Objective To explore the pharmacokinetic changes of single dose of fentanyl in rats in a simulated high-altitude and contributing factors.Methods Thirty-six healthy female SD rats(6～8 weeks old,250±20 g)were randomly divided into high-altitude-acute-exposure group(group A),high-altitude-chronic-exposure group(group S)and control group(group C)through random number table,with 12 rats in each group.The group A and S were housed in a low-pressure chamber simulating the high altitude of 5000 m above sea level for 3 and 30 d respectively,and the group C was housed out of the chamber(at an altitude of 300 m).A single dose of fentanyl was administered through the femoral vein to 6 rats randomly selected from each group.Liquid chromatography tandem mass spectrometry(LC-MS/MS)was used to detect blood concentrations of fentanyl and WinNonlin 8.2 software was used to calculate the pharmacokinetic parameters,while blood samples were taken through the femoral artery before and in 1,2,4,8,15,30,60,120 and 180 min after administration.The remaining 6 rats were ultrasonographically assessed for portal vein internal diameter(PVD),peak flow velocity(PVV)and blood flow(PVF),and liver tissues were collected for CYP3A1 protein content assay.Results The blood drug concentrations of fentanyl in the group A and group S were significantly lower than those in the group C at 60,120,and 180 min(P=0.002,P＜0.001,P= 0.001).Compared with the group C,the clearance rate(CL)of the group A was increased by 54.06%(P=0.021),and the mean residence time(MRTlast)was shortened by 24.21%(P=0.033);CL of the group S was increased by 50.10%(P=0.041),the area under the concentration-time curve(AUC0-t,AUC0-∞)and MRTlast were reduced by 18.92%(P=0.039),27.54%(P=0.018)and 33.61%(P= 0.004),respectively.PVD and PVF in the group S increased by 10.87%(P=0.006)and 42.50%(P= 0.006)when compared with the group C.The CYP3A1 protein content in the group A was 28.74%,which was higher than that in the group C(P=0.048).Conclusion Fentanyl is cleared significantly faster after a single dose in rats in simulated high-altitude,which may be related to the increased liver blood flow and increased CYP3A1 protein expression in liver.

Objective To analyze the molecular mechanism of Yupingfeng granules(YPFG)in the treatment of recurrent respiratory tract infection(RRTI),and provide a pharmacological basis for the diagnosis and treatment of RRTI in traditional Chinese medicine.Methods The TCMSP database and SwissTargetPredication database were used to screen the active ingredients and active ingredient targets of YPFG.All pathogenic targets of RRTI were obtained using the DisGeNET dataBase,DrugBank database,GeneCards database,and OMIM database.Drug-disease target-compound networks and protein-protein interaction networks were established to explore the main drugs,compounds,and target proteins.GO enrichment analysis and KEGG signaling pathway enrichment analysis were used to explore the main molecular mechanisms of YPFG in the treatment of RRTI.Results The main active ingredients of YPFG screened include three main active ingredients,including daylily lignans A,peucedanum praeruptorum B,and wogonin,which mainly target SRC and COX-2.Enrichment analysis showed that phosphorylation(biological process),cytoplasm perinuclear region(cellular component),and phosphotransferase activity(molecular function)were the main GO enrichment items.The signaling pathways mainly involve tumor signaling pathways,relaxin signaling pathways,Th17 signaling pathways,and so on.Conclusion YPFG mainly treats RRTI by participating in the signal transduction of certain key nodes in tumor signaling pathways,relaxin signaling pathways,Th17 signaling pathways,etc.It has a direct or indirect impact on multiple signaling pathways and has the characteristics of multi-component,multi-target,and multi-channel effects.

Objective: To establish a rat model of preeclampsia (PE) in early pregnancy and to observe the changes in phenotype，pregnancy outcome and cognitive ability of offspring． Methods : The pregnant rats were randomly divided into model group and control group．Ultra-low dose lipopolysaccharide (LPS) (0. 5 μg / kg) and an equal volume of normal saline were injected into the tail vein of pregnant rats on the fifth day of pregnancy．The levels of blood pressure ，12-hour urinary protein ，peripheral blood coagulation factors and placental cytokines in the two groups were measured．Furthermore，placental pathology，pregnancy outcomes，and cognitive abilities of offspring were observed. Results: Blood pressure and urinary protein levels of model group were significantly higher than those of control group levels．Compared with the control group，the levels of platelet and antithrombin Ⅲ (AT Ⅲ) in the peripheral blood of pregnant rats in the model group were lower than those in the control group，while D-dimer was higher than that in the control group，the weight of the fetus and placenta in the model group decreased (P ＜0. 001) ，the expression levels of interleukin ( IL) -6，tumor necrosis factor α ( TNF-α) and interferon gamma (INF-γ) in peripheral blood increased，while the expression level of transforming growth factor β1 (TGF-β1) decreased(P＜0. 001) ．The water maze test showed that the latency of the offspring of the model group to the plat- form was longer than that of the control group (P＜0. 05) ，while the frequency of crossing the platform quadrant and the time of staying in the platform quadrant of the model group were lower than those of the control group (P < 0. 05 ) ．HE and PAS staining showed that there were infiltration of inflammatory cells in the basal layer of placenta， obvious decrease of blood vessels in labyrinthine area，slight edema of renal interstitium and degeneration of local renal tubular epithelial cells in the model group，while there were no above pathological changes in placenta and kidney in the control group． Conclusion A single injection of LPS in early pregnancy can successfully induce PE- related symptoms and adverse pregnancy outcomes such as fetal growth restriction and lead to the decline of cogni- tive ability of offspring.

