Background The orbital fibroblasts (OFs) in thyroid associated ophthalmopathy (TAO) play important roles in the proliferative and inflammatory response.Seeking the drug which inhibit OFs growth is of a vital significance for the prevention and treatment of TAO.Research documented that colchicine has an anti-fibrosis effect.But its influence on OFs of TAO patient is few known.Objective This study was to investigate the effect of colchicine on growth and apoptosis of OFs in vitro.Methods The retroobital connective tissue was obtained form 3 TAO patients and cultured using explant method.OFs were passaged and identified by immunochemistry,and 3-8 genetaions of cells were used in the study.Colchicine at the concentrations of 1 × 10-8,1 × 10-7,1 × 10-6,1 × 10-5,1 ×10-4 mol/L was added into the RPMI 1640 with 10％ fetal bovine serum(FBS) to incubated the cells for 24,48 and 72 hours respectively,and only RPMI 1640 was used to culture the cells as the control group.Cell counting kit-8 (CCK-8)was used to detect the absorbance value (A450) of OFs for the evaluatuion of OFs and the inhibitory rate of colchicine to OFs.The colchicine of 1 ×10-6,1 ×10-5,1 × 10-4 mol/L was added into the culture medium for 48 hours,and then the apoptotic rate of the cells and the cell percentage in various cellular cycle was assayed by flow cytometry(FCM).The expression of transforming growth factor-β (TGF-β)in the cells was detected by immunochemistry to assess the influence of colchicine on the serection of the cells.Results Cultured cells showed the spindle-like in shape and the cell number was significantly increased with the incubation time.After incubated with 1 × 10-4,1 × 10 5,1 × 10-6,1 ×10-7,1 × 10-8 mol/L colchicines,the A450 values were gradually reduced with the increase of the concentrations of colchicine(F ion =62.004,P＜0.05),and significant differences were found between different contrations of colchicine groups(all P＜0.05).Aslo,gradually declined A450 values of the cells were seen with the lapse of culture time among the groups(Ftime =459.582,P＜0.05).The inbitory rate of colchicine to the cells was elevated with the increase of concentrations.The apoptotic rates of the cells were (1.73 ± 0.15) ％,(21.04 ± 4.56) ％,(31.84 ±6.21)％and(35.32±5.56)％ in the control group and 1 × 10-6,1 × 10-5,1 × 10 4 mol/L colchicine groups respectively,with statistically significant difference among the 4 groups (F =83.905,P＜0.05).With the increase of concentrations of colchicines,the cell percentage in G2 +M phase lessened gradually,showing significant difference among the control group and the 1 × 10-6,1 × 10-5,1 × 10-4 mol/L colchicine groups (F =20.443,P＜0.05).The expression of the TGF-β in the cells was (97.60± 2.09) ％ in the control group,and that in the 1 × 10-4 mol/L colchicine group was (44.43 ± 3.96) ％,presenting a significant difference between them (t =65.330,P ＜ 0.05).Conclusions Colchicine can induce apoptosis of OFs and inhibit the prolilferation of OFs in a time-and dose-dependent manner probably by decreasing the TGF-β secretion

Objective To make a systematic evaluation of the efficacy and safety of Eszopiclon and Alprazolam in the treatment of insomnia.Methods By searching the PubMed,Cochrance Library,CNKI, WANFANG,and VIP database,we studied the literature published between 2005 to 2016 on the efficacy and safety of Eszopiclon and Alprazolam in the treatment of insomnia.We collected the randomized controlled trials (RCTs), evaluated the quality of methods and then analyzed the data using RevMan5.3 software.Results A total of 18 RCTs were included,involving 2088 patients.According to Meta-analysis,Eszopiclon group had a significantly higher total efficacy rate [RR=1.07,95% CI (1.02,1.11),P=0.003],lower severity of adverse reactions [MD=-0.43,95% CI(-0.75,-0.12),P=0.008]and incidence of adverse reactions [RR=0.46,95% CI(0.32, 0.66),P<0.0001]than Alprazolam group.However,the two groups did not significantly differ in sleep quality scores after 4-week teatment [MD=-0.05,95% CI(-0.22,0.12),P=0.54].Conclusion Eszopiclon is more effective on insomnia than Alprazolam,with better safety,and it deserves wide clinical use.

