[Clinical characteristics and prognosis of patients with anti-glutamic acid decarboxylase antibody-related cerebellar ataxia].

The clinical data, diagnosis, treatment, and prognosis of 10 patients with anti-glutamic acid decarboxylase (GAD) antibody-related cerebellar ataxia in Department of Neurology, Peking Union Medical College Hospital, from May 2015 to November 2021 were retrospectively analyzed. There were 8 female patients with a median age of 55 years old. Patients mainly presented with gait ataxia (10/10), dizziness (8/10), diplopia (6/10), and dysarthria (5/10). Four of them were complicated with other autoimmune disease, including vitiligo (3/4), Hashimoto thyroiditis (1/4), thrombocytopenia (1/4), and small cell lung cancer (1/4). All patients received immunotherapy, 6 out of 10 exhibited a good response, and half of them had satisfied functional prognosis. Patients of anti-GAD antibody-related cerebellar ataxia may be complicated with other autoimmune diseases, but underlying tumor is rare. More than half of patients have a good response to immunotherapy and satisfied prognosis.

[Clinical, pathological and genetic characteristics of 8 patients with distal hereditary motor neuropathy].

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 correlation between PKIB and pAkt expression in breast cancer tissues.

OBJECTIVE: This study is to explore the expression of cyclic AMP (cAMP) dependent protein kinase inhibitor (PKIB) in human breast cancer and the correlation with phosphorylated protein kinase B (pAkt) expression in the tumor tissues. MATERIALS AND METHODS: Surgical removal of the tissue samples from 148 patients with primary breast cancer from 2011-2015 were selected, and then we detected the PKIB, estrogen receptor (ER), progesterone receptor (PR) and proto oncogene (HER2) by using immunohistochemical technique and the Allred score classification standard. The clinical pathological factors such as tumor diameter, lymph node metastasis and tumor stage, etc. were analyzed statistically. Then we detected that the PKIB and pAkt respectively of immunohistochemical expression and cellular localization of four subtypes in patients which were luminal A, luminal B, HER2+/ER-type and triple negative breast cancer type. RESULTS: Immunohistochemistry staining showed when pAkt was positive and there were significant correlations with the expression of PKIB (p<0.05). Both positive staining reactions occurred in the cytoplasm of the tumor. Histopathological type, tumor diameter, lymph node metastasis, tumor stage and other clinical pathological factors were not significantly associated with the expression of PKIB. In addition, the expression of PKIB was also significantly associated with the triple negative breast cancer in the four subtypes (p<0.05). CONCLUSIONS: The expression of PKIB in the cytoplasm of tumor is closely related to pAkt and the triple negative breast cancer. It was concluded that the PKIB promoted the occurrence and development of breast tumors by regulating the Akt signaling pathway. PKIB will be a potential therapeutic target for breast cancer, especially in the diagnosis and treatment of triple negative breast cancer.

Mechanism of action of EBV, Bcl-2, p53, c-Myc and Rb in non-Hodgkin's lymphoma.

OBJECTIVE: The aim of the present study is to explore the mechanism of action of several proteins, including Epstein-Barr virus (EBV), B-cell lymphoma (Bcl)-2, p53, c-Myc and retinoblastoma (Rb), in Non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Between July 2010 and July 2015, samples of 142 patients with pathologically confirmed NHL which presented at our institution were included in the observation group. In addition, samples from 55 patients with hyperplastic lymphadenitis presented during the same period were enrolled as control group. The expressions of EBV (+), p53(+), Bcl-2(+), Rb(-) and c-Myc(+) were determined and compared PATIENTS AND METHODS: Between July 2010 and July 2015, samples of 142 patients with pathologically confirmed NHL which presented at our institution were included in the observation group. In addition, samples from 55 patients with hyperplastic lymphadenitis presented during the same period were enrolled as control group. The expressions of EBV (+), p53(+), Bcl-2(+), Rb(-) and c-Myc(+) were determined and compared among different subtypes and stages of NHLs of observation group. Besides, the correlation of EBV with p53, Bcl-2, Rb and c-Myc were investigated in NHLs of observation group. RESULTS: In the observation group, the expression rates of EBV(+), p53(+), Bcl-2(+), Rb(-), and c-Myc(+) were significantly higher than those, respectively, in the control group (p < 0.05). No significant correlation was observed between EBV expression and the expressions of p53, Bcl-2, Rb and c-Myc in the observation group (p > 0.05). The expression rates of p53(+) and Bcl-2(+) were significantly higher in aggressive and highly-aggressive NHLs than in indolent NHLs of the observation group (p < 0.05). The expressions of EBV(+), p53(+), Bcl-2(+), Rb(-), and c-Myc(+) were significantly higher in stage III-IV NHLs than in stage I-II NHLs (p < 0.05). CONCLUSIONS: The expressions of EBV(+), p53(+), Bcl-2(+), Rb(-), and c-Myc(+) are closely associated with NHL pathogenesis. Expressions of these proteins are higher in later stages of NHLs, and expressions of p53(+) and Bcl-2(+) are higher in more aggressive NHLs.