Quality appraisal of clinical practice guidelines addressing massage interventions using the AGREE II instrument.

OBJECTIVE: The purpose of this study was to systematically evaluate the methodological quality of massage-related clinical practice guidelines (CPGs)/consensus on massage using the Appraisal of Guidelines Research and Evaluation (AGREE II) instrument and to summarize the current status of recommendations in the CPGs. METHODS: The Chinese National Knowledge Infrastructure (CNKI), WanFang Data, China Science and Technology Journal Database (VIP), China Biology Medicine disc (CBM), PubMed, Embase, and guideline websites (such as the Chinese Medical Ace Base, the China Association of Chinese Medicine, the World Health Organization, Guideline International Network, National Institute for Health and Care Excellence, Scottish Intercollegiate Guidelines Network) were searched from inception to October 31, 2022. In addition, the reference lists of relevant studies were reviewed to identify domestic and overseas massage CPGs/consensus. The search terms adopted a combination of subject words and free words, mainly including traditional Chinese medicine, complementary therapies, Tuina, massage, manipulation, chiropractic/osteopathic, spinal, acupressure, guideline, and consensus. Two researchers independently completed the eligible records and extracted the data. Before the formal research, calibrations were performed twice on AGREE II, and all reviewers completed the pilot test three times until they understood and reached an agreement on the assessment items. Three researchers appraised the methodological quality of the included guidelines using the AGREE II instrument and calculated the overall intraclass correlation coefficient (ICC) of agreement. RESULTS: The evaluation results showed that among the 49 eligible CPGs/consensus, 4 (8.2%) CPGs/consensus were considered "recommended", 15 (30.6%) CPGs/consensus were considered "recommended with modifications", and 30 (61.2%) CPGs/consensus were considered "not recommended", while the consensus was considered "not recommended". Generally, the scores in the six domains of the guidelines were all higher than the consensus. Evaluation results for the overall quality of 36 CPGs showed that 4 (11%) were "good quality", 15 (42%) were "sufficient quality" and 17 (47%) were "lower quality". The AGREE II quality scores of domains ranged from 0.30 to 0.75 ([ICC = 0.993, 95% CI (0.992, 0.995)]). The domain of scope and purpose (domain 1), with a median score of 0.75 (0.52~0.91), performed best in the guidelines with AGREE II, and stakeholder involvement (domain 2) [median 0.39 (0.31~0.56)] and application (domain 5) [median 0.30 (0.17~0.47] obtained lower scores. The consensus score of domain 1 was better at 26.0 (21.6~44.8), followed by rigor of development (domain 3) with a score of 18.0 (10.0~28.9). A total of 119 massage-related recommendations were extracted from 49 guidelines/consensuses, including "in favor" (102, 85.7%), "against" (9, 7.6%), and "did not make recommendations" (8, 6.7%). CONCLUSION: The overall quality of the included guidelines was low, and most of the guidelines were not "recommended". In future guideline updates, the existing evidence should be used, the professional composition of members of the expert group should be enriched, and patients' values and preferences should be fully considered. It is necessary to clearly propose recognizable recommendations and strengthen the rigor and standardization of guideline formulation. Thus, clear standard guidelines can be formulated to better guide clinical practice.

Mechanisms underlying the relationship between the intersectionality of multiple social identities with depression among US adults: A population-based study on the mediating roles of lifestyle behaviors.

