ObjectiveTo screen out the transcriptomes related to the intervention of Wuzi Yanzongwan on the spermatogenic function of semi-castrated male mice， and to explore its potential mechanism in the intervention of the progress of low spermatogenic function. MethodBalb/c mice were randomly divided into sham-operated group， model group， testosterone propionate group（0.2 mg·kg^-1·d^-1， intramuscular injection） and Wuzi Yanzongwan group（1.56 g·kg^-1·d^-1， intragastric administration） according to body weight， with 12 mice in each group. The right testicle and epididymis were extracted from the model group and the drug administration group to construct the semi-castrated model of low spermatogenic function， while the fur and the right scrotum of the sham-operated group were only cut and immediately sterilized and sutured. At the end of the intervention， hematoxylin-eosin（HE） staining was used to observe the histopathology of testis， enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of serum testosterone（T）， luteinizing hormone（LH） and follicle stimulating hormone（FSH）. The sperm count and motility of epididymis were measured by automatic sperm detector of small animal. Transcriptomic microarray technology was used to detect the mRNA expression level of testicular tissue in each group， the transcriptome of genes related to the regulation of Wuzi Yanzongwan was screened， and three mRNAs were selected for Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） to verify the transcriptome data. Through the annotation analysis of Gene Ontology（GO） and the signaling pathway analysis of Kyoto Encyclopedia of Genes and Genomes（KEGG）， the related functions of drugs regulating transcriptome were analyzed. ResultCompared with the sham-operated group， the testicular tissue of mice in the model group showed spermatogenic injury， contraction and vacuolization of the seminiferous tubules， reduction of spermatogenic cells at all levels， widening of the interstitial space， obstruction of spermatogonial cell development and other morphological abnormalities， and serum T significantly decreased， LH significantly increased（P<0.01）， and FSH elevated but no statistically significant difference， the count and vitality of epididymal sperm significantly decreased（P<0.01）. There were 882 differentially expressed mRNAs in the testicular tissues， of which 565 were up-regulated and 317 were down-regulated. Cluster analysis showed that these differentially expressed mRNA could effectively distinguish between the sham-operated group and the model group. Compared with the model group， the damage to testicular tissue in the Wuzi Yanzongwan group was reduced， the structure of the seminiferous tubules was intact， vacuolization was reduced， and the number of spermatogenic cells at all levels was significantly increased and arranged tightly. The serum T significantly increased， LH significantly decreased（P<0.01）， and FSH decreased but the difference was not statistically significant. The count and vitality of sperm in the epididymis were significantly increased（P<0.01）. Moreover， Wuzi Yanzongwan could regulate 159 mRNA levels in the testes of semi-castrated mice， of which 32 were up-regulated and 127 were down-regulated， and the data of the transcriptome assay was verified to be reliable by Real-time PCR. GO and KEGG analysis showed that the transcriptome functions regulated by Wuzi Yanzongwan were involved in the whole cell cycle process of sperm development such as sex hormone production of interstitial cells in testis， renewal， differentiation， metabolism， apoptosis and signal transduction of spermatogenic cells， and were closely related to the biological behaviors of signaling pathways such as spermatogenic stem cell function， endoplasmic reticulum protein processing and metabolic program. ConclusionWuzi Yanzongwan can effectively improve the low spermatogenic function of semi-castrated male mice， and its mechanism may be related to the regulation of testicular transcriptional regulatory network， the synthesis of sex hormones in testicular interstitial cells， the function of spermatogenic stem cells， the whole cell cycle process of spermatogenesis， as well as the expression of endoplasmic reticulum protein processing and metabolic program related genes transcription.

Percutaneous coronary intervention (PCI) is an important treatment strategy for patients with coronary artery disease. However, bleeding after PCI significantly increases the mortality risk. The search for prognostic predictors and optimal antiplatelet therapy for patients with high bleeding risk (HBR) after PCI has been a much researched upon topic in current cardiovascular research. However, there is no widely accepted prognostic model or recommended antiplatelet therapy for patients with PCI-HBR. In this trial, based on prospective multi-center database building, we will analyze the adverse prognostic predictors for patients with PCI-HBR, observe the types of antiplatelet drugs and duration of dual antiplatelet therapy in PCI-HBR patients, and compare the safety and feasibility of different antiplatelet regimens and treatment courses. The prognostic analysis and an appropriate antiplatelet strategy for patients with PCI and high bleeding risk (PPP-PCI) trial will help analyze bleeding risk factors in PCI-HBR patients and explore the appropriate antiplatelet treatment options. This study is registered with ClinicalTrials.gov (NCT05369442). The Research Ethics Committee of West China Hospital authorized this study (2022 Review #269). The trial results will be published in peer-reviewed journals and at conferences.

