To modify uricase with PEG reagent in order to decrease uricase immunogenieity and increase its stability.Methods:The branched PEG of 40 kD was chosen to modify native uricase.The properties of the mod-ified uricase including the stabilities to protease,pH and temperature,in vivo half-life time,as well as the immu-nogenicity were evaluated.The pharmacokinetic profiles of the midofied uricase were studied in mice.Results:It is demonstrated that the conjugation of PEG to lysine residues of Candida utilis uricase resulted in higher tryp-sin resistance.reduced immune response.and prolonged in vivo half-life.PEG modified uricase retained 80% of the enzymatic activity of native uricase.In addition,it was found that half-life in serum of the intravenously injec-ted PEGylated uriease of up to 696 min was longer that that of native uficase of 45 min.Higher plasma drug con-centrations were also reached with dosing of the PEGylated uricase to mice.Furthermore,the binding affinity Was shown to be reduced for the PEG-uricase using ELISA assay.and it was one-eishth that of native uricase.Final-ly,it Was indicated that the PEG uficase induced a delayed immunoresponse in mice following repeated adminis-trations.Conclusion:These findings demonstrate that this chemically modified form of uricase may serve as a potentially effective drug to treat gout patients.

Objective:To study the influence of some process parameters on the product granularity in pharmaceutical air jet pulverization process.Methods:The method of quadratic regressive orthogonal experiment was used.Results:The mathematics model describing the relationship between the parameters studied and product granularity was established.Conclusion:The conclusions in the experimental study have instructional significance for pharmaceutical production.

Objective To study the influence of valproate sodium(VPA)on neuroprotective effects of topiramate(TPM).Methods For-ty-eight 3-4 week-old male Wistar rats were randomly divided into 4 groups of 12 rats each.Group A was negative control rats,and groups B-D were rat model of epilepsy,induced by pentylenetetrazol(PTZ).The rats in 2 experimental groups were adminstered intragastrically with TPM 40 mg/kg and TPM 40 mg/kg+ VPA 200 mg/kg;2 control groups(groups A and B)with the equal amount of distilled water administration.After 2-month administration,changes of the behavior,levels of serum neuron-specific enolase(NSE)and the pathological in hippocampus were examined.Results The level of NSE in the group of TPM were significantly lower than that in masculine group,but no difference between masculine group and the TPM plus VPA.The pathological change in hippocampus were abatement in the group of TPM.Conclusion TPM plus high dosage of VPA will impaire the neuroprotective effects of TPM.

Objective To investigate the characteristics of the event related potential(ERP) P300 and analyze brain network connections in patients with first-episode depressions.Methods P300 auditory oddball task were administrated on twenty-nine patients and twenty-five healthy controls.The P300 amplitude and latency of two groups were compared,and the brain network connectivity of the two groups were analyzed using Granger's Causality analysis.Results The P300 amplitude in depression group were significantly different from those in control group (C3 of the central regions(15.77±7.35) μV vs (20.90±7.82)μV;C4 of the central regions(16.98±7.21) μV vs (22.11±7.50) μV;P3 of the parietal regions(15.65±6.92) μV vs (19.49±5.73) μV;P4 of the parietal(16.35± 6.46) μV vs P4(19.72±5.18) μV;P=0.009,P=0.007,P=0.017,P=0.024 respectively).However,the P300 latency had no significant difference comparing to the controls(P＞0.05).The results also showed that patients had more connections in the brain network.Conclusion As an effective evaluation index,ERP P300 can play an important role in clinical diagnosis of depression.Patients suffering from depression have significant cognition function deficit.

Objective To investigate the state of endemic fluorosis, running status of water improvement project to reduce fluoride in Jiangsu province, and to provide a scientific basis for prevention and control of endemic fluorosis. Methods In 2008, in the ten key counties of endemic fluorosis (zone), in Xuzhou,Lianyungang and Suqian, a stratified sampling method was employed to select 40 diseased villages according to their past water fluoride survey data. All children aged 8 to 12 were examined dental fluorosis, and all adults over 16 years were examined clinical skeletal fluorosis. Thirty per cent of the 40 diseased villages were selected, and 20 adults over the age of 16 in each selected village were examined by X-ray, respectively;50% of the 40 diseased villages were selected, and 30 any time urine samples of children aged 8 to 12 in each diseased village were tested urine fluoride. In each city, select a county, the status of water improvement project to reduce fluoride, water supply capacity and coverage in the county were investigated. Results A total of 3560 children aged 8 to 12 were examined, the detection rate of dental fluorosis was 38.51% (1371/3560), tooth defect rate was 5.34% (190/3560), and dental fluorosis index was 0.8. Seven hundred and eight urine samples were tested, the median urinary fluoride was 1.47 mg/L and the range was 0.08 ~ 10.08 mg/L. Clinical detection of skeletal fluorosis was 21.3% among adults over the age of 16, and X-ray detection rate of skeletal fluorosis was 39.2% (123/314).Investigated a total of 248 facilities of centralized water improvement projects, no funds to run or damaged 49, the water fluoride > 1.0 mg/L was 18. Conclusions Endemic fluorosis in Northern Jiangsu province has not been controlled completely, but has a rising trend, we should further strengthen the supervision of water fluoride reduction.

