Effects of chronic unpredictable mild stress on gut sensation and function in male mice.

Stress has been linked to the development of irritable bowel syndrome (IBS), and various methods have been explored to model IBS in combination with other stimuli. However, it remains unclear whether stress alone can induce IBS in animals. This study aimed to investigate the impact of chronic unpredictable mild stress (CUMS) on gastrointestinal sensation and function in mice and assess the potential of CUMS as a modeling approach for IBS. To evaluate the mice's behavior, we conducted open field test, sucrose preference test and weighed the mice, revealing that CUMS indeed induced anxiety and depression in the mice and caused weight loss. Further analyses, including fecal analysis, a total gastrointestinal transport test, and a colon propulsion test, demonstrated that CUMS led to abnormal defecation and disruptions in gastrointestinal motility in the mice. Additionally, the abdominal withdrawal reflex test indicated an increase in visceral sensitivity in CUMS-exposed mice. Histological examination using hematoxylin and eosin staining revealed no significant histological alterations in the colons of CUMS-exposed mice, but it did show a minor degree of inflammatory cell infiltration. In summary, the findings suggest that CUMS can replicate IBS-like symptoms in mice, offering a novel top-down approach to modeling IBS.

Affiliate Stigma among family caregivers of individuals with dementia in China: a cross-sectional study.

Background: Affiliate stigma experienced by family caregivers of individuals with dementia may seriously affect home care and prognosis of these patients. This study aimed to explore the levels of perceived affiliate stigma and its influencing factors among family caregivers of patients with dementia in mainland China, which remains a relatively unexplored topic. Methods: In this cross-sectional study, purposive sampling was used to recruit dementia family caregivers from an online communication group between April and May 2022. A total of 727 eligible caregivers were included and asked to complete the demographic questionnaire, the affiliate stigma scale, and the caregiver burden inventory. Descriptive statistics, independent sample t-test, one-way analysis of variance, Pearson correlation analysis, and multiple linear regression were used to explore the factors that influence perceived affiliate stigma among dementia family caregivers. Results: The mean score for affiliate stigma of dementia family caregivers was 48.09 ± 16.38 (range: 22-86). Whether there were regular breaks during patient care, time-dependent burden, developmental burden, physical burden, and social burden were significant factors influencing the affiliate stigma of dementia family caregivers. Conclusion: Dementia family caregivers showed a moderate to high level of affiliate stigma. Those who had regular breaks during patient care, higher time-dependent burden, developmental burden, and physical burden and lower social burden exhibited higher levels of affiliate stigma.

Caffeic acid mitigates myocardial fibrosis and improves heart function in post-myocardial infarction by inhibiting transforming growth factor-ß receptor 1 signaling pathways.

Myocardial fibrosis is a pathological, physiological change that results from alterations, such as inflammation and metabolic dysfunction, after myocardial infarction (MI). Excessive fibrosis can cause cardiac dysfunction, ventricular remodeling, and heart failure. Caffeic acid (CA), a natural polyphenolic acid in various foods, has cardioprotective effects. This study aimed to explore whether CA exerts a cardioprotective effect to inhibit myocardial fibrosis post-MI and elucidate the underlying mechanisms. Histological observations indicated that CA ameliorated ventricular remodeling induced by left anterior descending coronary artery ligation in MI mice and partially restored cardiac function. CA selectively targeted transforming growth factor-ß receptor 1 (TGFBR1) and inhibited TGFBR1-Smad2/3 signaling, reducing collagen deposition in the infarcted area of MI mice hearts. Furthermore, cell counting (CCK-8) assay, 5-ethynyl-2'-deoxyuridine assay, and western blotting revealed that CA dose-dependently decreased the proliferation, collagen synthesis, and activation of the TGFBR1-Smad2/3 pathway in primary cardiac fibroblasts (CFs) stimulated by TGF-ß1 in vitro. Notably, TGFBR1 overexpression in CFs partially counteracted the inhibitory effects of CA. These findings suggest that CA effectively mitigates myocardial fibrosis and enhances cardiac function following MI and that this effect may be associated with the direct targeting of TGFBR1 by CA.

TaoHe ChengQi decoction ameliorates sepsis-induced cardiac dysfunction through anti-ferroptosis via the Nrf2 pathway.

