A novel approach to sonographic examination in a patient with a calf muscle tear: a case report

© 2009 Chen et al; licensee Cases Network Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Molecular Basis of Gain-of-Function LEOPARD Syndrome-Associated SHP2 Mutations

The Src homology 2 (SH2) domain-containing protein tyrosine phosphatase 2 (SHP2) is a critical signal transducer downstream of growth factors that promotes the activation of the RAS-ERK1/2 cascade. In its basal state, SHP2 exists in an autoinhibited closed conformation because of an intramolecular interaction between its N-SH2 and protein tyrosine phosphatase (PTP) domains. Binding to pTyr ligands present on growth factor receptors and adaptor proteins with its N-SH2 domain localizes SHP2 to its substrates and frees the active site from allosteric inhibition. Germline mutations in SHP2 are known to cause both Noonan syndrome (NS) and LEOPARD syndrome (LS), two clinically similar autosomal dominant developmental disorders. NS-associated SHP2 mutants display elevated phosphatase activity, while LS-associated SHP2 mutants exhibit reduced catalytic activity. A conundrum in how clinically similar diseases result from mutations to SHP2 that have opposite effects on this enzyme’s catalytic functionality exists. Here we report a comprehensive investigation of the kinetic, structural, dynamic, and biochemical signaling properties of the wild type as well as all reported LS-associated SHP2 mutants. The results reveal that LS-causing mutations not only affect SHP2 phosphatase activity but also induce a weakening of the intramolecular interaction between the N-SH2 and PTP domains, leading to mutants that are more readily activated by competing pTyr ligands. Our data also indicate that the residual phosphatase activity associated with the LS SHP2 mutant is required for enhanced ERK1/2 activation. Consequently, catalytically impaired SHP2 mutants could display gain-of-function properties because of their ability to localize to the vicinity of substrates for longer periods of time, thereby affording the opportunity for prolonged substrate turnover and sustained RAS-ERK1/2 activation

Effectiveness of WeChat-Group-Based Parental Health Education in Preventing Unintentional Injuries Among Children Aged 0-3: Randomized Controlled Trial in Shanghai

BACKGROUND: Unintentional injuries to children are a major public health problem. The online social media is a potential way to implement health education for caregivers in online communities. Using WeChat, a free and popular social media service in China, this study evaluated the effectiveness of social online community-based parental health education in preventing unintentional injuries in children aged 0-3. METHODS: We recruited 365 parents from two community health centers in Shanghai and allocated them into intervention and control groups randomly. Follow-up lasted for one year. The intervention group received and followed their WeChat group and a WeChat official account for dissemination of reliable medical information. The control group received only the WeChat group. RESULTS: Between the intervention and control groups, changes in unintentional injuries (OR = 1.71, 95% CI: 1.02-2.87, P = .04), preventability (β = 0.344, 95% CI: 0.152-0.537, P \u3c .001), daily supervision behavior (β = 0.503, 95% CI: 0.036-0.970, P = .04), and behaviors for preventing specific injuries (β = 2.198, 95% CI: 1.530-2.865, P \u3c .001) were significantly different, and change in first-aid skills for treating a tracheal foreign body were nearly significant (P = .06). CONCLUSIONS: The WeChat-group-based parental health education can reduce the occurrence of unintentional child injuries by improving parents\u27 skills, beliefs, and behaviors. Online social communities promote health education and reduce unintentional injuries among children. TRIAL REGISTRATION: ChiCTR1900020753. Registered on January 17, 2019

Changes in Volatile Profiles and Activity of Hydroperoxide Lyase and Alcohol Dehydrogenase During the Development of Cabernet Sauvignon Grapes (Vitis vinifera L.)

