Hyperoxia exposure promotes endothelial-mesenchymal transition and inhibits regulatory T cell function in human pulmonary microvascular endothelial cells.

Objective: This study aims to investigate the effects of hyperoxia exposure on TGF-ß1-induced endothelial-mesenchymal transition (EndoMT) and regulatory T cell (Treg)-mediated immunomodulation in human pulmonary microvascular endothelial cells (HPMECs), which could provide a theoretical basis for further studies of the pathogenesis of bronchopulmonary dysplasia (BPD). Methods: A BPD cell model was established by exposing HPMECs to hyperoxia. Flow cytometry was used to isolate CD4 + CD3 + CD25 + CD127- Tregs from the peripheral blood samples of preterm infants. HPMECs were divided into four groups based on whether they were exposed to hyperoxia and/or co-cultured with Tregs. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to test the expression levels of TGF-ß1, α-SMA, Foxp3, IL-10, and reactive oxygen species (ROS). Results: The results showed that the expression levels of TGF-ß1 and α-SMA in HPMECs increased at 24 h, 48 h, and 72 h of hyperoxia exposure. In the co-culture group of HPMECs and Tregs, Foxp3 and IL-10 expressions decreased at 48 h and 72 h of hyperoxia exposure. ROS expression increased in the hyperoxia group of HPMECs at 24 h, 48 h, and 72 h of hyperoxia exposure, which were higher than those in the hyperoxia group of HPMECs and Tregs. Conclusion: These findings suggest that hyperoxia exposure promotes EndoMT in HMPECs and inhibits the immunosuppressive effect of Tregs. Despite this, Tregs still seem could protect HPMECs from oxidative stress injury.

EVs from cells at the early stages of chondrogenesis delivered by injectable SIS dECM promote cartilage regeneration.

Articular cartilage defect therapy is still dissatisfactory in clinic. Direct cell implantation faces challenges, such as tumorigenicity, immunogenicity, and uncontrollability. Extracellular vesicles (EVs) based cell-free therapy becomes a promising alternative approach for cartilage regeneration. Even though, EVs from different cells exhibit heterogeneous characteristics and effects. The aim of the study was to discover the functions of EVs from the cells during chondrogenesis timeline on cartilage regeneration. Here, bone marrow mesenchymal stem cells (BMSCs)-EVs, juvenile chondrocytes-EVs, and adult chondrocytes-EVs were used to represent the EVs at different differentiation stages, and fibroblast-EVs as surrounding signals were also joined to compare. Fibroblasts-EVs showed the worst effect on chondrogenesis. While juvenile chondrocyte-EVs and adult chondrocyte-EVs showed comparable effect on chondrogenic differentiation as BMSCs-EVs, BMSCs-EVs showed the best effect on cell proliferation and migration. Moreover, the amount of EVs secreted from BMSCs were much more than that from chondrocytes. An injectable decellularized extracellular matrix (dECM) hydrogel from small intestinal submucosa (SIS) was fabricated as the EVs delivery platform with natural matrix microenvironment. In a rat model, BMSCs-EVs loaded SIS hydrogel was injected into the articular cartilage defects and significantly enhanced cartilage regeneration in vivo. Furthermore, protein proteomics revealed BMSCs-EVs specifically upregulated multiple metabolic and biosynthetic processes, which might be the potential mechanism. Thus, injectable SIS hydrogel loaded with BMSCs-EVs might be a promising therapeutic way for articular cartilage defect.

Distinguished biomimetic dECM system facilitates early detection of metastatic breast cancer cells.

