Objective To establish and evaluate the CaV1?1?R528H gene knock?in mouse model of thyrotoxic hy?pokalemic periodic paralysis. Methods Thirty?six 8?week?old male CaV1?1?R528H gene knock?in mice and thirty?six 8?week?old wild?type male C57BL/6J mice were used in this study. Using three?factor two?level 2 × 2 × 2 factorial design ( the three factors including mutation, thyroxine and insulin, and two levels were with or without) , the mice were divided into 8 groups. The thyroxine groups were intraperitoneally injected with levothyroxine in a dose of 350 μg/kg once per day for 12 consecutive days to produce thyrotoxicosis. The insulin groups were intraperitoneally injected with short?acting insulin in a dose of 0?8 U/kg after the last administration of levothyroxine, and the potassium levels of different groups were meas?ured and recorded before (0 min) and after insulin injection (30 min, 60 min). Results (1) Compared with the control group, the following phenomena including irritability, dull coat, increased diet and water intake, and slow body weight gain, were observed in the thyrotoxic mice. Thyroid function tests showed that the levels of T3 and T4 in the thyrotoxic mice were significantly higher than those in the corresponding control mice (P<0?05), and the TSH level was significantly low?er than that of the corresponding control mice (P<0?05 ). (2) After administration of insulin or thyroxine alone, the po?tassium levels in the mutant and wild?type mice were not significantly different. However, after combined administration of thyroxine and insulin, the potassium levels in the mutant group were significantly lower than those in the wild?type mice at 30 min and 60 min ( P<0?05 for both). (3) The main effects and interactions:Mutation factor or thyroxine factor alone did not influence on the potassium level, only insulin showed hypokalemic effect (P<0?05). There were interactions be?tween thyroxine and mutation, and between insulin and mutation (P<0?05), but no interaction between thyroxine and in?sulin. Conclusions (1) A thyrotoxicosis state in mice is successfully developed in this study. (2) An CaV1?1?R528H gene knock?in mouse model of thyrotoxic hypokalemic periodic paralysis is successfully established.

Although current synthetic anti-gout drugs have significant therapeutic effects in reducing serum uric acid levels, they have serious side effects such as allergic reactions and liver and kidney damage. Natural products with a wide range of uric acid-lowering and high safety have played a critical role in anti-gout drug discovery and development. This paper reviews the natural products with uric acid-lowering or anti-gout pharmacological effects and the investigation on their mechanisms of action, to provide information for drug discovery and development.

Soft X-ray microscopy is a microimaging technique using soft X-ray as illuminative source. It fills the gap between optical and electron microscopy. Soft X-ray microscopes have better resolution than visible microscopes. In comparison with electron microscopes, it can examine thick (up to 10 micrometers for biological samples) and wet specimens in their natural states without being dehydrated, sectioned and stained. In addition, soft X-ray microscopy can map elements and analyze the biological macromolecules such as protein and DNA in the examined samples. In this paper, the advantages of soft X-ray microscopy for biology are briefly described. The applications of soft X-ray microscopy to the analysis of mammal and human sperm are illustrated.
Animals ; Humans ; Male ; Microscopy ; methods ; Spermatozoa ; ultrastructure ; X-Rays

Objective To investigate the application value of serum auto-antibody detection combined with low-dose spiral computed tomography (LDCT) in early lung cancer screening. Methods From 12568 medical examination crowd (7453 males and 5115 females), 1324 people with high-risk cases of lung cancer in our medical examination center were divided randomly into three groups (LDCT, serum auto-antibody, and serum auto-antibody combined with LDCT groups). All people in this research were screened by chest X-ray. Follow-up was conducted for one year, and the positive screening and diagnosis rates of early lung cancer screening were compared between these groups of high-risk people with lung cancer. Results The positive screening and diagnostic rates of high-risk lung cancer in the serum auto-antibody combined with LDCT group was significantly higher those that in other two groups (P < 0.001). The specificity and sensitivity of serum auto-antibody combined with LDCT group were 89.1% and 88.4%, respectively; the area under the ROC curve was 0.863. Conclusion Serum auto-antibody detection combined with low-dose spiral CT can significantly improve the positive screening rate of lung cancer in high-risk populations, providing a strong theoretical support for lung cancer screening pathway.

