Mass filtering combined with photochemical derivatization enables high throughput mass spectrometric analysis of unsaturated phosphatidylcholine isomers.

Phosphatidylcholines (PCs) are closely related to coronary heart disease, such as myocardial infarction. The analysis of the deep structure of PCs is of great significance for exploring the effects of exercise rehabilitation and lipid metabolism. Here, we present a mass filtering combined with photochemical derivatization method for rapid screening and accurate identification of the CC position and sn-location isomer of PCs. This method is simple to execute and easily implementable for routine analysis. The accurate qualitative and quantitative analysis of PCs and isomers facilitates the discovery of biomarkers for exercise rehabilitation of patients with myocardial infarction.

LncRNA NRON promotes tumorigenesis by enhancing MDM2 activity toward tumor suppressor substrates.

The E3 ligase MDM2 promotes tumor growth and progression by inducing ubiquitin-mediated degradation of P53 and other tumor-suppressing proteins. Here, we identified an MDM2-interacting lncRNA NRON, which promotes tumor formation by suppressing both P53-dependent and independent pathways. NRON binds to MDM2 and MDMX (MDM4) via two different stem-loops, respectively, and induces their heterogenous dimerization, thereby enhancing the E3 ligase activity of MDM2 toward its tumor-suppressing substrates, including P53, RB1, and NFAT1. NRON knockdown dramatically inhibits tumor cell growth in vitro and in vivo. More importantly, NRON overexpression promotes oncogenic transformation by inducing anchorage-independent growth in vitro and facilitating tumor formation in immunocompromised mice. Clinically, NRON expression is significantly associated with poor clinical outcome in breast cancer patients. Together, our data uncover a pivotal role of lncRNA that induces malignant transformation of epithelial cells by inhibiting multiple tumor suppressor proteins.

FOXM1 Contributes to Chemotherapy Sensitivity in Cervical Cancer by Regulating TTK.

BACKGROUND: The emergence of chemotherapy resistance usually causes therapeutic failure in advanced cervical cancer. Forkhead box protein M1 (FOXM1) and threonine tyrosine kinase (TTK) are closely associated with cancer drug sensitivity, but the mechanism of FOXM1 on TTK involvement in chemo-treated cervical cancer remains unclear. Here, we aimed to observe the effects of FOXM1 on TTK and on chemotherapy sensitivity in cervical cancer. METHODS: The expressions of FOXM1 and TTK in cervical cancer tissues and para-cancerous tissues were analyzed by immunohistochemistry. SiHa and Hela cells were transfected with human lentivirus-FOXM1, small interfering RNA (siRNA) or pcDNA3.1/FOXM1 to analyze the changes in TTK protein expression. Furthermore, the cells were treated with paclitaxel (8 µM) or cisplatin (10 µM) to analyze the effects of FOXM1 on chemotherapy sensitivity. SiHa cells were used to construct a xenograft model to study the effects of FOXM1 expression in response to paclitaxel treatment. The tumor size and weight were observed. The expressions of Ki-67, FOXM1, and TTK protein in tumor tissues were measured by immunohistochemistry. RESULTS: High expression of FOXM1 and TTK were found in the cervical cancer tissues (p < 0.05). The TTK protein expressions were decreased by FOMX1-siRNA transfection in SiHa and Hela cells (p < 0.01). The cell viability and cell cycle were also suppressed by FOMX1-siRNA transfection (p < 0.01) but enhanced by pcDNA3.1/FOXM1 transfection (p < 0.01). For paclitaxel or cisplatin treatment, the cell viability and cell DNA damage were improved due to the FOXM1 overexpression (p < 0.01). TTK inhibitor significantly suppressed the effects of FOXM1 overexpression (p < 0.01). CONCLUSIONS: FOXM1 regulated TTK and affected the therapeutic efficacy of cisplatin and paclitaxel in cervical cancer.

Matrix metalloproteinase-2 delivery to extracellular vesicles produced by HPV-positive cervical cancer cells enhances metastasis via the Akt pathway.

