Development of a Specific Aptamer-Modified Nano-System to Treat Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a prevalent gastrointestinal cancer characterized by high mortality and an unfavorable prognosis. While combination therapies involving surgery, chemotherapy, and radiation therapy are advancing, targeted therapy for ESCC remains underdeveloped. As a result, the overall five-year survival rate for ESCC is still below 20%. Herein, ESCC-specific DNA aptamers and an innovative aptamer-modified nano-system is introduced for targeted drug and gene delivery to effectively inhibit ESCC. The EA1 ssDNA aptamer, which binds robustly to ESCC cells with high specificity and affinity, is identified using cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX). An EA1-modified nano-system is developed using a natural egg yolk lipid nanovector (EA1-EYLNs-PTX/siEFNA1) that concurrently loads paclitaxel (PTX) and a small interfering RNA of Ephrin A1 (EFNA1). This combination counters ESCC's proliferation, migration, invasion, and lung metastasis. Notably, EFNA1 is overexpressed in ESCC tumors with lung metastasis and has an inverse correlation with ESCC patient prognosis. The EA1-EYLNs-PTX/siEFNA1 nano-system offers effective drug delivery and tumor targeting, resulting in significantly improved therapeutic efficacy against ESCC tumors. These insights suggest that aptamer-modified nano-systems can deliver drugs and genes with superior tumor-targeting, potentially revolutionizing targeted therapy in ESCC.

Longitudinal Dyadic Associations between Depressive Symptoms and Life Satisfaction among Chinese Married Couples and the Moderating Effect of Within-Dyad Age Discrepancy.

Family systems theory defines the family unit as a complex social system in which individual members influence and are influenced by each other. The current study aimed to investigate the longitudinal dyadic associations between life satisfaction and depressive symptoms among a sample of Chinese married couples and the moderating effect of within-dyad age discrepancy. The current sample included 5773 married couples who completed three waves of assessments of the China Family Panel Studies (CFPS) in 2012, 2016, and 2018. The sample was categorized into two groups based on the within-dyad age discrepancy: the younger-wife-older-husband dyads (n = 4280, 74.13%) and the older-wife-younger-husband dyads (n = 1493, 25.86%). The longitudinal actor-partner interdependence models with multiple-group analysis were used to analyze the data. The results showed that a majority of actor effects were significant across time, and the two groups exhibited the same pattern among the actor effects. The older-wife-younger-husband dyads showed fewer significant partner effects than the younger-wife-older-husband dyads, and most partner effects indicated mutual rather than unidirectional influence. These findings yielded support for the statement of family systems theory that family members interconnect and that the development of one's well-being needs to be understood in the context of the spouse's well-being.

The Association between Differentiation of Self and Life Satisfaction among Chinese Emerging Adults: The Mediating Effect of Hope and Coping Strategies and the Moderating Effect of Child Maltreatment History.

BACKGROUND: Differentiation of self (DoS) is a core construct in Bowen family systems theory. At the interpersonal level, it represents the capacity to maintain rational thinking rather than reacting emotionally, especially while under stress. Previous studies have demonstrated the positive association between DoS and life satisfaction. The current study aims to investigate the mediating roles of hope and coping strategies on this association, and whether the mediation mechanism was moderated by participants' experience of child maltreatment. METHODS: The current sample consisted of 447 Chinese college students recruited from three Chinese universities. DoS, life satisfaction, hope and coping strategies, as well as childhood maltreatment history, were measured via self-report. Structural equation modeling was used to test the proposed mediation and moderation effect. RESULTS: Participants who were maltreated in childhood (n = 149) exhibited significantly lower levels of DoS, hope, and positive coping strategies than the comparison group (n = 298) at baseline and lower life satisfaction at the 3-month follow-up. Structural equation modeling analysis showed that coping strategies mediated the association between DoS and life satisfaction for both the maltreated and comparison groups. Hope appeared to have a significant mediating effect only among those in the comparison group. CONCLUSIONS: The current findings lend support to Bowen's theoretical statement regarding the role of DoS on psychological well-being, with an incorporated viewpoint of Snyder's hope theory.

