Acupuncture for dystonia in brain-type Wilson's disease with internal retention of damp heat pattern: A randomized clinical trail针刺治疗湿热内蕴型肝豆状核变性脑型肌张力障碍-随机临床试验

ObjectiveTo observe the clinical efficacy of acupuncture on dystonia in brain-type Wilson's disease (WD) with internal retention of damp heat pattern.MethodsA total of 60 patients with WD dystonia with internal retention of damp heat pattern were randomized into acupuncture and medication groups using a random number table, with 30 participants in each group. All patients had a low-copper diet and consumed dimercaptopropanesulfonate sodium (DMPS) for copper excretion. In the acupuncture group, on the base of the same treatment as that given to the medication group, acupuncture was applied at B?ihuì (百会GV20), Shéntíng (神庭GV24), Chéngjiāng (承浆CV4), Jiānyú (肩髃LI5), Nàoshū (臑俞SI10), Wàiguān (外关TE5), Nèiguān (内关PC6), Sh?usānl? (手三里LI10), Hég? (合谷LI4), Yángxī (阳溪LI5), Huántiào (环跳GB30), Bìguān (髀关ST31), Yánglíngquán (阳陵泉GB34), Fēnglóng (丰隆ST40), Zúsānl? (足三里ST36), Sānyīnjiāo (三阴交SP6), Xuánzhōng (悬钟GB39), and Xíngjiān (行间LR2). Before and 24 days after treatment, the modified Ashworth scale (MAS) and Burke–Fahn–Marsden dystonia rating scale (BFMDRS) were used to evaluate dystonia symptoms.The allocation scheme was concealed for the outcome assessors.ResultsThe data of 30 cases were analyzed in each group.Before treatment, the MAS score difference between the acupuncture and medication groups was not statistically significant (P > 0.05). Compared with the score before treatment, the MAS score was lower significantly in both the acupuncture group (2.63 ± 0.76 vs 4.50 ± 0.78) and medication group (3.30 ± 0.65 vs 4.40 ± 0.77) after treatment (both P < 0.05). After treatment, the MAS score in the acupuncture group was significantly lower than that in the medication group (P < 0.01). Before treatment, the BFMDRS score was not significantly different between the two groups (P > 0.05). Compared with the score before treatment, the BFMDRS score was significantly lower in both the acupuncture (64.97 ± 14.26 vs 85.23 ± 16.99) and medication groups (11.33 ± 2.60 vs 75.40 ± 16.25) after treatment (both P < 0.05). The BFMDRS score of the acupuncture group was lower than that of the medication group after treatment (P < 0.05).During treatment, 1 case had allergic reaction of DMPS in the acupuncture group, manifested as reddish skin and skin rashes, and the allergic symptoms disappeared after anti-allergic treatment. There was no any adverse reaction in the medication group.ConclusionCombined treatment with acupuncture and Western medication is significantly effective against dystonia in brain-type WD with internal retention of damp heat pattern.     

Clinical evaluation of [18F]pitavastatin for quantitative analysis of hepatobiliary transporter activity

It is widely accepted that uptake and efflux transporters on clearance organs play crucial roles in drug disposition. Although in vitro transporter assay system can identify the intrinsic properties of the target transporters, it is not so easy to precisely predict in vivo pharmacokinetic parameters from in vitro data. Positron emission tomography (PET) imaging is a useful tool to directly assess the activity of drug transporters in humans. We recently developed a practical synthetic method for fluorine-18-labeled pitavastatin ([¹⁸F]PTV) as a PET probe for quantitative evaluation of hepatobiliary transport. In the present study, we conducted clinical PET imaging with [¹⁸F]PTV and compared the pharmacokinetic properties of the probe for healthy subjects with or without rifampicin pretreatment. Rifampicin pretreatment significantly suppressed the hepatic maximum concentration and biliary excretion of the probe to 52% and 34% of the control values, respectively. Rifampicin treatment markedly decreased hepatic uptake clearance (21% of the control), and moderately canalicular efflux clearance with regard to hepatic concentration (52% of the control). These results demonstrate that [¹⁸F]PTV is a useful probe for clinical investigation of the activities of hepatobiliary uptake/efflux transporters in humans.     

