.

PF-07321332 and PF-07304814, inhibitors against SARS-CoV-2 developed by Pfizer, exhibit broad-spectrum inhibitory activity against the main protease (Mpro) from various coronaviruses. Structures of PF-07321332 or PF-07304814 in complex with Mpros of various coronaviruses reveal their inhibitory mechanisms against different Mpros. However, the structural information on the lower pathogenic coronavirus Mpro with PF-07321332 or PF-07304814 is currently scarce, which hinders our comprehensive understanding of the inhibitory mechanisms of these two inhibitors. Meanwhile, given that some immunocompromised individuals are still affected by low pathogenic coronaviruses, we determined the structures of lower pathogenic coronavirus HCoV-229E Mpro with PF-07321332 and PF-07304814, respectively, and analyzed and defined in detail the structural basis for the inhibition of HCoV-229E Mpro by both inhibitors. Further, we compared the crystal structures of multiple coronavirus Mpro complexes with PF-07321332 or PF-07304814 to illustrate the differences in the interaction of Mpros, and found that the inhibition mechanism of lower pathogenic coronavirus Mpro was more similar to that of moderately pathogenic coronaviruses. Our structural studies provide new insights into drug development for low pathogenic coronavirus Mpro, and provide theoretical basis for further optimization of both inhibitors to contain potential future coronaviruses.

[Design and implementation of a modular pulse wave preprocessing and analysis system based on a new detection algorithm].

As one of the standard electrophysiological signals in the human body, the photoplethysmography contains detailed information about the blood microcirculation and has been commonly used in various medical scenarios, where the accurate detection of the pulse waveform and quantification of its morphological characteristics are essential steps. In this paper, a modular pulse wave preprocessing and analysis system is developed based on the principles of design patterns. The system designs each part of the preprocessing and analysis process as independent functional modules to be compatible and reusable. In addition, the detection process of the pulse waveform is improved, and a new waveform detection algorithm composed of screening-checking-deciding is proposed. It is verified that the algorithm has a practical design for each module, high accuracy of waveform recognition and high anti-interference capability. The modular pulse wave preprocessing and analysis software system developed in this paper can meet the individual preprocessing requirements for various pulse wave application studies under different platforms. The proposed novel algorithm with high accuracy also provides a new idea for the pulse wave analysis process.

Crystal structure of SARS-CoV 3C-like protease with baicalein.

The 3C-like protease (Mpro, 3CLpro) plays a key role in the replication process in coronaviruses (CoVs). The Mpro is an essential enzyme mediates CoVs replication and is a promising target for development of antiviral drugs. Until now, baicalein has been shown the specific activity for SARS-CoV Mpro in vitro experiments. In this study, we resolved the SARS-CoV Mpro with baicalein by X-ray diffraction at 2.25 Å (PDB code 7XAX), which provided a structural basis for the research and development of baicalein as an anti-CoVs drug.

Composite substrate of graphene/Ag nanoparticles coupled with a multilayer film for surface-enhanced Raman scattering biosensing.

In this paper, we designed a surface-enhanced Raman scattering (SERS) substrate for graphene/Ag nanoparticles (Ag NPs) bonded multilayer film (MLF) using the hybrid nanostructures composed of graphene and plasmonic metal components with significant plasmonic electrical effects and unique optical characteristics. This paper achieved the advantages of efficient utilization of electromagnetic field and reduction of fluorescence background based on the electromagnetic enhancement activity of Ag NPs and unique physical/chemical properties of graphene with zero gap structures. Au/Al2O3 was stacked periodically to construct MLF. As indicated by the electric field intensity at the Au/Al2O3 interface of the respective layer, bulk plasmon polariton (BPP) in the MLF was excited and coupled with localized surface plasmon (LSP) in the Ag NPs, which enhanced the electromagnetic field on the top-layer of SERS substrate. To measure the performance of the SERS substrate, rhodamine 6G (R6G) and malachite green (MG) were used as the probe molecules, with the detection limits of 10-11 M and 10-8 M, respectively. The SERS substrate had high sensitivity and uniformity, which indicated that it has a broad application prospect in the field of molecular detection.

