A study on the association between prefrontal functional connectivity and non-suicidal self-injury in adolescents with depression.

Objective: Among adolescents with depression, the occurrence of non-suicidal self-injury (NSSI) behavior is prevalent, constituting a high-risk factor for suicide. However, there has been limited research on the neuroimaging mechanisms underlying adolescent depression and NSSI behavior, and the potential association between the two remains unclear. Therefore, this study aims to investigate the alterations in functional connectivity (FC) of the regions in the prefrontal cortex with the whole brain, and elucidates the relationship between these alterations and NSSI behavior in adolescents with depression. Methods: A total of 68 participants were included in this study, including 35 adolescents with depression and 33 healthy controls. All participants underwent assessments using the 17-item Hamilton Depression Rating Scale (17-HAMD) and the Ottawa Self-Harm Inventory. In addition, functional magnetic resonance imaging (fMRI) data of the participants' brains were collected. Subsequently, the FCs of the regions in the prefrontal cortex with the whole brain was calculated. The FCs showing significant differences were then subjected to correlation analyses with 17-HAMD scores and NSSI behavior scores. Result: Compared to the healthy control group, the adolescent depression group exhibited decreased FCs in several regions, including the right frontal eye field, left dorsolateral prefrontal cortex, right orbitofrontal cortex, left insula and right anterior cingulate coetex. The 17-HAMD score was positively correlated with the frequency of NSSI behavior within 1 year (rs = 0.461, p = 0.005). The FC between the right anterior cingulate cortex and the right precuneus showed a negative correlation with the 17-HAMD scores (rs = -0.401, p = 0.023). Additionally, the FC between the right orbitofrontal cortex and the right insula, demonstrated a negative correlation with the frequency of NSSI behavior within 1 year (rs = -0.438, p = 0.012, respectively). Conclusion: Adolescents with depression showed decreased FCs of the prefrontal cortex with multiple brain regions, and some of these FCs were associated with the NSSI frequency within 1 year. This study provided neuroimaging evidence for the neurophysiological mechanisms underlying adolescent depression and its comorbidity with NSSI behavior.

Abnormal dynamic functional connectivity of thalamic subregions in patients with first-episode, drug-naïve major depressive disorder.

Background: Recent studies have shown that major depressive disorder (MDD) is associated with altered intrinsic functional connectivity (FC) of the thalamus; however, investigations of these alterations at a finer time scale and the level of thalamic subregions are still lacking. Methods: We collected resting-state functional MRI data from 100 treatment-naïve, first-episode MDD patients and 99 age-, gender- and education-matched healthy controls (HCs). Seed-based whole-brain sliding window-based dFC analyses were performed for 16 thalamic subregions. Between-group differences in the mean and variance of dFC were determined using threshold-free cluster enhancement algorithm. For significant alterations, there relationships with clinical and neuropsychological variables were further examined via bivariate and multivariate correlation analyses. Results: Of all thalamic subregions, only the left sensory thalamus (Stha) showed altered variance of dFC in the patients characterized by increases with the left inferior parietal lobule, left superior frontal gyrus, left inferior temporal gyrus, and left precuneus, and decreases with multiple frontal, temporal, parietal, and subcortical regions. These alterations accounted for, to a great extent, clinical, and neuropsychological characteristics of the patients as revealed by the multivariate correlation analysis. In addition, the bivariate correlation analysis revealed a positive correlation between the variance of dFC between the left Stha and right inferior temporal gurus/fusiform and childhood trauma questionnaires scores (r = 0.562, P < 0.001). Conclusion: These findings suggest that the left Stha is the most vulnerable thalamic subregion to MDD, whose dFC alterations may serve as potential biomarkers for the diagnosis of the disease.

A Chain Mediation Model of Perceived Stress, Neuroticism, and Psychological Inflexibility on Depressive Symptoms of Chinese New Fathers.

