1.Plasma concentration of 125 I labeled and polyethylene glycol conjugation to EILDVP peptide in mice
Tiehua ZHAO ; Zihui SHI ; Lingzhan ZHANG
Chinese Pharmacological Bulletin 2015;(12):1745-1748
Aim To study the pharmacokinetics of po-lyethylene glycol conjugation on EILDVP peptide in mice by injection through tail vein.Methods KM mice,saturated thyroid gland with compound of NaI, were injected for 1 25 I labeled EILDVP-Tyr-NH2 ,EILD-VP-Cys (mPEG2000-MAL)-Tyr-NH2 and EILDVP-Cys (mPEG20000-MAL)-Tyr-NH2 peptides (1 25 I:5 mL · kg -1 volume 3.441 GBq·L -1 concentration)by tail intravenous,respectively.Blood samples at different time intervals were obtained,blood plasma was separa-ted,and the radioactivity of precipitation after trichloro-acetic acid (TCA)treatment was tested.According to standard curve equation, the plasma concentration curve and pharmocokinetic parameters were depicted by means of 3P97 pharmocokinetics software.Results Concentration range of 3.75 ~480 μg·L -1 of three 1 25 I labled peptides in plasma from mice had good line-ar relationship.Recovery of method was 88.92% ~
1 06.66%,and RSD <1 0%.The half-life time (T1 /2 ) of EILDVP-Tyr-NH2 peptide modified by mPEG2000 and mPEG20000 ,labled by 1 25 I was 0.43h and 1 .94h,re-spectively,which was 1 .54 times and 6.93 times that of prototype peptide (T1 /2 =0.28h),and the clear-ances (Cl)were 1 .23 times and 24.71 times,respec-tively.The apparent distribution volume (V)values of the three species were small,which might mainly dis-tributed in the plasma.Conclusions Suitable for mo-lecular mass mPEG modified the EILDVP peptides could extend to maintain time in vivo,which could play a positive role in improving efficacy.In the experimen-tal range,EILDVP peptide modified by larger molecu-lar mass of mPEG20000 has better effect.
2.Effect of Electroacupuncture on Hand Function in Postoperative Patients with Hand Trauma
Xueqing CENG ; Xiaoqiu MOU ; Dongshi TENG ; Hongmei LV ; Zihui ZHANG
Shanghai Journal of Acupuncture and Moxibustion 2015;(11):1109-1110
Objective To investigate the rehabilitative effect of electroacupuncture on hand function in postoperative patients with hand trauma.Methods Sixty-eight postoperative patients with hand trauma were randomly allocated to treatment and control groups, 34 cases each. The control group received routine rehabilitation therapy and the treatment group, electroacupuncture in addition. Pre-/post-treatment changes in thumb motor function, the distance from index, middle, ring and little fingers to the palm and the distance from the finger nails to the table were observed in the two groups after three months of treatment.Results There was a statistically significant post-treatment difference in the thumb motor function (abduction and opposition) grade between the two groups (P<0.05). There were statistically significant pre-/post-treatment differences in the distance from index, middle, ring and little fingers to the palm and the distance from the finger nails to the table in the two groups (P<0.01). There were statistically significant post-treatment differences in the distance from index, middle, ring and little fingers to the palm and the distance from the finger nails to the table between the treatment and control groups (P<0.01).Conclusion Electroacupuncture can effectively improve hand function in postoperative patients with hand trauma.
