Synthesis of spiro[indolenine]-methanofullerenes via Deoxofluor promoted deoxygenative cyclopropanation of 1,2-(3-indole)-fullerenols.

Deoxofluor-promoted intramolecular cyclopropanation of 1,2-(3-indole)fullerenols has been developed as a straightforward and efficient protocol for the synthesis of various spiro[indolenine]-methanofullerenes. This approach exhibits low cost, operational simplicity, and convenient conditions, and thus has potential application value.

[Effect of moxibustion on JAK2/STAT3 signal pathway in synovial tissues of rabbits with adjuvant arthritis under the overexpression of NLRP3 inflammatory bodies].

OBJECTIVE: To observe the effect of moxibustion on Janus protein tyrosine kinase 2/signal transducer and activator of transcription 3 (JAK2-STAT3) signal pathway and interleukin (IL)-1ß and IL-18 in synovial fluid of adjuvant arthritis (AA) rabbits, so as to explore the mechanism of moxibustion in the treatment of rheumatoid arthritis. METHODS: Twenty-eight rabbits were randomized into control, model, moxibustion, and NLRP3 overexpression groups, with 7 rabbits in each group. AA rabbit model was established by injection of Freund's complete adjuvant (FCA, 0.5 mL/kg) into the rabbits' bilateral hind-knee joint cavities. On the third day after modeling, the NLRP3 lentiviral vector (40 µL) were injected into the bilateral hind-knee joint cavities of rabbits in NLRP3 overexpression group. Moxibustion was used to bilateral "Shenshu" (BL23) and "Zusanli" (ST36), 5 cones every time, once daily, 6 days a week for 3 weeks in the moxibustion and NLRP3 overexpression groups. The perimeters of rabbits' hind legs were measured after modeling and after the intervention. The contents of IL-1ß, IL-18 in synovial fluid were detected by ELISA and the expression levels of NLRP3, JAK2 and STAT3 mRNAs in synovial tissue were detected by real-time PCR. RESULTS: In comparison with the control group, the perimeters of bilateral knee joints were significantly increased at each time point (P<0.05),and the contents of IL-1ß, IL-18 in synovial fluid and the expression levels of NLRP3, JAK2, STAT3 mRNA in synovial tissue were significantly increased (P<0.05) in the model group. Compared with the model group, the perimeters of bilateral knee joints were significantly decreased (P<0.05), and the contents of IL-1ß, IL-18 in synovial fluid and the expression levels of NLRP3, JAK2, STAT3 mRNAs in synovial tissue were significantly decreased (P<0.05) in the moxibusion group. Compared with the moxibustion group, the above indexes were higher in the NLRP3 overexpression group (P<0.05). CONCLUSION: Moxibustion may play an anti-inflammatory and detumescent role in AA rabbits by regulating JAK2-STAT3 signal pathway, and its therapeutic effect may be closely related to the expression of NLRP3.

Nontraumatic convexal subarachnoid hemorrhage: A case report.

BACKGROUND: Nontraumatic convexal subarachnoid hemorrhage (cSAH) is a rare type of atypical subarachnoid hemorrhage. It mainly presents as a focal and transient neurological deficit with similar manifestations as transient ischemic attack. CASE SUMMARY: We report a case of a 64-year-old man who visited the hospital with paroxysmal left-sided numbness and weakness is presented in this study. Computed tomography examination indicated a high-density image of the right frontal-parietal sulcus. Digital subtraction angiography showed severe stenosis at the right anterior cerebral artery A2-A3 junction (stenosis rate approximately 70%). CONCLUSION: The findings of this case indicate that anterior cerebral artery stenosis may lead to the occurrence of cSAH.

Identifying Modifiable Risk Factors for Relapse in Patients With Schizophrenia in China.