There is a growing concern about mental health issues in new fathers, such as postpartum depression (PPD). Factors associated with PPD in men include personality traits and perceived stress. This study examined a set of hypothesized paths using perceived stress, neuroticism, and psychological inflexibility to predict depressive symptoms. A total of 189 participants took part. The mean age of these first-time fathers was 36.12 years (SD = 2.39). Perceived stress, neuroticism, and psychological inflexibility positively predicted new fathers' depressive symptoms (B = 0.13, 0.37, and 0.31, respectively). These predictors explained 48% (R2 = 0.48) of the variance in the measured outcome of depressive symptoms in these new Chinese fathers. The total standardized direct effects of the three variables on depressive symptoms were 0.47 (95% CI [0.38, 0.53]). In conclusion, this study provides novel information about the chain mediating role played by neuroticism and psychological inflexibility in the relationship between perceived stress and PPD. Perceived stress significantly predicted neuroticism and psychological inflexibility, which in turn significantly predicted depressive symptoms in new Chinese fathers. The relationship between perceived stress and depressive symptoms was also mediated by each of psychological inflexibility or neuroticism alone.

Abnormal Functional Connectivity of Posterior Cingulate Cortex Correlates With Phonemic Verbal Fluency Deficits in Major Depressive Disorder.

Background: Major depressive disorder (MDD) patients face an increased risk of developing cognitive impairments. One of the prominent cognitive impairments in MDD patients is verbal fluency deficit. Nonetheless, it is not clear which vulnerable brain region in MDD is interactively linked to verbal fluency deficit. It is important to gain an improved understanding for verbal fluency deficit in MDD. Methods: Thirty-four MDD patients and 34 normal controls (NCs) completed resting-state fMRI (rs-fMRI) scan and a set of verbal fluency tests (semantic VFT and phonemic VFT). Fourteen brain regions from five brain networks/systems (central executive network, default mode network, salience network, limbic system, cerebellum) based on their vital role in MDD neuropathology were selected as seeds for functional connectivity (FC) analyses with the voxels in the whole brain. Finally, correlations between the z-score of the FCs from clusters showing significant between-group difference and z-score of the VFTs were calculated using Pearson correlation analyses. Results: Increased FCs in MDD patients vs. NCs were identified between the bilateral posterior cingulate cortex (PCC) and the right inferior frontal gyrus (triangular part), in which the increased FC between the right PCC and the right inferior frontal gyrus (triangular part) was positively correlated with the z score of phonemic VFT in the MDD patients. Moreover, decreased FCs were identified between the right hippocampal gyrus and PCC, as well as left cerebellum Crus II and right parahippocampal gyrus in MDD patients vs. NCs. Conclusions: The MDD patients have altered FCs among key brain regions in the default mode network, the central executive network, the limbic system, and the cerebellum. The increased FC between the right PCC and the right inferior frontal gyrus (triangular part) may be useful to better characterize pathophysiology of MDD and functional correlates of the phonemic verbal fluency deficit in MDD.

Multiscale neural modeling of resting-state fMRI reveals executive-limbic malfunction as a core mechanism in major depressive disorder.

Major depressive disorder (MDD) represents a grand challenge to human health and society, but the underlying pathophysiological mechanisms remain elusive. Previous neuroimaging studies have suggested that MDD is associated with abnormal interactions and dynamics in two major neural systems including the default mode - salience (DMN-SAL) network and the executive - limbic (EXE-LIM) network, but it is not clear which network plays a central role and which network plays a subordinate role in MDD pathophysiology. To address this question, we refined a newly developed Multiscale Neural Model Inversion (MNMI) framework and applied it to test whether MDD is more affected by impaired circuit interactions in the DMN-SAL network or the EXE-LIM network. The model estimates the directed connection strengths between different neural populations both within and between brain regions based on resting-state fMRI data collected from normal healthy subjects and patients with MDD. Results show that MDD is primarily characterized by abnormal circuit interactions in the EXE-LIM network rather than the DMN-SAL network. Specifically, we observe reduced frontoparietal effective connectivity that potentially contributes to hypoactivity in the dorsolateral prefrontal cortex (dlPFC), and decreased intrinsic inhibition combined with increased excitation from the superior parietal cortex (SPC) that potentially lead to amygdala hyperactivity, together resulting in activation imbalance in the PFC-amygdala circuit that pervades in MDD. Moreover, the model reveals reduced PFC-to-hippocampus excitation but decreased SPC-to-thalamus inhibition in MDD population that potentially lead to hypoactivity in the hippocampus and hyperactivity in the thalamus, consistent with previous experimental data. Overall, our findings provide strong support for the long-standing limbic-cortical dysregulation model in major depression but also offer novel insights into the multiscale pathophysiology of this debilitating disease.

