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BackgroundNon-ergot dopamine agonists (NEDAs) have been used as monotherapy or as an adjunctive therapy to levodopa for many years. Novel long-acting formulations of NEDAs including pramipexole extended-release (ER), ropinirole prolonged-release (PR), and rotigotine transdermal patch have been developed. However, there is no strong evidence that a given NEDA is more potent than another. We performed a systematic review and network meta-analysis to evaluate the efficacy, tolerability and safety of six commonly used NEDAs in early Parkinson's disease (PD).MethodsSix NEDAs including piribedil, rotigotine transdermal patch, pramipexole immediate-release (IR)/ER, and ropinirole IR/PR were investigated. The efficacy outcomes including Unified Parkinson's Disease Rating Scale activities in daily life (UPDRS-II), motor function (UPDRS-III), and their subtotal (UPDRS-II + III), tolerability and safety outcomes were analyzed.ResultsA total of 20 RCTs (5,355 patients) were included in the current study. The result indicated that compared with placebo, all six investigated drugs had statistically significant differences in the improvement of UPDRS-II, UPDRS-III, and UPDRS-II + III (except ropinirole PR in UPDRS-II). There were no statistically significant differences between six NEDAs for the UPDRS-II and UPDRS-III. For UPDRS-II + III, the improvement of ropinirole IR/PR and piribedil were higher than that of rotigotine transdermal patch, and piribedil was higher than that of pramipexole IR. The surface under the cumulative ranking curve (SUCRA) indicated that piribedil resulted in best improvement in UPDRS-II and UPDRS-III (0.717 and 0.861, respectively). For UPDRS-II + III, piribedil and ropinirole PR exhibited similar improvement and both had high rates (0.858 and 0.878, respectively). Furthermore, piribedil performed better as monotherapy, ranking first in the improvement of UPDRS-II, III, and II + III (0.922, 0.960, and 0.941, separately). With regard to tolerability, there was a significant increase in overall withdrawals with pramipexole ER (0.937). In addition, the incidence of adverse reaction of ropinirole IR was relatively high (nausea: 0.678; somnolence: 0.752; dizziness: 0.758; fatigue: 0.890).ConclusionsIn this systematic review and network meta-analysis of six NEDAs, piribedil exhibited better efficacy, especially as monotherapy, and ropinirole IR was associated with a higher incidence of adverse events in patients with early PD.

BackgroundFree-living amoebae (FLA) including Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris can become pathogenic and cause severe cerebral infections, named primary amoebic meningoencephalitis (PAM), granulomatous amoebic encephalitis (GAE), and balamuthia amoebic encephalitis (BAE), respectively. FLA encephalitis has been reported across China, but the clinical data descriptions and analytical results of these different reports vary widely. Currently, no consensus treatment has been established. We conduct a systematic review to evaluate the exposure location, clinical symptoms, diagnosis, treatment, and prognosis of three FLA encephalitis and aim to reveal the differences between three FLA encephalitis in China.MethodsWe used MEDLINE (PubMed interface), EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang database, and China Biology Medicine disc (CBMdisc) databases for literatures published and manually retrieve the hospital records of our hospital. The search time was up to August 30, 2022, with no language restrictions.ResultsAfter excluding possible duplicate cases, a total of 48 patients of three FLA encephalitis were collected. One from the medical records of our hospital and 47 patients from 31 different studies. There were 11 patients of PAM, 10 patients of GAE, and 27 patients of BAE. The onset of PAM is mostly acute or subacute, and the clinical symptoms are acute and fulminant hemorrhagic meningoencephalitis. Most patients with GAE and BAE have an insidious onset and a chronic course. A total of 21 BAE patients (77.8%) had skin lesions before onset of symptoms. Additionally, 37 cases (77.1%) were diagnosed with FLA encephalitis before death. And there were 4 of PAM, 2 of GAE, and 10 of BAE diagnosed using next generation sequencing. No single agent can be proposed as the ideal therapy by itself. Only 6 cases were successfully treated.ConclusionsThis review provides an overview of the available data and studies of FLA encephalitis in China and identify some potential differences. FLA encephalitis is a rare but pathogenic infection, and physicians should early identify this encephalitis to improve survival.

