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Background: The objectives of this study were twofold: (1) to compare gait characteristics between cerebral small vessel disease (CSVD) patients with low-risk oral frailty (OF) and high-risk OF, particularly during dual-task walking (DTW); (2) to investigate the association of OF, the gait characteristics of DTW, and falls among older adults patients with CSVD., Methods: A total of 126 hospitalized patients diagnosed with CSVD were recruited and classified into a low-risk group (n = 90) and a high-risk group (n = 36) based on OF status in our study. Comprehensive data pertaining to basic parameters (cadence, as well as stride time, velocity and length), variability, asymmetry, and coordination were gathered during both single-task walking (STW) and DTW. Additionally, the number of falls was calculated. Subsequently, t-test or chi-squared test was used for comparison between the two groups. Furthermore, linear regression analysis was employed to elucidate the association of the OF index-8 score and gait parameters during cognitive DTW. Also, logistic regression models were utilized to assess the independent association of OF risk and falls., Results: During cognitive DTW, the high-risk group demonstrated inferior performance in terms of basic parameters (p < 0.01), coefficient of variation (CV) of velocity and stride length (p < 0.05), as well as phase coordination index (PCI) when compared with the low-risk group (p < 0.05). Notably, differences in basic gait parameters were observed in cognitive DTW and STW conditions between the two groups (p < 0.01). However, only the high-risk group evinced significant variations in CV and PCI during cognitive DTW, as opposed to those during STW (p < 0.05). Furthermore, our findings also revealed the association of OF, the gait characteristics of cognitive DTW, (p < 0.01) and falls (p < 0.05)., Conclusion: CSVD patients with a high risk of OF need to pay more attention to their gait variability or coordination. Also, they are recommended to undergo training involving dual-task activities while walking in daily life, thereby reducing the deterioration and mitigating the risk of falls. Besides, this study has confirmed an association of OF and DTW gait as well as falls in patients with CSVD., (© 2024. The Author(s).)

Background: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is a currently widely used strategy for locally advanced esophageal cancer (EC). However, the conventional imaging methods have certain deficiencies in the evaluation and prediction of the efficacy of nCRT. This study aimed to explore the value of functional imaging in predicting the response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced esophageal squamous cell carcinoma (ESCC)., Methods: Fifty-four patients diagnosed with locally advanced ESCC from August 2017 to September 2019 and treated with nCRT were retrospectively analyzed. DW-MRI scanning was performed before nCRT, at 10-15 fractions of radiotherapy, and 4-6 weeks after the completion of nCRT. 18 F-FDG PET/CT scans were performed before nCRT and 4-6 weeks after the completion of nCRT. These 18 F-FDG PET/CT and DW-MRI parameters and relative changes were compared between patients with pathological complete response (pCR) and non-pCR., Results: A total of 8 of 54 patients (14.8%) were evaluated as disease progression in the preoperative assessment. The remaining forty-six patients underwent operations, and the pathological assessments of the surgical resection specimens demonstrated pathological complete response (pCR) in 10 patients (21.7%) and complete response of primary tumor (pCR-T) in 16 patients (34.8%). The change of metabolic tumor volume (∆MTV) and change of total lesion glycolysis (∆TLG) were significantly different between patients with pCR and non-pCR. The SUVmax-T post , MTV-T post , and TLG-T post of esophageal tumors in 18 F-FDG PET/CT scans after neoadjuvant chemoradiotherapy and the ∆ SUVmax-T and ∆MTV-T were significantly different between pCR-T versus non-pCR-T patients. The esophageal tumor apparent diffusion coefficient (ADC) increased after nCRT; the ADC during , ADC post and ∆ADC during were significantly different between pCR-T and non-pCR-T groups. ROC analyses showed that the model that combined ADC during with TLG-T post had the highest AUC (0.914) for pCR-T prediction, with 90.0% and 86.4% sensitivity and specificity, respectively., Conclusion: 18 F-FDG PET/CT is useful for re-staging after nCRT and for surgical decision. Integrating parameters of 18 F-FDG PET/CT and DW-MRI can identify pathological response of primary tumor to nCRT more accurately in ESCC., (© 2021. The Author(s).)