G-MDSCs promote aging-related cardiac fibrosis by activating myofibroblasts and preventing senescence.

Aging is one of the most prominent risk factors for heart failure. Myeloid-derived suppressor cells (MDSCs) accumulate in aged tissue and have been confirmed to be associated with various aging-related diseases. However, the role of MDSCs in the aging heart remains unknown. Through RNA-seq and biochemical approaches, we found that granulocytic MDSCs (G-MDSCs) accumulated significantly in the aging heart compared with monocytic MDSCs (M-MDSCs). Therefore, we explored the effects of G-MDSCs on the aging heart. We found that the adoptive transfer of G-MDSCs of aging mice to young hearts resulted in cardiac diastolic dysfunction by inducing cardiac fibrosis, similar to that in aging hearts. S100A8/A9 derived from G-MDSCs induced inflammatory phenotypes and increased the osteopontin (OPN) level in fibroblasts. The upregulation of fibroblast growth factor 2 (FGF2) expression in fibroblasts mediated by G-MDSCs promoted antisenescence and antiapoptotic phenotypes of fibroblasts. SOX9 is the downstream gene of FGF2 and is required for FGF2-mediated and G-MDSC-mediated profibrotic effects. Interestingly, both FGF2 levels and SOX9 levels were upregulated in fibroblasts but not in G-MDSCs and were independent of S100A8/9. Therefore, a novel FGF2-SOX9 signaling axis that regulates fibroblast self-renewal and antiapoptotic phenotypes was identified. Our study revealed the mechanism by which G-MDSCs promote cardiac fibrosis via the secretion of S100A8/A9 and the regulation of FGF2-SOX9 signaling in fibroblasts during aging.

Mediating role of social support between sleep quality, anxiety and depressive symptoms in Chinese women undergoing in vitro fertilization treatment.

INTRODUCTION: Infertility is a significant health problem, and the prevalence of infertility among women is increasing in developing countries. This study aims to explore whether social support plays a mediating role in the links between exogenous variables, sleep quality, anxiety, and depressive symptoms in Chinese women undergoing in vitro fertilization. METHODS: This is a cross-sectional study comprising a sample of Chinese women undergoing in vitro fertilization treatment at a tertiary reproductive medicine center located in South China. RESULTS: The final testing model showed good fit, with normed χ2 = 39.317, p = 0.055, comparative fit index = 0.948, Tucker-Lewis index = 0.902, incremental fit index = 0.951, normed fit index = 0.906, root mean square error of approximation = 0.046). The final path model supported the proposed model: partner relationship, a woman's age, financial strain, duration of infertility, and cycles of in vitro fertilization were exogenous variables for depressive symptoms, while social support was a significant mediator between sleep quality, anxiety, and depressive symptoms. CONCLUSION: The empirical support from this study could facilitate the development of appropriate interventions to reduce depressive symptoms, and to promote the mental health of Chinese women undergoing in vitro fertilization treatment.

Effect of Electroacupuncture and Counseling on Sub-Threshold Depression: A Study Protocol for a Multicenter Randomized Controlled Trial.

