Objective To explore rapamycin's inhibitory effect on proliferation of H_(22) hepatic cancer in mice. Methods In vitro study: H_(22) hepatic cancer cell lines were cultured with rapamycin, CsA, FK506, and proliferation was determined through MTT. The influences of different agents on the H_(22) hepatic cancer cell cycle were observed by flow cytometry. The vascular endothelial growth factor (VEGF) concentration of the supernatant fluid of the cultured H_(22) hepatic cancer cell was detected by ELISA. In vivo study: C57BL/6 to Balb/c mice allogenic skin transplant was established, and the H_(22) hepatic cancer cell was implanted under skin. Rapamycin, CsA, FK506 and 5-FU were fed to the mice, respectively. The effect of different immunosuppressors on the survival of skin graft was observed while the proliferation of the transplant tumor was investigated. VEGF concentration of treated mice serum was examined by ELISA. The microvessel density of the transplanted tumor was observed through immunohistochemistry staining of CD34. Results The proliferation of the H_(22) hepatic cancer cells was inhibited by rapamycin at the concentration different dose of rapamycin, the VEGF concentration of the supernatant fluid decreased significantly (P<0.05). The number of S phase cells decreased significantly compared to that of other agents (P<0.05). When rapamycin, the lengthened survival time of the skin grafts was similar to that in CsA and FK506 groups. But the tumor volume was smaller than that in CsA and FK506 groups (P<0.05). Compared to that in the control group, the VEGF concentration of mice serum decreased in rapamycin group (P<0.05), and the microvessel density of the transplant tumor was reduced greatly (P<0.05). Conclusion Rapamycin, as an immunosuppressor, significantly resists immunologic rejection and inhibits the proliferation of H_(22) hepatic cancer, thus having its advantage in treating malignant hepatic cancer with liver transplantation.

Objective To investigate the isolation and drug resistance change trend of pathogens isolated from ce-rebrospinal fluid (CSF)of neurosurgical patients in Beijing Tian Tan Hospital.Methods Pathogens and antimicro-bial susceptibility of pathogens from CSF specimens of neurosurgical patients from August 1997 to August 2013 were analyzed.Results A total of 2 732 isolates of pathogens were detected,gram-positive and gram-negative bacte-ria accounted for 71 .23% (n = 1 946 )and 28.77% (n =786 )respectively.The top three isolated bacteria were Staphylococcus spp .(n =1 751 ,64.09%),Acinetobacter spp .(n =254,9.30%),and Enterococcus spp .(n =172,6.30%).Gram-positive bacteria were the major isolated pathogens,detection rate of methicillin-resistant Staphylococcus aureus (MRSA ) and methicillin-resistant coagulase-negative Staphylococcus (MRCNS ) was 74.34% and 80.73% respectively;gram-negative bacteria increased gradually in recent years.All Staphylococcus spp .isolates were highly sensitive to vancomycin and linezolid(>90%).The overall antimicrobial susceptibility rate of gram-negative bacteria decreased,susceptibility rates of Acinetobacter spp .to imipenem and meropenem was 51 % and 44% respectively.Conclusion The major pathogens causing intracranial infection in neurosurgical patients are gram-positive bacteria,the detection rates of MRSA and MRCNS are high;gram-negative bacteria,especially extensively drug-resistant Acinetobacter spp .shows an increasing tendency in recent years.

Objective To understand the changing characteristics of drug concentration in the serum and cerebrospinal fluid(CSF) after intravenous (IV) drip of norvancomycin in patients after neurosurgery procedure.Methods Patients with surgical cavity/ventricular drainages after neurosurgery procedure in a hospital in 2014 were selected, and they were divided into 2 groups according to the administration modes (12 in each group), conventional administration group: 0.8 g norvancomycin IV drip for 60 minutes, repeated every 12 hours;continuous administration group, 0.8 g norvancomycin, IV drip for 60 minutes, followed by 0.4 g of IV drip for 11 hours, then 0.4 g for 12 hours, serum and CSF specimens were collected at different time points after administration, concentration of norvancomycin was determined.Results Serum norvancomycin concentration reached a peak of (55.52±26.04) and (59.22±41.88) mg/L in conventional administration group and continuous administration group respectively, 24-hour serum concentration were (8.21±6.04) and (9.11±5.09)mg/L respectively;CSF norvancomycin concentration reached a peak of (16.31±11.15) and (8.82±8.91)mg/L in conventional administration group and continuous administration group respectively, 24-hour CSF concentration were (6.12±2.34)and (5.71±4.72)mg/L respectively;CSF penetration rate of conventional administration group was calculated by ratio of area under curve (AUCCSF/AUCserum), at 0-12 and 12-24 h hour were 63.3% and 59.0% respectively;in continuous administration group were 25.4% and 47.4% respectively.According to 95% of the minimum inhibitory concentration (MIC90) 2 mg/L of target bacteria methicillin-resistant Staphylococcus aureus (MRSA), AUC0-24/MIC90 in conventional administration group and continuous administration group were 192 and 184 respectively.Conclusion For patients who receives early use of standard dose of norvancomycin after neurosurgery procedure, CSF drug concentration after convention and continuous administration of norvancomycin can both reach MIC90 against target bacteria.

