Capecitabine or Capecitabine Plus Oxaliplatin Versus Fluorouracil Plus Cisplatin in Definitive Concurrent Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma (CRTCOESC): A Multicenter, Randomized, Open-Label, Phase 3 Trial.

PURPOSE: This phase 3 trial aimed to compare the efficacy and safety of capecitabine or capecitabine plus oxaliplatin (XELOX) with those of fluorouracil plus cisplatin (PF) in definitive concurrent chemoradiotherapy (DCRT) for inoperable locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Patients were randomly assigned to receive two cycles of capecitabine, XELOX, or PF along with concurrent intensity-modulated radiation therapy. Patients in each arm were again randomly assigned to receive two cycles of consolidation chemotherapy or not. The primary end points were 2-year overall survival (OS) rate and incidence of grade ≥3 adverse events (AEs). RESULTS: A total of 246 patients were randomly assigned into the capecitabine (n = 80), XELOX (n = 85), and PF (n = 81) arms. In capecitabine, XELOX, and PF arms, the 2-year OS rate was 75%, 66.7%, and 70.9% (capecitabine v PF: hazard ratio [HR], 0.91 [95% CI, 0.61 to 1.35]; nominal P = .637; XELOX v PF: 0.86 [95% CI, 0.58 to 1.27]; P = .444); the median OS was 40.9 (95% CI, 34.4 to 49.9), 41.9 (95% CI, 28.6 to 52.1), and 35.4 (95% CI, 30.4 to 45.4) months. The incidence of grade ≥3 AEs during the entire treatment was 28.8%, 36.5%, and 45.7%, respectively. Comparing the consolidation chemotherapy with the nonconsolidation chemotherapy groups, the median OS was 41.9 (95% CI, 34.6 to 52.8) versus 36.9 (95% CI, 28.5 to 44) months (HR, 0.71 [95% CI, 0.52 to 0.99]; nominal P = .0403). CONCLUSION: Capecitabine or XELOX did not significantly improve the 2-year OS rate over PF in DCRT for inoperable locally advanced ESCC. Capecitabine showed a lower incidence of grade ≥3 AEs than PF did.

Impact of Electromagnetic Stirring Roller Arrangement Pattern on Magnetic Field Simulation and Solidification Structure of PW800 Steel in the Second Cooling Zone.

Strand electromagnetic stirring (S-EMS), a technique applied in the secondary cooling zone, enhances the solidification structure of casting slabs. This study examines how the arrangement pattern of electromagnetic stirring rollers-face-to-face, side-to-side or up-down misalignment produces this enhancement. It uses simulations to analyze the electromagnetic field distribution in these configurations. The findings demonstrate that: (1) The magnetic flux density distribution in the casting slab is related to the arrangement pattern of the electromagnetic stirring rollers. (2) The face-to-face arrangement produces the largest and most concentrated electromagnetic force compared to the other two arrangement patterns. (3) S-EMS can effectively improve the equiaxed grain ratio of casting slabs. Before and after EMS is turned on, casting slabs' average equiaxed grain ratio goes up from 8% to 33%.

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.

The F-box protein RhSAF destabilizes the gibberellic acid receptor RhGID1 to mediate ethylene-induced petal senescence in rose.

Roses are among the most popular ornamental plants cultivated worldwide for their great economic, symbolic, and cultural importance. Nevertheless, rapid petal senescence markedly reduces rose (Rosa hybrida) flower quality and value. Petal senescence is a developmental process tightly regulated by various phytohormones. Ethylene accelerates petal senescence, while gibberellic acid (GA) delays this process. However, the molecular mechanisms underlying the crosstalk between these phytohormones in the regulation of petal senescence remain largely unclear. Here, we identified SENESCENCE-ASSOCIATED F-BOX (RhSAF), an ethylene-induced F-box protein gene encoding a recognition subunit of the SCF-type E3 ligase. We demonstrated that RhSAF promotes degradation of the GA receptor GIBBERELLIN INSENSITIVE DWARF1 (RhGID1) to accelerate petal senescence. Silencing RhSAF expression delays petal senescence, while suppressing RhGID1 expression accelerates petal senescence. RhSAF physically interacts with RhGID1s and targets them for ubiquitin/26S proteasome-mediated degradation. Accordingly, ethylene-induced RhGID1C degradation and RhDELLA3 accumulation are compromised in RhSAF-RNAi lines. Our results demonstrate that ethylene antagonizes GA activity through RhGID1 degradation mediated by the E3 ligase RhSAF. These findings enhance our understanding of the phytohormone crosstalk regulating petal senescence and provide insights for improving flower longevity.

