Benralizumab efficacy and safety in severe asthma: A randomized trial in Asia.

BACKGROUND: Benralizumab is indicated as add-on therapy in patients with uncontrolled, severe eosinophilic asthma; it has not yet been evaluated in a large Asian population with asthma in a clinical trial. OBJECTIVE: To evaluate the efficacy and safety of benralizumab in patients with severe asthma in Asia. METHODS: MIRACLE (NCT03186209) was a randomized, Phase 3 study in China, South Korea, and the Philippines. Patients aged 12-75 years with severe asthma receiving medium-to-high-dose inhaled corticosteroid/long-acting ß2-agonists, stratified (2:1) by baseline blood eosinophil count (bEOS) (≥300/µL; <300/µL), were randomized (1:1) to benralizumab 30 mg or placebo. Endpoints included annual asthma exacerbation rate (AAER; primary endpoint), change from baseline at Week 48 in pre-bronchodilator (BD) forced expiratory volume in 1 second (pre-BD FEV1) and total asthma symptom score (TASS). Safety was evaluated ≤ Week 56. RESULTS: Of 695 patients randomized, 473 had baseline bEOS ≥300/µL (benralizumab n = 236; placebo n = 237). In this population, benralizumab significantly reduced AAER by 74% (rate ratio 0.26 [95% CI 0.19, 0.36], p < 0.0001) and significantly improved pre-BD FEV1 (least squares difference [LSD] 0.25 L [95% CI 0.17, 0.34], p < 0.0001) and TASS (LSD -0.25 [-0.45, -0.05], p = 0.0126) versus placebo. In patients with baseline bEOS <300/µL, there were numerical improvements in AAER, pre-BD FEV1, and TASS with benralizumab versus placebo. The frequency of adverse events was similar for benralizumab (76%) and placebo (80%) in the overall population. CONCLUSIONS: MIRACLE data reinforces the efficacy and safety of benralizumab for severe eosinophilic asthma in an Asian population, consistent with the global Phase 3 results.

Acupuncture in the Treatment of Abnormal Muscle Tone in Children with Cerebral Palsy: A Meta-Analysis.

Objective: To analyse the clinical efficacy of acupuncture and routine treatment in improving dystonia in children with cerebral palsy. Method: The randomized controlled trials published from the establishment of the databases to August 2022 on acupuncture in the treatment of dystonia in children with cerebral palsy were collected and comprehensively searched in China national knowledge infrastructure (CNKI), weipu (VIP), Wanfang, SinoMed, PubMed, Excerpta medica database (EMBASE), and Cochrane Library. The literature was selected according to the established standards, the quality of the included studies was evaluated, the heterogeneity of the included studies was evaluated with the I2 test, and the appropriate model was selected for analysis. Sensitivity analysis was used to evaluate the reliability of the results, and a funnel plot was used to evaluate the publication bias. Results: Fifteen studies were included in the meta-analysis. The control group was treated with routine treatment and acupuncture combined with routine treatment. The outcome index showed that the effect in the treatment group was better: Modified Ashworth Scale score: -0.52, 95% confidence interval (CI) (-0.62 to -0.41), p < 0.01. The treatment group showed reduced muscle tension to a greater extent (integral eletromyographic (iEMG) score: standard mean square deviation = -2.97, 95% CI (-4.87 to -1.06), p < 0.01). The effective rate in the control group was 74.2% and that in the treatment group was 91.5%, odds ratio = 3.70, 95% CI (2.02-6.78), p < 0.01. The funnel plot showed publication bias. Conclusion: Acupuncture combined with routine training could improve muscle tension abnormalities and improve the efficiency of clinical treatment.

Scalp acupuncture Yikang therapy on Baihui (GV20), Sishencong (EX-HN1), Zhisanzhen, Niesanzhen improves neurobehavior in young rats with cerebral palsy through Notch signaling pathway.

OBJECTIVE: To investigate the efficacy of scalp acupuncture Yikang therapy on Baihui (GV20), Sishencong (EX-HN1), Zhisanzhen, Niesanzhen, on neurobehavior in young rats with cerebral palsy based on Notch signaling pathway. METHODS: Thirty 7-day-old rats were randomly divided into sham, model and acupuncture, 10 rats in each group. The cerebral palsy model was established by the accepted modeling method, the acupuncture group selected "Baihui (GV20)", "Sishencong (EX-HN1)", "Zhisanzhen" and "Niesanzhen" for intervention 24 h after the model was made. The body masses were recorded before and after the treatment, respectively. After the intervention, the rats were subjected to suspension experiment, slope experiment, tactile stimulation experiment and Morris water maze experiment. After the end of the experiment, the morphological changes of hippocampal histology were observed by hematoxylin-eosin (HE) staining under light microscope, and the expression of Notch1, Notch3 and Hes5 were detected by Western blot and quantitative real-time polymerase chain reaction (PCR). RESULTS: The changes in body mass of the rats in each group were different; in behavioral experiments, compared with the sham, the suspension time of the model was shortened, the slope experiment, tactile stimulation experiment, and escape latency time were prolonged, and the number of platform crossing was reduced in the model, compared with the model, the suspension time of the acupuncture was prolonged, the slope experiment, tactile stimulation experiment, and escape latency time were shortened, and the number of platform crossing times was increased; HE staining showed severe hippocampal damage in the model and reduced hippocampal damage in the acupuncture. Western Blot and real-time fluorescence quantitative PCR showed that the expression of Notch1, Notch3 and Hes5 were increased in the model and the expression of Notch1, Notch3, Hes5 in acupuncture were decreased. CONCLUSIONS: Scalp acupuncture Yikang therapy may improve neurobehavior and reduce brain injury in rats with cerebral palsy by downregulating the expression of Notch1, Notch3, and Hes5.

