ObjectiveThis paper aims to investigate the intervention effect and molecular mechanism of Gancao Fuzitang （GCFZT） in knee osteoarthritis （KOA）. MethodsNetwork pharmacology was employed to predict the key targets and signaling pathways of GCFZT. Fifty SD rats were randomly divided into a sham group， a model group （KOA）， a low-dose GCFZT group （GCFZT-L， 2.8 g·kg^-1）， a high-dose GCFZT group （GCFZT-H， 5.6 g·kg^-1）， and a positive drug celecoxib group （Celecoxib， 20 mg·kg^-1）， with 10 rats in each group. The rats in the sham group and the model group were given an equal volume of distilled water. Except for the sham group， the other four groups underwent anterior cruciate ligament transection to establish the KOA rat model. After successful modeling， the rats in each group received intragastric administration once a day for eight consecutive weeks. The structural changes of cartilage and subchondral bone were assessed via micro-computed tomography （micro-CT） and histological staining. The levels of inflammatory factors in the serum， such as interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α （TNF-α） were measured using an enzyme linked immunosorbent assay （ELISA） kit. Real-time quantitative polymerase chain reaction （Real-time PCR）， Western blot， and immunohistochemistry were used to detect changes in the expression of autophagy-related proteins such as microtubule-associated protein 1 light chain 3B （LC3B）， selective autophagy junction protein 62 （p62）， and autophagy key molecule yeast Atg6 homolog （Beclin-1） in articular cartilage， as well as key molecules of the phosphatidylinositol 3 kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. ResultsNetwork pharmacology analysis suggests that GCFZT may exert anti-osteoarthritic effects through regulating the PI3K/Akt/mTOR pathway. In vivo experiment shows that GCFZT can significantly improve cartilage degeneration and attenuate subchondral bone destruction in KOA rats. Detection results of inflammatory factors in the serum reveal that， compared with those in the sham group， the levels of IL-6， IL-1β， and TNF-α in the serum of rats in the KOA group are significantly increased （P<0.05）. Compared with those in the KOA group， the levels of these three inflammatory factors in the GCFZT-L， GCFZT-H， and Celecoxib groups were significantly decreased （P<0.05）. However， there was no statistically significant difference in these three inflammatory factor levels between the GCFZT-H group and the celecoxib group. These findings suggest that GCFZT can effectively inhibit the systemic inflammatory response in KOA rats. Mechanism research indicates that GCFZT inhibits activation of the PI3K/Akt/mTOR pathway， thereby enhancing autophagic activity and improving chondrocyte function and matrix degeneration. ConclusionGCFZT improves cartilage and subchondral bone damage in KOA rats by inhibiting the PI3K/Akt/mTOR signaling pathway and promoting autophagy. These findings provide theoretical evidence for the application of GCFZT in the prevention and treatment of osteoarthritis.

Objective:To analyze the clinical characteristics and prognosis of primary autoimmune cerebellar ataxia (PACA) patients with autoantibodies.Methods:Patients from the Department of Neurology, Peking Union Medical College Hospital (from March 2013 to December 2023) who met the modified diagnostic criteria of PACA were collected. Cell based assay and tissue based assay were used to detect anti-cerebellar antibodies. The clinical features, results of neuroimaging, cerebrospinal fluid examinations and the prognosis of the patients were analyzed. Modified Rankin Scale (mRS) score≤2 at the last follow-up was defined as a favorable prognosis. Exacerbation of cerebellar ataxia after clinical improvement or stabilization for at least 2 months was defined as relapse.Results:A total of 20 patients were included, including 7 males. The onset age was 48.4 (22.8, 59.3) years. Gait ataxia was the most common cerebellar symptom. Extracerebellar neurological abnormalities included pyramidal sign, peripheral neuropathy/radiculopathy and diplopia. Elevated cerebrospinal fluid white blood cells and positive specific oligoclonal bands were observed in 4/16 and 7/15 of patients, respectively. The brain magnetic resonance imaging examination of the patients showed that 8 patients had no obvious abnormalities, 9 patients showed cerebellar atrophy, and 3 patients showed abnormal signals in the brain or cerebellum. A total of 9 different anti-cerebellar antibodies were detected in the patient′s serum and (or) cerebrospinal fluid, with the most common being anti-Homer-3 antibodies ( n=7). After immunotherapy, 13/17 of patients improved. After 37.5 (21.0, 93.0) months of follow-up, the median mRS score of the patients was 3, and 8 patients (8/20) achieved good prognosis and 6 patients experienced disease recurrence. Conclusions:The clinical manifestations of PACA patients have certain heterogeneity, and positive anti-neuroantibodies and meeting PACA diagnostic criteria are the main basis for diagnosing the disease. Immunotherapy is effective for most patients, but there is still a considerable proportion of patients who have not achieved a good long-term functional prognosis.