3.Effect of Polysaccharides of Radix scrophulariae on Immune Functions in Mice under Normal Physiological and Hypoimmunical State
Zihui LI ; Ning ZHANG ; Wanru DONG ; Hui YU ; Shumin LIU
China Pharmacy 2017;28(10):1316-1319
OBJECTIVE:To study the effect of polysaccharides of Radix scrophulariae on immune function in mice under nor-mal physiological and hypoimmunical state. METHODS:80 mice were randomly divided into normal group,model group,treat-ment high-dose,medium-dose,low-dose groups and physiological high-dose,medium-dose,low-dose groups,10 in each group. Mice in normal group and model group were received distilled water (10 mL/kg) intragastrically,treatment high-dose,medi-um-dose,low-dose groups and physiological high-dose,medium-dose,low-dose groups were administrated 0.16,0.08,0.04 g/kg drug,ig,once a day,for 7 d. From the third day,mice in model group and treatment high-dose,medium-dose,low-dose groups were respectively received cyclophosphamide(100 mg/kg),ip,for 4 d to induce hypoimmunical model. Carbon clearance test was adopted to determine the carbon clearance indexes and organs(chest,spleen)indexes of mice. Another 80 mice were grouped with the same administration,serum half hemolytic value (HC50) was determined after compressed Mianyang red blood cell sensitiza-tion. Then another 80 mice were grouped with the same administration,1% dinitrofluorobenzene method was used to induce de-layed hypersensitivity in mice;its ear swelling was determined,as well as IL-2,IL-4,immunoglobulin G(IgG),immunoglobulin M(IgM),γ-interferon(IFN-γ)contents in serum,and the proliferation in vitro of splenic lymphocytes were detected. RESULTS:High-dose polysaccharides can promote the increasing of immune organ and carbon clearance indexes(P<0.05);enhance the inten-sity of delayed type hypersensitivity (HC50 increasing)(P<0.01) and improve the decreasing of serum hemolysin in model mice (P<0.01);promote the splenic lymphocytes proliferation and increase IL-2,IL-4,IgG,IgM,IFN-γ contents in serum(P<0.05 or P<0.01). CONCLUSIONS:Polysaccharides can enhance the immune function in mice under normal physiological and hypoim-munical state induced by cyclophosphamide.
4.Clinical Significance of Combined Detection of Serum Retinal-binding Protein,Cystatin C and β2-micoglobuimin in Diagnosis of Early Renal Injures of Gestational Diabetes Mellitus
Xuehua YUAN ; Weiwei ZHANG ; Quanlun LI ; Yingyue KE ; Zihui WANG
Journal of Modern Laboratory Medicine 2017;32(2):106-109
Objective To study the diagnosis value of serum retinol binding protein (RBP),cystatin C(Cys C) and β2 microglobulin (β2-M) in early renal injures of gcstational diabetes mellitus (GDM) patients.Methods 85 case of GDM pregnant women admitted to Shiyan Maternal and Child Health-Care Hospital from Jan.2009 to Jan 2015 were chosen as research objects,and were divided into simple diabetes group (35 cases),micro proteinuria group (30 cases) and massive proteinuria group (20 cases) according to the urinary albumin excretion rate (UAER),while 30 cases of healthy pregnant women were recruited randomly during the same period as control group.The 24h urine protein,serum RBP and renal function indicators [blood urea nitrogen (BUN),creatinine (Ser),Cys C and β2 M],the positive rates of RBP,Cys C,β2-M and combined detection of RBP,Cys C,β2-M of the four groups were compared.Results The 24h urine protein in simple diabetes group,micro proteinuria group and massive proteinuria group were significantly higher than that in the control group (t=3.91~ 16.33,all P<0.01),the difference between the 3 groups were statistically significant (t=6.78~ 16.94,all P<0.01).The levels of BUN,Scr,Cys C,β2-M and RBP in micro proteinuria group and massive proteinuria group were significantly higher than those in control group and simple diabetic group (t=3.68 ~ 18.54,all P<0.01),there were significant difference in above indexes between micro proteinurine group and massive proteinuria group (t=4.70~ 10.87,all P<0.01).The positive rates of RBP,Cys C,β2-M and combined detection of RBP,Cys C and β2-M in micro proteinuria group and massive proteinuria group were significantly higher than those in control group and simple diabetic group (x2 =20.27~38.57,all P<0.01).There was no significant difference in the positive rates between micro proteinuria group and massive proteinuria group (x2 =0.62~0.93,all P>0.05).The positive rate of combined detection of the three indicators was higher than that of the single detection in the same group (x2=3.97~6.65,P<0.05 or P<0.01).Conclusion The detection of serum Cys C,RBP and β2-M has a high clinical value in the diagnosis of early renal damage in patients with GDM.The positive rate of combined detection of 3 indexes was higher than that of single index.
