Mechanism on moxibustion for rheumatoid arthritis based on PD-1/PD-L1 signaling pathway / 中国针灸

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 (<0.01), and it was reduced significantly in the moxibustion group as compared with the model group (<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 (<0.01), and they were reduced significantly in the moxibustion group as compared with the model group (<0.01, <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 (<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 (<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 (<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 (<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 (<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 (<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.

Treatment of blood disease with chronic subdural hematoma / 基础医学与临床

Objective To understand the characteristics of patients with hematological illness and chronic subdural hematoma.,and the effect of blood disease on the treatment of chronic subdural hematoma. To guide the treatment of patients who both with hematological illness and chronic subdural hematoma. Methods Through a retrospective study of the cases of chronic subdural hematoma from January 1, 2000 to June 1, 2017 in Peking Union Medical College Hospital, the following items were investigated. 1).According to whether or not they were associated with blood disorders, the collected cases were divided into the blood disorders group and the non-blood disorders group. And the clinic data of the sex composition, average ages, treatment effect and mortality were compared. 2). Ac-cording to the treatment, the cases with blood disease were divided into the surgical group and the conservative group. And the treatment effect and mortality were compared. Results A total of 433 patients with chronic subdural hematoma were included in this study, including 35 patients associated with hematological illness. 1) Compared to the controls group, the patients group was younger( P＜0.01) ;the male ratio was lower ( P＜0.01) ; the treatment effect was lower( P＜0.001) and the mortality was higher( P＜0.001) . 2) Within the patients with hematological illness, the surgical group had the better treatment effect(78.9% vs 31.3%,P＜0.01) and the lower mortality (15.8% vs 50.0%,P＜0.05). Conclusions 1)The hematological illness group is younger and the male ratio is lower than the non-hematological illness group; 2) The hematological illness is a risk factor for the treatment of chronic subdural hematoma; 3) The patients who both with the hematological illness and the chronic subdural he-matoma should be treated by surgery.

Application of Preoperative CT/MRI Image Fusion in Target Positioning for Deep Brain Stimulation / 中国医学科学杂志(英文版)

<strong>Objective</strong> To explore the efficacy of target positioning by preoperative CT/MRI image fusion technique in deep brain stimulation.<strong>Methods</strong> 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.<strong>Results</strong> 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.<strong>Conclusion</strong> Target positioning by preoperative CT/MRI image fusion technique in deep brain stimulation has high accuracy and good clinical outcomes.

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 / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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).</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Research advances in the application of methylprednisolone in the treatment of acute spinal cord injury / 中国医学科学院学报

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.

Thyroid-stimulating hormone pituitary adenomas: clinical characteristics, diagnosis and treatment / 中华外科杂志

<p><b>OBJECTIVE</b>To study the clinical characteristics, diagnosis and surgical effects of thyroid-stimulating hormone pituitary adenomas (TSH-omas).</p><p><b>METHODS</b>The clinical data of 19 patients (14 female and 5 male) with TSH-omas were analyzed retrospectively in this study from January 2001 to December 2008. The patients ranged from 20 to 70 years old (average 40.5 years old) and had disease histories from 1 to 228 months (average 55 months). Among these patients, 15 of them complained of thyrotoxicosis symptoms, while the other 4 patients' symptoms were associated with headache and/or visual disturbance caused by the tumor mass effect. Initially, 12 of the 15 patients with thyrotoxicosis symptoms were misdiagnosed with Grave's disease. As a result 2 of them received (131) Iodine, and one received subtotal thyroidectomy. All of these patients underwent transsphenoidal microsurgery.</p><p><b>RESULTS</b>Average follow-up period was 3.6 years (6 months-7 years). Pathological analysis of the surgical specimen showed pituitary adenoma in all patients, immunohistochemistry were positive for TSH in 17 cases, negative for TSH in 2, positive for growth hormone in 2, positive for prolactin in 1, and positive for adrenocorticotrophic hormone in 1. Postoperative MRI revealed that the tumors in 15 patients were removed totally, though 4 patients still had residual tumors. The thyroid hormone level tests suggested that 13 patients could be considered normal 3 months after their tumors were removed, though 2 of patients with normal postoperative MRI and thyroid hormones showed increased levels of TSH. For these 2 patients, tumors did not recur and their thyroid hormone levels returned to normal after pituitary radiotherapy. The cure rate was 11/19 after surgery and 13/19 after surgery plus pituitary radiotherapy.</p><p><b>CONCLUSIONS</b>The screening test for hyperthyroidism patients with high TSH levels is a key point to improve the accuracy rate in early diagnoses of TSH-omas. The transsphenoidal microsurgery is first choice to treat TSH-omas, while pituitary radiotherapy and somatostatin analogs are beneficially adjunctive therapies.</p>

