[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.

[Establishment of a predictive model for acute respiratory distress syndrome and analysis of its predictive value in critical burn patients].

Objective: To establish a predictive model for acute respiratory distress syndrome (ARDS) in critical burn patients with the screened independent risk factors, and to validate its predictive value. Methods: Totally 131 critical burn patients (101 males and 30 females, aged 18-84 years) who met the inclusion criteria were admitted to the Department of Burns of the Second Affiliated Hospital of Zhejiang University School of Medicine from January 2018 to December 2019. A retrospective case-control study was conducted. The patients were divided into ARDS group (54 cases) and non-ARDS group (77 cases) according to whether ARDS occurred or not. The statistics of patients in the two groups were recorded including the gender, age, burn index, combination of inhalation injury, smoking history, delayed resuscitation, indwelling nasogastric tube, and complication of sepsis, and the data were statistically analyzed with independent sample t test, chi-square test, and Fisher's exact probability test. The multivariate logistic regression analysis was performed on the indicators with statistically significant differences between the two groups to screen the independent risk factors for developing ARDS in critical burn patients, and the corresponding nomograph prediction model for the risk of ARDS in critical burn patients was established. The risk scores for patients developing ARDS were therefore obtained based on the above-mentioned nomograph, and the corresponding receiver operating characteristic (ROC) curve was drawn to calculate the area under the curve. The internal validation of the above-mentioned ARDS prediction model was performed using the Bootstrap method, and the area under the ROC curve was calculated for modeling group (79 cases) and validation group (52 cases), respectively. A calibration curve was drawn to assess the predictive conformity of the above-mentioned ARDS prediction model for the occurrence of ARDS in critical burn patients. Results: The burn index, proportion of combination of inhalation injury, and proportion of complication of sepsis of patients were significantly higher in ARDS group than in non-ARDS group (t=0.36, χ2=33.78, 49.92, P<0.01). The gender, age, smoking history, delayed resuscitation, and indwelling nasogastric tube of patients in ARDS group were close to those in non-ARDS group (P>0.05). The multivariate logistic regression analysis showed that the burn index, combination of inhalation injury, and complication of sepsis were the independent risk factors for developing ARDS in critical burn patients (odds ratio=1.05, 15.33, 5.02, 95% confidence interval=1.01-1.10, 2.65-88.42, 1.28-19.71, P<0.05 or P<0.01). The overall area under the ROC curve of the above-mentioned ARDS prediction model was 0.92 (95% confidence interval=0.88-0.97), and the area under the ROC curve was 0.95 and 0.91 (95% confidence interval=0.90-1.00, 0.86-0.97) for validation group and modeling group, respectively. When applying the above-mentioned ARDS prediction model for ARDS incidence prediction, there might be some risk of overestimating ARDS incidence when the prediction probability was <35.0% or >85.0%, and some risk of underestimating ARDS incidence when the prediction probability was 35.0%-85.0%. Conclusions: The burn index, inhalation injury, and sepsis are the independent risk factors for the occurrence of ARDS in critical burn patients. The risk prediction model for ARDS based on these three indicators has good predictive ability for ARDS in critical burn patients.

[Pediatric autoimmune encephalitis associated with anti-glutamic acid decarboxylase 65 antibody: two cases report and literature review].