BACKGROUND: Sepsis-induced cardiac dysfunction (SICD) is a serious complication of sepsis that is associated with increased mortality. Ferroptosis has been reported in the SICD. TaoHe ChengQi decoction (THCQD), a classical traditional Chinese medicinal formula, has multiple beneficial pharmacological effects. The potential effects of THCQD on the SICD remain unknown. PURPOSE: To investigate the effect of THCQD on SICD and explore whether this effect is related to the regulation of myocardial ferroptosis through nuclear factor erythroid 2-related factor 2 (Nrf2) activation. METHODS: We induced sepsis in a mouse model using cecal ligation and puncture (CLP) and administered THCQD (2 and 4 g/kg) and dexamethasone (40 mg/kg). Mice mortality was recorded and survival curves were plotted. Echocardiography, hematoxylin and eosin staining, and analysis of serum myocardial injury markers and inflammatory factors were used to evaluate cardiac pathology. Myocardial ferroptosis was detected by quantifying specific biomarker content and protein levels. Through HPLC-Q-Exactive-MS analysis, we identified the components of the THCQD. Network pharmacology analysis and Cellular Thermal Shift Assay (CETSA) were utilized to predict the targets of THCQD for treating SICD. We detected the expression of Nrf2 using Western blotting or immunofluorescence. An RSL3-induced ferroptosis model was established using neonatal rat cardiomyocytes (NRCMs) to further explore the pharmacological mechanism of THCQD. In addition to measuring cell viability, we observed changes in NRCM mitochondria using electron microscopy and JC-1 staining. NRF2 inhibitor ML385 and Nrf2 knockout mice were used to validate whether THCQD exerted protective effects against SICD through Nrf2-mediated ferroptosis signaling. RESULTS: THCQD reduced mortality in septic mice, protected against CLP-induced myocardial injury, decreased systemic inflammatory response, and prevented myocardial ferroptosis. Network pharmacology analysis and CETSA experiments predicted that THCQD may protect against SICD by activating the Nrf2 signaling pathway. Western blotting and immunofluorescence showed that THCQD activated Nrf2 in cardiac tissue. THCQDs consistently mitigated RSL3-induced ferroptosis in NRCM, which is related to Nrf2. Furthermore, the pharmacological inhibition of Nrf2 and genetic Nrf2 knockout partially reversed the protective effects of THCQD on SICD and ferroptosis. CONCLUSION: The effect of THCQD on SICD was achieved by activating Nrf2 and its downstream pathways.

Effects of remote dignity therapy on mental health among patients with hematologic neoplasms and their significant others: A randomized controlled trial.

BACKGROUND: Families of patients with hematologic neoplasms involved in dignity therapy have exhibited a remarkable improvement in psychological well-being and family functioning. However, the applicability and generalizability of family participatory dignity therapy are limited as it is influenced by factors such as intervention time, place, and participants. Whether remote support from significant others is feasible and effective remains unknown. OBJECTIVES: This study aimed to confirm the efficacy of significant others participating in remote dignity therapy (r-DT) on hope, dignity loss, meaning of life, and sense of stigma among patients with hematologic neoplasms as well as their significant others' depression and anxiety. DESIGN: A randomized, single-blinded, two-arm, parallel-group controlled trial. SETTING(S) AND PARTICIPANTS: Participants included patients with hematologic neoplasms and their significant others, who were recruited from Fujian Medical University Union Hospital from May 2021 to January 2022. METHODS: A total of 72 eligible participants (patients and significant others) agreed to participate, and were randomly assigned to an intervention group (n = 35) or a control group (n = 37). Each pair of participants in the intervention group participated in two or three conversations based on the online video function of the WeChat platform, performed by one therapist in accordance with a specific communication outline. To evaluate the effects of the intervention, we assessed the patients' degree of dignity loss, hope level, meaning of life, and sense of stigma, as well as their significant others' depression, anxiety, and intimacy at baseline (T0), 15 days (T1), 30 days (T2), and 60 days (T3), and compared the scores between the two groups after the completion of the intervention. The Generalized Estimation Equation Model (GEE) was used to examine the effects of time, group, and their interaction. RESULTS: The intervention group statistically significantly differed in lower dignity loss (t = 2.190, p = 0.032), higher hope level (t = -2.010, p = 0.049), and higher meaning of life (t = -2.066, p = 0.043) than the control group at T1. Regarding their significant others, the results of the comparison between the two groups showed that significant others in the intervention group had reduced levels of anxiety and depression at T1 and T2 (p < 0.05). The majority of patients (84.38 %) and significant others (75.00 %) provided positive evaluations of the program. CONCLUSIONS: The r-DT showed a short-term positive effect on decreasing patients' dignity loss and promoting patients' hope and meaning of life; among their significant others, it decreased anxiety and depression. TRIAL REGISTRATION: Registered in the China Clinical Trial Registry on 17 March 2021(ChiCTR2100044374). TWEETABLE ABSTRACT: Remote dignity therapy decreased patients' dignity loss and promoted their hope and meaning of life; among their significant others, it decreased anxiety and depression.