BACKGROUND: Despite substantial efforts to investigate the inequalities in mental health among people with marginalized identities, most research has concentrated on single social identities rather than complete persons. The current study aimed to explore the mechanisms underlying the relationship between the intersectionality of multiple social identities with depression among US adults. METHODS: Data for this study came from the National Health and Nutrition Examination Survey waves between 2015 and 2018, including a total of 11,268 US adults. A latent class analysis (LCA) was conducted to identify latent subpopulations based on sex, race/ethnicity, immigrant status, disability, household income, employment status, and education level. Interclass differences in lifestyle factors and depression were examined. Multiple mediation analysis was used to examine the mediating roles of lifestyle behaviors. RESULTS: LCA identified four potential subpopulations: "least marginalized", "immigrant minorities", "disabled, less-educated non-workers", and "low-income minorities" groups. There was enormous heterogeneity in mental health among immigrant minority individuals. The "disabled, less-educated non-workers" group had the highest rates of depression; in contrast, the "immigrant minorities" group had the best mental health, even better than that of the "least marginalized" group. Distributions of lifestyle factors followed a similar pattern. In addition, lifestyle behaviors significantly mediated the relationship between intersectional social identities and depression. LIMITATIONS: The cross-sectional design prevented establishment of the causality of relationships. CONCLUSIONS: This study suggests that applying a person-centered approach is important when examining intersectional inequalities in mental health and highlights the effects of structural social hierarchies on individuals' health behaviors and mental health.

Associations of latent patterns of parent‒child communication with communication quality and mental health outcomes among Chinese left-behind children.

BACKGROUND: Parent‒child communication in migrant families is essential to family bonds and the mental health of left-behind children (LBC). Little is known about the different patterns of communication between migrant parents and LBC and associated communication quality and mental health outcomes. METHODS: A sample of 2,183 Chinese children (mean age = 12.95 ± 1.29 years) from Anhui province, including LBC whose parents had both migrated (n = 1,025) and children whose parents had never migrated (never-LBC, n = 1,158), was analyzed. With the LBC sample, latent class analysis was applied to identify the patterns of parent‒child communication. Multinomial logistic regression analysis was conducted to assess the associations between the sociodemographic variables and class membership of LBC. Analysis of covariance and chi-square tests were used to compare communication quality and mental health outcome differences among the classes of LBC and between each of the classes and never-LBC. RESULTS: Five latent classes of communication formed through different media or channels between migrant parents and their LBC were identified. Higher household economic status (OR = 2.81, p < 0.05) was associated with adequate communication. LBC in Class 1, defined by frequent technologically-mediated and face-to-face communication, had a significantly higher quality of communication with their migrant parents (F = 8.92, p < 0.001) and better mental health than those in other latent classes; these children did not have significantly worse mental health outcomes compared to never -LBC. CONCLUSIONS: Facilitating multichannel parent‒child communication is a practical way of reducing mental health inequities between LBC and their peers.

Associations of Lifestyle Patterns With Overweight and Depressive Symptoms Among United States Emerging Adults With Different Employment Statuses.

Objective: To identify lifestyle patterns in emerging adults and examine the association of lifestyle patterns with overweight and depression. Methods: Data was from the National Health and Nutrition Examination Survey between 2011 and 2018. A latent class analysis (LCA) was conducted with 2,268 US emerging adults based on sedentary behavior, moderate-to-vigorous physical activity, diet, sleep, alcohol drinking, and cigarette smoking. The associations of lifestyle groups with overweight and depression were examined by logistic regression and were further stratified by employment status. Results: The LCA results favored a four-class solution: "unhealthy but non-substance use" (59%), "healthy but sleepless and drinking" (12%), "unhealthy lifestyle" (15%), and "healthy but sedentary" group (14%). Compared to the "unhealthy lifestyle" group, participants in the "unhealthy but non-substance use" (coef. = -1.44, SE = 0.27; OR = 0.40, 95% CI [0.26, 0.61]), "healthy but sleepless and drinking" (coef. = -1.49, SE = 0.35; OR = 0.38, 95% CI [0.20, 0.72]), and "healthy but sedentary" (coef. = -1.97, SE = 0.34; OR = 0.29, 95% CI [0.14, 0.57]) groups had lower depression severity and reported fewer depressive symptoms. Moreover, lifestyle groups and health outcomes showed different relationships among employed and unemployed participants. Conclusion: This study found that the combinations of lifestyle behaviors had synergistic effects on mental health, and such effects differed by employment status.

Effects of a Psychosocial Intervention on the Subjective Experiences of Children Living with Atopic Dermatitis: A Qualitative Study in Hong Kong.