OBJECTIVETo investigate the clinicopathological features of testicular malignant Leydig cell tumor (TMLCT) and improve the non-invasive diagnosis of the disease.

METHODSWe retrospectively analyzed the clinicopathological data on a case of TMLCT, detected the circulating tumor cells (CTC) in the peripheral venous blood, and reviewed the related literature.

RESULTSThe patient, a 47-year-old male, underwent radical orchidoepididymectomy under general anesthesia. Postoperative pathology confirmed the lesion to be TMLCT, which was mainly composed of Leydig cells and suspected with vessel carcinoma embolus. Immunohistochemistry showed the tumor cells to be positive for α-inhibin, Ki67, CD30, vimentin, EMA, and PLAP, but negative for CK, CK7, S100, CD10, SMA, Des, AFP, hCG, CEA, CK19, CD117, Oct-4, LCA, CD20, Pax-5, CD3, and CD43. Two CTCs were detected in the peripheral venous blood. The patient received 3 courses of chemotherapy for retroperitoneal multiple lymph nodes metastasis post-operatively. Subsequent CT imaging manifested no obvious reduction of the retroperitoneal lymph nodes and consequently the patient again underwent retroperitoneal lymphadenectomy and cryoablation. At 8 months after treatment, CT examination revealed notably enlarged retroperitoneal lymph nodes with the right adrenal gland evidently invaded.

CONCLUSIONTMLCT is an extremely rare sex-gonad stromal tumor with high malignancy and poor prognosis, and CTCs may be used for its early diagnosis and prognostic prediction.

Biomarkers, Tumor ; metabolism ; Humans ; Immunohistochemistry ; Leydig Cell Tumor ; drug therapy ; pathology ; surgery ; Lymph Node Excision ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplastic Cells, Circulating ; Prognosis ; Retrospective Studies ; Sex Cord-Gonadal Stromal Tumors ; drug therapy ; pathology ; surgery ; Testicular Neoplasms ; drug therapy ; pathology ; surgery

Medullary thyroid cancer (MTC) is characterized hy the secretion of calcitonin that is derived from parafollicular cells.20％-25％ of MTC are hereditary.Compared with other types of thyroid cancer,MTC is prone to recurrence,metastasis,and younger onset age.RET gene germline mutation accounts for the hereditary MTC,and somatic mutation is responsible for part of sporadic cases.A good correlation between phenotype and genotype is reported.We present in this article a case of medullary thyroid cancer patient with genetic diagnosis and treatment as well as postoperative follow-up together with RET gene screening results in her family members in order to call attention to the diagnosis and treatment of MTC.

Objective To analyze clinical charaCteristics and diagnostic experience on thyrotropinoma (TSHoma).Methods Clinical characteristics,laboratory findings,diagnostic experience,and surgical outcome were summarized from 16 cases of TSHoma in our hospital from January 2006 to September 2011.Results ( 1 )Among 16 cases ( 9 male,7 female ) aged ( 51.63 ± 13.23 ) years,14 ( 87.5 ％ ) cases presented with hyperthyroidism and 2 were diagnosed by physical examination. None of them had exophthalmos, acropachy, or pre-tibial myxedema.( 2 ) Serum FT4 and FT3 levels were all above normal range with serum TSH ( 4.37 ± 2.77 ) μIU/ml.There were 25％ (4/16) cases with positive serum thyroglobulin antibody and/or thyroid peroxidase antibody,none with positive TSH receptor antibody.TRH stimulating test was performed in 9 cases,3 were with positive response ( peak TSH level increased by 5.45-9.20 μIU/ml compared with baseline),and 6 without response (peak TSH level increased by -0.01-3.15 μIU/ml compared with baseline).TSH was suppressed to 27.15％ (5.19％-99.15 ％ ) of the baseline in 11 cases in which somatostatin suppression test was carried out.Prolactin and insulin-like growth factor-Ⅰ levels were increased in 2 cases.MRI performed in 15 patients showed 10 cases of microadenomas and 5 cases of pituitary adenoma.A mass in nasal cavity was found in one case,where no mass was found in the pituitary.( 3 )Surgery was made in 11 cases ( 9 patients underwent transsphenoidal operation,one craniotomy,and one underwent operation via endoscopic nasal septum ). All patients (11/11) were proved to yield pituitary adenoma pathologically.Conclusion Thyrotropinoma should be considered in hyperthyroidism with unsuppressed TSH level,and dynamic tests facilitated early diagnosis.Ectopic thyrotropinoma shoull be considered when normal pituitary morphology was shown by MRI.