LSPR optical fiber sensor based on 3D gold nanoparticles with monolayer graphene as a spacer.

Localized surface plasmon resonance (LSPR) optical fiber biosensing is an advanced and powerful label-free technique which gets great attention for its high sensitivity to refractive index change in surroundings. However, the pursuit of a higher sensitivity is still challenging and should be further investigated. In this paper, based on a monolayer graphene/gold nanoparticles (Grm/Au NPs) three-dimensional (3D) hybrid structure, we fabricated a D-shaped plastic optical fiber (D-POF) LSPR sensor using a facile two-step method. The coupling enhancement of the resonance of this multilayer structure was extremely excited by the surface plasmon property of the stacked Au NPs/Grm layer. We found that the number of plasmonic structure layers was of high importance to the performance of the sensor. Moreover, the optimal electromagnetic field enhancement effect was found in three-layer plasmonic structure. Besides, the n*(Grm/Au NPs)/D-POF sensor exhibited outstanding performance in sensitivity (2160 nm/RIU), linearity (linear fitting coefficient R2 = 0.996) and reproducibility. Moreover, the sensor successfully detected the concentration of glucose, achieving a sensitivity of 1317.61 nm/RIU, which suggested a promising prospect for the application in medicine and biotechnology.

FGFC1 Exhibits Anti-Cancer Activity via Inhibiting NF-κB Signaling Pathway in EGFR-Mutant NSCLC Cells.

FGFC1, an active compound isolated from the culture of marine fungi Stachybotrys longispora FG216, elicits fibrinolytic, anti-oxidative, and anti-inflammatory activity. We have previously reported that FGFC1 inhibited the proliferation, migration, and invasion of the non-small cell lung cancer (NSCLC) cells in vitro. However, the precise mechanisms of FGFC1 on NSCLC and its anti-cancer activity in vivo remains unclear. Hence, this study was focused to investigate the effects and regulatory mechanisms of FGFC1 on two NSCLC cell lines, EGFR-mutant PC9 (ex19del) and EGFR wild-type H1299. Results suggested that FGFC1 significantly inhibited proliferation, colony formation, as well as triggered G0/G1 arrest and apoptosis of PC9 cells in a dose- and time-dependent manner, but no obvious inhibitory effects were observed in H1299 cells. Subsequently, transcriptome analysis revealed that FGFC1 significantly down-regulated 28 genes related to the NF-κB pathway, including IL-6, TNF-α, and ICAM-1 in the PC9 cells. We further confirmed that FGFC1 decreased the expression of protein p-IKKα/ß, p-p65, p-IκB, IL-6, and TNF-α. Moreover, NF-κB inhibitor PDTC could strengthen the effects of FGFC1 on the expression of CDK4, Cyclin D1, cleaved-PARP-1, and cleaved-caspase-3 proteins, suggesting that the NF-κB pathway plays a major role in FGFC1-induced cell cycle arrest and apoptosis. Correspondingly, the nuclear translocation of p-p65 was also suppressed by FGFC1 in PC9 cells. Finally, the intraperitoneal injection of FGFC1 remarkably inhibited PC9 xenograft growth and decreased the expression of Ki-67, p-p65, IL-6, and TNF-α in tumors. Our results indicated that FGFC1 exerted anti-cancer activity in PC9 cells via inhibiting the NF-κB signaling pathway, providing a possibility for FGFC1 to be used as a lead compound for the treatment of NSCLC in the future.

[Age distribution of nutrition and health knowledge among Chinese adults in 2021].

