AIM:To investigate the expression profile and biological significance of long noncoding RNA(lncRNA)zinc finger antisense 1(ZFAS1)in the brains of mice with diabetic encephalopathy(DE).METHODS:Ten db/m mice served as the normal control group,while twenty 22-week-old db/db mice were used to establish the DE model and randomly divided into two subgroups:ten as the db/db model control and the remaining ten receiving ZFAS1 gene knockdown(db/db+sh-ZFAS1)via lentiviral transfection.Weekly measurements of body weight and blood glucose levels were performed.Brain tissues were collected for Nissl staining to evaluate neuronal damage,TUNEL assay to detect apop-tosis,and immunofluorescence staining to examine neural biomarker expression.Serum levels of tumor necrosis factor-α(TNF-α)and oxidative stress markers,including reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT)and glutathione peroxidase(GSH-Px),were determined.Western blot was conducted to quantify the protein expression levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),p38 mitogen-activated protein kinase and phosphorylated p38(p-p38)in brain tissues.The expression levels of ZFAS1 and caspase-3 mRNA were determined by RT-qPCR.RESULTS:Knockdown of ZFAS1 in db/db mice significantly improved cognitive function,alleviated hippocampal neuronal damage,and reduced body weight and blood glucose levels(P<0.01).More-over,oxidative stress was mitigated,as evidenced by decreased MDA and ROS levels(P<0.01)and increased activity of antioxidant enzymes,GSH-Px,SOD and CAT(P<0.01 or P<0.05).Meanwhile,ZFAS1 silencing down-regulated Bax and p-p38/p38 protein expression(P<0.01 or P<0.05)while up-regulating Bcl-2(P<0.01).Consistently,RT-qPCR confirmed significant down-regulation of ZFAS1 and caspase-3 mRNA levels(P<0.01).CONCLUSION:lncRNA ZFAS1 is highly expressed in the hippocampus of DE mice.Down-regulation of ZFAS1 expression enhances cognitive func-tion,suppresses oxidative stress,and inhibits neuronal apoptosis,thereby attenuating neural damage in DE.

AIM:To investigate the expression profile and biological significance of long noncoding RNA(lncRNA)zinc finger antisense 1(ZFAS1)in the brains of mice with diabetic encephalopathy(DE).METHODS:Ten db/m mice served as the normal control group,while twenty 22-week-old db/db mice were used to establish the DE model and randomly divided into two subgroups:ten as the db/db model control and the remaining ten receiving ZFAS1 gene knockdown(db/db+sh-ZFAS1)via lentiviral transfection.Weekly measurements of body weight and blood glucose levels were performed.Brain tissues were collected for Nissl staining to evaluate neuronal damage,TUNEL assay to detect apop-tosis,and immunofluorescence staining to examine neural biomarker expression.Serum levels of tumor necrosis factor-α(TNF-α)and oxidative stress markers,including reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT)and glutathione peroxidase(GSH-Px),were determined.Western blot was conducted to quantify the protein expression levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),p38 mitogen-activated protein kinase and phosphorylated p38(p-p38)in brain tissues.The expression levels of ZFAS1 and caspase-3 mRNA were determined by RT-qPCR.RESULTS:Knockdown of ZFAS1 in db/db mice significantly improved cognitive function,alleviated hippocampal neuronal damage,and reduced body weight and blood glucose levels(P<0.01).More-over,oxidative stress was mitigated,as evidenced by decreased MDA and ROS levels(P<0.01)and increased activity of antioxidant enzymes,GSH-Px,SOD and CAT(P<0.01 or P<0.05).Meanwhile,ZFAS1 silencing down-regulated Bax and p-p38/p38 protein expression(P<0.01 or P<0.05)while up-regulating Bcl-2(P<0.01).Consistently,RT-qPCR confirmed significant down-regulation of ZFAS1 and caspase-3 mRNA levels(P<0.01).CONCLUSION:lncRNA ZFAS1 is highly expressed in the hippocampus of DE mice.Down-regulation of ZFAS1 expression enhances cognitive func-tion,suppresses oxidative stress,and inhibits neuronal apoptosis,thereby attenuating neural damage in DE.