Nonpharmaceutical interventions are important for addressing the psychosocial needs of children living with atopic dermatitis (AD). The current study aimed to investigate the effects of an integrative body-mind-spirit (IBMS) intervention on the subjective experiences of affected children and explore the mechanisms underlying the effects. Using a drawing-based, qualitative approach, the current study conducted two rounds of interviews with 13 children (aged 8-12 years) diagnosed with moderate or severe AD before and after they attended the IBMS intervention. Data were analyzed by using the thematic analysis method. The IBMS intervention worked by changing participants' perceptions at the cognitive level, improving their coping strategies at the behavioral level, and constructing their social support network at the environmental level. Cognitive, behavioral, and environmental factors might mediate the relationships between the IBMS intervention and participants' psychological and physical outcomes. This study highlighted the wider inclusion of child-centered qualitative research in the evaluation of the effects of psychosocial interventions designed for children.

Associations of parental attitudes and health behaviors with children's screen time over four years.

BACKGROUND: Parents are significantly important in shaping the screen use of children within a family system. This study aimed to examine the associations of Chinese children's screen time (ST) over four years with parents' attitudes toward their own screen use and physical activities (PA) and health behaviors including their ST, PA, cigarette smoking, and alcohol drinking. METHODS: The current study utilized data from two waves (2011 and 2015) of the China Health and Nutrition Survey (CHNS), including 1,941 mother-father-child triads in 2011 and 2,707 mother-father-child triads in 2015 (with children aged 0-17-years-old). The ST of children and the parental attitudes and health behaviors were measured via self-report or proxy-report (for children under 6 years old) questionnaires. Pool-OLS regression models were used to assess the associations of parental attitudes and health behaviors with the ST of children. Moderation models were built to assess whether these associations depended on the gender, age, and family income of children, as well as whether paternal and maternal influences were moderated by the other parent. A multilevel cross-lagged panel model (CLPM) was used to assess parental influences on children's ST over four years. RESULTS: Paternal ST (ß = 0.09, p < 0.001), maternal ST (ß = 0.10, p < 0.001), and paternal alcohol drinking (ß = 0.30, p < 0.05) were positively associated with children's ST. In addition, maternal smoking had a positive association with girls' ST (ß = 0.53, p < 0.05). Moreover, the association between maternal ST and children's ST was observed to decline as family income increased (ß = -0.03, p < 0.001). Paternal ST had a larger positive association with children's ST when the ST of mothers exceeded 14 h/week (ß = 0.06, p < 0.05). Furthermore, lagged associations were found between paternal attitudes toward PA (ß = -1.63, p < 0.05) or maternal cigarette smoking (ß = 1.46, p < 0.05) and children's ST measured four years later. CONCLUSION: Children establish a healthy lifestyle within the family system. From the perspective of the healthy family climate, the current study suggests that future programs for reducing children's ST should be built through an integrative approach with special attention to parental attitudes and health behaviors.

A qualitative synthesis of drawing-based research on the illness-related experiences of children living with physical health problems.

The strengths of drawing-based approaches for encouraging children's participation in health research and facilitating communication with them have been increasingly acknowledged in the medical literature. However, there is a lack of methodological discussion on drawing-based approaches suitable for researching children living with physical health problems. The present study systematically reviewed qualitative research using drawing-based approaches on the experiences of children living with physical health problems and summarised how the approaches were used as well. We identified 54 studies from five databases. The characteristics of qualitative methods and drawing-based approaches were analysed. To obtain an overall understanding of the illness-related experiences of these children, qualitative data generated from the included studies were synthesised using the thematic synthesis approach. This systematic review highlights the appropriateness and accuracy of the use of drawings-based approaches in health research with children on their illness-related experiences, fostering inclusive participation and engagement of young generations.

[Modified QuEChERS method based on multi-walled carbon nanotubes coupled with gas chromatography-tandem mass spectrometry for the detection of 10 pyrethroid pesticide residues in tea].

