Efficacy and safety of camrelizumab plus apatinib in patients with advanced esophageal squamous cell carcinoma previously treated with immune checkpoint inhibitors (CAP 02 Re-challenge): A single-arm, phase II study.

BACKGROUND: With the increasing use of immune checkpoint inhibitors (ICIs) in advanced esophageal squamous cell carcinoma (ESCC), there remains an unmet need for options to address disease progression after prior ICIs. This single-arm phase II study evaluated the efficacy and safety of re-challenge with camrelizumab plus apatinib in patients with advanced ESCC who were previously treated with ICIs. METHODS: This study enrolled patients aged 18-75 years with unresectable locally advanced, locally recurrent, or distant metastatic ESCC who received prior ICIs. Patients received intravenous camrelizumab 200 mg every 2 weeks and oral apatinib 250 mg daily until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was the investigator-assessed confirmed objective response rate (ORR). RESULTS: Between September 1, 2021 and March 29, 2023, 49 eligible patients were enrolled and received treatment. Among the 49 patients, the confirmed ORR was 10.2 % (95 % CI 3.4-22.2), the disease control rate (DCR) was 69.4 % (54.6-81.7), the median progression-free survival (PFS) was 4.6 months (95 % CI 3.8-6.5) and overall survival (OS) was 7.5 months (5.5-13.6). Grade ≥ 3 treatment-related adverse events occurred in 17 patients (34.7 %). No treatment-related deaths occurred. CONCLUSIONS: This study showed that the confirmed ORR was modest and did not reach clinically meaningful improvement for patients with ESCC who were previously treated with ICIs, with a manageable safety profile.

Hydrogen attenuates ischaemia-reperfusion injury in skeletal muscles post-limb replantation by activating the NRF2/HO-1 signalling pathway to reduce BAX expression.

Background: Ischaemia-reperfusion injury (IRI) is a critical complication post-limb replantation. The oxidative stress and cellular apoptosis due to IRI considerably hinder the healing process. This study aimed to investigate the modulatory effects of pre-perfusion with hydrogen-rich heparin sodium on the nuclear factor erythroid 2-related factor 2 (NRF2)/haeme oxygenase-1 (HO-1) pathway and its potential mechanisms in mitigating skeletal muscle IRI post-limb replantation. Methods: Forty healthy Sprague-Dawley rats (250-300 g) were classified into five groups (n = 8 each): normal control, IRI + heparin sodium pre-perfusion (heparin group), IRI + hydrogen-rich heparin sodium pre-perfusion (hydrogen-rich heparin group), IRI + hydrogen-rich heparin sodium pre-perfusion + NRF2 inhibitor (hydrogen-rich heparin + all-trans retinoic acid [ATRA] group), and IRI + heparin sodium pre-perfusion + NRF2 inhibitor (heparin + ATRA group). The activation of the NRF2/HO-1 pathway in skeletal muscle IRI was evaluated based on HO-1 expression using western blotting and immunofluorescence. Furthermore, haematoxylin and eosin staining and transmission electron microscopy were employed to determine the histopathological characteristics. Additionally, superoxide dismutase and malondialdehyde levels in skeletal muscle tissue were measured to assess antioxidant capacity and the degree of oxidative stress damage. Tissue hypoxia was assessed based on hypoxia-inducible factor 1-alpha expression, whereas apoptosis markers BCL-2-associated X protein (BAX) and Caspase-3 in skeletal muscle tissues were analysed using western blotting with terminal deoxynucleotidyl transferase dUTP nick end labelling staining to quantify cell apoptosis. Results: Compared with the control group, the heparin group exhibited significant pathological changes, including inflammatory infiltration and cellular hypertrophy, with increased apoptosis and oxidative stress. Notably, NRF2 suppression aggravated these effects. However, hydrogen-rich heparin sodium prominently activated the NRF2/HO-1 pathway, enhancing antioxidant defence and reducing BAX/Caspase-3-mediated apoptosis, thereby mitigating IRI-induced damage. The use of an NRF2 inhibitor to inhibit NRF2 excitation by hydrogen-rich heparin sodium notably weakened NRF2 activation and the antioxidant response, resulting in a substantial increase in cellular apoptosis. Conclusion: Pre-perfusion with hydrogen-rich heparin sodium markedly diminishes the BAX/Caspase-3-mediated apoptotic pathway in skeletal muscle tissues with IRI through the excitation of the NRF2/HO-1 pathway.