OBJECTIVE: To analyze the age distribution of nutrition and health knowledge level of Chinese residents aged 18-64. METHODS: A total of 102 398 residents aged 18-64 were selected from 302 survey sites in China by multi-stage cluster random sampling method, a total of 98 567 respondents were included in the study. Both mean and rate were calculated by complex sampling weighting. RESULTS: The nutrition and health knowledge score of residents aged 18-24, 25-34, 35-44, 45-54 and 55-64 years old in China were(65.1±11.4) points, (64.6±11.7) points, (64.7±12.0) points, (62.2±12.8) points and(59.5±13.3) points. The nutrition and health knowledge awareness rates were 20.3%, 19.1%, 20.3%, 16.9% and 12.1%, respectively(P<0.001). A decreasing trend in all dimensions and overall nutrition and health knowledge with increasing age was found(ß<0, P_(trend)<0.001). This trend was also reflected across gender or regions. While the trend of nutrition and health knowledge level with age varies with different literacy levels. Differences in knowledge points with positive response rates <30% by age groups. CONCLUSION: The level of nutrition and health knowledge among Chinese adult residents of all ages is relatively low in 2021, but the knowledge shortcomings are different.

[Access channels on nutrition and health knowledge of Chinese adults in 2021].

OBJECTIVE: To analyze the access channels on nutritional health knowledge of Chinese residents aged 18-64 years in 2021. METHODS: A multi-stage cluster random sampling was used to select 302 survey sites across the country, there were 102 398 people surveyed, with 98 424 valid questionnaires, 49.4% male and 42.0% urban, with an average age of(38.5±12.2) years old. A standardized questionnaire certified by experts and evaluated for reliability and validity was used to conduct the face-to-face survey. Descriptive statistics were used to report the access channels on nutrition and health knowledge of respondents, and the proportion of access channels of respondents with different characteristics was compared by chi-square test. RESULTS: The access channels on nutrition and health knowledge of Chinese residents aged 18-64 in 2021 were, in descending order, WeChat/Microblog/Tik Tok/Kuaishou and other software(77.0%), TV/radio(55.7%), family/relatives/friends(41.8%), books/newspapers/journals/magazines(32.5%), website search(30.7%), promotional lectures(29.3%) and other(1.9%). A high proportion of people who access nutrition and health knowledge through software, website searches and books/newspapers were mostly from the lower age groups, higher education groups, urban and eastern regions. People with a high proportion of access through TV/radio, family/relatives/friends and promotional lectures were mostly from the higher age groups, lower education groups, rural and western areas(P<0.001). Women are more likely than men to obtain nutrition and health information from all channels except website search. The higher the level of education, the higher the level of concern for nutrition and health knowledge(P<0.001). CONCLUSION: In 2021, the top access channel for Chinese residents aged 18-64 to obtain nutrition and health knowledge is WeChat/Microblog/Tik Tok/Kuaishou and other software. There are differences in access channels for different groups of people.

[Geographical distribution differences of nutrition and health knowledge among Chinese adults in 2021].

OBJECTIVE: To explore the geographical distribution of nutrition and health knowledge among 18-64 years old adults in China. METHODS: A total of 102 398 residents aged 18-64 from 302 survey sites were selected by multi-stage cluster random sampling method, a total of 98 567 respondents were included in the study. Both mean and rate were calculated by complex sampling weighting. RESULTS: The nutrition and health knowledge score in eastern region(65.5±12.0) was higher than that in central(62.4±11.9) and western(61.4±12.9), and the score in northern region(63.9±11.8) was higher than that in southern(63.1±12.8). In the seven geographical regions, the highest score was in north(65.8±11.4), and the lowest score was in northwest(61.6±12.2). The awareness rate of nutrition and health in eastern region(22.4%) was higher than that in central(14.7%) and western(14.9%), the highest awareness rate among the seven geographic regions was in east(23.2%), followed by north(22.5%) and the lowest was in northwest(13.2%). There were also differences in nutritional health knowledge levels of residents in different regions in the five dimensions(P<0.001). Northwest China had the lowest awareness of food characteristics and nutrition and disease dimensions, South China had the lowest awareness of dietary recommendations and food choices dimensions, and Southwest China had the lowest awareness of food safety dimensions. CONCLUSION: The level of nutrition and health knowledge of Chinese adults have large geographical differences.