Temporal trend in hospitalizations for malignant neoplasm and benign neoplasm: a nationwide study, China, 2004-2020.

The increasing cancer burden calls for reliably assessed changes in the hospitalizations for tumors over time and space in China. This study evaluated trends in hospitalization rate, in-hospital mortality, length of stay (LOS), and medical costs for malignant and benign neoplasms. Data were derived from China Health Statistical Yearbooks from 2004 to 2020. Temporal trends in hospitalization rates and in-hospital mortality rates were assessed through the Cochran-Armitage Test. We used the linear model with continuous variables to test for the trend. The malignant neoplasm hospitalization rate increased from 1.1‰ to 5.8‰ and the benign neoplasm increased from 1.0‰ to 2.0‰. The in-hospital mortality rate due to malignant neoplasm and benign neoplasm decreased from 5.11 to 2.87% (P for trend < 0.001) and 0.14-0.01% (P for trend < 0.001), respectively. Among all patients hospitalized with malignant neoplasm, the average cost per hospitalization significantly increased during the study period (P for trend < 0.001), adjusted for the Consumer Price Index. However, the average LOS gradually decreased (P for trend < 0.001). In line with the trend of malignant neoplasm, the average cost per hospitalization increased significantly among all patients hospitalized for benign neoplasm (P for trend < 0.001), and the average LOS showed a steady downward trend (P for trend < 0.001). We found upward trends in hospitalization rates, and medical costs in neoplasms. By contrast, substantial decreases in in-hospital mortality and LOS. The hospitalization rate gap between urban and rural areas is narrowed.

Stool-softening effect and action mechanism of free anthraquinones extracted from Rheum palmatum L. on water deficit-induced constipation in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese herbal medicine, rhubarb is said to remove accumulation with purgation, clearing heat, and discharging fire. Modern pharmacology has shown that rhubarb extract has a purgative effect when given to experimental animals in an appropriate dose. However, the active components and their mechanism of action are still not clearly defined. AIM OF THE STUDY: The current research aimed to evaluate the synergistic stool-softening effects and explore the action mechanism of rhubarb free anthraquinones (RhA) and their monomers on constipation in rats. MATERIALS AND METHODS: A rat model of water deficit-induced constipation was established to induce constipation, and these rats were treated with RhA and its monomers. ELISA, histopathology, immunohistochemistry, qPCR and Western blotting based on network pharmacology and molecular docking were conducted to explore the possible mechanism of action of RhA and its monomers. RESULTS: RhA, aloe-emodin, rhein, and chrysophanol showed stool-softening activity, and the combination of aloe-emodin and rhein had the strongest softening effect on faecal pellets. Aloe-emodin, rhein, and chrysophanol significantly increased the serum levels of vasoactive intestinal peptide (VIP), motilin (MTL), and substance P (SP), upregulated the expression of VIP, cyclase-associated protein 1 (CAP1), protein kinase A (PKA), cystic fibrosis transmembrane conductance regulator (CFTR), aquaporin 3 (AQP3), aquaporin 4 (AQP4), and aquaporin 8 (AQP8), decreased the expression of epithelial sodium channel (ENaC) and Na+/H+ exchanger 3 (NHE3), and reduced the colonic tissue concentration of Na+-K+-ATPase in the constipated rats. Osmolality of colonic fluid in model rats treated by RhA, aloe-emodin, rhein, and chrysophanol was increased. CONCLUSION: Aloe-emodin, rhein, and chrysophanol were the stool-softening components of the RhA extract, and there were certain drug-interactions between the components. RhA upregulated VIP expression, activated the cyclic adenosine monophosphate protein kinase A (cAMP/PKA) pathway, and further stimulated CFTR expression while inhibiting NHE3 and ENaC expression, resulting in a hypertonic state in the colonic lumen. Water transport could then be driven by an osmotic gradient, which in turn led to the upregulation of AQP3, AQP4, and AQP8 expression. In addition, RhA likely improved gastrointestinal motility by increasing serum VIP, SP, and MTL concentrations, thus promoting faecal excretion.

