OBJECTIVE: To promote rational use of drugs in clinic. METHODS: The difference of chronopharmacodynamics, chronopharmacokinetics and chronotoxicity of drugs were introduced, referring to the relevant literatures, journals and practices. RESULTS: The same drug represented different efficacy and toxicity for one day due to delivery at different time. CONCLUSION: According to chronopharmacology, administration at optimal time contributes to efficacy and reduces adverse reaction.

Purpose To establish a golden hamster model of intrahepatic cholangiocarcinoma (ICC) using BOP [N-nitrosobis (2-oxo-propyl) amine] and to explore the protein expression of Wisp-1,β-catenin, TGF-β1 and Smad4 in ICC and their relationship with the tumorigenesis. Methods 57 female golden hamsters aged 8 to 9 weeks (39 in experimental group, 18 in control group), the experi-mental animals were subjected to subcutaneous injection of BOP, the control group was injected with saline. The liver was removed and paraffin sections were prepared for histopathological observation. The protein expression of Wisp-1,β-catenin, TGF-β1 and Smad4 was detected by immunohistochemistry (IHC) in these blocks. Results Most of the animals in the experimental group (29/39) developed ICC, part of the animal (8/39) developed bile duct dysplasia, 1 developed focal bile duct hyperplasia, and 1 was not found bile duct hyperplasia. The positive expression rates of four protein markers in ICC, bile duct dysplasia and normal intrahepatic bile duct tissues were Wisp-1,79. 3%, 87. 5% and 5. 0%,β-catenin, 96. 6%, 100. 0% and 15. 0%, Smad4, 96. 6%, 100. 0% and 25. 0%, TGF-β1, 62. 1%, 12. 5% and 5. 0%, respectively. The positive expression rates of Wisp-1, beta-catenin and Smad4 protein in both the ICC and the tissue of bile duct dysplasia were higher than that of normal intrahepatic bile duct tissue ( P<0. 001 ) , The positive ex-pression of TGF-β1 in the ICC tissue was higher than that of normal intrahepatic bile duct tissue and bile duct dysplasia (P<0. 001). Conclusions The study showed that BOP can induce a golden hamster model of ICC and provides a reliable animal model for the study of ICC. The high expression of Wisp-1,β-catenin, TGF-β1 and Smad4 in BOP-induced intrahepatic cholangiocarcinoma is closely re-lated to occurrence, development and infiltration of ICC.

Objective To evaluate a serf-designed diagnostic protoeol which can early detect a femoral neck fracture for patients with a femoral shaft fracture. Methods From September 2005 to June 2007, a self-developed protocol was used to detect an ipsilateral femoral neck fracture for all the patients with femoral shaft fracture who had sought treatment in our department. This protocol consisted of anteroposterior plain radiography of internal rotator, intraoperative fluoroscopy of the hip, a fine (2 mm) cut computed to-mographic scan through the femoral neck, postoperative anteroposterior and lateral plain radiography of the hip in the operating room prior to awakening the patient, at the time of follow-up anteroposterior and lateral plain radiography of the hip in the presence of hip pain. The diagnostic effects of the protocol were compared with those of conventional diagnosis used for all the patients with femoral shaft fracture who had sought treatment in our department from September 2003 to August 2005. A chi-square analysis comparing the protocol group (September 2005 to June 2007) and the non-protocol group (September 2003 to August 2005) was used to assess the early and delayed diagnosis rates for an associated ipsilateral femoral neck fracture. Results The earlydiagnosis rate of an associated femoral neck fracture by the protocol was 93.8%, markedly higher than that by conventional method (46.2%), with statistically significant difference (χ2 = 4.069, P =0.044). Conclu-sion In presence of a femoral shaft fracture. this protocol consisting of plain radiography of intemal rotator, intraoperative fluoroscopy of the hip, fine cut computed tomographic scan of the femoral neck, postoperative plain radiography of the hip, and follow-up plain radiography of the hip in the presence of hip pain, may sig-nificantly improve the diagnostic rate of an associated femoral neck fracture.

To exploit the efficient application of the digital medical records information in the medical scientific research.The medical records department should improve the current management mode.To establish monitoring system concerning,and reduce the risk related to the safety of medical records,strictly regulate the authorization of user.

This paper summarized nursing experience of 11 patients with refractory or relapsed neuroblastoma who developed CAR-T adverse reaction after receiving the transfusion.Nursing key points included:close monitoring of changes of vital signs,especially body temperature and blood pressure;observation of changes of skin,avoiding scratching when skin rash occurred,and daub calamine lotion was applied;strict recording input and output volume of 24 hours,ensuring patency of venous catheters and constant infusion of liquid,observing changes of urine volume and color;strengthening prevention of infection,strict operation of antiseptic technique,protective isolation when moving in laminar flow clean room;monitoring changes of face,breathing,blood oxygen and so on.Through careful treatment and nursing care,the treatment of children was ensured.

