The mammalian central nervous system (CNS) is considered an immune privileged system as it is separated from the periphery by the blood brain barrier (BBB). Yet, immune functions have been postulated to heavily influence the functional state of the CNS, especially after injury or during neurodegeneration. There is controversy regarding whether adaptive immune responses are beneficial or detrimental to CNS injury repair. In this study, we utilized immunocompromised SCID mice and subjected them to spinal cord injury (SCI). We analyzed motor function, electrophysiology, histochemistry, and performed unbiased RNA-sequencing. SCID mice displayed improved CNS functional recovery compared to WT mice after SCI. Weighted gene-coexpression network analysis (WGCNA) of spinal cord transcriptomes revealed that SCID mice had reduced expression of immune function-related genes and heightened expression of neural transmission-related genes after SCI, which was confirmed by immunohistochemical analysis and was consistent with better functional recovery. Transcriptomic analyses also indicated heightened expression of neurotransmission-related genes before injury in SCID mice, suggesting that a steady state of immune-deficiency potentially led to CNS hyper-connectivity. Consequently, SCID mice without injury demonstrated worse performance in Morris water maze test. Taken together, not only reduced inflammation after injury but also dampened steady-state immune function without injury heightened the neurotransmission program, resulting in better or worse behavioral outcomes respectively. This study revealed the intricate relationship between immune and nervous systems, raising the possibility for therapeutic manipulation of neural function via immune modulation.

OBJECTIVE: To compare the histopathological features of the synovium between rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: We retrospectively analyzed the synovial specimens obtained after synovial surgery in 72 cases of RA and 24 cases of OA. Two independent pathologists reviewed the sections of the synovial tissues with HE staining, quantitatively scored the degree of fibroblast-like synoviocyte (FLS) hyperplasia, vascular hyperplasia, fibroplasia, and lymphocyte infiltration, and examined the presence plasma cell infiltration. The pathological morphology of the synovial tissues was evaluated in relation with the clinical data of the patients. RESULTS: Pannus formation was also detected in the synovium of OA patients, which showed a lesser degree of OA-FLS hyperplasia, fibrosis and lymphocyte infiltration and a significantly lower rate of plasma cell infiltration compared with the pannus in RA patients. Vascular proliferation was also milder in the pannus of OA patients than in RA pannus, but the difference was not statistically significant. In OA patients, the pannus could be observed under a microscope and was difficult to distinguish from that in RA patients. CONCLUSIONS Pannus formation occurs also in the synovium of OA patients but with milder FLS hyperplasia, fibrosis and lymphocyte infiltration and a lower rate of plasma cell infiltration compared with the pannus in RA patients. These differences in the pannus between OA and RA can be of potential value in the diagnosis and treatment of the patients.
Arthritis, Rheumatoid ; Cells, Cultured ; Humans ; Osteoarthritis, Knee ; Retrospective Studies ; Synovial Membrane

Objective: To describe the clinical manifestations of central nerve system inflammatory demyelinating disease associated with anti-myelin oligodendrocyte glycoprotein antibody (MOG-IDD) in children, and to explore the clinical characteristics of the children. Methods: The clinical and laboratory characteristics of the patients diagnosed in Beijing Children′s Hospital, Capital Medical University, from October 2016 to August 2018 were described, and the clinical data of the patients with unipolar and recurrent diseases were compared. Results: A total of 50 patients were included, among whom the ratio of male to female was 24:26, and the average age of onset was (6.7±3.1) years old (0.4-12.6 years old). There was no significant difference in the age of onset between boys and girls(t=0.712, P=0.480). The main symptoms included fever (31/50 cases), encephalopathy (26/50 cases) and optic neuritis (22/50 cases), etc.In the last follow-up, 26 patients (52.0%) had a monophasic course and 24 patients (48.0%) had a recurrent course.There were age differences in encephalopathy and ataxia in the first episode of [(5.7±2.8) years old vs.(8.1±3.0) years old, (5.0±2.5) years old vs. (7.7±3.0) years old](t=2.746, P=0.009; t=2.837, P=0.007). The average number of recurrence was (2.1±1.4) times (1-7 times), in which 17 cases (70.8%) of recurrence presented within 12 months and 20 cases (83.3%) of recurrence presented within 24 months after onset.Convulsion incidences of recurrent cases were 10 cases and 13 cases respectively in the first episode and recurrent courses, which were significantly higher than those of monophasic cases (4 cases, 4 cases)(χ²=7.912, P=0.005; χ²=8.365, P=0.004). All patients were sensitive to first-line immunotherapy.Seven patients with recu-rrence were treated with mycophenolatemofetil, and 17 patients with repeated first-line therapy.In the last follow-up, all patients were in remission and 2 patients had mild neurological dysfunction. Conclusions MOG-IDD can occur in childhood.Encephalopathy and optic neuritis are the most common symptoms.Encephalopathy and ataxia are more common in young children.Convulsions may indicate the course of recurrence.