Numerical and Experimental Study on Carbon Segregation in Shaped Billet of Medium Carbon Steel with Combined Electromagnetic Stirring.

Carbon segregation is the major and classical internal defect in the continuous casting process of carbon steel. Based on the combined electromagnetic stirring equipment for new billet in a steel plant, China, the influence of combined electromagnetic stirring (M-EMS + F-EMS) on the carbon segregation of 300 mm × 340 mm special-shaped billet was studied via numerical simulation and on-site industrialization tests. The Lorentz force and carbon solute distribution were simulated under different EMS parameters. The formation mechanism of the carbon segregation of medium carbon steel with different combined electromagnetic stirring processes was analyzed. The results show that: (1) with the combined action of "solute flushing" effect and gravity, the carbon concentration in the loose side of the medium carbon steel casting billet is gradually lower than the fixed side, while the carbon concentration on the fixed side gradually accumulates more; and (2) under the action of combined electromagnetic stirring, the segregation index of casting billet could be controlled to remain between 0.96-1.05 and shows an increasing change in solidification from the skin to the center. When the current and frequency of M-EMS are 250 A and 2.0 Hz and the F-EMS are 180 A and 8.0 Hz, the carbon segregation defects in the special-shaped (300 mm × 340 mm) casting billet can be significantly improved.

Simulation Study on the Influence of Different Molten Steel Temperatures on Inclusion Distribution under Dual-Channel Induction-Heating Conditions.

Impurity elimination in tundishes is an essential metallurgical function in continuous casting. If inclusions in a tundish cannot be effectively removed, their presence will have a serious impact on the quality of the bloom. As a result, this research investigates the locations of inclusion particles in a six-strand induction-heating tundish in depth, combining the flow, temperature, and inclusion trajectories of molten steel under electromagnetic fields. The results show that a pinch effect occurred in the induction-heating tundish, and a rotating magnetic field formed in the channel, with a maximum value of 0.158 T. The electromagnetic force was directed toward the center of the axis, and its numerical distribution corresponds to the magnetic flux density distribution, with a maximum value of 2.11 × 105 N/m3. The inclusion particles' movement speed accelerated as the molten steel's temperature rose, and their distribution in the channel was identical to the rotating flow field distribution. When the steel's temperature rose from 1750 K to 1850 K, the removal percentage of inclusion particles in the discharge chamber rose by 9.20%, the removal rate at the outlet decreased from 8.00% to 3.00%, and the adhesion percentage of inclusion particles in the channel decreased from 48.40% to 44.40%.

Flexible processing technology of coix seed prolamins by combined heat-ultrasound: Effects on their enzymatic hydrolysis characteristics and the hypoglycemic activities of derived peptides.

The self-assembled structures of coix seeds affected the enzymatic efficiency and doesn't facilitate the release of more active peptides. The influence of heating combined with ultrasound pretreatment (HT + US) on the structure, enzymatic properties and hydrolysates (CHPs) of coix seed prolamin was investigated. Results showed that the structural of coix seed prolamins has changed after HT + US, including increased surface hydrophobicity, reduced α-helix and random coil content, and a decrease in particle size. So that, leads to changes in thermodynamic parameters such as an increase in the reaction rate constant and a decrease in activation energy, enthalpy and enthalpy. The fractions of <1000 Da, degree of hydrolysis and α-glucosidase inhibitory were increased in the HT + US group compared to single pretreatment by 0.68%-17.34%, 12.69%-34.43% and 30.00%-53.46%. The peptide content and α-glucosidase inhibitory activity of CHPs could be maintained at 72.21 % and 57.97 % of the initial raw materials after in vitro digestion. Thus, the findings indicate that HT + US provides a feasible and efficient approach to can effectively enhance the enzymatic hydrolysis efficiency and hypoglycaemic efficacy of CHPs.

The Potential Strategies for Overcoming Multidrug Resistance and Reducing Side Effects of Monomer Tubulin Inhibitors for Cancer Therapy.