A modified QuEChERS method, based on multi-walled carbon nanotubes (MWCNTs), was established for the detection of 10 pyrethroid pesticides (cyfluthrin, flucythrinate, fenpropathrin, bifenthrin, cyhalothrin, permethrin, cypermethrin, etofenprox, fenvalerate, deltamethrin) in tea, in combination with gas chromatography-tandem mass spectrometry (GC-MS/MS). The purification effects and dosages of four carbon nanomaterials, viz. single-walled carbon nanotubes (SWCNTs), MWCNTs, amino-modified MWCNTs, and graphene, were compared. An orthogonal experimental design was used to determine the optimal experimental conditions for sample pretreatment. The experimental factors governing the process were analyzed using variance. The results showed that the optimized sample pretreatment parameters were as follows. Acetonitrile was used as the extraction solvent with ultrasonic extraction for 35 min, while 60 mg MWCNTs, 200 mg PSA, and 200 mg C18, were used as purifiers. The effects of the extraction solvent and the carbon nanomaterials used on the recoveries of the 10 pyrethroid pesticides were significantly different (p<0.001), and the effect of extraction time on the recoveries was statistically different (p<0.05). The dosage of carbon nanomaterials had no significant effect on the recoveries (p>0.05). Good linearities were observed for the 10 pyrethroid pesticides in the concentration range of 0.01-2 mg/L. The limits of detection (LODs) and limits of quantification (LOQs) were in the ranges of 0.001-0.01 mg/kg and 0.005-0.04 mg/kg, respectively. The average recoveries of the pyrethroid pesticides spiked into blank samples of green tea were 91.4%-109.7%, and the relative standard deviations were 0.12%-9.80% (n=6). Furthermore, the matrix effects (MEs) of scented green tea, green tea, and black tea were evaluated. It was found that the addition of MWCNTs to the purifier can effectively reduce the matrix effect in green tea and black tea matrices. The developed method and the national standard method were used to detect the residues of the 10 pyrethroid pesticides in 120 tea samples available in the market. The results showed that cyfluthrin, deltamethrin, fenvalerate, permethrin, fenpropathrin, cypermethrin, bifenthrin and cyhalothrin were detected, and the contents obtained with the two methods were similar. Although pyrethroids were detected in most tea samples, the contents of all pesticide residues were below the maximum residue limits (MRLs). Therefore, the developed method is suitable for the rapid quantitative analysis of pesticide residues in tea.

PELO facilitates PLK1-induced the ubiquitination and degradation of Smad4 and promotes the progression of prostate cancer.

PLK1 and Smad4 are two important factors in prostate cancer initiation and progression. They have been reported to play the opposite role in Pten-deleted mice, one is an oncogene, the other is a tumor suppressor. Moreover, they could reversely regulate the PI3K/AKT/mTOR pathway and the activation of MYC. However, the connections between PLK1 and Smad4 have never been studied. Here, we showed that PLK1 could interact with Smad4 and promote the ubiquitination and degradation of Smad4 in PCa cells. PLK1 and PELO could bind to different domains of Smad4 and formed a protein complex. PELO facilitated the degradation of Smad4 through cooperating with PLK1, thereby resulting in proliferation and metastasis of prostate cancer cell. Changes in protein levels of Smad4 led to the alteration of biological function that caused by PLK1 in prostate cancer cells. Further studies showed that PELO upregulation was positively associated with high grade PCa and knockdown of PELO expression significantly decreased PCa cell proliferation and metastasis in vitro and vivo. PELO knockdown in PCa cells could enhance the tumor suppressive role of PLK1 inhibitor. In addition, blocking the interaction between PELO and Smad4 by using specific peptide could effectively inhibit PCa cell metastasis ability in vitro and vivo. Overall, these findings identified a novel regulatory relationship among PLK1, Smad4 and PELO, and provided a potential therapeutic strategy for advanced PCa therapy by co-targeting PLK1 and PELO.

Self-stigma Among Children Living with Atopic Dermatitis in Hong Kong: a Qualitative Study.