Objective To evaluate the effect of propofol on the expression of programmed death-ligand-1 (PD-L1) in pancreatic cancer cells and the relationship with NMDA/Ca2+/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ)/hypoxia-inducible factor-1α (HIF-1α) pathway.Methods Human pancreatic cancer cells were divided into 5 groups (n=16 each) by a simple random sampling method:control group (group C),propofol group (group P),KN93 (CaMK Ⅱ inhibitor) group,MK801 (NMDA receptor antagonist) group and propofol plus rapastinel (NMDA receptor agonist) group (group PR).Cells were cultured in DMEM supplemented with 10％ fetal bovine serum in group C.Cells were incubated for 8 h with 50 μmol/L propofol in group P.Cells were incubated for 8 h with 10 μmol/L KN93 in group KN93.Cells were incubated for 8 h with 500 μmol/L MK801 in group MK801.Cells were incubated for 8 h with 50 μmol/L propofol and 20 μmol/L rapastinel in group PR.After the end of treatment in each group,the cell viability was measured using CCK8 assay,the expression of PD-L1,HIF-1α,CaMK Ⅱ and phosphorylated CaMK Ⅱ (p-CaMK Ⅱ) was detected by Western blot,and intracellular calcium concentrations were determined by Fluo3/AM probe.Results Compared with group C,the cell viability was significantly decreased,the expression of PD-L1,HIF-1α and p-CaMK Ⅱ was down-regulated,and intracellular calcium concentrations were decreased in P,KN93 and MK801 groups (P＜0.05),and no significant change was found in group PR (P＞0.05).Compared with group P,the cell viability was significantly enhanced,the expression of PD-L1,HIF-1α and p-CaMK Ⅱ was up-regulated,and intracellular calcium concentrations were increased in group PR (P＜0.05).Conclusion The mechanism by which propofol inhibits the malignant potential of pancreatic cancer cells may be related to inhibiting NMDA/CaMK Ⅱ/HIF-1α pathway and down-regulating PD-L1 expression.

Background:Family history of gastric cancer is an important indicator of genetic susceptibility.Studies have shown that the family history of gastric cancer might have impact on Helicobacter pylori (Hp) infection and clinicopathological manifestations in patients with chronic gastritis.Aims:To investigate the correlation of family history of gastric cancer with Hp infection and pathological changes of gastric mucosa in patients with chronic gastritis.Methods:A total of 312 patients with chronic gastritis were enrolled to study the relationship between family history of gastric cancer and Hp infection,degree of gastric mucosal inflammation,activity of inflammation,and degree of atrophy and intestinal metaplasia.Results:In the 312 patients with chronic gastritis,165 (52.9％) had family history of gastric cancer,and 147 (47.1％) without family history of gastric cancer.Incidence of Hp infection,degree of gastric mucosal atrophy and intestinal metaplasia in patients with family history of gastric cancer were significantly higher than those without (P ＜ 0.05),but no significant differences in degree and activity of inflammation were found between the two groups (P ＞ 0.05).Conclusions:The incidence of Hp infection is higher in chronic gastritis patients with family history of gastric cancer.Family history of gastric cancer may aggravate gastric mucosal atrophy and intestinal metaplasia.