Resting-State MEG Source Space Network Metrics Associated with the Duration of Temporal Lobe Epilepsy.

To evaluate the relationship between the network metrics of 68 brain regions and duration of temporal lobe epilepsy (TLE). Magnetoencephalography (MEG) data from 53 patients with TLE (28 left TLE, 25 right TLE) were recorded between seizures at resting state and analyzed in six frequency bands: delta (0.1-4 Hz), theta (4-8 Hz), lower alpha (8-10 Hz), upper alpha (10-13 Hz), beta (13-30 Hz), and lower gamma (30-48 Hz). Three local network metrics, betweenness centrality, nodal degree, and nodal efficiency, were chosen to analyze the functional brain network. In Left, Right, and All (Left + Right) TLE groups, different metrics provide significant positive or negative correlations with the duration of TLE, in different frequency bands, and in different brain regions. In the Left TLE group, significant correlation between TLE duration and metric exists in the delta, beta, or lower gamma band, with network betweenness centrality, nodal degree, or nodal efficiency, in left caudal middle frontal, left middle temporal, or left supramarginal. In the Right TLE group, significant correlation exists in lower gamma or delta band, with nodal degree, or nodal efficiency, in left precuneus or right temporal pole. In the All TLE group, the significant correlation exists in delta, theta, beta, or lower gamma band, with nodal degree, or betweenness centrality, in either left or right hemisphere. Network metrics for some specific brain regions changed in patients with TLE as the duration of their TLE increased. Further researching these changes may be important for studying the pathogenesis, presurgical evaluation, and clinical treatment of long-term TLE.

[Resting-state electroencephalogram classification of patients with schizophrenia or depression].

The clinical manifestations of patients with schizophrenia and patients with depression not only have a certain similarity, but also change with the patient's mood, and thus lead to misdiagnosis in clinical diagnosis. Electroencephalogram (EEG) analysis provides an important reference and objective basis for accurate differentiation and diagnosis between patients with schizophrenia and patients with depression. In order to solve the problem of misdiagnosis between patients with schizophrenia and patients with depression, and to improve the accuracy of the classification and diagnosis of these two diseases, in this study we extracted the resting-state EEG features from 100 patients with depression and 100 patients with schizophrenia, including information entropy, sample entropy and approximate entropy, statistical properties feature and relative power spectral density (rPSD) of each EEG rhythm (δ, θ, α, ß). Then feature vectors were formed to classify these two types of patients using the support vector machine (SVM) and the naive Bayes (NB) classifier. Experimental results indicate that: ① The rPSD feature vector P performs the best in classification, achieving an average accuracy of 84.2% and a highest accuracy of 86.3%; ② The accuracy of SVM is obviously better than that of NB; ③ For the rPSD of each rhythm, the ß rhythm performs the best with the highest accuracy of 76%; ④ Electrodes with large feature weight are mainly concentrated in the frontal lobe and parietal lobe. The results of this study indicate that the rPSD feature vector P in conjunction with SVM can effectively distinguish depression and schizophrenia, and can also play an auxiliary role in the relevant clinical diagnosis.

Feasibility study of stain-free classification of cell apoptosis based on diffraction imaging flow cytometry and supervised machine learning techniques.

