Oxygen-Propelled Dual-Modular Microneedles with Dopamine-Enhanced RNA Delivery for Regulating Each Stage of Diabetic Wounds.

Diabetic wounds are characterized by the disruption and cessation of essential healing stages, which include hemostasis, inflammation, proliferation, and remodeling. However, traditional treatments for diabetic wounds concentrate on individual stages of the healing process. Herein, this study utilizes mask-mediated sequential polymerization and varied cross-linking techniques to develop dual-modular microneedles (MNs) with fast- and slow-module, exhibiting varying degradation rates tailored for the full spectrum of diabetic wound healing. First, MNs incorporating calcium ions and dopamine synergistically promote rapid hemostasis. Second, fast-module physically cross-linked MNs rapidly D-mannose/dopamine-enhanced tripolyphosphate-quaternized chitosan (mDTC) nanoparticles (NPs) loaded with microRNA-147 (miRNA-147) to manage inflammation and oxidative stress in diabetic wounds. Additionally, dopamine in these NPs enhances their internalization and safeguards miRNA-147 from oxidative stress and RNase degradation. Finally, slow-module chemically cross-linked MNs facilitate the continuous release of deferoxamine (DFO) and dopamine, accelerating angiogenesis and tissue regeneration during the proliferation and remodeling stages. Manganese/dopamine-enhanced calcium peroxide NPs within the MNs initiate a blast-like generation of oxygen bubbles, not only enhancing the delivery of miRNA-mDTC NPs and DFO but also alleviating tissue hypoxia. Consequently, dual-modular MNs are instrumental in promoting rapid and complete healing of diabetic wounds through all stages of healing.

Core-shell ZnO@CoO nitrogen doped nano-composites as highly sensitive electrochemical sensor for organophosphate pesticides detection.

Core-shell ZIF-8@ZIF-67 was synthesized by growing a cobalt-based ZIF-67 on a ZIF-8 seed particle. Herein, through selective etching of the ZIF-8@ZIF-67 core and subsequent direct carbonization, core-shell hollow ZnO@CoO nitrogen-doped nanoporous carbon (HZnO@CoO-NPC) nanocomposites were prepared. HZnO@CoO-NPCs possessed a high nitrogen content, large surface area, high degree of graphitization and excellent electrical conductivity, all of which were attributed to successfully integrating the unique advantages of ZIF-8 and ZIF-67. HZnO@CoO-NPCs were used to assemble acetylcholinesterase (AChE) biosensors for organophosphorus pesticides (OPs) detection. The low detection limit of 2.74 × 10-13 M for chlorpyrifos and 7.6 × 10-15 M for parathion-methyl demonstrated the superior sensing performance. The results showed that the electrochemical biosensor constructed by HZnO@CoO-NPC provided a sensitive and efficient electrochemical strategy for OPs detection.

Design of a Capacitive Tactile Sensor Array System for Human-Computer Interaction.

This paper introduces a novel capacitive sensor array designed for tactile perception applications. Utilizing an all-in-one inkjet deposition printing process, the sensor array exhibited exceptional flexibility and accuracy. With a resolution of up to 32.7 dpi, the sensor array was capable of capturing the fine details of touch inputs, making it suitable for applications requiring high spatial resolution. The design incorporates two multiplexers to achieve a scanning rate of 100 Hz, ensuring the rapid and responsive data acquisition that is essential for real-time feedback in interactive applications, such as gesture recognition and haptic interfaces. To evaluate the performance of the capacitive sensor array, an experiment that involved handwritten number recognition was conducted. The results demonstrated that the sensor accurately captured fingertip inputs with a high precision. When combined with an Auxiliary Classifier Generative Adversarial Network (ACGAN) algorithm, the sensor system achieved a recognition accuracy of 98% for various handwritten numbers from "0" to "9". These results show the potential of the capacitive sensor array for advanced human-computer interaction applications.

A Wearable Visually Impaired Assistive System Based on Semantic Vision SLAM for Grasping Operation.