BACKGROUND: Sub-threshold depression is common and could impair function, as well as increase the risk of developing major depression. Despite evidence of efficacy for electroacupuncture (EA) and counseling in the treatment of sub-threshold depression, the sample size is insufficient and the level of evidence remains low. This study aims to evaluate the effectiveness of sub-threshold depression treatments by comparing the treatment effects among EA, counseling, and combination therapy, as well as to further study their mechanism. METHODS: This study is a multicenter, randomized, single blind clinical trial that will be conducted in settings at four clinical centers in China. The randomized controlled trial (RCT) will examine the effectiveness of EA intervention, compared with counseling and combination therapy. A total of 138 sub-threshold depression patients (18 to 55 years of age with Beck Depression Inventory (BDI-II) score ≥ 14 points and Hamilton Depression Scale (HAMD-17) score: 7 points ≤ HAMD total score <17 points) will be recruited. The participants will be randomly assigned to receive the above treatments. The interventions will be delivered over a 6-week period (EA: 3 times a week for 6 weeks; 30 min a session. Counseling: once a week for 6 weeks; 50-60 min a session). The primary outcome measure will be the HAMD-17; BDI-II. The secondary outcome measures will be: Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), and Pittsburgh Sleep Quality Index (PSQI). The assessments will occur at baseline, 2, 4, and 6 weeks and a follow-up period. Recruitment will commence in March 2020 and is anticipated to occur over a 2-year period. DISCUSSION: This study intends to conduct a multicenter randomized controlled trial to compare the effectiveness among EA, counseling and the combined therapy in the treatment of patients with sub-threshold depression, and to further study the mechanisms of effect. CHINESE CLINICAL TRIAL REGISTRY REGISTRATION: www.chictr.org.cn/, identifier ChiCTR1900028530.

Altered Resting-State Functional Connectivity of Multiple Networks and Disrupted Correlation With Executive Function in Major Depressive Disorder.

Background: Major depressive disorder (MDD) is one of the most common and costly psychiatric disorders. In addition to significant changes in mood, MDD patients face an increased risk of developing cognitive dysfunction. It is important to gain an improved understanding of cognitive impairments and find a biomarker for cognitive impairment diagnosis in MDD. Methods: One hundred MDD patients and 100 normal controls (NCs) completed resting-state fMRI (rs-fMRI) scan, in which 34 MDD patients and 34 NCs had scores in multiple cognitive domains (executive function, verbal fluency, and processing speed). Twenty-seven regions of interest from the default mode network (DMN), central executive network (CEN), salience network (SN), and limbic system (LS) were selected as seeds for functional connectivity (FC) analyses with the voxels in the whole brain. Finally, partial correlations were conducted for cognitive domain scores and FCs with significant differences between the MDD and NC groups. Results: Significant FC differences between groups were identified among the seeds and clusters in the DMN, CEN, LS, visual network, somatomotor network, ventral attention network, and dorsal attention network. In the MDD patients, the magnitude of the Stroop interference effect was positively correlated with the illness duration, and the illness duration was negatively correlated with the FC between the right ventral hippocampal gyrus and the left inferior frontal gyrus. However, the correlation between the Stroop interference effect and the FC of the right anterior prefrontal cortex with the left cerebellum_4_5 was disrupted in these patients. Conclusions: The MDD patients have altered FCs among multiple brain networks and a disrupted correlation between the FC of prefrontal cortex and executive function. The disrupted correlation could present before the symptoms develop and may be the core process in the development of executive function impairment.

Large-scale dynamic causal modeling of major depressive disorder based on resting-state functional magnetic resonance imaging.