BACKGROUND: Preventing relapse of schizophrenic patients is really a challenge. The present study sought to provide more explicit evidence and factors of different grades and weights by a series of step-by-step analysis through χ2 test, logistic regression analysis and decision-tree model. The results of this study may contribute to controlling relapse of schizophrenic patients. METHODS: A total of 1,487 schizophrenia patients were included who were 18-65 years of age and discharged from 10 hospitals in China from January 2009 to August 2009 and from September 2011 to February 2012 with improvements or recovery of treatment effect. We used a questionnaire to collect information about relapse and correlative factors during one year after discharge by medical record collection and telephone interview. The χ2 test and logistic regression analysis were used to identify risk factors and high-risk factors firstly, and then a decision-tree model was used to find predictive factors. RESULTS: The χ2 test found nine risk factors which were associated with relapse. Logistic regression analysis also showed four high-risk factors further (medication adherence, occupational status, ability of daily living, payment method of medical costs). At last, a decision-tree model revealed four predictors of relapse; it showed that medication adherence was the first grade and the most powerful predictor of relapse (relapse rate for adherence vs. nonadherence: 22.9 vs. 55.7%, χ2 = 116.36, p < 0.001). The second grade factor was occupational status (employment vs. unemployment: 19.7 vs. 42.7%, χ2 = 17.72, p < 0.001); the third grade factors were ability of daily living (normal vs. difficult: 28.4 vs. 54.3%, χ2 = 8.61, p = 0.010) and household income (household income ≥ 3000 RMB vs. <3000 RMB: 28.6 vs. 42.4%, χ2 = 6.30, p = 0.036). The overall positive predictive value (PPV) of the logistic regression was 0.740, and the decision-tree model was 0.726. Both models were reliable. CONCLUSIONS: For schizophrenic patients discharged from hospital, who had good medication adherence, more higher household income, be employed and normal ability of daily living, would be less likely to relapse. Decision tree provides a new path for doctors to find the schizophrenic inpatient's relapse risk and give them reasonable treatment suggestions after discharge.

[Mechanism on moxibustion for rheumatoid arthritis based on PD-1/PD-L1 signaling pathway].

OBJECTIVE: To explore the mechanism of moxibustion on the treatment of rheumatoid arthritis (RA) in the perspective of programmed cell death-1 and its ligand 1 (PD-1/PD-L1). METHODS: A total of 30 Japanese big ear white rabbits were randomly divided into a control group, a model group and a moxibustion group, 10 rabbits in each one. In the model group and the moxibustion group, RA model was prepared by the injection of Freund's complete adjuvant (FCA) into the hind knee joint cavities of each rabbit. In the control group, 0.9% sodium chloride solution of the same dose was injected. On the 8th day of experiment, in the moxibustion group, moxibustion was applied to "Shenshu" (BL 23) and "Zusanli" (ST 36), 5 cones at each acupoint, on the bilateral sides alternatively, once a day, 6 treatments as one course, with an interval of 1 days between the treatment courses. Totally, 3 courses of treatment were required. On the 1st, 7th, 14th, 21st and 28th days of experiment, successively, the circumference of the bilateral knee joints was measured with the tape. On the 28th day of experiment, H.E. staining was adopted to observe the histopathological morphology and to evaluate the score of knee synovial tissue. ELISA was used to determined the concentrations of soluble PD-1 (sPD-1) and its ligand 1 (sPD-L1), the interleukin 2 (IL-2) and IL-17 in knee synovial fluid and the concentrations of sPD-1 and sPD-L1 in serum. The histochemistry method was used to determine the expressions of membrane PD-1 (mPD-1) and its ligand 1 (mPD-L1) in spleen tissue. RESULTS: On the 14th, 21st and 28th days of experiment, the circumference of both knee joints was increased in each of the rabbits in the model group as compared with the control group (P<0.01), and it was reduced significantly in the moxibustion group as compared with the model group (P<0.01). Compared with the control group, the hyperplasia of synovial tissue and fibrous tissue, as well as inflammatory cell infiltration were increased obviously in the model group (P<0.01), and they were reduced significantly in the moxibustion group as compared with the model group (P<0.01, P<0.05). Compared with the control group, the concentrations of IL-2 and IL-17 in knee synovial fluid were increased in the rabbits of the model group (P<0.01). Compared with the model group, after the intervention with moxibustion, the concentrations of IL-2 and IL-17 in knee synovial fluid were reduced in the rabbits of the moxibustion group (P<0.05). Compared with the control group, the concentrations of sPD-1 and sPD-L1 in knee synovial fluid and serum in the rabbits of the model group were all increased (P<0.05). Compared with the model group, the concentration of sPD-1 in the knee synovial fluid and serum were reduced in the rabbits of moxibustion group (P<0.05). Compared with the control group, the expressions of mPD-1 and mPD-L1 in spleen tissue were increased obviously in the rabbits of the model group (P<0.05). Compared with the model group, the expression of mPD-L1 in spleen tissue was up-regulated in the rabbits of the moxibustion group (P<0.05). CONCLUSION: Moxibustion could inhibit the over-activation of T cells by enhancing the negative regulation of PD-1/PD-L1 signaling pathway so as to play its effect in treatment of RA.

