Trends in the prevalence of social isolation among middle and older adults in China from 2011 to 2018: the China Health and Retirement Longitudinal Study.

BACKGROUND: Epidemiological studies have shown that social isolation, which is prevalent in older adults, is associated with a range of adverse health outcomes, but the prevalence of and trends in regard to social isolation remain ambiguous in China. The aim of this study was to elucidate the trends regarding the prevalence of social isolation among middle-aged and older adults in China from 2011 to 2018 and to further identify associated risk factors. METHODS: A repeated cross-sectional study, The data were derived from panel sample data of four waves conducted from May 2011 to August 2018 in the nationally representative China Health and Retirement Longitudinal Study (CHARLS) using multistage probability sampling. Social isolation was ascertained by the five item Steptoe Social Isolation Index. The potential covariates were demographic characteristics, lifestyle factors, and health status. Linear-by-linear association was used to assess the trends in regard to social isolation over time under the influence of the potential covariates. Linear-by-linear association and an age-period-cohort analysis were used to explore the trends, and two-level (time, individual) generalized estimating equation models (GEE) linked multivariate binary logistic regression were performed to identify risk factors. RESULTS: A high prevalence of social isolation and a moderate upward trend from 2013 to 2018 were observed among a U-shaped trend prevalence of social isolation from 2011 to 2018 across China, with rates of 38.09% (95% CI = 36.73-39.45) in 2011, 33.66% (32.32-35.00) in 2013, 39.13% (37.59-40.67) in 2015, and 39.95% (38.59-41.31) in 2018 (p < 0.001). The prevalence of social isolation increased with age and educational attainment. Females had a higher prevalence than males. The prevalence of social isolation was found to be significantly lower in pensioners than in non-pensioners between 2011 and 2018 (p < 0.001). The prevalence of social isolation was 38.9%, 34.9%, 38.5%, and 44.08% about three times higher among those who doid not use the Internet and 13.44%, 11.64%, 12.93%, and 16.73% than among those who doid in 2011, 2013, 2015 and 2018 respectively. The participants with short (0-5 h) and long sleep (9 or more hours), and poor self-rated health had a higher prevalence of social isolation than the others. Older age, lower educational attainment, living in a rural region, lack of medical insurance or pension, lack of internet use and poor health were risk factors (p < 0.05). CONCLUSIONS: We found a U-shaped prevalence of social isolation trends from 2011 to 2018 and revealed increasing trends from 2013 to 2018 among middle-aged and older adults in China. The findings of the study highlight the urgent need for interventions to reduce social isolation including improving sleep quality and internet skills. Disadvantaged groups in terms of age, economic status, and health status should be the focus of such interventions, especially in the era of COVID-19.

Clinical phenotypes and prognoses of microscopic polyangiitis based on kidney biopsies.

BACKGROUND: To classify the different clinical phenotypes and compare the distinct prognoses of microscopic polyangiitis (MPA). METHODS: A retrospective analysis of 436 patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) from 2015 to 2022 was conducted in our center, of which 90 patients were diagnosed with MPA and underwent renal biopsy. RESULTS: Among the 90 MPA patients, 63% were female, and the median age at onset was 63 years (25th-75th percentile: 58-68). The median follow-up time was 26 months (25th-75th percentile: 10-53). We identified four subtypes: renal impairment type (cluster 1, 39%), pure type (cluster 2, 22%), systemic inflammation type (cluster 3, 26%), and rapid progress type (cluster 4, 13%). Cluster 1, characterized by renal dysfunction at onset (80%), demonstrated poor prognoses with only 26% achieved complete remission (CR), 11% dying, and 19% developing renal failure. In contrast, patients in cluster 2, exclusively female, most had only kidney involvement showed the best prognoses with 55% achieving CR and none experiencing death or renal failure within 10 years. Cluster 3 mostly consisted of males; high fever and C-reactive protein levels were the primary characteristics. These cases exhibited moderate prognoses with 53% achieving CR, 9% dying, and 4% developing renal failure. Finally, patients in cluster 4, which was characterized by rapidly progressive glomerulonephritis, had the worst prognoses, with none achieving CR, 8% dying, and 75% developing renal failure despite aggressive treatment. CONCLUSIONS: MPA is classified into four subtypes with distinct clinical manifestations and prognoses.

Creatine chemical exchange saturation transfer (CEST) CMR imaging reveals myocardial early involvement in idiopathic inflammatory myopathy at 3T: feasibility and initial experience.