Breast cancer is the most prevalent malignant tumor affecting women's health. Bone is the most common distant metastatic organ, worsening the quality of life and increasing the mortality of patients. Early detection of breast cancer bone metastasis is urgent for halting disease progression and improving tumor prognosis. Recently, extracellular matrix (ECM) with biomimetic tissue niches opened a new avenue for tumor models in vitro. Here, we developed a biomimetic decellularized ECM (dECM) system to recapitulate bone niches at different situations, bone mimetic dECM from osteoblasts (BM-ECM) and bone tumor mimetic dECM from osteosarcoma cells (OS-ECM). The two kinds of dECMs exhibited distinct morphology, protein composition, and distribution. Interestingly, highly metastatic breast cancer cells tended to adhere and migrate on BM-ECM, while lowly metastatic breast cancer cells preferred the OS-ECM niche. Epithelial-to-mesenchymal transition was a potential mechanism to initiate the breast cancer cell migration on different biomimetic dECMs. Importantly, in the nude mice model, the dECM system captured metastatic breast cancer cells as early as 10 days after orthotopic transplantation in mammary gland pads, with higher signal on BM-ECM than that on OS-ECM. Collectively, the biomimetic dECM system might be a promising tumor model to distinguish the metastatic ability of breast cancer cells in vitro and to facilitate early detection of metastatic breast cancer cells in vivo, contributing to the diagnosis of breast cancer bone metastasis.

Erythromycin Attenuates Hyperoxia Induced Lung Injury by Enhancing GSH Expression and Inhibiting Expression of Inflammatory Cytokines.

Introduction: Oxidative stress and inflammation have proven to be key factors contributing to the occurrence of BPD. Erythromycin has been shown to be effective in treating the redox imbalance seen in many non-bacterial infectious chronic inflammatory diseases. Methods: Ninety-six premature rats were randomly divided into air + saline chloride group, air + erythromycin group, hyperoxia + saline chloride group and hyperoxia + erythromycin group. Lung tissue specimens were collected from 8 premature rats in each group on days 1, 7 and 14, respectively. Results: Pulmonary pathological changes in premature rats after hyperoxia exposure were similar to those of BPD. Hyperoxia exposure induced high expression of GSH, TNF-α, and IL-1ß. Erythromycin intervention caused a further increase in GSH expression and a decrease in TNF-α and IL-1ß expression. Conclusion: GSH, TNF-α and IL-1ß are all involved in the development of BPD. Erythromycin may alleviate BPD by enhancing the expression of GSH and inhibiting the release of inflammatory mediators.

ATBF1 is a potential diagnostic marker of histological grade and functions via WNT5A in breast cancer.

BACKGROUND: Histological grade has been demonstrated to be an important factor of breast cancer outcome and is associated with cell differentiation and is currently being evaluated via H&E-stained sections. Molecular biomarkers are essential to improve the accuracy of histological grading. ATBF1, a large transcription factor, has been considered a tumor suppressor gene with frequent mutations or deletions in multiple cancers. In breast cancer, ATBF1 was reported to function in cell differentiation and mammary development. However, its role in the clinic has rarely been reported. METHODS: Breast cancer tissues (BCTs) and adjacent noncancerous tissues (ANCTs) were collected to analyze the expression of ATBF1 at the mRNA and protein levels. Three anti-ATBF1 antibodies recognizing independent peptides of ATBF1 (N-terminal end, middle region and C-terminal end) were applied for IHC staining. Small interfering RNA (siRNA) was used to silence ATBF1 expression and to investigate the roles of ATBF1 in MCF7 cells. Microarrays were introduced to analyze the differentially expressed genes, enriched GO terms and KEGG terms regulated by ATBF1 and its potential downstream genes, which were further confirmed in vitro and in clinical samples. RESULTS: The expression of ATBF1 was reduced in BCTs at both the mRNA and protein levels compared with that in ANCTs. ATBF1 protein was predominantly localized in the nucleus of ANCTs but in the cytoplasm of BCTs. Both the mRNA and protein levels of ATBF1 were significantly correlated with histological grade. Consistently, knockdown of ATBF1 increased stemness marker expression and reduced differentiation markers in vitro. Further analysis identified WNT5A as an essential downstream gene of ATBF1 in breast cancer cells. Treatment of WNT5A disrupted cell proliferation induced by ATBF1 silencing. In BCTs, a significant correlation was observed between the expression of WNT5A and ATBF1. CONCLUSION: The results indicated that ATBF1 expression might be a useful diagnostic marker associated with histological grade and breast cancer malignancy. WNT5A and its signaling pathway are novel mechanisms by which ATBF1 contributes to breast cancer tumorigenesis.