Objective To investigate the predictive value of serum thrombospondin-1(THBS-1),D-dimer(D-D)and tissue inhibitor of metalloproteinase-1(TIMP-1)levels in late pregnancy for postpartum hemorrhage(PPH)in re-pregnant women with scarred uterus.Methods Totally 108 re-pregnant women with scarred uterus admitted to the First Affiliated Hospital of Xinxiang Medical University from June 2020 to August 2022 were selected and divided into the PPH group(n=21)and the non-PPH group(n=87)according to whether PPH occurred after delivery.On the day of admission,5 mL elbow venous blood was collected from re-pregnant women in the two groups,and the levels of serum THBS-1,D-D and TIMP-1 of pregnant women in the two groups were detected by enzyme-linked immunosorbent assay.The serum THBS-1,D-D TIMP-1 levels and clinical data of pregnant women between the two groups were compared.The influencing factors on the occurrence of PPH in re-pregnant women with scarred uterus were analyzed by multivariate logistic regression,and the predictive value of serum THBS-1,D-D and TIMP-1 levels on the occurrence of PPH in re-pregnant women with scarred uterus was evaluated by receiver operating characteristic curve.Results The percentage of patients with ≥ 2 induced abortions,placental abruption,uterine incision laceration,uterine inertia or scar thickness＜0.3 cm,as well as serum THBS-1 and D-D levels in late pregnancy in the PPH group were significantly higher than those in the non-PPH group,and serum TIMP-1 level in late pregnancy were significantly lower than that in the non-PPH group(P＜0.05).The uterine inertia,as well as high D-D and THBS-1 levels,were independent risk factors for PPH in re-pregnant women with scarred uterus(P＜0.05),and low TIMP-1 level was a protective factor(P＜0.05).The area under the curve of combined serum THBS-1,D-D and TIMP-1 levels to predict PPH in re-pregnant women with scarred uterus was greater than that predicted by the three factors alone(P＜0.05).Conclusion Serum THBS-1,D-D and TIMP-1 levels in late pregnancy can be used as reference indicators for predicting the occurrence of PPH in re-pregnant women with scarred uterus,and the combination of the three indexes is more effective in predicting the occurrence of PPH.

OBJECTIVE To construct the evaluation index system for scientific research ability of hospital pharmacists， and provide reference for the improvement of hospital pharmacists’ scientific research ability and the formulation of relevant scientific research policies. METHODS The relevant indexes of scientific research evaluation of hospital pharmacists were extracted by literature analysis， and consultation questionnaire was designed according to Likert grade 5 scoring method. Delphi method was used to conduct two rounds of questionnaire consultation for 28 experts， and the weight of each index was determined by analytic hierarchy process. The reliability and validity of index system were analyzed by questionnaire survey. RESULTS After two rounds of expert correspondence， evaluation index system for scientific research ability of hospital pharmacists was finally determined from three core dimensions： basic scientific research ability， scientific research achievements and transformation ability， academic influence and personnel training （including 11 sub-dimensions and 34 measurement items）. The weight value of each dimension index was determined. The result of reliability and validity analysis confirmed the scientific rationality of the index system. CONCLUSIONS The established evaluation index system for scientific research ability of hospital pharmacists is innovative， comprehensive and scientific. The index system model can provide reference for the improvement of hospital pharmacists’ scientific research ability and the formulation of relevant scientific research policies.

Objective:Cushing′s disease(CD) is caused by the pituitary adrenocorticotroph hormone(ACTH) secreting adenomas, leading to increased serum cortisol levels and various abnormal metabolic processes. Untreated CD is linked to high mortality, thus it is critical to elucidate its pathogenesis. This study aims to explore the pathogenesis of pituitary ACTH adenomas using whole-genome sequencing analysis.Methods:Fresh tumor tissues and peripheral blood samples were collected in 9 confirmed cases of pituitary ACTH adenomas who underwent surgery. Whole genome sequencing was then performed, followed by analysis and verification of single nucleotide mutations, copy number variation(CNV) and chromosome structure variations.Results:Somatic USP8 mutations(p.Ser718del, p. Ser718Pro, p. Pro720Arg, p. Pro720Gln) were found in 5 patients, with a rate of 55.6%; CNV of USP8 was detected in 1 patient; TP53(p.Cys135Tyr), NF1(p.Val1049Glufs*11) and KMT2C(c.3323+ 1G>A) mutations were identified in 1 patient harboring wild-type USP8. CNV analysis showed a loss of heterozygosity in multiple chromosomes in a wild-type USP8 patient. Structural variations were found in 2 with unknown significance. No germline gene mutations were detected in this study.Conclusion:Somatic USP8 mutations, increased copy number of USP8, variations of tumor-related genes such as TP53 and extensive somatic CNV all contribute to pathogenesis of CD. Chromosomal structure variations may suggest high-risk pituitary ACTH adenomas, and call for frequent follow-up and aggressive treatment.

Lipid nanoemulsions are promising nanodrug delivery carriers that can improve the efficacy and safety of paclitaxel(PTX).However,no intravenous lipid emulsion of PTX has been approved for clinical treatment,and systemic safety profiles have not yet been reported.Here we outline the development of a PTX-loaded tumor-targeting intravenous lipid emulsion(PTX Emul)and describe its characteristics,colloidal stability,and systemic safety profiles in terms of acute toxicity,long-term toxicity,and tox-icokinetics.We also compare PTX Emul with conventional PTX injection.Results showed that PTX Emul exhibited an ideal average particle size(approximately 160 nm)with narrow size distribution and robust colloidal stability under different conditions.Hypersensitivity reaction and hemolysis tests revealed that PTX Emul did not induce hypersensitivity reactions and had no hemolytic potential.In addition,where the alleviated systemic toxicity of PTX Emul may be attributed to the altered toxicokinetic characteristics in beagle dogs,including the decreased AUC and increased plasma clearance and volume of distribution,PTX Emul alleviated acute and long-term toxicity as evidenced by the enhanced the median lethal dose and approximate lethal dose,moderate body weight change,decreased bone marrow suppression and organ toxicity compared with those under PTX injection at the same dose.A fundamental understanding of the systemic safety profiles,high tumor-targeting efficiency,and superior antitumor activity in vivo of PTX Emul can provide powerful evidence of its therapeutic potential as a future treatment for breast cancer.