Percutaneous coronary intervention (PCI) is an important treatment strategy for patients with coronary artery disease. However, bleeding after PCI significantly increases the mortality risk. The search for prognostic predictors and optimal antiplatelet therapy for patients with high bleeding risk (HBR) after PCI has been a much researched upon topic in current cardiovascular research. However, there is no widely accepted prognostic model or recommended antiplatelet therapy for patients with PCI-HBR. In this trial, based on prospective multi-center database building, we will analyze the adverse prognostic predictors for patients with PCI-HBR, observe the types of antiplatelet drugs and duration of dual antiplatelet therapy in PCI-HBR patients, and compare the safety and feasibility of different antiplatelet regimens and treatment courses. The prognostic analysis and an appropriate antiplatelet strategy for patients with PCI and high bleeding risk (PPP-PCI) trial will help analyze bleeding risk factors in PCI-HBR patients and explore the appropriate antiplatelet treatment options. This study is registered with ClinicalTrials.gov (NCT05369442). The Research Ethics Committee of West China Hospital authorized this study (2022 Review #269). The trial results will be published in peer-reviewed journals and at conferences.

Objective:This article aims to analyze and explore practical and effective operation and management mechanisms of the independent interdisciplinary institutes in universities.Methods:Adopting case analysis and literature review as research methodologies to explore the operation and management mechanisms of mature interdisciplinary research institutions in foreign universities, and providing constructive suggestions for domestic academic institutions.Results:Case analysis found that flexible talent structure, sufficient scientific research platform sharing mechanism, and close partnership with industry operation mechanism can effectively promote the virtuous circle of interdisciplinary knowledge generation, dissemination and transformation, thereby driving the efficient operation of interdisciplinary institutes. At the same time, scientific and appropriate management scheme and evaluation system provide a strong systematic administrative support.Conclusions:Interdisciplinary institutes in domestic universities should adopt a matrix-style team formation method to assure the flow of talents with diverse backgrounds, thereby enhancing the internal driving-force of interdisciplinary development. Besides, a substantial resource sharing mechanism should be created to promote the establishment of interdisciplinary research communities. Furthermore, exploring " extensional" knowledge transfer mechanisms to promote collaborative innovation with enterprises. At the same time, establishing scientific and clear institutional management which take into full consideration of the key factors of interdisciplinary research methods and evaluation system.

Objective　To investigate clinical effectiveness outcome and risk factors of endovascular treatment for acute anterior circulation ischemic stroke to instruct emergency thrombectomy in future. Methods　Between January 2016 and December 2018，stroke patients with acute anterior circulation occlusion and EVT within 24 h of symptom onset were retrospectively enrolled from stroke center in first hospital of Jilin university. The main outcomes were modified thrombolysis in cerebral ischemia （mTICI） assessing vascular recanalization，modified Rankin Scale （0~2 as functional independence） at 90 days，symptomatic intracranial hemorrhage （sICH） at 72 h，and death at 90 days. We also identified influence factors for poor functional outcomes at 90 days. Results　Of the 145 patients received acute endovascular treatment，128 （88.3%） patients had vascular recanalization. Symptomatic intracranial haemorrhage occurred in 16（11%） patients. 67（46.2%） patients had functional independence at 90 days. Mortality rate at 90 days was 17.9% （26/145）. Age，hypertension，diabetes mellitus，general anesthesia，tandem or multiple vascular lesions，high baseline NIHSS score，sICH and perioperative pneumonia were risk factors of poor functional outcomes at 90 days of endovascular treatment for acute anterior circulation large vessel occlusion ischemic stroke secondary to large artery occlusion. Conclusion　The vascular recanalization rate and clinical outcomes of endovascular treatment for acute anterior circulation ischemic stroke in Chinese experienced stroke center were consistent with those in developed European and American countries. Risk and mortality of emergency intervention are still high even at experienced stroke centers.