Clinical application of neuronavigation in transsphenoidal microsurgery of pituitary adenomas / 中华外科杂志

<p><b>OBJECTIVES</b>To summarize the experiences in clinical application of neuronavigation in transsphenoidal microsurgery of specific pituitary adenomas, and to discuss its indications.</p><p><b>METHODS</b>From January 2006 to December 2010, 138 cases of transsphenoidal microsurgery for specific pituitary adenomas under neuronavigation were reviewed. The indications for neuronavigation in transsphenoidal microsurgery includes: recurrent or regrowth of residual pituitary adenomas after former transsphenoidal surgery in 36 cases, invasive pituitary adenomas in 45 cases, extremely laterally or deeply situated microadenomas in 45 cases, poor pneumatization of the sphenoid in 4 cases, skull base anomalies due to osteodysplasia fibrosa in 3 cases, narrow space between bilateral internal carotid arteries in 4 cases, distortion of nasal septum in 1 case.</p><p><b>RESULTS</b>In the recurrence group, 12 were totally removed, 9 subtotally removed; postoperative complications included hematoma within the tumor cavity in 2 cases, cerebrospinal fluid (CSF) leakage in 4 cases among which 3 developed intracranial infection and 2 communicating hydrocephalus, oculomotor paralysis in 1 case and hypopituitarism in 3 cases; 9 were cured and 8 remission. In the invasive group, 5 were totally removed, 27 subtotally removed; postoperative complications included hematoma within the tumor cavity in 1 case, CSF leakage and intracranial infection in 1 case; 2 were cured and 22 remission. None of the 30 invasive hormone-secreting adenomas were cured or remission. The 45 cases of hormone-secreting microadenomas were all totally removed, among which 38 were cured. Among the poor sphenoid pneumatization group, total and subtotal tumor removal were achieved in 2 cases respectively with only one cured. In the skull base anomaly group, 2 were totally removed and 1 subtotally removed, with only one cured. For the cases with narrow space between bilateral internal carotid arteries and distortion of nasal septum, all were totally removed and cured.</p><p><b>CONCLUSIONS</b>Transsphenoidal microsurgery under neuronavigation can be applied for pituitary adenomas in above specific indications. It is an accurate, safe and effective approach for specific pituitary adenomas, which can not only expand the indication of transsphenoidal microsurgery for pituitary adenomas, but also reduce the harmful exposure of X-rays for the operating staff.</p>