This study was to explore the feasibility of prediction and classification of cells in different stages of apoptosis with a stain-free method based on diffraction images and supervised machine learning. Apoptosis was induced in human chronic myelogenous leukemia K562 cells by cis-platinum (DDP). A newly developed technique of polarization diffraction imaging flow cytometry (p-DIFC) was performed to acquire diffraction images of the cells in three different statuses (viable, early apoptotic and late apoptotic/necrotic) after cell separation through fluorescence activated cell sorting with Annexin V-PE and SYTOX® Green double staining. The texture features of the diffraction images were extracted with in-house software based on the Gray-level co-occurrence matrix algorithm to generate datasets for cell classification with supervised machine learning method. Therefore, this new method has been verified in hydrogen peroxide induced apoptosis model of HL-60. Results show that accuracy of higher than 90% was achieved respectively in independent test datasets from each cell type based on logistic regression with ridge estimators, which indicated that p-DIFC system has a great potential in predicting and classifying cells in different stages of apoptosis.

A self-sacrifice template route to iodine modified BiOIO3: band gap engineering and highly boosted visible-light active photoreactivity.

The development of high-performance visible-light photocatalysts with a tunable band gap has great significance for enabling wide-band-gap (WBG) semiconductors visible-light sensitive activity and precisely tailoring their optical properties and photocatalytic performance. In this work we demonstrate the continuously adjustable band gap and visible-light photocatalysis activation of WBG BiOIO3via iodine surface modification. The iodine modified BiOIO3 was developed through a facile in situ reduction route by applying BiOIO3 as the self-sacrifice template and glucose as the reducing agent. By manipulating the glucose concentration, the band gap of the as-prepared modified BiOIO3 could be orderly narrowed by generation of the impurity or defect energy level close to the conduction band, thus endowing it with a visible light activity. The photocatalytic assessments uncovered that, in contrast to pristine BiOIO3, the modified BiOIO3 presents significantly boosted photocatalytic properties for the degradation of both liquid and gaseous contaminants, including Rhodamine B (RhB), methyl orange (MO), and ppb-level NO under visible light. Additionally, the band structure evolution as well as photocatalysis mechanism triggered by the iodine surface modification is investigated in detail. This study not only provides a novel iodine surface-modified BiOIO3 for environmental application, but also provides a facile and general way to develop highly efficient visible-light photocatalysts.

The mediating role of general self-efficacy in the association between perceived social support and oral health-related quality of life after initial periodontal therapy.

BACKGROUND: Although initial periodontal therapy can ease some physical and psychological discomforts from periodontitis and improve patients' oral health-related quality of life (OHRQoL), it is also vital to find positive resources from psychological and social aspects to promote the overall OHRQoL. This study aims to explore the associations of perceived social support (PSS) and general self-efficacy with OHRQoL and the mediating role of general self-efficacy in PSS-OHRQoL association after initial periodontal therapy. METHODS: A prospective case series study was conducted among consecutive outpatients with chronic periodontitis during the period of July 2014-April 2015. A total of 145 eligible patients responded to OHRQoL questionnaire and periodontal examination at baseline. About 4 to 5 weeks after initial periodontal therapy, 120 patients completed the second OHRQoL measurement and periodontal examination, along with PSS and general self-efficacy measurement. The Wilcoxon matched-pairs signed-rank test was used to determine the difference between baseline and post-treatment OHRQoL scores and periodontal parameters. Hierarchical linear regression analysis was used to explore the associations of PSS and general self-efficacy with post-treatment OHRQoL after adjusting for some demographic and periodontal variables. Asymptotic and resampling strategies were performed to explore the mediating role of general self-efficacy. RESULTS: Initial periodontal therapy resulted in a significant improvement in the mean total score and all domains of OHRQoL and all periodontal parameters measured. In hierarchical linear regression analysis, clinical attachment loss (CAL) was significantly and positively associated with post-treatment OHRQoL score (ß = 0.265, p < 0.01), while PSS (ß = -0.303, p < 0.01) and general self-efficacy (ß = -0.221, p < 0.01) were significantly and negatively associated with post-treatment OHRQL score, respectively. A significant mediating role of general self-efficacy (a*b = -0.139, BCa 95 % CI: -0.298, -0.011) in the association between PSS and post-treatment OHRQoL was revealed, and the proportion of the mediating role of general self-efficacy was 31.4 %. CONCLUSIONS: Initial periodontal therapy could significantly improve all aspects of OHRQoL. PSS and general self-efficacy could be the positive resources for improving OHRQoL after initial periodontal therapy among patients with periodontitis. General self-efficacy partly mediated the association between PSS and post-treatment OHRQoL.

