To evaluate the immunogenicity and safety of simultaneous administration of the enterovirus 71 (EV71) vaccine with the measles and rubella (MR) combined vaccine.
In this phase 4, randomized, ...open-label and noninferiority study, a total of 680 infants aged 8 months were enrolled and assigned to the simultaneous administration group (infants received the first dose of EV71 vaccine and MR vaccine on Day 0, and the second dose of EV71 vaccine on Day 28), or the separate administration groups (EV71 group: infants received two doses of EV71 vaccine on Day 0 and Day 28, respectively; MR group: infants received MR vaccine on Day 0). Blood sample was obtained on Day 0 and Day 56 to measure antibody responses to each of the antigens in terms of antibody titer or concentration, respectively. Local and systemic adverse reactions (ARs) and other adverse events (AEs) following each dose were monitored and compared among groups.
After vaccination, simultaneous administration group showed similar seroconversion rates of antibody against EV71(97.9%), measles (97.4%), and rubella (94.3%) compared to EV71 group (99.6% for anti-EV71) or MR group (98.4% for anti-measles and 98.9% for anti-rubella, respectively). Noninferiority was demonstrated for all antibodies as the lower limits of two-sided 97.5% confidence intervals (CIs) of the difference in seroconversion rates between simultaneous administration group and separate administration groups were above the predefined margin of −10%. Additionally, the adverse reaction rates were comparable among groups (54.4% in the simultaneous group versus 43.9% in the MR group versus 52.6% in the EV71 group).
Antibody responses induced by simultaneous administration of EV71 vaccine with MR vaccine were robust and noninferior to those by single administration alone. Like the previous findings by single administration alone, simultaneous administration demonstrated comparable reactogenicity and safety profiles.
Fasting has been grown in popularity with multiple potential benefits. However, very few studies dynamically monitor physiological and pathological changes during long‐term fasting using noninvasive ...methods. In the present study, we recruited 37 individuals with metabolic syndrome to engage in a 5‐day water‐only fasting regimen, and simultaneously captured the molecular alterations through urinary proteomics and metabolomics. Our findings reveal that water‐only fasting significantly mitigated metabolic syndrome‐related risk markers, such as body weight, body mass index, abdominal circumference, blood pressure, and fasting blood glucose levels in metabolic syndrome patients. Indicators of liver and renal function remained within the normal range, with the exception of uric acid. Notably, inflammatory response was inhibited during the water‐only fasting period, as evidenced by a decrease in the human monocyte differentiation antigen CD14. Intriguingly, glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation underwent a sex‐dependent reprogramming throughout the fasting period, whereby males exhibited a greater upregulation of carbohydrate metabolism‐related enzymes than females. This disparity may be attributed to evolutionary pressures. Collectively, our study sheds light on the beneficial physiological effects and novel dynamic molecular features associated with fasting in individuals with metabolic syndrome using noninvasive methods.
We recruited 37 individuals with metabolic syndrome to engage in a 5‐day water‐only fasting regimen, and simultaneously captured the molecular alterations through urinary proteomics and metabolomics. The results showed that the inflammatory response was inhibited during the water‐only fasting period. Interestingly, glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation underwent a sex‐dependent reprogramming throughout the fasting period, whereby males exhibited a greater upregulation of carbohydrate metabolism‐related enzymes than females.
Long-term administration of chemotherapeutic agents often leads to multiple drug resistance (MDR), which greatly impairs the treatment outcome. To overcome this problem, a biodegradable nanocarrier ...based on an acid-sensitive calcium phosphate/silica dioxide (CAP/SiO
) composite was constructed for the codelivery of drug and siRNA. Anticancer drug doxorubicin (DOX) was encapsulated into the composite scaffold by interacting with the exposed Ca
of CAP/SiO
to achieve high drug loading (180 μg mg
). With further decoration of siRNA, the nanocarrier was applied to enhance the therapeutic efficacy by silencing MDR-relevant genes (P-gp) of DOX-resistance K562/ADR cancer cells. Benefiting from the intrinsic acid degradability of CAP/SiO
, the nanocomposite demonstrated pH-responsive release behavior, favoring drug/siRNA release within acidic endo-/lysosomes. Consequently, due to the drug and gene effects, this biodegradable nanomedicine demonstrated enhanced therapeutic efficiency, providing a novel strategy for cancer therapy.