Virtual mutagenesis of isocitrate dehydrogenase 1 involved in glioblastoma multiforme / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Site A132Arg mutations potentially impair the affinity of isocitrate dehydrogenase 1 (IDH1) for its substrate isocitrate (ICT), consequently reducing the production of α-ketoglutarate and leading to tumor growth through the induction of the hypoxia-inducible factor-1 (HIF-1) pathway. However, given that the roles of other active sites in IDH1 substrate binding remain unclear, we aimed to investigate IDH1 mutation pattern and its influence on enzyme function.</p><p><b>METHODS</b>Fifteen IDH1 catalytic active site candidates were selected for in silico mutagenesis and protein homology modeling. Binding free energy of the IDH1/ICT complexes with single-site mutations was compared with that of the wild type. The affinity of 10 IDH1 catalytic active sites for the ICT substrate was further calculated.</p><p><b>RESULTS</b>The IDH1 active site included seven residues from chain A (A77Thr, A94Ser, A100Arg, A132Arg, A109Arg, A275Asp, and A279Asp) and three residues from chain B (B214Thr, B212Lys, and B252Asp) that constituted the substrate ICT-binding site. These residues were located within 0.5 nm of ICT, indicating a potential interaction with the substrate. IDH1 changes of binding free energy (ΔE) suggested that the A132Arg residue from chain A contributes three hydrogen bonds to the ICT α-carboxyl and β-carboxyl groups, while the other nine residues involved in ICT binding form only one or two hydrogen bonds. Amino acid substitutes at A132Arg, A109Arg, and B212Lys sites, had the greatest effect on enzyme affinity for its substrate.</p><p><b>CONCLUSIONS</b>Mutations at sites A132Arg, A109Arg, and B212Lys reduced IDH1 affinity for ICT, indicating these active sites may play a central role in substrate binding. Mutations at sites A77Thr, A94Ser, and A275Asp increased the affinity of IDH1 for ICT, which may enhance IDN1 catalytic activity. Mutant IDH1 proteins with higher catalytic activity than the wild-type IDH1 could potentially be used as a novel gene therapy for glioblastoma multiforme.</p>

Cut-off points of fasting fingertip capillary blood glucose for detecting both undiagnosed diabetes and pre-diabetes / 中华流行病学杂志

Objective To determine the efficient cut-off points of fasting fingertip blood glucose test for undiagnosed diabetes mellitus(DM), impaired glucose tolerance(IGT), and impaired fasting glucose(IFG)in community-based residents aged above 45 years old. Methods A cluster-randomized study was conducted from May 2008 to January 2009. A total of 3250 subjects aged above 45 years in two communities of Baoding city received questionnaire investigation and tested for fingertip blood glucose. Those subjects whose capillary blood glucose level ≥5.1 mmol/L were subjected to 75 g oral glucose tolerance test. Undiagnosed diabetes mellitus and pre- diabetes were identified by fasting plasma glucose and OGTT. In this study, the cut-off points of fasting capillary blood glucose for detecting undiagnosed diabetes and pre-diabetes were evaluated, using receiver operator characteristic curve(ROC). Results Of 1351 subjects that having had oral glucose tolerance test, 230 cases were diagnosed as diabetes mellitus(7.3%), 166 cases(5.2%)as IFG, and 204(6.7%)as IGT under fasting capillary blood glucose as test variable and state variables according to the following criteria.(1)FPG≥7.0 mmol/L or/and 2hPG≥11.1 mmol/L(2)FPG<5.6 mmol/L (3)FPG<7.0 mmol/L and 7.8 mmol/L≤2hPG≤ 11.1 mmol/L, areas under three ROC curves were 0.905, 0.633 and 0.719, respectively. The cut-offvalues of screening for undiagnosed DM, IGT and IFG were 6.0 mmol/L, 5.7 mmol/L, and 5.7 mmol/L, respectively. When cut-off value of screening for undiagnosed DM was 6.0 mmol/L, the maximal sensitivity was 78.0% and specificity was 89.3%.But there were both lower sensitivity and specificity in screening for IFG and IGT according to the best predicting value(5.7 mmol/L)from the ROC curves(50.3% and 28.0% vs. 60.8% and 28.0%). Conclusion Fasting capillary blood glucose with the lower cut-point of 6.0 mmol/L in screening for undiagnosed diabetes mellitus alone, was relatively reliable, whereas for both IFG and IGT the fasting fingertip blood glucose tests were fallible. It was convenient and could be used in screening the DM at the community level.

Management of pulmonary thromboembolism in post-operative neurosurgical patients / 中国医学科学院学报

<p><b>OBJECTIVE</b>To summarize the diagnosis and treatment of pulmonary thromboembolism (PTE) in post-operative neurosurgical patients.</p><p><b>METHODS</b>We retrospectively analyzed the clinical data of 7 patients who experienced pulmonary thromboembolism after neurosurgical operations in our department from October 2009 to March 2010.</p><p><b>RESULTS</b>Of these 7 patients, 6 were confirmed with computed tomographic pulmonary angiography (CTPA) and 1 was diagnosed according to the clinical manifestations and other diagnostic examinations. All the patients were treated initially with low-dose heparin or low-molecular-weight heparin and then with warfarin. Two patients were implanted with permanent inferior vena cava filters before anticoagulation. One received anticoagulant therapy and died of respiratory failure due to pulmonary embolism on the fourth post-operative day. Six patients were discharged after significant improvement.</p><p><b>CONCLUSIONS</b>Many risk factors may cause PTE peri-operatively. Post-operative CTPA may be indicated. Anticoagulation and other management strategies may be applied to improve the outcome.</p>

