Efficacy and Safety of Pulse Magnetic Therapy System in Insomnia Disorder: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: This study's objective is to assess the efficacy and safety of Pulsed Magnetic Therapy System (PMTS) in improving insomnia disorder. METHODS: Participants with insomnia disorder were randomly assigned to receive either PMTS or sham treatment for four weeks (n= 153; PMTS: 76, sham: 77). Primary outcomes are the Insomnia Severity Index (ISI) scores at week 0 (baseline), 1, 2, 3, 4 (treatment), and 5 (follow-up). Secondary outcomes are the Pittsburgh Sleep Quality Index at baseline and week 4, and weekly sleep diary-derived values for sleep latency, sleep efficiency, real sleep time, waking after sleep onset, and sleep duration. RESULTS: The ISI scores of the PMTS group and the sham group were 7.13±0.50, 11.07±0.51 at week 4, respectively. There was a significant group×time interaction for ISI (F3.214, 485.271=24.25, p<0.001, ηp 2=0.138). Only the PMTS group experienced continuous improvement throughout the study; in contrast, the sham group only experienced a modest improvement after the first week of therapy. At the end of the treatment and one week after it, the response of the PMTS group were 69.7% (95% confidence interval [CI]: 58.6%-79.0%), 75.0% (95% CI: 64.1%-83.4%), respectively, which were higher than the response of the sham group (p<0.001). For each of the secondary outcomes, similar group×time interactions were discovered. The effects of the treatment persisted for at least a week. CONCLUSION: PMTS is safe and effective in improving insomnia disorders.

The fruit morphometric variation and fruit type evolution of the stone oaks (Fagaceae, Lithocarpus).

BACKGROUND: The great species diversity of Lithocarpus is associated with interspecific fruit morphological variation, represented by acorn (AC) and enclosed receptacle (ER) fruit types. Species representing both fruit types co-occur in the same forests and share two distribution centers in southern China and southeastern Asia. The predation selection hypothesis suggests that the fruit morphological mechanical trade-off between two fruit types could represent divergent dispersal strategies under varied predation pressures. By integrating phylogenetic construction with fruit morphometric study, we tried to verify the predation selection hypothesis and elucidate the fruit type evolution of Lithocarpus, which is critical in interpreting the distribution and diversification of the genus. RESULTS: We identified the functional trade-off between the two fruit types: ER species have bigger seeds which are enclosed mainly by receptacle representing stronger physical defense; whereas the seeds of AC species are smaller and enclosed mainly by thin pericarp representing lower mechanical protection. Despite some reversals from ER back to AC, the ancestral state reconstruction in combination with thermal analysis supports the hypothesis that ER is the derived fruit type from AC-like ancestors independently across all clades. CONCLUSION: Our results support the predation selection hypothesis by verifying the mechanical trade-off between the two fruit types. We propose a divergent selection theory for the two fruit types: the seed size and mechanical defense of AC species become smaller, whereas those of ER species become larger and require more morphological modifications in the receptacle. This signified the importance of the receptacle in differentiating the two fruit types and in the fruit morphological modification through evolutionary time. We found that the ER-type species evolved independently in all clades and across varied climates from tropical to warm temperate regions. As ER fruits are products of convergent evolution, we propose to examine the predation and dispersal variation between two fruit types in the future to verify whether predation selection is the reason behind fruit type evolution of the stone oaks.

Toll-like receptor 2 deficiency relieves splenic immunosuppression during sepsis.

Immunosuppression is associated with long-term mortality during sepsis. However, the underlying mechanism of immunosuppression remains poorly understood. Toll-like receptor 2 (TLR2) contributes to sepsis pathogenesis. We sought to determine the role of TLR2 in immunosuppression in the spleen during polymicrobial sepsis. Using an experimental model of polymicrobial sepsis induced by cecal ligation and puncture (CLP), we measured the expression of inflammatory cytokines and chemokines in spleen 6 and 24 h after CLP to evaluate the immune response, and compared the expression of inflammatory cytokines and chemokines, apoptosis, and intracellular ATP production in spleen of wild-type (WT) and TLR2-deficient (TLR2-/-) mice 24 h after CLP. We found that pro-inflammatory cytokines and chemokines, such as TNF-α and IL-1ß peaked 6 h after CLP, while IL-10, an anti-inflammatory cytokine, peaked 24 h after CLP in the spleen. At this later time point, TLR2-/- mice presented decreased levels of IL-10 and decreased caspase 3 activation but no significant difference in intracellular ATP production in spleen compared to WT mice. Our data imply that TLR2 has a pronounced effect on sepsis-induced immunosuppression in spleen.

TBC1D8 Amplification Drives Tumorigenesis through Metabolism Reprogramming in Ovarian Cancer.

Cancer cells undergo metabolic reprogramming to support their energy demand and biomass synthesis. However, the mechanisms driving cancer metabolism reprogramming are not well understood. Methods: The differential proteins and interacted proteins were identified by proteomics. Western blot, qRT-PCR and IHC staining were used to analyze TBC1D8 levels. In vivo tumorigenesis and metastasis were performed by xenograft tumor model. Cross-Linking assays were designed to analyze PKM2 polymerization. Lactate production, glucose uptake and PK activity were determined. Results: We established two aggressive ovarian cancer (OVCA) cell models with increased aerobic glycolysis. TBC1D8, a member of the TBC domain protein family, was significantly up-regulated in the more aggressive OVCA cells. TBC1D8 is amplified and up-regulated in OVCA tissues. OVCA patients with high TBC1D8 levels have poorer prognoses. TBC1D8 promotes OVCA tumorigenesis and aerobic glycolysis in a GAP activity-independent manner in vitro and in vivo. TBC1D8 bound to PKM2, not PKM1, via its Rab-GAP TBC domain. Mechanistically, TBC1D8 binds to PKM2 and hinders PKM2 tetramerization to decreases pyruvate kinase activity and promote aerobic glycolysis, and to promote the nuclear translocation of PKM2, which induces the expression of genes which are involved in glucose metabolism and cell cycle. Conclusions:TBC1D8 drives OVCA tumorigenesis and metabolic reprogramming, and TBC1D8 serves as an independent prognosis factor for OVCA patients.

[Distribution and drug resistance profiles of pathogenic bacteria isolated from patients with nosocomial infection in intensive care unit].

OBJECTIVE: To investigate the distribution and drug sensitivity of pathogenic bacteria isolated from patients with nosocomial infection in intensive care unit. METHODS: The clinical data were collected from 229 hospitalized patients with nosocomial infection in intensive care unit from 2009 to 2011. RESULTS: Gram-negative bacteria were the main pathogens (68.25%) in the intensive care unit. From 2009 to 2011, the annual isolation rate of multidrug-resistant baumannii showed a significant reduction with time (39.13%, 18.18%, and 15%, respectively, P<0.05), while the prevalence of multidrug-resistant Pseudomonas aeruginosa, ESBLs-producing Escherichia coli and Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus, coagulase-negative staphylococci methicillin-resistant strains showed no significant changes in the 3 years (P>0.05). The overall sensitivity of gram-negative bacilli to the antimicrobial agents tended to increase with time. The Gram-negative bacilli remained highly sensitive to carbapenems, tigecycline, amikacin and piperacillin/tazobactam; the Gram-positive bacilli were highly sensitive to vancomycin, quinoline Nupu Ting/dalfopristin, linezolid, and tigecycline with sensitivity rates all reaching 100%. CONCLUSION: Adherence to the principles of antibiotic use and effective monitoring and preventive measures are encouraged to reduce antibiotic resistance rates of the bacteria and the incidences of hospital infection.