Novel Subgroups in Subarachnoid Hemorrhage and Their Association With Outcomes-A Systematic Review and Meta-Regression.

Background and Purpose: Subarachnoid hemorrhage (SAH) has long been classified into two main forms, aneurysmal SAH (aSAH) and non-aneurysmal SAH (naSAH), but the related risk factors for aSAH and naSAH are heterogeneous. Our objective was to determine the risk factors for SAH of known or unknown origin with respect to diagnostic evaluation in a large patient cohort. We sought to determine whether our classification system can further predict middle long-term stroke and death. Methods: We performed a systematic review and meta-analysis to identify risk factors for each SAH subtype. The discovery phase analyzed 11 risk factors from case studies in the literature. Kruskal-Wallis, Cox regression, logistic regression, and Kaplan-Meier analyses were used to compare the two groups. Results: A total of 14,904 (34.53%) male and 22,801 (52.84%) female patients were eligible for this study. At a median follow-up of 45.6 months, the 5-years overall survival was 97.768% (95% CI: 0.259-0.292) for aSAH patients and 87.904% (95% CI: 1.459-1.643) for naSAH patients. The 10-years survival rate was 93.870% (95% CI: 2.075-3.086) and 78.115% (95% CI: 2.810-3.156), respectively. Multi-risk factor subgroups showed significant intergroup differences. We identified eight risk factors (drugs, trauma, neoplastic, vessels lesion, inflammatory lesion, blood disease, aneurysm, peri-mesencephalic hemorrhage) using logistic regression, which were optimally differentiated among the aSAH [aSAH-S (AUC: 1), a-d-SAH (AUC: 0.9998), aSAH-T (AUC: 0.9199), aSAH-N (AUC: 0.9433), aSAH-V (AUC: 1), aSAH-I (AUC: 0.9954), a-bd-SAH (AUC: 0.9955)] and naSAH [na-pmSAH (AUC: 0.9979), na-ni-ivl-SAH (AUC: 1), na-t-SAH (AUC: 0.9997), na-ne-SAH (AUC: 0.9475), na-d-SAH (AUC: 0.7676)] subgroups. These models were applied in a parallel cohort, showing eight risk factors plus survival rates to predict the prognosis of SAH. Conclusions: The classification of risk factors related to aSAH and naSAH is helpful in the diagnosis and prediction of the prognosis of aSAH and naSAH patients. Further validation is needed in future clinical applications.

Bromadiolone poisoning leading to subarachnoid haemorrhage: A case report and review of the literature.

WHAT IS KNOWN AND OBJECTIVE: Many cases of rodenticide poisoning have been reported. Bromadiolone, often called a super-warfarin, is a second-generation dicoumarin rodenticide with long half-life. The main clinical manifestations of bromadiolone poisoning are excessive or inappropriate bleeding of skin mucosa, digestive tract and urinary tract. However, the phenomenon of central nervous system (CNS) toxicity is an uncommon medical emergency. We present a case of SAH and intracerebral haematoma mediated by bromadiolone intoxication, revealing that bromadiolone poisoning might cause intracerebral haematoma. CASE DESCRIPTION: A 44-year-old woman presented with skin mucosa haemorrhage and haematuresis initially. The patient developed lethargy, headache, nausea and vomiting. The toxicology test result revealed that the presence of bromadiolone in her blood. Coagulation test results showed a longer prothrombin time (PT), activated partial thromboplastin time (APTT) and a high international normalized ratio (INR). SAH, frontal lobe haematoma, midline shift and brain oedema were discovered by skull CT examination. The coagulation disorders were addressed after the treatment of vitamin K and fresh frozen plasma. The intracranial symptoms were relieved after surgery and the treatment with mannitol. WHAT IS NEW AND CONCLUSION: This case suggests that bromadiolone poisoning should be diagnosed and treated as early as possible. Bromadiolone poisoning might cause SAH and intracerebral haematoma, which is rare but potentially lethal. It is important to strengthen the diagnosis and post-treatment monitoring.