A case-control study on risk factors of type 2 diabetes mellitus related chronic complications in Baoding city / 中华流行病学杂志

<p><b>OBJECTIVE</b>To recognize the main risk factors and to provide evidence for prevention and intervention of type 2 diabetes chronic complications.</p><p><b>METHODS</b>A hospital-based frequency matched case-control study including 200 type 2 diabetes mellitus (T2DM) chronic complications cases and 200 controls without T2DM chronic complications was carried out in Baoding city. Relationships between factors and T2DM chronic complications were analyzed by non-conditional uni-variate and multivariate logistic regression methodologies.</p><p><b>RESULTS</b>High C-reactive protein (CRP) (OR = 5.568), dyslipidemia (OR = 4.400), high blood urea nitrogen (BUN) (OR = 4.399), high low density lipoprotein-cholesterol (LDL-C) (OR = 3.594), time of hospitalization (OR = 2.612), grease food intake before developing DM (OR = 2.300), high HbA1c% (OR = 1.747), lack of exercise after the development of DM (OR = 1.672), duration of DM (OR = 1.509), mental stress (OR = 1.427), high-quality sleep (OR = 0.606), well control of blood glucose (OR = 0.517), well control of blood fat (OR = 0.299), insulin injections (OR = 0.155) etc. were all significantly associated with T2DM chronic complications.</p><p><b>CONCLUSION</b>The main risk factors of T2DM chronic complications seemed to be related to high CRP, dyslipidemia, high BUN and high LDL-C. The main protective factors were insulin injections, well control of blood fat and blood glucose, good-quality of sleep, while the unique risk factors of cardiovascular disease seemed to be high LDL-C and mental stress. The unique risk factors of neuropathy were lack of exercise after developing DM and the amount of sweet food intake. The duration of DM appeared to be the common risk factor and the common protective factor on those three complications was insulin injection.</p>

Construction and identification of RNA interference lentiviral expression vector of galectin-3 gene / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct a recombinant lentiviral U6 plasmids for RNA interference (RNAi) of galectin-3 gene and select the optimal target sequence of galectin-3 gene for RNAi.</p><p><b>METHODS</b>Double-stranded oligo DNAs were designed and synthesized according to the sequence of galectin-3 gene, and ligated into linearized pGCL-GFP/U6 plasmid followed by transformation into competent DH5alpha cells. After PCR and sequence analysis for verification of the positive clones, the plasmid pGCL-GFP/U6 Gal-3shRNA-1 was extracted and transfected into CaCl2-treated 293T cells to obtain the viral vectors containing the RNAi sequence. MCF-7 cells were infected with pGCL-GFP/U6 Gal-3shDNA-1, and at the infection rate over 50%, the cells were harvested to extract the RNA. Real time-PCR was performed to determine the expression level of galectin-3 mRNA in the infected cells.</p><p><b>RESULTS</b>The recombinant vector was successfully constructed as confirmed by sequence analysis. High titer of the virus was obtained, and after infection of MCF-7 cells, RNAi targeting the 1# and 3# sequences in galectin-3 gene resulted in suppression of galectin-3 mRNA expression by 95% and 85%, respectively.</p><p><b>CONCLUSION</b>The recombinant lentiviral U6 plasmid for RNAi of Galectin-3 gene has been successfully constructed, which provides the basis for further study of the role of galectin-3 gene in tumor cells.</p>