BACKGROUND: Tubulin is an essential target in tumor therapy, and this is attributed to its ability to target MT dynamics and interfere with critical cellular functions, including mitosis, cell signaling, and intracellular trafficking. Several tubulin inhibitors have been approved for clinical application. However, the shortcomings, such as drug resistance and toxic side effects, limit its clinical application. Compared with single-target drugs, multi-target drugs can effectively improve efficacy to reduce side effects and overcome the development of drug resistance. Tubulin protein degraders do not require high concentrations and can be recycled. After degradation, the protein needs to be resynthesized to regain function, which significantly delays the development of drug resistance. METHODS: Using SciFinder® as a tool, the publications about tubulin-based dual-target inhibitors and tubulin degraders were surveyed with an exclusion of those published as patents. RESULTS: This study presents the research progress of tubulin-based dual-target inhibitors and tubulin degraders as antitumor agents to provide a reference for developing and applying more efficient drugs for cancer therapy. CONCLUSION: The multi-target inhibitors and protein degraders have shown a development prospect to overcome multidrug resistance and reduce side effects in the treatment of tumors. Currently, the design of dual-target inhibitors for tubulin needs to be further optimized, and it is worth further clarifying the detailed mechanism of protein degradation.

Safety and efficacy of apatinib in patients with advanced gastric or gastroesophageal junction adenocarcinoma after the failure of two or more lines of chemotherapy (AHEAD): a prospective, single-arm, multicenter, phase IV study.

BACKGROUND: Apatinib, a highly selective VEGFR2 inhibitor, significantly improved efficacy versus placebo as a third- and later-line treatment for advanced gastric cancer in phase 2 and 3 trials. This prospective, single-arm, multicenter phase IV AHEAD study was conducted to verify the safety and efficacy of apatinib in patients with advanced or metastatic gastric or gastroesophageal adenocarcinoma after at least two lines of systematic therapy in clinical practice settings. METHODS: Patients with advanced gastric cancer who had previously failed at least two lines of chemotherapy received oral apatinib until disease progression, death or unacceptable toxicity. The primary endpoint was safety. The secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Adverse events were summarized by the incidence rate. Median OS and PFS were estimated using the Kaplan-Meier method. ORR, DCR, OS at 3 and 6 months, and PFS at 3 and 6 months were calculated, and their 95% CIs were estimated according to the Clopper-Pearson method. RESULTS: Between May 2015 and November 2019, a total of 2004 patients were enrolled, and 1999 patients who received at least one dose of apatinib were assessed for safety. In the safety population, 87.9% of patients experienced treatment-related adverse events (TRAEs), with the most common hypertension (45.2%), proteinuria (26.5%), and white blood cell count decreased (25.3%). Additionally, 51% of patients experienced grade ≥ 3 TRAEs. Fatal TRAEs occurred in 57 (2.9%) patients. No new safety concerns were reported. Among the 2004 patients included in the intention-to-treat population, the ORR was 4.4% (95% CI, 3.6-5.4%), and DCR was 35.8% (95% CI, 33.7-38.0%). The median PFS was 2.7 months (95% CI 2.2-2.8), and the median OS was 5.8 months (95% CI 5.4-6.1). CONCLUSIONS: The findings in the AHEAD study confirmed the acceptable and manageable safety profile and clinical benefit of apatinib in patients with advanced gastric cancer as a third- or later-line of treatment. TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov NCT02426034. Registration date was April 24, 2015.

Volumetric modulated arc therapy for hippocampal-sparing prophylactic cranial irradiation: Planning comparison of Halcyon and C-arm accelerators.