Objective:To explore the effect of Wnt/β-catenin signaling pathway on growth plate development of tibial growth plate in young chronic renal failure (CRF) rats.Methods:Four-week-old male SD rats were randomly divided into control group and CRF group ( n=20/per group). Control group was intragastric administration with distilled water, and CRF group was given adenine suspension (150 mg·kg -1·d -1). All the young rats were sacrificed after continuous gavages for 6 weeks. The full length of tibia was compared between the two groups. The width of tibia proximal growth plates was measured by micro-CT scanning, and the width of the growth plate was also measured in histological sections. Chondrocytes isolated from growth plate in two groups were cultured in vitro to P3 generation. Immunohistochemical staining was used to detect the expression of collagen Ⅱ, matrix metalloproteinase 13 (MMP-13) and β-catenin in chondrocytes. Western blotting was used to detect the protein expressions of collagen Ⅱ, MMP-13 and β-catenin. Results:Compared with the control group, the tibial length of rats in the CRF group was shorter [(27.32±5.81) mm vs (35.43±3.61) mm, t=5.226, P<0.001], the width of growth plate in micro-CT picture was more narrow [(0.72±0.22) mm vs (1.13±0.27) mm, t=5.096, P<0.001], and the relative width of the growth plate was also more narrow ( t=6.744, P<0.001) in histological sections. The results of immunohistochemistry and Western blotting showed the expressions of collagen Ⅱ in the CRF group decreased significantly ( t=8.212, P<0.001), MMP-13 ( t=13.091, P<0.001) and β-catenin ( t=7.534, P<0.001) increased significantly compared the control group in chondrocytes. Conclusion:The Wnt/β-catenin signaling pathway is highly expressed in the tibial growth plate of young rats with chronic renal failure, which leads to accelerated degeneration and differentiation of chondrocytes and a closure tendency of growth plate.

Identification of genetic variants via high-throughput sequencing (HTS) technologies has been essential for both fundamental and clinical studies. However, to what extent the genome sequence composition affects variant calling remains unclear. In this study, we identified 63,897 multi-copy sequences (MCSs) with a minimum length of 300 bp, each of which occurs at least twice in the human genome. The 151,749 genomic loci (multi-copy regions, or MCRs) harboring these MCSs account for 1.98％of the genome and are distributed unevenly across chromosomes. MCRs containing the same MCS tend to be located on the same chromosome. Gene Ontology (GO) anal-yses revealed that 3800 genes whose UTRs or exons overlap with MCRs are enriched for Golgi-related cellular component terms and various enzymatic activities in the GO biological function cat-egory. MCRs are also enriched for loci that are sensitive to neocarzinostatin-induced double-strand breaks. Moreover, genetic variants discovered by genome-wide association studies and recorded indbSNP are significantly underrepresented in MCRs. Using simulated HTS datasets, we show that false variant discovery rates are significantly higher in MCRs than in other genomic regions. These results suggest that extra caution must be taken when identifying genetic variants in the MCRs via HTS technologies.

Objective To investigate the image quality and radiation dose of coronary computed tomography argiograply(CCTA) with wide-body detector CT in single cardiac cycle with different heart rate.Methods A total of 821 patients with clinically suspected coronary artery lesions were performed CCTA examination continuously.They were divided into six groups:group A (＜65 bpm) with 132 cases,group B (66-75 bpm) with 244 cases,group C (76-85 bpm) with 145 cases,group D (86-95 bpm) with 101 cases,group E (96-105 bpm) with 101 cases and group F (106-135 bpm) with 98 cases.The CT values of the aorta root and the middle segment of LAD and RCA,the signal to noise ratios (SNRs),the contrast noise ratios (CNRs),the effective doses (E),the diagnostic rates and scores were compared among six groups of CCTA images.Results There was no significant difference in objective quality between the six groups (P＞0.05).There was no significant difference in the diagnostic rates of LAD,LCX and RCA (all P＞0.05).However,there were significant differences in LAD,LCX and RCA with 4 points (excellent) among the six groups (x2 =27.614,58.475,39.571,P ＜ 0.05).There were significant differences in radiation dose among the 6 groups (F=37.32,P＜0.05).The radiation dose of group B was highest,and that of group D,group E and group F was the lowest.Conclusions The CCTA images with wide-body detector CT in single heart cycle with different heart rate can meet the clinical diagnostic requirements,but image quality declined with heart rate increasing.The higher heart rate groups (heart rate ＞ 85 beats/min) had lower radiation doses.