BACKGROUND: Stigma has been recently identified as a crucial factor associated with the psychosocial burden of those who have chronic skin diseases. The self-stigma experiences of children living with atopic dermatitis (AD) have yet to be fully investigated, and questions of how these children respond to public stigma and how AD symptoms further affect their self-stigma experiences remain unresolved. The current qualitative study aimed to (1) describe the main manifestations of self-stigma in children living with AD; (2) investigate factors that might influence their self-stigma experiences; and (3) explore the potential mechanisms underlying the impacts of AD on their psychosocial well-being from the self-stigma perspective. METHODS: We performed a secondary analysis of the qualitative literal transcription data which were collected earlier by using the participatory, drawing-based qualitative interviews with 17 children aged 8-12 who were diagnosed with severe or moderate AD. RESULTS: The qualitative findings indicated that the visible and invisible symptoms of AD and its management exerted unique influences on self-stigma in children living with AD, which manifested in cognitive, affective, and behavioral aspects and ultimately affected their psychosocial well-being. CONCLUSIONS: Findings of this study allowed us to advocate for eliminating public stigma of people with skin diseases and propose recommendations for helping children living with AD relieve their self-stigma.

Associations Between Parental Employment and Children's Screen Time: A Longitudinal Study of China Health and Nutrition Survey.

Objectives: Parents are often torn between their parenting roles in the family and working roles at the workplace. This study focused on the associations of parental employment with children's screen time (ST) on weekdays, weekends, and during the entire week. Methods: Unbalanced panel data including 2,977 children (aged 0-17 years) from five waves of the China Health and Nutrition Survey data from 2004 to 2015 were utilized. Two-way fixed effects models were fitted to examine the associations of parental employment status, working hours, and overwork with children's ST. Results: Compared to unemployment status, maternal formal employment positively predicted children's ST on both weekdays and weekends, while maternal informal employment was associated with increased children's ST on weekends. The more hours they worked, the more time their children spent using screens. Neither employment status nor the overwork of fathers was significant. Conclusion: Parental employment, especially maternal employment, was linked with the ST of children. More childcare-friendly labor policies are needed to promote healthy lifestyles among the next generation.

Large Multicohort Study Reveals a Prostate Cancer Susceptibility Allele at 5p15 Regulating TERT via Androgen Signaling-Orchestrated Chromatin Binding of E2F1 and MYC.

Aberrant telomerase reverse transcriptase (TERT) expression is crucial for tumor survival and cancer cells escaping apoptosis. Multiple TERT-locus variants at 5p15 have been discovered in association with cancer risk, yet the underlying mechanisms and clinical impacts remain unclear. Here, our association studies showed that the TERT promoter variant rs2853669 confers a risk of prostate cancer (PCa) in different ethnic groups. Further functional investigation revealed that the allele-specific binding of MYC and E2F1 at TERT promoter variant rs2853669 associates with elevated level of TERT in PCa. Mechanistically, androgen stimulations promoted the binding of MYC to allele T of rs2853669, thereby activating TERT, whereas hormone deprivations enhanced E2F1 binding at allele C of rs2853669, thus upregulating TERT expression. Notably, E2F1 could cooperate with AR signaling to regulate MYC expression. Clinical data demonstrated synergistic effects of MYC/E2F1/TERT expression or with the TT and CC genotype of rs2853669 on PCa prognosis and severity. Strikingly, single-nucleotide editing assays showed that the CC genotype of rs2853669 obviously promotes epithelial-mesenchymal transition (EMT) and the development of castration-resistant PCa (CRPC), confirmed by unbiased global transcriptome profiling. Our findings thus provided compelling evidence for understanding the roles of noncoding variations coordinated with androgen signaling and oncogenic transcription factors in mis-regulating TERT expression and driving PCa.

Association between alcohol consumption and oesophageal microbiota in oesophageal squamous cell carcinoma.