Background: The purpose of the study was to evaluate the dosimetry of the Halcyon in prophylactic cranial irradiation (PCI) with volumetric modulated arc therapy (VMAT) and hippocampal-sparing for small cell lung cancer (SCLC). Methods: Five VMAT plans were designed on CT images of 15 patients diagnosed with SCLC and received PCI. Three plans with two full arcs were generated on the Trilogy and the TrueBeam accelerators, and flattening filter (FF) and flattening filter free (FFF) modes were used on TrueBeam. Two Halcyon plans with two and three full arcs were generated, referred to as H-2A and H-3A, respectively. The prescription dose was 25 Gy in 2.5-Gy fractions. The dose limit for hippocampus were D100 ≤ 9Gy and Dmax ≤ 16Gy. The Wilcoxon matched-paired signed-rank test was used to evaluate the significance of the observed differences between the five plans. Results: H-2A plans significantly increased the D2 of PTV, and H-3A plans showed comparable or even better target dosimetry (better conformity) compared to the three plans on C-arm accelerators. Compared to T and TB plans, the two Halcyon plans significantly reduced the D100 and mean doses of bilateral hippocampus, the mean doses of eyeballs, and the maximum doses of lenses. D100 of hippocampus was reduced in TrueBeam plans comparing to Trilogy plans. The FFF plans on TrueBeam also represented advantages in Dmean and D100 of hippocampas, Dmean and Dmax of eyeballs, and the Dmax of lenses compared to FF plans. Halcyon plans and TrueBeam plans with FFF mode increased the MUs compared to FF plans. Comparing to H-2A, the H-3A plans exhibited additional dosimetric advantages, including D2, CI and HI of PTV, as well as the maximum and mean doses of hippocampus and eyeballs, and the maximum doses of optic nerves and brainstem. The two Halcyon plans significantly reduced the delivery time and showed the higher gamma passing rate than the three plans of C-arm accelerators. Conclusions: Compared with the C-arm accelerators, the dose of hippocampus and the delivery times on Halcyon are relatively significantly reduced for hippocampal-sparing PCI. Three arcs are recommended for VMAT plans with the Halcyon in hippocampal-sparing PCI.

Jigsaw training-based background reverse attention transformer network for guidewire segmentation.

PURPOSE: Guidewire segmentation plays a crucial role in percutaneous coronary intervention. However, it is a challenging task due to the low signal-to-noise ratio of X-ray sequences and the great imbalance between the number of foreground and background pixels. Besides, most existing guidewire segmentation methods are designed for single guidewire segmentation. This paper aims to solve the task of single and dual guidewire segmentation in X-ray fluoroscopy sequences. METHODS: A jigsaw training-based background reverse attention (BRA) transformer network is proposed. A jigsaw training strategy is used to train the guidewire segmentation network. A BRA module is also designed to reduce the influence of background information. First, robust principal component is conducted to generate background maps for guidewire sequences. Then, BRA is computed on the basis of the background features. RESULTS: The experimental results on the dataset collected from three hospitals show that the proposed method can achieve single and dual guidewire segmentation in X-ray fluoroscopy sequences. Higher F1 score and precision than state-of-the-art guidewire segmentation methods can be obtained in most cases. CONCLUSION: The jigsaw training strategy helps reduce the need for dual guidewire data and improve the performance of the network. Our BRA module helps reduce the influence of background information and distinguish the guidewire. The proposed methods can obtain higher performance than state-of-the-art guidewire segmentation methods.

Advantages of IMRT optimization with MCO compared to IMRT optimization without MCO in reducing small bowel high dose index for cervical cancer patients-individualized treatment options.

Background: Traditional intensity-modulated radiation therapy (IMRT) planning for cervical cancer is time-consuming and require iterative repeated optimization. In this study, we focused on leveraging multi-criteria optimization (MCO) to reduce the impact of small bowel high-dose indices on other optimization targets, thereby providing a rapid approach to individualized IMRT for cervical cancer patients. Methods: Our research involved a cohort of 25 cervical cancer patients who underwent IMRT radiotherapy. The patient inclusion criteria were as follows: (I) histopathological confirmation of cervical cancer, (II) underwent IMRT radiation therapy, and (III) a prescribed dose of 180 cGy/28 fractions for the patient. All plans were replanned by an experienced dosimetrist without the MCO (W-IMRT). On the basis of the W-IMRT plan, the individualized IMRT (I-IMRT) plan was generated under the priority trade-off of reducing the D2cc (D2cc is the minimal dose to the 2 cm3 of the small bowel receiving the maximal dose) index of the small bowel using the MCO method, maintaining target coverage and protecting other organs at risk (OARs) as much as possible. Statistical analysis was performed using the Wilcoxon signature rank test. Results: When the MCO method was applied to the IMRT plan, the high dose index decreased in the overlapping area between the small bowel and the planning treatment volume (PTV) (P<0.001, respectively). The D2cc index of the small bowel decreased to below 5,200 cGy in all I-IMRT plans. On the other hand, in PTV, the I-IMRT plan achieved a better homogeneity index (HI) compared to the W-IMRT plan. Significant dose reductions were also observed in the bladder (Dmean 144.8 cGy and V40 1.45%) (P<0.001, respectively), rectum (Dmean 43.9 cGy and V40 2.7%) (P<0.001, respectively) and bilateral femur heads (Dmean 150 cGy) (P<0.001, respectively). Conclusions: Dosimetric differences suggest that the I-IMRT plan using the MCO method provides better protection of other OARs and equivalently in PTV coverage, while lowering the high-dose index in the small bowel as much as possible for patients with cervical cancer, thus providing a rapid approach to achieving individualized IMRT for cervical cancer patients.