Self-assembled RNA nanocarrier-mediated chemotherapy combined with molecular targeting in the treatment of esophageal squamous cell carcinoma.

BACKGROUND: Esophageal cancer is the fifth most common cancer affecting men in China. The primary treatment options are surgery and traditional radio-chemotherapy; no effective targeted therapy exists yet. Self-assembled RNA nanocarriers are highly stable, easily functionally modified, and have weak off-tumor targeting effects. Thus, they are among the most preferred carriers for mediating the targeted delivery of anti-tumor drugs. miR-375 was found to be significantly down-regulated in esophageal squamous cell carcinoma (ESCC) tissues and its overexpression effectively inhibits the proliferation, migration, and invasion of ESCC cells. Moreover, epidermal growth factor receptor (EGFR) was overexpressed in ESCC cells, and accumulation of RNA nanoparticles in ESCC tumors was enhanced by EGFR-specific aptamer (EGFRapt) modification. RESULTS: Herein, a novel four-way junction RNA nanocarrier, 4WJ-EGFRapt-miR-375-PTX simultaneously loaded with miR-375, PTX and decorated with EGFRapt, was developed. In vitro analysis demonstrated that 4WJ-EGFRapt-miR-375-PTX possesses strong thermal and pH stabilities. EGFRapt decoration facilitated tumor cell endocytosis and promoted deep penetration into 3D-ESCC spheroids. Xenograft mouse model for ESCC confirmed that 4WJ-EGFRapt-miR-375-PTX was selectively distributed in tumor sites via EGFRapt-mediating active targeting and targeted co-delivery of miR-375 and PTX exhibited more effective therapeutic efficacy with low systemic toxicity. CONCLUSION: This strategy may provide a practical approach for targeted therapy of ESCC.

Reciprocal effects of depressive symptoms and life satisfaction among Chinese older married couples from 2010 to 2014: evidence from the China Family Panel Studies.

Objectives: Depressive symptoms and life satisfaction are closely related among the older adults. However, investigation of the dyadic influence of depressive symptoms and life satisfaction among Chinese older married couples is limited. The current study aimed to investigate the reciprocal effects of life satisfaction and depressive symptoms longitudinally among a sample of Chinese older married couples.Method: The current sample consisted of 1,877 older married couples from the China Family Panel Studies (CFPS). Depressive symptoms and life satisfaction were measured at the 2010 baseline and the 2014 assessment. Age, income, education, physical health, and length of marriage measured at baseline were included as the controlled variables. Data was analyzed with the longitudinal actor-partner interdependence models.Results: One's life satisfaction and depressive symptoms were significantly associated with his/her own life satisfaction and depressive symptoms longitudinally. In addition, higher levels of wives' depressive symptoms in 2010 were associated with higher levels of depressive symptoms and lower levels of life satisfaction among their husbands in 2014. Higher levels of husbands' life satisfaction in 2010 were associated with higher levels of wives' life satisfaction in 2014.Conclusion: The current study found both actor and partner effects in the long-term association between depressive symptoms and life satisfaction. Among these older married couples, husbands were the 'receivers' of their wives' depressive symptoms and the 'senders' of life satisfaction. Practitioners aiming to promote the well-beings of older married adults need to consider the dyadic influences given the significant partner effects found in the current study.

Coping as a Mediator Between Parental Attachment and Resilience: An Examination of Differential Effects Between Chinese Adolescents From Single Parent Families Versus Those From Intact Families.