Because of the absence of visual perception, visually impaired individuals encounter various difficulties in their daily lives. This paper proposes a visual aid system designed specifically for visually impaired individuals, aiming to assist and guide them in grasping target objects within a tabletop environment. The system employs a visual perception module that incorporates a semantic visual SLAM algorithm, achieved through the fusion of ORB-SLAM2 and YOLO V5s, enabling the construction of a semantic map of the environment. In the human-machine cooperation module, a depth camera is integrated into a wearable device worn on the hand, while a vibration array feedback device conveys directional information of the target to visually impaired individuals for tactile interaction. To enhance the system's versatility, a Dobot Magician manipulator is also employed to aid visually impaired individuals in grasping tasks. The performance of the semantic visual SLAM algorithm in terms of localization and semantic mapping was thoroughly tested. Additionally, several experiments were conducted to simulate visually impaired individuals' interactions in grasping target objects, effectively verifying the feasibility and effectiveness of the proposed system. Overall, this system demonstrates its capability to assist and guide visually impaired individuals in perceiving and acquiring target objects.

The porous hollow cobalt-based oxides encapsulated with bimetallic PdAu Nanoparticles of electrochemical biosensor for highly sensitive pesticides detection.

Efficient and portable electrochemical biosensors are received to evaluation of pesticides in the environment, which can make great significance for food safety. In this study, the Co-based oxides with a kind of hierarchical porous hollow and nanocages were constructed, in which the materials (Co3O4-NC) were encapsulated with PdAu nanoparticles (NPs). Due to the unique porous structure, the changeable valence state of cobalt and the synergistic effect of bimetallic PdAuNPs, PdAu@Co3O4-NC possessed excellent electron pathways, and showed more exposed active sites. Accordingly, the porous Co-based oxides have been applied to construct an acetylcholinesterase (AChE) electrochemical biosensor, which showed good performance for organophosphorus pesticides (OPs) detection. The optimum biosensing platform based on nanocomposites was applied to exhibit highly sensitive determination of omethoate and chlorpyrifos, with the relative low detection limit of 6.125 × 10-15M and 5.10 × 10-13M, respectively. And a wide detection range of 6.125 × 10-15∼ 6.125 × 10-6M and 5.10 × 10-13∼ 5.10 × 10-6M for these two pesticides were achieved. Therefore, the PdAu@Co3O4-NC may represent a powerful tool for ultrasensitive sensing of OPs, and have great potential application.

Diagnostic value of procalcitonin and red blood cell distribution width at admission on the prognosis of patients with severe burns: A retrospective analysis.

The plasma procalcitonin (PCT) concentration and red blood cell distribution (RDW) value after severe burns can be used as prognostic indicators, but at present, it is difficult to give consideration to sensitivity and specificity in diagnosing the prognosis of severe burns with a single indicator. This study analysed the diagnostic value of plasma PCT concentration and RDW value at admission on the prognosis of severe burn patients to improve its sensitivity and specificity. A total of 205 patients with severe burns who were treated in the First Affiliated Hospital of Anhui Medical University from November 2017 to November 2022 were retrospectively analysed. The optimal cut-off values of plasma PCT concentration and RDW were analysed and counted through the subject curve (ROC curve). According to the cut-off value, patients were divided into high PCT group and low PCT group, high RDW group and low RDW group. The independent risk factors of severe burns were analysed by single-factor and multiple-factor COX regression. Kaplan-Meier survival was used to analyse the mortality of high PCT group and low PCT group, high RDW group and low RDW group. The area under the curve of plasma PCT concentration and RDW value at admission was 0.761 (95% CI, 0.662-0.860, P < .001), 0.687 (95% CI, 0.554-0.820, P = .003) respectively, and the optimal cut-off values of serum PCT concentration and RDW were 2.775 ng/mL and 14.55% respectively. Cox regression analysis found that age, TBSA, and RDW were independent risk factors for mortality within 90 days after severe burns. Kaplan-Meier survival analysis showed that there was a significant difference in the 90-day mortality rate of severe burns between the PCT ≥ 2.775 ng/mL group and the PCT < 2.775 ng/mL group (log-rank: 24.162; P < .001), with the mortality rate of 36.84% versus 5.49%, respectively. The 90-day mortality rate of severe burns was significantly different between the RDW ≥ 14.55% group and the RDW < 14.55% group (log-rank: 14.404; P < .001), with the mortality rate of 44% versus 12.2% respectively. The plasma PCT concentration and RDW value at admission are both of diagnostic value for the 90-day mortality of severe burns, but the plasma PCT concentration has higher sensitivity and the RDW value has higher specificity. Age, TBSA, and RDW were independent risk factors for severe burns, and then plasma PCT concentration was not independent risk factors.