Understanding the symptom experience and self-management strategies of adult hematopoietic stem cell transplantation patients during hospitalization: findings from a qualitative longitudinal study.

PURPOSE: The aim of this study was to explore the symptom experience and self-management strategies of adult hematopoietic stem cell transplantation patients during hospitalization. METHODS: This was a qualitative descriptive study. A heterogeneous sample of 19 patients who underwent hematopoietic stem cell transplantation from May to October 2021 were enrolled in the study. Semi-structured interviews were conducted at four time points during hospitalization, providing a total of 64 interview datasets. RESULTS: Four themes and 11 subthemes reflecting the symptom experience and self-management strategies of adult hematopoietic stem cell transplantation patients during hospitalization were observed. The four themes were (1) unexpected symptom burden: dynamic, disturbing, co-occurring, and correlative; (2) emotional complexity at different periods; (3) internal predicament: ineffectiveness of symptom management; and (4) external strength: desire for support from multiple sources. Hematopoietic stem cell transplantation patients experienced a complex and dynamic array of symptoms from admission to discharge, and they experienced the dual forces of internal predicament and external strength in symptom self-management during hospitalization. CONCLUSION: The findings of this study emphasize the need for a deeper understanding and precise management of the symptom experience of adult hematopoietic stem cell transplantation patients during hospitalization. Hematopoietic stem cell transplantation nurses need to assess symptoms on an ongoing basis; educate patients on ways to perceive, express, and self-manage multiple symptoms; and develop patients' self-symptom management skills to enhance their symptom relief and quality of life.

A dual-function luminescent probe for copper(II) ions and pH detection based on ruthenium(II) complex.

A new ruthenium complex-based luminescent probe Ru-impa for Cu2+ and pH detection has been synthesized and characterized. Ru-impa could rapidly and selectively detect Cu2+ in aqueous solutions and the working pH ranges from weakly acidic to alkaline. The detection limit calculated using the S/N and S/B ratio was 24.7 nM and 3.4 µM, respectively. The test strips for practical detecting application were also prepared and the actual detection limit in drinking water was found to be 3 µM, which is lower than the WHO-guided drinking water limit (30 µM) and the upper limit of human serum free copper content (1.7-3.9 µM). Luminescence imaging study showed that Ru-impa could monitor Cu2+ level fluctuation in the cells. In addition, Ru-impa also shows a sensitive on-off luminescence response when pH > 10, indicating that it can also be used as a pH sensor under extremely alkaline conditions.

Polymorphisms and association of GRM1, GNAQ and HCRTR1 genes with seasonal reproduction and litter size in three sheep breeds.

Litter size is one of the important economic traits of livestock. Seasonal oestrus, ovulation and lambing of sheep have severely restricted the development of sheep farming in Xinjiang, China. The purpose of this study was to investigate the polymorphisms and genetic correlation between GRM1, GNAQ and HCRTR1 genes and the seasonal reproduction and litter size in three sheep breeds. The DNA mixed pool sequencing and PCR-SSCP methods were used to detect single nucleotide polymorphisms (SNPs) of GRM1, GNAQ and HCRTR1 genes in seasonal oestrous (Kazakh and Chinese Merino [Xinjiang Junken type]) and perennial oestrous (Hu) sheep breeds. The association between genetic polymorphism and litter size was also analysed. The results showed that T945C in exon 2 of GRM1 gene, C589T in exon 2 of HCRTR1 gene and A191G in exon 2 of GNAQ gene were identified by Sanger sequencing, and three genotypes were existed in each SNP site, which all belonged to the synonymous mutation. GRM1 (CC), GNAQ (GA) and HCRTR1 (TC) were the dominant genotypes of seasonal reproduction and litter size in Kazakh sheep and Chinese Merino sheep, respectively, while, in perennial oestrous Hu sheep populations, the dominant genotypes were GRM1 (TC), GNAQ (GA) and HCRTR1 (TC), respectively, and association analysis also confirmed the results. The above results implied that GRM1, GNAQ and HCRTR1 genes are significantly associated with lambing traits in Kazakh, Chinese Merino and Hu sheep. Among them, the locus of GRM1 (T945C), GNAQ (A191G) and HCRTR1 (C589T) might be considered as a potential molecular marker, which controls seasonal reproduction and litter size in sheep.

Barriers to seeking psychosocial support among adult patients with hematologic neoplasms: a qualitative study.

