Objective To study the correlation between semen quality and bacterial infection in men with abnormal fer-tility,and provide clinical basis for guiding the reproductive health of men with abnormal fertility.Methods 200 male semen samples with abnormal fertility were collected,and then separated and cultured for 48 hours.According to the culture results,they were divided into three groups:the non-pathogenic group,the pathogenic group,and the sterile group.The bacterial resist-ance analysis of the pathogenic group was conducted,and the semen quality between each group was compared.Results After 48 hours of isolation and cultivation,200 semen samples had been tested,non-pathogenic bacteria was detected in 163 semen samples,accounting for 81.5% ;pathogenic bacteria was detected in 33 semen samples,accounting for 16.5% ;and bacteria was not detected in 4 semen samples,accounting for 2.0% .The top three strains of pathogenic bacteria in 33 cases were Escherichia coli,Streptococcus agalactiae,and Enterococcus faecalis,with drug resistance rates of 80.0% ,87.5% ,and 100.0% ,respec-tively.Conclusion The detection rate of bacterial culture in semen of men with abnormal fertility is relatively high,and patho-genic bacteria can affect semen quality.

ObjectiveTo investigate the effect of Shouwuwan on the synaptic plasticity of hippocampal neurons in the rat model of D-galactose-induced aging via the mammalian target of rapamycin （mTOR） signaling pathway. MethodA total of 50 male SPF-grade SD rats were randomized into normal group， model group， vitamin E （0.018 g·kg^-1） group， and low- and high-dose （1.08，2.16 g·kg^-1， respectively） Shouwuwan groups. Except the normal group， the other four groups were treated with D-galactose （120 mg·kg^-1） for the modeling of aging. The rats were simultaneously administrated with corresponding agents by gavage. After six weeks of modeling， Morris water maze test was carried out to examine the behavioral changes. The whole brain and hippocampus samples were collected. The expression of postsynaptic density protein-95 （PSD-95） and synaptophysin （SYN） in the hippocampus was detected by immunohistochemistry. Golgi staining was employed to observe the changes in the morphology and function of neurons. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were respectively employed to determine the mRNA and protein levels of mTOR， phosphorylated （p）-mTOR， p70 ribosome protein S6 kinase （p70S6K）， phosphorylated （p）-p70S6K， eukaryotic translation initiation factor 4E-binding protein 2 （4EBP2）， and phosphorylated （p）-4EBP2 in the hippocampus. ResultCompared with the normal group， the model group showed slow swimming （P<0.01）， extended total swimming distance （P<0.05）， prolonged latency （P<0.01）， and decreased crossing number （P<0.01）. The modeling inhibited the expression of PSD-95 and SYN in the CA1 region of the hippocampus （P<0.01）， with the weakest staining effect and the smallest region， decreased the intersections of hippocampal neuron dendrites with concentric circles at the concentric distance of 100， 140， 180， and 200 μm from the cell body （P<0.01）， and reduced the length and density of dendritic spine （P<0.01）. In addition， the modeling up-regulated the mRNA levels of mTOR and p70S6K and the protein levels of p-mTOR and p-p70S6K （P<0.01） and down-regulated the mRNA level of 4EBP2 and the protein levels of 4EBP2 and p-4EBP2 （P<0.01）. Compared with the model group， low- and high-dose Shouwuwan increased the average swimming speed （P<0.01）， shortened the latency （P<0.01）， increased the crossing number （P<0.01）， promoted the expression of PSD-95 and SYN in the hippocampal CA1 region （P<0.01）， increased the intersections between hippocampal neuronal dendrites and concentric circles at the concentric distance of 100， 140， 180，200 μm from the cell body （P<0.01）， and increased the number， length， and density of dendritic spine （P<0.01）. Furthermore， Shouwuwan down-regulated the protein levels of p-mTOR and p-p70S6K （P<0.01）， up-regulated the protein levels of 4EBP2 and p-4EBP2 （P<0.05，P<0.01）， down-regulated the mRNA levels of mTOR and p70S6K （P<0.01）， and up-regulated the mRNA level of 4EBP2 （P<0.01）. ConclusionShouwuwan can improve the learning and memory ability of rats exposed to D-galactose， promote the expression of proteins associated with synaptic plasticity， improve the morphology of neurons， repair neural function， reduce neuronal apoptosis， and inhibit mTOR signaling pathway to delay brain aging.

