[Effect and mechanism of CD4+CD25+ regulatory T cells on protective efficacy of protein vaccine against Schistosoma japonicum in mice].

OBJECTIVE: To explore the effect and mechanism of CD4+CD25+ Tregs (Tregs) on the protective efficacy of gluthatione-S-transferase (GST) against Schistosoma japonicum in mice. METHODS: Female BALB/c mice were divided randomly into five groups：a normal control group, an infected control group, an anti-CD25mAb group, a GST immunization group and a combination group with GST immunization and anti-CD25 mAb. The GST group and combination group were injected percutaneously with GST 50 µg each mouse, the other two groups were injected with equal volume PBS. The immunization was performed for 3 times for two-week interval, and 2 weeks after the last immunization, each mouse was challenged with 40 S. japonicum cercaria. Two weeks post-infection, the combination group and anti-CD25 mAb group were injected intraperitoneally with 300 µg antiCD25 mAb each mouse. The mice were succumbed 2 weeks, 3 weeks, 4 weeks and 5 weeks post-infection respectively. The percentages of CD4+CD25+ Tregs in splenocytes of mice were measured with flow cytometer. The levels of IFN-γ, IL-2, IL-4, IL-5 and TGF-ß in cell cultural supernatants were determined by sandwich-ELISA after stimulation with Con A. The liver sections were stained with hematoxylin and eosin. RESULTS: The worm burden in the combination group (15.80±2.74) was significantly lower than those of the infected control group (27.78±3.15), anti-CD25 mAb group (21.50±4.21), and GST group (20.84± 6.46). Compared to those of the infected control group, the percentages of CD4+CD25+ Tregs were significantly higher in the GST group, while the percentages of CD4+CD25+ Tregs were significantly lower post-anti-CD25 mAb-administration. Regardless of GST administration, the levels of IFN-γ, IL-2, IL-4 and IL-5 after anti-CD25 mAb were significantly higher than those of the infected control groups. There were no significant differences of egg granuloma and the level of TGF-ß between each group. CONCLUSIONS: CD4+CD25+ Tregs could be partially blocked by anti-CD25 mAb while Th1 and Th2 type immunization response could be enhanced, which plays a role in improving the protective efficacy of GST against of S. japonicum.

Mental health status and its influencing factors of the elderly / 中华疾病控制杂志

Objective To assess the current status and factors associated with the mental health condition of older adults. Methods A convenience sampling survey was conducted using symptom check list 90 (SCL-90) among the Chinese older adults aged 60 or above from January to March, 2018. The older adults aged 80 or above were selected for this study. Chi-square test and binary logistic regression model were used to analyze the influencing factors. Results The total participants were 485. The SCL-90 positive detection rate was 20.21%. The symptoms of the four highest detection rates were somatization (39.38%), others (25.15%), obsessive-compulsive symptoms (24.33%) and depression (22.68%). The older adults with normal BMI (OR=0.537, 95% CI: 0.250-0.857, P=0.027) and lived in county town (OR=0.224, 95% CI:0.075-0.667, P=0.007) showed lower SCL-90 positive detection rate. These who had been educated for 1-5 years (OR=11.092, 95% CI: 4.446-27.671, P<0.001), 6-8 years (OR=9.800, 95% CI: 3.464-27.721, P<0.001), 9~11 years (OR=19.279, 95% CI : 6.722-55.297, P<0.001), 12 years and above (OR=24.321, 95% CI: 7.894-74.929, P<0.001) had higher SCL-90 positive detection rate compared with those who were uneducated. Conclusion The mental health condition of Chinese older adults is mainly influenced by residence place, education level, family income self-evaluation and BMI status.

Analysis and validation of PI3K/AKT signaling pathway associated with overall survival time of patients with HER2-positive breast cancer / 解放军医学杂志

