The intervention mechanism of Tanshinone IIA in alleviating neuronal injury induced by HMGB1 or TNF-α-mediated microglial activation.

Tanshinone IIA (Tan IIA), a neuroprotective natural compound extracted from Salvia miltiorrhiza, is used in stroke treatment. However, elucidating Tan IIA's neuroprotective mechanisms remains challenging due to limitations in assessing drug efficacy and biochemical parameters in clinical studies. This study investigated Tan IIA's impact on neuroinflammatory responses and its neuroprotective mechanisms using HMGB1- or TNF-α-stimulated BV2 microglia in a co-culture system with primary neuron cells. The results indicated that Tan IIA significantly reduced microglial activation induced by TNF-α or HMGB1. Concurrently, Tan IIA disrupted the interactions between HMGB1 and toll-like receptor 4 (TLR4), and between TNF-α and TNF receptor 1 (TNFR1), modulating the HMGB1/TLR4/nuclear factor-kappa B (NF-κB) and TNF-α/TNFR1/NF-κB signaling pathways and related protein expressions. Moreover, co-culture experiments showed that neuronal apoptosis induced by microglial activation was reversed by Tan IIA. In conclusion, Tan IIA provides neuroprotection by modulating signaling pathways in microglia, thus preventing neuronal apoptosis. This study offers new insights into therapeutic targets for ischemic stroke.

Enhancing terminal erythroid differentiation in human embryonic stem cells through TRIB3 overexpression.

Tribbles pseudokinase 3 (TRIB3) expression significantly increases during terminal erythropoiesis in vivo. However, we found that TRIB3 expression remained relatively low during human embryonic stem cell (hESC) erythropoiesis, particularly in the late stage, where it is typically active. TRIB3 was expressed in megakaryocyte-erythrocyte progenitor cells and its low expression was necessary for megakaryocyte differentiation. Thus, we proposed that the high expression during late stage of erythropoiesis could be the clue for promotion of maturation of hESC-derived erythroid cells. To our knowledge, the role of TRIB3 in the late stage of erythropoiesis remains ambiguous. To address this, we generated inducible TRIB3 overexpression hESCs, named TRIB3tet-on OE H9, based on a Tet-On system. Then, we analyzed hemoglobin expression, condensed chromosomes, organelle clearance, and enucleation with or without doxycycline treatment. TRIB3tet-on OE H9 cells generated erythrocytes with a high proportion of orthochromatic erythroblast in flow cytometry, enhanced hemoglobin and related protein expression in Western blot, decreased nuclear area size, promoted enucleation rate, decreased lysosome and mitochondria number, more colocalization of LC3 with LAMP1 (lysosome marker) and TOM20 (mitochondria marker) and up-regulated mitophagy-related protein expression after treatment with 2 µg/mL doxycycline. Our results showed that TRIB3 overexpression during terminal erythropoiesis may promote the maturation of erythroid cells. Therefore, our study delineates the role of TRIB3 in terminal erythropoiesis, and reveals TRIB3 as a key regulator of UPS and downstream mitophagy by ensuring appropriate mitochondrial clearance during the compaction of chromatin.

[Chemical profiling of Xiaochaihu Granules and characterization of absorbed components in rat plasma after oral administration].

The chemical components of Xiaochaihu Granules and absorbed components in rats after oral administration were identified by using ultra performance liquid chromatography-quadrupole orbitrap mass spectrometry(UPLC-Q-Exactive-Orbitrap-MS)and UPLC-triple quadrupole mass spectrometry(UPLC-MS/MS). Separation was performed on a CORTECS UPLC C~+_(18)(2.1 mm×100 mm, 1.6 µm)column with gradient elution using acetonitrile-0.1% formic acid aqueous solution as the mobile phase. Data on the chemical components were collected in positive and negative ion modes and identified based on the retention time, precise molecular weight, fragment ion information in comparison with the reference substance, and literature report. The rat fever model was established by subcutaneous injection of dry yeast. Subsequently, the normal and model rats received oral administration of Xiaochaihu Granules. Blood samples were taken from the orbital vein at different time points after administration, and the plasma was isolated for scanning and identification of absorbed components using the multi reaction monitoring mode(MRM).A total of 112 chemical components were identified in Xiaochaihu Granules, including 63 flavonoids, 31 saponins, 6 organic acids, 4 phenylpropanoids, 3 amino acids and 5 other compounds. Additionally, 18 prototypical components were identified in rat plasma. This study lays the foundation for further study of the therapeutic material and quality control of Xiaochaihu Granules.

