Enhancing Escherichia coli Inactivation: Synergistic Mechanism of Ultraviolet Light and High-Voltage Electric Field.

This study investigated the bactericidal effects of ultraviolet (UV) radiation, a high-voltage electric field (HVEF), and their combination on Escherichia coli. The results indicated that UV and combined disinfection were more effective with longer exposure, leading to significant reductions in microbial activity. Specifically, the single UV disinfection alone reduced activity by 3.3 log after 5 min, while combined disinfection achieved a 4.2 log reduction. In contrast, short-term HVEF treatment did not exhibit significant bactericidal effects, only achieving a reduction of 0.17 log in 5 min. Furthermore, prolonged exposure to both UV disinfection and an HVEF was found to damage cell membranes, ultimately causing cell death, while shorter durations did not. Despite rapid cell count decreases, flow cytometry did not detect apoptotic or necrotic cells, likely due to rapid cell rupture. This study suggests that combining UV radiation and an HVEF could be a promising approach for inhibiting bacterial reproduction, with HVEF enhancing UV effects. These findings provide insights for using combined HVEF and UV disinfection in food safety and preservation.

Single-cell insights: pioneering an integrated atlas of chromatin accessibility and transcriptomic landscapes in diabetic cardiomyopathy.

BACKGROUND: Diabetic cardiomyopathy (DCM) poses a growing health threat, elevating heart failure risk in diabetic individuals. Understanding DCM is crucial, with fibroblasts and endothelial cells playing pivotal roles in driving myocardial fibrosis and contributing to cardiac dysfunction. Advances in Multimodal single-cell profiling, such as scRNA-seq and scATAC-seq, provide deeper insights into DCM's unique cell states and molecular landscape for targeted therapeutic interventions. METHODS: Single-cell RNA and ATAC data from 10x Multiome libraries were processed using Cell Ranger ARC v2.0.1. Gene expression and ATAC data underwent Seurat and Signac filtration. Differential gene expression and accessible chromatin regions were identified. Transcription factor activity was estimated with chromVAR, and Cis-coaccessibility networks were calculated using Cicero. Coaccessibility connections were compared to the GeneHancer database. Gene Ontology analysis, biological process scoring, cell-cell communication analysis, and gene-motif correlation was performed to reveal intricate molecular changes. Immunofluorescent staining utilized various antibodies on paraffin-embedded tissues to verify the findings. RESULTS: This study integrated scRNA-seq and scATAC-seq data obtained from hearts of WT and DCM mice, elucidating molecular changes at the single-cell level throughout the diabetic cardiomyopathy progression. Robust and accurate clustering analysis of the integrated data revealed altered cell proportions, showcasing decreased endothelial cells and macrophages, coupled with increased fibroblasts and myocardial cells in the DCM group, indicating enhanced fibrosis and endothelial damage. Chromatin accessibility analysis unveiled unique patterns in cell types, with heightened transcriptional activity in myocardial cells. Subpopulation analysis highlighted distinct changes in cardiomyocytes and fibroblasts, emphasizing pathways related to fatty acid metabolism and cardiac contraction. Fibroblast-centered communication analysis identified interactions with endothelial cells, implicating VEGF receptors. Endothelial cell subpopulations exhibited altered gene expressions, emphasizing contraction and growth-related pathways. Candidate regulators, including Tcf21, Arnt, Stat5a, and Stat5b, were identified, suggesting their pivotal roles in DCM development. Immunofluorescence staining validated marker genes of cell subpopulations, confirming PDK4, PPARγ and Tpm1 as markers for metabolic pattern-altered cardiomyocytes, activated fibroblasts and endothelial cells with compromised proliferation. CONCLUSION: Our integrated scRNA-seq and scATAC-seq analysis unveils intricate cell states and molecular alterations in diabetic cardiomyopathy. Identified cell type-specific changes, transcription factors, and marker genes offer valuable insights. The study sheds light on potential therapeutic targets for DCM.

Quantitative analysis of the protective performance of bicycle helmet with multi-direction impact protection system in oblique impact tests.