Objective To analyze and validate the key molecular targets correlated with the overall survival of patients with HER2-positive breast cancer.Methods First,the survival time and transcriptome data of patients with HER2-positive breast cancer in stage Ⅰ / Ⅱ and Ⅲ/Ⅳ were downloaded from the TCGA database.The significantly differential genes between overall survival ＜2 years and ＞8.5 years in stage Ⅰ / Ⅱ were picked out by edgeR package,and the pathways were enriched by KEGG.Similarly,the differential genes between overall survival ＜2 years and ＞7 years in stage Ⅲ/Ⅳ were analyzed.Furthermore,KEGG pathway analysis was performed using the differential genes overlapped by stage Ⅰ /Ⅱ and Ⅲ/Ⅳ.Second,the relationships between the expression levels of key node genes and other genes in enriched pathway and the overall survival of patients with HER2-positive breast cancer were validated by KMplot database.Last,the correlation between the activity of pathway enriched in KEGG and the resistance to anti-HER2 treatment was validated in HER2-positive breast cancer cell line BT474.Results In patients with stage Ⅰ / Ⅱ HER2-positive breast cancer whose overall survival was ＜2 years,PI3K/AKT was the 9th signaling pathway enriched by up-regulated differential genes.In patients with stage Ⅲ/Ⅳ whose overall survival was ＜2 years,PI3K/AKT was the 2nd signaling pathway enriched by up-regulated differential genes.Furthermore,PI3K/AKT was the first signal pathway enriched by the overlapping upregulated genes of patients in stage Ⅰ / Ⅱ and Ⅲ / Ⅳ whose overall survival was ＜2 years.Patients with high expression of PI3K and AKT (key node genes) or CFAP221 and COL4A6 (other genes) of PI3K/AKT pathway had shorter overall survival than those with low expression.PI3K inhibitors could enhance the growth inhibitory effect of HER2 small molecule inhibitor on HER2-positive breast cancer cell line BT474.Conclusions The overexpression of PI3K/AKT pathway is associated with the shorter overall survival in HER2-positive breast cancer patients,and associated with anti-HER2 resistance in HER2-positive breast cancer cell line.

Kangle Decoction for erectile dysfunction with liver-qi stagnation and kidney deficiency / 中华男科学杂志

<p><b>Objective</b>To observe the clinical efficacy of Kangle Decoction in the treatment of erectile dysfunction (ED) with liver-qi stagnation and kidney deficiency.</p><p><b>METHODS</b>A total of 79 ED patients with liver-qi stagnation and kidney deficiency were randomly assigned to an experimental group (aged ［36.62±8.05］ yr and with a disease course of ［18.15±6.41］ mo) and a control group (aged ［37.44±8.10］ yr and with a disease course of ［17.51±6.79］ mo), the former treated orally with Kangle Decoction at 0.5 dose bid while the latter with Cialis at 10 mg qd alt, both for 8 weeks. Before treatment, after 4 and 8 weeks of medication, and at 4 weeks after drug withdrawal, we obtained the scores of the patients in the International Index of Erectile Function-5 (IIEF-5), Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), and Short-Form Psychological and Interpersonal Relationship Scales (SF-PAIRS), and compared the indexes between the two groups of patients.</p><p><b>RESULTS</b>The IIEF-5 score was dramatically increased in both the treatment and control groups after 4 weeks (13.40±2.42 and 16.00±2.68) and 8 weeks of medication (18.60±3.50 and 18.59±3.80) and at 4 weeks after drug withdrawal (17.00±3.05 and 13.95±2.61) as compared with the baseline (10.78±2.28 and 10.77±2.33) (P<0.05 ), even higher in the treatment than in the control group after drug withdrawal (P<0.05 ). The EDITS scores in the treatment and control groups were (28.88±3.31 and 28.90±3.31) after 4 weeks of intervention, (29.68±3.30 and 29.13±3.32) after 8 weeks of intervention, and (29.20±2.92 and 26.82±3.23) at 4 weeks after drug withdrawal, all significantly higher in the former than in the latter group after drug withdrawal (P<0.05 ). The sexual self-confidence score (SSCS), sexual spontaneity score (SSS), and sexual time-concern score (STCS) were all improved in the treatment and control groups after medication as compared with the baseline (P<0.05 ), even higher in the former than in the latter group after drug withdrawal (P<0.05 ).</p><p><b>CONCLUSIONS</b>Kangle Decoction has a definite efficacy in the treatment of ED with liver-qi stagnation and kidney deficiency, with few adverse reactions and long-term post-withdrawal effect, and therefore deserves a wide clinical application.</p>

