Objective To observe the influence of different doses of intravenous immunoglobulin (IVIG) on function of T cells in cord blood of premature infants and to explore the immunomodulating mechanism of IVIG.Methods Cord blood mononuclear cells (CBMC) were isolated by density gradient centrifugation method from 15 preterm infants born between June 1,2011 to December 31,2011 at 32 34 gestational weeks.Three groups were formed according to the concentrations of IVIG used for CMBC culturing in vitro (Group A,6 mg/ml; Group B,9 mg/ml; Group C,12 mg/ml).After 72 hours in sterile conditions,the levels of IFN 7,IL 4,IL-10 and TGF β1 in the supernatant were determined by enzyme-linked immunosorbent assay.The expression of CD4+ CD25+ Foxp3+ Treg cells was examined by fluorescent activated cell sorter.Differences among groups were compared by one way analysis of variance.For comparison between two groups,LSD test was used.Results (1) The level of IFN γ secreted by CBMC in Group C was 0.03 ± 0.02,which was much lower than that in Group A(0.18±0.08) and Group B(0.13±0.05) (F=5.72,both P＜0.01).The level of IFN-γ in Group B and Group A did not show statistical difference (P＞0.05).Compared with Group A(0.03±0.01),the level of IL4 was much lower in Group B (0.02±0.01) and Group C(0.01±0.01) (F=20.38,both P＜0.01),while no significant difference was shown between Group B and Group C (P＞0.05).(2) No significant difference was found in the expression of CD4+CD25+Foxp3+Treg cells among different groups (F 0.67,P＞0.05).(3) The level of IL 10 in Group C was 3.02 ± 3.79,which was significantly lower than that in Group A (10.78±5.44) and Group B (6.90±4.64)(F=4.68,P＜0.01 and 0.05).The level of IL-10 inGroup B was still lower than that in Group A (P＜0.05).The levels of TGF-β1 in Group C(8.44± 13.71) and Group B(16.15 ±13.94) were significantly lower than that in Group A(30.23 ± 16.32) (F=5.22,P＜0.01,P＜0.05),but there was no significant difference between Group B and Group C (P＞0.05).Conclusions IVIG might inhibit the function of Th cells in CBMC of preterm infants in a dose dependent manner.IVIG could inhibit the function of natural Treg cells by regulating the secretion of cytokines IL-10 and TGF-β1 in a dose dependent effect.

BACKGROUND:Shengji Yuhong col agen showed good curative effect of promoting angiogenesis and tissue healing compared with Shengji Yuhong Gao and col agen alone or gelatin alone.
OBJECTIVE:To explore the curative effect and mechanism of subcutaneous implantation of Shengji Yuhong col agen in rabbits in promoting angiogenesis and repair.
METHODS:Shengji Yuhong col agen as the experimental group and collagen as the control group was implanted inside the rabbit subcutaneous pockets of the back of New Zealand rabbits. The implanted samples and
surrounding tissues were obtained at 3, 7, 14, 28 and 56 days fol owing surgery. Pathological sections were made and the repair of surrounding tissue was observed. Hemoglobin levels in col agen were measured.
Immunofluorescence and CD34 dyeing marking method were utilized to observe capil ary angiogenesis. Western blot assay was employed to examine vascular endothelial growth factor and angiogenin-1 expression.
Immunohistochemistry was used to observe the secretion of typeⅠ and Ⅲ col agen on the surrounding tissues.
RESULTS AND CONCLUSION:The experimental group showed increased subcutaneous vascularization. There were reduced inflammatory exudation, granulation tissue hyperplasia, and mature fiber connective tissue at 28 days.
Angiogenesis and hemoglobin contents were greater in the experimental group than in the control group (P<0.05 or P<0.01). At 3 and 7 days fol owing surgery, vascular endothelial growth factor and angiogenin-1 expression was greater in the experimental group than that in the control group (P<0.05 or P<0.01). The secretion of type Ⅰ col agen was
identical between the experimental and control groups. However, the secretion of type Ⅲ col agen was higher in the experimental group than in the control group at 28 and 56 days (P<0.05), and the proportion of type Ⅰ and Ⅲ
col agen was lower in the experimental group than in the control group at 28 and 56 days (P<0.01). These suggested that Shengji Yuhong col agen can significantly promote angiogenesis in the surrounding tissues with the possible
mechanisms of adjusting the protein expression of vascular endothelial growth factor and angiogenin-1. At the same time, it has the function of regulating col agen formation with better ratio of typeⅠ and type Ⅲ col agen to acquire higher
quality of wound healing with reduced scar formation.