OBJECTIVES: To measure creatine distribution in idiopathic inflammatory myopathy (IIM) patients' myocardial segments and investigate whether cardiovascular magnetic resonance (CMR) chemical exchange saturation transfer (CEST) creatine mapping can detect subclinical myocardial changes, CEST's ability was further compared with other conventional CMR mapping sequences. METHODS: Forty IIM patients (53.5 ± 10.5 years, 26 males) and eight healthy controls (35.4 ± 6 years, 5 males) underwent CMR scans on a 3.0-T MR scanner. Patients with IIM were further classified into two subgroups according to cardiac troponin T (cTn-T) values: the elevated cTn-T subgroup (n = 14) and the normal cTn-T subgroup (n = 26). Cine imaging, T2 SPAIR, LGE imaging, T1 mapping, T2 mapping, and Cr (creatine) CEST were performed. RESULTS: Cr mapping showed significantly reduced creatine in IIM patients among global myocardium (IIM: 0.109 ± 0.063, controls: 0.121 ± 0.021, p < 0.05), and decreased creatine signals were detected in all 16 cardiac segments (p < 0.05). Patients also had significantly prolonged native T1 and decreased enhanced T1 values in each cardiac segment (p < 0.05). There was no significant difference of LVEF and T2 values between IIM patients and controls. Between the two subgroups, elevated cTn-T was linked with creatine and extracellular volume fraction (ECV) values, providing a global average creatine signal of 0.107 vs 0.112 (p < 0.05) and 24.7 vs 32.4 (p < 0.05). CONCLUSION: Creatine CEST mapping can detect early-stage heart involvement with negative LGE findings in IIM. Compared with T1 mapping, CEST provides increased sensitivity to ECV measurement, making it significantly better than T1, and a promising CMR sequence for screening subclinical myocardial damage. KEY POINTS: • IIM patients with potential or ongoing heart involvement, elevated ECV, and reduced Cr CEST values could provide valuable information. • ECV and Cr CEST values were closely related to elevated cTn-T.

Effect of living arrangements on cognitive function in Chinese elders: a longitudinal observational study.

OBJECTIVE: To examine how living arrangement as a social contextual factor can affect Chinese elders' cognitive function. SETTING AND PARTICIPANTS: Our sample consists of 2486 Chinese elders from two waves (2014 and 2018) of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) that was administered in 22 of China's 31 provinces using a multi-stage, disproportionate, purposive random sampling method. The CLHLS aims to better understand the determinants of healthy longevity in China and collects extensive data on a large population of fragile elders aged 80-112 in China. OUTCOME MEASURES: Cognitive function was measured by the Mini-Mental State Examination (MMSE). Living arrangement was divided into living in an institution, living alone and living with household members. Generalised linear regressions were carried out to examine the associations between baseline characteristics and cognitive function, while controlling age, gender and residential area. RESULTS: A total of 2486 participants were included in the study at baseline in 2014. Of these, 1162 (46.7%) were men and 1324 (53.3%) were women. The mean age at baseline was 75.07 (±8.31) years. The mean years of schooling were 2.86 (±3.68). The number (proportion) of the three living arrangements (lived in institutions, lived alone and lived with household members) were 93 (3.8%), 463 (18.6%) and 1930 (77.6%), respectively. Among all participants, cognitive function declined over time. Those who lived alone presented with the highest MMSE scores at baseline and showed the lowest decline after 4 years. Living arrangements had significant effects on decreasing cognitive function. CONCLUSION: Chinese elders living in institutions were most vulnerable to cognitive decline. Living alone was not a risk condition in itself for the elderly in terms of cognitive decline. In addition, the benefits of living with household members to support cognitive function were not found in our study.

The Potential Win-win Strategy for Healthy Aging and Environmental Protection: Environmental Volunteering.

