Aim To elucidate the relationship between IgG antibodies and penicillin allergy.Methods Enzyme-linked immunosorbent assay was used to examine 8 kinds of specific IgG antibodies,including major antigenic determinants:benzylpenicilloyl(BPO),ampicilloyl(APO),amoxicilloyl(AXO)and phenoxomethylpenicilloyl(PVO),and minor antigenic determinants:benzyl-penicillanyl(BPA),amoxicillanyl(AXA),ampicillanyl(APA)and phenoxomethylpenicillany(PVA),in the sera of 241 patients with penicillin allergy.Results Except BPA-IgG,levels of 7 kinds of antigenic determinants IgG antibodies were significantly higher than those of control group(P

Objective To investigate the effect of hydrogen-rich water on cerebral edema and aquaporin 1 (AQP1) expression in rats with traumatic brain injury (TBI).Methods Ninety male Sprague-Dawley (SD) rats were randomly divided into sham operation group,TBI model group,hydrogen-rich water treatment group (H group),with 30 rats in each group.TBI model was reproduced by weight dropping method.The skulls of rats in sham operation group underwent only craniotomy without direct hit and with bone wax sealed suture.5 mL/kg of hydrogen-rich water injection was given intraperitoneally after model reproduction in H group,and equal amount of normal saline was given in sham and TBI groups,once a day for both groups for 5 days.Six rats from each group were sacrificed at 6,12,24,48 hours and 5 days after evaluating neurological severity scores (NSS).The cerebral cortex was harvested,and the pathological changes in morphology of brain tissue were observed with light microscope.The positive expression of AQP1 in cerebral cortex was observed with immunohistochemistry by light microscopy,the AQP1 mRNA expression in cerebral cortex was determined by real-time fluorescent quantization reverse transcription-polymerase chain reaction (RT-PCR),and the AQP1 protein expression in cerebral cortex was determined by Western Blot.Results ① All rats in sham operation group had a NSS of zero at each time point.NSS of TBI group was obviously raised with time prolongation,and peaked at 24 hours followed by a lower tendency,while the score in H group was significantly lower than that of TBI group,and the difference was the most obvious at 24 hours as compared with TBI group (9.83 ± 2.78 vs.13.50± 2.42,P ＜ 0.05).② It was shown by light microscope that in the TBI group there were pathological changes in cerebral cortex,including obvious irregular arrangement of nerve cells,cerebral edema,obvious bleeding,especially at 24 hours,then the cerebral edema became vanished gradually;and the positive expression of AQP1 in the pia mater at all the time points in the TBI group was significantly increased,and it was most obvious at 24 hours.Compared with TBI group,the pathological changes at time points of 12 hours to 5 days in H group was significantly lessened,and the positive expression of AQP1 in the cerebral pia mater was reduced obviously.③ Compared with sham operation group,the mRNA and protein expressions of AQP1 in cerebral cortex in TBI group were significantly elevated,peaked at 24 hours [AQP1 mRNA (2-△△Ct):7.50±0.26 vs.1,AQP1 protein (gray value):1.986±0.110 vs.0.336±0.034,both P ＜ 0.05],then they gradually declined.The mRNA and protein expressions of AQP1 in cerebral cortex were significantly decreased after hydrogen-rich water treatment [24-hour AQP1 mRNA (2-△△Ct):5.40±0.21 vs.7.50±0.26,24-hour AQP1 protein (gray value):1.246±0.137 vs.1.986±0.110,both P ＜ 0.05].Conclusions The up-regulation of AQP1 mRNA and protein in ratst cerebral cortex after TBI perhaps participates in edema formation which might be involved in the pathophysiology of cerebral edema in TBI.Early treatment with an intraperitoneally injection of hydrogen-rich water is capable of attenuating the extent of TBI-induced up-regulation of AQP1 mRNA and protein,alleviating cerebral edema,and achieving its protective effects.