Uncertainty exists about whether lowering systolic blood pressure to less than 120 mm Hg is superior to that of less than 140 mm Hg, particularly in patients with diabetes and patients with previous ...stroke.
In this open-label, blinded-outcome, randomised controlled trial, participants with high cardiovascular risk were enrolled from 116 hospitals or communities in China. We used minimised randomisation to assign participants to intensive treatment targeting standard office systolic blood pressure of less than 120 mm Hg or standard treatment targeting less than 140 mm Hg. The primary outcome was a composite of myocardial infarction, revascularisation, hospitalisation for heart failure, stroke, or death from cardiovascular causes, assessed by the intention-to-treat principle. This trial was registered with ClinicalTrials.gov, NCT04030234.
Between Sept 17, 2019, and July 13, 2020, 11 255 participants (4359 with diabetes and 3022 with previous stroke) were assigned to intensive treatment (n=5624) or standard treatment (n=5631). Their mean age was 64·6 years (SD 7·1). The mean systolic blood pressure throughout the follow-up (except the first 3 months of titration) was 119·1 mm Hg (SD 11·1) in the intensive treatment group and 134·8 mm Hg (10·5) in the standard treatment group. During a median of 3·4 years of follow-up, the primary outcome event occurred in 547 (9·7%) participants in the intensive treatment group and 623 (11·1%) in the standard treatment group (hazard ratio HR 0·88, 95% CI 0·78–0·99; p=0·028). There was no heterogeneity of effects by diabetes status, duration of diabetes, or history of stroke. Serious adverse events of syncope occurred more frequently in the intensive treatment group (24 0·4% of 5624) than in standard treatment group (eight 0·1% of 5631; HR 3·00, 95% CI 1·35–6·68). There was no significant between-group difference in the serious adverse events of hypotension, electrolyte abnormality, injurious fall, or acute kidney injury.
For hypertensive patients at high cardiovascular risk, regardless of the status of diabetes or history of stroke, the treatment strategy of targeting systolic blood pressure of less than 120 mm Hg, as compared with that of less than 140 mm Hg, prevents major vascular events, with minor excess risk.
The Ministry of Science and Technology of China and Fuwai Hospital.
For the Mandarin translation of the abstract see Supplementary Materials section.
Temporal lobe epilepsy (TLE) is a focal, recurrent, and refractory neurological disorder. Therefore, precisely targeted treatments for TLE are greatly needed. We designed anti-CB1 liposomes that can ...bind to CB1 receptors in the hippocampus to deliver photocaged compounds (ruthenium bipyridine triphenylphosphine γ-aminobutyric acid, RuBi-GABA) in the TLE rats. A 16-channel silicon microelectrode array (MEA) was implanted for simultaneously monitoring electrophysiological signals of neurons. The results showed that anti-CB1 liposomes were larger in size and remained in the hippocampus longer than unmodified liposomes. Following the blue light stimulation, the neural firing rates and the local field potentials of hippocampal neurons were significantly reduced. It is indicated that RuBi-GABA was enriched near hippocampal neurons due to anti-CB1 liposome delivery and photolyzed by optical stimulation, resulting dissociation of GABA to exert inhibitory actions. Furthermore, K-means cluster analysis revealed that the firing rates of interneurons were decreased to a greater extent than those of pyramidal neurons, which may have been a result of the uneven diffusion of RuBi-GABA due to liposomes binding to CB1. In this study, we developed a novel, targeted method to regulate neural electrophysiology in the hippocampus of the TLE rat using antibody-modified nanoliposomes, implantable MEA, and photocaged compounds. This method effectively suppressed hippocampal activities during seizure ictus with high spatiotemporal resolution, which is a crucial exploration of targeted therapy for epilepsy.
The natural product mangiferin (compound 7) has been identified as a potential glucokinase activator by structure-based virtual ligand screening. It was proved by enzyme activation experiment and ...cell-based assays in vitro, with potency in micromolar range. Meanwhile, this compound showed good antihyperglycemic activity in db/db mice without obvious side effects such as excessive hypoglycaemia.
Objectives
To develop a nomogram for the local tumor progression (LTP) in patients with early‐stage hepatocellular carcinoma (HCC) after computed tomography‐guided percutaneous microwave ablation ...(CT‐PMWA) and to assess clinical‐pathologic risk factors for individual LTP estimation. Furthermore, we compared the prognostic predictive ability for LTP between the nomogram and the traditional staging systems.