Major depressive disorder (MDD) is a serious mental illness characterized by dysfunctional connectivity among distributed brain regions. Previous connectome studies based on functional magnetic resonance imaging (fMRI) have focused primarily on undirected functional connectivity and existing directed effective connectivity (EC) studies concerned mostly task-based fMRI and incorporated only a few brain regions. To overcome these limitations and understand whether MDD is mediated by within-network or between-network connectivities, we applied spectral dynamic causal modeling to estimate EC of a large-scale network with 27 regions of interests from four distributed functional brain networks (default mode, executive control, salience, and limbic networks), based on large sample-size resting-state fMRI consisting of 100 healthy subjects and 100 individuals with first-episode drug-naive MDD. We applied a newly developed parametric empirical Bayes (PEB) framework to test specific hypotheses. We showed that MDD altered EC both within and between high-order functional networks. Specifically, MDD is associated with reduced excitatory connectivity mainly within the default mode network (DMN), and between the default mode and salience networks. In addition, the network-averaged inhibitory EC within the DMN was found to be significantly elevated in the MDD. The coexistence of the reduced excitatory but increased inhibitory causal connections within the DMNs may underlie disrupted self-recognition and emotional control in MDD. Overall, this study emphasizes that MDD could be associated with altered causal interactions among high-order brain functional networks.

Treatment-naïve first episode depression classification based on high-order brain functional network.

BACKGROUND: Recent functional connectivity (FC) studies have proved the potential value of resting-state functional magnetic resonance imaging (rs-fMRI) in the study of major depressive disorder (MDD); yet, the rs-fMRI-based individualized diagnosis of MDD is still challenging. METHODS: We enrolled 82 treatment-naïve first episode depression (FED) adults and 72 matched normal control (NC). A computer-aided diagnosis framework was utilized to classify the FEDs from the NCs based on the features extracted from not only traditional "low-order" FC networks (LON) based on temporal synchronization of original rs-fMRI signals, but also "high-order" FC networks (HON) that characterize more complex functional interactions via correlation of the dynamic (time-varying) FCs. We contrasted a classifier using HON feature (CHON) and compared its performance with using LON only (CLON). Finally, an integrated classification model with both features was proposed to further enhance FED classification. RESULTS: The CHON had significantly improved diagnostic accuracy compared to the CLON (82.47% vs. 67.53%). Joint classification further improved the performance (83.77%). The brain regions with potential diagnostic values mainly encompass the high-order cognitive function-related networks. Importantly, we found previously less-reported potential imaging biomarkers that involve the vermis and the crus II in the cerebellum. LIMITATIONS: We only used one imaging modality and did not examine data from different subtypes of depression. CONCLUSIONS: Depression classification could be significantly improved by using HON features that better capture the higher-level brain functional interactions. The findings suggest the importance of higher-level cerebro-cerebellar interactions in the pathophysiology of MDD.

Increased muscle coenzyme Q10 in riboflavin responsive MADD with ETFDH gene mutations due to secondary mitochondrial proliferation.

Multiple acyl-coenzyme A dehydrogenation deficiency (MADD) has a wide range of phenotypic variation ranging from a neonatal lethal form to a mild late-onset form. Our previous data showed that in a group of Chinese patients, a mild type of MADD characterized by myopathy with clinically no other systemic involvement was caused by mutations in electron transfer flavoprotein dehydrogenase (ETFDH) gene, which encodes electron transfer flavoprotein: ubiquinone oxidoreductase (ETF:QO). Coenzyme Q10 (CoQ10), a downstream electron receptor of ETF:QO was first reported deficient in muscle of MADD patients with ETFDH gene mutations. Nevertheless, this result was not confirmed in a recently published study. Therefore to elucidate muscle CoQ10 level in a large group of MADD patients may provide further insight into the pathomechanism and therapeutic strategies. In this study, we found that 34 riboflavin responsive patients with ETFDH gene mutations had an elevated CoQ10 pool in muscle by high performance liquid chromatography (HPLC). However, when CoQ10 levels were normalized to citrate synthase, a marker of mitochondrial mass, there was no significant difference between patients and normal controls. Meanwhile, the increased mitochondrial DNA copy number in muscle also supported that the elevated CoQ10 pool was mainly due to mitochondrial mass proliferation. The expression of CoQ10 biosynthesis genes showed no significant changes whereas genes involved in lipid metabolism, such as PPARα, were marked up regulated. Our results suggested that CoQ10 seems not to be a primary factor in riboflavin responsive MADD and the apparent increase in CoQ10 may be secondary to mitochondrial proliferation.