PURPOSE: To explore the physical activity level of community environmental volunteering (CEV) participants and the differences in physical functions and daily activity patterns between the older adults who engaged in intensive CEV (≥15 hours/week) and non-intensive CEV (<15 hours/week) groups. DESIGN: Cross-sectional study. SETTING: Three recycling stations in Taiwan. SAMPLE: In total, 113 community-dwelling older adults who regularly participated in CEV. The response rate was 53%. MEASURES: The ActiGraph wGT3x-BT accelerometer for the percentage of sedentary, light, and moderate to vigorous physical activity (MVPA) of CEV time and awaken time; the Jamar hand dynamometer for grip strength; and the MicroFET3 muscle testing dynamometer for knee extension strength. ANALYSIS: Analysis of covariance with the baseline characteristics as covariates. RESULTS: Overall, MVPA, light, and sedentary activities accounted for 53.73%, 41.10%, and 5.23% of CEV time, respectively. The intensive group (n = 61) displayed greater dominant handgrip strength (P = .004) and higher MVPA percentage in daily life (P = .044) than the non-intensive group (n = 52). CONCLUSION: CEV provides sufficient opportunities for older adults to perform physical activity. Intensive CEV is related to greater handgrip strength but not lower limb strength. Further study is needed to establish the causal relationship between CEV and health variates.

Association of Cytomegalovirus Infection With Anti-MDA5 Antibody-Positive Dermatomyositis: A Prospective Cohort Study.

Objectives: To investigate whether cytomegalovirus (CMV) infection plays a role in the pathogenesis and prognosis of idiopathic inflammatory myopathy (IIM), particularly in anti-MDA5 antibody-positive (anti-MDA5+) dermatomyositis (DM). Methods: A prospective cohort of 204 newly diagnosed IIM patients and 50 healthy individuals were enrolled in the study. CMV-IgM and CMV-IgG antibody concentrations and lymphocyte counts were analyzed. Differences in categorical data were compared using Fisher's exact test and the chi-square test. One-year survival rates were analyzed in MDA5+ DM patients with and without CMV infection. Results: In IIM patients, the median CMV-IgM level was significantly higher than in healthy controls (6 U/mL vs. 0 U/mL, p < 0.05) as was the median CMV-IgG level (114 U/mL vs. 105 U/mL, p < 0.05). The percentage of recent CMV infections in the MDA5+ DM group was much higher than it was in the MDA5- IIM group (19.1% vs. 7.0%, p = 0.009). MDA5+ DM patients with CMV DNA-emia had poorer 1 year survival than the CMV-DNA- group (33.3% vs. 86.3%, p = 0.010). CMV-IgM-positive (CMV-IgM+) MDA5+ DM patients had lower CD4+ T cell counts (245.7 cells/µL vs. 420.5 cells/µL, p < 0.05) and CD19+ B cell counts (97.3 cells/µL vs. 240.6 cells/µL, p < 0.05). Conclusion: The number of CMV infections was significantly higher in IIM patients, particularly in MDA5+ DM patients. Lower CD4+ T cells and CD19+ B cells were observed in CMV-IgM+ MDA5+ DM patients. CMV infection may have an important role in the pathogenesis and prognosis of MDA5+ DM by disrupting immunity.

High incidence and mortality of Pneumocystis jirovecii infection in anti-MDA5-antibody-positive dermatomyositis: experience from a single center.

BACKGROUND: Idiopathic inflammatory myopathies (IIM) are associated with a significantly higher risk of opportunistic infections including Pneumocystis jirovecii pneumonia (PJP), a potentially fatal opportunistic infection. However, no prior studies have evaluated PJP infection in subtypes of IIM. OBJECTIVES: To investigate the prevalence and mortality rate of PJP infection in subgroups of IIM patients stratified according to myopathy-specific antibodies. METHODS: In the first part of the study, 463 consecutive patients with IIM were prospectively followed for a period of at least 1 year to analyze the incidence of PJP. In the second part of the study, we enrolled 30 consecutive PJP patients with any rheumatic disease in order to identify the mortality rate and risk factors by Cox regression analysis. The Kaplan-Meier method with log-rank testing was used to assess differences in survival. RESULTS: The prevalence of PJP in IIM patients was found to be 3.0/100 person-years, while in MDA5+ DM patients it was 7.5/100 person-years and in MDA5- IIM patients 0.7/100 person-years (P < 0.05). PJP typically occurred in the first 2 months in the case of MDA5+ DM patients who had a significant decrease in their CD4+ T cell counts and lymphocyte counts (P < 0.05). In PJP patients, 3-month mortality was higher for MDA5+ DM patients than in those with other rheumatic diseases (83.3% vs 38.9%, P < 0.05). Alarmingly, MDA5+ DM patients seemed not to benefit from prompt anti-PJP treatment, unlike patients with other rheumatic diseases whose survival improved when anti-PJP treatment was started within 6 days (P < 0.05). CONCLUSION: PJP has an alarming high incidence and mortality in MDA5+ DM patients. Timely treatment for PJP seems not to improve the prognosis of patients with this particular subtype. Hence, there remains a crucial unmet need to develop PJP prophylaxis for MDA5+ DM patients.