Objective: To investigate the clinical features and prognosis of pediatric autoimmune encephalitis associated with anti-glutamic acid decarboxylase 65 (GAD65) antibody. Methods: Clinical data of 2 patients diagnosed as autoimmune encephalitis associated with anti-GAD65 antibody at Department of Neurology, Beijing Children's Hospital in 2019 were analyzed retrospectively. A literature search with "anti-GAD65 antibody""encephalitis""epilepsy" or "cerebellar ataxia" as key words was conducted at China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform and PubMed (up to January 2020). The clinical features and prognosis of pediatric cases with complete clinical data were retrieved and summarized. Results: Two patients with positive anti-GAD65 antibody of serum and cerebrospinal fluid were both females. The onset age of case 1 was 57 months and her main clinical manifestations were fever and unconsciousness. The cranial magnetic resonance imaging (MRI) showed diffuse T2 weighted imaging (T2WI) abnormal signals, and the electroencephalogram (EEG) showed slow waves. The onset age of case 2 was 80 months and her main clinical manifestations of were recurrent focal seizures, memory loss, and headache. The MRI showed high T2WI signal in bilateral hippocampus, and the EEG showed abnormal discharge involving the temporal area. Both cases were treated with methylprednisolone and intravenous immunoglobulin, the short-term symptoms of them were both improved. They were followed up for 6 months and 1 year respectively, the case 1 recovered completely, and the case 2 still had focal seizures. Six English reports which included 6 cases were retrieved. Together with these 2 cases, a total of 8 cases were analyzed. The clinical symptoms included seizures (6 cases), memory loss (4 cases), loss of consciousness (3 cases), behavioral abnormalities (3 cases), cognitive impairment (2 cases), headache (2 cases), autonomic symptoms (1 case), ataxia (1 case), dysphagia (1 case), and aphasia (1 case). There were 5 cases with cranial MRI abnormalities in the acute phase or sub-acute phase, of whom 3 cases had the limbic system involvement, and 2 cases were mainly had extra limbic area involvement. Three cases had hippocampal atrophy or sclerosis during follow-up. All 8 patients were treated with immunotherapy. After immunotherapy, all patients had short-term improvement. Follow-up for 6 months to 6 years showed that 3 cases with extra limbic encephalitis improved to baseline levels, and 5 limbic encephalitis cases had poor outcomes, including 1 death and 4 cases still had focal epilepsy. Conclusions: Pediatric anti-GAD65 antibody associated autoimmune encephalitis is a rare but treatable disease, including limbic encephalitis and extra limbic encephalitis. The most common clinical manifestations are seizures and memory impairment. Early diagnosis and immunotherapy can improve the symptoms in a short time. But patients with limbic encephalitis often had refractory epilepsy in the chronic phase, and have a poor long-term outcome.

[Neuropsychiatric symptoms and caregivers' distress in anti-N-methyl-D-aspartate receptor encephalitis].

Objective: To explore the characteristics of psychiatric symptoms and caregivers' distress in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Methods: Seventy-two patients with anti-NMDAR encephalitis were investigated in Peking Union Medical College Hospital from 2011 to 2018. The Chinese version of the Neuropsychiatric Inventory-Questionnaire (NPI-Q) was used to assess the severity of neuropsychiatric symptoms and caregivers' distress around the treatment. Results: A highly positive correlation existed between severity scores of neuropsychiatric symptoms and caregiver distress, and pre- and post-treatment correlation coefficients was 0.872 and 0.947, respectively (all P<0.001). The frequency of 12 symptom domains was higher than 45% before treatment, however, it significantly reduced to below 45% after treatment. Irritability/lability, agitation/aggression were the most common neuropsychiatric symptoms. Irritability/lability, agitation/aggression, and nighttime behavioral disturbances occurred concurrently. Patients with severe symptoms tended to be administrated antipsychotics (Z=-2.581, P=0.01). Neuropsychiatric symptoms significantly improved after immunotherapy (Z=-6.611, P<0.001). There was no significant difference in the symptom severity and distress subscale scores between the first episode and relapse around the therapy (P>0.05). Conclusion: Patients with anti NMDAR encephalitis often present severe neuropsychiatric symptoms, which aggravate the burden on caregivers. Immunotherapy significantly improves neuropsychiatric symptoms, and thus reduces the distress of caregivers.

[Clinical observation on the overlapping syndrome of myelin oligodendrocyte glycoprotein antibody and anti-N-methyl-D aspartate receptor in children].

Objective: To investigate the clinical features, imaging findings and prognosis of children with overlapping syndrome of myelin oligodendrocyte glycoprotein (MOG) antibody disease and anti-N-methyl-D aspartate receptor (NMDAR) encephalitis (MNOS). Methods: The clinical manifestations, immunological antibodies in blood and cerebrospinal fluid, cranial image, treatment and follow-up of 11 patients diagnosed as MNOS in the Department of Neurology, Beijing Children's Hospital from January 2011 to April 2019 were analyzed retrospectively. Results: A total of 11 patients, including 4 males and 7 females were analyzed, the age of onset was (10.4±2.3) years. A total of 29 episodes occurred in 11 children. At the last follow-up, 8 cases showed relapsed remission course, the interval of recurrence was 3 to 60 months. The onset symptoms of 11 patients included convulsions (10 cases), lethargy (6 cases), psychosis (6 cases). Among 29 episodes, the common symptoms were convulsions (16 episodes), psychosis (13 episodes),and lethargy (10 episodes). According to the diagnostic criteria of anti-NMDAR encephalitis and MOG-antibody disease, 29 episodes were divided into three phenotypes, including anti-NMDAR encephalitis(4 episodes), MOG-antibody diseases (10 episodes) and overlapping types (15 episodes).Twenty-seven times of acute stage cranial magnetic resonance imaging (MRI) were available, common lesions included cortical focus (22 times), subcortical white matter (7 times), brainstem (9 times). All patients were sensitive to first-line immunotherapy. Eight patients had recurrence during glucocorticoid reduction, 6 of them were treated with additional second-line immunosuppressive therapy, including cyclophosphamide (1 case) and mycophenolate mofetil (5 cases). The follow-up time of patients were 5-99 months. At the last follow-up, all patients were in remission, the pediatric cerebral performance category (PCPC) score was 1 (10 cases) and 2 (1 cases). Conclusions: MNOS mainly affects older children. In the period of acute episodes, convulsions and psychosis are common. The cranial MRI showed extensive brain involvement and mainly in the cortex. The recurrence rates of MNOS are relatively high, patients are sensitive to first-line immunotherapy. No significant neurological dysfunction was left in the remission stage.