ObjectiveTo observe the hong-huang antioxidant on oxidative stress in patients with breast cancer during chemotherapy, including their related blood indexes, blood rheology changes, and the effects on TCM clinical symptoms and symptoms of stress.MethodsA total of 60 cases of breast cancer patients during chemotherapy from Jiangsu Province Hospital of TCM was randomly divided into treatment group and control group, 30 cases in each group. On the basis of conventional therapy, patients in treatment group were given hong-huang antioxidant (100 mL per bag) from the 1st day to the 14th day of chemotherapy, 2 bags for each day (morning and evening). Patients in control group were given foundation treatment the same as the treatment group. Patients in the two groups had their serum NO, the content of SOD, and blood rheology tested on the day before chemotherapy, and the 4th, 7th, 14th days during chemotherapy. Meanwhile, their symptom score and the integral of stress reaction and TCM symptoms were also assessed. ResultsOn the 4th day, serum NO of treatment group decreased, while SOD content increased,without statistical significance between the two groups (P>0.05). Serum NO on the 7th, 14th days was significantly lower than that in the control group, but the content of SOD was higher than that in the control group, with statistical significance between the two groups (P<0.05). Hemorheology on the 4th day significantly decreased after treatment (P<0.05), and was significantly better than that in the control group (P<0.05); Clinical symptoms and stress symptoms integral in the treatment group were significantly lower than those in the control group on the 4th, 7th, 14th days of chemotherapy, with statistical significance (P<0.05).Conclusion Hong-huang antioxidant can significantly improve the oxidative stress status, serological indexes, related blood rheology indexes, and clinical symptoms in patients with breast cancer.

Objective To observe non-displaceable binding potential (BPND) changes of striatal dopamine D2 receptors(SDDR) in patients with first-episode major depressive disorder (MDD) using 11C-Raclopride PET/CT,and to analyze the relationship between BPND and Hamilton rating scale for depression (HAM-D).Methods From December 2014 to December 2015,patients with first-episode MDD and age/gender-matched healthy controls underwent brain MRI and 11C-Raclopride PET/CT in this prospective study.BPND of bilateral SDDR was calculated by molecular imaging and kinetic analysis toolbox (MIAKAT).BPND changes of bilateral SDDR and their relationship with HAM-D score were analyzed.Paired t test,two-sample t test and Pearson correlation analysis were used.Results A total of 20 MDD patients (8 males,12 females,average age: (32.80±9.76) years) and 20 healthy controls (9 males,11 females,average age:(29.25±6.93) years) were enrolled in this study.The 11C-Raclopride uptake in brain tissue of the MDD group and control group were mainly distributed in bilateral striatum,and very few 11C-Raclopride was distributed in bilateral cerebral cortex and cerebellum.In MDD group,the BPND level of bilateral SDDR had no statistical differences(t values: 0.69,0.35,both P>0.05),and similar results were found in the control group(t values: 0.28,0.24,both P>0.05).Compared with the control group,however,the MDD group had lower BPND level of bilateral SDDR(t values: 3.13-4.41,all P<0.05).The BPND of bilateral caudate nucleus and/or putamen D2 receptors was correlated with HAM-D total score,anxiety/somatization factor score,cognitive impairment factor score,retardation factor score and sleep disturbance factor score(r values: from-0.688 to-0.453,all P<0.05).Conclusions The binding potential of SDDR in patients with first-episode MDD is declined,and the BPND level of SDDR is correlated with symptoms of depression.The abnormality of SDDR may be an important molecular mechanism of the abnormality of midbrain-striatal dopamine reward circuits in MDD patients.