Here, we aimed to analyze the effects of matrix metalloproteinase-2 (MMP-2) delivery to extracellular vesicles (EVs) secreted by human papillomavirus (HPV)-associated cervical cancer cells on human umbilical vein endothelial cell (HUVEC) angiogenesis. First, MMP-2 expression was compared among SiHa (HPV16), HeLa (HPV18), and C-33A (negative) cells. Then, EVs were isolated from these cells, and MMP-2 expression in the EVs was compared. SiHa and HeLa cells were transfected with MMP-2 or control siRNA. HUVECs were treated with EVs isolating from transfected cells. Migration and angiogenesis of HUVECs were measured, and p-Akt protein expression in HUVECs was detected. An Akt inhibitor or activator was used to analyze the effect of MMP-2 delivery to EVs on the migration of HUVECs. The SiHa-induced xenograft tumors were treated with 2 µg of EVs every 3 d for a total of 27 d. Tumor growth, and the expression levels of p-Akt, MMP-2, and vascular endothelial growth factor (VEGF) were observed in the tumors. The results showed that MMP-2 expression was higher in SiHa- and HeLa-derived EVs than that in the C-33A-derived EVs. Interference with MMP-2 suppressed the invasion of SiHa and HeLa cells. The migration and angiogenesis of HUVECs were enhanced by MMP-2 delivery to EVs secreted by SiHa and HeLa cells through regulation of the Akt pathway. The growth of xenograft tumors was accelerated by EVs secreted by SiHa cell with differential MMP-2 expression. Our results indicate the delivered MMP-2 in EVs acts as a messenger between HPV-associated cancer cells and HUVECs.

Evaluation of metoprolol standard dosing pathway in Chinese patients with acute coronary syndrome: a prospective multicenter single-arm interventional study.

OBJECTIVE: To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS: In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS: Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS: In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.

[Correlation between video head impulse test parameters and DHI score in patients with vestibular neuritis].

Objective:To explore the correlation between the parameters of video head impulse test （vHIT）and dizziness handicap inventory （DHI） score in patients with vestibular neuritis. Methods:Clinical data of 46 patients with vestibular neuritis were retrospectively analyzed. All the patients underwent DHI evaluation and vHIT examination. They were divided into mild handicap group, moderate handicap group and severe handicap group according to DHI score. The correlations between the parameters of vHIT and DHI score were compared among the three groups. The important parameters of vHIT were compared including vestibulo-ocular reflex （VOR） gain, gain asymmetry ratio （GA）, abnormal saccade dispersion （PR%）. Results:Of the 46 patients, 10 were in the mild handicap group, 21 in the moderate handicap group, and 15 in the severe handicap group. ①In the comparison of the mean value of lateral semicircular canal VOR gain, the vHIT gain of patients with mild, moderate and severe handicap were 0.64±0.06, 0.53±0.11 and 0.37±0.10, respectively, the mean value of VOR gain was negatively correlated with DHI score among the three groups（r=-0.545, P<0.001）, and the pairwise comparisons among the three groups was statistically significant（P<0.05）. In comparison of the mean values of lateral semicircular canal GA, the GA values of mild, moderate and severe handicap groups were 46.40±21.81, 47.59±15.17 and 56.57±17.39, respectively, there was no significant linear correlation between GA values and DHI scores among the three groups（r=0.246, P>0.05）, there was no significant difference between the three groups（P>0.05）. In comparison of the mean PR% of the lateral semicircular canal, the mean PR% of patients with mild, moderate and severe handicap group were 32.00±10.62, 53.82±17.09 and 76.00±10.01, respectively, PR% was positively correlated with DHI score（r=0.726, P<0.001）, and the comparison among the three groups was statistically significant（P<0.05）. ②The vertical semicircular canal vHIT gain of patients with mild, moderate and severe handicap was 0.63±0.06, 0.52±0.15 and 0.38±0.16, respectively, the mean of VOR gain was negatively correlated with DHI score among the three groups（r=-0.487, P<0.01）, the comparison of mild-severe and moderate-severe group was statistically significant（P<0.05）, while there was no significant difference between the mild and moderate group（P>0.05）. In the comparison of the mean values of vertical semicircular canal GA, the GA values of mild, moderate and severe handicap groups were 40.40±15.31, 46.10±19.59 and 47.87±18.05, respectively, there was no significant linear correlation between GA values and DHI scores among the three groups（r=0.047, P>0.05）, there was no significant difference in GA among the three groups（P>0.05）. The PR% of patients with mild, moderate and severe handicap were 42.40±15.39, 54.14±17.60 and 64.93±10.95, respectively, there was a positive significant correlation between PR% and DHI score（r=0.454, P<0.05）, there was statistically significant in the comparison of mild-severe group（P<0.05）, while there was no statistical significance between the other groups（P>0.05）. Conclusion:The VOR gain and PR% value of vHIT in patients with vestibular neuritis are closely related to the DHI score, which can evaluate the vestibular function and the degree of vertigo.