Objective To investigate the expression of miRNA-31 in peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA) patients,and the relationship between miRNA-31 and disease activity of RA.Methods After obtaining the informed consent,peripheral blood samples of 56 RA patients,12 systemic lupus erythematosus (SLE) patients,6 Sj(o)gren's syndrome (SS) patients and 30 healthy controls were collected from the Department of Rheumatology,Peking University Third Hospital.RNA was extracted from the PBMCs which were separated by Ficoll-Paque PLUS.The expression of miRNA-31 in the PBMCs of RA patients,SLE patients,SS patients and healthy controls was detected by real-time Polymerase Chain Reaction (PCR).Furthermore,according to the RA disease activity score (DAS28),RA patients were divided into high,moderate and low disease activity groups and remission group,and miRNA-31 expression was compared between different groups.Data were analyzed using t test or Mann-Whitney U test.Results The expression of miRNA-31 in PBMCs of RA patients was 7.25 times (P=0.003 8) higher when compared with that of the control group.To be specific,the expression of miRNA-31 was 10.63 times in PBMCs of high activity RA group (P=0.01) and 8.95 times in moderate activity RA group (P=0.000 3) when compared with that of the control group,and there was no significant difference between low activity,remission groups and control groups in terms of miRNA-31 expression.Furthermore,the expression of miRNA-31 in PBMCs of SLE patients was not significantly different from the control and miRNA-31 expression in PBMCs of SS patients was 1.64 times (P=0.02) higher than that of the RA patients,but the average level of miRNA-31 was much less than that of RA patients.The increased miRNA-31 may serve as a diagnostic marker for disease activity of RA.

Objective To investigate the dynamic abnormality of anorectum in elderly patients with chronic constipation.Methods Anorectal perfusion manometry was performed to detect the change of anal canal pressure and the rectal sensation capacity in 58 elderly patients and 36 non-elderly adults with chronic constipation.The results were compared retrospectively.Results Anal resting pressure in a chronic constipation was significantly lower in elderly patients than in non-elderly adults,with statistically significant difference [(59.74 ± 2.31) mmHg vs.(68.22 ± 2.37) mmHg,t =2.430,P =0.017].The incidence of paradoxical motility of anal sphincter was significantly higher in elderly patients with three abnormalities(incomplete defecation,Bristol stool scale type 3-5 and straining at defecation) than in elderly patients without above three abnormalities (x2 =8.880、11.540、6.070,P =0.003、0.001、0.014).Maximal tolerable volume was significant lower in elderly patients with straining at defecation and abdominal pain than in control group (t =2.140,2.260,both P ＜ 0.05).No correlation was observed between sex and anorectal motility in elderly patients with chronic constipation.Conclusions Anorectal motility in elderly patients with chronic constipation is different from that in non-elderly patients with chronic constipation.The dynamic abnormalities of anorectum in chronic constipation are different in elderly patients with different symptoms.

Chronic gastritis has varied clinical symptoms and prolonged course,and seriously affects the life quality of patients.Studies have shown that mood disorders might affect the pathogenesis of chronic gastritis.Aims:To investigate the incidence of anxiety and depression and its relationship with digestive symptoms,Helicobacter pylori (Hp) infection,degree and activity of inflammation in patients with chronic gastritis.Methods:A total of 235 patients with chronic non-atrophic gastritis were enrolled.Anxiety,depression,gastrointestinal symptoms,gastric mucosal inflammation and activity were evaluated,and infection of Hp was detected.Results:In the 235 patients,144 (61.3%)were accompanied by anxiety and/or depression:108 patients (46.0%)were accompanied by anxiety,129 patients (54.9%) were accompanied by depression,93 patients (39.6%)were accompanied by anxiety and depression.Incidence of abdominal pain,abdominal distention and early satiety,scores of digestive symptoms,positive rate of Hp infection and incidence of severe inflammation in patients accompanied by anxiety and/or depression were significantly higher than those in patients without anxiety and depression (P<0.05 ),but no significant difference in inflammation activity was seen between the two groups (P>0.05).Conclusions:Incidence of anxiety and depression in patients with chronic gastritis is high.Anxiety and depression are associated with abdominal pain,abdominal distention and early satiety,and can affect the inflammatory degree of gastric mucosa.Patients with anxiety and depression are susceptible to Hp infection.