ObjectiveTo investigate the effect of Shouwuwan on apoptosis of hippocampal neurons in D-galactose-induced aging rats through phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） pathway. MethodFifty male SD rats of SPF grade were randomly divided into normal group， model group， vitamin E group， and Shouwuwan medium- and high-dose groups. Except the normal group， the other four groups were given D-galactose （120 mg·kg^-1） to prepare aging model. Additionally， Shouwuwan was used to intervene in the Shouwuwan medium- and high-dose groups （1.08 and 2.16 g·kg^-1， respectively）， and vitamin E group （0.018 g·kg^-1） was given vitamin E by gavage. After 6 weeks of modeling， the whole brain and hippocampal tissue were taken and the morphological changes of hippocampal neurons were observed by Nissl staining. The apoptosis of hippocampal cells was detected by in situ end labeling ［TdT-mediated dUTP nick-end labeling （TUNEL）］. The protein expression levels of PI3K， phosphorylated （p）-PI3K， Akt， p-Akt， Caspase-3， forkhead box protein O3a （FoxO3a）， p-FoxO3a， B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax） were detected by Western blot. Real-time fluorescence quantitative PCR （Real-time PCR） was performed to determine the mRNA expression level of FoxO3a in hippocampus. ResultCompared with the conditions in the normal group， the apoptotic cells of hippocampal neurons in the model group were significantly increased， and the apoptosis index was elevated （P<0.01）. Nissl staining of the hippocampal CA1 region showed that hippocampal neurons were lost and sparse， and the number of Nissl bodies was reduced， with pyknosis and deep staining. The relative protein expression of p-PI3K， p-Akt， Caspase-3 and Bax， p-PI3K/PI3K ratio and p-Akt/Akt ratio were all increased （P<0.01）， while the relative protein expression of FoxO3a， p-FoxO3a and Bcl-2， and p-FoxO3a/FoxO3a ratio were decreased （P<0.01）. The mRNA expression of FoxO3a was lowered （P<0.01）. Compared with the conditions in the model group， after treatment with Shouwuwan， the apoptotic cells were markedly reduced， and the apoptosis index of each treatment group was decreased （P<0.01）. Nissl staining of the hippocampal CA1 region demonstrated that the loss of neurons in each treatment group was improved， and Nissl bodies were increased and densely arranged. There was no statistically significant difference in the relative protein expression of PI3K and Akt in each group. In Shouwuwan medium- and high-dose groups， the relative protein expression of p-PI3K， p-Akt， Caspase-3 and Bax， p-PI3K/PI3K ratio and p-Akt/Akt ratio were decreased， while the relative protein expression of FoxO3a andp-FoxO3a， and Bcl-2， and p-FoxO3a/FoxO3a ratio were increased （P<0.01）. The mRNA expression of FoxO3a was up-regulated （P<0.01）. ConclusionShouwuwan could improve the structure of hippocampal neurons， inhibit PI3K/Akt signal pathway， down-regulate Caspase-3 and Bax， activate FoxO3a， and up-regulate Bcl-2 and Bcl-2/Bax ratio， to reduce neuronal apoptosis.

Background and Objectives: Although human-induced pluripotent stem cells (hiPSC) can be efficiently differentiated into cardiomyocytes (CMs), the heterogeneity of the hiPSC-CMs hampers their applications in research and regenerative medicine. Retinoic acid (RA)-mediated signaling pathway has been proved indispensable in cardiac development and differentiation of hiPSC toward atrial CMs. This study was aimed to test whether RA signaling pathway can be manipulated to direct the differentiation into sinoatrial node (SAN) CMs. Methods: and Results: Using the well-characterized GiWi protocol that cardiomyocytes are generated from hiPSC via temporal modulation of Wnt signaling pathway by small molecules, RA signaling pathway was manipulated during the differentiation of hiPSC-CMs on day 5 post-differentiation, a crucial time point equivalent to the transition from cardiac mesoderm to cardiac progenitor cells in cardiac development. The resultant CMs were characterized at mRNA, protein and electrophysiology levels by a combination of qPCR, immunofluorescence, flow cytometry, and whole-cell patch clamp. The results showed that activation of the RA signaling pathway biased the differentiation of atrial CMs, whereas inhibition of the signaling pathway biased the differentiation of sinoatrial node-like cells (SANLCs). Conclusions Our study not only provides a novel and simple strategy to enrich SANLCs but also improves our under-standing of the importance of RA signaling in the differentiation of hiPSC-CMs.