OBJECTIVE To map a comprehensive metabolic pathway of herbacetin in rats, specifically, to elucidate the biotransformation of herbacetin in vivo and to simultaneously monitor the pharmacokinetic process of both parent drug and its major metabolites. METHODS liquid chromatography/ion trap mass spectrometry (LC/MSn) and ultra-liquid chromatography coupled with mass spectrometry (UPLC/MS) were combined in the current study for qualitative and quantitative determinations of herbacetin and its metabolites in bile, urine and feces after both oral and intravenous administration of herbacetin to rats. Enzyme kinetic studies on the intestinal and hepatic metabolism of herbacetin were further conducted to elucidate metabolic profiles of herbacetin in rat tissues and organs. Additionally, plasma concentration profiles of herbacetin and its metabolites in rats were obtained to characterize the overall pharmacokinetic behavior of herbacetin. RESULTS It was found that herbacetin was excreted primarily from rat urine in the form of glucuronide-conjugations. Subsequent in vitro enzyme kinetic studies and in vivo pharmacokinetic investigations suggested an extensive hepatic metabolism of herbacetin and the high exposure of herbacetin- glucuronides in systemic circulation. The clearance, half- life and bioavailability of herbacetin in rats were determined as (16.4±1.92)mL·kg-1·min-1, (11.9±2.7)min, and 1.32%, respectively. On basis of these findings, a comprehensive metabolic pathway of herbacetin in rats was composed. In addition, a physiology based pharmacokinetic (PBPK) model was successfully developed with the aid of the GastroPlus to simulate the pharmacokinetic process of herbacetin in rats. Application of the PBPK modeling can provide a useful starting point to understand and extrapolate pharmacokinetic parameters among different species, populations, and disease states. CONCLUSION After oral administration, herbacetin was subjected to colonic degradation and extensive first pass metabolism, with glucuronidation as its dominating in vivo metabolic pathway.

OBJECTIVE To investigate the effect of hypoxia on the pharmacokinetic process of salidrosidein rats and to explore its underlying mechanisms. METHODS The Caco-2 cell monolayerwas exposed to 1% oxygen (O2) concentration for 24 h to build the hypoxiccell model. The transportation mode of salidroside was investigated with the aid of this hypoxia model by detecting the apparent permeability coefficient(Papp). Healthy Sprague Dawley (SD) rats were exposed to 9% O2 for 72 h for the construction of hypoxic rat model. Liver sample was subsequently collected from the hypoxic rats with an aim to identify enzymes responsible for salidroside metabolism. The expression levels of sali?droside-transporting and salidroside-metabolizing enzymes, including Sodium-dependent glucose cotrans?porters (SGLT1), β-glucosidase (GBA3)and sulfotransferase (SULT2A1), were thereafter detected by RT-PCR and Western blot. The metabolic activity of GBA3 and SULT2A1 was monitored by rat liver microsome incubation.In addition, the renal function of rats under hypoxia was assessed by detecting concentrations of blood urea nitrogen and creatinine. RESULTS The AUC and t1/2 values of salidroside in hypoxic rats were more than doubled, while the in vivo clearance was significantly reduced. Mechanistic study demonstrated that the PappA- B/PappB- A eualsto 10.3, indicating the potential active transport of salidrosile. The expression of SGLT1 and GBA3 was significantly decreased, which indicated a reduced metabolism of salidroside under hypoxia. Moreover, rat under hypoxia was found to suffer from renal dysfunction, with an abnormal value of blood urea nitrogen. CONCLUSION Due to the reduced metabolism and the abnormal renal function under hypoxia, the systemic exposure of salidroside in rats was signifi?cantly enhanced.

Objective To investigate the pathogenesis of gallbladder chaotic dynamics after partial gastrec-tomy. Methods 140 cases operated by partial gastrectomy after 6 months were randomly examined, they in-cluded one group of 40 cases by Billroth type and the other 100 cases by Eiselsberg type. The ultrasonograph was applied to evaluate the function of gallbladder dynamics and radio-immunity method to determine the content of CCK at the time of having no food and 30 minutes after med. Results BV and RV of Eiselsberg group were bigger than Billroth Ⅰ obviously P<0.05. Gallbladder contraction rate displayed not well obvi-ously as too. The plasm level of CCK had no manifested distinctions in empty stomach cases of the 2 groups, but the increasing gradient plasm level of CCK in Billroth Ⅰ exceeded Eiselsberg type. Conclusions The pathogenesis of gallbladder chaotic dynamics after partial gastrectomy was correlated with the alterative type of partial gastrectomy, the reduction of CCK plasm level, the damage of anterior vagal trunk hepatic branches during the operations and so on led to the disorder of gallbladder emptying and induced cholecystolithiasis.