Transsphenoidal microsurgical results of non-invasive prolactinomas / 中华外科杂志

<p><b>OBJECTIVE</b>To analyze the transsphenoidal microsurgical results of non-invasive prolactinomas, in order to provide reference for their treatment choice.</p><p><b>METHODS</b>To review the transsphenoidal microsurgical results of 234 non-invasive prolactinomas treated in our department in recent 10 years, and to analyze the prognostic factors. There were 18 males and 216 females, aged between 13 and 58 years, averaged (31.1 +/- 8.5) years. The course ranged from half a month to 20 years, averaged (47.3 +/- 44.9) months. The preoperative serum PRL level ranged between 41 and 8406 ng/ml, averaged (400.5 +/- 888.0) ng/ml, with a median of 164.1 ng/ml. The primary symptoms were amenorrhea, galactorrhea and/or infertility in 211 cases. The tumor size was small (< 1 cm) in 100, large (> or = 1 cm) in 116 and giant (> or = 3 cm) in 18 cases. All the patients received transsphenoidal microsurgery and were followed-up for 12 to 132 months, averaged (43.8 +/- 35.0) months.</p><p><b>RESULTS</b>There was no mortality. One hundred and twenty-seven (54.3%) cases had transient postoperative imbalance of water and electrolytes. One hundred and eighty-eight cases (80.3%) were cured, 12 (5.1%) experienced clinical remission, 20 (8.5%) were improved, and 14 (6.0%) were ineffective. The male patient, the giant prolactinomas and those with higher preoperative serum PRL level had a relative poor postoperative prognosis. While the other factors had no influence on prognosis, including the course, preoperative bromocriptine intake, tumor texture, tumor apoplexy and intraoperative descending extent of the diaphragm of sella. The overall operative expense for transsphenoidal microsurgery ranged from 8323.8 to 22898.5 yuan, averaged (12912.0 +/- 2361.2) yuan.</p><p><b>CONCLUSIONS</b>Transsphenoidal microsurgery may be chosen as the primary therapy for non-invasive prolactinomas, with the purposes of therapeutical efficacy, facilitating the patients, re-establishing the patients' self-confidence and reducing the overall expense.</p>

Effects of adrenalectomy on the treatment of Cushing disease / 中华外科杂志

<p><b>OBJECTIVE</b>To discuss the effects of adrenalectomy (ADX) on the treatment of Cushing's disease(CD).</p><p><b>METHODS</b>Clinical data of 15 cases of CD between January 1980 and December 2005 were analyzed to evaluate operative indications, complications and the changes of hypercortisolism and hormone levels pre- and post- adrenalectomy.</p><p><b>RESULTS</b>All the patients involved underwent transsphenoidal pituitary surgery previously. Repeated transsphenoidal surgery was performed in 4 cases. Pituitary radiotherapy was done in 4 cases. The average time from original transsphenoidal operation to ADX was 25.7 months. Pre- and post- adrenalectomy serum cortisol median level were 1156.4 nmol/L and 99.4 nmol/L, the 24 h urinary-free cortisol median level were 315.0 and 5.4 microg, respectively. Hormone replacement therapy was needed in all cases. Average follow-up period was 47 months (9-120 months). Nelson syndrome (NS) appeared in 5 cases (33.3%), while 10 cases showed no NS.</p><p><b>CONCLUSIONS</b>ADX is an effective and symptomatic treatment to relieve hypercortisolism caused by CD but with the risk of NS. Longtime hormone replacement therapy and follow up are needed after ADX.</p>