Multiple-dose up-titration study to evaluate the pharmacokinetics, safety and antitumor activity of apatinib in advanced gastric adenocarcinoma.

Background and purpose: The objective of this study was to investigate the pharmacokinetics, safety, and antitumor activity of apatinib, a vascular endothelial growth factor receptor 2 inhibitor, in advanced gastric adenocarcinoma or gastroesophageal junction adenocarcinoma and evaluate the effect of dose titration on dosage optimization for individual patients. Methods: Patient with advanced gastric adenocarcinoma progressed after at least one line of chemotherapy were enrolled. Apatinib was given orally once daily starting at 500 mg for 14 days, then up-titrated to 750 mg for 14 days, and then proceeded to a maximum dose of 850 mg. Dose up-titration determination was based on toxicity. The 28-day treatment cycles continued until disease progression, intolerable toxicities, withdrawal of consent, or investigator' decision. Results: A total of 60 patients were enrolled, with 17, 18, and 25 patients receiving a maximum dose of 500 mg, 750 mg, and 850 mg, respectively. The pharmacokinetic parameters varied considerably, with the interpatient coefficient of variation for steady state areas under the plasma concentration time curve (AUCss) and the mean maximum concentration of both > 50%. During 500 mg and 750 mg dosing stage, drug exposures in patients with a maximum dosage of 850 mg were lower than in those not titrated to 850 mg. Patients with total gastrectomy exhibited significantly lower AUCss than patients with partial or no gastrectomy (p = 0.004 and 0.032, respectively). Toxicities were tolerable, and disease control rate was 39.5% (95% CI 25.0%-55.6%). Conclusions: Apatinib dose titration based on toxicity could be used in clinical practice to provide optimal dosage for individual patients. Clinical Trial registration: https://clinicaltrials.gov/ct2/show/NCT02764268?term=NCT02764268&draw=2&rank=1, NCT02764268.

Comparative Analysis of the Metabolites and Biological Activity of Cultivated and Wild Lignosus rhinocerotis.

In this paper, Lignosus rhinocerotis (Cooke) Ryvarden (L. rhinocerotis) cultivated in rice medium (LRR) and in sawdust medium (LRS) was harvested. Then, in terms of the LRR, LRS, and wild L. rhinocerotis (LRW), the total flavonoid contents, total polyphenol contents, total polysaccharide contents, and metabolites were detected; antioxidants of their aqueous extracts and anti-inflammatory of their polysaccharides were performed. In addition, the possible mechanism of the polysaccharides of L. rhinocerotis inhibiting lung damage was elucidated. The results showed that 32 compounds were characterized in L. rhinocerotis, including flavonoids, terpenoids, lignans, and steroids and there were 20 compounds in cultivated and wild L. rhinocerotis; LRR has the highest total polyphenol and flavonoid contents, as well as ABTS and DPPH scavenging capacity. The total polysaccharide contents and the FRAP scavenging capacity of wild L. rhinocerotis were higher than those of cultivated L. rhinocerotis. The inhibition of polysaccharides of LRW (PLRW) on LPS-induced MRC-5 damage was stronger than that of the polysaccharides from cultivated L. rhinocerotis. The PLRW may alleviate lung damage by inhibiting the NLRP3 pathway and thereby suppressing the inflammatory response. In summary, both cultivated and wild L. rhinocerotis are abundant in bioactive components and have antioxidant and anti-inflammatory activities.

