Associations between cooking fuel use, its transitions, and worsening sensory impairments among Chinese middle-aged and older adults: a cohort study.

BACKGROUND: This study aimed to explore the associations between household air pollution (HAP), measured by cooking fuel use, sensory impairments (SI), and their transitions in Chinese middle-aged and older adults. METHODS: Participants were recruited from the 2011 China Health and Retirement Longitudinal Study (CHARLS) and were subsequently followed up until 2018. Data on SI were collected by self-reported hearing and vision impairments, which were divided into three categories: non-SI, single SI (hearing or vision impairment), and dual SI (DSI). Cooking fuels, including solid and clean fuels, are proxies for HAP. The transitions of cooking fuels and SI refer to the switching of the fuel type or SI status from baseline to follow-up. Cox proportional hazard regression models were used to explore associations, and hazard ratios (HRs) and 95% confidence intervals (CI) were used to evaluate the strength of the association. RESULTS: The prevalence of non-SI, single SI, and DSI was 59.6%, 31.8%, and 8.6%, respectively, among the 15,643 participants at baseline in this study. Over a median follow-up of 7.0 years, 5,223 worsening SI transitions were observed. In the fully adjusted model, solid fuel use for cooking was associated with a higher risk of worsening SI transitions, including from non-SI to single SI (HR = 1.08, 95% CI = 1.01-1.16) and from non-SI to DSI (HR = 1.26, 95% CI = 1.09-1.47), but not from single SI to DSI. In addition, compared to those who always used solid fuels, participants who switched from solid to clean fuel for cooking appeared to have attenuated the risk of worsening SI transitions. The statistical significance of the associations remained in the set of sensitivity analyses. CONCLUSION: Solid fuel use was associated with higher risks of worsening SI transitions, while converting the type of cooking fuel from solid to clean fuels may reduce the risk of worsening SI transitions. Our study suggests that tailored clean fuel interventions, especially in developing countries, should be implemented to prevent sensory impairments and hence reduce the burden of sensory impairment-related disability.

Effects of retirement on inpatient healthcare utilisation: an observational study in China.

OBJECTIVE: Previous studies have presented mixed evidence on retirement and inpatient healthcare utilisation. We aimed to examine the causal effect of retirement on inpatient healthcare utilisation in China and explore the heterogenous effects of sex, disease types and ways of hospital admission. DESIGN: This was a retrospective observational study from the electronic medical record at 376 tertiary hospitals in China between 2013 and 2018. SETTING: Nationwide data from China. PARTICIPANTS: We included the male sample aged between 50 and 70, and the female sample aged between 40 and 60 and with basic medical insurance system or public medical insurance. Observations with total expenditures per visit at the top or bottom 1% were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: Inpatient expenditures per visit and inpatient days per visit. METHODOLOGY: We examined the effects by a non-parametric fuzzy regression discontinuity design, exploiting the mandatory retirement age as a source of exogenous variation in retirement status. RESULTS: Retirement reduced drug expenditures (ß=-467.46, p<0.05) and inpatient days per visit (ß=-0.99, p<0.05). The mitigation effect was concentrated on people admitted into hospital due to chronic diseases (ß=-551.28, p<0.05 for drug expenditures; ß=-1.08, p<0.05 for inpatient days per visit) and people admitted into hospital through outpatient services (ß=-353.75, p<0.001 for drug expenditures). For males, retirement significantly reduced diagnostic tests expenditures (ß=-302.38, p<0.05) and drug expenditures (ß=-728.31, p<0.05). Retirement significantly reduced inpatient days per visit (ß=-1.13, p<0.05) for females. CONCLUSION: The empirical findings suggested that retirement may lead to a reduction in inpatient healthcare utilisation, which underlined the importance for policy-makers to consider the externalities of retirement policies on inpatient healthcare utilisation.

Relationship Between eHealth Literacy and Healthy Aging in Older Chinese People: The Mediating Effect of Health Behaviors.