In this study we focused on the development of Cabernet Sauvignon grapes and investigated changes in theactivity of alcohol dehydrogenase (ADH) and hydroperoxide lyase (HPL) in different tissues. We sampledgrape skin at four, six, seven, eight, nine, 10, 12, 14 and 16 weeks after anthesis; developing flowers whenblooming at 0%, 5%, 50%, and 90%; and leaves at two and four weeks before anthesis and at two, four,six, eight, nine, and 10 weeks after anthesis. We also examined the type and fluctuation of volatile contents.ADH activity increased with the development of flowers and grape skins, which led to the increasing oftypes and concentration of alcohols. Low levels of 9-HPL led to low concentrations of C9 compounds.According to this paper, C6 compounds became abundant with the development of grape berries, while theactivity of 13-HPL kept at a low level in the flowers and grape skins. There might have been a high level of13-HPL activity from the end of flowering until fruit setting that we did not detect. Furthermore, similarC6 and C5 compounds were detected across all tissues, including hexanal, (E)-2-hexenal, (Z)-3-hexenal,(Z)-2-penten-1-ol, (Z)-3-hexen-1-ol, 1-hexanol and 3-hexen-1-ol. Generally speaking, the concentrations ofC6 and C5 compounds could be used as the criterion of maturation of the three grape tissues

Traditional Chinese medicine for smoking cessation: An umbrella review of systematic reviews and meta-analysis of randomized controlled trials.

Traditional Chinese medicine (TCM) may have special advantages in facilitating smoking cessation, but consensus on effectiveness is lacking. We aim to comprehensively review, update, and refine current evidence on TCM effectiveness and safety. Nine databases were searched from their inception up to 28 February 2023. Systematic reviews (SRs) and meta-analysis of TCM for smoking cessation were identified and retrieved. Additional databases and hand searches of RCTs from included SRs were performed for data pooling. Cochrane ROB tools and AMSTAR-2 were used to evaluate the methodological quality of RCTs and SRs, respectively. RCT data are presented as relative risks (RR) or mean differences (MD) with 95% confidence intervals (CI) using RevMan 5.4. Thirteen SRs involving 265 studies with 33081 participants were included. Among these 265 studies, 157 were duplicates (58.36%) and 52 were non-RCTs (19.62%). Combined with the remaining 56 RCTs identified through hand searches, 88 RCTs involving 12434 participants were finally included for data synthesis. All the SRs focused on acupoint stimulation, and the majority were of low or very low quality. The methodological quality of RCTs was either unclear or high risk. For continuous abstinence rate, TCM external interventions were better than placebo in 6 months to 1 year (RR=1.60; 95% CI: 1.14-2.25; I =27%; n=5533 participants). Compared with placebo, TCM external application was effective in reducing nicotine withdrawal symptoms, and the effect was gradually stable and obvious in the fourth week (MD= -4.46; 95% CI: -5.43 - -3.49; n=165 participants). Twelve RCTs reported adverse events as outcome indicators for safety evaluation, and no serious adverse events occurred. Despite the methodological limitations of the original studies, our review suggests that TCM intervention shows potential effectiveness on the continuous abstinence rate. Extending the intervention time can enhance the effect of TCM on nicotine withdrawal symptoms. Referred to adverse events, more data for safety evaluation are required. [Abstract copyright: © 2023 Lu CL. et al.

Destabilization of Fatty Acid Synthase by Acetylation Inhibits De Novo Lipogenesis and Tumor Cell Growth

Fatty acid synthase (FASN) is the terminal enzyme in de novo lipogenesis and plays a key role in cell proliferation. Pharmacological inhibitors of FASN are being evaluated in clinical trials for treatment of cancer, obesity and other diseases. Here we report a previously unknown mechanism of FASN regulation involving its acetylation by KAT8 and its deacetylation by HDAC3. FASN acetylation promoted its degradation via the ubiquitin-proteasome pathway. FASN acetylation enhanced its association with the E3 ubiquitin-ligase TRIM21. Acetylation destabilized FASN and resulted in decreased de novo lipogenesis and tumor cell growth. FASN acetylation was frequently reduced in human hepatocellular carcinoma samples, which correlated with increased HDAC3 expression and FASN protein levels. Our results suggest opportunities to target FASN acetylation as an anticancer strategy