Analysis of the Current Situation of Drug Clinical Trial Institutions in Shaanxi Province

To understand the current situation of institutional registration in Shaanxi Province after the implementation ofregistration system management in drug clinical trial institutions.Relevant information was collected on the“Announcement on the Accreditation of Drug Clinical Trial Institutions”issued by the National Medical Products Administration from 2005 to August 2022,the record management information system of drug and medical device clinical trial institutions,and the drug clinical trial registration and information publicity platform.A retrospective analysis was carried out in terms of institutional development,regional distribution,registered majors,principal investigators,and the number of drug clinical trials.After the implementation of institution registration,the number of drug clinical trial institutions in Shaanxi Province increased by 47.4%,884 principal investigators were registered,the number of registered majors expanded from 58 qualified to 117,and the professional scope increased by 50.4%.The policy of institution registration is conducive to promoting the rational use of medical resources and the development of drug clinical trial institutions and improving the healthy development of the pharmaceutical industry in Shaanxi Province.

Bioinformatics and in vitro study reveal the roles of microRNA-346 in high glucose-induced human retinal pigment epithelial cell damage

AIM:To study microRNAs(miRNAs)and their potential effects in high glucose-induced human retinal pigment epithelial cell damage.METHODS:We screened the GSE52233 miRNA expression dataset for differentially expressed miRNAs(DEMs).The target genes of the top 10 DEMs were predicted using miRWalk 2.0 database,followed by function enrichment and protein-protein interaction analysis.miRNA expression was determined in the human retinal pigment epithelial cell line ARPE-19 treated with high glucose(HG)by quantitative reverse transcription-polymerase chain reaction(qRT-PCR).Cell proliferation was determined using cell counting kit(CCK)-8 assay.Cell cycle,apoptosis,and reactive oxygen species(ROS)levels were determined by flow cytometry.The direct interaction between miRNA and targets was validated using dual-luciferase reporter assay.RESULTS:Thirty-nine DEMs were screened,and we predicted 125 miRNA-mRNA pairs for the top 10 DEMs,including 119 target genes of seven DEMs such as miR-346,which was upregulated in diabetic retinopathy(DR).miR-346 target genes were substantially enriched in the regulation of intracellular transport and retinoic acidinducible gene I(RIG-I)-like receptor signaling pathway.Expression of three upregulated and downregulated miRNAs were verified by qRT-PCR in HG-treated ARPE-19 cells.Expression of miR-346 was elevated in HG treated ARPE-19 cells in a dose-dependent manner.HG inhibited cell proliferation and induced apoptosis,which were partly reversed by transfecting an miR-346 inhibitor,which even decreased the ROS levels elevated due to HG.Argonaute 2(AGO2)was a target of miR-346.CONCLUSION:miR-346 is a key miRNA and plays an important role in HG-induced damage in human retinal pigment epithelial cells.

Application Experience of Eyesi Operation Simulation Training System in the Teaching of Cataract Surgery for Ophthalmology Masters

Objective:To explore the application effect of the Eyesi surgical simulator in the teaching of cataract surgery for professional ophthalmology postgraduate students.Methods:The professional postgraduate students who were trained in the third year of ophthalmology at the First Affiliated Hospital of Xi’an Medical University were selected as the research objects.After passing the theoretical examination,they were randomly divided into the pig eyeball group,Eyesi group,and pig eye+Eyesi group,with 5 students in each group.The pig eyeball,Eyesi surgery simulator,and pig eye+Eyesi surgery simulator were used for microscopic technique operation and cataract surgery steps training,respectively.After the training,the overall training effects of the three groups of postgraduates were scored,and questionnaires were used to objectively evaluate the three training methods.Results:The scores of the students in the pig eye+Eyesi group were better than those in the Eyesi group,and the students in the Eyesi group were better than those in the pig eyeball group.Conclusion:The Eyesi surgical simulation training system can evaluate the microsurgical skills of professional masters and improve their surgical skills.This system is of great significance for the training of the cataract surgery skills of professional masters.

