Clinical, pathological and genetic characteristics of 8 patients with distal hereditary motor neuropathy / 北京大学学报(医学版)

OBJECTIVE@#Distal hereditary motor neuropathy (dHMN) comprises a heterogeneous group of inherited disorders associated with neurodegeneration of motor nerves and neurons, mainly charac-terized by progressive atrophy and weakness of distal muscle without clinical or electrophysiological sensory abnormalities. To improve the recognition and diagnosis of the disease, we summarized the clinical manifestations, electrophysiological, pathological, and genetic characteristics in eight patients with dHMN.@*METHODS@#Eight probands from different families diagnosed with dHMN were recruited in this study between June 2018 and April 2019 at Peking University People's Hospital. Eight patients underwent complete neurological examination and standard electrophysiological examinations. The clinical criteria were consistent with the patients presenting with a pure motor neuropathy with no sensory changes on electrophysiology. The detailed clinical symptoms, neurophysiological examinations, pathological features and gene mutations were analyzed retrospectively. Genetic testing was performed on the eight patients using targeted next-generation sequencing panel for inherited neuromuscular disorder and was combined with segregation analysis.@*RESULTS@#The age of onset ranged between 11 and 64 years (median 39.5 years) in our dHMN patients. All the cases showed a slowly progressive disease course, mainly characterized by distal limb muscle weakness and atrophy. The motor nerve conduction revealed decreased compound muscle action potential amplitude and velocity, while the sensory nerve conduction velocities and action potentials were not affected. Needle electromyography indicated neurogenic chronic denervation in all patients. Muscle biopsy performed in two patients demonstrated neurogenic skeletal muscle damage. Sural nerve biopsy was performed in one patient, Semithin sections shows relatively normal density and structure of large myelinated fibers, except very few fibers with thin myelin sheaths, which suggested very mild sensory nerve involvement. Eight different genes known to be associated with dHMN were identified in the patients by next-generation sequencing, pathogenic dHMN mutations were identified in three genes, and the detection rate of confirmed genetic diagnosis of dHMN was 37.5% (3/8). Whereas five variants of uncertain significance (VUS) were identified, among which two novel variants co-segregated the phenotype.@*CONCLUSION@#dHMN is a group of inherited peripheral neuropathies with great clinical and genetic heterogeneity. Next-generation sequencing is widely used to discover pathogenic genes in patients with dHMN, but more than half of the patients still remain genetically unknown.

Study on clinical efficacy and mechanism of Qingying Tang for treating psoriatic blood-heat syndrome based on IL-23/Th17 / 中国中药杂志

To observe the clinical curative effect of Qingying Tang in the treatment of psoriatic blood-heat syndrome and explore its intrinsic mechanism.In this study,we collected 72 patients with blood-heat syndrome psoriasis admitted to our dermatology clinic from January 2016 to December 2017 and divided into control group and observation group according to the random number table method,36 cases in each group.The patients in control group were given with Acitretin Capsules orally,10 mg/time,twice a day.The patients in observation group were given with Qingying Tang orally,150 mL/time,twice a day.The treatment period was 12 weeks in both groups.The traditional Chinese medicine(TCM) syndrome scores before and after treatment,psoriasis area and severity index(PASI) score,dermatology life quality index(DLQI) score,and the clinical efficacy of the two groups were compared between the two groups;flow cytometry was used to detect peripheral blood Th17 cell percentages before and after treatment in both groups;serum interleukin(IL)-17,IL-23,IL-22,and IL-21 levels in both groups before and after treatment were measured by ELISA;the expression levels of STAT3 and RORγt before and after treatment in patients were measured by using skin lesion immunohistochemical method.The results showed that the TCM symptoms were improved significantly in both groups(P<0.05),and the effect in observation group was significantly better than that in the control group(P<0.05).PASI and DLQI scores were decreased significantly after treatment in both groups(P<0.05),and the scores in observation group were significantly lower than those in the control group(P<0.05).The curative effect of the observation group was significantly higher than that of the control group(P<0.05).After treatment,the percentage of Th17 cells,as well as IL-17,IL-23,IL-22 and IL-21 levels in peripheral blood were significantly decreased in both groups(P<0.05),and the levels in observation group were significantly lower than those in the control group(P<0.05).The expression levels of STAT3 and RORγt in both groups were significantly lower than those before treatment(P<0.01),and the levels in observation group were significantly lower than those in the control group(P<0.05).All of the results indicted that Qingying Tang can effectively improve the skin lesions and TCM syndrome in patients with psoriasis and blood-heat syndrome,and improve patient health quality,which may be related to regulation of peripheral blood IL-23/Th17.