PURPOSE: This study aims to explore the barriers that adult patients with hematologic neoplasms experience when seeking psychosocial support. METHODS: A descriptive qualitative approach was used to investigate the experiences of patients with hematologic neoplasms. Face-to-face, semi-structured, in-depth individual interviews were conducted between June and October 2020 with 17 patients diagnosed with hematologic neoplasms. The interviews were audio-recorded and transcribed verbatim. A thematic analysis was performed to identify the essential themes. RESULTS: Seventeen patients aged 28-67 years completed the interviews. Two themes and six subthemes were identified that describe barriers to seeking psychosocial support. Internal barriers included limited communication, negative emotions, social avoidance, and focusing on treatment rather than psychosocial needs; external barriers included traditional cultural influences and lack of professional support. CONCLUSIONS: Significant others were the key source for psychosocial support for patients with hematologic neoplasms. Tackling diverse barriers to accessing psychosocial support remains a challenge for these patients. Healthcare providers should continually assess and provide effective support.

Effects of family participatory dignity therapy on the psychological well-being and family function of patients with haematologic malignancies and their family caregivers: A randomised controlled trial.

BACKGROUND: Strong family ties appear to buffer patient's and family members' difficult experiences during life and health crises. The family participatory dignity therapy programme, a patient-family-centred psychological intervention, was developed based on dignity therapy and performed by one therapist in the form of interview according to a specific question prompt. OBJECTIVES: This study aimed to confirm the efficacy of the family participatory dignity therapy programme in improving the psychological well-being and family cohesion and adaptability of patients with haematologic malignancies and their family caregivers. DESIGN: A single-blinded, two-arm parallel group, randomised controlled trial was conducted. SETTING(S): and Participants: Participants were patient-family caregiver dyads recruited from Fujian Medical University Union Hospital from March to September 2019. METHODS: A total of 68 eligible dyads agreed to participate and were randomly assigned to the intervention group (n = 33) or control group receiving usual care (n = 35). Each pair of patient-family dyads in the intervention group received two or three interviews (each interview approximately lasting 45 to 60 min) performed by one therapist according to a specific question prompt containing 10 questions for patients and 10 corresponding questions for their family caregivers. To evaluate the effects of the intervention, we assessed patients' hope, spiritual well-being, and family cohesion and adaptability, as well as their family caregivers' depression, anxiety, and family cohesion and adaptability at baseline (T0), 1 week (T1), 4 weeks (T2), and 8 weeks post-intervention (T3) and compared the scores between the groups. A two-way repeated-measures analysis of variance was conducted to examine the effects of time, group, and their interaction. RESULTS: For patients, there was a significant difference in hope (p = 0.001), spiritual well-being (p = 0.002), and family cohesion (p<0.001) and adaptability (p<0.001) between the intervention and control groups. The difference over time was also significant in family cohesion (p = 0.018) and adaptability (p = 0.003). The interaction effects were significant for hope (p = 0.034), spiritual well-being (p<0.001), and family cohesion (p<0.001) and adaptability (p<0.001). For family caregivers, there was a significant difference in anxiety (p = 0.037), depression (p = 0.001), and family adaptability (p = 0.036) between the intervention and control groups. Within groups, a significant difference in family adaptability (p = 0.012) was found. Moreover, the interaction effects were significant on anxiety (p = 0.001) and family cohesion (p = 0.038). CONCLUSIONS: The family participatory dignity therapy programme showed a positive effect on promoting patients' hope, spiritual well-being, and family cohesion and adaptability; amongst family caregivers, it decreased anxiety and depression, and enhanced family cohesion and adaptability. Registration number: ChiCTR1900021433 Tweetable abstract: The family participatory dignity therapy programme promoted patients' hope, spiritual well-being, and family cohesion and adaptability, decreased their family caregivers' anxiety and depression, and enhanced the caregivers' family cohesion and adaptability.

Real-Time Monitoring of Self-Aggregation of ß-Amyloid by a Fluorescent Probe Based on Ruthenium Complex.