A stable enzyme sensor via embedding enzymes into zeolitic imidazolate frameworks for pesticide determination.

The stability of biosensors is of significant importance for practical applications, and the natural biomineralization processes in living organisms have inspired us from a new perspective. In this work, acetylcholinesterase (AChE) was embedded into zeolitic imidazolate framework-8 carriers (with negligible cytotoxicity) via biomimetic mineralization, being demonstrated to be a stable strategy for enzyme immobilization. When further coupled with the conductive and catalytic Au nanoparticles, the biocomposites were explored as electrochemical pesticide detection biosensor, which showed favorable analytical performance, and improved stability comparing with other biosensors. This work provides a new strategy for the reasonable design of stable biosensors for different analytes monitoring.

An allosteric PGAM1 inhibitor effectively suppresses pancreatic ductal adenocarcinoma.

Glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) plays a critical role in cancer metabolism by coordinating glycolysis and biosynthesis. A well-validated PGAM1 inhibitor, however, has not been reported for treating pancreatic ductal adenocarcinoma (PDAC), which is one of the deadliest malignancies worldwide. By uncovering the elevated PGAM1 expressions were statistically related to worse prognosis of PDAC in a cohort of 50 patients, we developed a series of allosteric PGAM1 inhibitors by structure-guided optimization. The compound KH3 significantly suppressed proliferation of various PDAC cells by down-regulating the levels of glycolysis and mitochondrial respiration in correlation with PGAM1 expression. Similar to PGAM1 depletion, KH3 dramatically hampered the canonic pathways highly involved in cancer metabolism and development. Additionally, we observed the shared expression profiles of several signature pathways at 12 h after treatment in multiple PDAC primary cells of which the matched patient-derived xenograft (PDX) models responded similarly to KH3 in the 2 wk treatment. The better responses to KH3 in PDXs were associated with higher expression of PGAM1 and longer/stronger suppressions of cancer metabolic pathways. Taken together, our findings demonstrate a strategy of targeting cancer metabolism by PGAM1 inhibition in PDAC. Also, this work provided "proof of concept" for the potential application of metabolic treatment in clinical practice.

[Effects of bifid triple viable on chronic low-grade inflammation in obese mice induced by high fat diet].