The crude divorce rate has been increasing steadily for over a decade in China. Consequently, more and more children have to face the challenge of growing up in single parent families. The current study investigated the mediating effects of problem-oriented and emotion-oriented coping on the relationship between parental attachment and psychological resilience among a sample of Chinese adolescents from single parent families and intact families. Participants were 975 high school students (44.30% males; aged 15-19 years, M = 16.32 years, SD = 0.74), 871 from intact families and 104 from single parent families. Structural equation modeling showed that security in maternal attachment was positively associated with resilience through the indirect effect of reduced emotion-oriented coping among adolescents from single parent families. Among adolescents from intact families, security in maternal attachment was both directly associated with resilience and indirectly through enhanced problem-oriented and reduced emotion-oriented coping. Security in paternal attachment was associated with resilience both directly and indirectly through enhanced problem-oriented coping as well among those from intact families. Female adolescents exhibited significantly lower levels of resilience than male adolescents did regardless of the marital status of their parents. Limitations and suggestions for future research are discussed.

The Mediating Role of Autonomy and Relatedness on Maternal and Child Outcomes.

The current study examined the mediating role of both mother and child interactive behaviors, which granted or undermined autonomy and relatedness, on the bidirectional and longitudinal association between maternal depressive symptoms and child internalizing behaviors, as well as the association between maternal substance use and child externalizing behaviors. Child's sex and mother's drug of choice were explored as potential moderators of the mediation relationship. Data were collected from 183 dyads including treatment-seeking substance using mothers and their children (95 males, aged between 8 and 16 years old). Structural equation modeling analysis showed girls' internalizing and externalizing behaviors at the 3-month follow-up were negatively associated with the same behaviors at the 12-month follow-up through increased relatedness undermining behaviors from their mothers at the 6-month follow-up. Among mothers with opioids as their drug of choice (DOC), children's externalizing behaviors at the 3-month follow-up were positively associated with mothers' substance use at the 12-month follow-up through the elevated levels of mothers' relatedness undermining behaviors at the 6-month follow-up. Among mothers with alcohol as their DOC, maternal depressive symptoms at the 3-month follow-up were positively related to children's internalizing behaviors at the 12-month follow-up through reduced relatedness undermining behaviors exhibited by mothers at the 6-month follow-up. To our knowledge, this is one of the first studies to attempt to unravel these longitudinal and bidirectional influences as well as the moderated mediation pathways among families with a substance using mothers.

Reductions in Hard Drug Use Among Homeless Youth Receiving a Strength-Based Outreach Intervention: Comparing the Long-Term Effects of Shelter Linkage Versus Drop-in Center Linkage.

OBJECTIVES: The current study sought to test hard drug use outcomes for youth receiving a strengths-based outreach and advocacy intervention that linked youth to either a shelter or a drop-in center. METHODS: Homeless youth (14-24 years old) were engaged by research assistants (RAs) at soup kitchens, parks, libraries, and other locations that homeless youth were known to frequent. Youth were randomly assigned to receive six months of advocacy that focused on linking youth to a drop-in center (n = 40) or to a crisis shelter (n = 39). Follow-up assessments were conducted at 3, 6, and 9 months post-baseline. Hard drug use over time was the main outcome. Intervention condition and service connection were used as predictors for the baseline level and the slope of change in hard drug use over time. Data analysis was conducted with Bernoulli Hierarchical Generalized Linear Modeling in HLM7. RESULTS: The current study found that those who were in the drop-in linkage condition exhibited a greater reduction in their odds of using hard drugs during the follow-up points than their counterparts in the shelter linkage condition. And finally, those who utilized services more often during the follow-ups were those who exhibited less hard drug use at baseline and less reduction in their odds of using hard drugs. CONCLUSIONS: This study suggests that drop-in centers, which are often characterized by low-demand programming and few behavioral restrictions, are effective for addressing hard drug use among homeless youth.

Predictors of Outreach Meetings Among Substance Using Homeless Youth.

