To evaluate the efficacy and safety of recombinant human serum albumin /granulocyte colony-stimulating factor (rHSA/G-CSF) in breast cancer following receipt of cytotoxic agents.
The phase 1b trial ...assessed the pharmacokinetics, pharmacodynamics, and safety of dose-escalation, ranging from rHSA/G-CSF 1800 μg, 2100 μg, and 2400 μg. Randomized controlled phase 2b trial was further conducted to ensure the comparative efficacy and safety of rHSA/G-CSF 2400 μg and rhG-CSF 5 μg/kg. In multicenter, randomized, open-label, parallel, phase 2 study, participants treated with anthracycline-containing chemotherapy were assigned in a ratio 1:1:1 to receive double delivery of rHSA/G-CSF 1200 μg, 1500 μg, and continuous rhG-CSF 5 μg/kg.
Between December 16, 2014, to July 23, 2018, a total of 320 patients were enrolled, including 25 individuals in phase 1b trial, 80 patients in phase 2b trial, and 215 participants in phase 2 study. The mean duration of agranulocytosis during the first chemotherapeutic intermission was observed as 1.14 ± 1.35 days in rHSA/G-CSF 1500 μg, which was comparable with that of 1.07 ± 0.97 days obtained in rhG-CSF control (P = 0.71). Safety profiles were assessed to be acceptable ranging from rHSA/G-CSF 1800 μg to 2400 μg, while the double delivery of HSA/G-CSF 2400 μg failed to meet the noninferiority in comparison with rhG-CSF.
The prospective randomized controlled trials demonstrated that rHSA/G-CSF was efficacious and well-tolerated with an approachable frequency and expense of application for prophylactic management of agranulocytosis. The double delivery of rHSA/G-CSF 1500 μg in comparisons with paralleling G-CSF preparations is warranted in the phase 3 trial.
ClinicalTrials.gov identifiers: NCT02465801 (11/17/2014), NCT03246009 (08/08/2017), NCT03251768 (08/07/2017).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Group VIB transition metal dichalcogenides (TMDs) have been successfully demonstrated as saturable absorbers (SAs) for pulsed fiber lasers. For the group comprising IVB TMDs, applications in this ...field remain unexplored. In this work, ZrS₂-based SA is prepared by depositing a ZrS₂ nanostructured film onto the side surface of a D-shaped fiber. The nonlinear optical properties of the prepared SA are investigated, which had a modulation depth of 3.3% and a saturable intensity of 13.26 MW/cm². In a pump power range of 144⁻479 mW, the Er-doped fiber (EDF) laser with ZrS₂ can operate in the dual-wavelength Q-switching state. The pulse duration declined from 10.0 μs down to 2.3 μs. The single pulse energy reached 53.0 nJ. The usage of ZrS₂ as a SA for pulse generation in fiber lasers is presented for the first time. Compared to the experimental results of dual-wavelength Q-switched fiber lasers with two-dimensional (2D) materials, our laser performance was better. Our work indicates that the group comprising IVB TMD ZrS₂ has bright prospects for nonlinear optical applications.
This study was performed to analyze the rule of confluence of the caudate lobe bile duct (CLD) into the left hepatic duct (LHD) and to discuss the protective strategy during left hemihepatectomy.
MRI ...of 400 patients and T-tube angiography images of 100 patients were collected, and the imaging rules of the confluence of the CLD into the LHD were summarized. The clinical data of 33 patients who underwent left hemihepatectomy using the protective strategy were analyzed.
MRI and T-tube angiography images showed that the length from the confluence point of the CLD into the LHD to the confluence of the left and right hepatic ducts was 1.19 ± 0.40 cm and 1.26 ± 0.39 cm, respectively. The average angle between the longitudinal axis of the 2 bile ducts was 68.27° ± 22.59° and 66.58 ± 22.88°, respectively. Coronal and cross-sectional images showed that inflow from the foot side to the cranial side was noted in 79.8% and 82.0% of patients, respectively, and inflow from the dorsal to the ventral side was observed in 84.5% and 88.0%, respectively. Based on these imaging rules, the safe transection length and plane were summarized, and the CLD was effectively protected in 33 cases of left hemihepatectomy.
In left hemihepatectomy, the LHD should be transected at least 1.5 cm away from the confluence of the left and right hepatic ducts, and the plane of transection should be oblique to the dorsal side at an angle of 45° with the LHD, these parameters represent an effective strategy to protect the CLD.