Objective: To study the hypoglycemic activity of polysaccharides from Tremella aurantialba mycelium (TMP). Methods: The anti-hyperglycemic effect of TMP was investigated in normal mice and diabetic rats induced by alloxan in comparison with phenformin and acarbose. Results: TMP not only decreased serum glucose level in normal mice, but also in diabetic rats. After i.g.TMP to hyperglycemic rats for 1w, the glucose and TG in serum were decreased obviously , but serum TC did not change remarkably. After i.g. 100 mg/(kg ?d) TMP to hyperglycemic rats for 23 d, liver glycogen and BLA did not change significantly, but serum glucose was reduced obviously compared with the control . Conclusion: TMP has obvious hypoglycemic activity and can reduce hyperlipemic complications.

Objective To observe the change of six cytokines in mice infected with Echinococcus multilocularis as part of the study on immunological mechanism in the infection. Methods Mice were infected by abdominal inoculation of echinococcus protoscoleces. The change of serum level of the cytokines IL-2、IFN-?、TNF-?、IL-4、 IL-5 and IL-10 was determined by ELISA during the infection which lasted for 260 d. Results Compared with uninfected control, the levels of the cytokines all significantly increased in the 260 d. The level of IL-2 reached a peak after 80 d post-infection (p.i.), then decreased quickly after 140 d p.i., High level of TNF-? was detected after 40 d, compared to uninfected control, reached a peak at 100 d p.i., and decreased quickly after 140 d. The level of IFN-? reached a peak after 80 d p.i., and decreased slowly after 140 d p.i., The levels of IL-4, IL-5 and IL-10 remained lower before 80 d, and increased sharply after 100 days. The levels of IL-4 and IL-10 reached peaks at 100 d p.i., and that of IL-5 at 140 d p.i. Conclusion The data suggest that the induction of Th2 antibody-mediated immunity (AMI) with a parallel expansion of Th1 cell-mediated inflammatory (CMI) responses are important mechanism of the host in defending against the metacestodes. Th1 CMI plays an important role at the early stage of infection, and Th2 AMI is important in the later stage of infection.

Objective To analyse the clinical characteristics,gene mutation and enzymatic activity of αgalactosidase A(α-GalA)in a 15-year-old male patient with typical Fabry disease,whose mother was without any clinical manifestations.Methods Clinical features and laboratory data were collected from the patient and his mother.Genomie DNA was extracted from peripheral blood of the patient.his mother,and a healthy control subject.Seven exons of the GLA gene were amplified by PCR.PCR products were purified.cloned into T vector,and then sequenced.The enzymatic activity of α-GalA Was measured by fluorimetrie substrate assay. Results DNA sequencing results showed that a missense mutation of 10036-10038delAAG in exon 7 WaS identified in the patient,resulting in the replacement of 374 lysine and 375 glyeine by arginine,which Was not previously reported.The patient Was a hemizygote with gene mutation,his mother WaS a heterozygote carrying gene mutation,and the healthy control without mutation.α-GalA enzymatic activity assay showed that the enzymatic activity of the patient with GLA gene mutation was only 50%of the healthy control subject,while the enzymatic activity of the patient's mother Was about 70%of the heahhy control SObject.Conclusiolls Detecting GLA gene mutation and α-GalA enzymatic activity in patients with Fabry disease who have been clinically diagnosed seelns to be helpful in finding other patients in the family and in further understanding the molecular pathogenesis of that disease.

Objective To investigate the characteristics and significance of inflammatory factors and insulin resistance index in patients with type 2 diabetes mellitus complicated with depression.MethodsThe patients with type 2 diabetes mellitus complicated with depression were treated with IL-2, TNF-α and HOMA-IR in control group.The patients in type 2 diabetes mellitus had no complication and depression., Record the above indicators of test results.ResultsIL-2, TNF-α and HOMA-IR were the highest in the study group (P<0.05).The levels of IL-2, TNF-α and HOMA-IR in control group 1 and control group 2 were significantly higher than those in control group (P<0.05).There was no significant difference between the two groups.ConclusionThere is a high level of insulin resistance index and inflammatory factor in patients with type 2 diabetes mellitus complicated with depression.Therefore, it is suggested that the treatment of type 2 diabetes mellitus can be treated with anti-inflammatory and insulin resistance.The.