PURPOSE: The current study aimed to assess the protective performance of helmets equipped with a multi-directional impact protection system (MIPS) under various oblique impact loads. METHODS: Initially, a finite element model of a bicycle helmet with MIPS was developed based on the scanned geometric parameters of an actual bicycle helmet. Subsequently, the validity of model was confirmed using the KASK WG11 oblique impact test method. Three different impact angles (30°, 45°, and 60°) and 2 varying impact speeds (5 m/s and 8 m/s) were employed in oblique tests to evaluate protective performance of MIPS in helmets, focusing on injury assessment parameters such as peak linear acceleration (PLA) and peak angular acceleration (PAA) of the head. RESULTS: The results demonstrated that in all impact simulations, both assessment parameters were lower during impact for helmets equipped with MIPS compared to those without. The PAA was consistently lower in the MIPS helmet group, whereas the difference in resulting PLA was not significant in the no-MIPS helmet group. For instance, at an impact velocity of 8 m/s and a 30° inclined anvil, the MIPS helmet group exhibited a PAA of 3225 rad/s2 and a PLA of 281 g. In contrast, the no-MIPS helmet group displayed a PAA of 8243 rad/s2 and a PLA of 292 g. Generally, both PAA and PLA parameters decreased with increasing anvil angle. At a 60° anvil angle, PAA and PLA values were 664 rad/s2 and 20.7 g, respectively, reaching their minimum. CONCLUSION: The findings indicated that helmets incorporating MIPS offer enhanced protection against various oblique impact loads. When assessing helmets for oblique impacts, the utilization of larger angle anvils and rear impacts might not adequately evaluate protective performance during an impact event. These findings will guide advancements in helmet design and the refinement of oblique impact test protocols.

25-hydroxyvitamin D and Endometriosis: A bidirectional Mendelian randomization study.

Numerous studies have demonstrated a correlation between serum 25-hydroxyvitamin D (25OHD) and endometriosis. However, the precise nature of this association remains elusive. The causal connection between 25OHD and endometriosis remains uncertain, as it is yet to be determined whether one directly influences the other. The objective of our research was to investigate the cause-and-effect connection between 25OHD and endometriosis. The study employed Mendelian randomization (MR) in a bidirectional two-sample investigation to examine the causal relationship between 25OHD and endometriosis. The analysis utilized the most recent publicly accessible statistics from the genome-wide association study (GWAS) encompassing 25OHD, endometriosis, and its five subtypes. The primary analytical approach employed was Inverse-Variance Weighting (IVW), accompanied by supplementary analysis methods including weighted median, MR-Egger, simple mode, and weighted mode. Furthermore, sensitivity analyses were conducted to assess the potential influence of heterogeneity and pleiotropy on the MR outcomes. MR primary analysis showed no significant causal effect of 25OHD on endometriosis (OR = 0.892, 95%CI = 0.745 ~ 1.068, P = 0.213). Similarly, there was no evidence to support a causal relationship of endometriosis on 25OHD (IVW Beta = 0.005, 95%CI = 0.993 ~ 1.018, P = 0.406). However, when conducting MR analysis on different subtypes of endometriosis and 25OHD, we found a positive correlation between endometriosis of ovary and 25OHD level (IVW Beta = 0.012, 95%CI = 1.002 ~ 1.022, P = 0.024). This study indicates that there is no causal relationship between serum 25OHD and endometriosis. However, it is important to note that serum 25OHD levels will increase in patients with endometriosis of the ovary. Further observational studies and clinical trials are indispensable.

Progress in the treatment of advanced hepatocellular carcinoma with immune combination therapy.

Advanced hepatocellular carcinoma (HCC) is a severe malignancy that poses a serious threat to human health. Owing to challenges in early diagnosis, most patients lose the opportunity for radical treatment when diagnosed. Nonetheless, recent advancements in cancer immunotherapy provide new directions for the treatment of HCC. For instance, monoclonal antibodies against immune checkpoint inhibitors (ICIs) such as programmed cell death protein 1/death ligand-1 inhibitors and cytotoxic t-lymphocyte associated antigen-4 significantly improved the prognosis of patients with HCC. However, tumor cells can evade the immune system through various mechanisms. With the rapid development of genetic engineering and molecular biology, various new immunotherapies have been used to treat HCC, including ICIs, chimeric antigen receptor T cells, engineered cytokines, and certain cancer vaccines. This review summarizes the current status, research progress, and future directions of different immunotherapy strategies in the treatment of HCC.