PROTAC-mediated vimentin degradation promotes terminal erythroid differentiation of pluripotent stem cells.

BACKGROUND: Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), can undergo erythroid differentiation, offering a potentially invaluable resource for generating large quantities of erythroid cells. However, the majority of erythrocytes derived from hPSCs fail to enucleate compared with those derived from cord blood progenitors, with an unknown molecular basis for this difference. The expression of vimentin (VIM) is retained in erythroid cells differentiated from hPSCs but is absent in mature erythrocytes. Further exploration is required to ascertain whether VIM plays a critical role in enucleation and to elucidate the underlying mechanisms. METHODS: In this study, we established a hESC line with reversible vimentin degradation (dTAG-VIM-H9) using the proteolysis-targeting chimera (PROTAC) platform. Various time-course studies, including erythropoiesis from CD34+ human umbilical cord blood and three-dimensional (3D) organoid culture from hESCs, morphological analysis, quantitative real-time PCR (qRT-PCR), western blotting, flow cytometry, karyotyping, cytospin, Benzidine-Giemsa staining, immunofluorescence assay, and high-speed cell imaging analysis, were conducted to examine and compare the characteristics of hESCs and those with vimentin degradation, as well as their differentiated erythroid cells. RESULTS: Vimentin expression diminished during normal erythropoiesis in CD34+ cord blood cells, whereas it persisted in erythroid cells differentiated from hESC. Depletion of vimentin using the degradation tag (dTAG) system promotes erythroid enucleation in dTAG-VIM-H9 cells. Nuclear polarization of erythroblasts is elevated by elimination of vimentin. CONCLUSIONS: VIM disappear during the normal maturation of erythroid cells, whereas they are retained in erythroid cells differentiated from hPSCs. We found that retention of vimentin during erythropoiesis impairs erythroid enucleation from hPSCs. Using the PROTAC platform, we validated that vimentin degradation by dTAG accelerates the enucleation rate in dTAG-VIM-H9 cells by enhancing nuclear polarization.

Associations between Changes in Exposure to Air Pollutants due to Relocation and the Incidence of 14 Major Disease Categories and All-Cause Mortality: A Natural Experiment Study.