OBJECTIVES: Healthy aging is an important means of promoting the well-being of older individuals. However, no studies have examined the relationship between eHealth literacy and healthy aging or its mechanism. Therefore, this study aimed to examine the relationship between eHealth literacy and healthy aging and the mediating effect of health behaviors in older Chinese individuals. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: We recruited 2144 older individuals from Jinan, Shandong Province, China. METHODS: We used the eHealth Literacy Scale to assess eHealth literacy. Healthy aging was evaluated based on multimorbidity, functional limitations, mild cognitive impairment, depressive symptoms, and social isolation. Moreover, health behaviors were assessed using the Health-Promoting Lifestyle Profile. Logistic and linear regression models were used to analyze the relationships between eHealth literacy, healthy aging, and its components. Finally, a structural equation model was used to analyze the mediation. RESULTS: High eHealth literacy was associated with all healthy aging components (P < .05), including the absence of multimorbidity [odds ratio (OR), 1.014; 95% CI, 1.002-1.025], no functional limitation (OR, 1.035; 95% CI, 1.022-1.047), no mild cognitive impairment (OR, 1.042; 95% CI, 1.024-1.061), no depressive symptoms (OR, 1.049; 95% CI, 1.027-1.072), and no social isolation (OR, 1.033; 95% CI, 1.018-1.048). In the adjusted model, eHealth literacy (ß = 0.174; 95% CI, 0.132-0.217) was positively correlated with healthy aging. Health behaviors had a partial mediating effect on the relationship between eHealth literacy and healthy aging. CONCLUSIONS AND IMPLICATIONS: Higher eHealth literacy was associated with better healthy aging in older Chinese individuals, and health behaviors mediated this relationship. Improving eHealth literacy may be an effective intervention for achieving healthy aging.

Allostatic load and oral health later in life among middle-aged and older adults: An analysis of population-based panel data in China.

BACKGROUND: Oral health is a major global public health problem, but its risk factors have not been fully identified. The limited evidence suggests that AL may affect oral health conditions, but most of these studies focus only on middle-aged western populations. OBJECTIVES: To examine whether allostatic load is associated with oral health conditions later in life among middle-aged and older adults in China and there there is a correlation in both middle-aged and older people. MATERIALS AND METHODS: Data were collected from the China Health and Retirement Longitudinal Study 2011-2018 (N = 10 890) and were analysed using logistic regressions for the overall sample and subsamples by age. RESULTS: Results showed that higher inflammation load significantly increased the odds of edentulism (OR = 1.358, 95% CI = 1.020-1.809, p < .05). Higher metabolic load significantly increased the odds of denture use (OR = 1.375, 95% CI = 1.154-1.640, p < 0.001) and difficulty in chewing solid foods (OR = 1.100, 95% CI = 1.035-1.169, p < .01). These associations were manifested in older adults over 60 years of age, while in the middle-aged subsample, the associations were not significant. CONCLUSION: The findings suggested that higher allostatic load was associated with poorer oral health conditions later in life. It is critical to lower allostatic load and improve oral health conditions, especially for older adults over 60 years of age. Prospective studies and intervention trials help to better understand whether allostatic load is causally linked to oral health.

Primary hepatic lymphoma a case report and literature review.

RATIONALE: Primary hepatic lymphoma is a rare extranodal non-Hodgkin lymphoma that is primarily localized in the liver. It predominantly affects elderly males and presents with nonspecific laboratory findings, imaging results, and clinical symptoms, making diagnosis challenging. Histopathological examination serves as the gold standard for diagnosis, and treatment options include chemotherapy or surgical intervention combined with chemotherapy. PATIENT CONCERNS: A 50-year-old male patient came to our hospital for treatment after finding a mass in his liver. DIAGNOSES: Laboratory tests and clinical symptoms lack specificity for primary hepatic lymphoma, and imaging findings can be difficult to differentiate. Pathology is the gold standard. OUTCOMES: The patient was dead. CONCLUSION: A definitive diagnosis primarily relies on histopathological examination, and surgical resection combined with chemotherapy yields better treatment outcomes.

Willingness to vaccinate against herpes zoster in Chinese urban population: a mixed-methods study.

OBJECTIVE: Although the herpes zoster vaccine has been available in mainland China since June 2020, residents' knowledge of herpes zoster and the herpes zoster vaccine is poor, and vaccination rates are low, especially among the elderly, who are at high risk for herpes zoster. This study assessed willingness to be vaccinated against herpes zoster and factors associated with vaccination among urban residents in China. METHODS: A mixed-methods study was conducted in community health centres from August 2022 to September 2022. We used convenience sampling to select 2864 residents from 9 Chinese cities for the quantitative study and 67 adults for the qualitative study. A structured questionnaire was used for the quantitative study, and data were collected through face-to-face interviews. Multinomial logistic regression was used to analyse factors associated with willingness to vaccinate. Qualitative data were analysed using thematic analysis of barriers to herpes zoster vaccination. RESULTS: A total of 2864 eligible respondents were included in the study. Of these, 42.67% intended to receive the herpes zoster vaccine, 21.44% refused and 35.89% were hesitant. The results of the quantitative and qualitative analyses showed that the factors associated with respondents' willingness to be vaccinated against herpes zoster included: personal characteristics such as gender, age and income; knowledge and attitudes about herpes zoster and the vaccine; vaccine characteristics such as efficacy, safety and price; and other factors such as pain tolerance and accessibility to vaccination. CONCLUSION: The low willingness to vaccinate, especially among the elderly, is mainly related to their poor knowledge and negative attitude towards the infection and vaccination. Therefore, health education about herpes zoster, immunisation promotion, and improvement of accessibility and affordability would be valuable in China.