5.Experience of diagnosis and treatment of functional insulinoma:a report of 12 cases
Xuewen ZHANG ; Yongsheng YANG ; Lu ZHANG ; Yingjun JIE ; Dan ZHANG ; Zihui MENG
Journal of Endocrine Surgery 2010;04(3):167-169
Objective To improve the knowledge of the diagnosis and treatment of functional insulinoma. Methods The clinical data of 12 cases of functional insulinoma in China-Japan Union Hospital of Jilin University from 2000 to 2009 were analyzed retrospectively. Results For the 12 cases of functional insulinoma, preoperative fasting blood glucose and the positive rate of insulin were 92% and 89% respectively. The positive rate of IRI/G and C-Peptide reached 100%. The accuracy of the niveau diagnosis of preoperative abdomen ultrasound, CT and of MRI were 75%, 36% and 0% respectively; whereas the accuracy of localization of intraoperative palpation combined with ultrasonography reached 100%. The result of glucose increased by one time within one hour after excision and the rest excision. In the 7 follow-up cases, the symptom of hypoglycemia was not found. There were 3 cases of pancreatic fistula after operation. Conclusions For the suspected cases of functional insulinoma, the measurement of IRI/G and C-Peptide are needed besides measuring blood glucose and insulin. Intraoperative palpation and ultrasonography are effective methods of the localization of functional insulinoma. The complete resection of the insulinoma can be assessed by monitoring the change of the blood glucose after excision as well as the rapid intraoperative pathological examination.
6.Nonclinical safety evaluation of Insulin NPH, a biosimilar of Humulin NPH
Zongshang XIANG ; Zihui SONG ; Huixia ZHANG ; Chunyu LI ; Hairong WANG ; Yongming CAI ; Zongpeng ZHANG
Drug Evaluation Research 2017;40(5):652-658
Objective To investigate the toxic reaction,toxic organs or target tissues of protamine recombinant human insulin (Insulin NPH),and provide basis for clinical trials by single dose toxicity test in mice,repeated toxicity and immunogenicity of Beagle's dogs,and systemic active allergy in guinea pig.Methods ① Using maximum dose method,mice in single dose toxicity test were sc injected with normal saline (NS),vehicle,and Insulin NPH (2092-2488 IU/kg),the toxic reactions after injection were monitored.② In repeated toxicity study,Beagle's dogs were sc administrated with vehicle,the original (Humulin NPH,1.5 IU/kg)and different doses of Insulin NPH (0.5,1.0 and 1.5 IU/kg) for 30 d continuously,followed by a 14-d recovery.During the administration and recovery period,general observation,local irritation,body weight,anus temperature,blood glucose,and electrocardiogram (ECG) were checked,moreover,hematology,serum biochemistry and urine were detected.Also,organic weights and histopathological examination were conducted.Binding antibodies in dog serum were measured by indirect ELISA method in immunogenicity test.③ In systemic active allergy study,cavies were sc injected with low-and high-dose (4 and 12 IU/kg) Insulin NPH,normal saline and vehicle.Besides,ova as positive control was also included.After five times of sensitization test with above doses,the excitation reactions of iv injection with tripled sensitizing doses were observed.Results No obvious toxicity was observed in mice after injected with 165 times of usual clinical dose of Insulin NPH.Repeated toxicity study of Beagle's dogs revealed that 1.0 IU/kg was the no-toxic-effect dose (NOAEL) for Insulin NPH,which was equivalent to 2 times of clinical dose.No bindingantibodies were found in immunogenicity test.There was no obvious allergic symptom in the active systemic allergy study of guinea pig.Conclusion Under the experimental conditions,no serious toxicity of Insulin NPH is found.
7.Recombinant human thyroid stimulating hormone-aided 131I treatment for differentiated thyroid carcinoma
Zhongjing WANG ; Xuyan ZHANG ; Diyu LU ; Minxian SUN ; Zihui XU ; Sheng DING
Chinese Journal of Endocrine Surgery 2016;10(1):19-22
Objective To observe the infiuence of recombinant human thyroid stimulating hormone(rhTSH)-aided 131I treatment for patients with differentiated thyroid carcinoma (DTC)and its efficacy on thyroid hormone level.Methods 20 cases with DTC admitted from Nov.2010 to Jun.2014 were divided into 2 groups.11 cases received rhTSH-aided 131I treatment (rhTSH-aided group)and the other 9 cases received 131I treatment after thyroid hormone withdrawal (THs withdrawal group).The influence of the 2 treatment methods on the serum TSH,FT3,FT4,Tg was evaluated,and the therapeutic effects were assessed according to 131I whole body scintigraphy (WBS)and Tg-negative rate.Results The serum TSH was significantly higher in rhTSH-aided group than that before treatment(t=27.70,P< 0.001)and in THs withdrawal group (t=7.18,P<0.001).TSH levels of all patients were>30 mU/L.WBS displayed that the thyroid remnant clearance rate was 72.73%(8 cases)nd 66.67%(6 cases)respectively in rhTSH-aided group and THs with-drawal group and there was no statistical difference between the 2 groups(x2=0.178,0.673).Conclusion The rhTsH treatment can help to accomplish the preparation of 131I treatment for DTC and acquire satisfactory ablation efficacy.