Do Migration Characteristics Influence the Utilization of Basic Public Health Services in Internal Elderly Migrants in China?

Background: The literature shows that migration characteristics are a potential pathway through which migration can influence basic healthcare service utilization. The goal of the study was to explore the effect of migration characteristics on the utilization of basic public health services for internal elderly migrants in China and to identify the pathways that might promote their utilization of basic public health services. Methods: We studied 1,544 internal elderly migrants. The utilization of basic public health services was determined through participation in free health checkups organized by community health service institutions in the past year. Migration characteristics were represented by years of residence and reasons for migration. Other variables included demographic characteristics and social factors, e.g., the number of local friends and exercise time per day were measured to represent social contacts. Multivariate binary logistic regression was employed to explore the association of the variables with the likelihood of using community health services. Results: A total of 55.6% of respondents were men, and the mean age was 66.34 years (SD 5.94). A low level of education was observed. A total of 59.9% of migrants had been residents for over 10 years, and the main reason for migrating was related to family. Of these migrants, 12.9% had no local friends. Furthermore, 5.2% did not exercise every day. Social contacts were complete mediators of the impact of migration characteristics on the utilization of primary healthcare. Conclusion: Our study highlighted the mediating role of social factors in the relationship between migration characteristics and the utilization of basic public health services among Chinese internal elderly migrants. The findings supported the need to increase the opportunities for social contacts between local elderly individuals and internal elderly migrants.

Functional variant rs17525453 within RAB35 gene promoter is possibly associated with increased risk of Parkinson's disease in Taiwanese population.

Our previous study suggests that upregulated RAB35 is implicated in etiology of Parkinson's disease (PD). We hypothesized that upregulated RAB35 results from single nucleotide polymorphisms (SNPs) in RAB35 gene promoter. We identified SNPs within RAB35 gene promoter by analyzing DNA samples of discovery cohort and validation cohort. SNP rs17525453 within RAB35 gene promoter (T>C at position of -66) was significantly associated with idiopathic PD patients. Compared to normal controls, sporadic PD patients had higher C allele frequency. CC and CT genotype significantly increased risk of PD compared with TT genotype. SNP rs17525453 within RAB35 gene promoter leads to formation of transcription factor TFII-I binding site. Results of EMSA and supershift assay indicated that TFII-I binds to rs17525453 sequence of RAB35 gene promoter. Luciferase reporter assays showed that rs17525453 variant of RAB35 gene promoter possesses an augmented transcriptional activity. Our results suggest that functional variant rs17525453 within RAB35 gene promoter is likely to enhance transcriptional activity and upregulate RAB35 protein, which could lead to increased risk of PD in Taiwanese population.

Efficacy and safety of a selective URAT1 inhibitor SHR4640 in Chinese subjects with hyperuricaemia: a randomized controlled phase II study.

OBJECTIVE: To evaluate the efficacy and safety of SHR4640, a highly selective urate transporter 1 inhibitor, in Chinese subjects with hyperuricaemia. METHODS: This was a randomized double-blind dose-ranging phase II study. Subjects whose serum uric acid (sUA) levels were ≥480 µmol/l with gout, ≥480 µmol/l without gout but with comorbidities, or ≥540 µmol/l were enrolled. Subjects were randomly assigned (1:1:1:1:1) to receive once daily 2.5 mg, 5 mg, 10 mg of SHR4640, 50 mg of benzbromarone or placebo, respectively. The primary end point was the proportion of subjects who achieved target sUA level of ≤360 µmol/l at week 5. RESULTS: 99.5% of subjects (n = 197) were male and 95.9% of subjects had gout history. The proportions of subjects who achieved target sUA at week 5 were 32.5%, 72.5% and 61.5% in the 5 mg, 10 mg SHR4640 and benzbromarone groups, respectively, significantly higher than the placebo group (0%; P < 0.05 for 5 mg and 10 mg SHR4640 group). The sUA was reduced by 32.7%, 46.8% and 41.8% at week 5 with 5 mg, 10 mg SHR4640 and benzbromarone, respectively, vs placebo (5.9%; P < 0.001 for each comparison). The incidences of gout flares requiring intervention were similar among all groups. Occurrences of treatment-emergent adverse events (TEAEs) were comparable across all groups, and serious TEAEs were not reported. CONCLUSIONS: The present study indicated a superior sUA-lowering effect and well tolerated safety profile after 5-week treatment with once-daily 5 mg/10 mg of SHR4640 as compared with placebo in Chinese subjects with hyperuricaemia. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03185793.