Analysis of the HNF4A isoform-regulated transcriptome identifies CCL15 as a downstream target in gastric carcinogenesis

Objective:Hepatocyte nuclear factor 4α(HNF4 A)has been demonstrated to be an oncogene in gastric cancer(GC).However,the roles of different HNF4 A isoforms derived from the 2 different promoters(P1 and P2)and the underlying mechanisms remain obscure.Methods:The expression and prognostic values of P1-and P2-HNF4 A were evaluated in The Cancer Genome Atlas(TCGA)databases and GC tissues.Then,functional assays of P1-and P2-HNF4 A were conducted both in vivo and in vitro.High-throughput RNA-seq was employed to profile downstream pathways in P1-and P2-HNF4 A-overexpressing GC cells.The expression and gene regulation network of the candidate target genes identified by RNA-seq were characterized based on data mining and functional assays.Results:HNF4 A amplification was a key characteristic of GC in TCGA databases,especially for the intestinal type and early stage.Moreover,P1-HNF4 A expression was significantly higher in tumor tissues than in adjacent non-tumor tissues(P<0.05),but no significant differences were found in P2-HNF4 A expression(P>0.05).High P1-HNF4 A expression indicated poor prognoses in GC patients(P<0.01).Furthermore,P1-HNF4 A overexpression significantly promoted SGC7901 and BGC823 cell proliferation,invasion and migration in vitro(P<0.01).Murine xenograft experiments showed that P1-HNF4 A overexpression promoted tumor growth(P<0.05).Mechanistically,RNA-seq showed that the cytokine-cytokine receptor interactions pathway was mostly enriched in P1-HNF4 A-overexpressing GC cells.Finally,chemokine(C-C motif)ligand 15 was identified as a direct target of P1-HNF4 A in GC tissues.Conclusions:P1-HNF4 A was the main oncogene during GC progression.The cytokine-cytokine receptor interaction pathway played a pivotal role and may be a promising therapeutic target.

Effects of Yinzhihuang oral liquid and albumin on bilirubin, inflammatory factors, immune indexes and related factors in neonatal pathologic jaundice

Objective: To explore the effects of Yinzhihuang oral liquid and albumin on bilirubin, inflammatory factors, immune indexes and related factors in neonatal pathologic jaundice. Methods: A total of 134 neonates with pathologic jaundice admitted to our hospital from May 2017 to April 2018 were randomly selected as the control group (n=67) and the observation group (n=67), the control group was treated with albumin, the observation group was treated with Yinzhihuang Oral Liquid on the basis of the control group. The bilirubin, inflammatory factors, immune indicators, alpha-fetoprotein (AFP) and transferrin (TRF) were compared and analyzed before and after treatment. Results: After treatment, the levels of TBIL, DBIL and IBIL in both groups were significantly lower than those before treatment (P<0.05), and the levels of TBIL, DBIL and IBIL [(118.60±10.85) μmol/L, (6.95±1.52) μmol/L, (115.30±14.20)μmol/L] in observation group were significantly lower than those in control group;the levels of CRP and IL-6 in both groups were significantly lower than those before treatment (P<0.05), and the levels of CRP and IL-6 [(8.26±2.07) mg/L, (12.69±2.15) pg/mL] in observation group were significantly lower than those in control group (P<0.05);the levels of CD4+, CD4+/CD8+ in both groups were significantly higher than those before treatment (P<0.05), while the levels of CD8+ was significantly lower than that before treatment, the levels of CD4+, CD4+/CD8+ [(47.08±5.70)%, (2.08±0.41)] in observation group were significantly higher than those in control group (P<0.05), and the level of CD8+ [(22.90±2.05)%] was significantly lower than that in control group (P<0.05);the levels of AFP in significantly higher than before treatment (P<0.05), and the levels of AFP [(12.69±3.04)mg/L] in observation group were significantly lower than those in control group (P<0.05), the levels of TRF [(2.02±0.35) g/L] were significantly higher than those in control group (P<0.05). Conclusions: The combination of Yinzhihuang oral liquid and albumin can effectively reduce the bilirubin level in neonatal jaundice, inhibit its inflammatory reaction, enhance the cellular immune function and improve the expression of AFP and TRF, which is of clinical significance.

