Microsatellite instability as a marker of prognosis: a systematic review and meta-analysis of endometrioid endometrial cancer survival data.

INTRODUCTION: To investigate whether microsatellite instability (MSI) is an important prognostic biomarker for endometrioid endometrial cancer (EEC). METHODS: The PubMed, EMBASE, and the Cochrane Cooperative Library databases were searched from inception to July 2021. Overall survival, disease-free survival, progression-free survival, EEC-specific survival, recurrence-free survival, and the recurrence rate were pooled to analyze the correlation between MSI and EEC. In addition, Egger's regression analysis and Begg's test were used to detect publication bias. RESULTS: 17 studies met the inclusion criteria and were included in our meta-analysis with a sample size of 4723, and the included patients with endometrioid cancer (EC) all were EEC. The pooled hazard ratios (HR) in patients with EEC showed that MSI was significantly associated with shorter overall survival [HR = 1.37, 95% confidence interval (CI) (1.00-1.86), p = 0.048, I2 = 60.6%], shorter disease-free survival [HR = 1.99, 95% CI (1.31-3.01), p = 0.000, I2 = 67.2%], shorter EEC-specific survival [HR = 2.07, 95% CI (1.35-3.18), p = 0.001, I2 = 31.6%] and a higher recurrence rate [Odds ratios (OR) = 2.72, 95% CI (1.56-4.76), p = 0.000, I2 = 0.0%]. In the early-stage EEC subgroup, MSI was significantly associated with shorter overall survival [HR = 1.47, 95% CI (1.11-1.95), p = 0.07], shorter disease-free survival [HR = 4.17, 95% CI (2.37-7.41), p = 0.000], and shorter progression-free survival [HR = 2.41, 95% CI (1.05-5.54), p = 0.039]. No significant heterogeneity was observed in overall survival (I2 = 20.9%), disease-free survival (I2 = 0.0%), or progression-free survival (I2 = 0.0%) in patients with early-stage EEC. Meanwhile, publication bias was not observed, and the p-value for Egger's test of overall survival, disease-free survival, and EEC-specific survival were p = 0.131, p = 0.068, and p = 0.987, respectively. CONCLUSION: MSI is likely an important biomarker for poor prognosis in patients with EEC, and this correlation is even more certain in patients with early-stage EEC.

Ghrelin improves cognition via activation of the cAMP- CREB signalling pathway in depressed male C57BL/6J mice.

BACKGROUND: Depression leads to a cognitive decline and decreases in ghrelin are observed in depression. Ghrelin affects the level of Brain-derived nerve growth factor (BDNF) through the cAMP-CREB signalling pathway, and lower BDNF levels lead to cognitive decline. Therefore, it is reasonable to assume that in depression, lower ghrelin causes a decrease in BDNF levels and cognitive decline though the cAMP- CREB signalling pathway. METHODS: A total of 120 C57BL/6J male mice were randomly divided into six groups of 20 mice: non-depression groups (sham group, ghrelin group, and ghrelin + (D-lys3)-GHRP-6 group) and depression groups (depression group, depression + ghrelin group and depression + ghrelin + (D-lys3)-GHRP group). A depression mouse model was established by injecting normal saline, ghrelin or ghrelin + (D-lys3) -GHRP-6 into the lateral ventricle of each group. Cognition, hippocampal long-term potentiation (LTP), ghrelin mRNA and protein level, BDNF level and CREB level in the hippocampus were detected. RESULTS: In the depression mouse model groups, all comparison indexes (cognition and hippocampal levels of LTP, ghrelin mRNA and proteins, and BDNF and CREB) had significant negative changes. In the mice with depression, ghrelin or ghrelin + (D-lys3)-GHRP-6 was injected, and all the comparison indicators showed significant positive changes. Supplementation of ghrelin+(D-lys3))-GHRP-6 resulted in more significant positive changes in all comparison indexes than those of ghrelin alone. CONCLUSIONS: In the depression model, lower ghrelin causes hippocampal BDNF to decrease and results in cognitive decline via the cAMP-CREB signalling pathway.

A rat study model of depression-driven chronic prostatitis by modulating the PI3K/Akt/mTOR network.