Background Pupil atresia increases the difficulty of cataract surgery.The improper enlarging pupil will lead to many complications.The appropriate method of pupil dilation is very important to improve the postoperative effect.Objective This study was to evaluate the pupillary function after manually enlarged pupil to different sizes for pupil atresia complicated cataract.Methods A retrospective case-controlled study was designed.Thirty-eight eyes of 30 cases suffered from pupil atresia complicated cataract induced by chronic uveitis were enrolled in Shandong Eye Institute from May 2006 to May 2012.The eyes underwent pupil forming and phacoemulsification and assigned to the pupil enlarged to ≥6.0 mm group (15 eyes) and 4.5-5.5 mm group (23 eyes).The fibrosis membrane at pupil zone was removed,and the fibrosis strip at pupil collar was cut evenly by 23G intraocular microscissors as zigzag shape.Then the pupil was enlarged in multipoint by a pair of left and right iris hook from the main and lateral incisions.The pupils of 15 eyes in the pupil enlarged to ≥6.0 mm group were dilated above 6.0 mm and 23 pupils in the 4.5-5.5 mm group were dilated to 4.5-5.5 mm and followed by routine phacoemulsification and foldable intraocular lens implantation.Topical and systemic corticosteroids and nonsteroidal anti-inflammatory drugs combined topical mydriatic were applied before and after operation.The pupil diameter,light reflex and photophobia symptom in postoperation were compared between the two groups.The visual acuity before and after operation and intra-and post-operative complications were recorded.This study was approved by Ethic Committee of Shandong Eye Hospital,and written informed consent was obtined from each patient before operation.Results The pupil diameter in the pupil enlarged to ≥6.0 mm group was dilated to (6.9±0.4) mm and that of the 4.5-5.5 mm was dilated to (5.1 ±0.3) mm intraoperatively,with a statistical significance between them (t =16.100,P =0.000).Three months later,the pupil diameter in the pupil enlarged to ≥ 6.0 mm group was (4.9 ±0.4)mm,with different degrees of lacerated pupillary margins,and that in the pupil enlarged to 4.5-5.5 mm group was (3.5 ±0.5) mm,with rare lacerated pupillary margins,showing a statistically significant difference (t =9.820,P =0.000).The unresponsive or obtuse light reflex in the pupil enlarged to ≥6.0 mm group was significantly higher than in the pupil enlarged to 4.5-5.5 mm group(11 eyes vs.6 eyes) (x2 =8.200,P =0.005).The subjective photophobia symptom of 2-3 grades in the pupil enlarged to ≥6.0 mm group was in 12 eyes,which was higher than that in the pupil enlarged to 4.5-5.5 mm group (2 eyes) (H=19.840,P=0.000).The iris haemorrhage were seen in 3 eyes in the pupil enlarged to 4.5-5.5 mm group and 7 eyes in the pupil enlarged to ≥6.0 mm group (x2 =5.290,P=0.030).The visual acuities of the operated eyes in the two groups improved at different degrees.Conclusions Approximate physiological pupil and good visual quality can been obtained by manual releasing and enlarging pupil to less than 5.5 mm evenly during the surgery for pupil atresia complicated cataract induced by chronic uveitis.

Background Eyes with filamentary keratitis present with serious clinical symptoms.This disease is easy to relapse and the treatment is tricky.At present,its pathogenesis is still unclear,and few works were done on filamentous composition.Objective This study was to analyze the composition of corneal filament by imageological and histopathological method,and discuss the formation mechanism of filamentary keratitis.Methods Eighty-eight eyes of 82 cases who suffered from filamentary keratitis were collected in Shandong Eye Hospital between January 2008 and January 2011.The etiologies of the patients were classified and the clinical data were recorded.Firstly,the corneal filiform strip was detected by laser scanning confocal microscopy (LSCM),and the corneal structure was examined by high-definition optical coherence tomography (HD-OCT).Then the composition of filamentary strip was analyzed by Giemsa and Masson trichrome staining of stretched preparation of filiform strip.Results Etiological study showed that filamentary keratitis occurred after penetrating keratoplasty in 40 eyes,after cataract surgery and photorefractive keratectomy (PRK) in 18 eyes,dry eye and neural dystrophic corneal disease in 14 eyes,acute conjunctivitis in 10 eyes.HD-OCT revealed that filament lesion developed to Bowman layer.Filament was composed of epithelial cells,inflammatory cells,mucus and the high reflective strip core with spiral arrangement under the LSCM,and epithelial cells,inflammatory cells and fibrous tissue were seen in the strip core.Giemsa staining exhibited that filament contained corneal epithelial cells,inflammatory cells,mucus and dark blued strip core with helical arrangement.Masson trichrome discovered that the strip core was red fibrous tissue surrounding by blue mucus.Conclusions Epithelial cells,inflammatory cells,mucus and the high reflective strip core with spiral arrangement are the main elements of filament in filamentary keratitis.The lesion can reach Bowman layer.The results contribute to reveal the formation mechanism of corneal filament and assist treatment.