Enhancement of Tendon Repair Using Tendon-Derived Stem Cells in Small Intestinal Submucosa via M2 Macrophage Polarization.

(1) Background: Reconstruction of Achilles tendon defects and prevention of postoperative tendon adhesions were two serious clinical problems. In the treatment of Achilles tendon defects, decellularized matrix materials and mesenchymal stem cells (MSCs) were thought to address both problems. (2) Methods: In vitro, cell adhesion, proliferation, and tenogenic differentiation of tendon-derived stem cells (TDSCs) on small intestinal submucosa (SIS) were evaluated. RAW264.7 was induced by culture medium of TDSCs and TDSCs-SIS scaffold groups. A rat Achilles tendon defect model was used to assess effects on tendon regeneration and antiadhesion in vivo. (3) Results: SIS scaffold facilitated cell adhesion and tenogenic differentiation of TDSCs, while SIS hydrogel coating promoted proliferation of TDSCs. The expression of TGF-ß and ARG-1 in the TDSCs-SIS scaffold group were higher than that in the TDSCs group on day 3 and 7. In vivo, the tendon regeneration and antiadhesion capacity of the implanted TDSCs-SIS scaffold was significantly enhanced. The expression of CD163 was significantly highest in the TDSCs-SIS scaffold group; meanwhile, the expression of CD68 decreased more significantly in the TDSCs-SIS scaffold group than the other two groups. (4) Conclusion: This study showed that biologically prepared SIS scaffolds synergistically promote tendon regeneration with TDSCs and achieve antiadhesion through M2 polarization of macrophages.

The molecular basis of brain injury in preterm infants with sepsis - associated encephalopathy.

Sepsis-associated encephalopathy (SAE) is characterized by brain dysfunction during sepsis, without central nervous system infection. Here, we explored the molecular basis of brain injury in preterm infants with SAE. From Jan 2016 to Dec 2019, a total of 20 preterm infants were hospitalized in the neonatal intensive care unit (NICU) of our hospital, including 10 preterm infants with SAE (SAE group) and 10 preterm infants without encephalopathy after sepsis (no SAE group). Among the 20 premature infants, there were 12 males and 8 females, with mean gestational age 31.0 ± 2.46 weeks, 7 cases with birth weight ≤ 1500 g and 13 cases with birth weight 1500-2500 g. Blood cultures were negative in 6 cases and positive in 14 cases, including 10 cases of Gram-negative and 4 cases of Gram-positive bacteria, respectively. Expression levels of messenger RNA (mRNA) and MicroRNA (miRNA) were analyzed in peripheral blood samples from both groups during sepsis. There were 1858 upregulated and 2226 downregulated mRNAs [fold-change (FC) > |2|, p < 0.05], and 322 upregulated and 160 downregulated miRNAs (FC > |2|, p < 0.05), respectively, in the SAE group compared with the no SAE group. Expression levels of miRNA-1197 [95% confidence intervals (CI), 0.042 to 0.166] were 6.03-fold higher in the SAE group than the no SAE group, while those of miRNA-485-5p (95% CI, 0.064 to 0.024) were lower (0.31-fold). Both high expression of miRNA-1197 and low expression of miRNA-485-5p may be associated with pathogenic alteration of the oxidative respiratory chain and energy metabolism in preterm infants with SAE.

Exosome-based delivery nanoplatforms: next-generation theranostic platforms for breast cancer.

Breast cancer is the most frequent type of malignancy, and the leading cause of cancer-related death in women across the globe. Exosomes are naturally derived 50-150 nm nanovesicles with a variety of bioactive molecules to regulate the complex intracellular pathways involved in all stages of breast cancer development. Exosomes are also considered as a potential new generation of natural nanocarriers due to their intriguing endogenous functionalities. Recently, the development of exosome-based delivery nanoplatforms that combine the inherent unique advantages of exosomes with advanced nanotechnology has emerged as a promising area. In the present review, we first declare the fundamental principles of the relationship between exosomes and breast cancer, ranging from the initiation and progression of breast cancer, to drug resistance. More efforts are made to present a comprehensive overview of the recent advances of exosome nanotechnology for breast cancer therapy, including natural exosomes from different cell types, engineered exosomes with cargo loading and membrane modification, and artificial bionic exosomes with more stable and scalable properties. Based on the recent advanced nanotechnologies, exosome-based delivery nanoplatforms have been considered as the next-generation theranostic platforms, which sheds the light on the achievement of the clinical translation of exosomes for breast cancer therapy.