Algorithms ; Blood Vessels ; pathology ; Diagnostic Imaging ; methods ; Humans ; Retina ; pathology

OBJECTIVETo evaluate the efficiency of first trimester prenatal screening for fetal chromosome abnormality using maternal serum marker test and(or) plus nuchal translucency (NT) in Guangzhou region.

METHODSThe results of prenatal screening were retrospectively analyzed among 43 703 women with singleton pregnancies from January 2007 to September 2012. A total of 43 703 pregnancies between 9 and 13(+6) weeks of pregnancy were collected and analyzed for maternal serum pregnancy-associated plasma protein A (PAPPA), free β -human chorionic gonadotropin (free β -hCG) with or without crown-rump length (CRL). Nuchal translucency was measured by ultrasonographic scan between 11 and 13(+6) weeks of pregnancy. Gestational age was estimated by ultrasonographic scan. The risk values of Down syndrome (DS) and trisomy 18 were calculated using the software Lifcycle. Comparing the difference between the combined screening (PAPPA, free β -hCG and NT) and serum marker screening (PAPPA and free β -hCG).

RESULTSAmong the 43 703 pregnant women, screening showed that 1385 (3.17%) were Down syndrome positive and 55 (0.13%) were trisomy 18 positive. The final outcomes of pregnancy showed that 142 cases presented chromosomal abnormalities, of which 54 cases suffered from Down syndrome, 13 had trisomy 18, and 75 had other chromosome abnormalities. The total detection rate of Down syndrome and trisomy 18 were 83.33% and 76.92%, respectively.The positive rate is lower, and the detection rate is higher in combined screening group than serum marker screening group. The median PAPPA MoM was lower and the median free β -hCG MoM and NT measured value was higher in Down syndrome pregnancies than control group. The median PAPPA and free β -hCG MoM were lower and the median NT measured value was higher in trisomy 18 pregnancies than control group.

CONCLUSIONThe first trimester prenatal screening can effectively detect Down syndrome and trisomy 18 pregnancy. The combined screening method is superior to the serum marker screening and is the preferred strategy in the first trimester prenatal screening.

Adolescent ; Adult ; Asian Continental Ancestry Group ; genetics ; Biomarkers ; blood ; China ; Chorionic Gonadotropin, beta Subunit, Human ; blood ; Chromosome Disorders ; diagnosis ; embryology ; genetics ; Chromosomes, Human, Pair 18 ; genetics ; Down Syndrome ; diagnosis ; genetics ; Female ; Fetal Diseases ; diagnosis ; ethnology ; genetics ; Genetic Testing ; methods ; Humans ; Middle Aged ; Nuchal Translucency Measurement ; Pregnancy ; Pregnancy Trimester, First ; Pregnancy-Associated Plasma Protein-A ; metabolism ; Prenatal Diagnosis ; methods ; Reproducibility of Results ; Sensitivity and Specificity ; Trisomy ; diagnosis ; genetics ; Trisomy 18 Syndrome ; Young Adult

Objeelive To investigate the effect of rhG-CSF on mobilizing bone marrow-MSCs, reendothelialization and intima hyperplasia in carotid artery of rabbits post balloon catheter injury, nethods Rabbits were treated with rhG-CSF (25 μkg, twice daily, i. p, n =35) or saline (n =32) for 5 days, then, carotid arteries of rabbits were injured by balloon catheter. The number of peripheral MSCs was detected with FACS. The morphology of injuried artery was examined with hematoxylin and eosin stain, PCNA was determined with immunohistochemistry. Results (1) Number of peripheral MSCs was similar at baseline and significantly increased at 24 hours and peaked at 7 days and remained increased till 14 days post rhG-CSF. (2) Significant endothelial cell deletion was evidenced in the control group, while scatter endothelial cells was observed in the rhG-CSF group at 1 week post injury. Two weeks after injury, new endothelial area was significantly higher in rhG-CSF group compared to control group. At 4 weeks post injury, endothelial connection was evidenced and regularly displayed in rhG-CSF treated group. (3) PCNA-positive cells in the tunica intima were significantly lower in rhG-CSF treated rabbits at 7, 14 and 28 days compared that in control rabbits (all P ＜ 0.01). Conclusion rhG-CSF could mobilize the bone marrow-MSCs and promote re-endothelialization and attenuate intima hyperplasia post balloon catheter injury in carotid arteries of rabbits.