Micro-droplet printed ion-selective membrane sensors for in situ monitoring of marine heavy metal ions.

Fast, accurate, and reliable techniques for marine toxic heavy metal ions (HMI) detection are critical for the ecological environment and human health. One of the fatal drawbacks of traditional ion selective electrochemical sensors is that the modification of electrode cannot be accurately quantified, resulting in poor repeatability of the detection electrode and large error between the multi-electrode detection results. In order to tackle this challenge, this study presents ultra-fine micro-droplet printed electrodes for the in-situ detection of Cd2+, a carcinogenic and toxic HMI commonly found in the ocean. The ion selective membrane casting liquid was dispersed into tiny droplets with a diameter of micron through microfluidic technology, and the microdroplets were precisely arranged on the electrode surface. As a result, the modification error of electrode was reduced to pL level (accurate to 10 pL), which greatly improved the repeatability between electrodes prepared in different batches. The results of experiments with pure electrolyte, interference ions and artificial seawater indicated that the micro-droplet printed sensors possessed excellent properties of accuracy, precision, repeatability, and anti-interference. This novel micro-droplet printed sensor has the potential to capture an accurate picture of nearshore HMI in heterogeneous environments under shock conditions.

Neuroprotective effects of ulinastatin on Escherichia coli meningitis rats through inhibiting PKCα phosphorylation and reducing zonula occludens-1 degradation.

Ulinastatin, a broad-spectrum inflammatory inhibitor widely employed in the management of severe pancreatitis and sepsis, has not been extensively investigated for its therapeutic potential in bacterial meningitis. This study aims to assess the neuroprotective effects of ulinastatin on bacterial meningitis and elucidate its underlying mechanism. The rat model of bacterial meningitis was established by intracerebral injection of Escherichia coli. 3-week-old SD rats were randomly divided into 5 groups with 8 rats in each group, including control group, E.coli group, E.coli + UTI group (ulinastatin 50000IU/kg), E.coli + UTI + PMA group (ulinastatin 50000IU/kg + PMA 200 ug/kg), and E.coli + PMA group(PMA 200 ug/kg). Behavioral changes were assessed by Loeffler neurobehavioral score. Histomorphologic changes and apoptosis were assessed by hematoxylin and eosin staining, Nissl staining and TUNEL staining. Immunohistochemistry and immunofluorescence and western blotting were used to detect the expression levels of zonula occludens-1 (ZO-1) and phosphorylation protein kinase C (PKCα).It was found that ulinastatin treatment in Escherichia coli meningitis rats improved neurological function, alleviated meningeal inflammatory infiltration, reduced neuronal death, promoted the integrity of the blood-brain barrier structure. Moreover, phorbol myristate acetate (PMA, a protein kinase C activator), blocked the effective action of ulinastatin. These findings suggest that ulinastatin had neuroprotective effects on bacterial meningitis by inhibiting PKCα phosphorylation and reducing ZO-1 degradation, demonstrating that ulinastatin may be a promising strategy in the treatment of bacterial meningitis.

Uncovering the Interfacial Strengthening Mechanisms of α-Mg/Mg2Sn/ß-Li Interfaces Using First-Principle Calculations and HAADF-STEM.