Comparing Safety and Efficacy of TACE + Apatinib in Combination with a PD-1 Inhibitor versus a Non-triple Therapy for Treating Advanced Primary Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: This meta-analysis was performed to compare the efficacy and safety of a triple therapy, involving transcatheter arterial chemoembolization (TACE) + apatinib combined with a programmed-cell death protein-1 (PD-1) inhibitor versus TACE + apatinib, a dual therapy with apatinib and PD-1 inhibitor, and TACE alone for the treatment of advanced primary hepatocellular carcinoma (HCC). METHODS: A computerized systematic search of databases, such as PubMed, Embase, the Cochrane Library, CNKI, Wanfang Data, and VIP e-Journals was performed to retrieve studies comparing TACE + apatinib combined with a PD-1 inhibitor versus a non-triple therapy for the treatment of advanced primary HCC. The literature search, quality assessment, and data extraction were performed independently by two researchers. Stata 16.0 software was employed to analyze the data. Heterogeneity was assessed utilizing the I2 statistic and p-value, followed by conducting sensitivity analysis. RESULTS: A total of 2,352 patients were enrolled from 8 studies, including 900 patients in the triple therapy group of TACE + apatinib combined with a PD-1 inhibitor, 877 patients in the TACE + apatinib group, 52 patients in the apatinib + a PD-1 inhibitor group, and 112 patients in the TACE group. The results revealed that the objective response rate (ORR) was significantly higher in the triple therapy group of TACE + apatinib combined with a PD-1 inhibitor than that in the non-triple therapy group [odds ratio (OR)=2.47, 95% confidence interval (95%CI): 1.61-3.78]. Besides, disease control rate (DCR) was greater in the triple therapy group of TACE + apatinib combined with a PD-1 inhibitor than that in the non-triple therapy group (OR=1.87, 95%CI: 1.44-2.44). Patients in the triple therapy group experienced a significant extension of overall survival (OS) (HR=0.42, 95%CI: 0.36-0.49). In addition, there was no significant difference in the overall rate of adverse events (AEs) between the two groups (OR=1.05, 95%CI: 0.89-1.22). CONCLUSIONS: Compared with the non-triple therapy group, the triple therapy group of TACE + apatinib combined with a PD-1 inhibitor outperformed in terms of tumor response and long-term survival with manageable AEs.

Forecasting China carbon price using an error-corrected secondary decomposition hybrid model integrated fuzzy dispersion entropy and deep learning paradigm.

Forecasting China's carbon price accurately can encourage investors and manufacturing industries to take quantitative investments and emission reduction decisions effectively. The inspiration for this paper is developing an error-corrected carbon price forecasting model integrated fuzzy dispersion entropy and deep learning paradigm, named ICEEMDAN-FDE-VMD-PSO-LSTM-EC. Initially, the improved complete ensemble empirical mode decomposition with adaptive noise (ICEEMDAN) is used to primary decompose the original carbon price. Subsequently, the fuzzy dispersion entropy (FDE) is conducted to identify the high-complexity signals. Thirdly, the variational mode decomposition (VMD) and deep learning paradigm of particle swarm optimized long short-term memory (PSO-LSTM) models are employed to secondary decompose the high-complexity signals and perform out-of-sample forecasting. Finally, the error-corrected (EC) method is conducted to re-modify and strengthen the above-predicted accuracy. The results conclude that the forecasting performance of ICEEMDAN-type secondary decomposition models is significantly better than the primary decomposition models, the deep learning PSO-LSTM-type models have superiority in forecasting China carbon price, and the EC method for improving the forecasting accuracy has been proved. Noteworthy, the proposed model presents the best forecasting accuracy, with the forecasting errors RMSE, MAE, MAPE, and Pearson's correlation are 0.0877, 0.0407, 0.0009, and 0.9998, respectively. Especially, the long-term forecasting ability for 750 consecutive trading prices is outstanding. Those conclusions contribute to judging the carbon price characteristics and formulating market regulations.

Development of a head-weighted injury criterion for evaluation of multiple types of AIS 4+ injuries for vulnerable road users.