The impact of urban-rural medical insurance integration on medical impoverishment: evidence from China.

BACKGROUND: Financial protection is a key dimension of Universal Health Coverage (UHC), and social medical insurance is an effective measure to provide financial protection. The aim of this study is to examine the impact of urban-rural medical insurance integration on medical impoverishment in China. METHODS: We collected the time of integration policy in 337 prefecture-level cities across China, combined with the longitudinal database of China Labor-force Dynamics Survey (CLDS) from 2012-2016, and used a difference-in-differences (DID) method with multiple time periods at the city level to study the effect of urban-rural medical insurance integration on the medical impoverishment. Besides, to explore the heterogeneity of policy effects across populations, we conducted subgroup analyses based on respondents' age, household registration, and whether they were rural-urban migrants. FINDINGS: A total of 8,397 samples were included in the study. The integration policy has significantly reduced the incidence of medical impoverishment (average treatment effect on the treated (ATT) = - 0.055, p < 0.05). Subgroup analysis showed that the impacts on medical impoverishment varied by age group, and the integration policy has more effect on older people than on younger people (ATT for age 15-34 = - 0.018, p > 0.05; ATT for age 35-54 = - 0.042, p < 0.05; ATT for age 55-64 = - 0.163, p < 0.01). Moreover, the impacts also varied by household registration. The integration policy has a more significant impact on rural residents (ATT for rural = - 0.067, p < 0.05) compared to urban residents (ATT for urban = - 0.007, p > 0.05). Additionally, the policy has a bigger influence on rural-urban migrants (ATT for rural-urban migrated = - 0.086, p < 0.05) than on those who have not migrated (ATT for rural-urban unmigrated = - 0.071, p < 0.05). CONCLUSION: China's policy of integrating urban-rural medical insurance has been successful in reducing medical impoverishment, especially for older age, rural, and rural-urban migrated people. It can be speculated that the integrating policy may be adapted to other similar settings in developing countries to reduce medical impoverishment.

Targeted protein degradation in drug development: Recent advances and future challenges.

Targeted protein degradation (TPD) has emerged as a promising therapeutic approach with potential advantages over traditional occupancy-based inhibitors in terms of dosing, side effects and targeting "undruggable" proteins. Targeted degraders can theoretically bind any nook or cranny of targeted proteins to drive degradation. This offers convenience versus the small-molecule inhibitors that must function in a well-defined pocket. The degradation process depends mainly on two cell self-destruction mechanisms, namely the ubiquitin-proteasome system and the lysosomal degradation pathway. Various TPD strategies (e.g., proteolytic-targeting chimeras, molecular glues, lysosome-targeting chimeras, and autophagy-targeting chimeras) have been developed. These approaches hold great potential for targeting dysregulated proteins, potentially offering therapeutic benefits. In this article, we systematically review the mechanisms of various TPD strategies, potential applications to drug discovery, and recent advances. We also discuss the benefits and challenges associated with these TPD strategies, aiming to provide insight into the targeting of dysregulated proteins and facilitate their clinical applications.

Relationship between household financial debt and depressive symptoms: a longitudinal study in China.