High levels of KAP1 expression are associated with aggressive clinical features in ovarian cancer.

KAP1 is an universal corepressor for Kruppel-associated box zinc finger proteins in both normal and tumor cells. In this study, the biological function and clinical significance of KAP1 expression in ovarian cancer were investigated. Immunohistological staining of KAP1 was evaluated in 111 patients with ovarian epithelial cancer, 15 with ovarian borderline tumor, and 20 normal ovarian tissue. The correlations of KAP1 expression with clinicopathological features were studied. Kaplan-Meier analysis and Cox proportional hazard modeling were used to assess overall survival to analyze the effect of KAP1 expression on the prognosis of ovarian cancer. The positive rates of KAP1 were significantly higher in ovarian epithelial cancer (55.7%) and borderline tumor (20.0%) than in normal ovarian tissue (5.0%) (all p < 0.01). KAP1 expression correlated significantly with clinical stage (χ2 = 14.57, p < 0.0001), pathological grade (χ2 = 6.06, p = 0.048) and metastases (χ2 =10.38, p = 0.001). Patients with high KAP 1 levels showed poor survival (p < 0.0001). Multivariate analysis showed that KAP1 high expression was an independent predictor for ovarian cancer patients (hazard ratio = 0.463; 95% confidence interval = 0.230-0.9318, p = 0.031). Functionally, depletion of KAP1 by siRNA inhibited ovarian cancer cell proliferation, cell migration. KAP1 expression correlated with aggressive clinical features in ovarian cancer. High KAP1 expression was a prognostic factor of ovarian cancer.

Efficacy and safety of transarterial chemoembolization combined with targeted therapy and immunotherapy versus with targeted monotherapy in unresectable hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: The application of transarterial chemoembolization (TACE) in combination with targeted therapy and immunotherapy (TACE-T-I) for unresectable hepatocellular carcinoma (HCC) has gained increasing attention. However, there are variations in the efficacy and safety outcomes between TACE-T-I versus TACE combined with targeted drugs (TACE-T). This study aims to systematically evaluate the efficacy and safety of TACE-T-I versus TACE-T in unresectable HCC. METHODS: PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to August 21, 2023, for comparative studies on TACE-T-I versus TACE-T for unresectable HCC. Outcome measures included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and the incidence of treatment-related adverse events (TRAEs). OS was the primary outcome of this study. Weighted mean difference (WMD) or hazard ratio (HR) was used as the pooled statistic for OS and PFS. Relative risk (RR) was employed as the pooled statistic for ORR, DCR and the incidence of TRAEs. And 95% confidence intervals (CIs) were calculated for all effect measures. Data analysis was conducted using Stata 14.0 software. RESULTS: The meta-analysis included 14 studies with 2144 patients. The pooled results showed that compared with patients in the TACE-T group, patients in the TACE-T-I group had higher ORR (RR = 1.61; 95%CI: 1.38-1.89) and DCR (RR = 1.17; 95%CI: 1.09-1.26). Patients in the TACE-T-I group experienced prolonged PFS (WMD = 3.08; 95%CI: 2.63-3.53) and OS (WMD = 5.76; 95%CI: 4.68-6.84). And the risk of disease progression (HR = 0.45; 95%CI: 0.37-0.55) and death (HR = 0.43; 95%CI: 0.38-0.49) was lower in the TACE-T-I group. Common TRAEs included fever, pain, abdominal pain, nausea, vomiting, elevated ALT, elevated AST, hypertension, hand-foot syndrome, proteinuria, and diarrhea. The incidence and severity of TRAEs in the TACE-T-I group were similar to those in the TACE-T group, with no significant differences (P > .05). CONCLUSION: Current evidence suggests that, on the basis of TACE combined with targeted therapy, the addition of immunotherapy provides better clinical efficacy and survival benefits for unresectable HCC patients, with good tolerability.