BACKGROUND: Though observational studies have widely linked air pollution exposure to various chronic diseases, evidence comparing different exposures in the same people is limited. This study examined associations between changes in air pollution exposure due to relocation and the incidence and mortality of 14 major diseases. METHODS: We included 50,522 participants enrolled in the UK Biobank from 2006 to 2010. Exposures to particulate matter with a diameter ≤2.5µm (PM2.5), particulate matter with a diameter ≤10µm (PM10), nitrogen oxides (NOx), nitrogen dioxide (NO2), and sulfur dioxide (SO2) were estimated for each participant based on their residential address and relocation experience during the follow-up. Nine exposure groups were classified based on changes in long-term exposures due to residential mobility. Incidence and mortality of 14 major diseases were identified through linkages to hospital inpatient records and death registries. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incidence and mortality of the 14 diseases of interest. RESULTS: During a median follow-up of 12.6 years, 29,869 participants were diagnosed with any disease of interest, and 3,144 died. Significantly increased risk of disease and all-cause mortality was observed among individuals who moved from a lower to higher air polluted area. Compared with constantly low exposure, moving from low to moderate PM2.5 exposure was associated with increased risk of all 14 diseases but not for all-cause mortality, with adjusted HRs (95% CIs) ranging from 1.18 (1.05, 1.33) to 1.48 (1.30, 1.69); moving from low to high PM2.5 areas increased risk of all 14 diseases: infections [1.37 (1.19, 1.58)], blood diseases [1.57 (1.34, 1.84)], endocrine diseases [1.77 (1.50, 2.09)], mental and behavioral disorders [1.93 (1.68, 2.21)], nervous system diseases [1.51 (1.32, 1.74)], ocular diseases [1.76 (1.56, 1.98)], ear disorders [1.58 (1.35, 1.86)], circulatory diseases [1.59 (1.42, 1.78)], respiratory diseases [1.51 (1.33, 1.72)], digestive diseases [1.74 (1.58, 1.92)], skin diseases [1.39 (1.22, 1.58)], musculoskeletal diseases [1.62 (1.45, 1.81)], genitourinary diseases [1.54 (1.36, 1.74)] and cancer [1.42 (1.24, 1.63)]. We observed similar associations for PM10 and SO2 with 14 diseases (but not with all-cause mortality); increases in NO2 and NOx were positively associated with 14 diseases and all-cause mortality. CONCLUSIONS: This study supports potential associations between ambient air pollution exposure and morbidity as well as mortality. Findings also emphasize the importance of maintaining consistently low levels of air pollution to protect the public's health. https://doi.org/10.1289/EHP14367.

Prognostic Value of Estimated Glucose Disposal Rate and Systemic Immune-Inflammation Index in Non-Diabetic Patients Undergoing PCI for Chronic Total Occlusion.

BACKGROUND AND OBJECTIVES: Chronic total occlusion (CTO) is a complex lesion of coronary artery disease (CAD) with a detection rate of approximately 25% on coronary angiography. CTO patients generally experience poor quality of life and prognosis. This study aims to evaluate the association between the estimated glucose disposal rate (eGDR), a surrogate marker for insulin resistance (IR), and the prognosis of CTO PCI patients, as well as to investigate the potential role of the systemic immune-inflammation index (SII) in this process. METHODS: We retrospectively included 1482 non-diabetic patients who underwent successful CTO PCI at Anzhen Hospital between January 2018 and December 2021. The primary endpoint was major adverse cardiovascular events (MACEs). Clinical characteristics, biochemical markers, and interventional records were collected, and the eGDR and SII were calculated. Cox regression, restricted cubic splines (RCSs), receiver operating characteristic (ROC) analysis, and Kaplan-Meier curves were used to assess associations. RESULTS: MACEs occurred in 158 patients (10.67%). Patients with MACEs had lower eGDR and higher SII levels. A high eGDR significantly reduced MACE risk (Q4 vs. Q1: HR 0.06, 95% CI 0.03-0.12), while a high SII increased it (Q4 vs. Q1: HR 3.32, 95% CI 1.78-6.33). The combination of low eGDRs and high SIIs predicted the highest MACE risk (HR 4.36, 95% CI 2.71-6.01). The SII partially mediated the relationship between eGDR and MACEs. CONCLUSIONS: A low eGDR and high SII are significant predictors of poor prognosis in non-diabetic CTO PCI patients. Combining the eGDR and the SII provides a comprehensive assessment for better predicting cardiovascular outcomes.

Promoting medication compliance in epileptic children: a cross sectional survey.