Previously, we reported our new invention of an ultralight (ρ = 1.61 g/cm3) and super high modulus (E = 64.5 GPa) Mg-Li-Al-Zn-Mn-Gd-Y-Sn (LAZWMVT) alloy. Surprisingly, the minor additions of Sn contribute to significant strength and stiffness increases. In this study, we found that Mg2Sn was not only the simple precipitate but also acted as the glue to bind the α-Mg/ß-Li interface in a rather complicated way. To explore its mechanism, we have performed first-principle calculations and HAADF-STEM experiments on the interfacial structures. It was found that the interfacial structural models of α-Mg/ß-Li, α-Mg/Mg2Sn, and ß-Li/Mg2Sn composite interfaces prefer to form α-Mg/Mg2Sn/ß-Li ternary composite structures due to the stable formation enthalpy (ΔH: -1.95 eV/atom). Meanwhile, the interface cleavage energy and critical cleavage stress show that Mg2Sn contribute to the interfacial bond strength better than the ß-Li/α-Mg phase bond strength (σb(ß-Li/Mg2Sn): 0.82 GPa > σb(α-Mg/Mg2Sn): 0.78 GPa > σb(ß-Li/α-Mg): 0.62 GPa). Based on the interfacial electronic structure analysis, α-Mg/Mg2Sn and ß-Li/Mg2Sn were found to have a denser charge distribution and larger charge transfer at the interface, forming stronger chemical bonds. Additionally, according to the crystal orbital Hamiltonian population analysis, the bonding strength of the Mg-Sn atom pair was 2.61 eV, which was higher than the Mg-Li bond strength (0.39 eV). The effect of the Mg2Sn phase on the stability and interfacial bonding strength of the alloying system was dominated by the formation of stronger and more stable Mg-Sn metal covalent bonds, which mainly originated from the contribution of the Mg 3p-Sn 5p orbital bonding states.

Engineering the Blackbody Absorption of the Au-Branch-on-Au-Plate Heterostructures.

Utilizing the strong ligand control effects of l-cysteine (l-Cys), the growth of Au on Au triangular nanoplate (AuTN) seeds was continuously tuned from layer-by-layer (the Frank-van der Merwe) to layer-plus-island (the Stranski-Krastanov), and island (the Volmer-Weber) growth modes, leading to the formation of a series of Au-on-AuTN heterostructures. Within the window of VW growth mode (featured by the growth of Au spikes and branches on AuTNs), the effective localized surface plasmon resonance (LSPR) coupling led to the selective strengthening of the "valley" absorptions, leading to smooth and flat absorption curves. Interestingly, through engineering the number/density, size, and branching degree of the Au branches, except for the black color, full spectrum absorption within 400-1300 nm wavelength was achieved on Au-branch-on-AuTN structures. Mechanistic studies revealed that the blackbody absorption property of the Au-branch-on-AuTN originates from the well-balanced intraparticle LSPR couplings among the neighboring Au branches. The tunable blackness and the full spectrum absorption property made the Au-branch-on-AuTN heterostructure a suitable candidate for various plasmonic-related applications, such as a wide spectrum light absorber, photoacoustic imaging contrast agent, and photothermal therapy medium. In addition, our strong ligand control in Au-branch-on-AuTN heterostructures could be extended to other hybrid systems with diverse material combinations, so long as to find the proper strong ligand.

Neuromuscular Training Effects on Athletes' Jumping and Lower Limb Injury: A Systematic Review.

This study assessed the impact of integrated neuromuscular training (INT) on athletes' jumping performance and lower limb injury prevention. A thorough search across multiple databases, including PubMed, Web of Science, Science Direct, and the Cochrane Library, identified a sample of 19,805 athletes aged between 8.5 and 27.7 years. Results showed that INT led to a significant improvement in jumping ability (SMD = 0.45, 95% CI 0.30-0.60, P = 0.000) and a reduction in lower limb injuries (SMD = 0.68, 95% CI 0.62-0.74, P = 0.000). The most effective interventions lasted at least 25 minutes, conducted 2-5 times per week, for a minimum of 9 weeks. This approach was particularly beneficial for children and adolescents, as it enhanced their countermovement jump (CMJ) ability and helped in the prevention of injuries.

The Long Non-Coding RNA SNHG1 Predicts Severity of Acute Pancreatitis and Stimulates Pancreatic Cell Apoptosis and Inflammatory Response.

Acute pancreatitis (AP) is a common digestive emergency, needs early prediction and recognition. The study examined the clinical value of long non-coding RNA SNHG1 in AP, and explored its related mechanism for AP. A total of 288 AP cases and 150 healthy persons were recruited, the AP patients were grouped based on AP severity. AR42J cells were treated with 100nM caerulein to stimulate AP in vitro. qRT-PCR was performed for mRNA detection. Receiver operating characteristic (ROC) curve was drawn for diagnostic significance evaluation. The relationship of SNHG1 and miR-140-3p was verified via luciferase reporter and RNA immunoprecipitation (RIP) assay. AP cases had high expression of SNHG1, and it can differentiate AP cases from healthy people with the area under the curve (AUC) of 0.899. Severe AP cases had high values of SNHG1, which was independently related to AP severity. SNHG1 knockdown relieved caerulein-induced AR42J cell apoptosis and inflammatory response. miR-140-3p interacted with SNHG1, and reversed the role of SNHG1 in caerulein-induced AR42J cell injury. RAB21 was a candidate target of miR-140-3p, and was at high expression in AP cell models. SNHG1 may be a promising biomarker for the detection of AP, and serves as a potential biological marker for further risk stratification in the management of AP. SNHG1 knockdown can relieve inflammatory responses and pancreatic cell apoptosis by absorbing miR-140-3p.