Objective To determine the optimal cut-off value of critical-care pain observation tool (CPOT) in assessing degree of pain in patients undergone craniotomy, and to determine the sensitivity and specificity of CPOT with this cut-off value. Methods A prospective observational study was conducted in Beijing Tiantan Hospital. A total of 118 patients admitted to intensive care unit (ICU) after craniotomy was consecutively enrolled during August 2014 to August 2015. CPOT and visual analogue scale (VAS) were used to assess the pain before, during and 20 minutes after the removal of central venous catheters, and the difference was compared between two scores at three time points. Receiver operating characteristic (ROC) curve was used to determine the optimal cut-off values for evaluation of the sensitivity and specificity of CPOT. Patients' complaint of pain was considered the gold-standard. Results CPOT values (inter-quartile range) before, during and after the procedure were 0 (0-3), 0 (0-6) and 0 (0-2), respectively; while VAS values were 4 (1, 6), 3 (1, 6) and 4 (1, 6), respectively. CPOT value during the procedure was significantly higher than CPOT values before and after the procedure (both P < 0.01). When the optimal cut-off value of CPOT was 1, CPOT showed the highest Youden index before, during and after the procedure (1.183, 1.515, and 1.438, respectively), and showed high specificity (all 100%) and low sensitivity (18.3% and 43.8%, respectively) when assessing the pain before and after the removal of the catheter. The sensitivity and the specificity were high when assessing the pain during the procedure, the sensitivity was 69.4%, and the specificity was 82.1%. When the optimal cut-off value of VAS was 2 before and during the procedure, and was 4 after the procedure, VAS showed the highest Youden index, 1.568, 1.452, and 1.509, respectively. VAS demonstrated high sensitivity and specificity before, during and after the procedure (sensitivity was 97.2%, 95.2% and 75.0%, respectively; specificity was 59.6%, 50.0% and 75.9%, respectively). The area under ROC curve (AUC) of CPOT before, during and after the procedure were 0.592 [95% confidence interval (95%CI) = 0.490-0.693], 0.778 (95%CI= 0.693-0.863) and 0.719 (95%CI = 0.627-0.811), respectively; the AUC of VAS before, during and after the procedure were 0.846 (95%CI = 0.771-0.920), 0.767 (95%CI = 0.681-0.854) and 0.838 (95%CI = 0.767-0.909), respectively. The AUC of VAS before and after the procedure was significantly higher than the AUC of CPOT (P < 0.001 and P = 0.006), while there was no significant difference between the AUC of VAS and CPOT during the procedure (P = 0.826). Conclusion CPOT can be used to assess the pain during painful procedure, and it shows high accuracy, but with poor evaluation effect on pain in rest.

Objective To understand teicoplanin concentration in cerebrospinal fluid (CSF)during intravenous in-fusion in patients following neurosurgery operation,and evaluate whether drug concentration can be increased if blood-brain barrier was damaged, and effect of continuous pump of drug on drug concentration in CSF. Methods The post-neurosurgical surgery patients with surgical site/ventricular drainage were enrolled in the study, patients were divided into routine administration group(a dose of teicoplanin of 400 mg/12 h was administered for 30 min)and continuous administration group (a dose of 400 mg teicoplanin was administered for 30 min followed by a continuous infusion of 200 mg/6 h).CSF specimens were collected at respective time points of administration, teicoplanin concentration in specimens was measured.Results For routine administration group,drug concentration in CSF was (0.004 ± 0.0123 )mg/L immediately after teicoplanin was bumped,the peak concentration was (0.712 ± 1.028)mg/L after 1-hour bumping,then concentration decreased gradually,which were (0.254 ±0.222),(0.173 ± 0.152),and (0.355±0.207)mg/L at 12,18,and 24 hours of bumping respectively.For continuous administration group, drug concentration in CSF was(0.017±0.020))mg/L immediately after teicoplanin was bumped,the peak concentration reached (0.587±0.255)mg/L after 4-hour bumping,then concentration were (0.429±0.416),(0.325±0.254),(0.476 ±0.686),and (0.318 ±0.464)mg/L at 6,12,18,and 24 hours of bumping respectively,teicoplanin concentration was relatively stable 6 hours later,which were (0.318±0.464)mg/L-(0.476±0.686)mg/L.The area under the curve during 24 hours (AUC0-24 )in routine administration group and continuous administration group were 5.590 mg/L·h and 9.082 mg/L·h respectively.For two groups of patients,teicoplanin concentration only at the area near peak value a-chieved 50% minimum inhibitory concentration(MIC50 )for coagulase negative staphylococcus (CNS),but the time for a-chieving concentration higher than CNS MIC50 was far less than 50% of total administration time;teicoplanin concentration in CSF of both groups of patients didn’t achieve MIC50 for Staphylococcus aureus .Conclusion After continuous infusion of teicoplanin,drug concentration in CSF can be increased compared with routine administration group,but still can’t achieve the effective MIC;the increase of blood drug concentration is benefit to drug concentration in CSF,it is necessary to in-crease the dose appropriately to achieve clinical effectiveness.