Objective To compare the pharmacodynamics between different batches of recombinant decoy receptor innovative drug RC28-E1 and RC28-E2 in retinal angiogenesis and neovascularization,and analyze its mechanism.Methods Sixty postnatal Day 4 (P4) C57BL/6J mice were randomly divided into normal control group,vascular endothelial growth factor (VEGF)+fibroblast growth factor 2 (FGF2) group,VEGF+FGF2+RC28-E1 group,VEGF+FGF2+RC28-E2 group,VEGF+FGF2+conbercept group and VEGF+FGF2+FGF trap group by using a random number table,with 10 mice in each group.The mouse retinal explant culture system was established,and stimulated with the corresponding factors and drugs prepared in the starving culture media.The normal controls were treated with the starving media.Then the retinal explants were stained with Isolectin B4 and imaged.The number of filopodia per vascular length was quantified.In addition,ninety-six P7 C57BL/6J mice were randomly divided into normal control group,oxygen-induced retinopathy (OIR) model control group,OIR + RC28-E1 group,OIR + RC28-E2 group,OIR+conbercept group and OIR+FGF trap group by using a random number table,with 16 mice in each group.The normal controls were raised under normoxia for 10 days,and the rest of the groups were raised under hyperoxia for 5 days,then returned to normoxia for another 5 days.On P17,the retinas were isolated and stained with Isolectin B4.The stained retinas were mountedon the slides and photographed.The relative vessel obliteration and neovascularization in retina were analyzed with computer software.Then the protein levels of VEGF and FGF2 were examined by Western blot in the retinas of each group in the OIR experiment.Finally,in the RF/6A cells stimulated with VEGF and FGF2,the activities of the signaling pathways,including MEK-extracellular regulated protein kinases (Erk),protein kinase C (PKC) and protein kinase B (Akt) pathways,were examined by Western blot.All experimental procedures were evaluated and approved by the Institutional Animal Care and Use Committee of Tianjin Medical University (SYXK 2009-0001),and were in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research.Results The results of retinal explant cultures showed that the numbers of filopodia per vascular length in VEGF + FGF2 + RC28-E1,VEGF + FGF2 + RC28-E2,VEGF + FGF2 + conbcrcept,and VEGF+FGF2+FGF trap groups were all significantly less than that in the VEGF+FGF2 group (all at P ＜ 0.001).The filopodia number in retinal vascular front in RC28-E1 group was similar to that in the RC28-E2 group (P =0.15),whereas the filopodia numbers in both groups were significantly decreased as compared to those in VEGF+ FGF2+conbercept group and VEGF+FGF2+FGF trap group (all at P＜0.001).The results from the OIR mouse model showed that the relative vessel obliteration area in OIR model control group was dramatically higher than those in the drug intervention groups (all at P＜0.05).There was no statistical significance in the relative vessel obliteration area between OIR+RC28-E1 group and OIR+RC28-E2 group (P =0.17),while the obliteration areas in both RC28-E-intervened groups were significantly lower than those in the OIR+conbercept group and OIR+FGF trap group (all at P＜0.05).The relative neovascular pixels in the intervention groups were significantly lower than those in the OIR model control group (all at P＜0.001).The neovascular pixels in OIR+RC28-E1 group were significantly lower than those in VEGF+FGF2+conbercept group and VEGF + FGF2 + FGF trap group (both at P ＜ 0.05),but comparable to those in OIR+RC28-E2 group (P =0.39).Western blot result showed that,the protein expression of VEGF and FGF2 in the OIR mouse retinas were significantly upregulated compared to those in the normal ones (both at P＜0.001).The upregulation of both genes were normalized by both RC28-E1 and RC28-E2.In addition,the stimulation of VEGF and FGF2 induced an enhanced activity in MEK-Erk pathway in RF/6A cells,whereas RC28-E1 inhibited the overactivation.Conclusions RC28-E1 and RC28-E2 both can inhibit angiogenesis in the retinal explants isolated from neonatal mice;they also reduce vessel obliteration and mitigate neovascularization in the OIR mouse model.Therefore,the pharmacology batch and pilot test batch of RC28-E have similar efficacies and reliable stability,and are superior in the anti-angiogenic and anti-neovascular efficacy to the currently clinically available drugs conbercept and FGF trap.RC28-E1 may suppress pathological neovascularization through inhibiting the overactivation of MEK-Erk pathway in retinal vascular endothelial cells.