Objective To analyze the expression levels of IL-11 and connective tissue growth factor (CTGF) in patients with breast cancer and their correlation with bone metastasis .Methods The 108 cases of breast cancer(breast cancer group) ,30 cases of breast benign tumor (breast benign tumor group) and 30 cases of healthy controls (control group) were performed by ELISA to de-tect the expression of serum IL-11 ,CTGF ,and their relationship with bone metastases was analyzed .All the patients were followed up for 2 years ,survival rates between different expression levels of IL-11 ,CTGF were compared .Results Compared with those in control group and breast benign tumor group ,the expressions of IL-11 ,CTGF in breast cancer group were increased (P<0 .05) , while there was no significant difference between control group and breast benign tumor group (P<0 .05) .The levels of serum IL-11 ,CTGF in different stages of breast cancer with bone metastases were significantly higher than those in breast cancer without bone metastases(P<0 .05) ,and the levels of IL-11 ,CTGF in bone metastases stage of Ⅲ - Ⅳ were higher than those in bone me-tastases stage ofⅠ - Ⅱ(P<0 .05) .Serum IL-11 and CTGF was positively correlated in breast cancer patients with or without bone metastases(r=0 .514 ,0 .477 ,P<0 .05) .At 2 year after surgery ,the survival rate in patients with high expression of IL-11 and CT-GF was significantly lower than that with low expression (χ2 =4 .50 ,5 .18 ,P<0 .05) .Conclusion The levels of serum IL-11 ,CT-GF in breast cancer patients are overexpressed ,which could be used as an effective serological tumor markers for diagnosis of bone metastases and assessment of prognosis .

Objective To investigate the inhibition mechanism of tetramethylpyrazine combined with cisplatin on angiogenesis in Lewis lung cancer mice and to observe the mechanism of Arresten on angiogenesis in lung cancer. Methods The model of Lewis lung adenocarcinoma mouse xenograft was established in this work, and 40 mice were randomly divided into 4 groups: 0.9% sodium chloride solution group(NS group), tetramethylpyrazine group(TMP group), cisplatin group(DDP group), tetramethylpyrazine plus cisplatin group(TMP + DDP group), 10 mice in each group.Mice in NS group were given 0.2 mL of 0.9% sodium chloride solution, mice in DDP group were given 0.2 mL of 2 mg.kg-1 of cisplatin, mice in TMP group were given 0.2 mL of 100 mg.kg-1 of tetramethylpyrazine, mice in TMP+DDP group were given 2 mg.kg-1 of cisplatin and 100 mg.kg-1 of tetramethylpyrazine, each 0.1 mL .Tumor size was measured every day to calculate the tumor volume.The mice were sacrificed to stripp the subcutaneous tumor after continuous medication. The expressions of Arresten, integrin α1β1 and VEGF were determinated by immunhistochemistry and Western blotting. Results The tumor growth of NS group was the fastest and TMP+DDP group was the slowest. Compared with NS group, the expression of Arresten in the other three groups was increased( P<0.01) , and the TMP+DDP group exhibited the highest expression;at the same time, integrin α1β1 , VEGF in the other three groups was decreased(P<0.01), and the TMP+DDP group exhibited the lowest expression.The expression of integrinα1β1 and VEGF was negatively related to Arresten, and the expression of integrin α1β1 was positively correlated with VEGF. Conclusion TMP can inhibited the growth of Lewis lung carcinoma and angiogenesis. Moreover, in combination with cisplatin, TMP can also improved the effect of chemotherapy and then the survival state of mice. The mechanism of action, which TMP suppress tumor angiogenesis may be through improving Arresten and inhibiting integrin α1β1 and VEGF. And the action mechanism of Arresten may be implemented by inhibiting the expression of VEGF by incorporation with integrinα1β1 or by itself to inhibit the expression of VEGF.