[Clinical featuers of adult patients with post-viral-encephalitis autoimmune encephalitis].

Objective: To explore the clinical features of post-viral-encephalitis autoimmune encephalitis (PVEAE). Methods: Ten cases of PVEAE, who were hospitalized in the Neurology Department of Peking Union Medical College Hospital (PUMCH) between November 2014 and October 2019, were retrospectively reviewed. Clinical manifestation, immunology, neuroradiology, treatment and outcomes were analyzed. Results: There were 5 males and 5 females, with a median age of 44 (18, 66) years. Of 9 cases, the median interval between the two onsets of encephalitis was 37 (24, 60) days, and there was no obvious interval in case 7. In viral encephalitis phase, the peak modified Rankin scale (mRS) was 4.5 (4.0, 5.0) and the remission mRS was 2.0 (1.0, 3.0). In autoimmune encephalitis (AE) phase, the peak mRS was 4.0 (3.0, 5.0). Symptoms of AE included mental and behavioral abnormalities (10/10), amnesia (10/10), motor disorders (5/10), autonomic dysfunction (5/10), speech disorders (4/10), seizures (2/10) and consciousness disturbance (2/10). On average, each case presented with 4 (2, 6) symptoms. In AE phase, the positive rate of anti-N-methyl-D-aspartate (anti-NMDA) receptor antibody in cerebrospinal fluid (CSF) was 80% (8/10), while in serum it was only 20% (2/10). Neuroimaging showed that in AE phase, the lesions expanded in 8 cases, remained unchanged in 1 case and shrank in 1 case. In AE phase, 10 cases received first line treatments, and 2 cases accepted long-course immunotherapy. After treatment, symptoms of 9 cases were obviously relieved. The mRS for short-term and long-term outcomes was 2.0 (1.0, 4.0) and 1.0 (0, 2.0), respectively. Conclusions: PVEAE might present with either typical biphasic course or monophasic/pseudo-monophasic course. In AE phase, anti-NMDA receptor antibody turned positive in most cases. Much importance should be attached to the recognition and diagnosis of PVEAE and treat it actively thereafter.

[Clinical approach and prognosis of continuous neurological care after intensive care for the patients with severe and refractory anti-N-methyl-D-aspartate receptor encephalitis].

Objective: To study the clinical features, continuous care and prognosis of the patients with severe and refractory anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis after intensive care unit (ICU). Methods: Clinical data of patients with severe and refractory anti-NMDAR encephalitis, who were transferred from ICU to general ward of neurology between December 2015 and October 2019, were retrospectively reviewed and analyzed in the study. Results: Twenty patients (11 females and 9 males) were enrolled in the study. The median course of disease when patients were transferred to general ward was 4.4 (2.0, 6.0) months. Six cases were alert, 6 cases were in a coma, 5 were in the early recovery phase and 3 were in the late recovery phase. Severe malnutrition, pneumonia, urinary tract infections, bedsores and leukocytopenia were common complications. Seven out of 18 patients were tested positive for cerebrospinal fluid anti-NMDAR antibodies with high titers (≥1∶100). During this continuous therapy stage,10 patients were treated with intravenous immunoglobulin (IVIg), 1 with methylprednisolone, 2 with rituximab, 1 with intrathecal methotrexate and 1 received intravenous cyclophosphamide. All Patients were prescribed a long-term immunotherapy (mycophenolate mofetil 1.5-3.0 g/d). Sixteen patients (80%) had good prognosis (modified Rankin Scale (mRS)≤2), and the mortality was 10%, with follow-up time of 17.0 (8.0, 27.0) months. Conclusions: Patients with anti-NMDAR encephalitis, who are transferred from ICU, have severely impaired neurologic function. These patients need long-term individualized immunotherapy and continuous neurological care. Good outcomes can be achieved in most patients.

