17 research outputs found
A relative value method for measuring and evaluating cardiac reserve
BACKGROUND: Although a very close relationship between the amplitude of the first heart sound (S1) and the cardiac contractility have been proven by previous studies, the absolute value of S1 can not be applied for evaluating cardiac contractility. However, we were able to devise some indicators with relative values for evaluating cardiac function. METHODS: Tests were carried out on a varied group of volunteers. Four indicators were devised: (1) the increase of the amplitude of the first heart sound after accomplishing different exercise workloads, with respect to the amplitude of the first heart sound (S1)recorded at rest was defined as cardiac contractility change trend (CCCT). When the subjects completed the entire designed exercise workload (7000 J), the resulting CCCT was defined as CCCT(1); when only 1/4 of the designed exercise workload was completed, the result was defined as CCCT(1/4). (2) The ratio of S1 amplitude to S2 amplitude (S1/S2). (3) The ratio of S1 amplitude at tricuspid valve auscultation area to that at mitral auscultation area T1/M1 (4) the ratio of diastolic to systolic duration (D/S). Data were expressed as mean ± SD. RESULTS: CCCT(1/4) was 6.36 ± 3.01 (n = 67), CCCT(1) was 10.36 ± 4.2 (n = 33), S1/S2 was1.89 ± 0.94 (n = 140), T1/M1 was 1.44 ± 0.99 (n = 144), and D/S was 1.68 ± 0.27 (n = 172). CONCLUSIONS: Using indicators CCCT(1/4) and CCCT(1) may be beneficial for evaluating cardiac contractility and cardiac reserve mobilization level, S1/S2 for considering the factor for hypotension, T1/M1 for evaluating the right heart load, and D/S for evaluating diastolic cardiac blood perfusion time
Endovascular treatment of acute ischemic stroke with a fully radiopaque retriever: A randomized controlled trial
ObjectiveThe Neurohawk retriever is a new fully radiopaque retriever. A randomized controlled non-inferiority trial was conducted to compare the Neurohawk and the Solitaire FR in terms of safety and efficacy. In order to evaluate the efficacy and safety of endovascular treatment in acute ischemic stroke (AIS) caused by intracranial atherosclerotic disease (ICAD) larger vessel occlusion (LVO), a sub-analysis was performed.MethodsAcute ischemic stroke patients aged 18–80 years with LVO in the anterior circulation were randomly assigned to undergo thrombectomy with either the Neurohawk or the Solitaire FR. The primary efficacy endpoint was successful reperfusion (mTICI 2b-3) rate by the allocated retriever. A relevant non-inferiority margin was 12.5%. Safety outcomes were symptomatic intracranial hemorrhage (sICH) and all-cause mortality within 90 days. Secondary endpoints included first-pass effect (FPE), modified FPE, and favorable outcomes at 90 days. In subgroup analysis, the patients were divided into the ICAD group and non-ICAD group according to etiology, and baseline characteristics, angiographic, and clinical outcomes were compared.ResultsA total of 232 patients were involved in this analysis (115 patients in the Neurohawk group and 117 in the Solitaire group). The rates of successful reperfusion with the allocated retriever were 88.70% in the Neurohawk group and 90.60% in the Solitaire group (95%CI of the difference, −9.74% to 5.94%; p = 0.867). There were similar results in FPE and mFPE in both groups. The rate of sICH seemed higher in the Solitaire group (13.16% vs. 7.02%, p = 0.124). All-cause mortality and favorable outcome rates were comparable as well. In subgroup analysis, 58 patients were assigned to the ICAD group and the remaining 174 to the non-ICAD group. The final successful reperfusion and favorable outcome rates showed no statistically significant differences in two groups. Mortality within 90 days was relatively lower in the ICAD group (6.90% vs. 17.24%; p = 0.054).ConclusionThe Neurohawk retriever is non-inferior to the Solitaire FR in the mechanical thrombectomy of large vessel occlusion-acute ischemic stroke (LVO-AIS). The sub-analysis suggested that endovascular treatment including thrombectomy with the retriever and essential rescue angioplasty is effective and safe in AIS patients with intracranial atherosclerotic disease-larger vessel occlusion (ICAD-LVO).Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT04995757, number: NCT04995757
Multi-center pragmatic studies evaluating the time indicator of cardiac perfusion reserve
Enhancing Doxorubicin Delivery toward Tumor by Hydroxyethyl Starch‑<i>g</i>‑Polylactide Partner Nanocarriers
Doxorubicin (DOX),
a kind of wide-spectrum chemotherapeutic drug,
can cause severe side effects in clinical use. To enhance its antitumor
efficacy while reducing the side effects, two kinds of nanoparticles
with desirable compositions and properties were assembled using optimally
synthesized hydroxyethyl starch-grafted-polylactide (HES-<i>g</i>-PLA) copolymers and utilized as partner nanocarriers. The large
empty HES-<i>g</i>-PLA nanoparticles (mean size, <i>ca.</i> 700 nm), at an optimized dose of 400 mg/kg, were used
to block up the reticuloendothelial system in tumor-bearing mice 1.5
h in advance, and the small DOX-loaded HES-<i>g</i>-PLA
nanoparticles (mean size, <i>ca.</i> 130 nm) were subsequently
applied to the mice. When these partner nanocarriers were administered
in this sequential mode, the released DOX had a significantly prolonged
plasma half-life time and much slower clearance rate as well as a
largely enhanced intratumoral accumulation as compared to free DOX. <i>In vivo</i> antitumor studies demonstrated that the DOX-loaded
HES-<i>g</i>-PLA nanoparticles working together with their