Severe invasive Listeria monocytogenes rhombencephalitis mimicking facial neuritis in a healthy middle-aged man: a case report and literature review.

Neurolisteriosis is a foodborne infection of the central nervous system that is easily misdiagnosed, especially in healthy adults with atypical symptoms. A 50-year-old man presented with a 3-day history of distortion of the oral commissure. Facial neuritis was diagnosed and treated with intravenous dexamethasone. His condition deteriorated rapidly, and he presented with a slow pharyngeal reflex, stiff neck, and signs of peripheral facial paralysis. Brain magnetic resonance imaging revealed multiple ring-enhanced foci in the brainstem. Routine and biochemical cerebrospinal fluid (CSF) analyses showed increased white blood cells and microproteins. Blood culture and high-throughput genome sequencing revealed Listeria monocytogenes DNA in the CSF. Ampicillin, amikacin, and meropenem were administered, and the patient was transferred from the intensive care unit to a standard medical ward after 2 months. The patient could walk and eat normally; however, he required intermittent mechanical ventilation at 11 months after discharge. Although L. monocytogenes meningitis is rare in healthy immunocompetent adults, it must be considered as a differential diagnosis, especially in adults whose conditions do not improve with cephalosporin antibiotic administration. L. monocytogenes rhombencephalitis mimics facial neuritis and develops quickly. Prompt diagnosis is essential for rapid initiation of antibiotic therapy to achieve the best outcome.

(D620N) VPS35 causes the impairment of Wnt/ß-catenin signaling cascade and mitochondrial dysfunction in a PARK17 knockin mouse model.

Patients with familial type 17 of Parkinson's disease (PARK17) manifest autosomal dominant pattern and late-onset parkinsonian syndromes. Heterozygous (D620N) mutation of vacuolar protein sorting 35 (VPS35) is genetic cause of PARK17. We prepared heterozygous VPS35D620N/+ knockin mouse, which is an ideal animal model of (D620N) VPS35-induced autosomal dominant PARK17. Late-onset loss of substantia nigra pars compacta (SNpc) dopaminergic (DAergic) neurons and motor deficits of Parkinson's disease were found in 16-month-old VPS35D620N/+ mice. Normal function of VPS35-containing retromer is needed for activity of Wnt/ß-catenin cascade, which participates in protection and survival of SNpc DAergic neurons. It was hypothesized that (D620N) VPS35 mutation causes the malfunction of VPS35 and resulting impaired activity of Wnt/ß-catenin pathway. Protein levels of Wnt1 and nuclear ß-catenin were reduced in SN of 16-month-old VPS35D620N/+ knockin mice. Downregulated protein expression of survivin, which is a target gene of nuclear ß-catenin, and upregulated protein levels of active caspase-8 and active caspase-9 were observed in SN of VPS35D620N/+ mice at age of 16 months. VPS35 is involved in controlling morphology and function of mitochondria. Impaired function of VPS35 caused by (D620N) mutation could lead to abnormal morphology and malfunction of mitochondria. A significant decrease in mitochondrial size and resulting mitochondrial fragmentation was found in tyrosine hydroxylase-positive and neuromelanin-positive SNpc DAergic neurons of 16-month-old VPS35D620N/+ mice. Mitochondrial complex I activity or complex IV activity was reduced in SN of 16-month-old VPS35D620N/+ mice. Increased level of mitochondrial ROS and oxidative stress were found in SN of 16-month-old VPS35D620N/+ mice. Levels of cytosolic cytochrome c and active caspase-3 were increased in SN of VPS35D620N/+ mice aged 16 months. Our results suggest that PARK17 mutant (D620N) VPS35 impairs activity of Wnt/ß-catenin signaling pathway and causes abnormal morphology and dysfunction of mitochondria, which could lead to neurodegeneration of SNpc DAergic cells.

Comparing the reliability and validity of the SF-36 and SF-12 in measuring quality of life among adolescents in China: a large sample cross-sectional study.