BACKGROUND: Compliance with medication is crucial for the favorable prognosis of children with epilepsy. The objective of this study was to assess the determinants of medication compliance and to construct a predictive model for the risk of non-compliance among pediatric epilepsy patients. METHODS: The study included children diagnosed with epilepsy and treated at our hospital between February 1 and September 30, 2023. We evaluated the demographic characteristics and medication compliance profiles of these patients. The predictive model's performance was assessed using the receiver operating characteristic (ROC) curve to determine its sensitivity and specificity. RESULTS: A total of 168 children with epilepsy were analyzed. The rate of non-compliance with medication was found to be 32.74% (55 out of 168). Logistic regression identified the educational level of parents (OR = 2.844, 95% CI: 2.182-3.214), monthly household income (OR = 1.945, 95% CI: 1.203-2.422), the number of medications taken (OR = 1.883, 95% CI: 1.314-2.201), and the level of epilepsy knowledge received (OR = 2.517, 95% CI: 1.852-3.009) as significant factors influencing non-compliance (all p < 0.05). A total score threshold of 6 was set for the predictive model. The area under the ROC curve was 0.713 (95% CI: 0.686-0.751), indicating the model's discriminative ability. CONCLUSIONS: The compliance to medication regimens among children with epilepsy is suboptimal and influenced by a multitude of factors. This study has developed a predictive model for medication compliance, which could serve as a valuable tool for clinical assessment and intervention planning regarding medication compliance in pediatric epilepsy patients.

Straw Tar Epoxy Resin for Carbon Fiber-Reinforced Plastic: A Review.

The massive consumption of fossil fuels has led to the serious accumulation of carbon dioxide gas in the atmosphere and global warming. Bioconversion technologies that utilize biomass resources to produce chemical products are becoming widely accepted and highly recognized. The world is heavily dependent on petroleum-based products, which may raise serious concerns about future environmental security. Most commercially available epoxy resins (EPs) are synthesized by the condensation of bisphenol A (BPA), which not only affects the human endocrine system and metabolism, but is also costly to produce and environmentally polluting. In some cases, straw tar-based epoxy resins have been recognized as potential alternatives to bisphenol A-based epoxy resins, and are receiving increasing attention due to their important role in overcoming the above problems. Using straw tar and lignin as the main raw materials, phenol derivatives were extracted from the middle tar instead of bisphenol A. Bio-based epoxy resins were prepared by replacing epichlorohydrin with epoxylated lignin to press carbon fiber sheets, which is a kind of bio-based fine chemical product. This paper reviews the research progress of bio-based materials such as lignin modification, straw pyrolysis, lignin epoxidation, phenol derivative extraction, and synthesis of epoxy resin. It improves the performance of carbon fiber-reinforced plastic (CFRP) while taking into account the ecological and environmental protection, so that the epoxy resin is developed in the direction of non-toxic, harmless and high-performance characteristics, and it also provides a new idea for the development of bio-based carbon fibers.

Stereoselective Vinylic C-H Addition via Metallaphotoredox Migration.

Geometrically defined allylic alcohols with SE, SZ, RE and RZ stereoisomers serve as valuable intermediates in synthetic chemistry, attributed to the stereoselective transformations enabled by the alkenyl and hydroxyl functionalities. When an ideal scenario presents itself with four distinct stereoisomers as potential products, the simultaneous control vicinal stereochemistry in a single step would offer a direct pathway to any desired stereoisomer. Here, we unveil a metallaphotoredox migration strategy to access stereodefined allylic alcohols through vinylic C-H activation with aldehydes. This method harnesses a chiral nickel catalyst in concert with a photocatalyst to enable a 1,4-Ni migration by using readily accessible 2-vinyl iodoarenes as starting materials. The efficacy of this methodology is highlighted by the precise construction of all stereoisomers of allylic alcohols bearing analogous substituents and the efficient synthesis of key intermediates en route to Myristinin family. Experimental and computational studies have shed light on pivotal aspects including the synergy of metal catalysis and photocatalysis, the driving forces behind the migration, and the determination of absolute configuration in the C-H addition process.

Risk factors for acute pancreatitis post percutaneous transhepatic biliary stenting in patients with distal malignant obstruction.