This study was aimed to analyze the clinical and laboratorial characteristics of patients with chronic lymphocytic leukemia (CLL), as well as their relationship with outcomes of patients. The clinical and laboratorial data of 40 CLL patients admitted from 2004 to 2010 in our hospital were analyzed retrospectively. The results indicated that the most of CLL attacked the elderly male patients with median age 66 (from 42 to 80). Flow cytometric analysis showed that 25 cases were positive for typical immunophenotype of CLL. On the other hand, all the patients clearly expressed CD19 and CD5, 7 cases (17.5%) and 14 cases (35%) were positive for the expression of CD38 and Zap70 respectively. 8 cases harbored a mutated immunoglobulin heavy-chain (VH) gene, among them 4 cases belong to VH3 family. Interphase FISH analysis showed that P53 deletion, RB1 deletion, trisomy 12 and normal chromosome were detected in 6, 3, 1, and 5 cases, respectively. The median PFS in 31 patients received treatment of fludarabine based chemotherapy was 48 months (95%CI: 39 - 57 months), among them 27 cases (87.1%) achieved CR + PR. While PFS was 14 months (95%CI: 10 - 18 months, P < 0.001) in 9 patients received other treatment regimen, out of them only 3 cases (33.3%) achieved CR + PR. Patients with normal level of serum β2-microglobulin at diagnosis showed significantly higher overall survival (78%, 95%CI: 69% - 87%) in 36 months than those with abnormal level of serum β2-microglobulin (47%, 95%CI: 35% - 59%, P = 0.004). Significant difference in the rate of CR + PR was noted in the Zap70 positive group (50%) and in negative group (88.5%, P = 0.006). All of 8 patients with IgVH mutation displayed CR after treatment, while 4 cases (66.7%) archived CR among 6 patients without IgVH mutation. It is concluded that CLL is characterized by high heterogeneity in both clinical features and molecular markers, which are associated with prediction of outcomes for patients. The treatment with fludarabine-based chemotherapy results in a major benefit and long survival for patients with CLL.
ADP-ribosyl Cyclase 1 ; metabolism ; Adult ; Aged ; Aged, 80 and over ; Female ; Flow Cytometry ; Humans ; Immunoglobulin Variable Region ; genetics ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; metabolism ; Male ; Middle Aged ; Mutation ; Retrospective Studies ; ZAP-70 Protein-Tyrosine Kinase ; metabolism

This study was aimed to investigate the relationship between Richter's syndrome (RS) transformation and clinical characteristics as well as karyotype of patient with chronic lymphocytic leukemia (CLL). By the follow-up of a patient with CLL, the clinical characteristics, karyotype, treatment pattern and its effect, as well as disease progression were monitored regularly with serological test, flow cytometry and FISH technique. The results indicated that the patient typically presented with history of CLL at initial diagnosis, with expression of CD5(+), CD19(+) and CD23(+), Binet stage C, as well as karyotype aberration of trisomy 12, and poorly responded to 4 cycles of standard chemotherapy of FCR regimen. The disease progression was confirmed at 5 months with the symptoms of fever in the absence of infection, elevated lactate dehydrogenase level and rapidly enlarging lymphnodes which showed typically diffuse large B cell lymphoma by the biopsy. It is concluded that karyotype aberration of trisomy 12 is one of the risk factors for RS transformation, and treatment pattern of the patient with CLL may be associated with the transformation of RS.
Cell Transformation, Neoplastic ; genetics ; Chromosomes, Human, Pair 12 ; Female ; Humans ; Karyotype ; Karyotyping ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; Middle Aged ; Trisomy

OBJECTIVETo compare the clinical characteristics of gastric cancer between young and elderly patients,and bring forward corresponding countermeasures.

METHODSClinical characteristics, treatment and prognosis between 79 young (or= 65 years old) patients were compared.

RESULTSThe constituent ratio of gender between young and elderly group was not significantly different (P=0.226). There was no particularity of early symptom in young patients, but they had shorter course of disease (165 d vs 400 d, P=0.029) and more frequent inferior part of cancer (49.4% vs 41.7%, P=0.038) as compared to elderly patients. There was significant difference between two groups in pathological stage ratio (P=0.027). The median total survival time of young and elderly patients was 1006 d and 530 d respectively, which was not significantly different (P=0.108). Furthermore, median survival time of young and elderly patients after radical resection were 1197 d and 919 d respectively, and the difference was not significant as well (P=0.242).