Decondesation of the highly compacted chromatin architecture is essential for efficient DNA repair, but how this is achieved remains largely unknown. Here, we report that microrchidia family CW-type zinc finger protein 2 (MORC2), a newly identified ATPase-dependent chromatin remodeling enzyme, is required for nucleosome destabilization after DNA damage through loosening the histone-DNA interaction. Depletion of MORC2 attenuates phosphorylated histone H2AX (γH2AX) focal formation, compromises the recruitment of DNA repair proteins, BRCA1, 53BP1, and Rad51, to sites of DNA damage, and consequently reduces cell survival following treatment with DNA-damaging chemotherapeutic drug camptothecin (CPT). Furthermore, we demonstrate that MORC2 can form a homodimer through its C-terminal coiled-coil (CC) domain, a process that is enhanced in response to CPT-induced DNA damage. Deletion of the C-terminal CC domain in MORC2 disrupts its homodimer formation and impairs its ability to destabilize histone-DNA interaction after DNA damage. Consistently, expression of dimerization-defective MORC2 mutant results in impaired the recruitment of DNA repair proteins to damaged chromatin and decreased cell survival after CPT treatment. Together, these findings uncover a new mechanism for MORC2 in modulating chromatin dynamics and DDR signaling through its c-terminal dimerization.

Background: While buprenorphine/naloxone (B/N) is approved for opioid use disorder treatment, effective delivery of B/N comes with significant challenges. Most notably, many patients do not take medication daily as prescribed; this non-adherence worsens treatment outcomes, increases healthcare costs, and leads to persistent worries of diversion among providers and policymakers. The present study examines the feasibility, usability, and acceptability of MySafeRx-a mobile technology platform integrating motivational coaching, adherence monitoring, and electronic pill dispensing designed to address the challenges of office-based opioid treatment (OBOT) with B/N., Methods: The MySafeRx platform integrates electronic pill dispensers, text-messaging, and videoconferencing to provide supervised self-administration of medication and daily motivational coaching through an Android app interface. High-risk early adults (18-39 years old) who were enrolled in OBOT with B/N and had documented illicit opioid use in the past month during opioid agonist therapy (n = 12) participated in a 28-day single-arm observational study of the MySafeRx platform in addition to standard care., Results: Two-thirds of participants who completed the study achieved an average of > 5 days per week of supervised B/N self-administration. Visual confirmation of medication adherence was demonstrated for an average of 72% of study days among all participants. All participants achieved platform technical proficiency within 60 min, reporting good levels of usability and acceptability. Illicit opioid abstinence rates confirmed by urine toxicology increased by 53% during MySafeRx but fell 43% within 3 weeks post-intervention., Conclusion: The MySafeRx medication adherence and remote coaching mobile platform is acceptable and can be feasibly implemented in real-world opioid use disorder treatment settings during high-risk periods (i.e., initial stabilization, after illicit opioid lapse), resulting in reduced illicit opioid use; however, the effect did not last after intervention completion, suggesting longer duration or extended taper of program may be needed. ClinicalTrials.Gov NCT02942199 10/24/16 https://clinicaltrials.gov/ct2/show/NCT02942199.