Objective To investigate the risk factors for the occurrence of bronchiolitis obliterans (BO) in children with refractory Mycoplasma pneumoniae pneumonia (RMPP) and their predictive value of the factors. Methods A retrospective analysis was performed for the medical records of 156 children with RMPP who were admitted to the hospital from May 2020 to March 2024. According to the diagnostic criteria for BO,they were divided into a BO group (n=76) and a non-BO group (n=80). A logistic regression analysis was used to investigate risk factors for the occurrence of BO,and the receiver operating characteristic (ROC) curve was used to assess the value of the model established based on the risk factors in predicting BO. Results Compared with the non-BO group,the BO group had a significantly longer duration of fever,a significantly higher leukocyte count,and a significantly lower albumin level (P<0.05). Compared with the non-BO group,the BO group had a significantly lower proportion of children with initiation of macrolide antibiotic therapy within 5 days,initiation of glucocorticoid therapy within 2 weeks,or initiation of bronchoscopic therapy within<2 weeks (P<0.05). The ROC curve analysis showed that the logistic regression model established based on the above six indicators had an area under the curve of 0.901 (95％CI:0.849-0.953,P<0.001) in predicting the occurrence of BO,with a sensitivity of 0.893 and a specificity of 0.827 at the optimal cut-off value of 0.341. Conclusions The logistic regression model established based on duration of fever,leukocyte count,albumin,initiation of macrolide antibiotic therapy within 5 days,initiation of glucocorticoid therapy within 2 weeks,and initiation of bronchoscopic therapy within 2 weeks has relatively high sensitivity and specificity in predicting the occurrence of BO in children with RMPP.

OBJECTIVE Paeoniflorin (PF) and albiflorin (AF) are the major active components of total peony glucosides(TPG)from Paeonia lactiflora Pal,which have many biological activities such as anti-inflammatory, antioxidation and anti-hypertension effects. The drug-drug pharmacokinetic interaction among PF,AF and TPG,the pharmacokinetic comparisons of AF between hypoxia and normoxia,the transport of AF cross the blood-brain barrier cell model and the transport of AF/PF/TPG cross Caco-2 cell model were investigated.METHODS A highly sensitive and rapid UPLC-MS method with multiple-reaction monitoring(MRM)scanning via electrospray ionization(ESI)source operating both in the positive and negative ionization mode was successfully developed and validated for simultaneous quantitation of PF and AF in rat plasma after an oral administration of PF,AF and TPG. RESULTS The validated and developed UPLC-MS/MS method was successfully applied to simultaneously determine the AF and PF concentration in rat plasma and investigate pharmacokinetic interactions after a single intragastrical ad-ministration of PF,AF,co-administration of PF with AF and TPG,respectively.The elimination of both PF co-administered with AF and PF in TPG were slower than those for PF alone and the distribution in the tissues was wider.The combination of PF with AF or TPG could significantly increase the values of the AUC, MRT and t1/2of the drug PF, and reduce the values of CL of PF. From a comparison of the main pharmacokinetic parameters among AF alone, AF combined with PF and AF in TPG, the values of the MRT and t1/2of AF in TPG were greater than that of AF alone,and there were statistically signifi-cant differences in these parameters(P<0.05,P<0.01).It was also noticed that AUC and Cmaxof PF in hypoxia rats were significantly decreased compared with that of normaxia rats, suggesting that there was a decreased exposure of PF in rats under hypoxia. The multiple active components in TPG may lead to DDIs between some P-gp substrates. CONCLUSION The clinical performance of total peony glucosides would be better than that of single constitute. The outcomes of the study are expected to serve as a basis for development of clinical guidelines on total peony glucosides usage.