Objective: Empirical findings confirmed that autistic and schizotypal traits are associated with attentional function as well as include various dimensions. So far, no study has reported which dimension of these traits relates to attentional networks. This study aimed to find out whether there are associations between attentional networks and autistic traits; and between attentional networks and schizotypal traits. Methods: A total of 449 volunteers was included in this study, and autism-spectrum quotient (AQ), schizotypal personality questionnaire (SPQ), and attention network test (ANT) were used to measure autistic traits and schizotypal traits. The three independent attentional networks, including alerting network, orienting network, and executive control network, were also measured. Results: Autistic traits were associated with the orienting network, whereas schizotypal traits were associated with the orienting network and executive control network. Furthermore, attentional networks could be predicted by specific dimensions of autistic and schizotypal traits. AQ-attention switching [0.104 (-1.175– -0.025), p=0.041] and AQ-attention to detail [-0.097 (-0.798– -0.001), p=0.049] were significant predictors of orienting network and gender were significant predictor of executive network (Beta=0.107; 95% CI=-0.476–10.139; p=0.031). Whereas, schizotypal dimension “interpersonal” was a significant predictor of all three attentional networks [Alerting: 0.147 (-0.010–0.861), p=0.045; Orienting: 0.147 (0.018–0.733), p=0.040; Executive: 0.198 (0.215–1.309), p=0.006]. Conclusion This study demonstrated that autistic and schizotypal traits were associated with attentional networks. The specific dimensions of autistic and schizotypal traits could predict attentional networks. Nevertheless, the attentional networks predicted with these two traits were different.

Background and Objectives: Manipulating different signaling pathways via small molecules could efficiently inducecardiomyocytes from human induced pluripotent stem cells (hiPSC). However, the effect of transcription factors on the hiPSC-directed cardiomyocytes differentiation remains unclear. Transcription factor, p53 has been demonstrated indispensable for the early embryonic development and mesendodermal differentiation of embryonic stem cells (ESC).We tested the hypothesis that p53 promotes cardiomyocytes differentiation from human hiPSC. Methods: and Results: Using the well-characterized GiWi protocol that cardiomyocytes are generated from hiPSC via temporal modulation of Wnt signaling pathway by small molecules, we demonstrated that forced expression of p53 in hiPSC remarkably improved the differentiation efficiency of cardiomyocytes from hiPSC, whereas knockdown endogenous p53 decreased the yield of cardiomyocytes. This p53-mediated increased cardiomyocyte differentiation was mediated through WNT3, as evidenced by that overexpression of p53 upregulated the expression of WNT3, and knockdown of p53 decreased the WNT3 expression. Mechanistic analysis showed that the increased cardiomyocyte differentiation partially depended on the amplified mesendodermal specification resulted from p53-mediated activation of WNT3-mediated Wnt signaling. Consistently, endogenous WNT3 knockdown significantly ameliorated mesendodermal specification and subsequent cardiomyocyte differentiation. Conclusions These results provide a novel insight into the potential effect of p53 on the development and differentiation of cardiomyocyte during embryogenesis.

Objective:To explore the effect of flipped classroom combined with scenario simulation in the teaching reform on four basic medical puncture techniques of clinical skills training.Methods:A total of 1 275 students majoring in five-year clinical medicine in Guangzhou Medical University were enrolled in the study. The control group (647 cases from Batch 2015) were given the traditional teaching pattern and the experimental group (628 cases from Batch 2016) adopted flipped classroom combined with scenario simulation. At the end of the course, the performance in the tests of four basic medical puncture techniques in the objective structured clinical examination (OSCE) of the two groups were compared. The feedback and evaluation of this teaching mode in the experimental group were investigated by questionnaires. SPSS 19.0 was used for independent samples t test. Results:All the scores of the tests of four basic medical puncture techniques in the experimental group were significantly higher than those in the control group: abdominocentesis [(87.89±7.13) vs. (82.60±10.74) points], thoracocentesis [(85.20±7.39) vs. (81.96±7.76) points], bone marrow aspiration [(88.13±6.00) vs. (83.50±9.63) points], and lumbar puncture [(91.91±7.19) vs. (80.74±12.20) points], with significant differences ( P<0.001). The results about the feedback and evaluation in the experimental group showed that the students gave an average score of 8.4 points to their satisfaction with the new teaching mode. The approval rates of the teaching effect evaluation items such as teaching arrangement, improving learning ability, improving clinical practice ability and school promotion were higher than 90.0%. Conclusion:Flipped classroom combined with scenario simulation, which is worthy to be popularized, can not only improve the students' performance in the tests of four basic medical puncture techniques in the OCSE, but also improve teaching satisfaction and teaching effect.