CONCLUSIONSCharacteristics of young patients with gastric cancer are lower incidence, larvaceous symptoms, more malignancy and quick development, which still remain general features of gastric cancer. By correct therapy, the efficacy of above young patients is similar to elderly patients. The key to improve prognosis is to further fortify cognition for gastric cancer and elevate early diagnostic rate.

Adult ; Age Factors ; Aged ; Carcinoid Tumor ; pathology ; Female ; Humans ; Male ; Prognosis ; Stomach Neoplasms ; pathology ; Survival Rate

OBJECTIVETo establish a three-dimensional finite element model of mandibular distraction osteogenesis (DO) in order to study the influence of distraction orientations to mandibular DO.

METHODSBy using the two finite element models, Von Mises stress and the displacement under different loads were measured.

RESULTSThe maximum stress in the distract equipment paralleled to the mandibular corpus was two times of that when the distract equipment paralleled to the sagittal axis. Von Mises stress concentration mainly occurred in the loading position and the condylar ante inferior. This phenomenon may lead to partial bone resorption, consequently lead to screw loose and affect the stability of distraction device. When the displacement increased in the model, the maximum stress and displacement showed linear relation.

CONCLUSIONThe counterforce produced by the device makes lateral displacement in tail. The reaction force could be reduced to a minimum degree when the traction device parallel to the sagittal axis. This study provides theoretical basis for the position of distract equipment and distraction orientations in clinical application.

Biomechanical Phenomena ; Finite Element Analysis ; Humans ; Mandible ; Osteogenesis, Distraction

Abstract: Our previous work revealed berberine can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, which suggested that berberine has synergistic antifungal activity with fluconazole. Preliminary SAR of berberine needs to be studied for the possibility of investigating its target and SAR, improving its drug-likeness, and exploring new scaffold. In this work, 13-substitutited benzyl berberine derivatives and N-benzyl isoquinoline analogues were synthesized and characterized by 1H NMR and MS. Their synergetic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The 13-substitutited benzyl berberine derivatives 1a-1e exhibited comparable activity to berberine, which suggested that the introduction of functional groups to C-13 can maintain its activity. The N-benzyl isoquinolines, which were designed as analogues of berberine with its D ring opened, exhibited lower activity than berberine. However, compound 2b, 2c, and 4b showed moderate activity, which indicated that berberine may be deconstructed to new scaffold with synergistic antifungal activity with fluconazole. The results of our research may be helpful to the SAR studies on its other biological activities.
Antifungal Agents ; pharmacology ; Berberine ; pharmacology ; Candida albicans ; drug effects ; Drug Resistance, Fungal ; Drug Synergism ; Fluconazole ; pharmacology ; Isoquinolines ; pharmacology ; Microbial Sensitivity Tests

Aim Study the interaction between metho-trexate and levetiracetam after oral administration and hepatorenal toxicity in rats, to provide theoretical basis for the clinical rational use of two drugs. Methods Male SD rats ( 250 ± 20 ) g were selected as experi-mental animals. Rats were randomly divided into 3 groups ( 1 mg·kg-1methotrexate group, 180 mg· kg-1 levetiracetam group, combined group), 5 rats in each group. The following experiment was carried out:(1) pharmacokinetic parameters study; (2) renal ex-cretion study; (3) liver and kidney toxicity study. All samples were determined by ultra performance liquid chromatography-tandem mass spectrometry ( UPLC/MS/MS) . Results After the combination of two drugs, the Cmax, AUC0-t and Tmax of methotrexate in-creased, T1/2, Cl and MRT of methotrexate decreased, the differences was statistically significant. The Tmax, T1/2, Cl, MRT of levetiracetam had a certain upward trend, AUC0-t had a certain downward trend, the differences has no statistically significant. After combi-nation of two drugs, the renal excretion of methotrexate increased significantly, the renal excretion of levetirac-etam decreased significantly and hepatorenal toxicity increased significantly. Conclusion After combina-tion of two drugs by oral administration, Levetiracetam significantly increased methotrexate absorption in rats. Levetiracetam increased the plasma concentration and renal excretion of methotrexate and caused hepatorenal toxicity significantly. It is suggested that dose adjust-ment is necessary for combination of two drugs.