partner exhibited remarkably enhanced antitumor efficacy in comparison
to free DOX. In addition, these HES-<i>g</i>-PLA partner
nanocarriers showed negligible damage to the normal organs of the
treated mice. Considering safe and efficient antitumor performance
of DOX-loaded HES-<i>g</i>-PLA nanoparticles, the newly
developed partner nanocarriers in combination with their administration
mode have promising potential in clinical cancer chemotherapy
Digestive system is a potential route of COVID-19: An analysis of single-cell coexpression pattern of key proteins in viral entry process
Objective: Since December 2019, a newly identified coronavirus (severe acute respiratory syndrome coronavirus (SARS-CoV-2)) has caused outbreaks of pneumonia in Wuhan, China. SARS-CoV-2 enters host cells via cell receptor ACE II (ACE2) and the transmembrane serine protease 2 (TMPRSS2). In order to identify possible prime target cells of SARS-CoV-2 by comprehensive dissection of ACE2 and TMPRSS2 coexpression pattern in different cell types, five datasets with single-cell transcriptomes of lung, oesophagus, gastric mucosa, ileum and colon were analysed. Design: Five datasets were searched, separately integrated and analysed. Violin plot was used to show the distribution of differentially expressed genes for different clusters. The ACE2-expressing and TMPRRSS2-expressing cells were highlighted and dissected to characterise the composition and proportion. Results: Cell types in each dataset were identified by known markers. ACE2 and TMPRSS2 were not only coexpressed in lung AT2 cells and oesophageal upper epithelial and gland cells but also highly expressed in absorptive enterocytes from the ileum and colon. Additionally, among all the coexpressing cells in the normal digestive system and lung, the expression of ACE2 was relatively highly expressed in the ileum and colon. Conclusion: This study provides the evidence of the potential route of SARS-CoV-2 in the digestive system along with the respiratory tract based on single-cell transcriptomic analysis. This finding may have a significant impact on health policy setting regarding the prevention of SARS-CoV-2 infection. Our study also demonstrates a novel method to identify the prime cell types of a virus by the coexpression pattern analysis of single-cell sequencing data
Nanocolloidosomes with Selective Drug Release for Active Tumor-Targeted Imaging-Guided Photothermal/Chemo Combination Therapy
Selective drug release
is highly desirable for photothermal/chemo combination therapy when
two or even more theranostic agents are encapsulated together within
the same nanocarrier. A conventional nanocarrier can hardly achieve
this goal. Herein, doxorubicin and indocyanine green (DOX/ICG)-loaded
nanocolloidosomes (NCs), with selective drug release, were fabricated
as a novel multifunctional theranostic nanoplatform for photothermal/chemo
combination therapy. Templating from galactose-functionalized hydroxyethyl
starch-polycaprolactone (Gal-HES-PCL) nanoparticles-stabilized Pickering
emulsions, the resultant DOX/ICG@Gal-HES-PCL NCs had a diameter of
around 140 nm and showed an outstanding tumor-targeting ability, preferable
tumor penetration capability, and promotion of photothermal effect.
Moreover, these NCs can be used for NIR fluorescence imaging and thus
render real-time imaging of solid tumors with high contrast. Collectively,
such NCs achieved the best in vivo antitumor efficacy combined with
laser irradiation compared with DOX/ICG@HES-PCL NCs and DOX/ICG mixture.
These NCs are valuable for active tumor-targeted imaging-guided combination
therapy against liver cancer and potentially other diseases
α‑Amylase- and Redox-Responsive Nanoparticles for Tumor-Targeted Drug Delivery
Paclitaxel (PTX)
is an effective antineoplastic agent and shows potent antitumor activity
against a wide spectrum of cancers. Yet, the wide clinical use of
PTX is limited by its poor aqueous solubility and the side effects
associated with its current therapeutic formulation. To tackle these
obstacles, we report, for the first time, α-amylase- and redox-responsive
nanoparticles based on hydroxyethyl starch (HES) for the tumor-targeted
delivery of PTX. PTX is conjugated onto HES by a redox-sensitive disulfide
bond to form HES–SS-PTX, which was confirmed by results from
NMR, high-performance liquid chromatography-mass spectrometry, and
Fourier transform infrared spectrometry. The HES–SS-PTX conjugates
assemble into stable and monodispersed nanoparticles (NPs), as characterized
with Dynamic light scattering, transmission electron microscopy, and
atomic force microscopy. In blood, α-amylase will degrade the
HES shell and thus decrease the size of the HES–SS-PTX NPs,
facilitating NP extravasation and penetration into the tumor. A pharmacokinetic
study demonstrated that the HES–SS-PTX NPs have a longer half-life
than that of the commercial PTX formulation (Taxol). As a consequence,
HES–SS-PTX NPs accumulate more in the tumor compared with the
extent of Taxol, as shown in an in vivo imaging study. Under reductive
conditions, the HES–SS-PTX NPs could disassemble quickly as
evidenced by their triggered collapse, burst drug release, and enhanced
cytotoxicity against 4T1 tumor cells in the presence of a reducing
agent. Collectively, the HES–SS-PTX NPs show improved in vivo
antitumor efficacy (63.6 vs 52.4%) and reduced toxicity in 4T1 tumor-bearing
mice compared with those of Taxol. These results highlight the advantages
of HES-based α-amylase- and redox-responsive NPs, showing their
great clinical translation potential for cancer chemotherapy