OBJECTIVES: To examine the impacts of household financial debt on depressive symptoms and its possible mediating mechanisms. DESIGN: A nationally representative longitudinal study using the ordinary least squares regression model, fixed-effects model, and instrumental variable approach to explore the relationship between household financial debt and depressive symptoms and further using structural equation models and the Bootstrap method to analyse the mediating effects. SETTING: The China Family Panel Studies (CFPS) database. PARTICIPANTS: Three waves of longitudinal data in 2012, 2016, and 2018 from CFPS were used. A total of 103,247 individuals over the age of 18 were included in our study sample. OUTCOME MEASURES: Depression symptoms were assessed using an eight-item version of the Center for Epidemiologic Studies Depression Scale (CES-D8). We summed these eight items to conduct a depressive symptoms index to measure depressive symptoms. RESULTS: Among the sample, 35.3% of the households have financial debt, 49.7% of the sample are male, 73.2% of them have rural hukou, and the average age was 46.6. Regression results showed that household financial debt had a negative effect on depressive symptoms (ß=0.655, 95% CI 0.602 to 0.707, p<0.01). This result remained robust after using instrumental variables with fixed effects (ß=0.483, 95% CI 0.311 to 0.656, p<0.01). Household financial debt could affect depressive symptoms through mediating variables such as working pressure (p<0.05) and life happiness (p<0.01). CONCLUSION: Our study showed that household indebtedness in China had a negative effect on depressive symptoms. Also, we found some mediating mechanisms for this effect, which might help provide new guidance for psychological interventions to promote the mental health of indebted residents.

Community-based integrated care for patients with diabetes and depression (CIC-PDD): study protocol for a cluster randomized controlled trial.

BACKGROUND: Managing the multimorbidity of diabetes and depression remains a clinical challenge for patients and healthcare professionals due to the fragmented healthcare delivery system. To effectively cope with multimorbidity, there is an urgent need for the health system to transform into people-centered integrated care (PCIC) system globally. Therefore, this paper describes the protocol of community-based integrated care for patients with diabetes and depression (CIC-PDD) project, an integrated and shared-care intervention project. METHODS/DESIGN: CIC-PDD project is conducted in two phases, namely "care model development" and "implementation and evaluation." In the first phase, CIC-PDD model was designed and developed based on the four criteria of collaborative care model (CCM) and was subsequently adjusted to align with the context of China. The second phase entails a pragmatic, two-arm, cluster randomized controlled implementation trial, accompanied by parallel mixed-methods process evaluation and cost-effectiveness analysis. DISCUSSION: We anticipate CIC-PDD project will facilitate the development and innovation of PCIC model and related theories worldwide, particularly in low- and middle-income countries (LMICs). In addition, CIC-PDD project will contribute to the exploration of primary health care (PHC) in addressing the multimorbidity of physical and mental health issues. TRIAL REGISTRATION: ClinicalTrials.gov registration ChiCTR2200065608 (China Clinical Trials Registry https://www.chictr.org.cn ). Registered on November 9, 2022.

Data envelopment analysis on the efficiency of vaccination services and its influencing factors in Beijing, China.

OBJECTIVES: Vaccination is an important part of public health services. We aim to assess the efficiency of vaccination services in Beijing, the capital of China, and to further study the influencing factors of efficiency. METHODS: Using the immunization service data of Beijing, China in 2020, we firstly developed a data envelopment analysis (DEA) model to calculate the score of vaccination efficiency. Secondly, we used DEA model scenario simulations with different combinations of input-output factors to derive the magnitude of the effect of each input factor on the efficiency. Finally, combined with the data from the Beijing Regional Statistical Yearbook 2021, we developed the Tobit model to examine the effect of external social environmental factors on efficiency. RESULTS: The average scores of efficiency of POVs (Point of Vaccination) in different areas of Beijing vary greatly. Different input factors had different degrees of positive effects on the efficiency score. In addition, the number of populations served by POV was positively associated with efficiency, the GDP and financial allocation of the POVs' district was also positively associated with efficiency score, while the total dependency ratio of the POVs' district was negatively associated with efficiency score. CONCLUSION: The efficiency of vaccination services varied considerably across POVs. Constrained by limited resources, efficiency scores can be increased by increasing input factors that have a larger impact on efficiency score and reducing those that have a smaller impact on efficiency. In addition, the social environment should be considered in allocating vaccination resources, and more resources should be invested in areas with low levels of economic development, low financial allocation, and high population.

The Impact Mechanism of Household Financial Debt on Physical Health in China.

In recent years, Chinese household financial debt has been growing rapidly due to the expansion of mortgage lending. This study aims to examine the impact mechanism of Chinese household financial debt on physical health. Using the 2010-2018 China Household Tracking Survey (CFPS) panel data, we developed fixed effects models to explore the effect of household financial debt on individuals' psychical health, and we also used an instrumental variable to address endogeneity. The findings suggest that there is a negative effect of household financial debt on physical health and these findings still hold after a series of robustness tests. In addition, household financial debt can affect individuals' physical health through mediating variables, such as healthcare behaviors and mental health, and the effects are more significant for those who are middle-aged, married, and with low-income levels. The findings of this paper are important for developing countries to clarify the relationship between household financial debt and population health, and to develop appropriate health intervention policies for highly indebted households.