A case of subdural hematoma with a medical history of hemophilia a and a review of related literature.

BACKGROUND: Intracranial hemorrhage is the most common emergency in the neurology department, and patients with a medical history of hemophilia have a risk of severe bleeding. CASE PRESENTATION: A 56-year-old man was admitted to the emergency department in our hospital. He was diagnosed with hemophilia A and subdural hematoma. We administered an infusion of factor VIII to decrease the risk of bleeding and improve the prognosis. Factor VIII infusion is the most important factor in treating hemophilia A patients. CONCLUSION: We recommend carefully checking coagulation function and the medical history once these patients are admitted, especially in the emergency department.

Intraparenchymal endodermal cyst with spontaneous intracystic hemorrhage in the temporal lobe of an adult.

BACKGROUND: Endodermal cysts (EC) are rare but well-known congenial lesions of the central nervous system mainly located in the spinal subdural space. Intracranial ECs are rare and commonly encountered in the posterior cranial fossa as extra-axial lesions; an intraparenchymal location is exceedingly rare. A complete removal is the best surgical strategy and any residue can cause recurrence. It is necessary to exclude EC in patients with intracranial cystic lesions. We present a case of intraparenchymal EC with spontaneous intracystic hemorrhage in the temporal lobe of an adult. METHODS: A 43-year-old man presented with headache and memory deterioration. Brain computed tomography and magnetic resonance imaging showed a slightly enhanced temporal lobe cystic lesion, which was homogenously hyperintense on T1-and T2-weighted images. There was a suspicion of brain abscess at admission. The lesion was totally removed with a left subtemporal craniotomy. Histological examination revealed an EC with intracystic hemorrhage. RESULTS: The preoperative symptoms were relieved after surgery and 3-month follow-up magnetic resonance imaging found no cystic signs. CONCLUSION: This case suggests that EC should be considered in the differential diagnosis of intracranial cystic lesions and a complete removal is the best strategy of choice.

Application of Preoperative CT/MRI Image Fusion in Target Positioning for Deep Brain Stimulation.

Objective To explore the efficacy of target positioning by preoperative CT/MRI image fusion technique in deep brain stimulation.Methods We retrospectively analyzed the clinical data and images of 79 cases (68 with Parkinson's disease, 11 with dystonia) who received preoperative CT/MRI image fusion in target positioning of subthalamic nucleus in deep brain stimulation. Deviation of implanted electrodes from the target nucleus of each patient were measured. Neurological evaluations of each patient before and after the treatment were performed and compared. Complications of the positioning and treatment were recorded.Results The mean deviations of the electrodes implanted on X, Y, and Z axis were 0.5 mm, 0.6 mm, and 0.6 mm, respectively. Postoperative neurologic evaluations scores of unified Parkinson's disease rating scale (UPDRS) for Parkinson's disease and Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) for dystonia patients improved significantly compared to the preoperative scores (P<0.001); Complications occurred in 10.1% (8/79) patients, and main side effects were dysarthria and diplopia.Conclusion Target positioning by preoperative CT/MRI image fusion technique in deep brain stimulation has high accuracy and good clinical outcomes.

[Effects of Chronological Moxibustion on Circadian Rhythm Activities of Hypothalamus-Pituitary-Axis in Rheumatoid Arthritis Rats].