Long noncoding RNA DIO3OS induces glycolytic-dominant metabolic reprogramming to promote aromatase inhibitor resistance in breast cancer.

Aromatase inhibition is an efficient endocrine therapy to block ectopic estrogen production for postmenopausal estrogen receptor (ER)-positive breast cancer patients, but many develop resistance. Here, we show that aromatase inhibitor (AI)-resistant breast tumors display features of enhanced aerobic glycolysis with upregulation of long noncoding RNA (lncRNA) DIO3OS, which correlates with poor prognosis of breast cancer patients on AI therapies. Long-term estrogen deprivation induces DIO3OS expression in ER-positive breast tumor cells, which further enhances aerobic glycolysis and promotes estrogen-independent cell proliferation in vitro and in vivo. Mechanistically, DIO3OS interacts with polypyrimidine tract binding protein 1 (PTBP1) and stabilizes the mRNA of lactate dehydrogenase A (LDHA) by protecting the integrity of its 3'UTR, and subsequently upregulates LDHA expression and activates glycolytic metabolism in AI-resistant breast cancer cells. Our findings highlight the role of lncRNA in regulating the key enzyme of glycolytic metabolism in response to endocrine therapies and the potential of targeting DIO3OS to reverse AI resistance in ER-positive breast cancer.

The Novel LncRNA WASH5P Inhibits Colorectal Cancer Carcinogenesis via Targeting AKT Signaling Pathway.

Emerging evidence has shown that long non-coding RNAs (lncRNAs) play an important role in colorectal cancer (CRC) carcinogenesis, so more specific mechanisms of key lncRNAs in CRC initiation and development are needed. Here, we evaluated the expression profiles of lncRNAs in CRC tissues and identified a novel lncRNA generated from the pseudogene Wiskott-Aldrich syndrome protein (WASP) family homolog 5, termed lncRNA WASH5P. However, the role and potential molecular mechanism of this novel lncRNA in diseases, including CRC carcinogenesis, is unknown. Our present study found that WASH5P was significantly downregulated in CRC cell lines and tissues compared with normal controls. The ectopic expression of WASH5P in CRC cells could significantly inhibit CRC cell proliferation, invasion, and migration. In addition, WASH5P could increase the expression of E-cadherin and decrease Vimentin expression. WASH5P-overexpressing CRC cells developed tumors more slowly in different mouse models. Meanwhile, the overexpression of WASH5P could significantly inhibit AKT activation via suppressing AKT phosphorylation. The treatment of PI3K/AKT (phosphatidlinositol 3-kinase /protein kinase B) signaling agonist 740Y-P rescued WASH5P-reduced AKT phosphorylation and abolished the inhibitory effects of WASH5P on cell viability, migration, and invasion. Moreover, 740Y-P restored the WASH5P-induced downregulation of p-AKT and vimentin and the upregulation of E-cadherin via Western blot. In summary, our findings suggested that the novel lncRNA WASH5P might be a potential candidate biomarker and therapeutic target that could inhibit CRC by repressing the AKT signaling pathway.

The intestinal microbiome associated with lipid metabolism and obesity in humans and animals.

Intestinal microbiota is considered to play an integral role in maintaining health of host by modulating several physiological functions including nutrition, metabolism and immunity. Accumulated data from human and animal studies indicate that intestinal microbes can affect lipid metabolism in host through various direct and indirect biological mechanisms. These mechanisms include the production of various signalling molecules by the intestinal microbiome, which exert a strong effect on lipid metabolism, bile secretion in the liver, reverse transport of cholesterol and energy expenditure and insulin sensitivity in peripheral tissues. This review discusses the findings of recent studies suggesting an emerging role of intestinal microbiota and its metabolites in regulating lipid metabolism and the association of intestinal microbiota with obesity. Additionally, we discuss the controversies and challenges in this research area. However, intestinal micro-organisms are also affected by some external factors, which in turn influence the regulation of microbial lipid metabolism. Therefore, we also discuss the effects of probiotics, prebiotics, diet structure, exercise and other factors on intestinal microbiological changes and lipid metabolism regulation.

The P300 Auditory Event-Related Potential May Predict Segregation of Competing Speech by Bimodal Cochlear Implant Listeners.