OBJECTIVE: To explore the effects and possible mechanism of bifid triple viable(BTV) on chronic low-grade inflammation and insulin resistance in obese mice induced by high fat diet(DIO). METHODS: A total of 18 male C57 BL/6 J mice aged 6 weeks were randomly divided into two groups according to their body weight after adaptive feeding for 2 weeks. Six mice in one group were fed with normal rodent diet as control group. Twelve mice in the other group were fed with high fat diet(60% kcal% fat)(HF). After 8 weeks, it was confirmed that body weight and fasting blood glucose of the mice fed with high fat diet were significantly higher than those of the control group(P<0.001), and then they were randomly divided into HF group and HF+BTV group according to the body weight and fasting blood glucose. Six mice in the HF group continued to be fed with high fat diet. Six mice in the HF+BTV group were fed with high fat diet and administered bifid triple viable suspension by gavage(24 mg/kg body weight), once a day. Mice in the control group and HF group were given equal volume of water as control treatment. After 4 weeks of treatment, blood was collected from tail vein, and the fasting blood glucose was measured by automatic glucose meter. Then the animals were killed and collected blood, distal ileum, liver and epididymal white adipose tissue. The tight junctions between the epithelial cells of ileum mucosa were observed by transmission electron microscopy. Serum endotoxin(also called lipopolysaccharide, LPS) levels were determined by limulus amebocyte lysate assay. Immunohistochemical staining was used to observe the macrophage marker F4/80 in liver and epididymal white adipose tissue. Serum fasting insulin levels, tumor necrosis factor-α(TNF-α), interlukin-6(IL-6) and monocyte chemotactic protein-1(MCP-1) in liver and/or epididymal white adipose tissue were detected by ELISA. The index of homeostasis model assessment of insulin resistance(HOMA-IR) was calculated by formula. RESULTS: Compared with the mice fed with normal rodents diet, the tight junctions between the epithelial cells of ileum mucosa were loose, the levels of serum endotoxin, live TNF-α and IL-6, epididymal white adipose tissue TNF-α, IL-6, MCP-1 were significantly elevated(P<0.05), the number of macrophages increased in liver and epididymal white adipose tissue, fasting glucose, fasting insulin levels and HOMA-IR were significantly up-regulated(P<0.01) in the HF group. In comparison with the HF group, the structures of tight junctions between the epithelial cells of ileum mucosa were normalized, the levels of serum endotoxin, liver TNF-α, IL-6 and epididymal white adipose tissue TNF-α, IL-6, MCP-1 were obviously decreased(P<0.05), the number of macrophages reduced in liver and epididymal white adipocytes, fasting insulin levels and HOMA-IR were significantly down-regulated(P<0.05), but had no effect on fasting blood glucose levels in HF+BTV group. CONCLUSION: Bifid triple viable may protect intestinal mucosa barrier, alleviate metabolic endotoxemia, thus improve chronic low-grade inflammation in liver and adipose tissue, and partially restore insulin sensitivity in DIO mice by regulating gut microbiota.

Optimism and friendship quality as mediators between trait emotional intelligence and life satisfaction in Chinese adolescents: A two-wave longitudinal study.

Using a convenience sample of adolescents (N = 1609; 63.5% female; M age = 16.54), this study explored whether EI predicted adolescent life satisfaction and whether friendship quality and optimism mediated this relationship during the COVID-19 pandemic. The structural equation modeling revealed that EI predicted adolescent life satisfaction, friendship quality, and optimism, friendship quality partially mediated the relationship between EI and life satisfaction, and optimism partially mediated the relationship between EI and friendship quality. These findings prove that psychological or educative approaches focused on EI could increase life satisfaction in adolescents during difficult times such as COVID-19, but EI may be linked with life satisfaction via friendship quality only. Training in optimism approaches and friendship quality enhancement programs could also effectively promote life satisfaction.

Hybrid Transition-Metal Oxide and Nitride@N-Doped Reduced Graphene Oxide Electrodes for High-Performance, Flexible, and All-Solid-State Supercapacitors.

Nanoscale composites for high-performance electrodes employed in flexible, all-solid-state supercapacitors are being developed. A series of binder-free composites, each consisting of a transition bimetal oxide, a metal oxide, and a metal nitride grown on N-doped reduced graphene oxide (rGO)-wrapped nickel foam are obtained by using a universal strategy. Three different transition metals, Co, Mo, and Fe, are separately compounded with nickel ions, which originate from the nickel foam, to form three composites, NiCoO2 @Co3 O4 @Co2 N, NiMoO4 @MoO3 @Mo2 N, and NiFe2 O4 @Fe3 O4 @Fe2 N, respectively. These as-prepared active materials have similar regular variation patterns in their properties, including better conductivity and battery-mimicking pseudocapacitance, which result in their high whole-electrode capacitance performance [2598.3 F g-1 (39.85 F cm-2 ), 3472.6 F g-1 (41.43 F cm-2 ) and 1907.5 F g-1 (3.41 F cm-2 ) for the composites incorporating Co, Mo, and Fe, respectively]. The as-assembled flexible, all-solid-state NiCoO2 @Co3 O4 @Co2 N//KOH/PVA//NiCoO2 @Co3 O4 @Co2 N device can be easily bent and exhibits high energy density and power density of 92.8 Wh kg-1 and 1670.4 W kg-1 , respectively. The universality of this design strategy could allow it to be employed in producing hybrid materials for high-performance energy-storage devices.