Depression and chronic prostatitis (CP) are two common diseases that affect the human population worldwide. Clinically, it has been demonstrated that andrological patients often simultaneously suffer from depression and CP. Prior investigations have established that depression acts as an independent risk factor for CP. Herein, we explored the correlation between depression and CP using bioinformatics tools and through animal experiments. The potential targets and signalling pathways involved in depression and CP were predicted using bioinformatics tool, while depression in the rat model was established through chronic restraint stress. The expression of the related proteins and mRNA was assessed by Western blotting and real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Relative to those in the control rats, the protein contents of PI3K, p-Akt, and p-mTOR were lower in the model rats (p < 0.05). Similarly, the transcript levels of PI3K, Akt, and mTOR was also relatively lower in the model rats (p < 0.05). And PI3K/Akt agonists reduced inflammation in rat prostate tissue, accompanied by significant increases in the transcript and protein expression levels of PI3K, Akt, and mTOR. Thus, we proposed that depression model rats may induce CP as a result of mediation by the negative regulation of the PI3K/Akt/mTOR signalling network.

Explore the effects of pulmonary fibrosis on sperm quality and the role of the PI3K/Akt pathway based on rat model.

Researches were reported that respiratory diseases can lead to male infertility; however, it is unclear whether there is a relationship between pulmonary fibrosis (PF) and male infertility. This study examined the influence of PF on sperm quality and its mechanisms. The key signalling pathway of male infertility caused by PF was predicted based on bioinformatics research. After modelling, we evaluated semen quality. Real-time quantitative polymerase chain reaction and Western blotting were used to measure the protein and mRNA expression levels of phosphatidylinositol 3-kinase (PI3K), phosphorylation-protein kinase B (p-Akt) and B-cell lymphoma 2 (Bcl2) in rat testicular cells. Compared with group A (48.77 ± 4.67; 59.77 ± 4.79), the sperm concentration and total sperm viability of group B (8.44 ± 1.71; 15.39 ± 3.48) showed a downward trend (p < 0.05). Western blotting showed that the protein expressions of PI3K, p-Akt and Bcl2 in the testes of group B (0.30 ± 0.06; 0.27 ± 0.05; 0.15 ± 0.03) was significantly lower than those of group A (0.71 ± 0.07; 0.72 ± 0.06; 0.50 ± 0.06) (p < 0.05). The hypoxic environment induced by PF can inhibit the expression of PI3K, p-Akt and Bcl2 protein and eventually cause dysfunctional spermatogenesis.

Effect of leech-centipede medicine on improving erectile function in diabetes-induced erectile dysfunction rats via PDE5 signalling pathway-related molecules.

CONTEXT: The leech and centipede granules have good curative effects on many diabetic vascular diseases, including diabetes-induced erectile dysfunction (DIED). OBJECTIVE: To explore the effect of leech and centipede on erectile function in rats with diabetes-induced erectile dysfunction and its possible mechanism. MATERIALS AND METHODS: Thirty male Sprague-Dawley DIED rats were randomly divided into the model group (Group M), low-dose group (Group DD), high-dose group (Group DG) and tadalafil group (Group T) (n = 6); diabetic rats were induced by streptozotocin. Apomorphine was used to induce diabetic erectile dysfunction. The 'leech-centipede' granules (0.15 and 0.6 g/kg) were intragastrically administered in the DD and DG groups for 8 weeks. Blood glucose, serum insulin, testosterone, cGMP levels and protein expression changes were measured in each group. RESULTS: After 8 weeks, the erectile function of rats in the DG group significantly improved (1.26 ± 0.73). Penis tissue cGMP levels were higher in the DG group (1.48 ± 0.11) than in the M group (0.58 ± 0.15). Protein and mRNA expression levels of NOS were significantly higher (0.77 ± 0.05; 0.61 ± 0.02) but those of PDE5 (0.43 ± 0.05; 0.61 ± 0.03) were lower in the DG group than in the M group (0.37 ± 0.06; 0.51 ± 0.01; 0.78 ± 0.06; 0.81 ± 0.04). CONCLUSION: The leech-centipede can improve erectile dysfunction in DIED rats by regulating the expression of cGMP, NOS, and PDE5-related molecules in the PDE5 pathway. This study provides a potential mechanism for the treatment of DIED with leech-centipede.