AIM: To establish a method to determine the concentration of indinavir in human plasma and study indinavir bioavailability in Chinese healthy people. METHODS: In a random two-period crossover study, 18 healthy male volunteers received a single dose of indinavir capsules 800 mg of two formulations respectively.A sensitive and specific reversed phase HPLC method was developed to quantitate plasma levels of indinavir. The drug was extracted from plasma with acetonitrile. Analysis was performed on a Hy persil C18 column with a mobile phase of acetonitrile:0.01 mol · L -1 phosphate buffer(pH 5.5 ) (43: 57).The UV detector was set at 210 nm. The standard curve covered the concentration ranged from 0. 03 to 16.38 mg · L-1. RESULTS: The concentration-time curves of reference and tested formulations both fitted to a one-compartment open model. The main pharmacokinetic rameters of tested and reference formulations were (10.6 ±s 2.4) mg· L-1 and (9.8 ±2.2)mg· L-1 for cmax, (0. 71 ± 0. 19) h and (0. 8 ±0.3) h for tmax, (1.30±0.24) h and (1.31 ±0.23) h for t1/2ke, (23±6) mg·h· L-1 and (22±5) mg·h · L-1 forAUC0-10, (24±6) mg · h · L-1 and (22±5) mg · h · L-1 for AUC0-∞, respectively. Two one-sidet test and variance analysis were performed in bioequivalent assessment. No statistically significant difference was found in AUC0-10, AUC0-∞ and cmax values between the tested and reference formulations. CONCLUSION:The reversed phase HPLC is a reliable method to determine the concentration of indinavir in human plasma and the two formulations of indinavir are bioequivalent.

AIM: To develop a simple and sensitive high-performance liquid chromatography (HPLC) for the quantification of zidovudine and to study the pharmacokinetics of two kinds of zidovudine capsules in Chinese healthy volunteers. METHODS :The concentrations of zidovudine in plasma were determined by a validated HPLC method with UV detection. A randomized two-way crossover study was conducted in 18 fasting volunteers to compare plasma pharmacokinetic profile and single-dose tolerability of a new zidovudine capsules. RESULTS: The main pharmacokinetic parameters of two formulations, reference and test capsules, were as follows: cmax were (2 252±s 837) μg·L-1 and (2 300±1 099) μg·L-1; tmax were (0.49±0.19) h and (0.5±0.3) h;t1/2 ke were (0.93±0.19) h and (0.99±0.24) h; AUC0-t were (2 530±452) μg·h·L-1 and (2 467±605) μg·h·L-1;AUC0-∞ were(2 689 ± 414) μg·h·L-1 and (2 583±575) μg·h·L-1. The results of ANOVA and two one-side t test statistical analysis for lg AUC0-t, lg AUC0-∞ and lg cmax showed that two formulations were bioequivalent. CONCLUSION:The method is convenient, sensitive, accurate and reproducible, and could be applied to determining the plasma zidovudine concentration and studying on pharmacokinetics. Two zidovudine capsules are bioequivalent in Chinese healthy volunteers.

Objective To observe the effect of hydrogen-rich water on the CD34 expression and angiogenesis in lesion boundary brain tissue of rats with traumatic brain injury (TBI).Methods A total of 54 adult male SpragueDawley (SD) rats were divided into three groups by random number table:namely sham-operated group (sham group),trauma group (TBI group),and trauma + hydrogen-rich water group (TBI+HW group),the rats in each group were subdivided into 1,3 and 7 days subgroups according to the time points after trauma,with 6 rats in each subgroup.The TBI model was reproduced by using a modified Feency method for free fall impact,and the rats in sham group were not given brain impact after craniotomy.The rats in TBI+HW group were given intraperitoneal injection of hydrogen-rich water (5 mL/kg) after TBI model reproduction,and then once a day until being sacrificed,and the rats in sham group and TBI group were given the same amount of normal saline.The neurological severity scores (NSS) for neurologic deficits were calculated at corresponding time points,and then the rats were sacrificed for brain tissue at 3 mm around lesion boundary.After hematoxylin-eosin (HE) staining,the pathological changes in lesion boundary brain tissue were observed under light microscope.The expression of CD34+ cells was observed by immunohistochemical analysis,which markers were used to count the newborn blood capillary sprouts around the traumatic brain tissue.The protein expression of CD34was determined by Western Blot.Results NSS scores at all time points in sham group were 0.NSS scores in TBI and TBI+HW groups showed a decreased tendency with time prolongation after TBI,which showed more significant in TBI+HW group,NSS scores at 3 days and 7 days were significantly lower than those of TBI group (3 day:8.67 ± 0.52 vs.11.56 ± 1.94,7 days:7.33±0.52 vs.8.17±0.98,both P ＜ 0.05).Under light microscope,the brain tissue of rats in sham group was normal.After injury,pathological changes in lesion boundary brain tissue in TBI group were characterized by obvious hemorrhagic necrosis,severe brain edema,a large number of degeneration and necrosis of nerve cells and inflammatory cell infiltration,and the pathological changes were more obvious at 3 days.The edema area in TBI+HW group was slightly smaller than that of TBI group,and the surrounding edema was slightly reduced.It was shown by immunohistochemistry that only a very small number of neoformative capillaries were found in sham group.The number of neoformative capillaries in lesion boundary brain tissue was gradually increased with time prolongation in TBI group.The number of neoformative capillaries in TBI+HW group was more significantly,which was significantly higher than that of TBI group at 3 days and 7 days after injury (cells/HP:10.59 ± 1.88 vs.8.61 ± 1.22 at 3 days,23.20 ± 3.16 vs.17.01 ± 2.64 at 7 days,both P ＜ 0.05).It was shown by Western Blot that the expression of CD34 protein at all time points in TBI group was significantly increased as compared with that of sham group.The expression of CD34 protein at 1 day and 3 days in TBI+HW group was slightly increased as compared with that of TBI group without significant difference,but it was significantly up-regulated at 7 days after injury,which was significantly higher than that of TBI group (gray value:1.36 ± 0.36 vs.0.74±0.08,P ＜ 0.05).Conclusion Hydrogen-rich water promote CD34+ cells home to the site of injured tissue in rats with TBI,is involved in angiogenesis,and improve clinical outcomes during brain functional recovery.