BACKGROUND: Microbiota has been reported to play a role in cancer patients. Nevertheless, little is known about the association between alcohol consumption and resultant changes in the diversity and composition of oesophageal microbiota in oesophageal squamous cell carcinoma (ESCC). METHODS: We performed a hospital-based retrospective study of 120 patients with pathologically diagnosed primary ESCC. The relevant information for all study participants were collected through a detailed questionnaire. The differences in adjacent tissues between non-drinkers and drinkers were explored using 16S rRNA gene sequencing. Raw sequencing data were imported into QIIME 2 to analyse the diversity and abundance of microbiota. Linear discriminant analysis effect size (LEfSe) and unconditional logistic regression were performed to determine the bacterial taxa that were associated with drinking. RESULTS: The Shannon diversity index and Bray-Curtis distance of oesophageal microbiota were significantly different among drinkers(P < 0.05). The alcohol-related bacteria were primarily from the orders Clostridiales, Gemellales and Pasteurellales, family Clostridiaceae, Lanchnospiraceae, Helicobacteraceae, Alcaligenaceae, Bacteroidaceae, Pasteurellaceae and Gemellaceae; genus Clostridium, Helicobacter, Catonella, Bacteroides, Bacillus, Moraxella, and Bulleidia; and species B. moorei and longum (genus Bifidobacterium). In addition, the diversity and abundance of these microbiota were observed to be affected by the age, residential districts of the patients, and sampling seasons. Moreover, the higher the frequency and years of alcohol consumption, the lower was the relative abundance of genus Catonella that was observed. CONCLUSION: Alcohol consumption is associated with alterations in both the diversity and composition the of the oesophageal microbiota in ESCC patients.

The Counterintuitive Relationship between Telomerase Activity and Childhood Emotional Abuse: Culture and Complexity.

BACKGROUND: A burgeoning literature has found relationships between telomere length, telomerase activity, and human health and longevity. Although some research links a history of childhood adversity with shortened telomere length, our review found no prior research on the relationship between child maltreatment history and telomerase activity in adulthood. We hypothesized a negative relationship between child maltreatment and telomerase activity and hypothesized that the association would be moderated by sex. METHODS: These relationships were tested on a sample of 262 Hong Kong Chinese adults (200 females versus 62 males) with mild to moderate depression. RESULTS: Counterintuitively, emotional abuse was positively associated with telomerase activity, while other maltreatment types were non-significant. The positive relationship between emotional abuse and telomerase activity was significantly moderated by the sex of the participant. CONCLUSIONS: We advance two possible explanations for this finding (1) a culturally informed resilience explanation and (2) a homeostatic complexity explanation. The two explanations are not mutually exclusive. This trial is registered under Hong Kong Clinical Trial Register number HKCTR-1929. SIGNIFICANCE STATEMENT: Emotional abuse was significantly positively associated with telomerase activity. There are at least two non-mutually exclusive explanations for the findings. Simply put, either (1) in the cultural context of Hong Kong emotional abuse was not a risk factor, and/or (2) the conceptualization of telomerase activity as a straightforward indicator of longevity is overly simplistic. The first story we might term a "resilience explanation" while the second we might call a "homeostatic complexity" story.

Upregulated expression of serum exosomal hsa_circ_0026611 is associated with lymph node metastasis and poor prognosis of esophageal squamous cell carcinoma.

Background: To identify the diagnostic and prognostic values of serum exosomal hsa_circ_0026611 in esophageal squamous cell carcinoma (ESCC). Methods: ESCC serum exosome global circRNA expression was detected using a circRNA microarray. The expression levels of candidate serum exosome circRNAs were detected by quantitative polymerase chain reaction (qRT-PCR). A receiver operating characteristic curve (ROC) was generated to confirm the diagnostic value. Survival data and their differences were observed by the Kaplan-Meier method and log-rank tests. The Cox regression analysis was employed to identify prognostic factors. Results: The expression levels of serum exosomal has_circ_0026611 in ESCC with lymph node metastasis were significantly higher than those in ESCC without lymph node metastasis (P =0.001). In addition, serum exosomal hsa_circ_0026611 expression could be used as a significant parameter to discriminate between non-lymph node-metastatic and lymph node-metastatic ESCC with an area under curve (AUC) of 0.724 (95% CI: 0.604~0.865). The multivariate Cox regression analysis indicated that survival was poor in patients with high serum exosomal hsa_circ_0026611 expression levels compared to those with low serum exosomal hsa_circ_0026611 levels (for OS, HR [95% CI]: 3.79 [1.27, 11.29], for DFS, HR [95% CI]: 2.77 [1.06, 7.22]). Conclusion: Serum exosomal hsa_circ_0026611 expression is significantly upregulated in ESCC with lymph node metastasis and is a predictor of ESCC prognosis.