Objective: To investigate the association between the internal exposure levels of phthalic acid esters (PAEs) and executive function (EF) of preschool children. Methods: Between October 2008 and October 2010, pregnant women who accepted pregnancy health care services in four municipal medical and health institutions in Ma'anshan city, Anhui Province, were recruited as study objects. A total of 5 084 pregnant women and 4 669 singleton live births were enrolled in this cohort. The follow-up study was conducted from April 2014 to April 2015. A total of 3 725 data-completed preschool children aged 3 to 6 years older entered in this study. The method of analysis seven metabolites of phthalates in urine was high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and divided objects into low (P₀-P₂₄), medium (P₂₅-P₇₄) and high (P₇₅-P₁₀₀) groups according to their exposure concentrations. To investigate the executive function of preschool children, we used the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P). Univariate and multivariate statistical method was used to analyze the etiology association between the phthalate metabolites levels and preschool children's executive function. Results: In this study, 53.6% (1 997/3 725) of preschoolers were boys, children's age was (51.5±5.6) months. The detection rates of seven phthalate esters were: mono-n-methyl phthalate (MMP) was 99.89% (3 721/3 725); mono-ethyl phthalate (MEP) was 99.97% (3 724/3 725); mono-benzyl phthalate (MBzP) was 69.10% (2 574/3 725); mono-butyl phthalate (MBP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono- (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) were 100.00% and mono-ethylhexyl phthalate (MEHP) was 99.95% (3 723/3 725). The median concentrations of the seven phthalate metabolites were: 17.71, 15.36, 0.07, 155.24, 10.73, 14.67, 3.59 µg/L, respectively. The median concentrations corrected by urinary creatinine were 29.65, 26.65, 0.12, 257.73, 17.94, 24.80, 6.27 µg/g Cr, respectively. The P₂₅ and P₇5 concentration of the total PAEs metabolites corrected by urinary creatinine were 1.20 µmol/g Cr and 3.04 µmol/g Cr. After adjusted the relevant demographic information: children sex, children age in month, maternal age, parental education levels, household exposure to secondhand smoke and whether the child is the only child as confounds, multivariate logistic regression model showed that the risk of inhibitory self-control index (ISCI) dysplasia in MEHHP high concentration group and MEOHP high concentration group were 1.71 and 1.54 times (OR=1.71, 95% CI: 1.11-2.62; OR=1.54, 95% CI: 1.01-2.34) than in low concentration group. The risk of ISCI dysplasia in total PAEs metabolites high concentration group was 1.55 times (OR=1.55, 95% CI: 1.00-2.38) than in low concentration group. Conclusion Phthalates exposure may damage the executive function of preschool children.

Background Reasearches showed that α-melanocyte-stimulating hormone (α-MSH) inhibits inflammation and ameliorates the ocular surface abnormalities in a scopolamine-induced dry eye rat model,and the managing effect of sodium carboxymethylcellulose (CMC) on dry eyes also has been determined.However,whether α-MSH can enhance the therapeutic effects of CMC remains to be investigated.Objective This study was to investigate the protective effects of α-MSH combined with CMC on ocular surface in a scopolamine-induced dry eye rat model.Methods Sixty clean female Wistar rats were randomly divided into normal control group,model control group,NaCl group,CMC group,α-MSH group and α-MSH+CMC group,and 10 rats for each group.The dry eye models were established by subcutaneous injection of scopolamine hydrobromide at 9:00,12:00,15:00 and 18:00 per day for 28 days.0.9％ NaCl solution,1×10 3 mg/ml α-MSH solution,0.5％ CMC eye drop,and 1 ×10-3 mg/ml α-MSH+0.5％ CMC solution were topically administered twice a day (8:00,17:00) since the initial day of modeling according to grouping.Shirmer Ⅰ test (S Ⅰ t),breakup time of tear film (BUT) and corneal fluorescence staining were performed before and 7,14,21,28 days after the application of drugs.At 28 days following the administration of drugs,the eyeballs of the rats were collected.Hemotoxylin and eosin staining was employed to examine the morphology of corneas,and periodic acid schiff (PAS) staining was used to count the conjunctival goblet cells.This study protocol was approved by Experimental Animal Ethic Committee of Tianjin Medical University (SYXK 2009-0001),and the use and care of the rats complied with ARVO Statement.Results The S Ⅰ t and BUT values were significantly reduced,and the corneal fluorescence staining scores were significantly increased over time following modeling in the model control group (all at P＜0.01).No significant differences were found in the S Ⅰ t,BUT and corneal fluorescence staining scores between model control group and NaCl group at various time points (all at P＞0.05).At 7,14 and 21 days after intervention,the S Ⅰ t values were (4.800±0.789),(4.100±0.516) and (4.300±0.856) mm in the α-MSH+CMC group,which were considerably higher than (2.875 ±0.719),(2.375 ±0.619) and (2.532±0.957)mm in the NaCl group (all at P＜0.01).At 7 days after intervention,the BUT values were (4.938± 1.843) seconds and (5.000±1.491) seconds in the α-MSH group and α-MSH+CMC group,which were significantly higher than (3.250±1.000) seconds in the NaCl group (both at P＜0.01).The corneal fluorescence staining scores in the CMC group,α-MSH group and α-MSH+CMC group were significantly lower than that in the NaCl group,with the lowest score in the α-MSH +CMC group (all at P＜0.05).The thickening of corneal epithelial layer,corneal edema and arrangement disorder of corneal stroma were found in the model control group and NaCl group;while slight corneal edema and epithelial cell proliferation were exhibited in the α-MSH+CMC group by hemotoxylin and eosin staining.PAS staining showed that the number of goblet cells was much more in the CMC group,α-MSH group and α-MSH+ CMC group than that in the model control group and NaCl group (all at P ＜ 0.01).Conclusions The sole application of α-MSH or CMC alleviates ocular surface damage and morphological abnormality to certain extent,and the combination of α-MSH and CMC generates more effective protection in comparison with sole administration of α-MSH or CMC.The early application of the drugs plays an improvement role in tear secretion and tear film stability in dry eyes.