Self-Assembly of Strain-Adaptable Surface-Enhanced Raman Scattering Substrate on Polydimethylsiloxane Nanowrinkles.

Flexible surface-enhanced Raman scattering (SERS) substrates adaptable to strains enable effective sampling from irregular surfaces, but the preparation of highly stable and sensitive flexible SERS substrates is still challenging. This paper reports a method to fabricate a high-performance strain-adaptable SERS substrate by self-assembly of Au nanoparticles (AuNPs) on polydimethylsiloxane (PDMS) nanowrinkles. Nanowrinkles are created on prestrained PDMS slabs by plasma-induced oxidation followed by the release of the prestrain, and self-assembled AuNPs are transferred onto the nanowrinkles to construct the high-performance SERS substrate. The results show that the nanowrinkled structure can improve the surface roughness and enhance the SERS signals by ∼4 times compared to that of the SERS substrate prepared on flat PDMS substrates. The proposed SERS substrate also shows good adaptability to dynamic bending up to ∼|0.4| 1/cm with excellent testing reproducibility. Phenolic pollutants, including aniline and catechol, were quantitatively tested by the SERS substrate. The self-assembled flexible SERS substrate proposed here provides a powerful tool for chemical analysis in the fields of environmental monitoring and food safety inspection.

All-in-one bio-derived poly(L-lactic acid)-based composite with fire-resistance and smoke-suppression performance.

The flammability of bio-derived poly(L-lactic acid) (PLA) greatly limits its application and eco-friendly multifunctional fire-fighting PLA-based composites are highly desired. In this work, a fully bio-based modified CS (C-CS) and commercially available eco-friendly ammonium polyphosphate (APP) were used as a synergistic flame retardant agent (C-CS/APP) to investigate its effects on fire-proofing performance and diverse properties of the PLA. The PLA/5%C-CS/5%APP composite exhibited excellent fire-resistant performance with anti-droplet, smoke-suppression and self-extinguishing property, and its limited oxygen index enhanced by 37 % (compared with neat PLA). This composite reached the highest V-0 fire safety rating, and its peak of heat release rate and total smoke production reduced by 26.5 % and 68.3 %, respectively. In addition, the char residue yield after the cone calorimeter test increased by 46 times in the composite, indicating an outstanding char-forming capacity. The condensed phase flame retardancy played a crucial role on the fire-fighting of this composite, that is, significantly enhanced char residue (as a physical barrier) blocked the heat exchange and O2 entry, and further suppressed the combustion reaction. Additionally, the PLA-based composite showed outstanding UV-absorption property, good anti-bacterial effect, and increased hydrophilicity and crystallizability.

Power and velocity performance of swing movement in the adolescent male volleyball players - age and positional difference.