Objective:To retrospectively analyze the urodynamics quality in Southwest China, and find out the main issues of urodynamics quality in Southwest China and try to find out the improvement ways.Methods:In this study, a two-stage sampling method was used.In the first stage, 10 medical institutions in Southwest China were selected by cluster sampling from March to June, 2020.In the second stage, according to the development of UDS in Southwest China, the sample size estimation formula was adopted, and the loss of follow-up rate in reports extraction was considered, the initial sample size was 350. As the workload of UDS in the 10 medical institutions involved in the study was equivalent, 35 urodynamics traces from each medical institution were selected. The initial samples should also meet the inclusion criteria: ①patients with clear medical history and complete clinical data; ②UDS traces were clear; ③UDS system was water filled system; ④age>18, and 150 urodynamic traces were included in the final study. We evaluated the quality of enrolled urodynamics traces, and the quality evaluation standard according to the guidelines established by the International Continence Society (ICS). The evaluation conducted by two independent urologist with more than 10 years working experience. Artifacts were divided into non-technical artifacts: abnormal abdominal pressure changes, urine volume <150 ml when did the uroflow test, and technical artifacts: non-standard zero setting, fail to record all urodynamics parameters, baseline drift, catheter displacement, misjudgment of detrusor physiological contraction and detrusor overactive in voiding phase, misjudgment between detrusor overactive and bladder low compliance in filling phase.Results:non-technical artifacts: 32 cases were found abnormal abdominal pressure changes (21.3%), 21 cases (14.0%) were found when did the uroflow test the urine volume <150 ml, and technical artifacts: Non-standard zero setting in 28 cases (18.7%), fail to record all urodynamics parameters in 8 cases, baseline drift in 16 cases, catheter displacement in 9 cases and misjudgment of detrusor physiological contraction and detrusor overactive in voiding phase in 12 cases, misjudgment between detrusor overactive and bladder low compliance in filling phase in 24 cases (16.0%).Conclusions:At present, the urodynamics quality in Southwest China need to be improved. The main issues were that the operator didn’t obey the basic operation and quality control process, and the operator did not have enough basic knowledge of urodynamics. It can be improved by strictly carry out the operation standard of UDS, identifying and correcting artifacts in time, and promoting the standardized urodynamic training courses.

The outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus continually lead to worldwide human infections and deaths. Currently, there is no specific viral protein-targeted therapeutics. Viral nucleocapsid protein is a potential antiviral drug target, serving multiple critical functions during the viral life cycle. However, the structural information of SARS-CoV-2 nucleocapsid protein remains unclear. Herein, we have determined the 2.7 Å crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein. Although the overall structure is similar as other reported coronavirus nucleocapsid protein N-terminal domain, the surface electrostatic potential characteristics between them are distinct. Further comparison with mild virus type HCoV-OC43 equivalent domain demonstrates a unique potential RNA binding pocket alongside the -sheet core. Complemented by binding studies, our data provide several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain, guiding the design of novel antiviral agents specific targeting to SARS-CoV-2.

Objective To investigate the diagnostic value of the texture analysis in differentiating adult pilocytic astrocytomas (PA)from hemangioblastomas(HB).Methods 22 adult patients with PA and 20 patients with HB which were confirmed by postoperative pathological were retrospectively reviewed.The conventional MRI features and texture parameters were analyzed.Eight texture parameters were extracted using run-length matrix(RLM),and the differences of texture parameters of the two groups were analyzed by independent-samples t test.Results The short run emphasis(SRE),grey-level non-uniformity(GLNU),run-length non-uniformity(RLNU),high grey-level run emphasis(HGRE)and short run high grey-level emphasis(SRHGE)were higher in adult PA than in HB.The long run emphasis(LRE),low grey-level run emphasis(LGRE)and short run low grey-level emphasis(SRLGE)were lower in adult PA than in HB.The eight texture parameters had significant differences between the two groups(P<0.05).Conclusion Texture analysis can provide reliably objective basis for differentiating adult PA from HB.