Experiment Study for Wrist-Wearable Electro-Tactile Display.

Tactile sensation is a promising information display channel for human beings that involves supplementing or replacing degraded visual or auditory channels. In this paper, a wrist-wearable tactile rendering system based on electro-tactile stimulation is designed for information expression, where a square array with 8 × 8 spherical electrodes is used as the touch panel. To verify and improve this touch-based information display method, the optimal mode for stimulus signals was firstly investigated through comparison experiments, which show that sequential stimuli with consecutive-electrode-in-active mode have a better performance than those with single-electrode-in-active mode. Then, simple Chinese and English characters and 26 English characters' recognition experiments were carried out and the proposed method was verified with an average recognition rate of 95% and 82%, respectively. This wrist-wearable tactile display system would be a new and promising medium for communication and could be of great value for visually impaired people.

An Anisotropic Hydrogel Based on Mussel-Inspired Conductive Ferrofluid Composed of Electromagnetic Nanohybrids.

Anisotropic hydrogels with a hierarchical structure can mimic biological tissues, such as neurons or muscles that show directional functions, which are important factors for signal transduction and cell guidance. Here, we report a mussel-inspired approach to fabricate an anisotropic hydrogel based on a conductive ferrofluid. First, polydopamine (PDA) was used to mediate the formation of PDA-chelated carbon nanotube-Fe3O4 (PFeCNT) nanohybrids and also used as a dispersion medium to stabilize the nanohybrids to form a conductive ferrofluid. The ferrofluid can respond to an orientated magnetic field and be programed to form aligned structures, which were then frozen in a hydrogel network formed via in situ free-radical polymerization and gelation. The resulted hydrogel shows directional conductive and mechanical properties, mimicking an oriented biological tissue. Under external electrical stimulation, the orientated PFeCNT nanohybrids can be sensed by the myoblasts cultured on the hydrogel, resulting in the oriented growth of cells. In summary, the mussel-inspired anisotropic hydrogel with its aligned structural complexity and anisotropic properties together with the cell affinity and tissue adhesiveness is a potent multifunctional biomaterial for mimicking oriented tissues to guide cell proliferation and tissue regeneration.

A Mussel-Inspired Persistent ROS-Scavenging, Electroactive, and Osteoinductive Scaffold Based on Electrochemical-Driven In Situ Nanoassembly.

Conductive polymers are promising for bone regeneration because they can regulate cell behavior through electrical stimulation; moreover, they are antioxidative agents that can be used to protect cells and tissues from damage originating from reactive oxygen species (ROS). However, conductive polymers lack affinity to cells and osteoinductivity, which limits their application in tissue engineering. Herein, an electroactive, cell affinitive, persistent ROS-scavenging, and osteoinductive porous Ti scaffold is prepared by the on-surface in situ assembly of a polypyrrole-polydopamine-hydroxyapatite (PPy-PDA-HA) film through a layer-by-layer pulse electrodeposition (LBL-PED) method. During LBL-PED, the PPy-PDA nanoparticles (NPs) and HA NPs are in situ synthesized and uniformly coated on a porous scaffold from inside to outside. PDA is entangled with and doped into PPy to enhance the ROS scavenging rate of the scaffold and realize repeatable, efficient ROS scavenging over a long period of time. HA and electrical stimulation synergistically promote osteogenic cell differentiation on PPy-PDA-HA films. Ultimately, the PPy-PDA-HA porous scaffold provides excellent bone regeneration through the synergistic effects of electroactivity, cell affinity, and antioxidative activity of the PPy-PDA NPs and the osteoinductivity of HA NPs. This study provides a new strategy for functionalizing porous scaffolds that show great promise as implants for tissue regeneration.