[Anti-myelin-associated glycoprotein antibody positive IgM monoclonal gammopathy related peripheral neuropathy: 11 cases and literature review].

Objective: To improve the understanding of rare anti-myelin-associated glycoprotein (MAG) positive IgM monoclonal gammopathy related peripheral neuropathy (IgM-PN) . Methods: Eleven cases of IgM paraproteinemia and anti-MAG antibody positive neuropathy diagnosed since 2014 in Peking Medical Union College Hospital were summarized. The medical records including clinical manifestation, lab results, treatment and prognosis were analyzed. Results: Among the 11 patients (8 male and 3 female) , the median onset age is 63 years old (range from 52 to 77 years old) . The peripheral neuropathy of 9 patients were characterized by distal onset of numbness, 6 patients suffered from muscle weakness. The nerve conduction velocity study indicated that all 11 patients had demyelinating peripheral nerve damage, which was sensory predominant and more severe in lower limbs, 6 of them had secondary axonal damage. Monoclonal IgM gammopathy was identified in all 11 patients, among which 6 were IgM κ, 2 IgG κ and IgM κ bi-clonal, 3 IgM λ. Three patients were diagnosed with Waldenström's macroglobulinaemia. The anti-MAG-IgM antibody was positive in all 11 cases. After diagnosis, 9 patients received combination chemotherapy including rituximab or rituximab treatment alone. The monoclonal IgM level declined significantly in 7 patients. The neuropathy was stable or improved. Conclusions: Anti-MAG antibody positive IgM-PN is a rare M protein related disease. In peripheral neuropathy with undetermined etiology, we suggest to screen M protein and anti-MAG antibody. Chemotherapy including rituximab or rituximab alone is recommended as first-line therapy.

[Epidemiological investigation of burn patients with Klebsiella pneumoniae infection and the analysis of risk factors for sepsis in them].

Objective: To analyze the prevalence trend of Klebsiella pneumoniae (KP) infection in the Department of Burns of the Second Affiliated Hospital of Zhejiang University School of Medicine (hereinafter referred to as the author's department) from 2015 to 2017, and to screen out the independent risk factors for sepsis in burn patients with KP infection. Methods: The clinical and bacteriological data of burn patients with KP infection from January 1, 2015 to December 31, 2017 were collected from the author's department. The variation trend in infection rates of KP and carbapenems-resistant KP (CRKP) during the three years were statistically analyzed, and the data were processed with chi-square test. Clinical data were processed with binary logistic regression analysis to screen out the independent risk factors for sepsis in burn patients with KP infection. Results: (1) From 2015 to 2017, 91 patients (50 males and 41 females, aged 15-90 years) with KP infection were diagnosed in the author's department, of which 65 cases were CRKP positive, and 26 cases were carbapenems-sensitive KP positive. The KP infection rates of patients in 2015, 2016, and 2017 were 5.79% (35/605), 4.08% (23/564), and 5.54% (33/596), respectively. The CRKP infection rates of patients in 2015, 2016, and 2017 were 3.31% (20/605), 3.37% (19/564), and 4.36% (26/596), respectively. There were no statistically significant differences in KP infection rate and CRKP infection rate of patients among the three years (χ(2)=2.007, 1.175, P>0.05). (2) Total burn area and CRKP infection were independent risk factors for sepsis in burn patients with KP infection (odds ratios=1.03, 5.88, 95% confidence intervals=1.01-1.05, 1.08-31.94, P<0.05). Conclusions: From 2015 to 2017, the infection rates of KP and CRKP in the author's department did not increase obviously, but the proportion of CRKP infection was high. CRKP infection is one of the independent risk factors for sepsis in burn patients with KP infection. Strengthening the prevention and treatment of CRKP infection may have certain value in decreasing the incidence of burn sepsis.

Flexible modulation of electronic and magnetic properties of zigzag H-MoS2 nanoribbons by crack defects.

The effects of crack defects on electronic and magnetic properties of zigzag MoS2 nanoribbons are investigated systematically by first-principles calculations based on spin-polarized density functional theory. We find that not only the electronic and spin transport ability of zigzag MoS2 nanoribbons can be enhanced significantly by the armchair crack defects, but also their magnetism could be modulated flexibly by crack defects. Our study suggests that the introduction of crack defect is a feasible way to modulate the electronic and magnetic properties of zigzag MoS2 nanoribbons. We further propose that the crack defects may also provide a useful tool for improving the performance of devices.

[Clinical experience and next-generation sequencing analysis of encephalitis caused by pseudorabies virus].