PURPOSE: The performance of swing movement during spikes and serves plays a crucial role in determining the outcomes of volleyball matches. This study aims to explore the effects of the participation of the trunk and lower limbs' involvement on the velocity and power of the swing movement of adolescent male volleyball players, as well as the differences in power and velocity performance of the swing movement among different ages and specific positions. METHODS: The study involved 22 adolescent male volleyball players, with 11 high school students and 11 middle school students. The Kineo Globus equipment was used to assess the swing movement performance involving different segments, including arm swing movement only involving arm limb participation; upper swing movement involving trunk and arm limb participation; and whole body swing movement involving lower limb, trunk, and arm limb participation. The measured parameters included power and velocity performance levels. Before the test, each subject practiced three movement patterns twice. RESULTS: The study found that swing movement involving both the trunk and arm limbs had significantly higher average (F = 17.70, p < 0.001) and peak power performance (F = 31.47, p < 0.001), as well as in average (F = 9.14, p = 0.03) and peak velocity performance (F = 23.17, p < 0.001). There were no significant differences in average (F = 17.70; p = 0.46) and peak power (F = 31.47, p = 0.94), as well as in average (F = 9.14, p = 0.99) and peak velocity performance (F = 23.17, p = 0.90) between movements involving the whole body and those involving the trunk and upper limbs. Among different age groups, the swing movement performance of middle school athletes showed significant enhancements in both average (F = 9.20, p < 0.001) and peak power (F = 19.93, p < 0.001), as well as in average (F = 10.75, p < 0.001) and peak velocity (F = 34.35, p < 0.001) when arm swing with trunk involvement was compared to arm swing movement. High school athletes also showed significant improvements in peak velocity (F = 34.35, p < 0.001), peak power (F = 17.31, p < 0.001), and average power (F = 9.41, p < 0.001) during upper swing movements, except for average velocity performance (F = 1.56, p = 0.21), when compared to arm swing movement. The increase rate in average velocity performance of swing movements involving trunk participation was significantly higher in middle school athletes than in high school athletes (p < 0.001). Among athletes in specific positions, Middle Blocker (MB) players exhibited significantly better average power performance in swing movements involving trunk and arm limb participation compared to Outside Hitter (OH) players (p = 0.04). Furthermore, the rate of average (p = 0.01) and peak (p = 0.03) power change during upper swing movements involving lower limb participation was significantly higher among OH players than MB players. CONCLUSIONS: The involvement of the trunk segment has been observed to significantly improve power and velocity in swing movements during spike and serves among adolescent male volleyball players. This underscores the importance of coordination between the trunk and arm in influencing swing movement performance during spikes and serves. High school athletes demonstrate superior power and velocity in arm swing movements compared to middle school athletes. MB exhibits greater power in upper limb swing movements than OH, although OH players show better coordination between the arm, trunk, and lower limb segments in the swing movement. To enhance swing movement performance in adolescent male volleyball players, particularly focusing on the trunk segment was crucial. Specialized physical training programs should target improving both arm strength and rotational power of the trunk simultaneously. This approach would help in consistently enhancing coordination between the trunk and arms, ultimately leading to optimized force generation during swing movements such as spikes and serves.

Analysis of fecal microbiota and related clinical indicators in ICU patients with sepsis.

Background: To analyze the characteristics of fecal microbiota disturbance in the intensive care unit (ICU) patients with sepsis and the correlation with related clinical indicators. Methods: This study included 31 patients with sepsis admitted to the emergency ICU ward between September 2019 and December 2021. They were divided into Group without septic shock (ND_NS group, 7 cases) and Group with septic shock (ND_S group, 24 cases) according to the presence or absence of septic shock. Furthermore, we divided these 31 sepsis patients into Clinical Improvement group (21 cases) and Death or DAMA group (10 cases) based on clinical outcome, 15 cases of Physical Examiner recruited in the same period were included as control group: ND_HC group (15 cases). The fecal samples of the patients with sepsis within 24 h of admission and random fecal samples of the control group were collected and analyzed by 16S rDNA gene sequencing used for the analysis of fecal microbiota. At the same time, the relevant clinical data of these patients with sepsis were also collected for analysis. Results: There were 15 cases with drug-resistant bacteria in the ND_S group and only 2 cases in the ND_NS group (P = 0.015). There were significant differences in APACHE II score, length of ICU stay, lactate level, and oxygenation index of patients between the Death or DAMA group and Clinical Improvement group (all P < 0.05). For phylum level, the abundance of Firmicutes, Actinobacteria, and Bacteroidetes decreased in the ND group compared with the ND_HC group, while the abundance of Proteobacteria increased (P < 0.05). For genus level, the relative abundance of Escherichia-Shigella and Klebsiella were significantly increased in the ND group compared with the ND_HC group (P < 0.05). The top six genera in relative abundance in the ND_S group were Escherichia-Shigella, Enterococcus, Bifidobacterium, Lactobacillus, Akkermansia, and Klebsiella. Compared with the Clinical Improvement group, the relative abundance of Escherichia-Shigella and Klebsiella in the Death or DAMA group showed an increasing trend with no significant significance, while the relative abundance of Enterococcus and Faecalibacterium decreased in the Death or DAMA group (P < 0.05). Alpha diversity analysis showed that compared with the ND_HC group, the alpha diversity of the fecal microbiota in the ND group decreased. There were significant differences in the Observed_species index, Chao1 index, and ACE index of patients between the ND_HC group and ND group (all P < 0.05). Moreover, compared with the ND_NS group, the Alpha diversity of the ND_S group was more abundant. PCoA analysis showed significant differences in microbial community structure between the ND group and ND_HC group (P = 0.001). There also were significant differences in microbial community structure between the ND_S group and ND_NS group (P = 0.008). LEfSe analysis showed that compared with the ND_HC group, there were significant differences in the species of the ND group, including Enterobacteriaceae, Escherichia-Shigella, Enterococcus, Elizabethkingia, and Family_XIII_AD3011_group. Conclusions: ICU patients with sepsis suffered intestinal microecological disturbances with significantly decreased abundance of fecal microbiota, diversity, and beneficial symbiotic bacteria. For these patients, the ratio of pathogenic bacteria, including Escherichia-Shigella and Klebsiella increased and became the main bacterial genus in some samples. Moreover, the increasing trend of these two pathogenic bacteria may be correlated with the development of septic shock and the risk of death in patients with sepsis.