MIR210HG is aberrantly expressed in the seminal plasma of varicocele patients and associated with varicocele-related dyszoospermia.

This study aimed to confirm the expression of the seminal plasma long noncoding RNAs (lncRNAs) microRNA210 host gene (MIR210HG) in varicocele (VC) patients, to further explore the association between MIR210HG and VC severity and to evaluate whether MIR210HG can predict VC-related dyszoospermia. Semen samples from 188 VC patients and 92 healthy men were collected. Quantitative reverse transcriptase PCR detected seminal plasma MIR210HG levels. Receiver operating characteristic analysis assessed the ability of MIR210HG to screen patients with VC, or to screen VC patients with abnormal semen quality. Logistic analysis assessed the value of MIR210HG in predicting dyszoospermia in VC patients. The levels of MIR210HG in seminal plasma of VC patients were upregulated, which could screen VC patients. In addition, the levels of seminal plasma MIR210HG were upregulated with VC severity and were downregulated at 6 months after surgery in VC patients. Moreover, elevated MIR210HG levels in VC patients with abnormal semen quality could screen patients with abnormal semen quality and could independently predict the occurrence of dyszoospermia in VC patients. Seminal plasma MIR210HG expression is upregulated in VC patients, is associated with the severity of VC and may function as an independent predictor of VC-related dyszoospermia.

BMSCs and Osteoblast-Engineered ECM Synergetically Promotes Osteogenesis and Angiogenesis in an Ectopic Bone Formation Model.

Bone mesenchymal stem cells (BMSCs) have been extensively used in bone tissue engineering because of their potential to differentiate into multiple cells, secrete paracrine factors, and attenuate immune responses. Biomaterials are essential for the residence and activities of BMSCs after implantation in vivo. Recently, extracellular matrix (ECM) modification with a favorable regenerative microenvironment has been demonstrated to be a promising approach for cellular activities and bone regeneration. The aim of the present study was to evaluate the effects of BMSCs combined with cell-engineered ECM scaffolds on osteogenesis and angiogenesis in vivo. The ECM scaffolds were generated by osteoblasts on the small intestinal submucosa (SIS) under treatment with calcium (Ca)-enriched medium and icariin (Ic) after decellularization. In a mouse ectopic bone formation model, the SIS scaffolds were demonstrated to reduce the immune response, and lower the levels of immune cells compared with those in the sham group. Ca/Ic-ECM modification inhibited the degradation of the SIS scaffolds in vivo. The generated Ca/Ic-SIS scaffolds ectopically promoted osteogenesis according to the results of micro-CT and histological staining. Moreover, BMSCs on Ca/Ic-SIS further increased the bone volume percentage (BV/TV) and bone density. Moreover, angiogenesis was also enhanced by the Ca/Ic-SIS scaffolds, resulting in the highest levels of neovascularization according to the data ofCD31 staining. In conclusion, osteoblast-engineered ECM under directional induction is a promising strategy to modify biomaterials for osteogenesis and angiogenesis. BMSCs synergetically improve the properties of ECM constructs, which may contribute to the repair of large bone defects.

Risk factors and clinical characteristics for bronchopulmonary dysplasia associated pulmonary hypertension in very-low-birth-weight infants.