Status Epilepticus in Children: A Study of 54 Cases

Objectives: To review the clinical character, the management and outcome of status epilepticus in children. Methodology: We conducted a retrospective review of 54 cases treated between 1996 and 1997 at the Royal Alexandra Hospital for Children, Sydney, Australia. Among the variables collected for analysis in this study were age, sex, etiology of status epilepticus, median length of Paediatric Intensive Care Unit (PICU) stay and days of mechanical ventilation, and mortality of status epilepticus. Results: Of the patients with status epilepticus, 61% were male and 39% female, with an age range of 3 months to 15 years (mean 5.3 years). The etiology of status epilepticus is largely age related, with acute causes common in 1 - 3 year and 4 - 7 year ages, 44 cases (81.5%). The etiology of status epilepticus included febrile (35.18%), acute symptomatic (27.58%) and idiopathic (16.6%), total was 44 cases (81.4%). Median length of PICU stay and days of mechanical ventilation were 3.02 ± 1.6 days and 1.24 ± 0.5 days respectively. Mortality was 5.3%. Most patients were treated with diazepam and phenytoin. The total number of the patients with a favorable outcome was 41 (75.89%). Conclusions: One of the most common neurologic emergencies in children of status epilepticus remains a major problem in morbidity and mortality. There are multiple causes of status epilepticus that include the categories of idiopathic, febrile, acute symptomatic and remote symptomatic. Intravenously administered phenytoin and diazepam remains the first-line therapy for status epilepticus. Most of the patients will respond to this treatment. The etiology of status epilepticus included febrile (35.18%), acute symptomatic (27.58%), idiopathic (16.6%) and total was 44 (81.4%).

Investigation and Analysis of the Cognition of Menopause in Women Over 40 Years Old

Objective:To investigate and analyze the cognition of menopause in women over 40 years old.Methods:Using the stratified sampling method,224 females,age ranging from 40 to 60,from our university staff(Xi’an Medical University)and the surrounding communities were selected,and both online and offline questionnaires were distributed.Results:(1)224 questionnaires were recovered,with 204 valid questionnaires,among which 100 questionnaires were from our university staff(aged 42-60 years old)and 104 questionnaires from the surrounding communities(aged 40-60 years old);(2)the cognition of menopause among the surveyed population was found to be related to occupation and education level;the cognition of menopause among university staff(76%)was significantly higher than that of the surrounding communities(45.19%);(3)most people were able to accept menopausal hormone therapy;the degree of acceptance among the university staff(80%)was found to be higher than that among the surrounding communities(60.58%).Conclusion:According to the recovered data,women over the age of 40 have less than ideal cognition of menopause,and although the cognitive level of the university staff on menopause was found to be significantly higher than that of the surrounding communities,their cognitive level still requires improvement.

Effect and Safety of Iron Supplementation on Mild Thalassemia Complicated by Iron Deficiency in Late Pregnancy

Aim:To study the clinical effect and safety of iron supplementation in the treatment of mild thalassemia complicated by iron deficiency in late pregnancy.Methods:376 patients with mild thalassemia complicated by iron deficiency in late pregnancy treated in our hospital from July 2019 to June 2021 were selected and recruited in the research group,and 200 normal pregnant women treated in the same period were selected and recruited in the control group.Hemoglobin(Hb),reticulocyte blood,red blood protein(RET he)level,ferritin(SF)level,soluble transferrin receptor(sTfR)level,adverse maternal and infant outcomes,etc.were analyzed.Results:There was no significant difference in the levels of SF,Hb,RET he and sTfR between the two groups before treatment.After treatment,the levels of SF,Hb,RET he and sTfR in the research group were significantly improved,which was statistically significant compared with the control group.The frequencies of intrapartum hemorrhage,premature delivery,stillbirth,hemorrhagic shock,and neonatal asphyxia in the research group were 289±47.88,36(9.57%),0(0.00%),25(6.65%),and 6(1.26%),respectively.The frequencies of intrapartum hemorrhage,premature delivery,stillbirth,hemorrhagic shock,and neonatal asphyxia in the control group were 284±46.99,7(3.50%),0(0.00%),6(3.00%),and 0(0.00%),respectively.There were significant differences in preterm delivery and hemorrhagic shock,and there was no significant difference in other delivery outcomes.Conclusions:Under the premise of strictly controlling the iron reserve in pregnant women,continuous medication until the end of delivery may be conducive to the control of maternal thalassemia complicated by iron deficiency and the improvement of pregnancy outcome.