Health-related quality of life and treatment modality among esophageal squamous cell carcinoma survivors: A prospective study using time to deterioration model analysis.

BACKGROUND AND OBJECTIVES: This study aimed to analyze the association between health-related quality of life and treatment modality among esophageal squamous cell carcinoma (ESCC) survivors. METHODS: Patients completed the EORTC QLQ-C30 and EORTC QLQ-OES18 at baseline and follow-up. A time to deterioration model analysis was performed to compare longitudinal EORTC QLQ-C30/QLQ-OES18 data between surgery alone and surgery with adjuvant chemotherapy. RESULTS: For EORTC QLQ-C30 scale, compared with surgery alone, significant delays in time to deterioration in role functioning (16.05 months vs. 15.00 months; p = .045), cognitive functioning (20.80 months vs. 16.26 months; p = .017), social functioning (19.09 months vs. 12.35 months; p = .001), and dyspnea (18.53 months vs. 14.62 months; p = .011) were observed for surgery with adjuvant chemotherapy. For QLQ-OES18 scale, compared with surgery alone, significant delays in time to deterioration in dysphagia (13.75 months vs. 8.16 months; p = .005), choking when swallowing (20.67 months vs. 15.08 months; p = .001), and dry mouth (21.78 months vs. 17.28 months; p = .039) were observed for surgery with adjuvant chemotherapy. CONCLUSIONS: Patients who received postoperative chemotherapy had significant delay in time to deterioration in multiple ESCC-related symptoms, functions of EORTC QLQ-C30 and EORTC QLQ-OES18.

Manipulating the position of DNA expression cassettes using location tags fused to dCas9 (Cas9-Lag) to improve metabolic pathway efficiency.

BACKGROUND: Deactivated Cas9 (dCas9) led to significant improvement of CRISPR/Cas9-based techniques because it can be fused with a variety of functional groups to form diverse molecular devices, which can manipulate or modify target DNA cassettes. One important metabolic engineering strategy is to localize the enzymes in proximity of their substrates for improved catalytic efficiency. In this work, we developed a novel molecular device to manipulate the cellular location of specific DNA cassettes either on plasmids or on the chromosome, by fusing location tags to dCas9 (Cas9-Lag), and applied the technique for synthetic biology applications. Carotenoids like ß-carotene serve as common intermediates for the synthesis of derivative compounds, which are hydrophobic and usually accumulate in the membrane compartment. RESULTS: Carotenoids like ß-carotene serve as common intermediates for the synthesis of derivative compounds, which are hydrophobic and usually accumulate in the membrane components. To improve the functional expression of membrane-bound enzymes and localize them in proximity to the substrates, Cas9-Lag was used to pull plasmids or chromosomal DNA expressing carotenoid enzymes onto the cell membrane. For this purpose, dCas9 was fused to the E. coli membrane docking tag GlpF, and gRNA was designed to direct this fusion protein to the DNA expression cassettes. With Cas9-Lag, the zeaxanthin and astaxanthin titer increased by 29.0% and 26.7% respectively. Due to experimental limitations, the electron microscopy images of cells expressing Cas9-Lag vaguely indicated that GlpF-Cas9 might have pulled the target DNA cassettes in close proximity to membrane. Similarly, protein mass spectrometry analysis of membrane proteins suggested an increased expression of carotenoid-converting enzymes in the membrane components. CONCLUSION: This work therefore provides a novel molecular device, Cas9-Lag, which was proved to increase zeaxanthin and astaxanthin production and might be used to manipulate DNA cassette location.

Protocol of the Development of a Core Outcome Set for Ischemic Stroke in Clinical Trials of Chinese Medicine.