In studies of pulse wave analysis, single-channel sensors only adopt single temporal pulse signals without spatial information to show pulse-feeling patterns. Multi-channel arterial pulse signals, ...also named as three-dimensional pulse images (3DPIs), provide the spatial and temporal characteristics of radial pulse signals. When involving single or few-channel sensors, pressing offsets have substantial impacts on obtaining inaccurate physiological parameters like tidal peak (P
).
This study discovers the pressing offsets in multi-channel pulse signals and analyzes the relationship between the pressing offsets and time of P2 (T
) by qualifying the pressing offsets. First, we employ a data acquisition system to capture 3DPIs. Subsequently, the errorT
is developed to qualify the pressing offsets.
The outcomes display a central low and peripheral high pattern. Additionally, the errorT
increase as the distances from the artery increase, particularly at the radial ends of the blood flow direction. For every 1 mm increase in distances between sensing elements and center sensing elements, the errorT
in the radial direction escalates by 4.87%. When the distance is greater than 3.42 mm, the errorT
experiences a sudden increase.
The results show that increasing the sensor channels can overcome the pressing offsets in radial pulse signal acquisition.
We fabricated a compact reflective molybdenum disulfide (MoS 2 ) saturable absorber (SA) by coating a few layers of a MoS 2 thin film on a silver mirror using the Langmuir-Blodgett (LB) method. The ...LB method showed to be effective in producing a thin film with smooth surface, low optical scattering, and low nonsaturable losses. By inserting the LB MoS 2 -SA into a V-shaped Nd:GdVO 4 laser cavity, a stable Q-switched laser operation with the maximum average output power of 0.89 W corresponding to a pulse width of 91.6 ns is obtained. The slope efficiency is as high as 44.4% and the optical conversion efficiency is 15.6%, indicating low losses of the LB MoS 2 -SA.
Thyroid autoimmunity is common in papillary thyroid carcinoma (PTC) and was believed to confer a better prognosis; however, controversy still remains. This study aimed to investigate the prognostic ...value of chronic lymphocytic thyroiditis (CLT) and preoperative thyroid peroxidase antibody (TPOAb) in PTC patients.
A retrospective analysis was performed on 5,770 PTC patients who underwent surgical treatment with pathologically confirmed PTC in our institution between 2012 to 2016. The patients were divided into groups with respect to the coexistence of CLT or preoperative TPOAb levels. The clinicopathological characteristics and disease-free survival (DFS) rates were compared between the groups.
The coexistence of CLT was likely to have bilateral, multifocal tumors. Particularly, PTC patients with TPOAb++ (>1,000 IU/L) had a larger tumor size (
= 0.007) and higher rates of bilaterality and multifocality than those with TPOAb- (TPOAb< 100 IU/L), while for lymph node metastasis and extrathyroidal extension, there is no statistical difference. Tumor recurrence was found in 15 of 425 (3.5%), 9 of 436 (2.1%), and 56 of 3,519 (1.6%) patients with TPOAb++, TPOAb+, and TPOAb-, respectively (
= 0.017). On univariate analysis, TPOAb++ was correlated with tumor recurrence, with a hazard ratio of 2.20 95% confidence interval (CI), 1.25-3.89, which remained as an independent risk factor at 1.98 (95% CI, 1.10-3.55) on multivariate analysis. PTC patients with TPOAb++ had the lowest DFS rates (96.5
97.9
98.4%,
= 0.020).
CLT is not a protective factor in PTC patients. We provide initial evidence that the preoperative TPOAb instead predicts recurrence in papillary thyroid carcinoma.
Metastasis is responsible for at least 90% of colon cancer (CC)‐related deaths. Lipid metabolism is a critical factor in cancer metastasis, yet the underlying mechanism requires further ...investigation. Herein, through the utilisation of single‐cell sequencing and proteomics, we identified sulfotransferase SULT2B1 as a novel metastatic tumour marker of CC, which was associated with poor prognosis. CC orthotopic model and in vitro assays showed that SULT2B1 promoted lipid metabolism and metastasis. Moreover, SULT2B1 directly interacted with SCD1 to facilitate lipid metabolism and promoted metastasis of CC cells. And the combined application of SCD1 inhibitor CAY with SULT2B1‐ konockout (KO) demonstrated a more robust inhibitory effect on lipid metabolism and metastasis of CC cells in comparison to sole application of SULT2B1‐KO. Notably, we revealed that lovastatin can block the SULT2B1‐induced promotion of lipid metabolism and distant metastasis in vivo. Further evidence showed that SMC1A transcriptionally upregulated the expression of SULT2B1. Our findings unveiled the critical role of SULT2B1 in CC metastasis and provided a new perspective for the treatment of CC patients with distant metastasis.