Potential mechanism of Achyranthis bidentatae radix plus semen vaccariae granules in the treatment of diabetes mellitus-induced erectile dysfunction in rats utilizing combined experimental model and network pharmacology.

CONTEXT: Achyranthes bidentata Blume (Amaranthaceae) (ABR) and semen vaccariae (SV) are used commonly in the clinical treatment of erectile dysfunction in males with diabetes mellitus (DMED) to strengthen the kidney and promote blood circulation, and often achieve good curative effects. OBJECTIVE: Explore mechanistic details of ABR + SV treatment against DMED. MATERIALS AND METHODS: Prediction of key targets by network pharmacology. A rat model of DM was established by streptozotocin injection (55 mg/kg). Apomorphine (100 µg/kg) was injected into rats to screen the DMED model. Group C (n = 6) and group M (n = 6) were gavaged with deionized water; group T (n = 6) was given Achyranthis bidentatae radix-semen vaccariae granule suspension (2.5 g/kg). It lasted 8 weeks. Real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB) were used to measure the expression of tissue-related proteins and mRNA. RESULTS: The predicted key targets are albumin (ALB), caspase-3 (CASP3), vascular endothelial growth factor A (VEGFA), angiotensin-converting enzyme (ACE), and endothelial nitric oxide synthase (eNOS). Compared with the M group (0.52 ± 0.04; 0.50 ± 0.03; 0.49 ± 0.02; 0.23 ± 0.03), CASP3, VEGFA, and ACE protein expression reduced in the T group (0.39 ± 0.06; 0.34 ± 0.03; 0.39 ± 0.03), and eNOS protein expression increased (0.34 ± 0.03). CONCLUSION: ABR + SV can improve erectile function in DMED rats. This study provides a potential mechanism for the treatment of DMED with ABR + SV and can benefit from more patients.

[Asthma affects erectile function in rats: An experimental study].

Objective: To investigate the impact of asthma on erectile function in rats and the expressions of related proteins. METHODS: Male rats were injected intraperitoneally with ovalbumin solution to induce asthma followed by subcutaneous injection of apomorphine at 100 µg/kg into the neck, and then observed for reduced frequency or loss of penile erection. Based on the results of observation, a model of asthma-induced ED (AED) was made in 6 of the animals, and another 6 normal male rats were taken as controls. The histomorphology of the corpus cavernosum was observed by HE staining, and the mRNA and protein expressions of phosphodiesterase 5 (PDE5) and nitric oxide synthase 3 (eNOS) in the testis tissue were determined by RT-qPCR and Western blot. RESULTS: Compared with the normal controls, the rats in the AED model group showed disorderly distribution of sinusoids and decreased density of endothelial and smooth muscle cells in the corpus cavernosum. The mRNA and protein expressions of PDE5 were significantly higher (P < 0.05), while those of eNOS remarkably lower in the AED model than in the control group (P < 0.05). CONCLUSIONS: Asthma can induce ED and change the histomorphology of the corpus cavernosum in rats by affecting the expressions of PDE5 and eNOS proteins.

Research of stroke combined hyperlipidemia-induced erectile dysfunction in rat model.

Objective: The study was aimed to evaluate the influences of erectile dysfunction (ED) in a rat model of stroke combined with hyperlipidemia (HLP). Methods: Male Sprague-Dawley rats were divided into control and hyperlipidemia (HLP) groups. HLP model was constructed by feeding with high-fat and cholesterol diets. Serum levels of total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride (TG), and non-HDL were identified to check the model was success. Stroke model was established by FeCl3. ICP/MAP value was detected to evaluate the erectile function of rats. Serum level of lipoproteins and the expressions of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) were detected by ELISA. Hematoxylin-eosin (HE) staining of corpus cavernosum and measurement of penis length were utilized to assessment erectile function. Western blot was used. Results: TC, TG, LDL, and non-HDL-C in serum were up-regulated, while HDL level was attenuated. After treatment, the serum lipid level recovered. From the ICP/MAP values, the erectile function of both two treatment groups recovered. The expression of PDE5A was up-regulated, while the levels of eNOS and cGMP were suppressed after surgery. The length of penis was decreased, and corpus cavernosum was damaged following HLP and stroke. However, the erectile function was recovered after treatment. Conclusion: Stroke combined HLP caused ED through NO-cGMP-PDE5 pathway.