Objective To evaluate the effects of Chuanglingye decoction on angiogenesis and wound healing. Methods With a series of dosages of Chuanglingye decoction, their optimal effects of angiogenesis were searched for through the chicken embryo allantois membrane model(CAM). The vascular endothelial cell proliferation experiment (MTT) and the migration assay were used for the detection of effects. The gauze loading with Chuanglingye decoction of 0.2 ml as the experimental group and with saline of 0.2ml as the control group were applied on the total skin mechanical round wound of 1.5cm diameter and changed every other day. The sizes of area were detected on the day of 0,3,7,14 and 28 as well as the scores of inflammatory response, contains of TNF-αand Il-6 were detected on the day of 3 and 7. Results The CAM experiments showed that the angiogenic effects of 0.2 ml and 0.3 ml dosage of the Chuanglingye group were significantly lower than those of the control group(P<0.05). The 0.2 ml dosage of Chuanglingye decoction was chosen for the further experiment. The HUVEC proliferation rate of the experimental group decreased 21%, as compared with the results of control group. The cell migration movement of 12 hours, 24 hours in the experimental group were significantly lower than those in the control group. For theanimal experiments, the area sizes of the wound were similar in the experimental and control group without any significant differences. The scores of inflammatory response and contains of TNF-α(768±107)ng/L,(380±47)ng/L and Il-6(664±133)ng/L,(363±43)ng/L in the experimental group were significant decreased than those of the control group on the day of 3(958± 140)ng/L,(2215±314)ng/Land 7(512±62)ng/L,(1562±174)ng/L. Conclusion It showed that Chuanglingye decoction had negative effects on vascular endothelial cell migration and proliferation and thus inhibiting angiogenesis. These effects did not infer the process of the wound healing due to its ameliorating the inflammatory response which may be a help to wound healing.

Objective To investigate the feasibility of ovariectomized cynomolgus monkey as an animal model of postmenopausal dry eye.Methods Six healthy adult female cynomolgus monkeys (aged 4-6 years old)were selected.Cynomolgus monkeys were divided into ovariectomized group and sham operation group by random number table.Bilateral ovariectomy was performed in each cynomolgus of the ovariectomy group,and the same operation was operated in the sham group but the ovaries were not removed.The venous blood of the lower extremities of each cynomolgus monkey was collected before operation and at 1 month,3 and 6 months after operation respectively.The concentrations of estradiol and testosterone were measured by radioimmunoassay.At the above time points,tear-liquid osmotic pressure detector 5600 was used to detect the tear osmotic pressure of cynomolgus monkeys in each group,and dry eye related examinations,including Schirmer Ⅰ test (S Ⅰ t),corneal fluorescein staining and conjunctive impression cytology were performed.Results Preoperative and postoperative serum estradiol,testosterone concentrations in the ovariectomy group were lower than those in the sham operation group,but there were no significant differences between the two groups (Fgroup =5.16,P =0.09;Fgroup =1.46,P =0.29).There was no significant difference in the osmotic pressure between the two groups (Fgroup =0.83,P=0.37).The osmotic pressure in the 3 months after ovariectomy was higher than that in the 1 month after ovariectomy in the ovariectomy group,with a significant difference between them (t =5.12,P ＜ 0.05).There was no significant difference in S Ⅰ t between ovariectomized group and sham operation group (Fgroup =0.06,P=0.82),the S Ⅰ t in the 3 months after ovariectomy was lower than that in the 1 month after ovariectomy in the ovariectomy group,with a significant difference between them (t =1.13,P＜0.05).There was no corneal fluorescein staining at each time points before and after ovariectomy in each group.The conjunctive impression cytology examination showed that,in the ovariectomy group,the morphology of conjunctival epithelial cells was normal,the number of conjunctival goblet cells was large,the periodic acid Schiff staining was purple before and 1 month after ovariectomy,which were similar to those in the sham operation group;three months after ovariectomy,the conjunctiva epithelial cell body was larger and had diverse forms,goblet cells were shrinked;six months after ovariectomy,the shapes of conjunctival epithelial cells were diverse and not easily been distinguished,the number of goblet cells was distinctly decreased.Conclusions The ocular conjunctival cells in the ovariectomized cynomolgus monkey have abnormal changes in morphology,and tear osmotic pressure increase,the ocular surface dynamic changes are consistent with the decrease of serum estrogen level,so ovariectomized cynomolgus monkeys can be used as sex hormone-related dry eye animal models.