Compared to normal-hearing (NH) listeners, cochlear implant (CI) listeners have greater difficulty segregating competing speech. Neurophysiological studies have largely investigated the neural foundations for CI listeners' speech recognition in quiet, mainly using the P300 component of event-related potentials (ERPs). P300 is closely related to cognitive processes involving auditory discrimination, selective attention, and working memory. Different from speech perception in quiet, little is known about the neurophysiological foundations for segregation of competing speech by CI listeners. In this study, ERPs were measured for a 1 vs. 2 kHz contrast in 11 Mandarin-speaking bimodal CI listeners and 11 NH listeners. Speech reception thresholds (SRTs) for a male target talker were measured in steady noise or with a male or female masker. Results showed that P300 amplitudes were significantly larger and latencies were significantly shorter for the NH than for the CI group. Similarly, SRTs were significantly better for the NH than for the CI group. Across all participants, P300 amplitude was significantly correlated with SRTs in steady noise (r = -0.65, p = 0.001) and with the competing male (r = -0.62, p = 0.002) and female maskers (r = -0.60, p = 0.003). Within the CI group, there was a significant correlation between P300 amplitude and SRTs with the male masker (r = -0.78, p = 0.005), which produced the most informational masking. The results suggest that P300 amplitude may be a clinically useful neural correlate of central auditory processing capabilities (e.g., susceptibility to informational masking) in bimodal CI patients.

Novel heterozygous mutations in the otogelin-like (OTOGL) gene in a child with bilateral mild nonsyndromic sensorineural hearing loss.

Hearing loss is a common disease, of which genetic factors are the main cause. The incidence of mild or moderate postlingual deafness in children is not high, and the impact on life and learning is not as severe as that of prelingual deafness. This leads to insufficient attention to the disorder in the clinic. To date, only a few disease-causing genes have been reported. This report describe a case of novel heterozygous mutations in OTOGL that causes nonsyndromic mild sensorineural hearing loss. Basic information, imaging examinations, audiological examination, and vestibular function tests of the proband were collected. Blood samples of the proband's family were collected and analyzed by whole exome sequencing and Sanger sequencing. A pedigree diagram was drawn and the genetic patterns were analyzed. The proband is a 16-year-old female student with mild sensorineural hearing loss. High-resolution CT of the inner ear and vestibular function tests showed no abnormalities. The age of onset was approximately 4 years old. Except for hearing loss, no lesions were seen in other organs. The parents of the proband were not close relatives and had normal hearing. Two novel heterozygous mutations were found in the OTOGL gene. The c.5038del (p.D1680Ifs*6) variant was inherited from the father, and the c.2770C > T (p.R924X) variant from the mother. They enriched the mutation spectrum of OTOGL, which provides the basis for gene function research and genetic consultation.

A novel MYH9 mutation related to non-syndromic delayed post-lingual sensorineural hearing loss.

OBJECTIVE: Hearing loss (HL) is the most common sensory organ dysfunction disease. The cause is often complex, though genetics are the main factor. METHODS: In this study, we investigated a Chinese family with non-syndromic delayed post-lingual deafness. Comprehensive data collection was performed on this family's members, including basic information, audiological examinations, blood system examinations and imaging examinations. A pedigree diagram was drawn and the genetic patterns were analyzed. RESULTS: A new gene mutation, c.314A>T:p.Y105F in the MYH9 exon, was confirmed by next generation sequencing and Sanger sequencing. This mutation co-segregated with the phenotype in the pedigree. Patients in this family present bilateral symmetry and gradual and delayed high-frequency sensorineural hearing loss. The age of onset was approximately 30 years old. Except for hearing loss, no lesions were seen in other organs, especially the blood system. CONCLUSION: The identification and detection of a novel MYH9 mutation may be of great significance to provide the basis for gene function research and genetic consultation.

Perceived Stress Among Chinese Medical Students Engaging in Online Learning in Light of COVID-19.