Vulnerable Road users (VRUs) often suffer multiple fatal head injury types simultaneously in road accidents. In this study, a head-weighted injury criterion (HWIC4) was proposed for assessing the risk of head AIS 4+ injuries considering multiple injury types. Firstly, the kinematic characteristics of VRUs in the 50 in-depth accidents were reconstructed by using multi-body system models, and head injuries were reconstructed using eight head kinematic-based injury criteria and eight brain tissue injury criteria via the THUMS (Ver. 4.0.2) head finite element model. The predictive capability of each injury criterion to predict head AIS 4+ injuries was assessed and four better predictors (HIC15, angular acceleration, coup pressure, and maximum principal strain) were selected. The different head injury types and the weighting parameters for each injury type were taken into account in the development of HWIC4. Finally, the effectiveness and evaluation of HWIC4 for head AIS 4+ injury was validated based on the area under of receiver operating characteristic (AUROC) curve and reconstruction results from 10 additional selected accident cases. The results showed that HWIC4 has a good predictive capability for head AIS 4+ injuries with an AUROC of 0.983, which means that HWIC4 is superior and more reliable than a single head injury criterion. This knowledge further improves the capability of head injury criteria to predict head AIS 4+ injuries.

Aspiration Pneumonia.

Aspiration pneumonia is a lower respiratory tract infection that results from inhalation of foreign material, often gastric and oropharyngeal contents. It is important to distinguish this from a similar entity, aspiration with chemical pneumonitis, as treatment approaches may differ. An evolving understanding of the human microbiome has shed light on the pathogenesis of aspiration pneumonia, suggesting that dysbiosis, repetitive injury, and inflammatory responses play a role in its development. Risk factors for aspiration events involve a complex interplay of anatomical and physiological dysfunctions in the nervous, gastrointestinal, and pulmonary systems. Current treatment strategies have shifted away from anaerobic organisms as leading pathogens. Prevention of aspiration pneumonia primarily involves addressing oropharyngeal dysphagia, a significant risk factor for aspiration pneumonia, particularly among elderly individuals and those with cognitive and neurodegenerative disorders.

Development of Biaryl-Containing Aldo-Keto Reductase 1C3 (AKR1C3) Inhibitors for Reversing AKR1C3-Mediated Drug Resistance in Cancer Treatment.

Aldo-keto reductase 1C3 (AKR1C3) is correlated with tumor development and chemotherapy resistance. The catalytic activity of the enzyme has been recognized as one of the important factors in inducing anthracycline (ANT) resistance in cancer cells. Inhibition of AKR1C3 activity may provide a promising approach to restore the chemosensitivity of ANT-resistant cancers. Herein, a series of biaryl-containing AKR1C3 inhibitors has been developed. The best analogue S07-1066 selectively blocked AKR1C3-mediated reduction of doxorubicin (DOX) in MCF-7 transfected cell models. Furthermore, co-treatment of S07-1066 significantly synergized DOX cytotoxicity and reversed the DOX resistance in MCF-7 cells overexpressing AKR1C3. The potential synergism of S07-1066 over DOX cytotoxicity was demonstrated in vitro and in vivo. Our findings indicate that inhibition of AKR1C3 potentially enhances the therapeutic efficacy of ANTs and even suggests that AKR1C3 inhibitors may serve as effective adjuvants to overcome AKR1C3-mediated chemotherapy resistance in cancer treatment.

Optimising Two-Stage Vacuum Heat Treatment for a High-Strength Micro-Alloyed Steel in Railway Spring Clip Application: Impact on Microstructure and Mechanical Performance.

The heat treatment process is a vital step for manufacturing high-speed railway spring fasteners. In this study, orthogonal experiments were carried out to obtain reliable optimised heat treatment parameters through a streamlined number of experiments. Results revealed that a better comprehensive mechanical performance could be obtained under the following combination of heat treatment parameters: quenching temperature of 850 °C, holding time of 35 min, medium of 12% polyalkylene glycol (PAG) aqueous solution, tempering temperature of 460 °C, and holding time of 60 min. As one of the most important testing criteria, fatigue performance would be improved with increasing strength. Additionally, a high ratio of martensite to ferrite is proven to improve the fatigue limit more significantly. After this heat treatment process, the metallographic microstructure and mechanical properties satisfy the technical requirements for the high-speed railway practical operation. These findings provide a valuable reference for the practical forming process of spring fasteners.

The hepatic GABAergic system promotes liver macrophage M2 polarization and mediates HBV replication in mice.