Comparison of MLC positioning deviations using log files and establishment of specific assessment parameters for different accelerators with IMRT and VMAT.

BACKGROUND AND PURPOSE: The study evaluated the differences in leaf positioning deviations by the log files of three advanced accelerators with two delivery techniques, and established specific assessment parameters of leaf positioning deviations for different types of accelerators. METHODS: A total of 420 treatment plans with 5 consecutive treatment log files were collected from the Trilogy, TrueBeam and Halcyon accelerators. Millennium MLC was equipped on the Trilogy and TrueBeam accelerators. A jawless design and dual-layer MLC were adopted on the Halcyon accelerator. 70 IMRT and 70 VMAT plans were selected randomly on each accelerator. The treatment sites of all plans included head and neck, chest, breast, pelvis and other sites. The parsing tasks for 2100 log files were proceeded by SunCheck software from Sun Nuclear Corporation. The maximum leaf root mean square (RMS) errors, 95th percentile errors and percentages of different leaf positioning errors were statistically analyzed. The correlations between these evaluation parameters and accelerator performance parameters (maximum leaf speed, mean leaf speed, gantry and arc angle) were analyzed. RESULTS: The average maximum leaf RMS errors of the Trilogy in the IMRT and VMAT plans were 0.44 ± 0.09 mm and 0.79 ± 0.07 mm, respectively, which were higher than the TrueBeam's 0.03 ± 0.01 mm, 0.03 ± 0.01 mm and the Halcyon's 0.05 ± 0.01 mm, 0.07 ± 0.01 mm. Similar data results were shown in the 95th percentile error. The maximum leaf RMS errors were strongly correlated with the 95th percentile errors (Pearson index > 0.5). The leaf positioning deviations in VMAT were higher than those in IMRT for all accelerators. In TrueBeam and Halcyon, leaf position errors above 1 mm were not found in IMRT and VMAT plans. The main influencing factor of leaf positioning deviation was the leaf speed, which has no strong correlation with gantry and arc angles. CONCLUSIONS: Compared with the quality assurance guidelines, the MLC positioning deviations tolerances of the three accelerators should be tightened. For both IMRT and VMAT techniques, the 95th percentile error and the maximum RMS error are suggested to be tightened to 1.5 and 1 mm respectively for the Trilogy accelerator. In TrueBeam and Halcyon accelerators, the 95th percentile error and maximum RMS error of 1 and 0.5 mm, respectively, are considered appropriate.

Induction Chemotherapy Followed by Chemoradiotherapy With or Without Consolidation Chemotherapy Versus Chemoradiotherapy Followed by Consolidation Chemotherapy for Esophageal Squamous Cell Carcinoma.

Objective: This study aimed to compare the efficacy and safety of induction chemotherapy followed by concurrent chemoradiotherapy (I-CCRT), induction chemotherapy followed by concurrent chemoradiotherapy and consolidation chemotherapy (I-CCRT-C), and concurrent chemoradiotherapy followed by consolidation chemotherapy (CCRT-C) for locally advanced esophageal squamous cell carcinoma (ESSC). Patients and Methods: Patients with locally advanced ESCC who underwent definitive chemoradiotherapy with cisplatin plus fluorouracil or docetaxel from February 2012 to December 2018 were retrospectively reviewed. Kaplan-Meier curve was used to estimate survival. Efficacy was assessed using RECIST, version 1.0. Prognosis factors were identified with Cox regression analysis. Results: Patients were treated with CCRT-C (n = 59), I-CCRT (n = 20), and I-CCRT-C (n = 48). The median follow-up duration was 73.9 months for the entire cohort. The ORR of the CCRT-C, I-CCRT, and I-CCRT-C groups was 89.8%, 70.0%, and 77.1%, respectively (p = 0.078). The median PFS in the CCRT-C, I-CCRT, and I-CCRT-C groups was 32.5, 16.1, and 27.1 months, respectively (p = 0.464). The median OS of the CCRT-C, I-CCRT, and I-CCRT-C groups was 45.9, 35.5, and 54.0 months, respectively (p = 0.788). Cox regression analysis indicated that I-CCRT-C and I-CCRT did not significantly prolong PFS and OS compared with CCRT-C (p > 0.05). Neutropenia grade ≥3 in CCRT-C, I-CCRT, and I-CCRT-C groups was 47.5%, 15%, and 33.3% of patients, respectively (p = 0.027). Conclusions: I-CCRT and I-CCRT-C using cisplatin plus fluorouracil or docetaxel regimen are not superior to CCRT-C in survival but seem to have less severe neutropenia than CCRT-C. Further randomized controlled studies are warranted.