Predictors of HBsAg seroclearance in patients with chronic HBV infection treated with pegylated interferon-α: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The identification of reliable predictors for hepatitis B surface antigen (HBsAg) seroclearance remains controversial. We aimed to summarize potential predictors for HBsAg seroclearance by pegylated interferon-α (PegIFNα) in patients with chronic HBV infection. METHODS: A systematic search of the Cochrane Library, Embase, PubMed, and Web of Science databases was conducted from their inception to 28 September 2022. Meta-analyses were performed following the PRISMA statement. Predictors of HBsAg seroclearance were evaluated based on baseline characteristics and on-treatment indicators. RESULTS: This meta-analysis encompasses 27 studies, including a total of 7913 patients. The findings reveal several factors independently associated with HBsAg seroclearance induced by PegIFNα-based regimens. These factors include age (OR = 0.961), gender (male vs. female, OR = 0.537), genotype (A vs. B/D; OR = 7.472, OR = 10.738), treatment strategy (combination vs. monotherapy, OR = 2.126), baseline HBV DNA (OR = 0.414), baseline HBsAg (OR = 0.373), HBsAg levels at week 12 and 24 (OR = 0.384, OR = 0.294), HBsAg decline from baseline to week 12 and 24 (OR = 6.689, OR = 6.513), HBsAg decline from baseline ≥ 1 log10 IU/ml and ≥ 0.5 log10 IU/ml at week 12 (OR = 18.277; OR = 4.530), and ALT elevation at week 12 (OR = 3.622). Notably, subgroup analysis suggests no statistical association between HBsAg levels at week 12 and HBsAg seroclearance for treatment duration exceeding 48 weeks. The remaining results were consistent with the overall analysis. CONCLUSIONS: This is the first meta-analysis to identify predictors of HBsAg seroclearance with PegIFNα-based regimens, including baseline and on-treatment factors, which is valuable in developing a better integrated predictive model for HBsAg seroclearance to guide individualized treatment and achieve the highest cost-effectiveness of PegIFNα.

Blood-Brain Barrier-Penetrating and Lesion-Targeting Nanoplatforms Inspired by the Pathophysiological Features for Synergistic Ischemic Stroke Therapy.

Ischemic stroke is a dreadful vascular disorder that poses enormous threats to the public health. Due to its complicated pathophysiological features, current treatment options after ischemic stroke attack remains unsatisfactory. Insufficient drug delivery to ischemic lesions impeded by the blood-brain barrier (BBB) largely limits the therapeutic efficacy of most anti-stroke agents. Herein, inspired by the rapid BBB penetrability of 4T1 tumor cells upon their brain metastasis and natural roles of platelet in targeting injured vasculatures, a bio-derived nanojacket is developed by fusing 4T1 tumor cell membrane with platelet membrane, which further clothes on the surface of paeonol and polymetformin-loaded liposome to obtain biomimetic nanoplatforms (PP@PCL) for ischemic stroke treatment. The designed PP@PCL could remarkably alleviate ischemia-reperfusion injury by efficiently targeting ischemic lesion, preventing neuroinflammation, scavenging excess reactive oxygen species (ROS), reprogramming microglia phenotypes, and promoting angiogenesis due to the synergistic therapeutic mechanisms that anchor the pathophysiological characteristics of ischemic stroke. As a result, PP@PCL exerts desirable therapeutic efficacy in injured PC12 neuronal cells and rat model of ischemic stroke, which significantly attenuates neuronal apoptosis, reduces infarct volume, and recovers neurological functions, bringing new insights into exploiting promising treatment strategies for cerebral ischemic stroke management.