Stress and Deformation Analysis of Prestressed Wound Composite Components with an Arch-Shaped Metal Liner.

The stress distribution in prestressed filament wound components plays a crucial role in determining the quality of these components during their operational lifespan. This article proposes a physical model to analyze the stress and deformation of prestressed wound composite components with arch-shaped sections. Drawing upon the principles of beam theory, we delve into the analysis of prestressed wound components with metal liners featuring arch-shaped sections. Our investigation revealed a noteworthy phenomenon termed the "additional bending moment effect" within prestressed wound components with arch-shaped sections. Furthermore, this study establishes a relationship between this additional bending moment and the external pressure. In addition, a 3D finite element (FE) model for prestressed wound components with arch-shaped sections incorporating metal liners was developed. The model's accuracy was validated through a comparison with prestressed wound experiments, showcasing an error margin of less than 2%. In comparison with prestressed wound components with circular cross-sections under identical load and dimensional parameters, it was observed that prestressed wound components with arch-shaped sections exhibit stress distributions in the arc segments akin to their circular counterparts, with differences not exceeding 5%. Notably, when the ratio of the straight segment length to the inner diameter of the arc segment inner is less than 4, the deformation on the symmetric plane of the arc segment in an arch-shaped component can be effectively considered as the summation of deformations in equivalent-sized arc and straight segments under identical loading conditions. This yields an equivalent physical model and a streamlined analysis and design methodology for describing the deformation characteristics of prestressed wound components with arch-shaped sections.

Hydrogen Bond-Mediated Strong Plasticization for High-Performance Alginate Plastics.

The increasingly severe plastic pollution has urged an inevitable trend to develop biodegradable plastic products that can take over synthetic plastics. As one of the most abundant natural polymers, polysaccharides are an ideal candidate to substitute synthetic plastics. The rigidity of polysaccharide chains principally allows for high strength and stiffness of their materials, however, challenges the facile orientation in material processing. Here, a general hydrogen bond-mediated plasticization strategy to regulate isotropic sodium alginate (SA) chains to a highly ordered state is developed, and alginate plastics with high performances are fabricated. It is revealed that hydroxyl groups in glycerol modulate the viscoelasticity of SA solids by forming strong hydrogen bonds with SA chains, achieving a large stretchability at a high solid content. Highly orientated alginate films exhibit a superior tensile strength of 575 MPa and toughness of 60.7 MJ m-3, outperforming most regenerated biomass films. The high solid content and large stretchability mediated by strong hydrogen bonding ensure plastic molding of solid-like SA with high fidelity. This hydrogen bond-mediated plasticity provides a facile but effective method to justify the high performances of polysaccharide-based plastics.

Numerical simulation of the effect of hypergravity on the dendritic growth characteristics of aluminum alloys.