Background: Up to now, numerous case-control studies have reported the associations between fat mass and obesity associated (FTO) gene rs9939609 A/T polymorphism and polycystic ovary syndrome (PCOS), however, without a consistent result. Hence we performed current systematic review and meta-analysis to clarify the controversial results., Methods: Case-control studies reporting the relationship of rs9939609 A/T polymorphism and PCOS published before April 2015 were searched in Pubmed database without language restriction. Data was analyzed by Review Manager 5.2., Results: A total of five studies involving 5010 PCOS patients and 5300 controls were included for further meta-analysis. The results of meta-analysis showed that the FTO gene rs9939609 A/T polymorphism was significantly different between PCOS group and control group in different gene models (For AA + AT vs. TT: OR = 1.41, 95% CI = 1.28-1.55, P < 0.00001. For AA vs. AT + TT: OR = 1.54, 95% CI = 1.25-1.89, P < 0.0001. For AA vs. TT: OR = 1.74, 95% CI = 1.38-2.18, P < 0.00001. For A vs. T: OR = 1.36, 95% CI = 1.25-1.47, P < 0.00001, respectively) suggesting that A allele was a risk factor for PCOS susceptibility. Furthermore, subgroup analysis in Asian and Caucasian ethnicities also found significant association between rs9939609 A/T polymorphism and PCOS (In Asian subgroup: OR = 1.43, 95% CI = 1.29-1.59, P < 0.0001. In Caucasian subgroup: OR = 1.33, 95% CI = 1.08-1.64, P = 0.008) CONCLUSION: This meta-analysis suggests that rs9939609 A/T polymorphism of FTO gene is associated with PCOS risk, and that A allele is a risk factor for PCOS susceptibility simultaneously.

Distant metastasis to specific target organs is responsible for over 90% of breast cancer-related deaths, but the underlying molecular mechanism is unclear. Mounting evidence suggests that the interplay between breast cancer cells and the target organ microenvironment is the key determinant of organ-specific metastasis of this lethal disease. Here, we highlight new findings and concepts concerning the emerging role of the tumor microenvironment in breast cancer metastasis; we also discuss potential therapeutic intervention strategies aimed at targeting components of the tumor microenvironment.

Background: This study is aimed to evaluate the clinical significance of heart rate turbulence (HRT) parameters in predicting the prognosis in patients with chronic heart failure (CHF)., Methods: From June 2011 to December 2012, a total of 104 CHF patients and 30 healthy controls were enrolled in this study. We obtained a 24-hour Holter ECG recording to assess the HRT parameters, included turbulence onset (TO), turbulence slope (TS), standard deviation of N-N intervals (SDNN), and resting heart rate (RHR). The relationships between HRT parameters and the prognosis of CHF patients were determined., Results: The assessment follow-up period lasted until January 31, 2013. The overall mortality of CHF patients was 9.6% (10/104). Our results revealed that CHF patients had higher levels of TO than those of healthy subjects, but the TS levels of CHF patients were lower than that of the control group. CHF patients with NYHA grade IV had higher HRT1/2 rate than those with NYHA grade II/III. There were statistical differences in TS, LVEF, SDNN and RHR between the non-deteriorating group and the non-survivor group. Significant differences in TS among the three groups were also found. Furthermore, CHF patients in the non-survivor group had lower levels of TS than those in the deteriorating group. Correlation analyses indicated that TO negatively correlate with SDNN, while TS positively correlated with SDNN and left ventricular ejection fraction (LVEF). We also observed negative correlations between TS and left ventricular end-diastolic cavity dimension (LVEDD), RHR, homocysteine (Hcy) and C-reactive protein (CRP). Multivariate Cox regression analysis further confirmed that LVEF (≤30%), HRT2, SDNN and RHR were independent risk factors which can indicate poor prognosis in CHF patients., Conclusions: Our findings indicate that HRT may have good clinical predictive value in patients with CHF. Thus, quantifying HRT parameters could be a useful tool for predicting mortality in CHF patients.