OBJECTIVE: To observe the effect of chronological moxibustion on plasma corticosterone (CORT), corticotrophin releasing factor (CRF) and adrenocorticotropic hormone (ACTH) levels in rheumatoid arthritis (RA) rats, so as to explore its mechanisms underlying improvement of RA. METHODS: A total of 144 SD rats were randomly divided into normal control, model, moxibustion, sham-adrenalectomy (ADX, sham-ADX), ADX and ADX+moxibustion groups which were further separately divided into 4 subgroups (4 time-points: 12 pm, 6 am, 12 am, 6 pm, n = 6/subgroup). The RA model was established by subcutaneous injection of Freund's complete adjuvant (FCA, 0. 1 mL) into the right footpad (for rats of the latter 5 groups). In rats of the ADX and ADX+ moxibustion groups, bilateral adrenal glands were removed under anesthesia. Moxibustion was applied to unilateral "Shenshu" (BL 23) and "Zusanli" (ST 36) for 10 min, once daily for 6 days in a week, and continuously for 3 weeks. The paw swelling volume was measured and plasma CORT, ACTH and CRF contents were assayed by ELISA and the circadian rhythm was analyzed by cosine curve fitting (cosinor) method. RESULTS: The paw swelling volume was significantly increased in the model group than in the normal control group (P<0.05), and decreased remarkably in the moxibustion group (P<0.05). The paw volume was markedly increased in the ADX +moxibustion group in comparison with the moxibustion group (P<0.05). In intact rats, plasma CRF and ACTH contents were significantly increased (P<0.05), and plasma CORT was obviously decreased in the model group (P<0.05). After moxibustion, the increased plasma CRF and ACTH contents and the decreased plasma CORT level Nere considerably reversed (P<0.05). In ADX rats, plasma ORE, ACTH and CORT contents of ADX and ADX + moxibustion groups had no significant.changes compared with the sham-ADX group (P>0.05). Results of the cosine curve fitting analysis showed that the peak phases of plasma CORT contents were -355.78 degrees at about 23:43 in the normal control group, -309.05 degrees at about 20:36 in the model group, -326.5 degrees at about 21:46 in the moxibustion group, -291.65 degrees at about 19:27 in the ADX group and -300.87 degrees at about 20:31 in the ADX + moxibustion group. The peak phases of plasma ACTH contents were -324.08 degrees at about 21:37 in the normal control group, -295.39 degrees at about 19:41 in the model group, -310.81 degrees at about 20:43 in the moxibustion group, -146.51 degrees at about 9:46 in the ADX group and -267.64 degrees at about 17:50 in the ADX+ moxibustion group. The peak phases of plasma CRF contents were -257.47 degrees at about 17:10 in the normal control group, -184.74 degrees at about 12:19 in the model group, -263.00 degrees at about 17:32 in the moxibustion group, -202.46 degrees at about 13:30 in the ADX group and -232.84 degrees at about 15:31 in the ADX+ moxibustion group. It suggests that in the intact RA rats, moxibustion intervention may inhibit modeling-induced decrease of the circadian rhythm of plasma CORT, and hyperactivity of ACTH and CRF circadian rhythm. CONCLUSION: VAoxibustion intervention can relieve paw swelling in RA rats and modulate the circadian rhythm activities of plasma CORT, ACTH and ORE levels (HPA axis activities) in intact animals.

Does Early Postsurgical Temozolomide Plus Concomitant Radiochemotherapy Regimen Have Any Benefit in Newly-diagnosed Glioblastoma Patients? A Multi-center, Randomized, Parallel, Open-label, Phase II Clinical Trial.

BACKGROUND: The radiochemotherapy regimen concomitantly employing temozolomide (TMZ) chemotherapy and radiotherapy (RT) 4 weeks after surgery, followed by 6 cycles of TMZ is a common treatment for glioblastoma (GBM). However, its median overall survival (OS) is only 14.6 months. This study was to explore the effectiveness and safety of early TMZ chemotherapy between surgery and chemoradiotherapy plus the standard concomitant radiochemotherapy regimen. METHODS: A randomized, parallel group, open-label study of 99 newly diagnosed GBM patients was conducted at 10 independent Chinese neurosurgical departments from June 2008 to June 2012. Patients were treated with concomitant radiochemotherapy regimen plus early postsurgical temozolomide (early TMZ group) or standard concomitant radiochemotherapy regimen (control group). Overall response was assessed based on objective tumor assessments, administration of corticosteroid and neurological status test. Hematological, biochemical, laboratory, adverse event (AE), and neurological condition were measured for 24 months of follow-up. The primary efficacy endpoint of this study was overall survival (OS). The secondary endpoint was progression free survival (PFS). RESULTS: The median OS time in the early TMZ group was 17.6 months, compared with 13.2 months in the control group (log-rank test P = 0.021). In addition, the OS rate in the early TMZ group was higher at 6, 12, and 18 months than in the control group, respectively (P < 0.05). The median PFS time was 8.7 months in the early TMZ group and 10.4 months in the control group (log-rank test P = 0.695). AEs occurred in 29 (55.8%) and 31(73.8%) patients respectively in early and control groups, including nausea (15.4% vs. 33.3%), vomiting (7.7% vs. 28.6%), fever (7.7% vs. 11.9%), and headache (3.8% vs. 23.8%). Only 30.8% and 33.3% were drug-related, respectively. CONCLUSIONS: Addition of TMZ chemotherapy in the early break of the standard concomitant radiochemotherapy regimen was well tolerated and significantly improved the OS of the GBM patients, compared with standard concomitant radiochemotherapy regimen. However, a larger randomized trial is warranted to verify these results.