Characterization and phylogenetic analysis of the complete mitochondrial genome of Rhinogobius wuyanlingensis (Gobiiformes: Gobiidae: Gobionellinae).

Rhinogobius wuyanlingensis is endemic to the upper reaches of Feiyunjiang river basin. In this article, the complete mitochondrial genome (mtDNA) for this freshwater goby was first determined. Sequence analysis showed the genome consisted of 13 protein-coding genes, 22 tRNA genes, two ribosomal RNA genes, and two main non-coding regions (the control region and the origin of the light strand replication). This circular molecule was 16,491 bp in length with a slight AT bias of 53.5%. In the phylogenetic tree, R. wuyanlingensis was closer to Rhinogobius brunneus, Rhinogobius yonezawai, Rhinogobius flumineus, and Rhinogobius cliffordpopei. The mitochondrial genome of R. wuyanlingensis reported here would provide basal molecular data for evolution, taxonomy, and population genetics of Rhinogobius.

Clinical and Immunological Effects of rhIL-2 Therapy in Eastern Chinese Patients with Multidrug-resistant Tuberculosis.

It is urgent to find an optimised therapy regimen for the control of MDR-TB globally. This study aimed to evaluate the efficiacy and safety of a combined regimen of rhIL-2 injection and standard chemotherapy within 18-month duration in a randomized controlled trial conducted in 14 centres in eastern China. From Jan. 2009 to July. 2016, 271 MDR-TB cases were enrolled and followed up in two groups, 142 cases in study group while 129 cases in control group. Clinical efficacy, safety and immune activity (Th1, Th17, Treg, IFN-γ, IL-17) among the two groups were evaluated and compared. After 24-month following up, cure rate in IL-2 group show higher than that in control group (56% VS 36%, P < 0.01). Rate of mycobacterium clearance (sputum negative) within 3 months was significantly higher in IL-2 group (74% VS 59%, P < 0.05) with no adverse events raised. Patients after rhIL-2 treatment showed increasing of Th1 populations and decreasing of Th17 and Regulatory T cells (Treg) populations, while levels of IL-17A, ROR-γt, and Foxp3 mRNA decreased and level of IFN-γ mRNA increased in PBMCs. Thus, rhIL-2 combined regimen within shorter duration achieved high conversion and success rates and improved Th1/Th17 immune responses, with no safety concerns emerging in MDR-TB patients.

Complexity analysis of resting state fMRI signals in depressive patients.

Analysis of brain signal complexity reveals the intrinsic network dynamics and is widely utilized in the investigation of mechanisms in mental disorders. In this study, the complexity of resting-state functional magnetic resonance imaging (fMRI) signals was explored in patients with depression using multiscale entropy (MSE). Thirty-five patients diagnosed with depression and 22 age- and gender-matched healthy controls were considered. The MSE profiles in five brain networks of the two participant groups were evaluated and analyzed. The results showed that depressive patients exhibited higher complexity in the left frontoparietal network than that seen in healthy controls, which is known to be critical for executive control functions. Through this study, the efficacy of MSE in identifying and understanding the mental disorders was also demonstrated.

A preconcentrator chip employing µ-SPME array coated with in-situ-synthesized carbon adsorbent film for VOCs analysis.

We report the design, fabrication, and evaluation of a µ-preconcentrator chip that utilizes an array of solid-phase microextraction (SPME) needles coated with in-situ-grown carbon adsorbent film. The structure of the SPME needle (diameter=100 µm, height=250 µm) array inside the sampling chamber was fabricated using a deep reactive-ion etching (DRIE) process to enhance the attachable surface area for adsorbent film. Heaters and temperature sensors were fabricated onto the back of a µ-preconcentrator chip using lithography patterning and a metal lift-off process. The devices were sealed by anodic bonding and diced prior to the application of the adsorbent film. An adsorbent precursor, cellulose was dissolved in water and dynamically coated onto the SPME needle array. The coated cellulose film was converted into a porous carbon film via pyrolysis at 600 °C in a N(2) atmosphere. The surface area of the carbon adsorbent film was 308 m(2)/g, which is higher than that of a commercial adsorbent Carbopack X. A preconcentration factor as high as 13,637-fold was demonstrated using toluene. Eleven volatile organic compounds (VOCs) of different volatilities and functional groups were sampled and analyzed by GC-FID, and the desorption peak widths at half height were all less than 2.6 s after elution from a 15m capillary GC column. There was no sign of performance degradation after continuous operation for 50 cycles in air.