Riboflavin-responsive lipid-storage myopathy caused by ETFDH gene mutations.

BACKGROUND: Lipid-storage myopathy (LSM), defined by triglyceride accumulation in muscle fibres, is a heterogeneous group of lipid metabolic disorders predominantly affecting skeletal muscle. In the past 15 years, more than 200 cases of LSM have been reported in the Chinese literature, but the accurate pathogenic mechanisms are still unknown. OBJECTIVE: In order to gain more insight into the metabolic and genetic dysfunctions of LSM, the authors described a group of Chinese patients with LSM who were very responsive to isolated riboflavin treatment (riboflavin responsive LSM, RR-LSM). METHODS: Nineteen consecutive LSM patients collected during 1995-2007 in our Neuromuscular Laboratory who were dramatically responsive to riboflavin and presented with proximal muscle weakness, exercise intolerance and elevated serum CK but without episodic encephalopathy were subjected to pathological, biochemical and molecular analysis. RESULTS: On the basis of muscle pathology, all 19 patients were diagnosed as LSM. Seventeen patients were suspected of having multiple acyl-coenzyme A dehydrogenase deficiency (MADD) according to blood acylcarnitine profiles and urine organic acid analysis. Genetic analysis identified 19 novel mutations in ETFDH gene in 18 patients, among which one was homozygote, 16 were compound heterozygotes, and one was a single heterozygote. No pathogenic mutation was detected in ETFA or ETFB genes. Western blot analysis showed there was no significant decrease in ETF:QO expression except for one patient. CONCLUSIONS: The research findings suggest that the majority of Chinese patients with RR-LSM are caused by a mild type of MADD with unique myopathy which is due to ETFDH gene mutation.

[Clinical and biopsy-based myopathological features of 5 cases with centronuclear myopathy].

OBJECTIVE: To analyze the clinical and pathological features of the centronuclear myopathy (CNM) in 5 Chinese patients and evaluate their diagnostic and differential diagnostic value. METHODS: A standard series of histochemical and enzymohistochemical investigations were performed on all muscle specimens of CNM cases obtained via biopsy. The clinical manifestations and myopathological features of 5 CNM patients were retrospectively analyzed. RESULTS: The age of onset ranged from 3 to 12 years. All patients primarily presented with limb girdle muscle weakness. In 3 patients extraocular muscles, facial muscles and cervical muscles were affected, respectively. The proximal muscles were affected more seriously than the distal and the lower limbs more seriously than the upper. Tendon reflex was reduced and no evident muscular atrophy was seen. The course of the disease ranged from 4 to 46 years and progressed slowly. The ability of walking could be maintained for many years and the fast movements such as running and jumping were impaired early. The serum creatine kinase (CK) level was normal or elevated slightly. Electromyography showed myopathic pattern in all cases. Two patients (mother and son) were from the same family and the son's two siblings had similar symptoms indicating autosomal dominant inherited pattern. There was mild variation in fiber size and most small fibers were round. Interstitial tissue increase slightly. Fibers with centrally placed nuclei accounted for 23% - 93%. Neither necrotic and regenerated fibers nor infiltration of inflammatory cells were seen. Type I fiber predominance and hypotrophy were present in all patients. Abnormal arrangement of the sarcoplasmic strands in appearance of "spokes of a wheel", increased oxidative enzyme activity around centronuclear and perinuclear halo were observed in 2 patients by NADH-TR staining. CONCLUSIONS: For the patients who had the onset during the childhood and presented with slow progressive limb girdle muscle weakness, disability of fast movements and normal serum CK level, the possibility of benign congenital myopathy should be considered. High percentage of centronuclear fibers as well as type I fiber predominance and hypotrophy in muscle biopsy pathology may provide a morphological evidence for the definite diagnosis of CNM.