Macrophages display functional phenotypic plasticity. Hepatitis B virus (HBV) infection induces polarizations of liver macrophages either to M1-like pro-inflammatory phenotype or to M2-like anti-inflammatory phenotype. Gamma-aminobutyric acid (GABA) signaling exists in various non-neuronal cells including hepatocytes and some immune cells. Here we report that macrophages express functional GABAergic signaling components and activation of type A GABA receptors (GABAARs) promotes M2-polarization thus advancing HBV replication. Notably, intraperitoneal injection of GABA or the GABAAR agonist muscimol increased HBV replication in HBV-carrier mice that were generated by hydrodynamical injection of adeno-associated virus/HBV1.2 plasmids (pAAV/HBV1.2). The GABA-augmented HBV replication in HBV-carrier mice was significantly reduced by the GABAAR inhibitor picrotoxin although picrotoxin had no significant effect on serum HBsAg levels in control HBV-carrier mice. Depletion of liver macrophages by liposomal clodronate treatment also significantly reduced the GABA-augmented HBV replication. Yet adoptive transfer of liver macrophages isolated from GABA-treated donor HBV-carrier mice into the liposomal clodronate-pretreated recipient HBV-carrier mice restored HBV replication. Moreover, GABA or muscimol treatment increased the expression of "M2" cytokines in macrophages, but had no direct effect on HBV replication in the HepG2.2.15 cells, HBV1.3-transfected Huh7, HepG2, or HepaRG cells, or HBV-infected Huh7-NTCP cells. Taken together, these results suggest that increasing GABA signaling in the liver promotes HBV replication in HBV-carrier mice by suppressing the immunity of liver macrophages, but not by increasing the susceptibility of hepatocytes to HBV infection. Our study shows that a previously unknown GABAergic system in liver macrophage has an essential role in HBV replication.

Fabrication of a protein-dextran conjugates formed oral nanoemulsion and its application to deliver the essential oil from Alpinia zerumbet Fructus.

The injury of vascular endothelial cells caused by high glucose (HG) is one of the driving factors of vascular complications of diabetes. Oral administration is the most common route of administration for the treatment of diabetes and its vascular complications. Essential oil extracts from Chinese medicine possess potential therapeutic effects on vascular endothelial injury. However, low solubility and volatility of essential oils generally result in poor oral absorption. Development of nanocarriers for essential oils is a promising strategy to overcome the physiological barriers of oral absorption. In this study, a nanoemulsion composed of bovine serum albumin (BSA)-dextran sulfate (DS) conjugate and sodium deoxycholate (SD) was constructed. The nanoemulsions were verified with promoted oral absorption and prolonged circulation time. After the primary evaluation of the nanoemulsion, essential oil from Alpinia zerumbet Fructus (EOFAZ)-loaded nanoemulsion (denoted as EOFAZ@BD5/S) was prepared and characterized. Compared to the free EOFAZ, EOFAZ@BD5/S increased the protective effects on HG-induced HUVEC injury in vitro and ameliorative effects on the vascular endothelium disorder and tunica media fibroelastosis in a T2DM mouse model. Collectively, this study provides a nanoemulsion for the oral delivery of essential oils, which holds strong promise in the treatment of diabetes-induced vascular endothelial injury.

TS-1 Synthesis via Subcrystal Aggregation: Construction of Highly Active Hydrogen-Bonded Titanium Species for Alkene Epoxidation.

The construction and determination of highly active Ti sites comprise one of the most significant challenges in the rational design and synthesis of Ti-containing porous catalysts. The pathway to efficiently build highly catalytically active titanium species remains to be proposed in spite of deliberate post treatments or ambiguous batch composition adjustments. In this study, we developed a bottom-up strategy to construct a TS-1 catalyst with highly active hydrogen-bonded Ti species via subcrystal aggregation crystallization. The microstructure of the hydrogen-bonded Ti species was verified by vacuum FT-IR and 1H MAS SSNMR spectroscopies. Noteworthy features of the hydrogen-bonded Ti species were also revealed, including a pentahedral coordination state and Brønsted acidity, as identified by the UV-Raman, XPS, XAFS, and FT-IR spectra of adsorbed pyridine. Significantly, the hydrogen-bonded Ti species exhibits extraordinary activity in allyl chloride epoxidation (nearly 70% higher than that of traditional Ti species). This study provides a new approach to building highly active Ti sites, which may provide new insights into the design and synthesis of high-performance titanosilicate catalysts.