Objective: To detect potential pathogens including pseudorabies virus in patients with encephalitis of unknown etiology in China and describe novel encephalitic entities. Methods: Patients with clinically suspected infectious encephalitis were enrolled in a multicenter study to identify the pathogens in PUMCH Encephalitis Program.Next-generation sequencing(NGS) of cerebrospinal fluid (CSF) was used in patients with encephalitis of unknown etiology enrolled from 2016 to 2017.The patients diagnosed as PRV encephalitis were studied to describe this novel entity. Results: The four patients(3 male, 1 male, 38-54 years old) had occupational exposure to raw park when working in the production or marketing of pork and at least one got injured during pork-cutting.Two of them were confirmed with NGS of CSF, and anti-PRV antibodies were positive in 3 patients whose serum was available for serological analysis.They all presented with an acute onset of fever, convulsion, loss of consciousness and respiratory failure within 1 to 4 days and rapidly deteriorated even on extensive treatment.All the patients needed ICU admission and 3 needed mechanical ventilation.Two patients also had bilateral retinitis.Neuroimaging revealed symmetric gray matter lesions including limbic system, basal ganglia and midbrain without obvious hemorrhage.Lumbar puncture revealed elevated intracranial pressure and lymphocytic pleocytosis [(6-64)×10(6)/L] of CSF.The patients failed to response to the treatment of acyclovir combined with intravenous immunoglobulin and steroids.Modified Rankin Score was 3, 5, 5 and 6 (died) for the 4 patients respectively on last follow-up. Conclusions: PRV could be a cause of severe encephalitis.The patients with suspected pseudorabies encephalitis (PRE) need to be tested for PRV DNA timely.Severe encephalitis with bilateral involvement of limbic system, basal ganglion, thalamus and midbrain in patient with occupational exposure indicate this emerging infectious encephalitis.

Calcium-/calmodulin-dependent protein kinase II in occlusion-induced degenerative cartilage of rat mandibular condyle.

Activated calcium-/calmodulin-dependent protein kinaseII (CaMKII) is important to promote chondrocytes from proliferative to pre-hypertrophic state, which probably plays a role in osteoarthritis (OA), a widespread degeneration disease with enhanced aberrant chondrocyte differentiation. Our aim was to detect the role of CaMKII, and its relationship with the feedback loop of Indian hedgehog (Ihh) and Parathyroid-related peptide (PTHrP) in the temporomandibular joints (TMJs) OA. KN93, the competitive inhibitor of CaMKII, was added to the culture medium in vitro and was locally injected to rats TMJs (n = 54, female) every other day for 4 weeks from the beginning of the 5th and 9th week after installing of unilateral anterior crossbite (UAC), termed as 4 wk+4 wk and 8 wk+4 wk, accordingly. The RNA expression of CaMKII α (1.49 ± 0.09), CaMKII ß (3.36 ± 0.20), Ihh (1.88 ± 0.06) and PTHrP (1.87 ± 0.12) was all enhanced, especially at 24 dyn/cm2 in vitro (all P < .05), accompanied with downregulated expression of cartilage matrix, but upregulated markers of chondrocytes differentiation (all P < 0.05). Similarity was observed in the 4 wk+4 wk group in vivo. In the 8 wk+4 wk group, UAC upregulated the RNA expression of CaMKII α (1.81 ± 0.24), CaMKII ß (1.36 ± 0.07) and Ihh (1.70 ± 0.21), however, down-regulated PTHrP (0.53 ± 0.04) (all P < .05), in consonance with the protein expression. All these changes were attenuated by KN93 (all P < .05). In conclusion, CaMKII took a role, via Ihh and PTHrP pathways, in promoting biomechanically induced TMJ chondrocytes differentiation, the initiation issue of UAC stimulated osteoarthritic changes in rodent TMJs. Inhibiting CaMKII is helpful to rescue the biomechanically stimulated cartilage degradation and prospective to be a target treatment of OA.

[Effects of endostatin pretreatment on fibrosis of human skin fibroblasts and the mechanisms].