Background. Ischemic stroke (IS) seriously impacts the quality of life of survivors. Chinese medicine (CM) has been developed for more than 2000 years and plays a key role in the treatment of ischemic stroke. Many Chinese medicine clinical trials have been conducted; however, the heterogeneity of outcome measurements and reporting limits implications of the findings in clinical practice and health policy development. Therefore, it is important to develop a core outcome set (COS) that should be used and reported in trials for ischemic stroke treated by Chinese medicine. This protocol describes the process of developing the IS-CM-COS. Methods and Analysis. The development of the COS will involve the following four steps: (1) A list of outcomes reported in the registered and published Chinese medicine trials of ischemic stroke will be extracted by conducting a systematic literature review. (2) An additional outcome list will be collected by semistructured interview to patients with ischemic stroke. (3) A two-round Delphi survey will be performed to prioritize and condense the outcomes. (4) In the consensus meeting, a final recommended COS will be developed. Discussion. The COS could improve the reliability and consistency of outcome reporting. We hope that this IS-CM-COS will be used in the future Chinese medicine trials for the treatment of ischemic stroke and improve research quality. Trial Registration. This study was registered with the Core Outcome Measures in Effectiveness Trials Initiative (http://www.comet-initiative.org/studies/details/1282).

Acupuncture combined with speech rehabilitation training for post-stroke dysarthria: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The evidence of Acupuncture combined with speech rehabilitation training for post-stroke dysarthria is insufficient and there is no consensus on its efficacy. METHODS: We searched seven Chinese and English medicine databases for randomized controlled trials (RCTs) from their inception to November 2019. The primary outcome measure was the clinical response rate, assessed with the Frenchay Dysarthria Assessment (FDA) tool. We assessed risk of bias using the Cochrane risk-of-bias tool. We used GRADE to assess the certainty of evidence (CoE). RESULTS: Thirty studies were included in this systematic review, 23 of which were pooled in meta-analysis. Acupuncture combined with speech rehabilitation training is likely beneficial for was response rate (n = 1685; RR = 1.37; 95% CI [1.29, 1.46], P < 0.01, I 2 = 34%; 17 studies, low CoE) compared to speech rehabilitation treatment alone. CONCLUSION: The combination of acupuncture and speech rehabilitation training may improve total response rate of stroke patients with dysarthria. However, more RCTs with rigorous study design and validated outcome measures are needed to confirm the evidence.

Serum exosomal microRNA-766-3p expression is associated with poor prognosis of esophageal squamous cell carcinoma.

The aim was to analyze the association between exosomal microRNA (miR)-766-3p expression levels in serum and the prognosis of esophageal squamous cell carcinoma (ESCC). The serum global exosomal miRNA expression of ESCC patients was measured by microRNA microarray. Quantitative real-time PCR was used to analyze the expression levels of candidate miRNAs in both serum and tissues from ESCC patients. Wilcoxon tests were applied to evaluate clinical characteristics and their association with serum levels of exosomal miR-766-3p. A Cox regression model was used to identify prognostic factors. The effects of miR-766-3p expression on cell migration and invasion were examined using Transwell assays, and CCK-8 assays were carried out to measure cell proliferation. The TNM stage was associated with high serum exosomal miR-766-3p levels of ESCC patients (P = .030). Higher serum exosomal miR-766-3p expression levels were associated with poor prognosis (for overall survival, hazard ratio [HR] [95% confidence interval (CI)], 2.21 [1.00, 4.87]; for disease-free survival, HR [95% CI], 2.15 [1.01, 4.59]). However, we found no association between the expression of miR-766-3p in tissue and ESCC prognosis. In vitro results showed that miR-766-3p promotes cell migration and invasion, but not cell proliferation. By using dual-luciferase reporter assay, HOXA13 was confirmed as a direct target gene of miR-766-3p. The ESCC patients with highly expressed serum exosomal miR-766-3p had a significantly worse survival. Therefore, serum exosomal miR-766-3p could serve as a prognostic marker for the assessment of ESCC.