Sertraline hydrochloride combined with four-spot caressing for primary premature ejaculation / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the clinical effectiveness of sertraline hydrochloride combined with four-spot caress in the treatment of primary premature ejaculation (PE).</p><p><b>METHODS</b>We randomly assigned 90 primary PE patients to three groups of equal number. The patients in group A (aged [28.1 ± 5.2] yr and with a disease course of [3.1 ± 1.9] yr) were treated with oral sertraline hydrochloride at 50 mg qd, those in B (aged [27.8 ± 4.1] yr and with a disease course of [3.2 ± 2.0] yr) by four-spot caressing (caressing the tongue, breasts, and vulva prior to intercourse), and those in C (aged [27.1 ± 4.7] yr and with a disease course of [3.1 ± 2.0] yr) by the combination of oral sertraline hydrochloride and four-spot caressing, all for 12 weeks. Before and after 4, 8, and 12 weeks of treatment, we obtained the intravaginal ejaculatory latency time (IELT) and Chinese Index of Sexual Function for Premature Ejaculation-5 (CIPE-5) scores and compared them among the three groups of patients.</p><p><b>RESULTS</b>The IELT was dramatically prolonged in groups A, B, and C after 4 weeks ([1.08 ± 0.29], [0.93 ± 0.28] and [1.21 ± 0.27] min), 8 weeks ([1.43 ± 0.30], [1.20 ± 0.33] and [1.72 ± 0.42] min) and 12 weeks of treatment ([2.12 ± 0.63], [1.90 ± 0.65] and [2.67 ± 0.82] min) as compared with the baseline ([0.63 ?0.14] , [0.60 ?0.14] and [0.62 ?0.11] min) (P < 0.05), even longer in group C than in A and B (P < 0.05). The CIPE-5 scores were markedly improved in groups A, B and C after 4 weeks ([15.17 ± 1.74], [14.57 ± 1.94] and [15.60 ± 1.63] min), 8 weeks ([17.13 ± 1.63], [16.37 ± 1.97] and [18.00 ± 1.05] min) and 12 weeks of intervention ([18.93 ± 1.57], [18.53 ± 1.67] and [20.00 ± 1.46] min ) as compared with the baseline ([12.57 ± 2.05], [13.20 ± 2.51] and [13.07 ± 2.01] min) (P < 0.05), even higher in group C than in A and B (P < 0.05).</p><p><b>CONCLUSION</b>Sertraline hydrochloride combined with four-spot caressing, with its definite efficacy and rare adverse reactions, deserves wide clinical application in the treatment of primary PE.</p>

Distribution, combination, and evolution of syndromic etiologies of erectile dysfunction / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore the distribution, combination and evolution of various syndromic etiologies of erectile dysfunction (ED) based on the syndrome etiology theory.</p><p><b>METHODS</b>Using the ED Syndromic Etiology Scale, we collected the clinical data on the Chinese medicine diagnoses of 297 cases of ED, extracted the core syndromic etiologies by analysis of principal components and factors, and analyzed the patterns of distribution, combination, and evolution of ED syndromic etiologies according to the general information of the patients.</p><p><b>RESULTS</b>Through analysis of principal components and factors, 9 core syndromic etiologies were extracted, i. e. , liver constraint with qi stagnation, kidney yin deficiency, damp-heat, liver constraint transforming into liver-fire, blood stasis, kidney yang deficiency, heart-spleen paired deficiency, qi-yin paired deficiency, and phlegm-damp. Each of these syndrome etiologies exhibited its own specific distribution patterns. Of the total number of cases studied, 51.52% had 2 or 3 core syndromic etiologies and 36.03% had only one.</p><p><b>CONCLUSION</b>In the early stage of ED, its syndromic etiologies are usually liver constraint with qi stagnation, kidney yin deficiency, damp-heat, liver constraint transforming into liver-fire, and blood stasis. With the natural progres- sion of the disease, its syndromic etiologies gradually evolve into kidney yang deficiency, heart-spleen paired deficiency, qi-yin paired deficiency, phlegm-damp, and blood stasis, and finally into yin-yang deficiency of the heart, spleen and kidneys, combined with phlegm-damp and blood stasis.</p>

Differentially expressed microRNAs at different stages of atherosclerosis in ApoE-deficient mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Atherosclerosis is the primary cause of cardiovascular disease, carotid artery disease, and peripheral vascular disease. However, it is hard to obtain human arterial tissue at different stages of atherosclerosis for a systematic study. The ApoE-deficient (ApoE(-/-)) mice predictably develop spontaneous atherosclerotic plaques with numerous features similar to the human lesions and contain nearly the entire spectrum of lesions observed during atherogenesis in humans. MicroRNA expression profiles at different stages of atherosclerosis in ApoE-deficient mice were screened to find out the differentially expressed microRNAs.</p><p><b>METHODS</b>ApoE-deficient mice were euthanized at 4, 8, and 20 weeks of age and divided into three groups according to the three time points, including groups A4 (fed a Western-type diet for 0 week), A8 (fed a Western-type diet for 4 weeks), and A20 (fed a Western-type diet for 16 weeks). Atherosclerotic lesions were analyzed. Fifteen aortas were collected and combined into three pools (five aortas in one pool) in each group. MicroRNA microarray analysis was replicated thrice in each group. The threshold of fold change ≥ 2.0 was used to screen up or down-regulated microRNAs. Differentially expressed microRNAs were subsequently verified with quantitative real-time polymerase chain reaction. Those increasingly up or down-regulated microRNAs during the progression of atherosclerosis were selected.</p><p><b>RESULTS</b>Atherosclerotic lesions first appeared in the aortic arch in group A8. Severe atherosclerotic lesions were observed in group A20. In group A8, seven MicroRNAs were up-regulated while two were down-regulated. In group A20, 15 microRNAs were up-regulated while two were down-regulated. miR-34a-5p and miR-497-5p were increasingly up-regulated, while miR-434-3p was progressively down-regulated when atherosclerosis progressed.</p><p><b>CONCLUSIONS</b>In this study, we described that microRNAs are differentially expressed at different stages of atherosclerosis in ApoE-deficient mice. Those increasingly up or down-regulated microRNAs during the progression of atherosclerosis may play an important role in the pathogenesis of atherosclerosis and provide us opportunities for investigating atherosclerosis from early to advanced stages.</p>