Self-accumulation of amyloid-ß protein (Aß) into insoluble fibrils is the major hallmark of Alzheimer's disease. Real-time monitoring of fibril growth is essential for clarifying the mechanism underlying aggregation and discovering therapeutic targets. A variety of approaches including NMR, electron microscopy (EM), atomic force microscopy (AFM), and total internal reflection fluorescence microscopy (TIRFM) have been explored to monitor the fibril growth or reveal morphology of Aß aggregates. However, none of the methods allow real-time observation under physiological conditions while without any perturbations. Here, we present a fluorescent probe [Ru(phen)2(fipc)]2+ (Ru-fipc) (phen = 1,10-phenanthroline, fipc = 5-fluoro-N-(1,10-phenanthrolin-5-yl)-1H-indole-2-carboxamide) that can bind to all the Aß forms, i.e., monomers, oligomers, and fibrils, while not perturbing aggregation. Using this probe in combination with laser confocal microscopy, the entire aggregation process could be clearly and exactly imaged at the single fibril level. The reliability of Ru-fipc was confirmed based on colocalization with thioflavin T (ThT). Importantly, Ru-fipc can be used to monitor the very early nucleation and oligomerization process, which is thought to be a critical step in the development of neurotoxicity while it cannot be visualized with ThT. To our knowledge, this is the first fluorescent probe developed for real-time monitoring of Aß aggregation, especially for the very early assembly stage, in solution with minimal perturbation. This method is suitable for in vitro and in vivo studies. We believe this would provide a valuable complementary tool for the study of pathogenesis and discovery of therapeutic targets of neurodegenerative diseases.

The interaction effects of risk factors for hypertension in adults: a cross-sectional survey in Guilin, China.

BACKGROUND: The prevalence of hypertension in adults is increasing each year and has become a main public health issue worldwide. We must consider the impact of both individual factors and interactions among these factors on hypertension in adults. This study was designed to elucidate the clinical and metabolic characteristics of the prevalence of hypertension in adults and to explore the risk factors and interactions among these factors in adults with hypertension. METHODS: We used overall random sampling to conduct a cross-sectional survey of 6660 individuals undergoing a health check from July to November 2012, the subjects were aged 20 to 89 years, including 3480 men and 3180 women. The survey content included a questionnaire, anthropometry, laboratory measurements, and liver Doppler ultrasonography. The clinical and metabolic characteristics were compared between the cases (adult hypertensive patients) and the controls (normotensives). The classification tree model and the non-conditional logistic regression were used to analyze the interactions of risk factors for hypertension in adults. RESULTS: In total, 1623 adult hypertensive patients (940 men and 683 women) were detected. The results showed that adult hypertensive patients were older and had higher levels of systolic blood pressure, diastolic blood pressure, body mass index, fasting plasma glucose, uric acid, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and prevalence of non-alcoholic fatty liver disease (P < 0.001). The classification tree model comprising 5 layers, 39 nodes, and 20 terminal nodes showed that two variables, age and BMI, were closely related to hypertension in adults. The area under the receiver operating characteristic curve for classification tree model was 81.6 % (95 % CI: 80.6 % ~ 82.5 %). Both univariate and multivariate logistic regression analyses revealed that advanced age and high BMI had a significant positive interaction in terms of hypertension in adults. After controlling for confounding factors, the percentage of attributed interaction was 47.62 %. CONCLUSIONS: This study showed that age, BMI, UA, TG, and TC were closely associated with the risk of hypertension in adults, and the positive interaction effect between advanced age and high BMI was an important risk factor for the prevalence of hypertension in adults.

[Multiresidue analysis of 63 veterinary drugs in meat by dispersive solid-phase extraction and high performance liquid chromatography-tandem mass spectrometry].

A novel multiresidue analytical method has been developed and validated for the determination of five classes of veterinary drugs including 18 ß-lactams, 15 quinolones, 21 sulfonamides, 3 sulfonamide potentiators and 6 antiparasitics in meat using dispersive solid-phase extraction (dispersive-SPE) and high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The analytes were extracted with a vortex mixer by 0.1 mol/L Na2 EDTA solution and acetonitrile containing 1% (v/v) acetic acid, and then the extracts were purified using dispersive-SPE with C18 sorbent. Electrospray ionization mass spectrometry was operated in positive mode using dynamic multiple reaction monitoring (DMRM) for the qualitative and quantitative analysis of the 63 analytes after the separation on a Poroshell EC-C18 column (100 mm x 2.1 mm, 2.4 µm). The correlation coefficients of linear calibration curves were over 0.99 in the corresponding concentration ranges. The average recoveries of the 63 analytes ranged from 62.2% to 112.0%, and the relative standard deviations (RSDs) were 3.1%-16.3% in spiked meat (pork, beef and chicken muscle) at three levels. The limits of detection (LODs, S/N ≥ 3) and the limits of quantification (LOQs, S/N ≥ 10) were 0.1-3.0 µg/kg and 0.5-10.0 µg/kg, respectively. The method is simple, rapid, sensitive, reliable and suitable for the determination of residues in animal products.