Background: Percutaneous transhepatic biliary stenting (PTBS) is an effective treatment for distal malignant biliary obstruction (MBO). Postoperative acute pancreatitis (AP) is a dangerous complication of this procedure. This study sought to investigate the risk factors for AP after PTBS. Methods: A total of 463 patients who underwent PTBS to treat suspected MBO from October 2012 to October 2021 were enrolled in this retrospective study. Among them, 26 individuals met the diagnostic criteria for postoperative pancreatitis following PTBS. The incidence of AP at 1 month postoperatively was recorded and analyzed. Several risk factors for AP were analyzed, and the odds ratios (ORs) were calculated by univariate and multivariate logistic analyses. Results: The incidence of AP after PTBS was 10.88% (26/239). The results of the multivariate analyses showed that repeated bile duct hemorrhage (OR =14.370, P=0.0001), intraoperative dilation (OR =7.848, P=0.0003), an operation time >50 min (OR =5.783, P=0.0009), and previous endoscopic intervention (OR =5.468, P=0.0021) were correlated with a high incidence of AP, while sex, age, time to biliary obstruction, body mass index, Eastern Cooperative Oncology Group score, previous anticancer treatments, forceps biopsy, obstruction length, stent size, contrast volume, operators, 125I strand placement, and blood parameters were not significantly correlated with AP (all P>0.05). Conclusions: A long operation time, intraoperative dilation, repeated bile duct hemorrhage, and previous endoscopic intervention were independent risk factors for AP. These factors should be considered by clinicians in future practice.

The fabrication of ZIF-L derived ZnS/MoS2@NC anode materials for remarkable lithium-ion storage.

The enhancement of electrochemical performance in lithium-ion batteries can be achieved through the incorporation of MoS2 with carbon materials and various metal sulfides. In this investigation, a MoS2/ZnS heterostructure was devised incorporating a two-dimensional nitrogen-doped carbon nanosheet (NC) backbone. The synthesis of ZnMo-ZIF-L precursors was achieved by introducing a Mo source in a 1:1 molar ratio during ZIF-L synthesis. Subsequent to high-temperature carbonization and vulcanization treatment, ZnS/MoS2@NC composite materials were successfully synthesized. Compared to the unvulcanized ZnO/MoO3@NC and MoS2 samples, the ZnS/MoS2@NC composite exhibits remarkable lithium storage performance. At a current density of 500 mA g-1, the initial discharge specific capacity is 2547 mAh g-1, with an initial charge specific capacity of 1674 mAh g-1, resulting in a first Coulombic efficiency of 65.76%. Furthermore, this composite material demonstrates optimal rate capabilities and a significant pseudocapacitance contribution. The nitrogen-doped carbon framework effectively mitigates volume effects, while the heterostructural design provides more active sites for lithium ions, thereby enhancing lithium storage performance.

Structural basis for the ligand recognition and G protein subtype selectivity of kisspeptin receptor.

Kisspeptin receptor (KISS1R), belonging to the class A peptide-GPCR family, plays a key role in the regulation of reproductive physiology after stimulation by kisspeptin and is regarded as an attractive drug target for reproductive diseases. Here, we demonstrated that KISS1R can couple to the Gi/o pathway besides the well-known Gq/11 pathway. We further resolved the cryo-electron microscopy (cryo-EM) structure of KISS1R-Gq and KISS1R-Gi complexes bound to the synthetic agonist TAK448 and structure of KISS1R-Gq complex bound to the endogenous agonist KP54. The high-resolution structures provided clear insights into mechanism of KISS1R recognition by its ligand and can facilitate the design of targeted drugs with high affinity to improve treatment effects. Moreover, the structural and functional analyses indicated that conformational differences in the extracellular loops (ECLs), intracellular loops (ICLs) of the receptor, and the "wavy hook" of the Gα subunit may account for the specificity of G protein coupling for KISS1R signaling.

Arctiin Mitigates Neuronal Injury by Modulating the P2X7R/NLPR3 Inflammasome Signaling Pathway.