The cellular automata-lattice Boltzmann method is used to simulate the dendritic growth process of aluminum alloys under the action of hypergravity by performing coupling heat and mass transfer, solidification and flow. The dendrite arm spacing, growth rate, and dendrite morphology vary greatly with the size and direction of hypergravity, and solute segregation occurs. Compared with the gravity of the earth (1 g), hypergravity strongly strengthens the buoyancy-driven flow and considerably affects the morphology of the solidified grain. The dendritic growth rate is also accelerating. According to the direction of hypergravity in relation to the dendritic growth direction, there exist different flow states that show stable or unstable dendritic growth dynamics. For columnar crystal growth, when the hypergravity and growth direction are identical, the dendrite tip undergoes downward melt flow, and the dendrite grows in a stable manner. When the hypergravity and the growth direction are opposite, the dendrite tip undergoes upward melt flow, the dendrite grows in an unstable manner, and the primary dendrite spacing decreases. For the growth of equiaxed crystals, the convection induced by hypergravity causes the equiaxed crystals to be asymmetric, and the solute segregates in the direction of gravity. Channel segregation occurs in the mushy zone in the presence of equiaxed crystal chains.

Numerical studies of manipulation and separation of microparticles in ODEP-based microfluidic chips.

A novel optical-induced dielectrophoresis (ODEP) method employing a pressure-driven flow for the continuous separation of microparticles is presented in this study. By applying alternate current electric field on conductive indium tin oxide substrate and projecting the light geometry into the photoconductive layer, an inhomogeneous electric field is locally induced. The particles experience the dielectrophoretic force when passing through the lighting area, where the strongest electrical field gradient exists. By optimizing the structure of the lighting pattern, a stronger nonuniform electric field gradient is generated which predicts the separation of 1 and 3 µm polystyrene particles. Moreover, the effects of key parameters, including the light pattern geometry, applied voltage, and flow rate, were investigated in this study, leading to the successful sorting of 700 nm and 1 µm particles. To further examine the separation sensitivity and practicability of the proposed ODEP microfluidic method, the isolation of two different types of circulating tumor cells from T-cells and red blood cells are demonstrated, providing a novel method for the manipulation and separation of microparticles and nanoparticles.

Sintilimab with two cycles of chemotherapy for the treatment of advanced squamous non-small cell lung cancer: a phase 2 clinical trial.

This was a single-arm, multicenter phase 2 clinical trial (ChiCTR1900021726) involving advanced squamous non-small cell lung cancer (sq-NSCLC) patients undergoing 2 cycles of nab-paclitaxel/carboplatin and sintilimab (anti-PD-1), followed by sintilimab maintenance therapy. The median progression-free survival (PFS) was 11.4 months (95% CI: 6.7-18.1), which met the pre-specified primary endpoint. Secondary endpoints included objective response rate reaching 70.5% and a disease control rate of 93.2%, with a median duration of response of 13.6 months [95% CI: 7.0-not evaluable (NE)]. The median overall survival was 27.2 months (95% CI: 20.2-NE) with treatment-related adverse events grades ≥3 occurring in 10.9% of patients. Predefined exploratory endpoints comprised relationships between biomarkers and treatment efficacy, and the association between circulating tumor DNA (ctDNA) dynamics and PFS. Biomarker analysis revealed that the breast cancer gene 2, BMP/Retinoic Acid Inducible Neural Specific 3, F-box/WD repeat-containing protein 7, tyrosine-protein kinase KIT and retinoblastoma 1 abnormalities led to shorter PFS, while ctDNA negative at baseline or clearance at 2 cycles of treatment was associated with longer PFS (18.1 vs. 4.3 months). Taken together, sintilimab in combination with 2 cycles of nab-paclitaxel/carboplatin treatment produced encouraging PFS and better tolerability as first-line treatment for advanced sq-NSCLC.

Multiple Equine Therapies for the Treatment of Gross Motor Function in Children with Cerebral Palsy: A Systematic Review.