PURPOSE: After a year of the COVID-19 pandemic, countries have repeatedly imposed strict quarantine regimes as the virus mutates and becomes more contagious. Medical undergraduate education has been disrupted and transformed into prolonged home isolation and online learning. Although studies have reported that the COVID-19 pandemic tends to increase perceived stress (PS) and affect the mental health of medical students, the influencing factors are unclear. Therefore, based on the stress process model, this study will comprehensively evaluate the distribution of stressors of medical students and explore the personal and environmental predictors of PS during the epidemic. PARTICIPANTS AND METHODS: An online survey was conducted among medical students (n=369) from three medical universities in western China who engaged in online learning. A stress process conceptual framework was formed to explore the influencing factors of PS. The survey items contained four sections: (a) the potential stressors derived from academic, psychosocial and health-related demands; coping resources such as (b) online learning environment support and (c) personal resilience, including online learning behavior and individual characteristics; and (d) PS, perception of imbalanced demands and coping resources. RESULTS: The mean PS score was 17.39 (SD=4.58), and over four-fifths (82.3%) of the students had moderate to high levels of stress. The average item scores of academic, psychosocial and health-related stressors were 2.72 (SD=0.55), 2.31 (SD=0.55) and 2.07 (SD=0.50), respectively. Gender, grade, psychosocial stressors, health-related stressors, specific online learning behavior (persistence, attitude and flexibility), and the online learning environment (teaching, social and cognitive presence) were predictors of PS. CONCLUSION: Our results specify that a reduction in psychological and health-related stressor stimulation, specific online learning behavior promotion, and well-established online learning environment support could be considered essential for alleviating the negative impacts of COVID-19 on the psychosocial health of medical undergraduates.

Screening of lipid metabolism biomarkers in patients with coronary heart disease via ultra-performance liquid chromatography-high resolution mass spectrometry.

Coronary heart disease (CHD) has a high mortality worldwide. This study aimed to screen lipid metabolism biomarkers in patients with coronary heart disease via ultra-performance liquid chromatography-high resolution mass spectrometry. Extraction and reconstitution solvents, liquid chromatographic and mass spectrometry conditions were optimized to detect more plasma lipid metabolites. In this study, the chromatographic and mass spectra characteristics of lipid metabolites were summarized. A total of 316 lipid metabolites were annotated via diagnostic fragment ion filtration, nitrogen rule filtration, and neutral loss filtration. Glycerophospholipid metabolism and sphingolipid metabolism were revealed as the main lipid disorders of CHD. This study provides a novel insight for high-throughput detection of lipid metabolites in plasma and provides a further understanding of the occurrence of CHD, which can provide valuable suggestions for the prevention of CHD.

Suppression of delayed rectifier K+ channels by gentamicin induces membrane hyperexcitability through JNK and PKA signaling pathways in vestibular ganglion neurons.

Aminoglycoside antibiotics, such as gentamicin, are known to have vestibulotoxic effects, including ataxia and disequilibrium. To date, however, the underlying cellular and molecular mechanisms are still unclear. In this study, we determined the role of gentamicin in regulating the sustained delayed rectifier K+ current (IDR) and membrane excitability in vestibular ganglion (VG) neurons in mice. Our results showed that the application of gentamicin to VG neurons decreased the IDR in a concentration-dependent manner, while the transient outward A-type K+ current (IA) remained unaffected. The decrease in IDR induced by gentamicin was independent of G-protein activity and led to a hyperpolarizing shift of the inactivation Vhalf. The analysis of phospho-c-Jun N-terminal kinase (p-JNK) revealed that gentamicin significantly stimulated JNK, while p-ERK and p-p38 remained unaffected. Blocking Kv1 channels with α-dendrotoxin or pretreating VG neurons with the JNK inhibitor II abrogated the gentamicin-induced decrease in IDR. Antagonism of JNK signaling attenuated the gentamicin-induced stimulation of PKA activity, whereas PKA inhibition prevented the IDR response induced by gentamicin. Moreover, gentamicin significantly increased the number of action potentials fired in both phasic and tonic firing type neurons; pretreating VG neurons with the JNK inhibitor II and the blockade of the IDR abolished this effect. Taken together, our results demonstrate that gentamicin decreases the IDR through a G-protein-independent but JNK and PKA-mediated signaling pathways. This gentamicin-induced IDR response mediates VG neuronal hyperexcitability and might contribute to its pharmacological vestibular effects.

Stressor-Oriented MUlticomponent Intervention and the WeLl-Being of Patients with Alzheimer's Disease: A Randomized Controlled Trial (SOUL-P).