Depression, recognized globally as a primary cause of disability, has its pathogenesis closely related to neuroinflammation and neuronal damage. Arctiin (ARC), the major bioactive component of Fructus arctii, has various pharmacological activities, such as anti-inflammatory and neuroprotective effects. Building on previous findings that highlighted ARC's capability to mitigate depression by dampening microglial hyperactivation and thereby reducing neuroinflammatory responses and cortical neuronal damage in mice, the current study delves deeper into ARC's therapeutic potential by examining its impact on hippocampal neuronal damage in depression. Utilizing both chronic unpredictable mild stress (CUMS)-induced depression model in mice and corticosterone (CORT)-stimulated PC12 cell model of neuronal damage, the techniques including Nissl staining, immunohistochemistry, western blotting, ELISA, lactate dehydrogenase assays, colony formation assays, immunofluorescence staining and molecular docking were employed to unravel the mechanisms behind ARC's neuroprotective effects. The findings revealed that ARC not only mitigates hippocampal neuropathological damage and reduces serum CORT levels in CUMS-exposed mice but also enhances cell activity while reducing lactate dehydrogenase release in CORT-stimulated PC12 cells. ARC attenuated neuroinflammatory responses and neuronal apoptosis by inhibiting the overactivation of the P2X7 receptor (P2X7R)/NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome signaling pathway, similar to the effect of A438079 (P2X7R antagonist). Interestingly, pretreatment with A438079 blocked the neuroprotective effect of ARC. Computer modeling predicted that both ARC and A438079 have strong binding with P2X7R and they have the same binding site. These results suggested that ARC may exert a neuroprotective role by binding to P2X7R, thereby inhibiting the P2X7R/NLRP3 inflammasome signaling pathway.

Tertiary lymphoid structures as potential biomarkers for cancer prediction and prognosis.

Tertiary lymphoid structures (TLSs) are ectopic lymphocyte aggregates formed in non-lymphoid tissues, including cancers, and are loci for the generation of in situ anti-tumor immune responses, which play a crucial role in cancer control. The state of TLS presence in cancer and its composition can significantly impact the treatment response and prognosis of patients. TLSs have the potential to serve as predictive and prognostic biomarkers for cancer. However, the mechanisms underlying TLS formation in cancer and how the essential components of TLSs affect cancer are not fully understood. In this review, we summarized TLS formation in cancer, the value of the TLS in different states of existence, and its key constituents for cancer prediction and prognosis. Finally, we discussed the impact of cancer treatment on TLSs.

Coixol mitigates Toxoplasma gondii infection-induced liver injury by inhibiting the Toxoplasma gondii HSP70/TLR4/NF-κB signaling pathway in hepatic macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: Coix seed, the dry mature seed kernel of the gramineous plant coix (Coix lacryma-jobi L. var. ma-yuen Stapf), is widely consumed as a traditional Chinese medicine and functional food in China and South Korea. We have previously demonstrated the protective effect of coixol, a polyphenolic compound extracted from coix, against Toxoplasma gondii (T. gondii) infection-induced lung injury. However, the protective effect of coixol on hepatic injury induced by T. gondii infection have not yet been elucidated. AIM OF THE STUDY: This study explores the impact of coixol on T. gondii infection-induced liver injury and elucidates the underlying molecular mechanisms. MATERIALS AND METHODS: Female BALB/c mice and Kupffer cells (KCs) were employed to establish an acute T. gondii infection model in vivo and an inflammation model in vitro. The study examined coixol's influence on the T. gondii-derived heat shock protein 70 (T.g.HSP70)/toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling pathway in T. gondii-infected liver macrophages. Furthermore, a co-culture system of KCs and NCTC-1469 hepatocytes was developed to observe the impact of liver macrophages infected with T. gondii on hepatocyte injury. RESULTS: Coixol notably inhibited the proliferation of tachyzoites and the expression of T.g.HSP70 in mouse liver and KCs, and attenuated pathological liver injury. Moreover, coixol decreased the production of high mobility group box 1, tumor necrosis factor-α, and inducible nitric oxide synthase by suppressing the TLR4/NF-κB signaling pathway in vitro and in vivo. Coixol also mitigated KCs-mediated hepatocyte injury. CONCLUSIONS: Coixol protects against liver injury caused by T. gondii infection, potentially by diminishing hepatocyte injury through the suppression of the inflammatory cascade mediated by the T.g.HSP70/TLR4/NF-κB signaling pathway in KCs. These findings offer new perspectives for developing coixol as a lead compound for anti-T. gondii drugs.