BACKGROUND: Pulmonary hypertension (PH) is a common complication of bronchopulmonary dysplasia (BPD) in very-low-birth-weight infants (VLBWIs). Although recent studies have increased awareness that PH contributes significantly to the high morbidity and mortality of BPD, the risk factors and clinical characteristics for PH in VLBWIs are little known. OBJECTIVES: To investigate the risk factors and clinical characteristics for BPD-associated pulmonary hypertension (BPD-PH) in VLBWIs. METHODS: A retrospective case-control observational study of VLBWIs with BPD admitted to a neonatal intensive care unit (NICU) over 4 years. According to echocardiograms confirming elevated pulmonary artery pressure after 28 days after birth, we divided BPD infants into PH group (n = 18) and non-PH group (n = 65). We compared pre- and postnatal characteristics between VLBWIs with or without PH. Multivariable logistic regression analysis was conducted with backward selection. RESULTS: A total of 83 infants with BPD were divided into PH group (n = 18) or non-PH group (n = 65). The average birth weight of the infants with BPD was 1078.1 g. Compared with those infants of the non-PH group, the birth weight of BPD-PH infants was significantly lower (968.1 ± 187.7 vs. 1108.5 ± 185.8, P = 0.006). Infants in the PH group had a higher incidence of patent ductus arteriosus (PDA) and underwent longer durations of oxygen therapy and mechanical ventilation compared to those in the non-PH group. In all subjects, birth weight (OR 0.995; 95% CI 0.991-0.999; P = 0.025) and PDA (OR 13.355; 95% CI 2.950-60.469; P = 0.001) were found to be specific risk factors for BPD-PH in this cohort. CONCLUSIONS: The study shows PDA and birth weight are specific risk factors for BPD-PH in VLBWIs.

Efficiency Evaluation of Neuroprotection for Therapeutic Hypothermia to Neonatal Hypoxic-Ischemic Encephalopathy.

Background: To evaluate the safety and neurological outcomes of therapeutic hypothermia to neonatal hypoxic-ischemic encephalopathy (HIE). Materials and Methods: Medical records of 61 neonates with moderate to severe HIE were retrospectively enrolled and divided into a therapeutic hypothermia group (n = 36) and conventional therapy group (n = 25). Results: No significant difference in the incidence of severe adverse events was found between the two groups. Minimum and maximum voltages of amplitude-integrated electroencephalography (aEEG) recording results showed statistically significant differences in therapeutic hypothermia group after 72 h. The neonatal behavioral neurological assessment (NBNA) on the 28th day after birth and Bayley Scales of Infant Development, second edition (BSID II) scores at 18 months old were significant higher in the therapeutic hypothermia group than the conventional therapy group. Conclusion: Therapeutic hypothermia for neonates with moderate to severe HIE improved the development of the nervous system in 0-18-month-old infants and showed a predominant role in reducing death and major neuron development-associated disabilities.

A Case of Sepsis Due to Carbapenem-Resistant Klebsiella pneumoniae in an Extremely Low-Birth Weight Infant Treated with Trimethoprim-Sulfamethoxazole.

In recent years, there have been an increasing number of infections due to multidrug-resistant organisms in the neonatal intensive care unit. Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a challenge in clinical anti-infection treatment. Herein, we report the case of CRKP sepsis in an extremely low-birth weight infant (ELBWI) who did not respond to meropenem and vancomycin, but was treated successfully after a 10-day antibiotic course with trimethoprim-sulfamethoxazole (TMP-SMZ). Recent research on CRKP-associated sepsis and the application of TMP-SMZ therapy in children and neonates were reviewed to offer a reference for clinical practice.

Nrf2­Keap1­ARE­NQO1 signaling attenuates hyperoxia­induced lung cell injury by inhibiting apoptosis.

Bronchopulmonary dysplasia (BPD) is one of the main causes of chronic lung disease in premature infants. Acute lung injury following exposure to hyperoxia contributes to the development of BPD in preterm infants. The nuclear factor­erythroid 2­related factor 2 (Nrf2) signaling pathway is an endogenous antioxidant defense mechanism that is involved in the pathogenesis of numerous hyperoxia­induced diseases. In the present study, the expression of Nrf2, Kelch­like ECH­associated protein 1 (Keap1) and NAD(P)H quinone oxidoreductase 1 enzyme (NQO1) was detected in A549 cells exposed to hyperoxia and transfection with small interfering RNA (siRNA) using reverse transcription­quantitative polymerase chain reaction and western blotting, and cellular apoptosis was detected using flow cytometry. The results demonstrated that apoptosis increased significantly following exposure of the cells to hyperoxia, and Nrf2, Keap1 and NQO1 expression levels were significantly upregulated under hyperoxic conditions. Furthermore, following transfection with Nrf2 siRNA, the expression levels of these genes were significantly downregulated and apoptosis was significantly increased compared with the respective values in untransfected cells. These findings suggest that the Nrf2­Keap1­antioxidant response element­NQO1 signaling pathway may play a protective role in hyperoxia­induced lung injury via the inhibition of apoptosis.