Objective: To explore the effects of endostatin pretreatment on fibrosis of human skin fibroblasts and the mechanisms. Methods: Human skin fibroblasts were routinely cultured in vitro, and then the cells of passage 3 to 5 were used in the following experiments. The cells were divided into blank control, endostatin, platelet-derived growth factor-BB (PDGF-BB), endostatin+ PDGF-BB, transforming growth factor-ß(1) (TGF-ß(1)), and endostatin+ TGF-ß(1) groups according to the random number table, with 3 wells in each group. Cells in blank control group were cultured with DMEM medium for 24 h. Cells in endostatin group were cultured with DMEM medium containing 5 µg/mL endostatin for 24 h. Cells in PDGF-BB group and TGF-ß(1) group were cultured with DMEM medium containing 200 ng/mL PDGF-BB and 10 ng/mL TGF-ß(1) for 24 h, respectively. Cells in endostatin+ PDGF-BB group were pretreated with DMEM medium containing 5 µg/mL endostatin for 48 h and then cultured with DMEM medium containing 200 ng/mL PDGF-BB for 24 h. Cells in endostatin+ TGF-ß(1) group were pretreated with DMEM medium containing 5 µg/mL endostatin for 48 h and then cultured with DMEM medium containing 10 ng/mL TGF-ß(1) for 24 h. The content of type Ⅰ collagen in the cell culture supernatant of three wells in each group was determined by enzyme-linked immunosorbent assay. The protein expression levels of α-smooth muscle actin (α-SMA), PDGF receptor ß (PDGFRß), phosphorylated PDGFRß (p-PDGFRß), and phosphorylated extracellular signal-regulated protein kinases 1/2 (p-ERK1/2) of three wells in each group were detected by Western blotting. Data were processed with one-way analysis of variance and SNK test. Results: (1) Compared with (5.05±0.29) pg/mL in blank control group, content of type Ⅰ collagen in the cell culture supernatant of endostatin group [(4.72±0.37) pg/mL] was close to it (P>0.05), content of type Ⅰ collagen in the cell culture supernatant of PDGF-BB group and TGF-ß(1) group [(8.60±0.57) and (9.20±0.64) pg/mL, respectively] was higher (with P values below 0.05). Content of type Ⅰ collagen in the cell culture supernatant of endostatin+ PDGF-BB group [(5.32±0.17) pg/mL] was lower than that of PDGF-BB group (P<0.05), and content of type Ⅰ collagen in the cell culture supernatant of endostatin+ TGF-ß(1) group [(5.41±0.20) pg/mL] was lower than that of TGF-ß(1) group (P<0.05). (2) Compared with those in blank control group, protein expression levels of α-SMA, PDGFRß, p-PDGFRß, and p-ERK1/2 of cells in endostatin group showed no obvious differences (with P values above 0.05), while those in PDGF-BB and TGF-ß(1) group were significantly higher (with P values below 0.01). Protein expression levels of α-SMA, PDGFRß, p-PDGFRß, and p-ERK1/2 of cells in endostatin+ PDGF-BB group and endostatin+ TGF-ß(1) group were significantly lower than those in PDGF-BB group and TGF-ß(1) group, respectively (with P values below 0.05). Conclusions: Pretreatment of endostatin can inhibit the fibrosis of human skin fibroblast and its transformation into myofibroblast, which may be related to the down-regulation of protein expression of p-PDGFRß, PDGFRß, and p-ERK.

[Clinical analysis of paraneoplastic neurological syndrome associated with thymoma].

Objectives: To investigate the clinical features, diagnosis and treatment of antibody mediated paraneoplastic neurological syndrome associated with thymoma. Methods: From 2012 to 2017, the paraneoplastic antibody and neuron antibody were tested from both blood and cerebrospinal fluid (CSF) in consecutive patients clinically suspected with neurological paraneoplastic syndromes/unknown encephalitis in Peking Union Medical College Hospital.The clinical data, lab results, electrophysiological examinations, imaging features, treatment and clinical prognosis were collected.In this study, the patients who met the diagnostic criteria of both thymoma and neurological paraneoplastic syndrome were retrospectively analyzed.The functional severity was assessed by modified Rankin score(mRS). Results: Six patients (4 female and 2 male) were included for the analysis.Of them, 4 patients presented with limbic encephalitis, 1 with peripheral neuropathy accompanying with myasthenia gravis and 1 with spinal and cerebella degeneration.Three patients were in severe condition (mRS=5). Positive α-amino-3-hydroxy-5-methyl-4-iso xazolepropionic acid receptor, antibody (AMPAR) was identified in 3 patients(2 in blood and CSF, 1 in blood), CV2 plus acetylcholine receptor antibody (ACH-Ab) positive in blood was seen in 1 patient and positive N-methyl-D-aspartate receptor (NMDAR) in blood and CSF in 1 patient. Brain MRI showed abnormalities in 2 patients.The CT scan revealed thymoma in all 6 patients.All patients received intravenous immunogloblin (IVIG) and/or glucocorticoid immediately after diagnosis.Furthermore, thymectomy was performed in 5 patients. All the patients were remarkably improved with mRS 0-1 at discharge.Five patients were clinical stable within follow-up of 1-2.5 years.However, one patient who refused thymectomy experienced several clinical recurrencs. Conclusions: Antibodies mediated paraneoplastic neurological syndrome/autoimmune encephalitis can occur in patients with thymoma with typical characteristics. The correlated antibody test and chest CT might be important in patients clinically suspected with neurological paraneoplastic syndrome or encephalitis with unknown reason. Surgical thymectomy combining with active immunological treatment may play a role in the favorable prognosis, even in those clinical severe patients.