OBJECTIVE:To provide reference for rational use of antipsychotic drugs in schizophrenia patients. METHODS:The general information and antipsychotic treatment information,which were extracted from the database of prior drug investigation in Mental Health Center of Hebei Province in 2002,2006 and investigation data in 2012 of 5014 schizophrenia patients,were ana-lyzed. RESULTS:Over time,the frequency of the first generation antipsychotic drugs decreased(P<0.05),while that of the sec-ond generation antipsychotic drugs increased (P<0.01). The frequency of long-acting antipsychotic drugs were generally low among outpatients and inpatients in 2002,2006,2012,with statistical significance(P<0.01). There were no significant difference in the proportion of outpatients receiving antipsychotic drugs combination treatment and monotherapy (P>0.05). Over time,the proportion of inpatients receiving monotherapy decreased,while that of inpatients receiving combination treatment increased (χ2=18.682,P<0.01). CONCLUSIONS:The second generation antipsychotic drugs have gradually replaced the first generation antipsy-chotic drugs,and have became the leading drugs in the treatment of schizophrenia in Hebei province. The proportion of inpatients receiving combination treatment has increased,which is different from the domestic and foreign prevention and treatment guide-lines.

Objective To investigate the blood-saving effect of tranexamic acid in off-pump coronary artery bypass (OPCAB). Methods Two hundred and sixty ASA Ⅰ- Ⅲ and NYHA Ⅰ- Ⅲ patients of both sexes,aged 18-64 yr, with body mass index 16-22 kg/m2 , undergoing OPCAB, were randomly divided into 2 groups (n = 130 each): control group (group C) and tranexamic acid group (group T) . Anesthesia was induced with iv injection of midazolam 0.1 mg/kg, fentanyl 5-10μg/kg and pipecuronium 0.1 mg/kg. The patients were tracheal intubated and mechanically ventilated. PEr CO2 was maintained at 35-45 mm Hg. A bolus of tranexamic acid 1 g was infused intravenously within 30 min after indution followed by continuous infusion at 400 mg/h until the end of operation in group T. While equal volume of normal saline was given in control group. Anesthesia was maintained with inhalation of isoflurane and intermittent iv injection of fentanyl and pipecuronium. Venous blood samples were taken before induction, at the end of operation and at 24 h after operation for determination of Hb, platelet count (P1t), prothrombin time (PT) and international normalized ratio (INR). The volume of chest tube drainage was collected and recorded at 6 and 24 h after operation. The requirement for transfusion of allogeneic red blood cells and fresh frozen plasma was also recorded. Results There was no significant difference in Hb, Plt, PTand INR at each time point between the two groups ( P ＞ 0.05). The requirement for transfusion of allogeneic red blood cells and fresh frozen plasma was significantly reduced in group T as compared with group C ( P ＜ 0.05 or 0.01 ). No deaths and complications occurred during hospital stay in the two groups. Conclusion Tranexamic acid exerts the blood-saving effect in OPCAB.

