OBJECTIVE:To discuss the manifestation characteristics of mezlocillin injection-induced ADR.METHODS:Mezlocillin injection-induced ADR cases reported in domestic pharmaceutical journals between 1999 and July.2006 were retrieved from China Hospital Digital Library(CHDL) and analyzed statistically.RESULTS:The clinical manifestation of ADR induced by mezlocillin was characterized by allergic reactions or even anaphylactic shock.The major ADR types were first-using immediate type and the speedy outbreak type.CONCLUSION:Great importance should be attached to allergic reactions induced by mezlocillin injection.

OBJECTIVE:To discuss the general rules and characteristics of adverse drug reactions(ADRs)of lamivudine.METHODS:43national case reports of ADRs of lamivudine between1999and2005were classified and analyzed statistically.RESULTS:The affected patients ranged in age from8years to45years,with more males than females.There were no rules in the onset time of ADRs.The ADRS were mainly characterized by nervous system responses and aggravation of hepatitis in clinic.CONCLUSION:Great importance should be attached to ADRs of lamivudine to ensure the safety of drug use in clinic.

Objective To explore the role of Beclin 1 and PTEN in gastric caicinoma genesis and the effects on prognosis.Methods The expression of Beclin 1 and PTEN in 199 gastric caicinoma specimens and corresponding adjacent noncancerous tissues were examined by tissue microarrays and immunohistochemistary,and the relation with gastric cancer was analyzed.The rate of Beclin 1 and PTEN expression in 15 fresh gastric carcinoma samples and corresponding adjacent noncancerous tissues were detected by Western blot.All the samples were from Changzheng Hospital.Results The Results of immunohistochemistary showed that the rates of Beclin 1 and PTEN positive expression in cancinoma tissues were 47.2％ (94/199) and 55.8％ (111/199),both were lower than that of adjacent noncancinoma tissues (94.5％,188/199 and 92.5％,184/199; P ＜ 0.01).The lower expression of Beclin 1 and PTEN in gastric carcinoma were associated with gender,differentiation degree,depth of tumor invasion,lymph node metastases and disease stage(P＜0.05).There was a positive correlation between Beclin 1 and PTEN expression in gastric carcinoma tissues (r =0.680,P＜0.01). The survival analysis indicated that Beclin 1 and PTEN were independent factors in determining the prognosis of gastric cancinoma patients.The 5-year survival rate of Beclin 1 positive patients was 67.0％ (63/94),and of negative patients was 33.3％ (35/105).The 5-year survival rate of PTEN positive patients was 71.2％ (79/111),and of negative patients was 21.6％ (19/88) ( all P＜0.001).The Results of Western blot indicated that the expression of Beclin 1 and PTEN in gastric carcinoma tissues were significantly lower than that in the adjacent noncarcinoma tissues ( all P＜0.001).Conclusion The abnormal expression of Beclin 1 and PTEN may be related to carcinogenesis and the development of gastric carcinoma.

Objective This study was to assess the three-dimensional gross tumor volume(GTV)motion of lung cancer caused by respiration using four-dimensional computed tomography(4DCT),and to analyze the influenee factors.Methotis Four-DCT scans of 22 lung focuses in 21 patients with lung cancer were analyzed.The gross tumor volume was contoured in all 10 respiration phases of 4DCT scans.The changes in volume of GTV,the 3D motion of the centroid,boundary of GTV and the 3D spatial motion vectors were calculated and the irdluenee factors were analyzed.Results The average change in volume of GTV was+14.3%(0.2%.42.5%)/-8.4%(0.4%-38.6%),the average movement amplitude of GTV centroid and GTV boundary were(0.18±0.12)cm,(0.20±0.16)cm,(0.53±0.59)cm and(0.42±0.23)cm,(0.41±0.22)cm,(0.57±0.70)cm in medio-lateral,vertro-dorsal,cranio-caudal(CC) direction,respectively.The CC movement was larger than other directions(Z=-2.12,P=0.034;Z:-2.10,P=0.035),and no significant difference was observed in 3D motion of GTV boundary(Z=-0.81.P=0.417;Z=-0.86,0.391).The CC motion of GTV eentroid in lower lobe was larger than that in upper lobe[(0.87±0.64)and(0.35±0.49)cm,(t=-2.12,P=0.047)],and no significant difference was found in other directions[(0.23±0.10)and(0.19±0.18)em(t=-0.49,P=0.629),(0.21±0.13)and(0.17±0.11)cm(t=0.76,P=0.460)].There was no correlation of the 3D movement and 3D spatial motion vector of GTV to the volume of GTV(r=-0.306,-0.062,-0.279,-0.300;P=0.189,0.796.0.234,0.199).Conclusions GTV motion of patients with lung cancer is individual,the CC movement is the moat obvious,using 4DCT to assess is comparatively accurate.The motion amplitude of lower lobe focuses is larger.No significant correlation of the GTV motion to the volume was observed.Larger sample study is needed to analyze the influence of adjacency to the GTV motion.