Objective To explore potential genes associated with the pathogenesis of hypospadias using weighted Gene co-expression network analysis(WGCNA).Methods The WGCNA algorithm was used to process the hypospadias-related dataset GSE35034,and then a gene co-expression weight network was constructed to screen the modules with the highest correlation with hypospadias,and the genes in the modules were enriched and detected by gene ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG).Differential analysis was also performed to screen out differential genes.The differential genes were imported into the String database.Using Cytoscape software,the hub genes in the network were identified.The results screened by the above three methods were combined and analyzed,and the core genes in the intersection set were screened.Using the external dataset GSE121712,the core genes were verified by mRNA expression changes and subject work characterization receiver operating characteristic(ROC)curve diagnosis.Results Fifteen co-expression modules were obtained based on the WGCNA method.Ninety-three common differential genes meeting the conditions were obtained by differential analysis.Ten core genes were finally obtained by Cytoscape software analysis.Finally MEbrown module,differential genes and the 10 core genes yielded a total of 2 intersecting genes:FBXL16 and SYNDIG1.ROC curves verified that the intersecting genes were differentially expressed in patients with hypospadias versus normal subjects.Conclusion In this study,two key genes with significant correlation with hypospadias were obtained by WGCNA,which may be used for the early diagnosis and treatment of hypospadias after further study.

Objective To explore the correlation between changes of striatal dopamine D2receptors non-displaceable binding potential (BPND) in 11C-Raclopride PET-CT and brain regional homogeneity (ReHo) derived from resting state functional MRI (fMRI) in patients with first-episode major depressive disorder (MDD) . Methods Patients with first-episode MDD and age and sex matched healthy volunteers accepted brain 11C-Raclopride PET-CT and resting state fMRI. MIAKAT based on MATLAB and Rest 1.8 were used to calculate BPNDof brain dopamine D2receptors and brain ReHo, respectively. Changes of striatal dopamine D2receptors BPNDand brain ReHo values were analyzed by paired-sample t test and two independent sample t-test, and Pearson correlation analysis was used to analyze the correlation between BPNDand ReHo. Results Twenty patients with first-episode MDD were enrolled as MDD group, and 20 healthy volunteers as the control group. The two groups were all right-handed, and there were no statistical differences for age (t =1.33,P=0.19)and gender(χ2=0.10,P=0.75). Compared with the control group, the ReHo in MDD patients increased in the bilateral striatum (caudate nucleus and putamen), bilateral medial prefrontal lobes, and right thalamic (27 to 56 voxels, P＜0.05) and decreased in the left middle frontal gyrus, the left anterior cingulate, the left hippocampal and the right amygdala (21 to 35 voxels, P＜0.05). In addition, compared with the control group, BPNDof bilateral caudate nucleus and putamen dopamine D2receptors in the MDD group were decreased (t=－4.41 to －3.13, P＜0.05). Furthermore, there was a negative correlation between D2 receptors BPNDand ReHo of bilateral caudate nucleus and putamen (r=－0.81 to－0.62, P＜0.05). And there was a negative correlation between ReHo of the bilateral medial prefrontal lobes and BPNDof the same lateral caudate nucleus and putamen D2receptors in the MDD group (r=－0.86 to－0.52, P＜0.05). Besides, ReHo of the left middle frontal gyrus, right thalamic, left anterior cingulate, left hippocampal and right amygdala had no correlation with the D2receptors BPNDof the striatum in the MDD group (－0.27 to 0.39, P＞0.05). Conclusion There were abnormal levels of dopamine neurotransmitter in the cerebral striatum regions and abnormal brain activities in the brain region associated with dopamine reward circuit in the first-episode MDD patients, and there was a correlation between the two abnormalities.