[Erectile dysfunction and psychological status in infertile males].

OBJECTIVE: To investigate the relationship of erectile dysfunction (ED) with psychological factors in male patients with infertility. METHODS: We conducted a questionnaire investigation among 252 male patients with infertility, which involved the general condition, results of semen routine examination, sexual life, and scores in IIEF-5, self-reported 9-item patient health questionnaire (PHQ-9) and 7-item generalized anxiety disorder scale (GAD-7). We analyzed the prevalence of ED, depression, and anxiety and their correlations among the patients in comparison with 100 fertile male controls. RESULTS: In 245 of the infertility patients, the most common symptoms of depression and anxiety were "feeling tired or no vitality" and "easily getting worried or impatient", 20.4% of them with depression disorder and 42.9% with anxiety disorder. The PHQ-9 and GAD-7 scores were significantly higher in the infertile males than in the normal fertile controls (P <0.05), and so was the incidence of ED (28.6% vs 12.4%, P <0.05), while the IIEF-5 scores were markedly lower in the former than in the latter group (P <0.01), and so were sex frequency and sexual satisfaction (P <0.05). The PHQ-9 and GAD-7 scores were remarkably higher in the infertility patients with ED than in those without (P <0.01). Logistic regression analysis showed that the level of libido and results of semen routine examination were the risk factors for depression disorder, while age, education level, disease course and experience of assisted reproduction were those for anxiety disorder. CONCLUSIONS: Male infertility patients have a poorer mental health and a higher incidence of ED than normal fertile men, and there is some interaction between psychological status and ED prevalence.

Generation, identification, formation mechanism and application of plant haploids.

Haploids are individuals with gametophytic chromosome numbers. Homozygous doubled haploids can be quickly gained by genome doubling. Haploids and doubled haploids play an important role on crop breeding, mutant screening, gene functional analysis, cytological studies, construction of genetic population and so on, and have been a research hotspot of plants in recent years. In this review, we summarize the production means, identification, the genetic mechanism and the applications of haploids and doubled haploids. We hope to provide a reference for study and application of haploids and doubled haploids.

Clinical benefit analysis of PD-1 inhibitors in patients with advanced, recurrent or metastatic cervical cancer: a meta-analysis and systematic review.

Purpose: This study aims to comprehensively evaluate the efficacy and safety of programmed cell death protein-1 (PD-1) in patients with advanced, recurrent, or metastatic cervical cancer (ARMCC) and identify the population that may benefit the most. Methods: We conducted a search of PubMed, EMBASE, and the Cochrane Collaboration Library from their inception to September 2023. We extracted and analyzed the results related to the efficacy and safety of PD-1 in patients with ARMCC. The primary endpoints included the overall objective response rate (ORR) and adverse events (AEs), while the secondary endpoints encompassed the 1-year overall survival (OS) rate, 1-year progression-free survival (PFS) rate, as well as OS and PFS. We used a random effects model to conduct a meta-analysis on single-group rates, and the Mantel-Haenszel method was utilized to compare the ORR and the incidence of AEs. Results: Our study included a total of 21 trials involving 2,097 patients. The ORR of the combination of PD-1 inhibitors with chemotherapy was 56.36%, the combination of PD-1 inhibitors with anti-angiogenic agents was 38.72%, the combination of PD-1 inhibitors with Cytotoxic T-lymphocyte antigen 4 inhibitors was 25.60%, and PD-1 inhibitor monotherapy was 15.99%. The subgroup analysis showed that the group of patients with squamous cell carcinoma (SCC) exhibited a significantly higher ORR compared to the non-SCC group in patients who received PD-1 inhibitors combined with other anti-tumor drugs (Odds Ratio =2.43, P=0.002). Additionally, the group of patients with a programmed death-ligand 1 combined positive score (PD-L1 CPS) ≥1 exhibited a significantly higher ORR compared to the PD-L1 CPS <1 group in patients who received PD-1 inhibitor monotherapy (OR=4.14, P=0.02). PD-1 inhibitor monotherapy or PD-1 inhibitors combined with chemotherapy did not significantly increase the incidence of all grades of adverse events (Relative Risk=0.99, p=0.788) or the incidence of serious adverse events (RR=0.99, p=0.788) compared to chemotherapy alone. Conclusion: PD-1 inhibitors demonstrate outstanding efficacy in the treatment of patients with ARMCC. Patients with SCC may benefit more from treatments including PD-1 inhibitors in combination with other anti-tumor drugs, and PD-L1 CPS ≥1 can be considered a favorable indicator of immune therapy response. Importantly, the use of PD-1 inhibitor monotherapy or PD-1 inhibitors in combination with chemotherapy did not lead to an increased incidence of AEs compared with chemotherapy alone, indicting safety during treatment. Systematic Review Registration: PROSPERO (CRD42023457945).