MiR-25 suppresses 3T3-L1 adipogenesis by directly targeting KLF4 and C/EBPα.

In the past decade, miRNA emerges as a vital player in orchestrating gene regulation and maintaining cellular homeostasis. It is well documented that miRNA influences a variety of biological events, including embryogenesis, cell fate decision, and cellular differentiation. Adipogenesis is an organized process of cellular differentiation by which pre-adipocytes differentiate towards mature adipocytes. It has been shown that adipogenesis is tightly modulated by a number of transcription factors such as PPARγ, KLF4, and C/EBPα. However, the molecular mechanisms underlying the missing link between miRNA and adipogenesis-related transcription factors remain elusive. In this study, we unveiled that miR-25, a member of miR-106b-25 cluster, was remarkably downregulated during 3T3-L1 adipogenesis. Restored expression of miR-25 significantly impaired 3T3-L1 adipogenesis and downregulated the expression of serial adipogenesis-related genes. Further experiments presented that ectopic expression of miR-25 did not affect cell proliferation and cell cycle progression. Finally, KLF4 and C/EBPα, two key regulators of adipocyte differentiation, were experimentally identified as bona fide targets for miR-25. These data indicate that miR-25 is a novel negative regulator of adipocyte differentiation and it suppressed 3T3-L1 adipogenesis by targeting KLF4 and C/EBPα, which provides novel insights into the molecular mechanism of miRNA-mediated cellular differentiation.

Research advances in the application of methylprednisolone in the treatment of acute spinal cord injury.

Acute spinal cord injury(ASCI),mainly caused by traffic accidents and fall injuries,is a catastrophic event that can profoundly affect the trajectory of a patient's life. Debate continues over the medical management of ASCI,in particular the usefulness,dosage,and potential risks of methylprednisolone(MP). Although the results of American National Acute Spinal Cord Injury Study 2 and 3 trials led to the wide adoption of a high-dose MP regimen for ASCI patients,the reliabilities of their study methods and data were still questionable. Based on the currently available literature,we conclude that high-dose MP is no longer a recommended therapy for ASCI;however,due to the lack of effective treatment,it remains a useful option for this condition.

[Significance of pseudocapsule in the excision of pituitary adenomas in transsphenoidal surgery].

OBJECTIVE: To explore the significance of pseudocapsule in the excision of pituitary adenomas in transsphenoidal surgery. METHODS: For 22 patients with pituitary adenomas over a period of 2 years at Peking Union Medical College Hospital, resection of pseudocapsule was applied for complete tumor removal. Pituitary function test and radiological imaging were performed at pre-operation, 3 months post-operation and at subsequent 6-12 months intervals postoperatively. RESULTS: All pituitary adenomas were totally removed under microscope. The symptoms of headache, disorder of sight and visual field disappeared postoperatively in nonfunctional pituitary adenomas. The GH levels of 2/5 growth hormone secreting adenoma patients were 4.2 and 7.7 µg/L while it was under 1 µg/L for another 3. The postoperative level of prolactin was 4.3 µg/L in prolactin secreting adenoma. The level of adrenocorticotropic hormone decreased under 5 ng/L except one was 15.7 ng/L. Leakage of cerebrospinal fluid occurred intraoperatively in 3 patients and postoperatively in 1. No leakage was found after repair. Diabetes insipidus occurred in one patient and was controlled with Minirin. Pseudocapsule was confirmed by pathological examination. Special staining revealed reticulum fibers in pseudocapsule. CONCLUSION: Resection of pseudocapsule may achieve a higher remission rate without deteriorating pituitary function.