Simplified daptomycin dosing regimen for adult patients with methicillin-resistant Staphylococcus aureus infections based on population pharmacokinetic analysis

Daptomycin is used to treat methicillin-resistant Staphylococcus aureus (MRSA) infections. Current guidelines recommend higher daptomycin doses (8–10 mg/kg) for severe infections; however, pharmacokinetic (PK) and pharmacodynamic-based dosing strategies are still limited. Therefore, we designed a new optimal daptomycin dosing regimen for patients with MRSA infections using a population PK modeling approach. A total of 110 plasma concentrations from 47 adult patients who received daptomycin in general wards were enrolled for population PK modeling. The target area under the concentration-time curve/minimum inhibitory concentration (MIC) ratio, target peak/MIC ratio, and threshold of the trough concentration for safety were set to >666, >60, and 24.3 mg/L, respectively. Renal function was indicated as a significant covariate for daptomycin clearance. The simulated probability of target attainment was more than 90% at MIC values of 0.25 and 0.5 mg/L in all patients at the standard dose (6 mg/kg). In contrast, comprehensive simulation assessments recommended 10 mg/kg every 24 h in patients with creatinine clearance >60 mL/min for MIC values of 1.0 mg/L. We propose a new simplified daptomycin dosing regimen stratified by renal function and MIC values based on PK model-based simulation analyses. The proposed regimen is expected to maximize clinical efficacy and minimize adverse events.     

A UPLC-MS/MS method reveals the pharmacokinetics and metabolism characteristics of kaempferol in rats under hypoxia

As a natural flavonoid, kaempferol is widely distributed in natural medicines. Our study was aimed at analyzing and comparing the pharmacokinetic differences of kaempferol between normoxia and hypoxia in rats, to further explore the effect of hypoxia on drug metabolism enzymes. A sensitive UPLC-MS/MS method was established and validated for the determination of kaempferol in rat plasma. The results indicated that AUC, MRT, t_1/2 and C_max of kaempferol significantly increased and the clearance reduced in hypoxic rats. Based on the comparison of pharmacokinetics, the metabolites of kaempferol in hypoxic rats were identified by using UPLC-QTOF-MS and UNIFI 1.8 software. Then we explored the effect of hypoxia on the mRNA and protein expression of CYP1A2 and UGT1A9. The study revealed that hypoxia could markedly reduce the mRNA and protein expression of CYP1A2 and UGT1A9, resulting in the reduction of metabolic rate and enhancement of systematic exposure. Our data also indicated that we should pay attention to adjusting the dosage regimen and reducing drug interactions when drugs metabolized by CYP1A2 and UGT1A9 are used in combination with kaempferol. Our findings suggested the potential requirement for dose adjustment of kaempferol or its structural analogs in hypoxic condition.     

Fully automated left atrium segmentation from anatomical cine long-axis MRI sequences using deep convolutional neural network with unscented Kalman filter

This study proposes a fully automated approach for the left atrial segmentation from routine cine long-axis cardiac magnetic resonance image sequences using deep convolutional neural networks and Bayesian filtering. The proposed approach consists of a classification network that automatically detects the type of long-axis sequence and three different convolutional neural network models followed by unscented Kalman filtering (UKF) that delineates the left atrium. Instead of training and predicting all long-axis sequence types together, the proposed approach first identifies the image sequence type as to 2, 3 and 4 chamber views, and then performs prediction based on neural nets trained for that particular sequence type. The datasets were acquired retrospectively and ground truth manual segmentation was provided by an expert radiologist. In addition to neural net based classification and segmentation, another neural net is trained and utilized to select image sequences for further processing using UKF to impose temporal consistency over cardiac cycle. A cyclic dynamic model with time-varying angular frequency is introduced in UKF to characterize the variations in cardiac motion during image scanning. The proposed approach was trained and evaluated separately with varying amount of training data with images acquired from 20, 40, 60 and 80 patients. Evaluations over 1515 images with equal number of images from each chamber group acquired from an additional 20 patients demonstrated that the proposed model outperformed state-of-the-art and yielded a mean Dice coefficient value of 94.1%, 93.7% and 90.1% for 2, 3 and 4-chamber sequences, respectively, when trained with datasets from 80 patients.     

Multi-level semantic adaptation for few-shot segmentation on cardiac image sequences

Obtaining manual labels is time-consuming and labor-intensive on cardiac image sequences. Few-shot segmentation can utilize limited labels to learn new tasks. However, it suffers from two challenges: spatial-temporal distribution bias and long-term information bias. These challenges derive from the impact of the time dimension on cardiac image sequences, resulting in serious over-adaptation. In this paper, we propose the multi-level semantic adaptation (MSA) for few-shot segmentation on cardiac image sequences. The MSA addresses the two biases by exploring the domain adaptation and the weight adaptation on the semantic features in multiple levels, including sequence-level, frame-level, and pixel-level. First, the MSA proposes the dual-level feature adjustment for domain adaptation in spatial and temporal directions. This adjustment explicitly aligns the frame-level feature and the sequence-level feature to improve the model adaptation on diverse modalities. Second, the MSA explores the hierarchical attention metric for weight adaptation in the frame-level feature and the pixel-level feature. This metric focuses on the similar frame and the target region to promote the model discrimination on the border features. The extensive experiments demonstrate that our MSA is effective in few-shot segmentation on cardiac image sequences with three modalities, i.e. MR, CT, and Echo (e.g. the average Dice is 0.9243), as well as superior to the ten state-of-the-art methods.