An Innovative Model of Bronchopulmonary Dysplasia in Premature Infants.

Bronchopulmonary dysplasia (BPD) is one of the common chronic lung diseases (CLD) of premature infants, which causes unpredictable consequences to the family and society. Therefore, the pathogenesis and prevention methods of BPD are the focus of current research, and the establishment of an effective and appropriate animal model of BPD in premature infants is the key to the research. In this study, premature rats were exposed to hyperoxia environment. Compared with the air group, the body weight and alveolar radiation count of the hyperoxia group decreased significantly, but there was no significant difference in body length. HE staining was used to observe the pathological changes of BPD in the lung tissue. The above results proved that under the hyperoxia condition, the BPD animal model of premature infants was successfully established, which provided a new choice for the future research of BPD.

[Effect of hyperoxic exposure on the expression of heme oxygenase-1 and glutamate-L-cysteine ligase catalytic subunit in lung tissue of preterm rats].

OBJECTIVE: To study the effect of hyperoxic exposure on the dynamic expression of heme oxygenase-1 (HO-1) and glutamate-L-cysteine ligase catalytic subunit (GCLC) in the lung tissue of preterm neonatal rats. METHODS: Cesarean section was performed for rats on day 21 of gestation to obtain 80 preterm rats, which were randomly divided into air group and hyperoxia group after one day of feeding. The rats in the air group were housed in room air under atmospheric pressure, and those in the hyperoxia group were placed in an atmospheric oxygen tank (oxygen concentration 85%-95%) in the same room. Eight rats each were selected from each group on days 1, 4, 7, 10, and 14, and lung tissue samples were collected. Hematoxylin and eosin staining was used to observe the pathological changes of lung tissue at different time points after air or hyperoxic exposure. Western blot and RT-qPCR were used to measure the protein and mRNA expression of HO-1 and GCLC in the lung tissue of preterm rats at different time points after air or hyperoxic exposure. RESULTS: Compared with the air group, the hyperoxia group had a significant reduction in the body weight (P<0.05). Compared with the air group, the hyperoxia group had structural disorder, widening of alveolar septa, a reduction in the number of alveoli, and simplification of the alveoli on the pathological section of lung tissue. Compared with the air group, the hyperoxia group had significantly lower relative mRNA expression of HO-1 in the lung tissue on day 7 and significantly higher expression on days 10 and 14 (P<0.05). Compared with the air group, the hyperoxia group had significantly lower mRNA expression of GCLC in the lung tissue on days 1, 4, and 7 and significantly higher expression on day 10 (P<0.05). Compared with the air group, the hyperoxia group had significantly higher protein expression of HO-1 in the lung tissue on all days, and the protein expression of GCLC had same results as HO-1, except on day 1 (P<0.05). CONCLUSIONS: Hyperoxia exposure may lead to growth retardation and lung developmental retardation in preterm rats. Changes in the protein and mRNA expression of HO-1 and GCLC in the lung tissue of preterm rats may be associated with the pathogenesis of hyperoxia-induced lung injury in preterm rats.

Downregulation of fatty acid synthase complex suppresses cell migration by targeting phosphor-AKT in bladder cancer.

The aim of the present study was to investigate the effect of fatty acid synthase complex (FASN) on the migration capacity of bladder transitional cell carcinoma (BTCC) cells and the involvement of matrix metalloproteinase­9 (MMP­9) via targeting of phospho­AKT (p­AKT). FASN­specific small­interfering RNA (FASN­siRNA) was used to inhibit FASN gene expression in the 5637 and 253J BTCC cell lines. The knockdown efficiency of FAM­conjugated FASN­siRNA was confirmed by fluorescence microscopy. The migratory abilities of BTCC cells were assessed using a Transwell assay. Furthermore, protein and mRNA expression of FASN, p­AKT, AKT, and migration­associated protein MMP­9 were detected by western blot analysis. Treatment with FASN inhibitor Cer and FASN­siRNA decreased the migratory capacity of bladder cancer cells and reduced the levels of p­AKT as well as the expression of MMP­9. These results indicated that FASN inhibition suppressed the migratory capacity of BTCC cells through suppressing AKT activation and consequently reducing MMP­9 expression. Targeting FASN may represent a promising novel therapeutic strategy for BTCC.