Homeless youth have high rates of substance use and often lack connection to social services. Outreach is critical for connecting youth to services, but factors influencing their outreach engagement are unknown. This study examined predictors of meetings with outreach workers among 79 non-service connected, substance using homeless youth between 14 and 24 years of age. Results provide direction to service providers in that older age, higher levels of depressive symptoms, fewer drug-related problems, and no use of hard drugs within the prior 30 days predicted higher meeting attendance. Future research is needed testing strategies that overcome barriers to outreach engagement.

A Test of Outreach and Drop-in Linkage Versus Shelter Linkage for Connecting Homeless Youth to Services.

Outreach and service linkage are key for engaging marginalized populations, such as homeless youth, in services. Research to date has focused primarily on engaging individuals already receiving some services through emergency shelters, clinics, or other programs. Less is known about those who are not connected to services and, thus, likely the most vulnerable and in need of assistance. The current study sought to engage non-service-connected homeless youth (N = 79) into a strengths-based outreach and advocacy intervention. Youth were randomly assigned to receive 6 months of advocacy that focused on linking youth to a drop-in center (n = 40) or to a crisis shelter (n = 39). All youth were assessed at baseline and 3, 6, and 9 months post-baseline. Findings indicated that youth prefer drop-in center services to the shelter. Also, the drop-in center linkage condition was associated with more service linkage overall (B = 0.34, SE = 0.04, p < 0.01) and better alcohol-l [B = -0.39, SE = 0.09, t(75) = -4.48, p < 0.001] and HIV-related outcomes [B = 0.62, SE = 0.10, t(78) = 6.34, p < 0.001] compared to the shelter linkage condition. Findings highlight the importance of outreach and service linkage for reconnecting service-marginalized youth, and drop-in centers as a primary service option for homeless youth.

Housing and Support Services with Homeless Mothers: Benefits to the Mother and Her Children.

This study reports the mental health outcomes of a small randomized clinical trial (n = 60) that compared housing and supportive services (Ecologically-Based Treatment, EBT) to community based housing and support services (treatment as usual, TAU). Mothers receiving EBT, but not those receiving TAU, reported reductions in their children's behavioral health problems. Reductions in mothers' mental health problems and intimate partner violence were observed in both TAU and EBT. The current findings provide evidence supporting the efficacy of independent housing and integrated support services. Given that EBT showed similar, and in some cases superior findings to TAU, EBT may be an effective alternative for communities that do not have shelters available for those families experiencing homelessness.

Changes in Family Relationships among Substance Abusing Runaway Adolescents: A Comparison between Family and Individual Therapies.

Eligible adolescents (12-17 years old) were recruited from a short-term crisis shelter for runaway adolescents in a large Midwestern city. Adolescents (N = 179) were randomly assigned to Ecologically-Based Family Therapy (EBFT, n = 61), the Community Reinforcement Approach (CRA, n = 57), or brief Motivational Enhancement Therapy (MET, n = 61) with the primary focus on substance abuse. A significant increase in perceived family cohesion and a significant reduction in perceived family conflict were found among all treatment conditions from baseline to the 24-month follow-up. Adolescents who received EBFT demonstrated more improvement in family cohesion after treatment than those who received CRA or MET, and more reduction in family conflict during treatment than those who received MET.

A comparison of three interventions for homeless youth evidencing substance use disorders: results of a randomized clinical trial.

While research on homeless adolescents and young adults evidencing substance use disorder is increasing, there is a dearth of information regarding effective interventions, and more research is needed to guide those who serve this population. The current study builds upon prior research showing promising findings of the community reinforcement approach (CRA) (Slesnick, Prestopnik, Meyers, & Glassman, 2007). Homeless adolescents and young adults between the ages of 14 to 20 years were randomized to one of three theoretically distinct interventions: (1) CRA (n = 93), (2) motivational enhancement therapy (MET, n = 86), or (3) case management (CM, n = 91). The relative effectiveness of these interventions was evaluated at 3, 6, and 12 months post-baseline. Findings indicated that substance use and associated problems were significantly reduced in all three interventions across time. Several moderating effects were found, especially for sex and history of childhood abuse. Findings show little evidence of superiority or inferiority of the three interventions and suggest that drop-in centers have choices for addressing the range of problems that these adolescents and young adults face.