[Research progress of mechanisms through which dipeptidyl peptidase-4 inhibitors regulate glycemia].

Dipeptidyl peptidase-4 (DPP-4) inhibitors are promising new antidiabetic drugs. It had been proposed that DPP-4 inhibitors exert their antidiabetic effect by inhibiting the degradation of glucagon-like peptide 1(GLP-1) . However, new evidence has shown that the increase of GLP-1 is not notable after the use of these drugs in patients with type 2 diabetes. Therefore, the specific mechanisms via which DPP-4 inhibitors in controlling blood glucose has became questionable. In recent years, studies have revealed many possible mechanisms through which DPP-4 inhibitors regulate glycemia: DPP-4 inhibitors may selectively reduce DPP-4 activity in the intestine, causing the increase of portal plasma GLP-1 level and thus promoting the release of insulin via nerve reflex;also, they may decrease the cleavage product of GLP-1 and reduce the degradation of other bioactive peptides.

Genetically predicted hypertension, antihypertensive drugs, and risk of erectile dysfunction: a Mendelian randomization study.

Background: The causal relationship between hypertension, antihypertensive drugs and the risk of erectile dysfunction is still uncertain. We performed a univariable and multivariable Mendelian randomization study to investigate whether they are causally related to erectile dysfunction. Methods: Genetic variants associated with blood pressure were derived from the genome-wide association study meta-analysis of the UK Biobank and International Consortium of Blood Pressure (N = 757,601). Summary association data for hypertension were obtained from the UK Biobank (N = 463,010) and the FinnGen study (N = 356,077). The summary statistics of erectile dysfunction were obtained from the European ancestry with 223,805 subjects. The SNP instruments used to assess the effect of the protein targets of antihypertensive drugs on erectile dysfunction were obtained from previous studys. Causal effects were estimated using the univariate Mendelian randomization method (inverse variance weighted, MR-Egger, weighted median, MR-PRESSO and Wald ratios) and the multivariate Mendelian randomization method. Sensitivity analyses were implemented with the Cochran's Q-test, MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis. Results: Univariate MR found that elevated diastolic blood pressure may increase the occurrence of erectile dysfunction (odds ratio [OR] = 1.012; 95% confidence interval [CI]: 1.000-1.024; P = 0.047). Genetically predicted hypertension is also associated with ED (For the FinnGen, OR = 1.106; 95% CI: 1.027-1.191; P = 0.008. For the UK Biobank, OR = 3.832; 95% CI: 1.410-10.414; P = 0.008). However, after adjusting for systolic blood pressure, diastolic blood pressure and hypertension using multivariate Mendelian randomization, only hypertension was causally associated with ED occurrence (For the FinnGen, OR = 1.103; 95% CI: 1.018-1.195; P = 0.017. For the UK Biobank, OR = 5.037; 95% CI: 1.601-15.846; P = 0.006). We found no evidence that the use of angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and thiazide diuretic increased the risk of erectile dysfunction. Conclusions: Genetically predicted hypertension increases the risk of erectile dysfunction, but we found no causal relationship between elevated systolic/diastolic blood pressure and erectile dysfunction. We speculate that the relationship between elevated blood pressure and erectile dysfunction risk may be nonlinear. We found little evidence that antihypertensive drugs increase the risk of erectile dysfunction.

[Application of intraoperative contrast-enhanced ultrasound in different pathological grades of glioma].