Dual-targeting of artesunate and chloroquine to tumor cells and tumor-associated macrophages by a biomimetic PLGA nanoparticle for colorectal cancer treatment.

The regimens on colorectal cancer (CRC) are clinically limited due to the ignorance of tumor-supportive microenvironments. To combine the therapeutic effects on both tumor cells growth and immunosuppressive tumor microenvironments (TME), we propose the artesunate (AS) and chloroquine (CQ) combination and develop a poly (d,l-lactide-co-glycolide) (PLGA)-based biomimetic nanoparticle for dual-targeting delivery of the drug combination. Hydroxymethyl phenylboronic acid conjugated PLGA (HPA) is synthesized to form a reactive oxygen species (ROS)-sensitive core of biomimetic nanoparticles. A mannose-modified erythrocyte membrane (Man-EM) obtained by a novel surface modification method is cloaked on the AS and CQ-loaded HPA core to receive a biomimetic nanoparticle-HPA/AS/CQ@Man-EM. It holds a strong promise in inhibiting the proliferation of CRC tumor cells and reversing the phenotypes of TAMs via targeting both tumor cells and M2-like tumor-associated macrophages (TAMs). Verifying in an orthotopic CRC mouse model, the biomimetic nanoparticles showed improved accumulation at tumor tissues and effectively suppressed the tumor growth via both inhibition of tumor cell growth and repolarization of TAMs. Notably, unbalanced distribution to the tumor cells and TAMs is the key to realize the remarkable anti-tumor effects. This work proposed an effective biomimetic nanocarrier for the CRC treatment.

1,8-Cineole ameliorates diabetic retinopathy by inhibiting retinal pigment epithelium ferroptosis via PPAR-γ/TXNIP pathways.

1,8-Cineole, the main component of volatile oil in aromatic plants, has diverse pharmacological properties, including antioxidant, anti-inflammatory, and anti-cancer properties. Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus (DM). Here, we investigated the protective effect of 1,8-cineole on DR and found that 1,8-cineole treatment could alter the expression of several genes in both high glucose (HG)-induced ARPE-19 cells and retinal tissues of DM mice, as well as inhibit ferroptosis. Subsequent investigations into the molecular mechanisms underlying this inhibition revealed that expression of thioredoxin-interacting protein (TXNIP) was significantly upregulated while that of peroxisome proliferator-activated receptor γ (PPAR-γ) was significantly downregulated in HG-induced ARPE-19 cells, and treatment with 1,8-cineole could effectively reverse these changes. Treatment with a PPAR-γ pharmacological agonist (rosiglitazone), alone or combined with 1,8-cineole, significantly inhibited the transcription of TXNIP and ferroptosis in HG-induced ARPE-19 cells. Conversely, pretreatment with GW9662, a PPAR-γ inhibitor, upregulated the transcription and expression of TXNIP in HG-induced ARPE-19 cells; 1,8-cineole failed to reverse this upregulated expression. To explore these relationships, we constructed a PPAR-γ adenovirus shRNA to elucidate the effect of 1,8-cineole on the negative regulation of TXNIP by PPAR-γ. Taken together, the present findings indicate that HG-induced ferroptosis in retinal tissue plays an essential role in the pathogenesis of DR, which can be ameliorated by 1,8-cineole.

Safety and Efficacy of TACE + Lenvatinib in Treating Advanced Hepatocellular Carcinoma: A Systematic Review and Meta- analysis.