Serum sCD44v6 and sE-cadherin levels in patients with esophageal squamous cell carcinoma / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the serum levels of sCD44v6 and sE-cadherin (sE-cad) in patients with esophageal squamous cell carcinoma.</p><p><b>METHODS</b>The serum samples were collected from 65 cases of esophageal squamous cell carcinoma, 32 cases of erosive esophagitis and 35 healthy subjects. Serum sCD44v6 and sE-cad levels were measured by enzyme linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>The mean levels of serum sCD44v6 and sE-cad in esophageal squamous cell carcinoma patients were significantly higher than those of erosive esophagitis patients and normal controls (both P<0.05). There was no significant difference in serum sCD44v6 and sE-cad levels between erosive esophagitis patients normal controls (P=0.566 and P=0.708, respectively). Serum sCD44v6 and sE-cad levels of esophageal cancer patients were not correlated with their clinicopathological features. Serum sCD44v6 level is not correlated with sE-cad level in squamous cell carcinoma patients(P=0.651).</p><p><b>CONCLUSION</b>Serum sCD44v6 and sE-cad might be a potential marker for screening of esophageal squamous cell carcinoma.</p>

Assessment of the mechanical properties and biocompatibility of a new electrospun polyurethane vascular prosthesis / 南方医科大学学报

<p><b>OBJECTIVE</b>To develop a small-caliber vascular grafts and study its morphologies, mechanical properties and biocompatibility.</p><p><b>METHODS</b>The effects of electrospinning conditions on the microstructure and porosity of the resulting scaffolds were investigated for preparation of a small-caliber (4 mm) polyurethane vascular grafts with optimum microstructures and mechanical properties. The mechanical properties and biocompatibility of the prepared grafts were evaluated.</p><p><b>RESULTS</b>The polyurethane vascular grafts showed a three-dimensional reticular structure consisting of nanofibers, with an average porosity of (51.48∓4.47)% and tensile strength of 5.85 ∓ 0.62 MPa. The grafts provided a better long-term support than e-PTFE graft for endothelial cell growth and endothelialization.</p><p><b>CONCLUSION</b>The polyurethane vascular prosthesis possessed favorable microstructures, excellent mechanical properties and good biocompatibility for potential clinical application.</p>

Effects of aging on time course of neovascularization-related gene expression following acute hindlimb ischemia in mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Molecular analysis of neovascularization related genes by time course in response to ischemia has not been described in the context of aging. We aimed to provide a progressively deeper understanding of how aging compromises neovascularization.</p><p><b>METHODS</b>Young (3-month) and old (18-month) C57Bl mice were subjected to left hindlimb ischemia. Necrosis score was evaluated in calf muscles. Calf muscles, peripheral blood, bone marrow were harvested at different time points. The expressions of matrix metalloproteiniase-9 (MMP9), endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), stromal derived growth factor-1 (SDF1), hypoxia inducible factor-1α (HIF1α), VEGF receptor-1 (Flt1), VEGF receptor-2 (Flk1), angiopoietin-1 (Ang1), CD133, CD26 were detected by RT-PCR or Western blotting. White blood cells were counted in the peripheral blood. Gene expression data were compared by two-way analysis of variance.</p><p><b>RESULTS</b>MMP9, HIF-1α and SDF-1 were more upregulated during acute ischemia in old vs. young mice, reflecting increased ischemia in aging mice. However VEGF and eNOS exhibited lower expression in old vs. young mice, despite greater ischemia intensity. Ang1 and Flk1 showed similar expression in old vs. young mice. MMP9 peaked earlier in peripheral blood in young vs. old mice. Concurrent decreasing CD26 and increasing CD133 expression in aging bone marrow suggest aging impairs progenitor cell mobilization,</p><p><b>CONCLUSIONS</b>Our results indicate that a complex array of defects occur with aging that interfere with optimal neovascularization. These include potential impaired mobilization of progenitor cells to ischemic tissue, decreased levels of eNOS and VEGF and delayed responses to ischemia.</p>