OBJECTIVE:To provide reference for rational drug use in elderly patients with depression. METHODS:A total of 96 elderly outpatients and inpatients with depression were selected from 39 mental health institutions of Hebei province during Jul. 2nd to 9th,2012. The drug use were surveyed by using self-made questionnaires on the basis of prescriptions/medical orders. The results of investigation were analyzed statistically. RESULTS:In this study,96 questionnaires were distributed and all were collect-ed with effective recovery rate of 100%. Among 96 respondents,95 elderly patients used a new type of antidepressants,mainly by selective serotonin reuptake inhibitors(SSRIs),accounting for 75.0% of the total. The top 5 drugs in the list of use frequency were sertraline(23 cases,24.0%,daily dose:25-200 mg),paroxetine(22 cases,22.9%,daily dose:20-60 mg),escitalopram(20 cas-es,20.8%,daily dose:5-40 mg),venlafaxine (13 cases,13.5%,daily dose:75-300 mg),mirtazapine (12 cases,12.5%,daily dose:8-30 mg). Among all respondents,22 patients (22.9%) were treated with mono-antidepressant and the other 74 patients (77.1%) were treated with drug combination therapy among which 47 cases were treated with two antidepressant drugs,22 were treated with three drugs,4 were treated with four drugs and 1 was treated with five drugs. 6 cases combined with mood stabilizers, 21 cases with antipsychotic,50 cases with benzodiazepine(6 of them combined with two benzodiazepine),2 cases with other hyp-notic drugs,14 cases with anxiolytic drugs and 2 cases with anticholinergic drugs. CONCLUSIONS:The drug use of elderly pa-tients with depression in mental health institutions of Hebei province basically in line with current trends. However,there are still the phenomenon of irrational drug use as drug dose meets or exceeds the prescribed maximum dose;many varieties are used in combination therapy;route of administration is improper.

Objective To investigate the effects of hydrogen-rich water (HRW) on brain edema and the expression of aquaporin 4 (AQP4) in brain tissue of rats after acute traumatic brain injury (TBI) and explor the mechanism of its action. Methods Ninety male adult Sprague-Dawley (SD) rats were randomly divided into three groups: Sham group, TBI model group (TBI group) and HRW intervention group (HRW group), each group n = 30 rats. The TBI rat models were replicated by craniocerebral collision, while the Sham group rats underwent only craniotomy without collision and the cranial opening was closed by suturing and bone wax. After successful modeling, in HRW group the rats received intraperitoneal injection of HRW 5 mL/kg, and in the TBI group and Sham group, equal amount of 5 mL/kg 0.9% normal saline was given by the same method, once a day for 5 days in all the groups. The neurological severity scores (NSS) and brain water contents were detected at postoperative 6, 12, 24, 48 hours and 5 days in the three groups;the cerebral cortex expression levels of AQP4 mRNA, positive expression levels of AQP4, the cerebral cortex AQP4 protein expression, protein kinase C (PKC) activity were detected in each group. Results ① The NSS of each time point in Sham group was 0; in TBI group, the rats levels of NSS and brain water contents showed a tendency of firstly rising and then decreasing, and after postoperative 24 hours, the levels reached the peak values and then gradually decreased; in HRW group, the levels of NSS and brain water contents were reduced significantly and at postoperative 24 hours when compared with those in TBI group, the levels of decreasing amplitude in HRW group were more significant [NSS score: 5.50±1.87 vs. 10.50±2.42, brain water content: (78.78±0.65)% vs. (79.98±0.61)% , all P ＜ 0.05].② The AQP4 mRNA expression levels of sham group at all time points were 1; compared with the Sham group, the AQP4 mRNA levels of TBI group and HRW group at the time points showed a tendency of firstly decreasing and then rising and reaching the valley level at 24 hours (2-ΔΔCt: 0.33±0.06, 0.36±0.12 vs. 1, both P ＞ 0.05). ③ The immunohistochemistry detection showed that the brain AQP4 mainly expressed in astrocytes in Sham group at various time points. However, in TBI group, the positive expression of AQP4 in astrocytes in injury area at each time point was decreased, at postoperative 24 hours being the most significant; the positive expression of AQP4 in HRW group was significantly higher than that in the TBI group at each time point and since postoperative 12 hours the statistical significant difference appeared in the comparison between the two groups [Absorbance (A) value: 0.206±0.010 vs. 0.170±0.014, P ＜ 0.05]. ④ The expressions of AQP4 protein at various time points were significantly lower in TBI group compared with those of Sham group, and reached the minimum at postoperative 24 hours (gray value: 0.282±0.100 vs. 1.281±0.115, P ＜ 0.05); but in HRW group, the expressions of AQP4 protein at various time points showed significantly higher than those of TBI group, and since postoperative 12 hours the statistical significant difference occurred (gray value:0.681±0.096 vs. 0.420±0.090, P ＜ 0.05). ⑤ The activity of PKC in TBI group at each time point was significantly decreased compared with that in Sham group, but it was significantly increased in HRW group at each time point and reached the maximum at postoperative 24 hours (A value: 2.67±0.52 vs. 1.51±0.42, P ＜ 0.05). ⑥ Correlation analysis:there was an obvious negative correlation between the brain activity of PKC and brain water content (r2= 0.209, P ＜ 0.001);but there was a significant positive correlation between the activity of PKC and the expression of AQP4 protein (r2= 0.406, P ＜0.001). Conclusion HRW can improve the brain edema in rats following TBI, and the mechanism may be associated with the up-regulation of expression of AQP4 protein and PKC activity in brain tissue.