Reducing High Risk Behaviors among Street Living Youth: Outcomes of an Integrated Prevention Intervention.

Research efforts to reduce Human Immunodeficiency Virus (HIV) risk behavior among street living youth have shown disappointing outcomes, with few studies reporting reduced risk behaviors. The current study tested the impact of an integrated HIV prevention intervention, and predictors of change, for youth (N=270) between the ages of 14 to 20 years receiving substance use treatment through a drop-in center. Condom use, HIV knowledge, number of sexual partners and behaviors associated with an overall HIV risk index were assessed at baseline, 3, 6 and 12 months post-baseline. Findings suggest that HIV prevention integrated with substance use treatment is associated with increased condom use and reduced sex partners. However, the effects on condom use were short lived and dissipated by 12 months post-baseline. Higher treatment attendance and baseline substance use predicted increased condom use. Although no significant change was observed in the overall HIV risk index, increases in depressive symptoms were associated with increases in the index score, as well as more sexual partners. Future research should determine whether successful intervention requires reinforcement of risk reduction behaviors while youth remain homeless.

A randomized pilot clinical trial to evaluate the efficacy of Community Reinforcement and Family Training for Treatment Retention (CRAFT-T) for improving outcomes for patients completing opioid detoxification.

BACKGROUND: Detoxification with psychosocial counseling remains a standard opioid-use disorder treatment practice but is associated with poor outcomes. This study tested the efficacy of a newly developed psychosocial intervention, Community Reinforcement Approach and Family Training for Treatment Retention (CRAFT-T), relative to psychosocial treatment as usual (TAU), for improving treatment outcomes. METHODS: A randomized, 14-week trial with follow-up visits at 6 and 9 months post-randomization conducted at two substance use disorder (SUD) treatment programs. Opioid-dependent adults (i.e., identified patient - IP) enrolled in a residential buprenorphine-detoxification program and their identified concerned significant other (CSO) was randomized to CRAFT-T (n=28 dyads) or TAU (n=24 dyads). CRAFT-T consisted of two sessions with the IP and CSO together and 10 with the CSO alone, over 14 weeks. TAU for the CSOs was primarily educational and referral to self-help. All IPs received treatment as usually provided by the SUD program in which they were enrolled. The primary outcome was time to first IP drop from treatment lasting 30 days or more. Opioid and other drug use were key secondary outcomes. RESULTS: CRAFT-T resulted in a moderate but non-significant effect on treatment retention (p=0.058, hazard ratio=0.57). When the CSO was parental family, CRAFT-T had a large and significant effect on treatment retention (p<0.01, hazard ratio=.040). CRAFT-T had a significant positive effect on IP opioid and other drug use (p<0.0001). CONCLUSION: CRAFT-T is a promising treatment for opioid use disorder but replication is needed to confirm these results.

Reductions in depressive symptoms among substance-abusing runaway adolescents and their primary caretakers: a randomized clinical trial.

This study reports secondary outcome findings on depressive symptoms from a randomized clinical trial testing three interventions for substance-abusing runaway adolescents. In particular, the effect of a family systems therapy, Ecologically Based Family Therapy (EBFT), and two individual therapies, the Community Reinforcement Approach (CRA) and Motivational Enhancement Therapy (MET), on adolescent and primary caretaker (PC) depressive symptoms were compared. Findings showed that youth's depressive symptoms were significantly reduced in each treatment to 2 years postbaseline. However, the trajectory of change differed across treatments, with adolescents receiving MET showing a more rapid reduction in depressive symptoms but a quicker increase in symptoms compared with adolescents receiving EBFT. PCs receiving EBFT showed a statistically significant decline in depressive symptoms, but this was not observed for the CRA and MET conditions. These findings can be interpreted to favor EBFT, although future research is needed to test training and implementation strategies for family systems therapies in community-based runaway shelters.