1. SULT2B1 promoted lipid metabolism and metastasis of colon cancer.
2. SULT2B1 interacted with SCD1 to facilitate lipid metabolism and metastasis.
3. SMC1A transcriptionally upregulated the expression of SULT2B1 in colon cancer.
Pulse wave analysis (PWA) has been widely used in the medical field. A novel multi-channel sensor is employed in arterial pulse acquisition and brings richer physiological information to PWA. ...However, the noise of this sensor is distributed in the main frequency band of the pulse signal, which seriously interferes with subsequent analyses and is difficult to eliminate by existing methods. This study proposes a cross-channel dynamic weighting robust principal component analysis algorithm. A channel-scaled factor technique is used to manipulate the weighting factors in the nuclear norm. This factor can adaptively adjust the weights among the channels according to the signal pattern of each channel, optimizing the feature extraction in multi-channel signals. A series of performance evaluations were conducted, and four well-known de-noising algorithms were used for comparison. The results reveal that the proposed algorithm achieved one of the best de-noising performances in the time and frequency domains. The mean of h1 in the amplitude relative error (ARE) was 23.4% smaller than for the WRPCA algorithm. Moreover, our algorithm could accelerate convergence and reduce the computational time complexity by approximately 34.6%. These results demonstrate the performance and efficiency of the algorithm. Meanwhile, the idea can be extended to other multi-channel physiological signal de-noising and feature extraction fields.
We report the temperature dependence of the spin pumping effect for Y
3
Fe
5
O
12
(YIG, 0.9 μm)/NiO (
t
NiO
)/W (6 nm) (
t
NiO
= 0 nm, 1 nm, 2 nm, and 10 nm) heterostructures. All samples exhibit a ...strong temperature-dependent inverse spin Hall effect (ISHE) signal
I
c
and sensitivity to the NiO layer thickness. We observe a dramatic decrease of
I
c
with inserting thin NiO layer between YIG and W layers indicating that the inserting of NiO layer significantly suppresses the spin transport from YIG to W. In contrast to the noticeable enhancement in YIG/NiO (
t
NiO
≈ 1–2 nm)/Pt, the suppression of spin transport may be closely related to the specific interface-dependent spin scattering, spin memory loss, and spin conductance at the NiO/W interface. Besides, the
I
c
of YIG/NiO/W exhibits a maximum near the
T
N
of the AF NiO layer because the spins are transported dominantly by incoherent thermal magnons.
Background
BAT1706 is a proposed biosimilar of bevacizumab (Avastin®). We aimed to compare the efficacy and safety of BAT1706 with that of EU‐sourced reference bevacizumab (EU‐bevacizumab) in ...patients with advanced nonsquamous non‐small cell lung cancer (NSCLC).
Methods
Patients were randomized 1:1 to BAT1706 plus paclitaxel and carboplatin (BAT1706 arm) or EU‐bevacizumab plus paclitaxel and carboplatin (EU‐bevacizumab arm) given every 3 weeks for six cycles, followed by maintenance therapy with BAT1706 or EU‐bevacizumab. The primary endpoint was overall response rate at week 18 (ORR18). Clinical equivalence was demonstrated if the 90% confidence interval (CI) of the BAT1706:EU‐bevacizumab ORR18 risk ratio was contained within the predefined equivalence margins of 0.75–1.33 (China National Medical Products Administration requirements), or 0.73–1.36 (US Food and Drug Administration), or if the 95% CI of the ORR18 risk difference between treatments was contained within the predefined equivalence margin of −0.12 to 0.15 (EMA requirements).
Results
In total, 649 randomized patients (BAT1706, n = 325; EU‐bevacizumab, n = 324) received at least one cycle of combination treatment. The ORR18 was comparable between the BAT1706 and EU‐bevacizumab arms (48.0% and 44.5%, respectively). The ORR18 risk ratio of 1.08 (90% CI: 0.94–1.24) and the ORR18 risk difference of 0.03 (95% CI: −0.04 to 0.11) were within the predefined equivalence margins, demonstrating the biosimilarity of BAT1706 and EU‐bevacizumab. The safety profile of BAT1706 was consistent with that of EU‐bevacizumab and no new safety signals were observed.
Conclusion
In patients with advanced nonsquamous NSCLC, BAT1706 demonstrated clinical equivalence to EU‐bevacizumab in terms of efficacy, safety, pharmacokinetics, and immunogenicity.
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