PURPOSE: This study aimed to evaluate the impact of three equine therapy approaches on gross motor function in children with cerebral palsy. METHODS: The studies were retrieved from PubMed, Web of Science, Science Direct, and the Cochrane Library, in accordance with the style commonly found in scientific journal publications:(1) peer-reviewed articles written in English; (2) experimental or quasi-experimental; (3) three Equine Therapy Interventions as experiment's independent variable; (4) children with cerebral palsy; and (5) measurement of outcomes related to Gross Motor Function. RESULTS: The study examined 596 patients with cerebral palsy, whose average age was 8.03 years. The three types of horse therapy interventions had a significant impact on gross motor function in children with cerebral palsy (SMD = 0.19, 95% CI 0.02-0.36, p = 0.031). Additionally, the interventions positively affected dimensions C (SMD = 0.31, 95% CI 0.00-0.62, p = 0.05), D (SMD = 0.30, 95% CI 0.06-0.56, p = 0.017), and B (SMD = 0.72, 95% CI 0.10-1.34, p = 0.023). The Gross Motor Function Measure (GMFM) consists of 88 or 66 items, which are divided into five functional dimensions: GMFM-A (lying down and rolling), GMFM-B (sitting), GMFM-C (crawling and kneeling), GMFM-D (standing), and GMFM-E (walking, running, and jumping). Each subsection of the GMFM can be used separately to evaluate motor changes in a specific dimension of interest. Subgroup analysis revealed that different horse-assisted therapy approaches, types of cerebral palsy, exercise duration, frequency, and intervention periods are important factors influencing treatment outcomes. CONCLUSION: The intervention period ranged from 8 to 12 weeks, with session durations of 30 to 45 minutes, 2 to 3 times per week. Equine-assisted therapy (EAT) demonstrated significant improvements in the overall gross motor function score, Dimension B, Dimension C, and Dimension D among children with cerebral palsy. The most effective treatment is provided by Equine-Assisted Therapy, followed by Horseback Riding Simulator (HRS). Due to its economic practicality, HRS plays an irreplaceable role. CLINICAL EVIDENCE: Equine-Assisted Therapy (EAT) demonstrates the most effective treatment outcomes, suggesting that hospitals and healthcare professionals can form specialized teams to provide rehabilitation guidance. 2. Within equine-assisted therapy, Horseback Riding Simulator (HRS) exhibits treatment efficacy second only to Equine-Assisted Therapy (EAT), making it a cost-effective and practical option worthy of promotion and utilization among healthcare institutions and professionals. 3. In equine-assisted therapy, Therapeutic Horseback Riding (THR) holds certain value in rehabilitation due to its engaging and practical nature.

In situ monitoring of toxic effects of algal toxin on cells by a novel microfluidic flow cytometry instrument.

Algal toxins produced by microalgae, such as domoic acid (DA)1, have toxic effects on humans. However, toxicity tests using mice only yield lethal doses of algal toxins without providing insights into the mechanism of action on cells. In this study, a fast segmentation of microfluidic flow cytometry cell images based on the bidirectional background subtraction (BBS)2 method was developed to get the visual evidence of apoptosis in both bright-field and fluorescence images. This approach enables mapping of changes in cell morphology and activity under algal toxins, allowing for fast (within 60 s) and automated biological detection. By combining microfluidics with flow cytometry, the intricate cellular-level reaction process can be observed in micro samples of 293 T cells and mouse spleen cells, offering potential for future in vitro experiments.

Effect of hospital-community online management on medication management of elderly patients with peritoneal dialysis during COVID-19.

INTRODUCTION: The study aimed to explore feasibility and effect of hospital-community online management on the medication management of elderly peritoneal dialysis (PD) patients with end-stage renal disease (ESRD) during COVID-19. METHODS: A total of 160 patients receiving PD were randomly divided into the control (n = 80, outpatient follow-up management mode) and observation (n = 80, hospital-community online management mode) groups. The self-efficacy (General Self-Efficacy Scale [GSES]), medication adherence (8-item Morisky medication adherence scale [MMAS-8]), quality of life (kidney disease quality of life short form [KDQOL-SF]), and degree of depression (beck depression inventory [BDI]) before and after the intervention were compared. RESULTS: After the intervention, the scores of GSES (4.20 ± 0.46 vs. 3.09 ± 0.33), MMAS-8 (5.82 ± 0.92 vs. 5.13 ± 1.25), and KDQOL-SF were significantly higher, whereas the BDI score (9.50 ± 2.86 vs. 12.08 ± 2.95) was significantly lower in the observation group than in the control group (p < 0.05). CONCLUSION: Hospital-community online management presents good effects in the medication management of PD patients with ESRD.