[Expression of nNOS and ultrastructural changes in the penile tissue of rats with prolactinoma-induced erectile dysfunction].

OBJECTIVE: To study the expression of nNOS and ultrastructural changes in the penile tissue of rats with prolactinoma-induced erectile dysfunction (ED). METHODS: We established the model of prolactinoma in 20 male Westar rats by peritoneal injection of diethylstilbestrol (DES) and treated the control rats with normal saline (n = 10) or sterilized arachis oil (n = 10). After 8 weeks, we performed the apomorphine test and measured the weight of the pituitary gland and the levels of serum prolactin (PRL) and testosterone (T) to confirm the successful construction of the prolactinoma-induced ED model. Then we determined the expression of nNOS in the penile tissue by immunohistochemistry and examined the ultrastructural changes of the penile cavernosum under the transmission electron microscope. RESULTS: The prolactinoma-induced ED model was successfully established in 15 rats. The weight of the pituitary gland was significantly increased in the rats treated with DES as compared with the normal saline and sterilized arachis oil controls ([46.7 ± 15.5] vs [11.7 ± 2.4] and [12.4 ± 2.3] mg, both P < 0.05). The level of serum PRL was markedly higher while that of T remarkably lower in the former than in the latter two groups ([1,744.9 ± 304.5] vs [11.5 ± 2.4] and [10.6 ± 1.9] ng/ml, both P < 0.0l; [1.54 ± 0.46] vs [3.11 ± 1.08] and [3.04 ± 1.11] ng/ml, both P < 0.05). The rate of penile erection was significantly reduced in the prolactinoma-induced ED model rats in comparison with the normal saline and arachis oil controls (16.7% vs 100% and 87.5%, both P < 0.05), and so was the expression of nNOS in the penile tissue (0.024 ± 0.011 vs 0.066 ± 0.019 and 0.058 ± 0.021, both P < 0.05). Transmission electron microscopy manifested significant ultrastructural changes in the endothelial and smooth muscle cells of the cavernous tissue in the prolactinoma-induced ED models. CONCLUSION: The ultrastructural changes of the penile cavernous tissue and the reduced expression of nNOS in penile tissue may be the most important mechanisms of prolactinoma-induced ED in rats.

[Risk factors of prostate cancer in urban Qingdao: a case-control study].

OBJECTIVE: To investigate the risk factors of prostate cancer in urban Qingdao and provide some theoretical evidence for the scientific prevention and treatment of the disease. METHODS: We performed a hospital-based matched case-control study in Qingdao Municipal Hospital. The cases and controls were matched in age, gender, nationality and the place of residence. All the subjects were interviewed face to face in the hospital using a questionnaire, and the data analyzed by the conditional logistic regression method. RESULTS: According to the 258 valid questionnaires collected, the prostate cancer risk was significantly higher in the cases with a family history of cancer than in those without (OR = 2.58), and so was it in the men with the first spermatorrhea at the age of < or = 15 years than in those at the age of > or = 18 years (OR = 2.27). A decreased risk of prostate cancer was found among the men with the first experience of sexual intercourse between 25 to 30 years of age (OR = 0.76). An increased risk was shown in those with sexual intercourses > or = 4 times per week before 35 years old (OR = 2.57), masturbations > or = 3 times per week (OR = 2.30) and a drinking history (alcohol > or = 150 g/d) of > or = 10 years (OR = 2.83). CONCLUSION: Positive family history of cancer, earlier age of the first spermatorrhea, sexual intercourses > or = 4 times per week before 35 years old, frequent masturbations, and heavy drinking for more than 10 years are risk factors for prostate cancer.