Introduction: Alopecia areata (AA) is an autoimmune hair loss mediated by CD8 + T cells. Treatment for moderate-to-severe AA is still challenging. Janus kinase inhibitors, such as tofacitinib, have been recently investigated as a promising treatment option for AA. Evidence on the combination use of oral tofacitinib and systemic corticosteroids (SCs) for AA is still lacking.Objective: To compare the efficacy and safety of monotherapy of oral tofacitinib and SCs, as well as their combination in patients with moderate-to-severe AA.Methods: Patients with moderate-to-severe AA, who have been treated with at least 3 months of monotherapy of tofacitinib or SCs, or in their combination, were included in this study. The efficacy and adverse events of these treatments were retrospectively analyzed.Results: Sixty-one patients with moderate-to-severe AA were included in this study. There were 12 (66.7%) of 18 patients in the SCs group, 12 (60.0%) of 20 patients in the tofacitinib group, and 18 (78.3%) of 23 patients achieved SALT₅₀, with no significant difference among the three groups. The ratio of patients who achieved SALT₅₀ was significantly higher in patients with a short duration of current hair loss episode (≤2 years) than in those with a duration of current hair loss episode (>2 years) in all the three groups. There were 66.7% patients in the SCs group, 35.0% patients in the tofacitinib group, and 56.5% patients in the combined group that showed adverse effects.Conclusion: Tofacitinib was an effective treatment for patients with moderate-to-severe AA, and it was more tolerated than SCs. A combination of tofacitinib and SCs may have higher efficacy than SCs alone. Efficacy significantly decreased in patients with a current episode of disease for more than 2 years.

Parkinson's disease (PD) patients exhibit an imbalance between neuronal activity and perfusion, referred to as abnormal neurovascular coupling (NVC). Nevertheless, the underlying molecular mechanism and how levodopa, the standard treatment in PD, regulates NVC is largely unknown. A total of 52 drug-naïve PD patients and 49 normal controls (NCs) were enrolled. NVC was characterized in vivo by relating cerebral blood flow (CBF) and amplitude of low-frequency fluctuations (ALFF). Motor assessments and MRI scanning were conducted on drug-naïve patients before and after levodopa therapy (OFF/ON state). Regional NVC differences between patients and NCs were identified, followed by an assessment of the associated receptors/transporters. The influence of levodopa on NVC, CBF, and ALFF within these abnormal regions was analyzed. Compared to NCs, OFF-state patients showed NVC dysfunction in significantly lower NVC in left precentral, postcentral, superior parietal cortex, and precuneus, along with higher NVC in left anterior cingulate cortex, right olfactory cortex, thalamus, caudate, and putamen (P-value <0.0006). The distribution of NVC differences correlated with the density of dopaminergic, serotonin, MU-opioid, and cholinergic receptors/transporters. Additionally, levodopa ameliorated abnormal NVC in most of these regions, where there were primarily ALFF changes with limited CBF modifications. Patients exhibited NVC dysfunction primarily in the striato-thalamo-cortical circuit and motor control regions, which could be driven by dopaminergic and nondopaminergic systems, and levodopa therapy mainly restored abnormal NVC by modulating neuronal activity.

Rapid eye movement (REM) sleep behavior disorder (RBD) could develop preceding or come after motor symptoms during Parkinson's disease (PD). It remains unknown that whether PD with different timing of RBD onset relative to motor symptoms suggests different spatiotemporal sequence of neurodegeneration. This study aimed to explore the sequence of disease progression in crucially involved brain regions in PD with different timing of RBD onset. We recruited 157 PD, 16 isolated RBD (iRBD), and 78 healthy controls. PD patients were identified as (1) PD with RBD preceding motor symptoms (PD-preRBD, n = 50), (2) PD with RBD posterior to motor symptoms (PD-postRBD, n = 31), (3) PD without RBD (PD-nonRBD, n = 75). The volumes of crucial brain regions, including the basal ganglia and limbic structures in T1-weighted imaging, and the contrast-noise-ratios of locus coeruleus (LC) and substantia nigra (SN) in neuromelanin-sensitive magnetic resonance imaging, were extracted. To simulate the sequence of disease progression for cross-sectional data, an event-based model was introduced to estimate the maximum likelihood sequence of regions' involvement for each group. Then, a statistical parameter, the Bhattacharya coefficient (BC), was used to evaluate the similarity of the sequence. The model predicted that SN occupied the highest likelihood in the maximum likelihood sequence of disease progression in the all PD subgroups, while LC was specifically positioned earlier to SN in iRBD, a prodromal phase of PD. Subsequent early involvement of LC was observed in the both PD-preRBD and PD-postRBD. In contrast, atrophy in the para-hippocampal gyrus but relatively intact LC in the early stage was demonstrated in PD-nonRBD. Then, the similarity comparisons indicated higher BC between PD-postRBD and PD-preRBD (BC = 0.76) but lower BC between PD-postRBD and PD-nonRBD group (BC = 0.41). iRBD had higher BC against PD-preRBD (BC = 0.66) and PD-postRBD (BC = 0.63) but lower BC against PD- nonRBD (BC = 0.48). The spatiotemporal sequence of neurodegeneration between PD-pre and PD-post were similar but distinct from PD-nonRBD. The presence of RBD may be the essential factor for differentiating the degeneration patterns of PD, but the timing of RBD onset has currently proved to be not.