Objective:To explore the relationship between the dynamic alterations of immune cell subsets in a patient with autoimmune encephalitis and the clinical relapses.Methods:For a patient with multiple relapses of anti-N-methyl-D-aspartate receptor encephalitis superimposed with myelin oligodendrocyte glycoprotein antibody-associated disease who visited Peking Union Medical College Hospital on July 18, 2018, the lymphocyte subsets were monitored dynamically over a long period and the relationship between lymphocyte subsets and the relapses was summarized.Results:The 38-year old male patient experienced a total of 5 episodes (including 4 relapses) during the six-year immunotherapy and follow-up process, and responded well to first-line and maintenance immunotherapy. His relapses occurred during drug reduction. Finally, the neurological symptoms resolved after rituximab treatment. A total of 39 tests of peripheral blood lymphocyte subsets were conducted during the follow-up, and 5 peaks of elevated CD19 positive B cells, 9 peaks of elevated CD3 positive T cells and 11 peaks of elevated natural killer cells were observed. The peak period of peripheral blood CD19 positive B cells exactly coincided with clinical relapses. While the consistency rates of clinical relapse and the peaks of peripheral blood CD3 positive T cells and natural killer cells were 5/9 and 2/11, respectively.Conclusions:The dynamic alterations of CD19 positive B cells in peripheral blood are correlated with the clinical relapse of autoimmune encephalitis and can predict clinical relapse.

Objective:To analyze the clinical characteristics and prognosis of primary autoimmune cerebellar ataxia (PACA) patients with autoantibodies.Methods:Patients from the Department of Neurology, Peking Union Medical College Hospital (from March 2013 to December 2023) who met the modified diagnostic criteria of PACA were collected. Cell based assay and tissue based assay were used to detect anti-cerebellar antibodies. The clinical features, results of neuroimaging, cerebrospinal fluid examinations and the prognosis of the patients were analyzed. Modified Rankin Scale (mRS) score≤2 at the last follow-up was defined as a favorable prognosis. Exacerbation of cerebellar ataxia after clinical improvement or stabilization for at least 2 months was defined as relapse.Results:A total of 20 patients were included, including 7 males. The onset age was 48.4 (22.8, 59.3) years. Gait ataxia was the most common cerebellar symptom. Extracerebellar neurological abnormalities included pyramidal sign, peripheral neuropathy/radiculopathy and diplopia. Elevated cerebrospinal fluid white blood cells and positive specific oligoclonal bands were observed in 4/16 and 7/15 of patients, respectively. The brain magnetic resonance imaging examination of the patients showed that 8 patients had no obvious abnormalities, 9 patients showed cerebellar atrophy, and 3 patients showed abnormal signals in the brain or cerebellum. A total of 9 different anti-cerebellar antibodies were detected in the patient′s serum and (or) cerebrospinal fluid, with the most common being anti-Homer-3 antibodies ( n=7). After immunotherapy, 13/17 of patients improved. After 37.5 (21.0, 93.0) months of follow-up, the median mRS score of the patients was 3, and 8 patients (8/20) achieved good prognosis and 6 patients experienced disease recurrence. Conclusions:The clinical manifestations of PACA patients have certain heterogeneity, and positive anti-neuroantibodies and meeting PACA diagnostic criteria are the main basis for diagnosing the disease. Immunotherapy is effective for most patients, but there is still a considerable proportion of patients who have not achieved a good long-term functional prognosis.

Objective:To explore the relationship between the dynamic alterations of immune cell subsets in a patient with autoimmune encephalitis and the clinical relapses.Methods:For a patient with multiple relapses of anti-N-methyl-D-aspartate receptor encephalitis superimposed with myelin oligodendrocyte glycoprotein antibody-associated disease who visited Peking Union Medical College Hospital on July 18, 2018, the lymphocyte subsets were monitored dynamically over a long period and the relationship between lymphocyte subsets and the relapses was summarized.Results:The 38-year old male patient experienced a total of 5 episodes (including 4 relapses) during the six-year immunotherapy and follow-up process, and responded well to first-line and maintenance immunotherapy. His relapses occurred during drug reduction. Finally, the neurological symptoms resolved after rituximab treatment. A total of 39 tests of peripheral blood lymphocyte subsets were conducted during the follow-up, and 5 peaks of elevated CD19 positive B cells, 9 peaks of elevated CD3 positive T cells and 11 peaks of elevated natural killer cells were observed. The peak period of peripheral blood CD19 positive B cells exactly coincided with clinical relapses. While the consistency rates of clinical relapse and the peaks of peripheral blood CD3 positive T cells and natural killer cells were 5/9 and 2/11, respectively.Conclusions:The dynamic alterations of CD19 positive B cells in peripheral blood are correlated with the clinical relapse of autoimmune encephalitis and can predict clinical relapse.