Internet use and rural-urban mental health inequalities: Evidence from China.

Introduction: In the context of the new digital era, clarifying the relationship between Internet use and urban and rural residents' mental health is of important value for reducing rural-urban health inequalities. This paper aims to study the association between Internet use and rural-urban mental health inequalities. Methods: Based on the data of the China Family Panel Studies (CFPS) in 2020, we firstly examined the existence and specific manifestation of mental health inequalities between urban and rural residents. Secondly, we examined the mediating effect of Internet use by the Bootstrap mediating effect measure. Finally, we verified the robustness of the mediating effect. Results: There are significant mental health inequalities between urban and rural residents, and urban residents have better mental health than rural residents (p < 0.01). In addition, the test results for the mediating effect of Internet use on mental health inequalities between urban and rural residents were significant (p < 0.01), with a direct effect of -0.028 (p < 0.01) and an indirect effect of -0.49 (p < 0.01), and this result remained significant in the robustness test. Discussion: In such a new age of the Internet, mental health inequalities between urban and rural residents objectively did exist, and the use of the internet played a positive mediation effect on the formation of mental health inequalities between urban and rural areas.

Regulation of epidermal stratification and development by basal keratinocytes.

The epidermis is a stratified squamous epithelium distributed in the outermost layer of the skin and is intimately involved in the formation of a physical barrier to pathogens. Basal keratinocytes possess the properties of stem cells and play an essential role in epidermal development and skin damage recovery. Therefore, understanding the molecular mechanism of how basal keratinocytes participate in epidermal development and stratification is vital for preventing and treating skin lesions. During epidermal morphogenesis, the symmetric division of basal keratinocytes contributes to the extension of skin tissues, while their asymmetric division and migration facilitate epidermal stratification. In this review, we summarize the process of epidermal stratification and illustrate the molecular mechanisms underlying epidermal morphogenesis. Furthermore, we discuss the coordination of multiple signaling pathways and transcription factors in epidermal stratification, together with the roles of cell polarity and cell dynamics during the process.

The dynamic relationship between subjective social status and health: Evidence from a Chinese cohort study.

PURPOSE: Using nationally representative longitudinal data from 2010 to 2018 in China, this study systematically investigates the relationship between Subjective Social Status (SSS) and health (physical health and mental health) in the Chinese adult population. METHODS: By applying between-within model, we disentangle the relationship between health outcomes and: (1) between-individual differences in SSS and (2) within-individual variations of SSS across time. In addition, to explore SSS mobility and trajectory, we further decomposed SSS into lagged SSS and the change between the current and lagged SSS (mobility). RESULTS: We find that there is significantly positive and unique relationship (independent of Objective Social Status (OSS)) between SSS and physical and mental health. However, for physical health, we observed an Inverse-U effect of average SSS, after some point (SSS = 3.93), higher average SSS is associated with a score decrease. Through heterogeneity analysis, we find that for physical health, within- and between-effects decreases with age and for mental health, the within effect is only significant among the urban population. Individuals with high expected mobility are also found to have significantly better health. CONCLUSIONS: These findings show that the personal relative deprivation has negative, particularly salient and unique effects on the health of the Chinese population, and it is important to consider the dynamic nature of SSS.

Effects of the Long-term Care Insurance on Health Among Older Adults: A Panel Data From China.

BACKGROUND: China's long-term care insurance (LTCI) has been launched since 2016 to ensure that older disabled people obtain affordable care services. However, rigorous evaluations of the health effects of China's LTCI pilots have been limited. This paper aimed to examine the effects of LTCI on health among older adults aged 60 years and above. METHODS: Drawing from panel data of the China Health and Retirement Longitudinal Study (CHARLS), we used a propensity score matching (PSM) and difference-in-difference (DID) approach to identify the health effects of the LTCI program and reduce the selection bias. Further, heterogeneity of the effects was examined by physical and intellectual function to evaluate whether the effects differed among subgroups of older population. RESULTS: The implementation of LTCI significantly improved self-rated health (ß = 0.15, P<.05) and cognitive function (ß = 0.59, P<.01) for older adults. The results were robust when keeping only those living in pilot cities (ß = 0.31, P<.05 for self-rated health status; ß = 0.98, P<.001 for cognitive function) or non-pilot cities (ß = 0.14, P<.05 for self-rated health status; ß = 0.60, P<.01 for cognitive function) as the control group. The effects of LTCI were especially manifested in older adults with physical disability (ß = 0.13, P<.01 for self-rated health; ß = 0.76, P<.001 for cognitive function) or intellectual disability (ß = 0.16, P<.01 for self-rated health). CONCLUSION: From a policy perspective, these findings suggested that LTCI in China could benefit the health outcomes of older adults, especially those with physical or cognitive disabilities. Policy-makers can target resources more effectively to improve health outcomes for the most vulnerable populations.