Objective To assess the clinical value of serum uric acid levels in patients with acute ST-elevation myocardial infarction(STEMI).Methods A total of 502 consecutive patients with STEMI were enrolled from January 2005 to December 2010 for retrospective study.The level of serum lipid,echocardiographic data and in-hospital major adverse cardiovascular events(MACE)in patients with hyperuricemia(n =119)were compared with those in patients without hyperuricemia(n =383).The relationship between the level of serum uric acid and the degree of diseased coronary artery was analyzed.All data were analyzed with SPSS version 17.0 software to make t test and x2 test and Pearson correlation analysis.Results Serum uric acid level was positively correlated with serum triglyceride level.Compared with non-hyperuricemia patients,hyperlipidemia was more commonly found among hyperuricemia patients (43.7％ vs.33.7％,P =0.047),and serum triglyceride level was significantly higher in hyperuricemia patients[(2.11 ± 1.24)mmol/L vs.(1.78 ± 1.38)mmol/L,P =0.014].But a significant association between serum uric acid level and one or more diseased vessels was not observed(P ≥ 0.05).Leftventricular end-diastolic diameter(LVEDd)was found to be larger in hyperuricemia patients than non-hyperuricemia patients[(53.52 ±6.19)mm vs.(52.18 ±4.89)mm,P =0.041].Higher incidence in left systolic dysfunction and diastolic dysfunction was discovered in hyperuricemia patients(36.4％ vs.15.1％,P ＜0.01; 68.2％ vs.55.8％,P =0.023).Also,hyp-eruricemia patients had more in-hospital MACE(P ＜ 0.05).Conclusions Serum uric acid level is positively correlated with serum triglyceride level,but not with the severity of coronary artery disease.Hyperuricemia patients after STEMI tended to have higher incidence in left systolic dysfunction and diastolic dysfunction,and have more in-hospital MACE.

Atopic dermatitis (AD) is a chronic, relapsing, inflammatory dermatosis with a variety of clinical manifestations and difficult to cure. Currently, many AD drug candidates have entered the research and development pipeline. In order to provide technical specifications for the clinical development of AD drugs, the Center for Drug Evaluation of National Medical Products Administration released the "Technical Guidelines for Clinical Trials of Drugs for AD Treatment" (Draft for Comments) in November 2022. Non-clinical pharmacodynamics evaluation is an important research before the drug enters clinical trials. Oxazolone (OXA)- and 2,4-dinitro-fluorobenzene (DNFB)-induced models are the most popular classical hapten-induced AD murine models, but variations of modeling are existing in the methods from different studies, including sensitization sites, haptens' dosages, the period of challenges, and the skin lesions severity evaluation as well. In this study, the investigation of OXA- and DNFB-induced AD murine models with various conditions of modeling was performed to compare the characteristics of hapten-induced AD murine models in the pathological process and severity according to the appearance of AD patients, and the guidance of pharmacodynamics evaluation of AD-therapeutic drugs in clinical trials as well, which may provide a proposal for AD treatment drug candidates in the non-clinical pharmacodynamics evaluation. All animal experiments were approved by the Animal Care & Welfare Committee of Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (approval No.: 00007782 and 00007784).