Background: Monilethrix is a rare hereditary hair loss disorder characterized by hair fragility and beaded hair shaft alterations. Monilethrix is classically inherited in an autosomal dominant (AD) fashion caused by variants in the hair keratin genes KRT81, KRT83, or KRT86. Interestingly, an autosomal recessive (AR) form of monilethrix with variants in DSG4 gene has also been reported in recent years.Objective: To identify causative variants in Chinese patients with autosomal recessive (AR) form of monilethrix.Methods: Three families with AR form of monilethrix were observed and sequence variant analysis of DSG4 was performed by polymerase chain reaction (PCR), quantitative real‐time PCR, and DNA sequencing.Results: All the patients had sparse, fragile hair involving the scalp, eyebrows, and eyelashes with keratotic follicular papules and pruritus since birth. Atypical‐beaded hairs and broken hair shaft fragments were identified in all the patients under dermoscopy. Heterozygous variants c.837del and c. 2389C > T, a homozygous splice site variant c.2355 + 1G > A, and a homozygous 48,644 bp large deletion variant g.31381440_31430084del in the DSG4 gene were identified and verified in the families.Conclusion: This report provided further evidence for the phenotypic spectrum and clinical features of, and the expanded variant database of AR form of monilethrix.

Purpose: The aim of this study is to establish a refined wash test (RWT) and explore the characteristics of daily shedding hair parameters in normal individuals and patients with androgenetic alopecia (AGA) or telogen effluvium (TE). Materials and Methods: Chinese subjects diagnosed as normal, AGA or TE were enrolled. For the RWT procedure, the subjects were asked to pre-wash their hair 24 hours before the first collection, then to wash and rinse their hair with flowing water above a sink covered with a piece of filtering cloth. All hairs entrapped in the filtering cloth were air dried and collected. This “wash-and-collect” process was repeated for 3 consecutive days with a 24 ± 2 hour interval. Collected hairs were counted manually, and hair diameter was measured by videodermoscope. Number and diameter of daily shedding hairs and percentage of vellus and terminal hairs were analyzed. Results: A total of 176 subjects participated in and completed the study. Shedding hair number during daily shampooing was 27.9 ± 12.2, 52.2 ± 28.5 and 125.5 ± 62.7 hairs in normal, AGA and TE participants, respectively, and the differences between each two of the three groups were all statistically significant. Diameter of shedding hairs was 76.9 ± 9.0 μm, 60.0 ± 9.5 μm and 82.7 ± 9.2 μm in normal, AGA and TE, respectively. Along with advancement of AGA severity, shedding hair number was generally increased, while hair diameter decreased. The percentage of vellus hairs in AGA was significantly higher than in the normal and TE groups (8.3 ± 6.6% vs 1.0 ± 1.6% and 1.0 ± 1.0%). The combination of shedding hair number and percentage of vellus hairs had a high diagnostic confidence (AUC = 0.957) to diagnose AGA from normal. Shedding hair number alone showed high confidence to diagnose TE from normal (AUC = 0.999). Conclusion: The non-invasive, easy-to-use RWT established in this study is a valuable tool to evaluate daily shedding hairs, which may be useful in diagnosis, dynamic monitoring of disease progression and treatment efficacy.