Pharmacological interventions for preventing opioid-induced hyperalgesia in adults after opioid-based anesthesia: a systematic review and network meta-analysis.

Background: Opioid-induced hyperalgesia (OIH) is an adverse event of prolonged opioid use that increases pain intensity. The optimal drug to prevent these adverse effects is still unknown. We aimed to conduct a network meta-analysis to compare different pharmacological interventions for preventing the increase in postoperative pain intensity caused by OIH. Methods: Several databases were searched independently for randomized controlled trials (RCTs) comparing various pharmacological interventions to prevent OIH. The primary outcomes were postoperative pain intensity at rest after 24 h and the incidence of postoperative nausea and vomiting (PONV). Secondary outcomes included pain threshold at 24 h after surgery, total morphine consumption over 24 h, time to first postoperative analgesic requirement, and shivering incidence. Results: In total, 33 RCTs with 1711 patients were identified. In terms of postoperative pain intensity, amantadine, magnesium sulphate, pregabalin, dexmedetomidine, ibuprofen, flurbiprofen plus dexmedetomidine, parecoxib, parecoxib plus dexmedetomidine, and S (+)-ketamine plus methadone were all associated with milder pain intensity than placebo, with amantadine being the most effective (SUCRA values = 96.2). Regarding PONV incidence, intervention with dexmedetomidine or flurbiprofen plus dexmedetomidine resulted in a lower incidence than placebo, with dexmedetomidine showing the best result (SUCRA values = 90.3). Conclusion: Amantadine was identified as the best in controlling postoperative pain intensity and non-inferior to placebo in the incidence of PONV. Dexmedetomidine was the only intervention that outperformed placebo in all indicators. Clinical Trial Registration: https://www.crd.york.ac. uk/prospero/display_record.php?, CRD42021225361.

A TRPV4 mutation caused Charcot-Marie-Tooth disease type 2C with scapuloperoneal muscular atrophy overlap syndrome and scapuloperoneal spinal muscular atrophy in one family: a case report and literature review.

BACKGROUND: Charcot-Marie-Tooth disease 2C (CMT2C) and scapuloperoneal spinal muscular atrophy (SPSMA) are different clinical phenotypes of TRPV4 mutation. The mutation of p.R316C has been reported to cause CMT2C and SPSMA separately. CASE PRESENTATION: Here, we reported a Chinese family harboring the same p.R316C variant, but with an overlap syndrome and different clinical manifestations. A 58-year-old man presented with severe scapula muscle atrophy, resulting in sloping shoulders. He also exhibited distinct muscle atrophy in his four limbs, particularly in the lower limbs. The sural nerve biopsy revealed severe loss of myelinated nerve fibers with scattered regenerating clusters and pseudo-onion bulbs. Nerve conduction study showed axon damage in both motor and sensory nerves. Sensory nerve action potentials could not be evoked in bilateral sural or superficial peroneal nerves. He was diagnosed with Charcot-Marie-Tooth disease type 2C and scapuloperoneal muscular atrophy overlap syndrome, whereas his 27-year-old son was born with clubfoot and clinodactyly. Electromyogram examination indicated chronic neurogenic changes and anterior horn cells involvement. Although there was no obvious weakness or sensory symptoms, early SPSMA could be considered for him. CONCLUSIONS: A literature review of the clinical characteristics in CMT2C and SPSMA patients with TRPV4 mutation suggested that our case was distinct due to the overlap syndrome and phenotype variation. Altogether, this case broadened the phenotype spectrum and provided the nerve biopsy pathological details of TRPV4-related neuropathies.

Hippo Pathway in Schwann Cells and Regeneration of Peripheral Nervous System.

Hippo pathway is an evolutionarily conserved signaling pathway comprising a series of MST/LATS kinase complexes. Its key transcriptional coactivators YAP and TAZ regulate transcription factors such as TEAD family to direct gene expression. The regulation of Hippo pathway, especially the nuclear level change of YAP and TAZ, significantly influences the cell fate switching from proliferation to differentiation, regeneration, and postinjury repair. This review outlines the main findings of Hippo pathway in peripheral nerve development, regeneration, and tumorigenesis, especially the studies in Schwann cells. We also summarize other roles of Hippo pathway in damage repair of the peripheral nerve system and discuss the potential future research which probably contributes to novel therapeutic strategies.

Metabolomic modulations of HepG2 cells exposed to bisphenol analogues.