Reference values of carotid intima-media thickness and arterial stiffness in Chinese adults based on ultrasound radio frequency signal:A nationwide,multicenter study

Background:Carotid intima-media thickness(IMT)and diameter,stiffness,and wave reflections,are independent and important clinical biomarkers and risk predictors for cardiovascular diseases.The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods:A total of 3053 healthy Han Chinese adults(1922 women)aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022.The real-time tracking of common carotid artery walls was achieved by the radio frequency(RF)ultrasound system.The IMT,diameter,compliance coefficient,βstiffness,local pulse wave velocity(PWV),local systolic blood pressure,augmented pressure(AP),and augmentation index(AIx)were then automatically measured and reported.Data were stratified by age groups and sex.The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions.The major clinical determinants of carotid properties were identified by Pearson’s correlation,multiple linear regression,and analyses of covariance.Results:All the parameters of carotid properties demonstrated significantly age-related trajectories.Women showed thinner IMT,smaller carotid diameter,larger AP,and AIx than men.Theβstiffness and PWV were significantly higher in men than women before forties,but the differences reversed after that.The increase rate of carotid IMT(5.5µm/year in women and 5.8µm/year in men)and diameter(0.03 mm/year in both men and women)were similar between men and women.For the stiffness and wave reflections,women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes(all P for age by sex interaction<0.05).The blood pressures,body mass index(BMI),and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex.Conclusions:The age-and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established.The blood pressures,BMI,and triglyceride levels should be considered for clinical application of corresponding reference values.

Nanoengineered sonosensitive platelets for synergistically augmented sonodynamic tumor therapy by glutamine deprivation and cascading thrombosis

Ultrasound(US)-activated sonodynamic therapy(SDT)stands for a distinct antitumor modality because of its attractive characteristics including intriguing noninvasiveness,desirable safety,and high tissue penetration depth,which,unfortunately,suffers from compromised therapeutic efficacy due to cancer cell-inherent adaptive mechanisms,such as glutathione(GSH)neutralization response to reactive oxygen species(ROS),and glutamine addictive properties of tumors.In this work,we developed a biological sonosensitive platelet(PLT)pharmacytes for favoring US/GSH-responsive combinational therapeutic of glutamine deprivation and augmented SDT.The amino acid transporter SLC6A14 blockade agentα-methyl-DL-tryptophan(α-MT)-loaded and MnO_(2)-coated porphyrinic metal-organic framework(MOF)nanoparticles were encapsulated in the PLTs through the physical adsorption of electrostatic attraction and the intrinsic endocytosis of PLTs.When the sonosensitive PLT pharmacytes reached tumor sites through their natural tendencies to TME,US stimulated the PLTs-loaded porphyrinic MOF to generate ROS,resulting in morphological changes of the PLTs and the release of nanoparticles.Subsequently,intracellular high concentration of GSH and extracellular spatio-temporal controlled US irradiation programmatically triggered the release ofα-MT,which enabled the synergistically amplified SDT by inducing amino acid starvation,inhibiting mTOR,and mediating ferroptosis.In addition,US stimulation achieved the targeted activation of PLTs at tumor vascular site,which evolved from circulating PLTs to dendritic PLTs,effectively blocking the blood supply of tumors through thrombus formation,and revealing the encouraging potential to facilitate tumor therapeutics.