Electrochemical Performance of Free-Standing and Flexible Graphene and TiO2 Composites with Different Conductive Polymers as Electrodes for Supercapacitors.

The advantage of using composite electrode materials for energy storage is, to a large extent, the synergistic role of their components. Our work focuses on the investigation of the interactions of each phase, exploring the patterns found with the change of materials to provide theoretical or experimental foundations for future study. Here, conductive polymers (CPs), including polyaniline (PANi), polypyrrole (PPy), and polythiophene (PTh), as well as reduced graphene oxide (rGO), and TiO2 with the different crystalline phases of anatase and rutile were applied to form a series of free-standing and flexible binary or ternary composite electrodes. The electrochemical behaviors of these composite electrodes are presented. The results indicate that the synergistic improvement in electrochemical performance is due to the incorporation of the different components. CPs significantly increase the current density of these composite films and contribute their pseudocapacitance to improve the specific capacitance, but lead to a decline in cycle stability. After introducing TiO2 , both the specific capacitance and the cycle-stability of rGO-TiO2 -CP were synergistically improved. A CP can magnify the pseudocapacitance behavior of any of the TiO2 crystalline phases, and interactions vary with the specific CP and the specific TiO2 crystalline phase employed. The synergistic effects of the as-prepared composites were theoretically predicted and explored.

Amorphous metal boride as a novel platform for acetylcholinesterase biosensor development and detection of organophosphate pesticides.

The exploration of new materials for modifying electrodes is important to advance electrochemical biosensors. Herein, we demonstrated that amorphous bimetallic boride material (Co-2Ni-B) prepared by a simple and facile aqueous reaction is an efficient matrix to immobilize acetylcholinesterase (AChE) to construct a biosensor for the determination of organophosphate pesticides. The effects of different composition and crystallinity on its electrochemical performance are investigated, and the optimization studies of the biological transducer were also discussed. Under optimal conditions, the fabricated sensor showed good analytical performance for the determination of chlorpyrifos with a low limit of detection (2.83 pM) and a wide linear range (3 pM-300 nM). The proposed biosensor also demonstrated high reproducibility, stability and accuracy. The impressive performance was due to the excellent conductivity and the unique amorphous bimetal-metalloid complex nanostructure. These results introduce a new class of promising materials as a robust platform for biosensor applications.

Ultrathin Wall (1 nm) and Superlong Pt Nanotubes with Enhanced Oxygen Reduction Reaction Performance.

The synthesis of Pt nanotubes catalysts remains a substantial challenge, especially for those with both sub-nanometer wall thickness and micrometer-scale length characteristics. Combining techniques of insulin fibril template with Pd nanowire template, numerous Pt nanotubes with diameter of 5.5 nm, tube-length of several micrometers, and ultrathin wall thickness of 1 nm are assembled. These tubular catalysts with both open ends deliver electrochemical active surface area (ECSA) of 91.43 m2 gpt-1 which results from multiple Pt atoms exposed on the inner and outer surfaces that doubled Pt atoms can participate in catalytic reactions, further with enhanced electrocatalytic performance for oxygen reduction reaction (ORR). The ultrafine Pt nanotubes represent a class of hollow nanostructure with increased Pt-utilization and large ECSA, which is regarded as a type of cost-effective catalysts for ORR.

A Mussel-Inspired Conductive, Self-Adhesive, and Self-Healable Tough Hydrogel as Cell Stimulators and Implantable Bioelectronics.

A graphene oxide conductive hydrogel is reported that simultaneously possesses high toughness, self-healability, and self-adhesiveness. Inspired by the adhesion behaviors of mussels, our conductive hydrogel shows self-adhesiveness on various surfaces and soft tissues. The hydrogel can be used as self-adhesive bioelectronics, such as electrical stimulators to regulate cell activity and implantable electrodes for recording in vivo signals.