Objective:To investigate the reference ranges for thyroid function and its influencing factors in preterm infants at 14 d after birth.Methods:This retrospective study involved 514 preterm infants who met the inclusion criteria in Affiliated Hospital of Inner Mongolia Medical University from January 1, 2019 to December 31, 2021. They were divided into three group according to their gestational age [early premature group (26-31 +6 weeks, n=153), middle premature group (32-33 +6 weeks, n=129) and late premature group (34-36 +6 weeks, n=232)] or birth weight (BW) [<1 500 g group ( n=129), 1 500-2 000 g group ( n=120) and ≥2 000 g group ( n=265)]. Venous blood samples were collected from the infants at 14 d after birth and their thyroid function was determined by chemiluminescence immunoassay. The reference values of free triiodothyronine (FT 3), free thyroxine (FT 4) and thyroid stimulating hormone (TSH) were calculated based on the values of 95% confidence intervals ( CI) and expressed as percentiles in the range from P2.5 to P97.5. Mann-Whitney U test or Kruskal-Wallis H test was used to compare those thyroid hormone levels between groups. Spearman correlation analysis was used to study the correlation of gestational age or birth weight with FT 3, FT 4 and TSH levels. The factors influencing the levels of thyroid hormones were analyzed by multiple linear regression. Results:The reference ranges for FT 3, FT 4 and TSH were 1.53-3.72 pg/ml, 0.81-1.91 ng/dl and 1.32-7.80 μIU/ml in the early premature infants, 1.74-4.16 pg/ml, 0.90-2.82 ng/dl and 0.63-7.64 μIU/ml in middle prematures and 2.07-4.88 pg/ml, 1.09-2.27 ng/dl and 1.14-7.06 μIU/ml in late prematures. The reference ranges for the above three indexes were 1.53-4.06 pg/ml, 0.81-1.83 ng/dl and 1.14-7.84 μIU/ml in premature infants with BW<1 500 g, 1.67-3.98 pg/ml, 0.88-2.97 ng/dl and 0.94-7.64 μIU/ml in those whose BW between 1 500 g and 2 000 g and 1.91-4.75 pg/ml, 1.09-2.31 ng/dl and 1.14-6.32 μIU/ml in those whose BW≥2 000 g. Multiple linear regression showed that the level of FT 3 was positively correlated with gestational age ( β=0.119, P<0.05) and birth weight ( β=1.950×10 －4, P<0.05); that of FT 4 was positively correlated with gestational age only ( β=0.031, P<0.05); and TSH level was negatively correlated with birth weight ( β=－4.250×10 －4, P<0.05). Conclusions:Gestational age and birth weight are the factors influencing thyroid function in preterm infants at 14 d after birth. Evaluation of thyroid function with FT 4 and TSH should based on the references ranges of different gestational age and birth weight .