[Clinical and pathological features and prognosis of Chinese patients with distal myopathy with rimmed vacuoles: study of 17 cases].

OBJECTIVE: To clarify the clinical and pathological features and prognosis of Chinese patients with distal myopathy with rimmed vacuoles (DMRV). METHODS: The clinical data of 17 Chinese DMRV patients with the courses of disease of 1-21 years, 5 males and 12 females, aged 28.9 (19-41), were collected. Biopsy of muscle specimens of 17 Chinese DMRV patients were summarized retrospectively. Muscle specimens were collected from the biceps brachii, tibialis anterior, gastrocnemius, or quadriceps femoris and underwent light microscopy. Eight muscle specimens underwent electron microscopy. 11 patients were followed up for 4 months to 15 years. RESULTS: The age of onset ranged from 5 to 40 years (averaging 23 years). Distal muscle weakness and atrophy of the lower extremities, especially anterior tibial muscle, was predominant in the early stage. Proximal and trunk muscles were involved in the advanced stage. Quadriceps femoris were slightly involved. The striking and characteristic pathological finding was the presence of rimmed vacuoles in atrophic muscle fibers with little evidence of necrotic or regenerative processes. Electron microscopy showed accumulation of myeloid structure and cytoplasmic or intranuclear tubofilamentous inclusion bodies. Although atrophy and weakness of the leg muscle appeared as initial symptoms, severe generalized skeletal muscle involvement with sparing of the facial, extraocular, bulbar, intercostals, and diaphragm muscles was recognized in the advanced stage. The patients became non-ambulant about 7-10 years after the onset of the disease. They lost the self-care ability and the quality of their life was rather low. CONCLUSION: The clinical and pathological features of the Chinese DMRV patients are basically similar to those of the Japanese patients. With the disease progressing slowly, the patients become wheelchair-bound and lose the self-care ability. As to daily life, the prognosis of DMRV is extremely poor.

[Dysferlin expression in limb-girdle muscular dystrophy and Miyoshi myopathy: analysis of 45 cases].

OBJECTIVE: To clarify the expression patterns of dysferlin in limb-girdle muscular dystrophy (LGMD) and Miyoshi myopathy (MM), and to investigate the frequency and clinicopathologic features of dysferlinopathy. METHODS: The expressing patterns of dysferlin were analyzed by immunohistochemistry, with a set of antibodies against dystrophin, alpha-sarcoglycan and dysferlin, in the biopsied muscle specimens from 45 patients with LGMD or MM diagnosed on the basis of clinical manifestations and muscle pathological features. The specimens with abnormal dysferlin expression shown by IHC were further analyzed with Western blotting for a quantitative evaluation. RESULTS: Eight patients were proved to be primary dysferlinopathy according to total dysferlin deficiency or a significant decrease of dysferlin (less than 15% that of normal value). The clinical manifestations of 5 of the 8 dysferlinopathy patients were consistent with those of typical MM, and the other 3 were diagnosed as with LGMD. All patients had an average onset at the age of 18.8 years. Two of them had family history, and one patient had consanguineous mating parents, meaning an autosomal recessive inheritance pattern. The serum CK levels were 6240 IU/L on average. EMG showed myogenic patterns in all patients. Muscular pathology showed typical changes of muscular dystrophy in all patients. Focal or scattered inflammatory cellular infiltrations were found in 3 cases. CONCLUSION: The clinical and pathological features of dysferlinopathy are nonspecific. Inflammatory cellular infiltrations are relatively common in biopsied muscles of dysferlinopathy patients, which may cause misdiagnosis of inflammatory myopathy. Identification of dysferlin expression by IHC and Western blotting are essential for the diagnosis of dysferlinopathy and differential diagnosis of inflammatory myopathy.