Centrosome Defects in Hematological Malignancies: Molecular Mechanisms and Therapeutic Insights.

Defects in centrosomes are associated with a broad spectrum of hematological malignancies, such as leukemia and lymphoma. Centrosomes in these malignancies display both numerical and structural aberrations, including alterations in the number and size of centrioles, inappropriate post-translational modification of centrosomal proteins, and extra centrosome clustering. There is accumulating evidence that centrosome defects observed in hematological malignancies result from multiple factors, including dysregulation of the centrosome cycle and impairment of centriole biogenesis. In this review, we discuss the plausible mechanisms of centrosome defects and highlight their consequences in hematological malignancies. We also illustrate the latest therapeutic strategies against hematological malignancies by targeting centrosome anomalies.

Effectiveness of Collaborative Care for Depression and HbA1c in Patients with Depression and Diabetes: A Systematic Review and Meta-Analysis.

Background and Aim: The collaborative care (CC) is emerging as an effective method in treating patients with multimorbidity, but evidence whether this model is effective for people with comorbid depression and diabetes is unclear. This study aimed to investigate whether CC could improve depression outcomes and HbA1c in patients with depressive symptoms and diabetes, and assess its effects on Quality of Life (QoL). Method: The author searched Embase, Scopus, PubMed, Cochrane, PsycINFO and CINAHL to identify randomized controlled trials (RCTs) and cluster RCTs published up to October 21, 2020. Studies were required to assess CC in patients with depressive symptoms and diabetes. The primary outcomes were depression treatment response rate and HbA1c and secondary outcome was Quality of Life (QoL). Available individual patient data was collected from all eligible studies. Studies were independently screened by two reviewers and critically appraised using the Cochrane Risk of Bias tool. This study conducted a systematic review and meta-analysis, and the fixed effects and random effects model were used to pool Relative Risks (RRs) and Standard Mean Differences (SMDs). Results: Our research identified 7906 articles, and finally 12 RCTs were included. Study sample sizes ranged from 58 to 417. The total follow-up period ranged from 12 weeks to 24 months. At follow-up, depression treatment response rate had a significant increase (RR = 1·31, 95% CI 1·23 to 1·39, I2 = 0%) in CC patients compared to controls. There was no statistically significant difference in HbA1c between CC group and the control group (SMD = 0·15, 95% CI -0·35 to 0·65, I2 = 97·6%). Overall QoL at follow-up was greater (SMD = 0·12, 95% CI 0·03 to 0·21, I2 = 54·2%) in CC patients compared to controls but the difference was minor. Conclusion: This systematic review and meta-analysis supported the effectiveness of CC in reducing depression and improving QoL in people with comorbid depression and diabetes.

Mitochondria dysfunction in Charcot Marie Tooth 2B Peripheral Sensory Neuropathy.

Rab7 GTPase regulates mitochondrial morphology and function. Missense mutation(s) of Rab7 underlies the pathogenesis of Charcot Marie Tooth 2B (CMT2B) peripheral neuropathy. Herein, we investigate how mitochondrial morphology and function are impacted by the CMT2B associated Rab7V162M mutation. In contrast to recent studies of using heterologous overexpression systems, our results demonstrate significant mitochondrial fragmentation in both human CMT2B patient fibroblasts and CMT2B embryonic fibroblasts (MEFs). Primary cultured E18 dorsal root ganglion (DRG) sensory neurons also show mitochondrial fragmentation and altered axonal mitochondrial movement. In addition, we demonstrate that inhibitors to either the mitochondrial fission protein Drp1 or to the nucleotide binding to Rab7 normalize the mitochondrial deficits in both MEFs and E18 cultured DRG neurons. Our study reveals, for the first time, that expression of CMT2B Rab7 mutation at the physiological level enhances Drp1 activity to promote mitochondrial fission, potentially underlying selective vulnerability of peripheral sensory neurons in CMT2B pathogenesis.