[Analysis of prodromal phase and prodromal events in anti-N-methyl-D-aspartate receptor encephalitis].

Objective: To analyze prodromal phase and prodromal events of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Methods: Clinical data of 179 patients hospitalized and diagnosed during 2010-2016 including adults and children in Peking Union Medical College Hospital and Beijing Children's Hospital were collected.Patients with prodromal phase or prodromal events were selected.A retrospective analysis of clinical characteristics including prodromal phase or prodromal events, course of disease, brain imaging, laboratory results and therapeutic effect was performed. Results: Prodromal phase was presented in 31.8% (57/179) of patients.Most common symptoms included fever (73.7%) and headache (68.4%). Prodromal phase was prolonged in 6 patients, the longest being 64 days.Among those 6 patients (10.5%), headache and fever were the only symptoms throughout disease courses in 3 cases.Prodromal events were reported in 6.1% (11/179) of patients, including 5 patients after HSV1 encephalitis, 1 after Japanese encephalitis, and 2 after resection of melanocytic nevi. Conclusions: Anti-NMDAR encephalitis can be preceded with prolonged prodromal phase.In some patients prodromal symptoms are the only clinical presentation.Clinical features of those atypical cases suggest that infection may be the precipitating factor.Viral encephalitis including HSV1 encephalitis and Japanese encephalitis may be prodromal events in some cases.

[Immunotherapy strategy for 35 cases of severe anti-N-methyl-D-aspartate receptor encephalitis].

OBJECTIVE: To provide evidence for establishing standardized treatment strategy of severe anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in China, by demonstrating the clinical characteristics and comparing the treatment strategy with that adopted in foreign countries. METHODS: A total of 35 hospitalized cases who met the diagnostic criteria for severe anti-NMDAR encephalitis were retrospectively analyzed. Demographic data, clinical history, past medical history, laboratory tests, imaging studies, treatment and the follow-up information were recorded using unified forms. RESULTS: Mental and behavioral abnormalities, seizures and consciousness disturbance occurred in all cases; involuntary movements, speech disorders, memory loss, central hypoventilation and autonomic dysfunction happened in 45%-65% of cases. Sixteen patients (45.71%) required mechanical ventilation. Modified Rankin score (mRS ) arranged 4-5 (mean mRS 4.86). The percentage of patients with elevated intracranial pressure, white blood cell and protein in cerebrospinal fluid were 42.86%, 60.00%, and 14.29%, respectively. Abnormal findings in brain magnetic resonance imaging scan happened in 31.43% cases, located in frontal lobe, temporal lobe, insular lobe, hippocampus, cingulate gyrus, corpus callosum, brain stem, and cerebellum. All cases received intravenous immunoglobulin, for one to maximum seven cycles, with an average of three cycles. 91.43% of cases received glucocorticoid therapy, including 54.29% of cases received high-dose methylprednisolone. Two patients (5.71%) received plasma exchange. Five patients(14.29%) received second-line therapy including rituximab for 4 patients and intravenous cyclophosphamide (CTX) for one. Fifteen patients(42.86%) received long-term immunosuppression therapy. All cases acquired improvement after immunotherapy and were transferred out from ICU, the median ICU time was 46 days and median hospitalized duration was 72 days. The mRS were 5 for 2 cases, 1-4 for the rest patients, and no patient died during hospitalization. During a median follow-up period of 17.6 months, 30 of 35 patients (85.71%) achieved complete recovery or a good outcome (mRS 0-2). Eleven patients (31.43%) relapsed. One patient(2.90%) died 2 years after discharge. CONCLUSION: Intravenous immunoglobulin combined with high-dose methylprednisolone therapy is effective for severe anti-NMDAR encephalitis. Retrial of the first-line immunotherapy is an option for initially unresponsive cases.

Improvements of PKU PMECRIS for continuous hundred hours CW proton beam operation.