BACKGROUND: Patients with Alzheimer's disease (AD) experience various stressors that negatively impact well-being. Most studies have, however, small effect size and are limited by the experiences of severe patients. Therefore, we conducted a single-blind, randomized controlled trial, which has included patients at different stages. OBJECTIVE: The stressor-oriented multicomponent program was designed as an intervention for AD patients to enhance well-being. METHODS: Patients were randomly assigned to control or SOUL-P conditions according to disease severity. The SOUL-P group received 15 intensive sessions over 6 months and 6 maintenance sessions over a 6-month follow-up by a multidisciplinary team comprising psychologists, occupational therapists, and community nurses. The control group received a similar number of sessions by community nurses. Stress-related outcomes (primary stressors and well-being outcomes) were obtained from in-person baseline and follow-up interviews conducted at 6- and 12-months post-baseline. A treatment compliance survey was conducted at the intervention endpoint for patients. RESULTS: Of the 863 patients screened, 218 (25.3%) were eligible. At 6 months, compared to controls, SOUL-P patients had improved quality of life (QoL) (p < 0.001; Cohen d = 0.56), depression (p = 0.020; Cohen d = -0.33), neurobehavioral symptoms (p = 0.034; Cohen d = -0.30), perceived stress (p = 0.030; Cohen d = -0.31), and family conflict (p = 0.026; Cohen d = -0.32). QoL, depression, perceived stress, and family conflict were still significantly different at 12 months. Most patients were satisfied with SOUL-P, while caregivers in the SOUL-P group reported overloading tasks. CONCLUSION: SOUL-P may reduce perceived stress and improve psychological outcomes in AD patients. Stressor-based interventions, patient-oriented goals, and a multidisciplinary team are essential features for a successful SOUL-P.

Predictors of Perceived Social Support for Patients with Dementia: A Mixed-Methods Study.

PURPOSE: Perceived social support (PSS) is closely linked to health outcomes in dementia patients. However, its continuous benefits are unclear. This mixed-methods study examined the impact of social support perceptions and differentiation among patients and carers during disease progression. PATIENTS AND METHODS: Persons with dementia (PWDs), family caregivers, and community family physicians were recruited from nine community health centers. Semi-structured interviews conducted with 12 PWDs (7 PWDs in mild dementia and 5 in moderate dementia), 12 family caregivers, and 6 community family physicians and conventional content analysis were used to explore social support perspectives at different dementia stages. A total of 470 PWDs were divided into mild (n=224), moderate (n=190), and severe (n=56) groups. Demographic, physical, and psychological factors related to PSS were examined by the group using multiple regression analysis. The group-based characteristics were entered into three prediction models. RESULTS: In the qualitative study, three themes of social support were identified: two viewpoints refer to social support; different needs and preferences in each stage; non-personalized support services. Quantitatively, the mild group scored lowest in perceived social support, while the severe group scored highest (χ2=64.70, P<0.001). The mild group PSS was predicted by depression (ß=-0.07, P=0.04), cognitive capacity (ß=-0.18, P<0.001), and instrumental ability (ß=-0.78, P<0.001), which differed from the moderate and severe groups. CONCLUSION: This study provided comprehensive insight into PSS from PWDs' perspective at different stages of the disease. Results indicated the need for a stratified care approach and direction for further research on intervention.

Effect of neuregulin-1 on the auditory cortex in adult C57BL/6J mice.

OBJECTIVES: We sought to explore whether neuregulin-1(NRG1) would have a protective effect on the auditory cortices of adult C57BL/6J mice. MATERIALS AND METHODS: We used RTPCR and Western blot (WB) to detect the expression of NRG1 and ERBB4 (the receptor of NRG1) in the auditory cortices of C57BL/6J mice of different ages (6-8 weeks and 42-44 weeks). Three groups of 42-44 week-old C57BL/6J mice were intraperitoneally injected with mouse neurotrophic factor (m-NGF), NRG1, or saline for two months. We observed the ultrastructures of the auditory cortices of adult mice after treatment using transmission electron microscopy. Additionally, we observed expression of NRG1 in the auditory cortices by immunohistochemistry. RESULTS: Expression of NRG1 and ERBB4 in the auditory cortices of C57BL/6J mice at the age of 42-44 weeks was lower compared with 6-8 week-old mice. The ultra-structures of the auditory cortices, including the neurons and myelin sheaths, as revealed by transmission electron microscopy were healthier in the m-NGF and NRG1 treatment groups than those in the saline group. We found that expression of NRG1 in the auditory cortices after treatment in the m-NGF and NRG1 groups, especially in the NRG1 group, was higher than that in the saline group. CONCLUSION: We concluded that with increasing age, NRG1 in the auditory cortices of C57BL/6J mice gradually decreased, and that NRG1 had a protective effect on the auditory cortices in adult C57BL/J mice.