OBJECTIVE: We compare the reliability and validity of the Short Form 36 (version 1, SF-36) and the Short Form 12 (version 1, SF-12) in adolescence, the period of life when a child develops into an adult, i.e., the period from puberty to maturity terminating legally at the age of majority (10-19 years), thus supplying evidence for the selection of instruments measuring the quality of life (QOL) and decision-making processes of adolescents in China. METHODS: Stratified cluster random sampling was adopted according to geographical location, and the SF-36 was administered to assess QOL. The Pearson correlation coefficient was used to show correlation. Cronbach's alpha and construct reliability (CR) were used to evaluate the reliability of SF-36 and SF-12, while criterion validity and average variance extracted (AVE, convergence validity) were used to evaluate validity. Confirmatory factor analysis was used to calculate the load factors for the items of the SF-36 and SF-12, then to obtain the CR and AVE. The Semejima grade response model (logistic two-parameter module) in item response theory was used to estimate item discrimination, item difficulty, and item average information for the items of the SF-36 and SF-12. RESULTS: 19,428 samples were included in the study. The mean age of respondents was 14.78 years (SD = 1.77). Reliability of each domain of the SF-36 was better than for the corresponding domain of the SF-12. The domains of PF, RP, BP, and GH in SF-36 had good construct reliability (CR > 0.6). The criterion validities of some domains of the SF-36 were a little higher in some corresponding dimensions of the SF-12, except for PCS. The convergence validities of the SF-12 were higher than the SF-36 in PF, RP, BP, and PCS. The items of BP, SF, RP, and VT in the SF-12 had acceptable discrimination of items that were higher than in the SF-36. The items' average amounts of information on BP, VT, SF, RE, and MH in the SF-36 and SF-12 were poor. CONCLUSION: Two component (PCS and MCS) measurements of the SF-12 appeared to perform at least as well as the SF-36 in cross-sectional settings in adolescence, but the reliability and validity of the 8 domains of the SF-36 were better than those of the SF-12. Some domains, for instance SF and BP, were not suitable for adolescents or need to be studied further.

Factors influencing utilization of primary health care by elderly internal migrants in China: the role of social contacts.

BACKGROUND: Utilization of primary health care is an important aspect of elderly internal migrants' access to screening and preventive services in China. It has been evident that social contacts, such as community engagement, social mobilization, and the ability to communicate were related to health service delivery, but little has been done to explore the relationship between social contacts and utilization of primary health care for this group. This study aimed to explore the factors influencing utilization of primary health care from the perspective of social contacts among elderly internal migrants in China. METHODS: This was a cross-sectional study including 1544 elderly internal migrants in eight cities. Whether these indivdiuals had chosen to participate in the free health checkup organized in the previous year was adopted as an indicator of the utilization of primary health care. The number of local friends and amount of exercise time per day were measured as a proxy for social contacts. Multivariate binary logistic regression was used to investigate the association of social contacts with the likelihood of using primary health care. RESULTS: 55.6% of the respondents were men, and the mean age was 66.34 years (SD, 5.94). 88.6% had received an education of high school or below. 12.9% had no local friends. 5.2% did not exercise. Just 33.1% had participated in a free medical check-up. Social contacts, age, and medical insurance were associated with more use of primary health care among elderly internal migrants in China. CONCLUSION: The role of the community in promoting the use of primary health care should be expanded, such as creating community-based campaigns specifically targeting elderly internal migrants or designing social or sports activities tailored to increase the opportunity for contact between local elders and their internal migrant peers.

Alda-1, an activator of ALDH2, ameliorates Achilles tendinopathy in cellular and mouse models.

Achilles tendinopathy has a high re-injury rate and poor prognosis. Development of effective therapy for Achilles tendinopathy is important. Excessive accumulation of ROS and resulting oxidative stress are believed to cause tendinopathy. Overproduction of hydrogen peroxide (H2O2), the most common ROS, could lead to the tendinopathy by causing oxidative damage, activation of endoplasmic reticulum (ER) stress and apoptotic death of tenocytes. Activation of mitochondrial aldehyde dehydrogenase 2 (ALDH2) is expected to alleviate oxidative stress and ER stress. Alda-1 is a selective and potent activator of ALDH2. In this study, we examined the cytoprotective benefit of Alda-1, an activator of ALDH2, on H2O2-induced Achilles tendinopathy in cellular and mouse models. We prepared cellular and mouse models of Achilles tendinopathy by treating cultured Achilles tenocytes and Achilles tendons with oxidative stressor H2O2. Subsequently, we studied the protective benefit of Alda-1 on H2O2-induced Achilles tendinopathy. Alda-1 pretreatment attenuated H2O2-induced cell death of cultured Achilles tenocytes. Treatment of Alda-1 prevented H2O2-induced oxidative stress and depolarization of mitochondrial membrane potential in tenocytes. Application of Alda-1 attenuated H2O2-triggered mitochondria- and ER stress-mediated apoptotic cascades in cultured tenocytes. Alda-1 treatment ameliorated the severity of H2O2-induced Achilles tendinopathy in vivo by preventing H2O2-induced pathological histological features of Achilles tendons, apoptotic death of Achilles tenocytes and upregulated expression of inflammatory cytokines IL-1ß and TNF-α. Our results provide the evidence that ALDH2 activator Alda-1 ameliorates H2O2-induced Achilles tendinopathy. Alda-1 could be used for preventing and treating Achilles tendinopathy.