In order to improve the source stability, a long term continuous wave (CW) proton beam experiment has been carried out with Peking University compact permanent magnet 2.45 GHz ECR ion source (PKU PMECRIS). Before such an experiment a lot of improvements and modifications were completed on the source body, the Faraday cup and the PKU ion source test bench. At the beginning of 2015, a continuous operation of PKU PMECRIS for 306 h with more than 50 mA CW beam was carried out after success of many short term tests. No plasma generator failure or high voltage breakdown was observed during that running period and the proton source reliability is near 100%. Total beam availability, which is defined as 35-keV beam-on time divided by elapsed time, was higher than 99% [S. X. Peng et al., Chin. Phys. B 24(7), 075203 (2015)]. A re-inspection was performed after another additional 100 h operation (counting time) and no obvious sign of component failure was observed. Counting the previous source testing time together, this PMECRs longevity is now demonstrated to be greater than 460 h. This paper is mainly concentrated on the improvements for this long term experiment.

Duty factor variation possibility from 1% to 100% with PKU microwave driven Cs-free volume H⁻ sources.

Microwave driven cesium-free volume H(-) sources, that have the ability to deliver tens of mA H(-) at 35 keV both in CW and 10% duty factor (100 Hz/1 ms), were developed at Peking University (PKU) [S. X. Peng et al., in Proceeding of IPAC 2015, WEPWA027, Richmond, Virginia, USA, 3-8 May 2015]. Recently, special efforts were paid on the investigation of duty factor variation possibility from 1% to 100% with them. Most of the experiments were carried out with a pulsed length (τ) of 1 ms and different intervals of 99 ms, 49 ms, 39 ms, 29 ms, 19 ms, 9 ms, 4 ms, 2 ms, 1 ms, 0.5 ms, and 0 ms, respectively. Other experiments were focused on CW operation and fixed duty factor of 1%. Experimental results prove that PKU H(-) sources can deliver tens of mA H(-) at duty factor from 1% to 100%. The RF power efficiency increases steadily with the increasing of duty factor from 1% to CW at a fixed pulsed length. Under a given duty factor and pulsed length, RF power efficiency keeps constant and the H(-) current increases with RF power linearly. Details will be presented in the paper.

Study on space charge compensation in negative hydrogen ion beam.

Negative hydrogen ion beam can be compensated by the trapping of ions into the beam potential. When the beam propagates through a neutral gas, these ions arise due to gas ionization by the beam ions. However, the high neutral gas pressure may cause serious negative hydrogen ion beam loss, while low neutral gas pressure may lead to ion-ion instability and decompensation. To better understand the space charge compensation processes within a negative hydrogen beam, experimental study and numerical simulation were carried out at Peking University (PKU). The simulation code for negative hydrogen ion beam is improved from a 2D particle-in-cell-Monte Carlo collision code which has been successfully applied to H(+) beam compensated with Ar gas. Impacts among ions, electrons, and neutral gases in negative hydrogen beam compensation processes are carefully treated. The results of the beam simulations were compared with current and emittance measurements of an H(-) beam from a 2.45 GHz microwave driven H(-) ion source in PKU. Compensation gas was injected directly into the beam transport region to modify the space charge compensation degree. The experimental results were in good agreement with the simulation results.

HDAC Inhibitor Oxamflatin Induces Morphological Changes and has Strong Cytostatic Effects in Ovarian Cancer Cell Lines.

Ovarian epithelial carcinoma is the leading cause of deaths from gynecologic malignancy. New reagents with therapeutic potentials against ovarian cancer, especially the drug-resistant cases, are required for better treatment of ovarian cancer patients. Epigenetic events such as changes in DNA methylation and histone modification, through their effects on DNA-protein interaction, chromatin conformation, and gene expression, affect cell function, cancer behavior, clinical manifestations, and outcomes. Previous studies have shown that histone deacetylase (HDAC) inhibitors have strong cytostatic and apoptotic activities in hematologic and some solid cancer cells. Oxamflatin, a compound containing the aromatic sulfonamide and hydroxamic acid groups, is known to be a potent HDAC inhibitor capable of inhibiting the growth of mouse and human cancer cell lines. In this study we found that oxamflatin in the nM range induced morphological changes in OVCAR-5 and SKOV-3 ovarian cancer cell lines. Treatment with oxamflatin also led to decreased cell viability. Moreover, results of BrdU incorporation assay, cell counting, and Ki-67 immunostaining indicated that oxamflatin was able to significantly inhibit DNA synthesis and cell proliferation. Using real-time PCR and Western blot analyses we demonstrated that oxamflatin was capable of downregulating the expression of c-Myc, CDK4, E2F1, and the phosphorylation levels of Rb protein, but upregulating p21. These findings pave the way to examine if oxamflatin along with or in combination with other reagents could deliver anticancer effects against ovarian cancers in vivo.