Objective:To evaluate the changes in the blood-cerebrospinal fluid barrier in postoperative delirium rats.Methods:One hundred and forty-seven healthy female Sprague-Dawley rats, aged 3 months, weighing 240-300 g, were divided into 3 groups ( n=49 each) using a random number table method: control group (group C), anesthesia group (group A) and postoperative delirium group (group P). Group C received no treatment.Group A received 2-h anesthesia with 1.4% isoflurane.Group S underwent an exploratory laparotomy under 1.4% isoflurane anesthesia.The behaviors of rats in each group were tested at 24 h before surgery and 6, 9 and 24 h after surgery using buried food test, open field test and Y maze test.Sodium fluorescence was injected through the tail vein at 6, 9 and 24 h after surgery.Then the rats were sacrificed, the choroid plexus (CP) was obtained, and cerebrospinal fluid (CSF) of bilateral cerebral ventricles was collected, and the expression of ZO-1, occludin, claudin1, E-cadherin and VE-cadherin in CP was detected using Western blot.FITC-dextran 10, 40 and 70 kDa was injected through the tail vein at 6 h after surgery, and then CSF was collected for determination of the concentrations of NaFI, 10, 40 and 70 kDa fluorescein isothiocyanate labeled dextran (FITC-dextran) in CSF by fluorescence spectrophotometry.CP was obtained to observe the morphology of choroid plexus epithelial cells (CPECs) of bilateral cerebral ventricles with a transmission electron microscope. Results:Compared with group C and group A, the latency to eat food in buried food test was significantly prolonged, the time of staying at the central region was shortened, the percentage of the number of entries into novel arm and percentage of time of staying at novel arm in Y maze test were decreased, the freezing time in open field test was shortened, the expression of ZO-1, occludin and claudin1 in CP was down-regulated, the concentrations of NaFI and 10 kDa and 40 kDa FITC-dextranin CSF were increased ( P<0.05 or 0.01), the CPECs arranged at random and loose, the microvilli of CPECs were absent, the tight junction was blurred, and the gap became wider in group P. Conclusion:The occurrence of postoperative delirium is related to the change in blood-cerebrospinal fluid barrier.

Objective:To evaluate the role of miR-146a in hippocampal inflammatory responses in postoperative cognitive dysfunction (POCD) in mice.Methods:One hundred and sixty clean-grade male C57BL/6 mice, aged 12-16 weeks, weighing 22-28 g, were divided into 5 groups ( n=32 each) using a random number table method: control group (group C), group POCD, miR-146a agomir group (group Ag), miR-146a antagomir group (group At) and negative control group (group NC). The mice were subjected to an intramedullary fixation for tibial fracture under 1.5% isoflurane anesthesia to establish POCD model.At 2 days before operation, miR-146a agomir 0.5 nmol (0.1 nmol/μl) was injected into bilateral hippocampi in group Ag, miR-146a antagomir 2.5 nmol (0.5 nmol/μl) was injected in group At, miR-146a negative control solution 2.5 nmol (0.5 nmol/μl) was given in group NC, and the animals in group C did not receive any treatment.At 1 day before operation and at 1, 3 and 7 days after operation, open-field test was performed to evaluate spontaneous motor activity, and contextual fear conditioning test was performed to evaluate cognitive ability 15 min later.At 1 and 3 days after operation, the animals were sacrificed and hippocampi was removed for determination of expression of CD11b (a marker for activation of microglia) in hippocampal CA1 region by immunofluorescence staining.At 6, 12 and 24 h after operation, the expression of miR-146a was detected by quantitative real-time polymerase chain reaction, the expression of interleukin-1 receptor-associated kinase 1 (IRAK1), tumor necrosis factor receptor-associated factor 6 (TRAF6), nuclear factor kappa B p65 (NF-κB p65) and tumor necrosis factor-alpha (TNF-α) was determined by Western blot and interleukin-1beta (IL-1β) and IL-6 contents were determined by enzyme-linked immunosorbent assay. Results:There was no significant difference in the total exploring distance in the open-field test or percentage of freezing time in tone-fear conditioning test at each time point among the five groups( P>0.05). Compared with group C, the percentage of freezing time in the contextual fear conditioning test was significantly decreased at 1, 3 and 7 days after operation, the expression of CD11b at 1 and 3 days after surgery and expression of miR-146a, IRAK1, TRAF6, NF-κB p65 and TNF-α were up-regulated and the contents of IL-1 β and IL-6 were increased at 6, 12 and 24 h after operation in group POCD ( P<0.05). Compared with group NC, the percentage of freezing time in the contextual fear conditioning test was significantly increased at 1, 3 and 7 days after operation, and the expression of CD11b was down-regulated at 1 and 3 days after surgery, and the expression of miR-146a, IRAK1, TRAF6, NF-κB p65 and TNF-α was up-regulated and IL-1β and IL-6 contents were decreased at 6, 12 and 24 h after operation in group Ag, and the percentage of freezing time in the contextual fear conditioning test was decreased at 1, 3 and 7 days after operation, the expression of CD11b at 1 and 3 days after surgery was up-regulated, the expression of miR-146a was down-regulated and IRAK1, TRAF6, NF-κB p65 expression was up-regulated at 6, 12 and 24 h after operation, TNF-α expression was up-regulated and IL-1β and IL-6 contents were increased at 12 and 24 h after operation in group At ( P<0.05). Conclusion:miR-146a is involved in the process of hippocampal inflammatory responses, and the mechanism may be related to the inhibition of IRAK1-TRAF6-NF-κB signaling pathway in mice.