BACKGROUND AND AIMS: To compare the efficacy and safety of transarterial chemoembolization (TACE) + lenvatinib (TACE+L) versus lenvatinib (L) monotherapy in the treatment of advanced hepatocellular carcinoma by a meta-analysis. METHODS: PubMed, Embase, the Cochrane Library, CNKI, VIP e-Journals Database, and Wanfang Data were systematically searched to collate literature comparing TACE+L with L alone for the treatment of advanced liver cancer. The literature search, quality assessment, and data extraction were performed independently by two reviewers. The Stata 16 software package was used to process and analyze the data. We assessed heterogeneity using both I2 and the p-value, performed a publication bias assessment, and conducted a sensitivity analysis. RESULTS: Five studies were finally included, including one randomized controlled study and four retrospective studies; these involved a total of 1,167 patients, including 523 patients in the TACE+L combination group and 644 patients in the L monotherapy group. In this meta-analysis, the TACE+L group showed a significantly better objective response rate (ORR) (OR=2.54, 95%CI: 1.34 - 4.80) and disease control rate (DCR) compared to the L monotherapy group (OR=2.68, 95%CI: 1.75 - 4.08). The combined group had significantly improved progression-free survival (PFS) (HR=0.47, 95%CI: 0.40 - 0.56) and overall survival (OS) (HR=0.48, 95%CI: 0.39-0.59). In addition, there was no significant difference found in the overall adverse events of any grade between the two groups (OR=1.13, 95%CI: 0.99 - 1.29). CONCLUSIONS: Compared to L alone, TACE+L treatment resulted in better tumor response, better long-term survival, and was accompanied by controllable adverse events.

Transarterial Chemoembolization plus Apatinib with or without Camrelizumab for the Treatment of Advanced HBV-related Hepatocellular Carcinoma.

AIMS: To compare the effectiveness and safety of transarterial chemoembolization (TACE) combined with apatinib plus camrelizumab (TACE+AC) versus TACE combined with apatinib alone (TACE+A) for patients with advanced HBV-related hepatocellular carcinoma (HBV-HCC). METHODS: The clinical data of patients with HBV-HCC who received either TACE+AC or TACE+A treatment were retrospectively analyzed. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were compared between the two groups. Multivariate Cox proportional hazards model regression analysis was used to identify the independent prognostic factors of OS. RESULTS: Between March 2019 to January 2022, 76 patients were assigned to the TACE+AC group (n = 37) and the TACE+A group (n=39). The median OS and PFS in the TACE+AC group were significantly longer than those in the TACE+A group (OS, 15.4 vs. 11.3 months; p=0.008; PFS, 7.4 vs. 5.1 months; p=0.001) and the ORR and DCR in the TACE + AC group were significantly greater than those in the TACE+A group (ORR, 43.2% vs. 20.5%; p=0.033; DCR, 67.6% vs. 43.6%; p=0.036). There was no significant difference in the incidence of grade ≥3 AEs between the two groups (p=0.483). Multivariate regression analysis identified the treatment modalities, AFP level, and extrahepatic metastasis as independent prognostic factors (p<0.05). CONCLUSION: TACE+AC significantly improved the clinical outcomes of patients with HBV-HCC and elicited relatively controllable AEs.

Analysis of TiO2 Nanolubricant Influence in Micro Deep Drawing of Stainless Steel SUS301.

To improve the quality of products produced from microforming, various nanolubricants have been applied in the field of micromanufacturing in recent years. In this paper, the effects of glycerol-based lubricant containing TiO2 NPs (NPs) on micro deep drawing (MDD) of austenitic stainless steel (ASS) SUS301 were studied, and the lubrication mechanism involved was discussed. The MDD experiments were conducted with the SUS301 foils under dry, 1, 2, and 4 wt% TiO2 NP lubrication conditions. The results show that the use of the TiO2 nanolubricants can significantly improve the quality of the drawn cups in terms of decreased wrinkling and surface roughness. Besides, the concentration of TiO2 NPs influences lubricity by reducing friction during the MDD process. The peak drawing force is the lowest when 2 wt% nanolubricant is applied, which drops to 72.54 N from 77.38 N under dry conditions. The micro cup drawn under 2 wt% TiO2 nanolubricant has the best quality among those obtained under all the lubrication conditions. The lubrication mechanisms are derived from the mending effects of TiO2 NPs and the formation of thin lubricant films associated with the open lubricant pockets (OLPs) and close lubricant pocket (CLPs) theory in the MDD. The CLPs function as reservoirs that retain lubricants to counteract the load pressure, whereas the OLPs lead to lubricant leakage due to the higher flow resistance. It was found that the lubricant film and NPs are insufficient at a low concentration (1 wt%), while the lubrication performance can be enhanced with increased NP concentration. However, there exist apparent agglomerations on the surface of the produced micro cup when using 4 wt% nanolubricant, which greatly deteriorates the lubricant performance in the MDD process. It is concluded that the lubricant containing 2 wt% TiO2 NPs demonstrates the best lubrication performance during the MDD of ASS SUS301.