Objective: Empirical findings confirmed that autistic and schizotypal traits are associated with attentional function as well as include various dimensions. So far, no study has reported which dimension of these traits relates to attentional networks. This study aimed to find out whether there are associations between attentional networks and autistic traits; and between attentional networks and schizotypal traits. Methods: A total of 449 volunteers was included in this study, and autism-spectrum quotient (AQ), schizotypal personality questionnaire (SPQ), and attention network test (ANT) were used to measure autistic traits and schizotypal traits. The three independent attentional networks, including alerting network, orienting network, and executive control network, were also measured. Results: Autistic traits were associated with the orienting network, whereas schizotypal traits were associated with the orienting network and executive control network. Furthermore, attentional networks could be predicted by specific dimensions of autistic and schizotypal traits. AQ-attention switching [0.104 (-1.175– -0.025), p=0.041] and AQ-attention to detail [-0.097 (-0.798– -0.001), p=0.049] were significant predictors of orienting network and gender were significant predictor of executive network (Beta=0.107; 95% CI=-0.476–10.139; p=0.031). Whereas, schizotypal dimension “interpersonal” was a significant predictor of all three attentional networks [Alerting: 0.147 (-0.010–0.861), p=0.045; Orienting: 0.147 (0.018–0.733), p=0.040; Executive: 0.198 (0.215–1.309), p=0.006]. Conclusion This study demonstrated that autistic and schizotypal traits were associated with attentional networks. The specific dimensions of autistic and schizotypal traits could predict attentional networks. Nevertheless, the attentional networks predicted with these two traits were different.

Objective: To investigate the clinical features, treatment and prognosis of the children with malignancy-associated hemophagocytic syndrome (MAHS) in Beijing in recent decade. Methods: The clinical data of the patients with MAHS under 18 years old from July 2007 to February 2018 collected by the Society of Beijing hemophagocytic syndrome were analyzed retrospectively. Results: There were 46 patients under 18 years old with MAHS in all(male 27, female 19). The patients with MAHS took up 8.9% of the patients with hemophagocytic lymphohistiocytosis (HLH)(46/519 cases) from the area during that period.The median age of onset had 13.5 years (0.9-18.0 years). Thirty-five patients had lymphoma (76.0%), 9 cases had leukemia (19.6%), 1 case had myelodysplastic syndrome with refractory anemia with excess blast(RAEB-T), and 1 case had Epstein-Barr virus(EBV) associated lymphoproliferative disease (borderline tumor stage). All the patients had a fever.A half of them suffered from hepatosplenomegaly and 7 patients(15.2%) had neurological symptoms.The common laboratory abnormalities included cytopenias, hemophagocytosis in bone marrow (81.8%, 36/44 cases), elevated serum ferritin (87.8%, 36/41 cases), and elevated sCD₂₅ (100.0%, 15/15 cases), decreased nature killer(NK) activity (61.1%, 11/18 cases), and plasma EBV-DNA positive (57.9%). Four patients did not receive treatment, the rest were treated by several chemotherapy protocols including the HLH-94/2004 protocol.Five patients (10.8%) received the allogeneic hematopoietic stem cell transplantation, and 1 case received the splenectomy therapy.The mortality was 58.7%.Four heterozygous mutations of SH2D1A, UNC13D and PRF1 genes were found in 2 patients. Conclusions MAHS in children progresses rapidly, with poor prognosis, and it is often complicated with EBV infection.The children with MAHS may develop genetic defects similar to primary hemophagocytic syndrome.Nowadays, there is no standard treatment for MAHS, so the individualized treatment is to be explored.

Objective?To explore the effects of ideation and imitation behavior training on rehabilitation in patients with chronic schizophrenia. Methods?Totally 200 schizophrenia patients admitted and treated in 2016 from Fuzhou Neuro-Psychiatric Hospital were selected and equally randomized to treatment group (n=100) and control group (n=100) according to the random number table. Patients in the control group received conventional nursing, while patients in the treatment group received ideation and imitation behavior training for 8 weeks on this basis. Wisconsin Card Sorting Test (WCST), Nurses' Observation Scale for Inpatient Evaluation (NOISE) and Personal and Social Performance Scale (PSP) were used to compare the rehabilitation effects between the two groups. Results?After intervention for 8 weeks, the score for correct response in WCSI in patients in the treatment group was (24.78±7.39), higher than that of patients in the control group, and the score for continuous mistakes in WCSI in patients in the treatment group was (14.78±5.27), lower than that of patients in the control group (t=3.800, 3.640;P＜0.01). After intervention for 8 weeks, the scores for NOISE (200.06±26.09) and PSP (79.83±4.21) in patients in the treatment group were higher than those of patients in the control group (t=6.880, 19.040;P＜0.01). Conclusions?Ideation and imitation behavior training helps to improve the patients' cognitive performance, including attention, memory, linguistic competence and reasoning ability, as well as self-care ability of daily living and social function, and promotes chronic schizophrenia patients' rehabilitation.