Two-year predictors of runaway and homeless episodes following shelter services among substance abusing adolescents.

Given high levels of health and psychological costs associated with the family disruption of homelessness, identifying predictors of runaway and homeless episodes is an important goal. The current study followed 179 substance abusing, shelter-recruited adolescents who participated in a randomized clinical trial. Predictors of runaway and homeless episodes were examined over a two year period. Results from the hierarchical linear modeling analysis showed that family cohesion and substance use, but not family conflict or depressive symptoms, delinquency, or school enrollment predicted future runaway and homeless episodes. Findings suggest that increasing family support, care and connection and reducing substance use are important targets of intervention efforts in preventing future runaway and homeless episodes amongst a high risk sample of adolescents.

Change in parent- and child-reported internalizing and externalizing behaviors among substance abusing runaways: the effects of family and individual treatments.

Shelter-recruited adolescents are known to have high rates of substance abuse and co-occurring internalizing and externalizing problem behaviors. Many studies have documented these mental health concerns, but only a small number of studies have tested interventions that may be useful for ameliorating these vulnerabilities. The current study compared three empirically supported psychotherapy interventions, Motivational Interviewing (MI), the Community Reinforcement Approach (CRA), and Ecologically-Based Family Therapy (EBFT) with 179 substance abusing runaway adolescents (47 % female, 74 % minority) and their primary caretaker recruited through a Midwestern runaway crisis shelter. Examining both child and primary caretaker reports, each treatment was associated with significant reductions in internalizing and externalizing behaviors to 24 months post-baseline. However, the trajectory of change differed among the treatments. Adolescents receiving MI showed a quicker reduction in internalizing and externalizing behaviors but also a quicker increase in these behaviors compared to adolescents receiving EBFT, who continued to evidence improvements to 24 months. The findings provide support for continued evaluation of these treatments for use with this vulnerable population of adolescents.

Treatment desires and symptomatology among substance-abusing homeless mothers: what I want versus what I need.

The current study sought to identify information that may inform treatment providers regarding services for, and engagement of, substance-abusing homeless mothers. Shelter-recruited, substance-abusing homeless mothers' desires for treatment in several commonly reported problem areas including substance use, parenting, depressive symptoms/mood, physical health, and childhood abuse history were assessed. The correspondence between mother's desire for treatment and self-reported problem severity was also examined. The majority of mothers reported at least some desire (versus no desire at all) for assistance with substance use, depressive symptoms/mood, and parenting. A series of independent-sample t tests and chi-square tests showed that mothers indicating any treatment desire in the areas of substance use, depressive symptoms/mood, health problems, and sexual abuse also reported higher levels of severity in the corresponding problem areas. The findings imply that psychosocial treatment should be available to all homeless mothers entering the shelter system, especially given that problem severity appears to be a fair indicator of interest in treatment.

Predictors of follow-up completion among runaway substance-abusing adolescents and their primary caretakers.

Follow-up rates reported among longitudinal studies that focus on runaway adolescents and their families are relatively low. Identifying factors associated with follow-up completion might be useful for improving follow-up rates and therefore study validity. The present study explored how individual- and family-level constructs, as well as research project activities, influence the follow-up completion rate among runaway adolescents (N = 140) and their primary caregiver. Results showed that follow-up completion rates decreased as the number of research assistants (RA) assigned to each case increased and as participants' address changes increased. Additionally, among adolescents, more frequent alcohol use was associated with lower follow-up rates. The current findings suggest that researchers should (1) design their research so that one RA is assigned to each specific case, and (2) adjust their retention strategies to account for the differences in follow-up rates based upon the participants' drug of choice and residential stability.