Objective To investigate the expression and clinical significance of silent mating type information regulation 2 homolog-1(SIRT-1)and nuclear factor-κB(NF-κB)in non-small cell lung cancer (NSCLC). Methods The expressions of SIRT-1 and NF-κB were evaluated by immunohistochemistry in 108 selected cases of primary NSCLC and 48 samples of para-carcinoma normal tissue. The relationships of the expressions of SIRT-1 and NF-κB and clinical pathological features were analyzed,respectively. Results Immunohistochemical results showed that the positive expression rates of SIRT-1 and NF-κB in NSCLC tissue were 90. 7%(98 / 108)and 94. 4%(102 / 108),respectively,significantly higher than those in normal lung tissue 4. 2%(2 / 48),16. 7%(8 / 48),χ2 = 108. 237,P = 0. 000;χ2 = 96. 683,P = 0. 000,and the expre-ssion of SIRT-1 and NF-κB showed a positive correlation(r = 0. 480,P = 0. 001). There were significant posi-tive correlations between the expression of SIRT-1 and tumor size(r = 0. 227,P = 0. 018),TNM stage(r =0. 298,P = 0. 002)and lymph node metastasis(r = 0. 280,P = 0. 003),and there was negative correlation between the expression of SIRT-1 and differentiation(r = - 0. 300,P = 0. 002),and there were no correlation between the expression of SIRT-1 and sex,age and histological type in NSCLC tissues. There were significant positive correlation between the expression of NF-κB and TNM stage(r = 0. 256,P = 0. 009)and lymph node metastasis(r = 0. 261,P = 0. 006),and there was negative correlation between the expression of NF-κB and differentiation(r = - 0. 235,P = 0. 013),and there were no correlation between the expression of NF-κB and sex,age,histological type and tumor size in NSCLC tissues. Conclusion The positive expression rates of SIRT-1 and NF-κB in NSCLC tissue are significantly higher than those in normal lung tissue,and they are rela-ted to TNM stage,lymph node metastasis and differentiation,and the former is also related to tumor size. High expression of SIRT-1 and NF-κB may play important roles in the occurrence and development of NSCLC.

Objective To investigate the expression and clinical significance of Sir2?related enzymes?1(SIRT1)in colorectal cancer. Methods The expression of SIRT1 was evaluated by immunohistochemistry in 86 selected cases of primary Colorectal cancer and 30 samples of normal rectum tissues besided carcinoma. The relationship of the expression and clinical pathological features were analyzed. Results The positive expression rate of SIRT1 in Colorectal cancer tissue was 88.4%,and significantly higher than in normal rectum tissue besided carcinoma(P<0.001). There were no correlation between the expression of SIRT1 and sex,age and tumor diameter,and significant positive correlation between the expression of SIRT1 and TNM stage (P<0.05),lymph node metastasis(P<0.05),infiltrating depth(P<0.05),and negagtive correlation between the expression of SIRT1 and tumor differentiation(P<0.05). Conclusion The positive expression rate of SIRT1 in colorectal cancer tissue was significantly higher than in normal rectum tissue besided carcinoma and intimate correlation with tumor differentiation,TNM stage,lymph node metastasis and Infiltrat?ing depth. Conclusion SIRT1 may be an important assistance gene to diagnose and judge prognosis,and may improve diagnostic rate and auxiliari?ly judge prognosis as a important Colorectal cancer marker.