Aurantii Fructus is the dried and immature fruit of Citrus aurantium and its cultivars. To investigate the chemical constituents of Aurantii Fructus, the separation and purification of constituents were performed by column chromatography on silica gel LH-20, HW-40, ODS, PHPLC and PTLC. Fourteen flavonoids, including four flavone glycosides and ten polymethoxyflavones (PMFs) were isolated from the EtOAc fraction and Petroleum ether fraction of Aurantii Fructus and their structures were identified by physicochemical properties and spectral data (NMR and MS) as (2R) -and (2S)-6"-O-acetylprunin (1,2), naringenin-7-O-β-D-glucopyranside (3), 5,7,4'-trihydroxy-8,3'-dimethoxyflavone-3-O-6"-(3-hydroxyl-3-methylglutaroyl)-β-D-glucopyranoside(4), 4'-hydroxy-5,6, 7-trimethoxyflavone (5), natsudaidain (6), nobiletin (7), sinensetin (8), 5,6,7,4'-tetramethoxyflavone (9), 5,7,8,4'-tetramethoxyflavone (10), 3,5,6,7,8,3',4'-heptamethoxyflavone (11), tangeretin (12), 5-demethyl nobiletin (13), and 5-hydroxy-6,7,3', 4'-tetramethoxyflavone (14). Compound 3-5 s were isolated from this plant for the first time and compound 1 was a new one.
Citrus ; chemistry ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Flavonoids ; chemistry ; isolation & purification ; Fruit ; chemistry ; Mass Spectrometry ; Molecular Structure

Objective To summarize the characteristics of treatment and outcomes of extremely low birth weight infants (ELBWI).Methods The clinical data of 81 cases of ELBWI admitted to Bayi Children's Hospital Affiliated to General Hospital of Beijing Military Command from October 1st.2008 to August 31st.2011 were retrospectively analyzed.The survival rate and mortality of ELBWI with different gestational age and birth weight were compared with Chi-square test.Results Of 81 ELBWI,43 were male and 38 were female; the mean gestational age at birth was (28.4 ±2.1) weeks; the average birth weight was (903.5 ± 95.4) g.Complications of them included respiratory distress syndrome (68/81,84.0％),patent ductus arteriosus (47/81,58.0％),retinopathy of prematurity (41/81,50.6％),intraventricular hemorrhage (23/81,28.4％),bronchopulmonary dysplasia (17/81,21.0％),sepsis (15/81,18.5％),periventricular leukomalacia (2/81,2.5％) and necrotizing enterocolitis (1/81,1.2％).Among 81 infants,96.3％ (n =78)received oxygen inhalation with the average time was 19.1 d (median 11 d,0-121 d) ; 70.4％ (n=57)received pulmonary surfactant; 27.2％ (n =22) received nasal continuous positive airway pressure;34.6％ (n =28) received normal frequency mechanicalfrequency ventilation.All 47 ELBWI with patent ductus arteriosus received ibuprofen treatment,among which 6 cases received arterial canal ligation after failure of ibuprofen treatment.20 out of 41 cases of retinopathy of prematurity received laser surgery.Total parenteral nutrition was required in 74 infants(91.4％),the average age of beginning enteral feeding was 5.2 d (median 6 d,0-17 d)and achieved full gastrointestinal feeding time was 31 d (median 28 d,7-65 d).The survival rate of ELBWI with gestational age of ≤26,-28 and ＞28 weeks was 25.0％ (4/16),72.0％ (18/25) and 77.5％ (31/40),respectively; the corresponding mortality was 12.5％ (2/16),8.0％ (2/25) and 2.5％ (1/40),respectively.The survival rate of ELBWI with birth weight ≤800,-900 and ＞900 g was 33.3％ (4/12),58.3％ (14/24) and 77.8％ (35/45),respectively; and corresponding mortality of them was 16.7％ (2/12),8.3％ (2/24) and 2.2％ (1/45),respectively.Conclusions The outcome of ELBWI is closely related to gestational age and birth weight.Professional and sophisticated treatment might improve the survival rate and general outcome of ELBWI.