Magnetic resonance imaging characteristics and surgical results of adrenocorticotropin-secreting pituitary adenomas / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate magnetic resonance imaging (MRI) characteristics and surgical results of adrenocorticotropin (ACTH)-secreting pituitary adenomas.</p><p><b>METHODS</b>MRI characteristics and relationship between MRI positive rate and surgical results of 266 patients with pathologically confirmed Cushing's disease were analyzed retrospectively. All patients underwent thin-section sagittal and coronal scans of the pituitary gland before and after administration of gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) on a 1.5 Tesla MRI scanner, and dynamic enhanced MRI was performed in 39 patients. All patients underwent transsphenoidal adenomectomy. Endocrinological examinations and assessments were performed.</p><p><b>RESULTS</b>Preoperative MRI revealed normal results in 41 (15.4%) cases, microadenoma in 179 (67.3%), macroadenoma in 42 (15.8%), and huge adenoma in 4 (1.5%). Pituitary apoplexy was found in 13 (4.9%) cases. Positive rate of ACTH-secreting adenomas was 84.6% (225/266) on MRI scans, and that of small microadenomas was 87.2% (34/39) on dynamic enhanced MRI scans. Preoperative endocrinological tests of 199 cases supported the diagnosis of typical Cushing's disease, while the other 67 cases had atypical endocrinological results. The endocrinological cure rate, remission rate, and inefficacy rate were 85.7%, 7.9%, and 6.4%, respectively. There was no difference in the initial endocrinological cure rate between the patients with positive and normal MRI results (90% vs. 87.8%, P = 0.904).</p><p><b>CONCLUSIONS</b>Enhanced coronal pituitary MRI is helpful for preoperative localization of ACTH-secreting pituitary microadenoma. Dynamic enhanced MRI may improve detection rate of microadenoma. There is no marked difference in the surgical results for patients with preoperative MRI results indicating presence or absence of microadenoma.</p>

Ferumoxide labeled Flk1+ CD31- CD34- human bone marrow mesenchymal stem cells and its in vivo tracing in the brains of Macaca Fascicularis / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the method for labeling Flk1+ CD31- CD34- human bone marrow mesenchymal stem cells (hBMSCs) with ferumoxide-PLL and evaluate the feasibility of its tracing after transplantation into the brains of Macaca Fascicularis.</p><p><b>METHODS</b>The hBMSCs were incubated with ferumoxide-PLL. Trypan blue staining, Prussian blue staining, and transmission electron microscope were performed to show intracellular iron, marking efficiency, and the vigor of the labeled cells. After the hBMSCs were transplanted into the brains of cynomolgus monkeys by stereotaxis, magnetic resonance imaging (MRI) was performed to trace the cells in vivo. Cell survival and differentiation were studied with immunohistochemistry, Prussian blue staining, and HE staining.</p><p><b>RESULTS</b>The marking efficiency of the ferumoxide-PLL was 96%. Iron particles were found intracytoplasmic of the hBMSCs by Prussian blue staining and transmission electron microscopy. The relaxation rates of labeled cells in MRI were 4.4 and 4.2 times higher than those of the unlabeled cells. Hypointensity area was found by MRI three weeks after transplantation. Many hBMSCs and new vessels were found in the transplantation zone by pathological and immunofluorescence methods.</p><p><b>CONCLUSIONS</b>Ferumoxide-PLL can effectively label hBMSCs and thus increase its contrast in MRI results. The cells can survive in the brains of cynomolgus monkeys. The labeled hBMSCs can be traced in vivo by MRI.</p>

In vivo tracking of bone marrow mesenchymal stem cells labeled with superparamagnetic iron oxide after cerebral ischemia in rats by magnetic resonance imaging / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the feasibility of in vivo tracking of bone marrow mesenchymal stem cells (BMSCs) labeled with superparamagnetic iron oxide (SPIO) by magnetic resonance imaging (MRI) in rats after cerebral ischemia, and to analyze the influence of stem cell therapy on the volume of cerebral infarction.</p><p><b>METHODS</b>The samples of rat bone marrow were collected. BMSCs separated by density gradient centrifugation were cultivated and harvested until the third passage. BMSCs were labeled with SPIO, which was mixed with poly-L-lysine. The labeling efficiency was evaluated by Prussian blue staining. Transient middle cerebral arterial occlusion (MCAO) was performed successfully in 18 adult Sprague-Dawley rats that scored from 6 to 12 by the modified neurological severity test. The 18 rats were then randomly divided into group A, B, and C, with 6 rats in each group and Group C was regarded as control group. BMSCs were injected into the contralateral cortex of ischemia in group A, ipsilateral corpora striata in group B, while D-Hank's solution was injected into ipsilateral corpora striata (group C) 24 hours after MCAO. MRI was performed 1 day after MCAO, 1 day and 14 days after transplantation. The volume of infarcted brain tissue was measured and analyzed. Prussian blue staining of brain tissues was performed to identify the migration of BMSCs.</p><p><b>RESULTS</b>The labeling efficiency of BMSCs with SPIO was 96%. The transplanted BMSCs migrated to the ischemic hemisphere along the corpus callosum and to the border of the infarction, which was confirmed by MRI and Prussian blue staining. The changes of infarction volume were not significantly different among these three groups.</p><p><b>CONCLUSIONS</b>MRI is feasible for in vivo tracking of BMSCs labeled with SPIO in rats. The stem cell therapy may not be able to affect the volume of cerebral infarction.</p>