Regulating the Grain-Growth Surface for Efficient Near-Infrared Perovskite Light-Emitting Diodes.

Metal halide perovskites hold great potential for next-generation light-emitting diodes (PeLEDs). Despite significant progress, achieving high-performance PeLEDs hinges on optimizing the interface between the perovskite crystal film and the charge transport layers, especially the buried interface, which serves as the starting point for perovskite growth. Here, we develop a bottom-up perovskite film modulation strategy using formamidine acetate (FAAc) to enhance the buried interface. This multifaceted approach facilitates the vertical-oriented growth of high-quality perovskites with minimized defects. Meanwhile, the in situ deprotonation between FA+ and ZnO could eliminate the hydroxyl (-OH) defects and modulate the energy level of ZnO. The resulting FAPbI3-PeLED exhibits a champion EQE of 23.84% with enhanced operational stability and suppressed EQE roll-off. This strategy is also successfully extended to other mixed-halide PeLEDs (e.g., Cs0.17FA0.83Pb(I0.75Br0.25)3), demonstrating its versatility as an efficient and straightforward method for enhancing the PeLEDs' performance.

Efficacy and Safety of TACE Combined with Regorafenib versus TACE Combined with Camrelizumab in Hepatocellular Carcinoma With Untreatable Progression After TACE Combined with Sorafenib Therapy: A Case Control Study.

PURPOSE: To evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with regorafenib (hereafter, TACE-regorafenib) or camrelizumab (hereafter, TACE-camrelizumab) for treating hepatocellular carcinoma (HCC) with untreatable progression after TACE and sorafenib therapy. METHODS: The medical records of patients with HCC who received TACE-regorafenib or TACE-camrelizumab between September 2018 and December 2023 were retrospectively evaluated. Therapeutic response, overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were compared between the two groups. RESULTS: A total of 76 patients were enrolled in this study, with 41 and 35 patients in the TACE-regorafenib and TACE-camrelizumab groups, respectively. The objective response rates in the TACE-regorafenib and TACE-camrelizumab groups were 9.8% and 8.6%, respectively, with no statistically significant difference between the two groups (P = 0.859). Similarly, there was no statistically significant difference in disease control rates between the two groups (61.0% vs 68.6%, P = 0.838). The median OS was 11 months in the TACE-regorafenib group and 10 months in the TACE-camrelizumab group, with no significant difference between the two groups (P = 0.348). The TACE-regorafenib group had a median PFS of 7 months, which was significantly longer than that of the TACE-camrelizumab group (4 months, P = 0.004). There was no significant difference in the incidence of AEs between the two groups (P = 0.544). CONCLUSIONS: TACE-regorafenib was safe, well-tolerated, and showed promising efficacy in patients with sorafenib-refractory advanced HCC, whereas TACE-camrelizumab demonstrated similar survival benefits.

Effects of epidural anesthesia and analgesia on the incidence of chronic pain after thoracoscopic lung surgery: A retrospective cohort study.