Methods
This retrospective study was approved by the institutional review board. Five hundred and forty treatment‐naïve patients with HCC according to the Milan criteria, who subsequently underwent CT‐PMWA were reviewed from 2009 to 2019. Baseline characteristics were collected to identify the risk factors for the determination of LTP after CT‐PMWA. The multivariate Cox proportional‐hazards model based on significant prognostic factors of LTP was used to construct the nomogram, which was then assessed for its predictive accuracy using mainly the Harrell's C‐index and time‐dependent area under the curve (tAUC).
Results
After a median follow‐up time of 28.7 months, 6.5% (35/540) patients had LTP. The nomogram was developed based on the tumor size, tumor number, Child‐Turcotte‐Pugh (CTP) grade, platelet, and alanine aminotransferase (ALT). The nomogram had good calibration and discriminatory abilities in the training set, with C‐indexes of 0.799 (95% confidence interval (CI): 0.738, 0.860), and tAUCs of 0.844 (CI: 0.728, 0.895), that were greater than those of traditional staging systems. Internal validation with 1000 bootstrap resamples had a good C‐index of 0.735 (CI: 0.648, 0.816).
Conclusions
The nomogram model can be used to predict accurately LTP after CT‐PMWA for early‐stage HCC, as well as to assist physicians during the therapeutic decision‐making process.
Local tumor progression (LTP) is a key criterion for evaluating the technical success of various thermal ablation techniques. Insufficient ablation margin is an independent risk factor associated with LTP, however, it is difficult to measure accurately. This normogram demonstrated higher predictive accuracy compared with traditional staging systems and may prove to be useful in centers that do not have the facilities for measuring ablation margin.
A new ferrocene‐pyrene dyad Fc‐PYS for anion recognition was rationally designed and synthesized, in which the ferrocene and the pyrene groups were combined by the imidazolium and sulfonamide anion ...donors. The structure of the probe was characterized by single‐crystal X‐ray diffraction. The anion recognition performance of the probe was studied by fluorescence spectroscopy and electrochemical techniques. In acetonitrile solution, Fc‐PYS can fluorescently recognize F− and H2PO4− with different models. Upon the addition of H2PO4−, the fluorescence of Fc‐PYS was increased. However, the complexation with F− quenched its fluorescence. At the same time, Fc‐PYS showed electrochemical response toward basic anions F−, H2PO4−, and AcO− with the ferrocene‐based red/ox potential a negative shift with H2PO4− > F− > AcO−. Furthermore, the binding mechanism between Fc‐PYS and anion has been investigated in detail by 1H NMR titration.
Objectives
To develop a clinicopathological‐based nomogram to improve the prediction of the seeding risk of after percutaneous thermal ablation (PTA) in primary liver carcinoma (PLC).
Methods
A total ...of 2030 patients with PLC who underwent PTA were included between April 2009 and December 2018. The patients were grouped into a training dataset (n = 1024) and an external validation dataset (n = 1006). Baseline characteristics were collected to identify the risk factors of seeding after PTA. The multivariate Cox proportional hazards model based on the risk factors was used to develop the nomogram, which was used for assessment for its predictive accuracy using mainly the Harrell's C‐index and receiver operating characteristic curve (AUC).
Results
The median follow‐up time was 30.3 months (range, 3.2‐115.7 months). The seeding risk was 0.89% per tumor and 1.5% per patient in the training set. The nomogram was developed based on tumor size, subcapsular, α‐fetoprotein (AFP), and international normalized ratio (INR). The 1‐, 2‐, and 3‐year cumulative seeding rates were 0.1%, 0.7% and 1.2% in the low‐risk group, and 1.7%, 6.3% and 6.3% in the high‐risk group, respectively, showing significant statistical difference (P < .001). The nomogram had good calibration and discriminatory abilities in the training set, with C‐indexes of 0.722 (95% confidence interval CI: 0.661, 0.883) and AUC of 0.850 (95% CI: 0.767, 0.934). External validation with 1000 bootstrapped sample sets showed a good C‐index of 0.706 (95% CI: 0.546, 0.866) and AUC of 0.736 (95% CI: 0. 646, 0.827).
Conclusions
The clinicopathological‐based nomogram could be used to quantify the probability of seeding risk after PTA in PLC.
Seeding on the thoracoabdominal wall from primary liver carcinoma is a potential complication after percutaneous thermal ablation. Seeding risk is a liver ablation complication that affects future oncology management. A calibrated and objective model to predict seeding risk after liver ablation may guide patient selection and ablation treatment.
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