Objective To report one case with congenital ichthyosiform eruption, neurosensory deafness and vascularizing keratitis. Methods The overall clinical and laboratory examinations were conducted to confirm the diagnosis of keratitis, ichthyosis and deafness (KID) syndrome. Results The case presented with the typical hypotrichosis features of the eye lashes and eyebrows, alopecia of the scalp, and ophtalmological lesions. The keratotic plaques over the face, nose, ears, and the extremities were characterstic, and the skin of the trunk was leather-like, dry and hyperkeratotic. Dysplasia of cerebellum, and cystic enlargement of the fourth ventricle of cerebrum, and Dandy Walker syndrome were observed on MRI scanning. Treatment with oral acitretin for 3 weeks cleared the hyperkeratotic ichthyotic lesions on her posterior scalp and also improved other lesions on the extremities and the trunk. Conclusion Acitretin seems to be promising in the treatment of keratotic skin lesions in KID syndrome.

Objective To analyze the clinical characteristics,imaging manifestations and prognoses of anti-GABAB receptor antibodies encephalitis.Methods The clinical manifestations,laboratory findings and radiological data of 13 patients with anti-GABAB receptor encephalitis,admitted to our hospital from September 2015 to March 2017,were retrospectively analyzed.Modified Rankin scale (mRs) was performed to evaluate the prognoses (good prognosis:mRs scores ＜ 2;poor prognosis mRs scores≥3).Results These 13 patients had an average age of 58 years (ranged 49-76 years) with a male to female ratio of 12:1.The major clinical features,including epileptic seizure,were found in 12 patients,psychiatric symptoms in 11 patients,cognitive disorder in 7 patients,and disturbance of consciousness in 4 patients.Brain MR imaging showed abnormal signal in 5 patients:4 were located in the hippocampus and amygdaloid,and one in the pons and left temporal lobe.Five patients showed abnormalities in PET-CT,including 4 with temporal hypermetabolism and 1 with cortical hypometabolism.Chest CT showed lung occupying lesions in 4 patients,of which 2 patients were diagnosed as having small cell lung cancer (SCLC) by pathological examination.Ten patients received immunomodulatory therapy,and three were with supportive care.After the average of 8 months of follow-up,7 patients had good prognosis,5 patients had poor prognosis and one patient lost of follow up.Conclusions Anti-GABAB receptor encephalitis frequently occurs in elderly male subjects and the main characteristic includes prominent refractory epilepsy and shows neurological improvement on immunotherapy.It can accompany by SCLC and have a relatively poor prognosis.

Zinc transporter 8 (ZnT8) is an important candidate antigen for type Ⅰ diabetes. The autoantibody detection kit based on ZnT8 can be used to help diagnose type Ⅰ diabetes, and the related products have been launched in Europe and the United States. Since the recombinant production system of active ZnT8 has not been established in China, this key raw material is heavily dependent on imports. We used Saccharomyces cerevisiae to carry out the recombinant expression of ZnT8. First, multiple antigenic forms of ZnT8 were designed as C-terminal haploid (C), C-terminal diploid (C-C), and N-terminal and C-terminal concatemers (N-C). The proteins were expressed, purified and tested for antigenicity by bridging-type ELISA. The serum of 13 patients with type Ⅰ diabetes and the serum of 16 healthy volunteers were detected. C, N-C, and C-C proteins had similar detection rates, which were 53.8% (7/13), 61.5% (8/13) and 53.8% (7/13). The specificity of the three groups was 100% (16/16). The detection value on positive samples P3, P4, and P8 increased by more than 90%, indicating better serum antibody recognition ability. Finally, N-C protein was selected for further serum sample testing, and the test results were characterized by receiver operating characteristic (ROC) curve for sensitivity and specificity. Compared with imported gold standard antigen, the sensitivity was 76.9% (10/13) and the specificity was 87.5% (14/16). There was no significant difference in the sensitivity of the method, but the specificity needed to be improved. In conclusion, the ZnT8 N-terminal and C-terminal concatemer protein developed based on S. cerevisiae expression system is expected to be a key alternative raw material in the development of in vitro diagnostic reagents for type Ⅰ diabetes.
Antigens ; Autoantibodies ; Diabetes Mellitus, Type 1/diagnosis* ; Enzyme-Linked Immunosorbent Assay ; Humans ; Saccharomyces cerevisiae/genetics* ; Zinc Transporter 8/genetics*