Objective: Chronic postoperative pain (CPSP) is common after thoracic surgery, even after the less invasive video-assisted thoracoscopic surgery (VATS). This study investigated the effect of thoracic epidural anesthesia (TEA) on the development of CPSP. Materials: We retrospectively analyzed the data of patients who underwent VATS at our center between 2020 and 2022. The enrolled patients were divided into the epidural block (EPI) and patient-controlled intravenous analgesia (PCIA) groups. A telephone questionnaire was used to collect information regarding CPSP, which was defined as a numerical rating scale (VAS) score ≥1 at 3 or 6 months postoperatively. Additionally, statistical analyses were performed to identify the risk factors for CPSP in the two groups. Results: Overall, 894 patients completed the follow-up interviews at 3 and 6 months, with 325 and 569 patients in the PCIA and EPI groups, respectively. The incidence rates of CPSP in the PCIA group at 3 and 6 months were 16.9 % (95 % confidence interval [CI]: 9.3-32.7 %) and 13.5 % (95 % CI: 8.7-33.4 %), and 10.3 % (95 % CI: 8.1-30.5 %) and 3.6 % (95 % CI: 3.5-21.5 %) in EPI group, respectively. The incidence of CPSP at 3 months (P = 0.0048) and 6 months (P < 0.005) was statistically significant in both groups. Age and lymph node dissection were significantly associated with CPSP. Conclusions: Compared to PCIA, TEA was associated with a lower incidence of CPSP after VATS, and should be considered an important part of the analgesia regimen for patients with VATS.

Radiofrequency-responsive black phosphorus nanogel crosslinked with cisplatin for precise synergy in multi-modal tumor therapies.

Radiofrequency-responsive nanoparticles (RFNPs) have drawn increasingly attentions as RF energy absorbing antenna to enhance antitumor efficacy of radiofrequency ablation (RFA). However, it remains a huge challenge for inorganic RFNPs to precisely synergize RFA with other antitumor modes in a clinically acceptable way on bio-safety and bio-compatibility. In this work, RF-responsive black phosphorus (BP) nanogel (BP-Pt@PNA) was successfully fabricated by crosslinking coordination of cisplatin with BP and temperature sensitive polymer PNA. BP-Pt@PNA exhibited strong RF-heating effect and RF-induced pulsatile release of cisplatin. Under RF irradiation, BP-Pt@PNA exhibited cytotoxic enhancement on 4T1 cells. By the synergistic effect of BP and cisplatin, BP-Pt@PNA achieved RF-stimulated systemic immune effect, thus induced enhance suppression on tumor growth and metastasis. Moreover, BP-Pt@PNA realized long-term drug retention in tumor and favorable embolization to tumor-feeding arteries. With high drug loading capacity and favorable bio-safety and bio-degradability, BP-Pt@PNA is expected as an ideal RFNP for precisely synergizing RFA with other antitumor modes in clinical application.

Preparation, characterization, antimicrobial evaluation, and grape preservation applications of polyvinyl alcohol/gelatin composite films containing zinc oxide@quaternized chitosan nanoparticles.

This study employed a precipitation method to synthesize zinc oxide@quaternised chitosan nanoparticles (ZnO@QAC NPs) containing different concentrations of zinc oxide, namely ZnO@QAC-2, ZnO@QAC-4, and ZnO@QAC-6. Subsequently, these nanoparticles were incorporated into matrices consisting of gelatine (Gn) and polyvinyl alcohol (PVA) separately, which were prepared by casting to form a biodegradable film. We assessed the physicochemical properties of ZnO@QAC NPs and physicochemical characteristics, antioxidant properties, antimicrobial activity and grape preservation efficacy of the film. Compared to the control group, the films showed a reduction in water vapor permeability by >9.38 %, an increase in tensile strength by over 51.95 %, over 70 % scavenging of ABTS free radicals, and good biocompatibility. Additionally, the antimicrobial activity of the films containing ZnO@QAC-6 increased by 37.6 %. In the grape preservation experiment, the weight loss of grapes wrapped in ZnO@QAC-2 film was reduced by 40.13 % on day 15 compared to unwrapped grapes. These results demonstrate that ZnO@QAC/PVA/Gn films have considerable potential for food packaging applications.