Objective:To investigate associations between cardiac biomarkers with stroke severity and short-term outcome in patients with acute ischemic stroke (AIS).Methods:Patients with AIS admitted to the Affiliated Hospital of Qingdao University from June 2018 to February 2024 whose etiological classification was large artery atherosclerosis (LAA), small vessel occlusion (SVO) or cardioembolism (CE) were included retrospectively. According to the National Institutes of Health Stroke Scale score at admission, patients were divided into mild stroke group (≤8) and moderate to severe stroke group (>8). According to the modified Rankin Scale score at discharge, patients were divided into good outcome group (≤2) and poor outcome group (>2). Multivariate logistic regression analysis was used to determine the independent correlation between cardiac biomarkers and short-term outcome. The predictive value of cardiac biomarkers for poor outcome in patients with AIS and different stroke etiology subtypes were evaluated using receiver operating characteristic (ROC) curves. Results:A total of 2 151 patients with AIS were enrolled, including 1 256 males (58.4%), aged 67.40±11.34 years. 1 079 patents were LAA type (50.2%), 679 were SVO type (31.6%), and 393 were CE type (18.3%); 1 223 were mild stroke (56.86%) and 928 (43.14%) were moderate to severe stroke; 1 357 patients (63.09%) had good short-term outcome, and 794 (36.91%) had poor short-term outcome. Multivariate logistic regression analysis showed that N-terminal pro-B type natriuretic peptide (NT-proBNP), NT-proBNP/creatine kinase (CK) isoenzyme MB (CK-MB) ratio, and CK-MB/CK ratio were independent risk factors for poor short-term outcome. ROC curve analysis shows that the CK-MB/CK ratio had a higher predictive value for short-term poor outcome in patients with AIS (the area under the curve, 0.859, 95% confidence interval 0.839-0.879). Various cardiac biomarkers had a higher predictive value for short-term outcome of CE type and LAA type, but the predictive value for short-term outcome of SVO type was lower. Conclusions:Cardiac biomarkers are associated with the severity and poor outcome of AIS. NT-proBNP/CK-MB and CK-MB/CK ratios have higher predictive value for short-term poor outcome of AIS, especially in patients with CE type.

Objective:To evaluate the clinical radiological features combined with circulating tumor cells in the diagnosis of benign and malignant pulmonary solid nodules.Methods:Clinical data of 437 patients from Shanghai Pulmonary Hospital(SPH cohort) from January to April 2021 and 82 patients from Lanzhou University First Hospital (LZH cohort) from August 2019 to May 2022 were retrospectively included. Patients in Shanghai pulmonary hospital were randomly divided into training set and internal validation set in a ratio of 4∶1 by random number table method and patients in Lanzhou University First Hospital were as external validation set. Independent risk factors were selected by regression analysis of training set constructed a Nomogram prediction model. The performance of the Nomogram prediction model was estimated by applying receiver operating curve( ROC) analysis, tested in different nodules size and intermediate risk IPSNs and tested by calibration curve. Results:Independent risk factors selected by regression analysis for solid pulmonary nodules were age, the level of CTC, pleural Indentation, lobulation, spiculation. The Nomogram prediction mode provided an area under ROC( AUC) of 0.888, 0.833 in internal validation set and external validation set, outperforming radiological features model(0.835, P=0.007; 0.804, P=0.043) Mayo clinical model(0.781, P=0.019; 0.726, P=0.033) and CTCs(0.699, P=0.002; 0.648, P=0.012) in both two validation sets, C-index of 0.888, 0.871 and corrected C-index of 0.853, 0.842 in both two validation sets . The AUC of the prediction model with internal validation set was 0.905 and 0.871 for nodule diameter of 5-20 mm and intermediate risk probability. Conclusion:The prediction model in this study has better diagnostic value and practicability, and is more effective in clinical diagnosis of diseases.