A reversed CD4/CD8 ratio of tumor-infiltrating lymphocytes and a high percentage of CD4^(+)FOXP3^(+) regulatory T cells are significantly associated with clinical outcome in squamous cell carcinoma of the cervix

In this study,40 biopsy samples collected from cervical cancer patients at the First Affiliated Hospital of Xi’an Jiaotong University,China,were retrospectively assessed using immunohistochemistry for CD4^(+) and CD8^(+) tumor-infiltrating lymphocytes(TILs)and were analyzed for the expression of FOXP3,OX40,granzyme B(GrB)and perforin(Prf).The proliferating index of the TILs was determined by assessing Ki67 expression.We determined the prognostic value of low and high numbers of TILs on survival by performing Kaplan–Meier analysis using median values as the cut-off points.Except for the number of CD4^(+)FOXP3^(+) regulatory T cells(Tregs)and the CD4/CD8 ratio,none of the CD4^(+),CD8^(+),OX401,GrB^(+) or Prf^(+) TILs were associated with the overall 5-year survival rate.The 5-year survival rate was significantly lower in patients who had a high percentage of Tregs as compared with the those who had a lower percentage(35.3%versus 88.9%,P50.001),while the 5-year survival rate was significantly higher in patients with a high CD4/CD8 ratio as compared with patients who had a low CD4/CD8 ratio(82.4%versus 44.4%,P50.029).When we considered the deaths and surviving cases as separate groups,we found that both the number of CD4^(+) T cells and the CD4/CD8 ratio were significantly lower in patients who died as compared with those who survived(26.33±11.80 versus 47.79±38.18,P=0.023 and 0.60±0.25 versus 1.17±1.02,P=0.019,respectively).In conclusion,decreased proportions of tumor-infiltrating CD4^(+) T cells with high percentages of Tregs and reversed CD4/CD8 ratios were significantly associated with the clinical outcome of patients with cervical carcinoma.

Application of N-terminal pro-brain natriuretic peptide concentration and the Global Registry of Acute Coronary Events risk score to predict major adverse cardiac events in patients with ST-elevation myocardial infarction after PCI

Identifying patients with high risk of death after myocardial infarction is a cornerstone of modern cardiovascular health care.The purpose of this study was to explore the predictive ability of N-terminal probrain natriuretic peptide(NT-pro-BNP)concentration and global acute coronary event register(GRACE)risk score in the prognosis of ST-segment elevation myocardial infarction(STEMI)patients,to find a better method for early risk stratification and prognosis judgment in the clinical diagnosis and treatment of STEMI patients,and to provide reliable clinical basis for making the best individualized treatment strategies for patients.Methods The final analysis included 118 confirmed STEMI patients who had received acute percutaneous coronary intervention(PCI).Thirty patients with STEMI were included in the major cardiac adverse events(MACEs)group,and the rest were included in the non-MACEs group.Multivariate Cox regression analysis was used to assess the relationship between the risk factors and MACEs.The receiver operator curves(ROC)were used to determine the area under the statistical curve(AUC).The linear correlation analysis confirmed the relationship between NT-proBNP concentration and GRACE score.Results After adjustment for sex,history of current smoking,hypertension,diabetes mellitus,cerebral artery disease and coronary artery vessel lesion(single-vessel lesion,2-vessel lesion,3-vessel lesion),onset time and medication,the multivariate Cox’s regression analysis showed that NT-proBNP concentration and GRACE score were the independent predictors for MACEs in STEMI patients who received PCI.Linear regression analysis showed that the level of NT-pro-BNP was positively correlated with GRACE score(r=0.612,P=0.000).The area under the curve(AUC)for GRACE,NT-pro-BNP and their combination were 0.757,0.723 and 0.782,respectively.Conclusions In a one-year follow-up,the concentration of NTpro-BNP and GRACE score were valuable of prediction for MACEs in STEMI patients who received PCI.In addition,NT-pro-BNP concentration was positively correlated with GRACE score.Additionally,the concentration of NT-pro-BNP could moderately enhance the GRACE score prediction of 1-year MACEs in STEMI patients who received PCI.