Upregulated Expression of MicroRNA-204-5p Leads to the Death of Dopaminergic Cells by Targeting DYRK1A-Mediated Apoptotic Signaling Cascade.

MicroRNAs (miRs) downregulate or upregulate the mRNA level by binding to the 3'-untranslated region (3'UTR) of target gene. Dysregulated miR levels can be used as biomarkers of Parkinson's disease (PD) and could participate in the etiology of PD. In the present study, 45 brain-enriched miRs were evaluated in serum samples from 50 normal subjects and 50 sporadic PD patients. The level of miR-204-5p was upregulated in serum samples from PD patients. An upregulated level of miR-204-5p was also observed in the serum and substantia nigra (SN) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Expression of miR-204-5p increased the level of α-synuclein (α-Syn), phosphorylated (phospho)-α-Syn, tau, or phospho-tau protein and resulted in the activation of endoplasmic reticulum (ER) stress in SH-SY5Y dopaminergic cells. Expression of miR-204-5p caused autophagy impairment and activation of c-Jun N-terminal kinase (JNK)-mediated apoptotic cascade in SH-SY5Y dopaminergic cells. Our study using the bioinformatic method and dual-luciferase reporter analysis suggests that miR-204-5p positively regulates mRNA expression of dual-specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) by directly interacting with 3'UTR of DYRK1A. The mRNA and protein levels of DYRK1A were increased in SH-SY5Y dopaminergic cells expressing miR-204-5p and SN of MPTP-induced PD mouse model. Knockdown of DYRK1A expression or treatment of the DYRK1A inhibitor harmine attenuated miR-204-5p-induced increase in protein expression of phospho-α-Syn or phospho-tau, ER stress, autophagy impairment, and activation of JNK-mediated apoptotic pathway in SH-SY5Y dopaminergic cells or primary cultured dopaminergic neurons. Our results suggest that upregulated expression of miR-204-5p leads to the death of dopaminergic cells by targeting DYRK1A-mediated ER stress and apoptotic signaling cascade.

Impact of acculturation and psychological adjustment on mental health among migrant adolescents in Guangzhou, China: a cross-sectional questionnaire study.

OBJECTIVES: The aim of this study was to examine the pathway and associations among acculturation (ie, language, social interaction and lifestyle), psychological adjustment and mental health of internal migrant adolescents in China. DESIGN: Cross-sectional questionnaire study. SETTING: Six private migrant junior high schools located in Tianhe and Baiyun districts in Guangzhou were chosen as the study sites. PARTICIPANTS: A total of 1122 migrant adolescents aged 11-17 years old completed the study. MAIN OUTCOME MEASURES: Mental health was measured by using the Social Anxiety Scale for Children (SASC) and major depression disorder (MDD) in a Brief Child and Family Phone Interview. Acculturation and psychological adjustment were measured by a self-designed and verified questionnaire. Multiple regression models and structural equation models were performed to analyse the association among acculturation, psychological adjustment and mental health while controlling for participant demographic characteristics. RESULTS: The average MDD score for boys was 8.78 (SD=2.17) and for girls was 8.56 (SD=2.22), while the average SASC score for boys was 14.67 (SD=3.72) and for girls was 13.41 (SD=4.01). Psychological adjustment had a direct positive effect on MDD (p<0.001, ß=0.30) and SASC (p<0.001, ß=0.28), and it was the key variable fully mediating the impact of acculturation components on MDD and partly mediating the impact of acculturation on SASC, whereas lifestyle showed a direct negative effect (p=0.003, ß=-0.17) on SASC. Of the three acculturation components, lifestyle had the strongest influence on psychological adjustment (p<0.001, ß=0.37 and 0.51), followed by social interaction (p<0.001, ß=0.24 and 0.13) and language (p<0.001, ß=0.17 and 0.11). CONCLUSIONS: The association between acculturation and the mental health of internal migrant adolescents was complex and could be mediated by psychological adjustment. Interventions such as promoting local language and social interaction are needed to enhance psychological adjustment and further improve the mental health of migrant adolescents.