Background: In many parts of the world, including in China, extreme heat events or heat waves are likely to increase in intensity, frequency, and duration in light of climate change in the next decades. Risk perception and adaptation behaviors are two important components in reducing the health impacts of heat waves, but little is known about their relationships in China. This study aimed to examine the associations between risk perception to heat waves, adaptation behaviors, and heatstroke among the public in Guangdong province, China., Methods: A total of 2,183 adult participants were selected using a four-stage sampling method in Guangdong province. From September to November of 2010 each subject was interviewed at home by a well-trained investigator using a structured questionnaire. The information collected included socio-demographic characteristics, risk perception and spontaneous adaptation behaviors during heat wave periods, and heatstroke experience in the last year. Chi-square tests and unconditional logistic regression models were employed to analyze the data., Results: This study found that 14.8%, 65.3% and 19.9% of participants perceived heat waves as a low, moderate or high health risk, respectively. About 99.1% participants employed at least one spontaneous adaptation behavior, and 26.2%, 51.2% and 22.6% respondents employed <4, 4-7, and >7 adaptation behaviors during heat waves, respectively. Individuals with moderate (OR=2.93, 95% CI: 1.38-6.22) or high (OR=10.58, 95% CI: 4.74-23.63) risk perception experienced more heatstroke in the past year than others. Drinking more water and wearing light clothes in urban areas, while decreasing activity as well as wearing light clothes in rural areas were negatively associated with heatstroke. Individuals with high risk perception and employing <4 adaptation behaviors during heat waves had the highest risks of heatstroke (OR=47.46, 95% CI: 12.82-175.73)., Conclusions: There is a large room for improving health risk perception and adaptation capacity to heat waves among the public of Guangdong province. People with higher risk perception and fewer adaptation behaviors during heat waves may be more vulnerable to heat waves.

Background: Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies in humans, and its prognosis is generally poor even after surgery. Many advances have been made to understand the pathogenesis of HCC; however, the molecular mechanisms that lead to hepatocarcinogenesis and progression are still not clearly understood., Methods: The expression of DACT2 in specimens from 30 paired HCCs and an additional 61 HCC patients after liver transplantation was evaluated by quantitative RT-PCR and immunohistochemical analysis. We investigated the methylation status of the DACT2 promoter region. We also analyzed the alterations of the cell cycle, migration and invasion after DACT2 knockdown., Results: The expression level of DACT2 was significantly lower in HCC tissues than in non-cancerous tissues. Reduced DACT2 expression was associated with large tumor size. DACT2 transcripts were at low levels in hypermethylated liver cancer cells and were restored by exposure to a demethylating agent. Reduced expression of DACT2 in MHCC97L cells induced G1/S arrest, increased cell proliferation, and promoted cell invasion., Conclusions: Our study suggests that DACT2 is silenced by promoter hypermethylation, and reduced DACT2 can promote liver cancer progression. DACT2 may serve as a novel tumor suppressor gene in HCC.

Background: To explore the anti-tumor effects of parthenolide in human pancreatic cancer., Methods: BxPC-3 cell, a human pancreatic cancer, was treated with parthenolide at different concentrations. The MTT assay was used to analyze cell viability. Flow cytometry and DNA fragmentation analysis were applied to evaluate apoptosis after parthenolide treatment. The wound closure and cell invasion assay were also employed in the study. Western blotting was used to demonstrate Bad, Bcl-2, Bax, caspase-9 and pro-caspase-3 expression., Results: The MTT assay indicated that the pancreatic cancer growth could be dose-dependently inhibited by parthenoolide. This phenomenon was confirmed by flow cytometry and DNA fragmentation analysis. The wound closure assay and cell invasion assay showed that BxPC-3 cell was significantly suppressed by parthenolide at 7.5 microM and 15 microM. Western Blotting demonstrated the Bcl-2 and pro-caspase-3 were down-regulated while the Bax and caspase-9 were up-regulated. No alteration in Bad expression was found after treatment., Conclusions: The parthenolide can inhibit the cell growth, migration, and induce the apoptosis in human pancreatic cancer. These findings may provide a novel approach for pancreatic cancer treatment.

Background: CpG island methylator phenotype (CIMP), in which multiple genes concordantly methylated, has been demonstrated to be associated with progression, recurrence, as well as overall survival in some types of cancer., Methods: We examined the promoter methylation status of seven genes including P16, CDH1, GSTP1, DAPK, XAF1, SOCS1 and SYK in 65 cases of HCC treated with LT by methylation-specific PCR. CIMP+ was defined as having three or more genes that are concordantly methylated. The relationship between CIMP status and clinicopathological parameters, as well as tumor recurrence was further analyzed., Results: CIMP+ was more frequent in HCC with AFP > 400 ng/ml than those with AFP