Identification of IL-7 as a candidate disease mediator in osteoarthritis in Chinese Han population: a case-control study.

OBJECTIVES: Little is known about the biochemical mediators IL-7 that correlate with the initiation and progression of OA. We performed this study to assess the role of variants of IL-7 in OA susceptibility in the Chinese Han population. METHODS: We performed a retrospective, case-control study in the Chinese Han population from 2013 to 2015. Four single nucleotide polymorphisms were genotyped (using a ligase detection reaction) in 602 patients and 454 controls. Differences between groups were analysed, and association was assessed by the odds ratio (OR) and 95% CI. RESULTS: Among these polymorphisms, rs2583764, rs2583760 and rs6993386 showed no significant association with OA in the Chinese Han population {rs2583764 [P-allele = 0.98651, P-genotype = 0.40392, OR (95% CI): 1.00162 (0.83066, 1.20775)]; rs2583760 [P-allele = 0.384500, P-genotype = 0.58752, OR (95% CI): 0.69859 (0.30996, 1.57449)]; rs6993386 [P-allele = 0.69525, P-genotype = 0.50712, OR (95% CI): 0.96432 (0.80406, 1.15653)]}. However, the results showed that the rs2583759 polymorphism was significantly associated with OA [P-allele = 0.00 P-genotype = 3.86 × 10(-30), OR (95% CI): 0.27794 (0.22407, 0.34476)], even when the 10 000 times permutation was performed (P-allele-permutation < 0.00010, P-genotype-permutation = 0.00010). Haplotype analyses showed A-G-A-C, A-G-A-T and G-G-G-C of rs2583764-rs2583760-rs6993386-rs2583759 were risk factors for OA, both before or after the 10 000 times permutation, indicating IL-7 to be associated with OA. CONCLUSION: There was a significant association between IL-7, especially rs2583759, and OA in the Chinese Han population.

Raltitrexed plus oxaliplatin-based transarterial chemoembolization in patients with unresectable hepatocellular carcinoma.

Raltitrexed has shown efficacy and safety in many tumor types; however, the clinical data on the treatment of hepatocellular carcinoma is rare. In this report, we aim to assess the efficacy and safety of raltitrexed plus oxaliplatin (OXA)-based transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (uHCC). Patients with uHCC were recruited from multi-centers in China and assigned randomly to raltitrexed+OXA-based (n=76), fluorouracil+OXA-based (n=76), and doxorubicin+OXA-based (n=75) TACE treatment. The primary end point was overall survival (OS). Tumor response was assessed using response evaluation criteria in solid tumors (RECIST), modified response evaluation criteria in solid tumors (mRECIST), and European Association for the Study of the Liver criteria (EASL). Safety and toxicity were evaluated using the National Cancer Institute Common Toxicity Criteria. The raltitrexed group showed a better disease control rate evaluated using RECIST (raltitrexed vs. fluorouracil vs. doxorubicin: 96.1 vs. 84.2 vs. 86.7%, P=0.05) and a better overall response rate on the basis of mRECIST (67.1 vs. 47.4 vs. 50.7%, P=0.03) and EASL (67.1 vs. 47.4 vs. 49.3%, P=0.02). The median OS and median progression-free survival (PFS) were higher in the raltitrexed group (median OS: 13.4 vs. 9.6 vs. 8.5 months; median PFS: 6.7 vs 4.9 vs 4.6 months). The most common toxicities included elevated aspartate aminotransferase (78.9 vs. 86.8 vs. 81.3%) and abdominal nonspecific pain (68.4 vs. 81.6 vs. 78.7%). No significant differences were found in the overall number of patients who experienced any toxicity. Raltitrexed plus OXA-based TACE suggested a safe and efficacious regimen in uHCC patients. The results warrant further clinical investigation.