Objective: To survey the conduction and evaluate the effectiveness of extracorporeal membrane oxygenation (ECMO) therapy in pediatric intensive care unit (PICU) in China mainland. Methods: In a questionnaire-based survey, we retrospectively reviewed the application of ECMO in children's hospital and general hospital in China mainland to summarize and analyze the categories of diseases and prognosis of children treated with ECMO therapy. Results: By December 31, 2017, a total of 23 hospitals using ECMO, including 22 tertiary referral hospitals and 1 secondary hospital, among which 16 were children′s hospitals and 7 were general hospitals. Thirty-seven ECMO equipment was available. A total of 518 patients treated with ECMO, within whom 323 (62.4%) successfully weaned from ECMO and 262 (50.6%) survived to discharge. Among 375 pediatric patients, 233 (62.1%) were successfully weaned from ECMO and 186 (49.6%) survived to discharge. Among 143 newborn patients, 90 (62.9%) successfully weaned from ECMO, 76 (53.1%) survived to discharge. ECMO was applied in veno-arterial (VA) mode to 501 (96.7%) patients, veno-venous (VV) mode to 14 (2.7%) patients, and VV-VA conversion mode to 3 (0.6%) patients. Sixty-nine patients required extracorporeal cardiopulmonary resuscitation (ECPR), including 20 newborn patients (29.0%) and 38 pediatric patients (71.0%), who were all with cardiovascular disease. Neonatal respiratory distress syndrome (26/61), persistent pulmonary hypertension of the newborn (PPHN) (12/61), and meconium aspiration syndrome (MAS) (11/61) are the most common pulmonary diseases in newborn patients; among whom, infants with PPHN had highest survival rate (10/12), followed by MAS (9/11). Among newborn patients with cardiovascular diseases, those who admitted were after surgery for congenital cardiac disease were the most common (54/82), while those with septic shock had the highest survival rate (2/3). In pediatric pulmonary diseases, acute respiratory distress syndrome was the most common (42/93), while plastic bronchitis was with the highest survival rate (4/4), followed by viral pneumonia (13/16). Among pediatric cardiovascular diseases, congenital cardiac defect was the most common (124/282), while fulminant myocarditis had the highest survival rate (54/77). Conclusion The application of ECMO as a rescue therapy for children with severe cardiopulmonary failure has dramatically developed in China mainland.

A total of 185 patients with type 2 diabetes mellitus (T2DM) were consisted of male group (n =95) and postmenopausal female group (n =90).The parameters of fasting plasma glucose,HbA1c,fasting insulin,fasting C peptide,homeostasis model assessment insulin resistant index (HOMA-IR) and β-cell function (HOMA-β),blood lipid,body mass index,and waist to hip ratio were collected and analyzed by Pearson correlation analysis and stepwise multiple regression analysis.The relationships between osteocalcin and these parameters were investigated.The results revealed that osteocalcin was negatively correlated with HbA1C (P＜0.05),and osteocalcin was an independent relevant factor affecting HbA1Clevels.Osteocalcin may be involved in the regulation of glucose metabolism in T2DM.

Objective To observe the effect of the outpatient mobile infusion system in the department of infectious outpatient night infusion.Methods From July to December in 2012,520 patients in department of infectious outpatient infusion in our hospital were selected and were divided into the observation group (using outpatient mobile infusion system)and the control group (adopting conventional infusion) with 260 cases in each group.The infusion effect was compared between two groups.Results The average occupancy per patient care time in the observation group was less than the control group,the difference was statistically significant.The satisfaction degree in the observation group was higher than that of the control group,the difference was statistically significant.There was no nursing error occurred in both of the observation group or the control group.Conclusion The use of outpatient mobile infusion system can significantly improve the nurses work efficiency,ensure nursing safety,improve quality of care and patients' satisfaction degree.

Objective To explore the value of the electronic colposcopy Reid Score in diagnosis of cervical lesions and HPV infection in women with HIV infection, so as to find out an inexpensive, convenient and feasible screening methods. Methods 95 cases of HIV-infected women were screened by cervical liquid based cytology, HPV testing, colposcopy and Reid Score. The patients with abnormal results in any one test mentioned above underwent cervical biopsy. The colposcopy was combined with pathological as a gold standard for case-control study. Results There was a statistically signi?cant correlation between colposcopic ndings and histopathological ndings and the score was increased as parallel as malignancy grade (r=0.753,P=0.00) . The specificity of Reid score for high grade CIN was better than high-risk HPV testing for CIN diagnosis and the sensitivity was better than liquid based cytology. Acetic acid staining has relatively high sensitivity and specificity in the diagnosis of cervical lesions. Conclusions Colposcope Reid score for cervical lesions has a predictive value, especially for high grade cervical precancerous lesions. Colposcopy for HIV-positive women cervical cancer screening is an efficient and feasible way, especially for the area where lack of medical resources.