Neuronavigation guidance for motor cortex stimulation in resection of gliomas involving the precentral gyrus / 中华显微外科杂志

Objective To explore surgical treatment of gliomas involving the motor eloquent area. Methods Twelve cases of gliomas involving precentral gyrus were underwent awake surgery procedures assis- ted with neuronavigation and brain functional mapping by cortical electrical stimulation.Results Eleven ca- ses acquired accurate location of both lesions and eloquent areas by neuronavigation and direct cortical stimula- tion.7 cases of motor cortices and 2 cases of motor speech centers were confirmed during the operation.Re- section,verified by postoperative MRI,was total in 8 cases (66.7%) and subtotal in 4 patients.Histological examination revealed an infiltrative glioma in all cases (8 low grade astrocytomas,2 high grade astrocytomas and 2 glioblastoma).Four patients had no postoperative deficit,while the other 8 patients were impaired, with,in all cases except one,complete recovery in 7 days to one month.Conclusion Direct cortical elec- trical stimulations and awake surgery offer a reliable,precise and safe method,allowing functional mapping es- pecially useful in case of infiltrative cerebral tumors in eloquent areas.This technique allows improvement in the quality of tumoral resection and concurrently a minimization of the risk of definitive postoperative neurologi- cal deficit.

Factors influencing the recurrence of Cushing's disease treated by transsphenoidal surgery / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore factors influencing the recurrence of patients with Cushing's disease after transsphenoidal surgery.</p><p><b>METHODS</b>We retrospectively analyzed the clinical data of 182 patients treated by transsphenoidal surgery with Cushing's disease in our department in PUMC Hospital from 1992 to 2002.</p><p><b>RESULTS</b>The recurrence rates were significantly different when patients had different radiological findings (P = 0.001), operative methods (P = 0.001), histological findings (P = 0.04), and postoperative cortisol levels (P = 0.02); however, such difference was not found in term of tumor size (P = 0.43).</p><p><b>CONCLUSION</b>Radiological findings, operative methods, histological findings, and postoperative cortisol estimates may be the factors influencing the recurrence of patients treated by transsphenoidal surgery.</p>

Relationship between invasive pituitary adenomas and cavernus sinus and cariod artery and surgical outcomes / 中国医学科学院学报

<p><b>OBJECTIVE</b>To analyze the relationship between invasive pituitary adenomas and cavernus sinus and cariod artery and to predict their surgical outcomes.</p><p><b>METHODS</b>Totally 270 patients with pituitary tumors were investigated in this retrospective study, including 113 men and 157 women, with a mean age of 40.8 years. The mean disease history was 3.6 years. Pituitary microadenomas were diagnosed in 56 cases, macroadenomas in 118 cases, and hugeadenomas in 96 cases. Adrenocorticotropic hormone-releasing adenomas (Cushing's diseases) were diagnosed in 40 cases, growth hormone-releasing adenomas in 58 cases, prolactinomas in 57 cases, and non-functional pituitary adenomas in 115 cases. Transsphenoidal microsurgery were performed on 260 patients, while transcranial microsurgery on 6 patients.</p><p><b>RESULTS</b>The percentage of invasive pituitary adenomas was about 3.6% in microadenomas, 20.4% in macroadenomas, and 61.4% in hugeadenomas. Rate of total removal was 94.1% in non-invasive pituitary adenomas, and was 58.8% in invasive pituitary adenomas.</p><p><b>CONCLUSIONS</b>It is important to analyze the grade of invasive pituitary adenomas to improve the removal of pituitary adenomas, avoid injuring cariod artery, and increase the rate of total removal.</p>