Clinical efficacy and safety of norepinephrine combined with ulinastatin in the treatment of septic shock.

To analyze the clinical efficacy and safety of norepinephrine combined with ulinastatin in the treatment of septic shock. 100 patients with septic shock treated in our institution from May 2019 to May 2021 were recruited and randomly assigned to receive either norepinephrine (control group) or norepinephrine plus ulinastatin (experimental group) according to the treatment scheme. The treatment efficacy, time for shock improvement, intensive care unit (ICU) stay, total hospital stay, in-hospital mortality, 30-day survival, and changes in inflammatory factors (plasma C-reactive protein (CRP), serum lactic acid (LAC), serum procalcitonin (PCT), and interleukin-10 (IL-10)) before and after treatment were analyzed, and the sequential organ failure scores of the two groups were compared. The experimental group exhibited superior performance with respect to efficacy, ICU stays, and total hospital stay, in-hospital mortality to the control group (all P<0.05). After treatment, the experimental group presented lower levels of CRP, LAC, PCT and IL-10 and higher SOFA scores than the control group (P<0.05). Norepinephrine plus ulinastatin achieved remarkable results in the treatment of septic shock, improving the treatment efficiency, shortening the time for shock improvement and hospitalization, reducing hospital mortality, driving down the expression of inflammatory factors and enhancing the survival of patients, with high safety.

Pyrotinib plus capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases (PERMEATE): a multicentre, single-arm, two-cohort, phase 2 trial.

BACKGROUND: Patients with HER2-positive metastatic breast cancer have a high risk of developing brain metastases. Efficacious treatment options are scarce. We investigated the activity and safety of pyrotinib plus capecitabine in patients with HER2-positive metastatic breast cancer and brain metastases. METHODS: We did a multicentre, single-arm, two-cohort, phase 2 trial in eight tertiary hospitals in China. Patients aged 18 years or older who had radiotherapy-naive HER2-positive brain metastases (cohort A) or progressive disease after radiotherapy (cohort B), with an Eastern Cooperative Oncology Group performance status of 0-2, received pyrotinib 400 mg orally once daily, and capecitabine 1000 mg/m2 orally twice daily for 14 days, followed by 7 days off every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was confirmed intracranial objective response rate by investigator assessment according to the Response Evaluation Criteria In Solid Tumours (version 1.1). Activity and safety were analysed in patients with at least one dose of study drug. The study is ongoing, but recruitment is complete. The study is registered with ClinicalTrials.gov, NCT03691051. FINDINGS: Between Jan 29, 2019, and July 10, 2020, we enrolled 78 women: 51 (86%) of 59 patients in cohort A and 18 (95%) of 19 patients in cohort B had previous exposure to trastuzumab. Median follow-up duration was 15·7 months (IQR 9·7-19·0). The intracranial objective response rate was 74·6% (95% CI 61·6-85·0; 44 of 59 patients) in cohort A and 42·1% (20·3-66·5; eight of 19 patients) in cohort B. The most common grade 3 or worse treatment-emergent adverse event was diarrhoea (14 [24%] in cohort A and four [21%] in cohort B). Two (3%) patients in cohort A and three (16%) in cohort B had treatment-related serious adverse events. No treatment-related deaths occurred. INTERPRETATION: To our knowledge, this is the first prospective study showing the activity and safety of pyrotinib plus capecitabine in patients with HER2-positive breast cancer and brain metastases, especially in radiotherapy-naive population. This combination deserves further validation in a randomised, controlled trial. FUNDING: National Cancer Centre Climbing Foundation Key Project of China, Jiangsu Hengrui Pharmaceuticals. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.