8.Research and Design of Hypertensive Patients Health Management App Which Aims at Medication Compliance
Yibo WU ; Chenxin QUAN ; Zihui CHEN ; Xiaotao LIU ; Xiaoxiao YUAN ; Yunxi ZHANG
Journal of Medical Informatics 2017;38(5):34-38
The paper analyzes the cause for poor medication compliance of hypertensive patients,indicates the necessity of development of hypertensive health management APP,designs three core functions of the APP including health science popularization,medication reminding and blood pressure monitoring,promotes the improvement of medication compliance of patients,and improves the use intensity of users of the APP through the internal incentive measures that combining health belief and effect monitoring and the external incentive measures that focus on the reward system.
9.Effect of atopic dermatitis-related cytokines on skin barrier
Nan ZHANG ; Lian WANG ; Lian LIU ; Zihui ZHANG ; Xian JIANG
Chinese Journal of Dermatology 2019;52(1):46-49
The skin is the largest organ of the human body,and is an important barrier.There is dysfunction of skin barrier in patients with atopic dermatitis (AD),and the composition of cytokines in patients with AD is different from healthy persons.Many cytokines found in the skin of AD patients can affect the differentiation and cornification of keratinocytes.This review summarizes the latest advances in AD-related cytokines and their effect on skin barrier function.These results are helpful to understand the pathogenesis of AD,and may provide new directions for the treatment of AD.
10.Role of p38 MAPK/CREB signaling pathway in tetramethylpyrazine-induced reduction of hippocampal inflammatory responses in mice with sepsis-associated encephalopathy
Jue WANG ; Hao ZHU ; Changshun HUANG ; Zihui LU ; Yijun CHEN ; Yiwei ZHANG ; Jing SHEN
Chinese Journal of Anesthesiology 2021;41(7):870-873
Objective:To evaluate the role of p38 mitogen-activated protein kinase (MAPK)/cyclic adenosine monophosphate response element-binding protein (CREB) signaling pathway in tetramethylpyrazine-induced reduction of hippocampal inflammatory responses in mice with sepsis-associated encephalopathy (SAE).Methods:Sixty healthy male C57BL6 mice, weighing 24-27 g, were divided into 4 groups ( n=15 each) using a random number table method: sham operation group (group Sham), sepsis group (group Sep), tetramethylpyrazine group (group TMP) and p38 MAPK inhibitor SB203580 group (group SB). The model of SAE was established by cecal ligation and puncture in anesthetized mice.Tetramethylpyrazine 10 mg/kg was injected intraperitoneally once a day at 3 days before the establishment of the model in TMP group, and SB203580 2.0 mg/kg was intraperitoneally injected at 30 min after the establishment of the model in SB group.The equal volume of normal saline was given intraperitoneally in Sham and Sep groups.At 1 day after operation, cognitive function was assessed by Morris water maze, and the escape latency and ratio of time spent in the target quadrant were recorded.The animals were sacrificed after the test, and hippocampal tissues were taken for determination of the contents of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-6 (by enzyme-linked immunosorbent assay) and for detection of the expression of phosphorylation of p38 MAPK, GSK3 and CREB and expression of brain-derived neurotrophic factor (BDNF) (by Western blot). Results:Compared with group Sham, the escape latency was significantly prolonged, the ratios of time spent in the target quadrant were decreased, the contents of IL-1β, TNF-α and IL-6 were increased, the phosphorylation of hippocampus p38 MAPK was increased, the phosphorylation of GSK3 and CREB were decreased, and the expression of BDNF was down-regulated in Sep, TMP and SB groups ( P<0.05). Compared with group Sep, the escape latency was significantly shortened, the ratios of time spent in the target quadrant were increased, the contents of IL-1β, TNF-α and IL-6 were decreased, the phosphorylation of hippocampus p38 MAPK was decreased, the phosphorylation of GSK3 and CREB were increased, and the expression of BDNF was up-regulated in TMP and SB groups ( P<0.05). Compared with group TMP, no significant change was found in the parameters mentioned above in group SB ( P>0.05). Conclusion:p38 MAPK/CREB signaling pathway is involved in the process of tetramethylpyrazine-induced reduction of hippocampal inflammatory responses in mice with SAE.