Objective:To analyze the correlation between peripheral blood lymphocyte subsets, especially B cells, and the relapse of autoimmune encephalitis (AE).Methods:A retrospective analysis was conducted on patients with AE who were diagnosed and treated in Peking Union Medical College Hospital from January 2012 to January 2023. The clinical data including gender, age and changes in related indicators of CD19 +B cells, CD16/56 +NK cells, CD3 +T cells, CD4 +T cells, CD8 +T cells, IgG, IgA, and IgM before and after recurrence were analyzed.Binary Logistic regression analysis was applied to the study of correlation between AE recurrence and gender, age, CD19 +B cells, CD16/56 +NK cells, CD3 +T cells, CD4 +T cells, CD8 +T cells, IgG, IgA and IgM. The receiver operating characteristic (ROC) curves of the cells that affect AE recurrence (CD19 +B cells, CD16/56 +NK cells, CD3 +T cells, CD4 +T cells and CD8 +T cells) were plotted separately. Results:A total of 198 eligible AE patients were included, including 98 males and 100 females, aged (39.52±17.91) years. Among these patients, 78 cases had relapses, with a recurrence rate of 39.4%. The results of Logistic regression analysis showed that CD19 +B cells ( B=0.006, P<0.001), CD16/56 +NK cells ( B=0.004, P<0.05), CD3 +T cells ( B=-0.011, P<0.05), CD4 +T cells ( B=0.014, P<0.05) and CD8 +T cells ( B=0.010, P<0.05) were highly correlated with the relapse of AE. ROC curve analysis showed that CD19 +B cells (area under the curve: 0.833, P<0.001, critical value: 73.5/μl; sensitivity: 69.2%, specificity: 86.7%), CD3 +T cells (area under the curve: 0.784, P<0.001), CD4 +T cells (area under the curve: 0.808, P<0.001), and CD8 +T cells (area under the curve: 0.742, P<0.001) all had a certain predictive value for AE relapse. Among all the indicators, the area under the curve of CD19 +B cells was the largest, which had a higher value in predicting AE recurrence. Conclusion:The increase in peripheral blood CD19 +B cells has high predictive value for the relapse of AE.

Cerebellar ataxia mediated by autoimmune mechanisms is a common cause of sporadic cerebellar ataxia. According to the presence of underlining malignancy, autoimmune cerebellar ataxia (ACA) can be divided into paraneoplastic ACA and non-paraneoplastic ACA. The typical manifestations of various types of ACA include gait disorder, limb and trunk ataxia, mild inflammatory response and specific oligoclonal bands in cerebrospinal fluid. Immunosuppressive therapy might be effective. Anti-neuronal antibodies are of great significance to the diagnosis of ACA, and the discovery of the new antibody profile has promoted a deeper understanding of ACA. This article reviews the clinical features and progress of diagnosis and treatment of ACA.

Objective:To analyze and summarize the clinical characteristics of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis patients with cerebellar ataxia.Methods:The clinical manifestations, laboratory examinations, treatment and prognosis of anti-NMDAR encephalitis patients with cerebellar ataxia diagnosed and treated in Peking Union Medical College Hospital from 2011 to 2019 were retrospectively analyzed.Results:About 4.3% (15 cases) of a total of 347 anti-NMDAR encephalitis patients were complicated with cerebellar ataxia, of which one patient had ovarian teratoma. There were seven male cases and eight female cases, with a median age of 28 years. The average duration from the onset of encephalitis to the onset of cerebellar symptoms was 30.8 days.The average modified Rankin Scale (mRS) score was 3.73. In the acute phase, the median cerebrospinal fluid leukocyte count was 28×10 6/L. All patients received first-line immunotherapy, of which one case additionally received second-line immunotherapy with rituximab and nine patients received long-term immunotherapy with mycophenolate mofetil. The follow-up time ranged from seven to 66 months. The average mRS score of the last time was 2.73, and only six patients (6/15) had good prognosis (mRS score≤2). Conclusions:Patients with anti-NMDAR encephalitis and cerebellar ataxia are rare, and have relatively poor prognosis in terms of neurological function. Symptoms of cerebellar ataxia in anti-NMDAR encephalitis patients should be recognized in time, and standardized immunotherapy regimens and long-term immunotherapy should be adopted to improve the prognosis.