Purpose: We aim to analyze the clinical and genetic features in a Chinese family with congenital retinoschisis by whole-exome sequencing and comprehensive clinical examination.Methods: Six members were recruited from a Chinese family. Three of them were diagnosed as congenital retinoschisis, including two twin siblings. All subjects received a full eye examination. Whole-exome sequencing (WES) and Sanger sequencing were performed on two twin probands and all participants, respectively.Results: A novel splice site mutation RS1.c.53-1G>A was identified in a Chinese congenital retinoschisis family. The mean onset age was 16.7 ± 2.4 years old. The average BCVA in patients was 0.37 ± 0.05. A typical spoke-wheel pattern was observed in all affected eyes. OCT examination results showed fovea schisis and schisis cavities were located in the inner nuclear layer in 100% eyes (6/6). ERG b/a ratio was decreased markedly, but was still more than 1 in the four eyes that were available.Conclusion: The present study discovered a new pathogenic splice cite variant of RS1 in congenital retinoschisis, which expands the mutational spectrum. In contrast to previous research, the phenotype of patients with the same mutation within one family was highly similar. Early molecular testing is crucial for early diagnosis, clinical management, and genetic counseling of patients with congenital retinoschisis.

Burkholderia pyrrocinia JK-SH007 is a plant growth-promoting bacteria (PGPB), that can promote the growth of poplar and other trees, and, production of the plant hormone indole-3-acetic acid (IAA) is one of the reasons for this effect. Therefore, the aims of this study were to evaluate the effect of the external environment on the synthesis of IAA by B. pyrrocinia JK-SH007 and to perform a functional analysis of its IAA synthesis pathway. In this study, IAA and its synthetic intermediates indole-3-acetamide (IAM), indole-3-pyruvic acid (IPyA), tryptamine (TAM), and indole-3-acetonitrile (IAN) were detected in B. pyrrocinia JK-SH007 fermentation broth by high-performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS), and these indolic compounds were also found in the cell-free extraction of B. pyrrocinia JK-SH007, but the genomic analysis of B. pyrrocinia JK-SH007 indicated that IAA biosynthesis was mainly through the IAM and TAM pathways. The effects of L-tryptophan (L-Trp), temperature and pH on the synthesis of IAA were investigated, and the results showed that L-Trp exerted a significant effect on IAA synthesis and that 37°C and pH 7 were the optimal conditions IAA production by B. pyrrocinia JK-SH007. In addition, the protein expression of tryptophan 2-monooxygenase and indoleacetamide hydrolase, which are the key enzymes of the indole acetamide-mediated IAA synthesis pathway, was analyzed, and their activity was verified by substrate feeding experiments. The results revealed the existence of an IAA synthesis pathway mediated by IAM and indicated that this pathway plays a role in B. pyrrocinia JK-SH007. This study lays the foundation for further exploration of the specific pathway and mechanism of IAA synthesis in B. pyrrocinia JK-SH007.

Flipped teaching is one of the most popular innovative teaching methods which has attracted a lot of attention and lead to amount of discussion in recent years. Many educators have generally encountered same doubt when implementing flipped education: Is this kind of teaching mode only applicable to students with high learning achievements? In addition, collaborative learning is often applied in flip teaching and it is also an issue worth to explore. In this study, both quantitative and qualitative studies were conducted to examine the potential factors in affecting the learners’ satisfaction in flipped education. The survey results from 171 participants showed that collaborative learning and need for cognition are significant predictors of learning satisfaction. In addition, a deeper look at the collaborative learning process was further examined by conducting deep interview. A total of 12 students from 6 different flipped-teaching courses participated the interview. The findings suggested that arranging some activities to encourage students to know each other before class that helps students find corresponding group and facilitates their expertise for collaborative learning. The mechanism significantly influenced team members’ engagement, discussion atmosphere, and efficiency. In addition, when learning tasks diversity, it will also enhance students’ innovative ability, empathy, and even promote mutual learning.

PurposeTo adopt molecular screening in asymptomatic individuals at high risk of developing keratoconus as a combinative approach to prevent subclinical patients from post-refractive surgery progressive corneal ectasia.MethodsIn this study, 79 Chinese and nine Greek families with keratoconus were recruited, including 91 patients with clinically diagnosed keratoconus as well as their asymptomatic but assumptive high-risk first-degree relatives based on underlying genetic factor. Mutational screening of VSX1, TGFBI, and ZEB1 genes and full clinical assessment including Pentacam Scheimpflug tomography were carried out in these individuals.ResultsFive variants in VSX1 and TGFBI genes were identified in three Chinese families and one Greek family, and four of them were novel ones. Surprisingly, ultra-early corneal changes in Belin/Ambrosio Enhanced Ectasia Display of Pentacam corneal topography together with co-segregated variants were revealed in the relatives who had no self-reported symptoms.ConclusionsVariants of VSX1 and TGFBI genes identified in both the clinically diagnosed and subclinical patients may cause the keratoconus through an autosomal dominant inheritance pattern, with different variable expressivity. Combining genetic with Belin/AmbrosioEnhanced Ectasia Display can be used to identify patients with latent keratoconus. This study indicates that genetic testing may play an important supplementary role in re-classifying the disease manifestation and evaluating the preoperative examination of refractive surgery.