Bisphenol analogues including bisphenol A (BPA), bisphenol AF (BPAF), bisphenol F (BPF), and bisphenol S (BPS) share similar chemical structures and endocrine disrupting effects. Their effects on metabolisms, however, are so far only marginally understood. In this study, NMR-based metabonomic profiles of HepG2 cell culture media and PCR array were used to assess the metabolomics disturbances and gene expression levels of HepG2 in response to four BPs (BPA, BPAF, BPF, and BPS). The results indicated that BP analogues resulted in disturbances in 7-15 metabolites that were classified as amino acid (alanine, glutamine, glutamate), intermediates and end-products in the glycolysis (pyruvate) and the tricarboxylic acid cycle (acetate, lactate). Their rank in order according to the number of metabolites and pathways was BPF > BPA > BPAF > BPS. The common disrupted pathways (pyruvate metabolism; alanine, aspartate, and glutamate metabolism) indicated enhanced glycolysis. The following glucometabolic PCR array analysis suggested that although four BPs shared the capability of disrupting glucose metabolism, they may act through different mechanisms: BPAF has increased the pyruvate kinase (PKLR) expression level, which implied enhanced glycolysis that was agreed with NMR results. The other three BP analogues, however, decreased the expression level of glucokinase (GCK) that indicated glucose sensing impairment. Our results demonstrated the potential for using metabolomic and PCR array to understand the underlying action of mechanisms and identify the potential targets for future targeted risk assessment.

[Expression of interferon-λ1 in respiratory epithelial cells of children with RSV infection and its relationship with RSV load].

OBJECTIVE: To investigate the expression of IFN-λ1 in respiratory epithelial cells of children with respiratory syncytial virus (RSV) infection and its relationship with RSV load. METHODS: The nasopharyngeal swabs were collected from the children who were hospitalized with respiratory tract infection from June 2015 to June 2016. A direct immunofluorescence assay was used to detect the antigens of seven common respiratory viruses (including RSV) in the nasopharyngeal swabs. A total of 120 children who were only RSV positive were selected as the RSV infection group. A total of 50 children who had negative results in the detection of all viral antigens were selected as the healthy control group. Fluorescence quantitative real-time PCR was used to determine the RSV load and the expression of IFN-λ1 mRNA in the nasopharyngeal swabs of children in the two groups. RESULTS: The expression of IFN-λ1 in the RSV infection group was significantly higher than that in the healthy control group (P<0.05). The expression of IFN-λ1 was positively correlated with RSV load (r=0.56, P<0.05). CONCLUSIONS: RSV can induce the expression of IFN-λ1 in respiratory epithelial cells, suggesting that IFN-λ1 may play an important role in anti-RSV infection.

A high-throughput method to detect RNA profiling by integration of RT-MLPA with next generation sequencing technology.

RNA in formalin-fixed and paraffin-embedded (FFPE) tissues provides large amount of information indicating disease stages, histological tumor types and grades, as well as clinical outcomes. However, Detection of RNA expression levels in formalin-fixed and paraffin-embedded samples is extremely difficult due to poor RNA quality. Here we developed a high-throughput method, Reverse Transcription-Multiple Ligation-dependent Probe Sequencing (RT-MLPSeq), to determine expression levels of multiple transcripts in FFPE samples. By combining Reverse Transcription-Multiple Ligation-dependent Amplification method and next generation sequencing technology, RT-MLPSeq overcomes the limit of probe length in multiplex ligation-dependent probe amplification assay and thus could detect expression levels of transcripts without quantitative limitations. We proved that different RT-MLPSeq probes targeting on the same transcripts have highly consistent results and the starting RNA/cDNA input could be as little as 1 ng. RT-MLPSeq also presented consistent relative RNA levels of selected 13 genes with reverse transcription quantitative PCR. Finally, we demonstrated the application of the new RT-MLPSeq method by measuring the mRNA expression levels of 21 genes which can be used for accurate calculation of the breast cancer recurrence score - an index that has been widely used for managing breast cancer patients.

Comparative genomics analyses on EPS biosynthesis genes required for floc formation of Zoogloea resiniphila and other activated sludge bacteria.

Activated sludge (AS) process has been widely utilized for municipal sewage and industrial wastewater treatment. Zoolgoea and its related floc-forming bacteria are required for formation of AS flocs which is the key to gravitational effluent-and-sludge separation and AS recycling. However, little is known about the genetics, biochemistry and physiology of Zoogloea and its related bacteria. This report deals with the comparative genomic analyses on two Zoogloea resiniphila draft genomes and the closely related proteobacterial species commonly found in AS. In particular, the metabolic processes involved in removal of organic matters, nitrogen and phosphorus were analyzed. Furthermore, it is revealed that a large gene cluster, encoding eight glycosyltransferases and other proteins involved in biosynthesis and export of extracellular polysaccharides (EPS), was required for floc formation. One of the two asparagine synthase paralogues, associated with this EPS biosynthesis gene cluster, was required for floc formation in Zoogloea. Similar EPS biosynthesis gene cluster(s) were identified in the genome of other AS proteobacteria including polyphosphate-accumulating Candidatus Accumulibacter phosphatis (CAP) and nitrifying Nitrosopira and Nitrosomonas bacteria, but the gene composition varies interspecifically and intraspecifically. Our results indicate that floc formation of desired AS bacteria, including CAP strains, facilitate their recruitment into AS and gradual enrichment via repeated AS settling and recycling processes.