Multiparameter diffusion-weighted imaging for characterizing pathological patterns in lupus nephritis patients: A preliminary study.

BACKGROUND: Microstructural changes of lupus nephritis (LN) kidney such as inflammatory cell infiltration or fibrosis could influence water molecular movement or diffusion, which indicates that diffusion-weighted imaging (DWI) may become a valuable tool in evaluation of this disease. PURPOSE: To explore whether multiparameter diffusion-weighted imaging (mDWI) could contribute to characterize pathological patterns in LN patients. STUDY TYPE: Retrospective. POPULATION: Twenty-two patients with LN. FIELD STRENGTH/SEQUENCE: Multi-b value DWI was performed with a 3.0 T scanner. ASSESSMENT: Apparent diffusion coefficient (ADC)m , perfusion-related diffusion coefficient (Df ), molecular diffusion coefficient (Ds ), perfusion fraction (f), ADCs , α, ADCk , and mean kurtosis (MK) were calculated by monoexponential, biexponential, stretched-exponential, and kurtosis models fits, respectively. STATISTICAL TESTS: Independent sample t-test, Pearson analysis and receiver operating characteristic (ROC). RESULTS: In the whole group, the activity index (AI) correlated significantly with alpha values in the medulla (rho = -0.54, P = 0.03). The chronicity index (CI) correlated significantly with Ds values in the medulla (rho = -0.61, P = 0.02). No significant association was found between any other diffusion parameter and histologic grade with all P > 0.05. For differentiating proliferative LN (Class III or IV) from Class V, the area under the ROC curve (AUC) of alpha in the medulla was 0.833 (P = 0.023). DATA CONCLUSION: mDWI might be used for the characterization of pathological patterns in LN patients. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:1075-1084.

PARK14 (D331Y) PLA2G6 Causes Early-Onset Degeneration of Substantia Nigra Dopaminergic Neurons by Inducing Mitochondrial Dysfunction, ER Stress, Mitophagy Impairment and Transcriptional Dysregulation in a Knockin Mouse Model.

PARK14 patients with homozygous (D331Y) PLA2G6 mutation display motor deficits of pure early-onset Parkinson's disease (PD). The aim of this study is to investigate the pathogenic mechanism of mutant (D331Y) PLA2G6-induced PD. We generated knockin (KI) mouse model of PARK14 harboring homozygous (D331Y) PLA2G6 mutation. Then, we investigated neuropathological and neurological phenotypes of PLA2G6D331Y/D331Y KI mice and molecular pathogenic mechanisms of (D331Y) PLA2G6-induced degeneration of substantia nigra (SN) dopaminergic neurons. Six-or nine-month-old PLA2G6D331Y/D331Y KI mice displayed early-onset cell death of SNpc dopaminergic neurons. Lewy body pathology was found in the SN of PLA2G6D331Y/D331Y mice. Six-or nine-month-old PLA2G6D331Y/D331Y KI mice exhibited early-onset parkinsonism phenotypes. Disrupted cristae of mitochondria were found in SNpc dopaminergic neurons of PLA2G6D331Y/D331Y mice. PLA2G6D331Y/D331Y mice displayed mitochondrial dysfunction and upregulated ROS production, which may lead to activation of apoptotic cascade. Upregulated protein levels of Grp78, IRE1, PERK, and CHOP, which are involved in activation of ER stress, were found in the SN of PLA2G6D331Y/D331Y mice. Protein expression of mitophagic proteins, including parkin and BNIP3, was downregulated in the SN of PLA2G6D331Y/D331Y mice, suggesting that (D331Y) PLA2G6 mutation causes mitophagy dysfunction. In the SN of PLA2G6D331Y/D331Y mice, mRNA levels of eight genes that are involved in neuroprotection/neurogenesis were decreased, while mRNA levels of two genes that promote apoptotic death were increased. Our results suggest that PARK14 (D331Y) PLA2G6 mutation causes degeneration of SNpc dopaminergic neurons by causing mitochondrial dysfunction, elevated ER stress, mitophagy impairment, and transcriptional abnormality.