OBJECTIVE: To explore the feasibility and value of intra-operative contrast-enhanced ultrasound in different pathological grades of glioma. METHODS: A total of 46 patients with glioma were selected to undergo the contrast-enhanced ultrasound. They were divided into 3 groups according to their pathological grades. RESULTS: All 46 tumors were hyperechoic after examinations and the borders became much more distinct. Different level of tumors had their representative ultrasonic findings. CONCLUSIONS: Intraoperative contrast-enhanced ultrasound is quite useful for determining the position and border of tumors. And it is also excellent in detecting the residual tumor tissues post-operatively. And it can improve the resection accuracy and operative precision, especially for Grade IV glioma with internal necrosis, cyst and surrounding brain edema.

Gastric cancer incidence, mortality and burden in adolescents and young adults: a time-trend analysis and comparison among China, South Korea, Japan and the USA.

OBJECTIVES: To evaluate and compare the burden of gastric cancer in adolescents and young adults (GCAYA) among China, South Korea, Japan and the USA, four countries with similar or different rates of gastric cancer (GC) incidence, development levels and cancer control strategies. DESIGN: This population-based observational study collected the epidemiological data of GCAYA from the Global Burden of Diseases Study 2019. The trend magnitude and directions over time for incidence and mortality of GCAYA were analysed and compared among four countries. MAIN OUTCOMES AND MEASURES: Outcomes included new cases, deaths, mortality-to-incidence ratios (MIRs), disability-adjusted life years, and their age-standardised rates and estimated annual percentage changes (AAPCs). RESULTS: There were 49 008 new cases and 27 895 deaths from GCAYA in 2019, nearly half of which occurred in China. The AAPCs for the age-standardised incidence and mortality rate were 0.3 (-0.1 to 0.7), -3.6 (-3.7 to -3.4), -3.2 (-3.8 to -2.6), -0.1 (-0.6 to 0.5) and -2.0 (-2.3 to -1.6), -5.6 (-6.2 to -5.0), -4.4 (-4.7 to -4.1), -0.7 (-1.0 to -0.3) in China, South Korea, Japan and the USA, respectively. The incidence rate for females in the USA rose by 0.4% annually. GC ranks fifth, first, fourth and ninth in China, South Korea, Japan and the USA regarding burdens caused by cancer in adolescents and young adults. The MIRs declined constantly in South Korea and China, and the MIR in the USA became the highest in 2019. CONCLUSIONS: Although not covered by prevention and screening programmes, variations in disease burden and time trends may reflect variations in risk factors, cancer control strategies and treatment accessibility of GC among the four countries. Investigating the reasons behind the varying disease burden and changing trends of GCAYA across countries will inform recommendations for prevention measures and timely diagnosis specific to this underserved population to further decrease the GC burden.

Mechanistic analysis of erectile dysfunction in a depression rat model.

OBJECTIVE: Most men suffering from depression have different degrees of erectile dysfunction (ED), but the relationship between depression and ED is not clear. This study explored the effect of depression on erectile function in rats and the underlying mechanism. METHODS: The potential targets and key signaling pathways of depression and ED were predicted through bioinformatics analysis, and a depression rat model was established by inducing chronic restraint stress. Pathological changes in rat penis tissue were studied by hematoxylin and eosin staining. The serum dopamine level was quantified by an enzyme-linked immunosorbent assay. The expression of related proteins and mRNA was detected by western blotting and real-time quantitative reverse transcription-polymerase chain reaction. RESULTS: Hematoxylin and eosin staining showed pathological damage in the penile tissue of the model group rats. The serum dopamine level, dopamine receptor D2 (DRD2) and solute carrier family 6 member 3 (SLC6A3) protein levels in penile tissue, and DRD2 and SLC6A3 mRNA levels were lower in the model group than in the control group. CONCLUSION: The decrease in erectile function in the depression rat model was related to dysfunction of the dopamine system and dopaminergic synapse signaling pathway.

Mechanism by which Huoxue Tongluo Qiwei Decoction improves the erectile function of rats with diabetic erectile dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Huoxue Tongluo Qiwei Decoction is a classical herbal formula, which can improve the symptoms of erectile dysfunction (ED) patients and has a good therapeutic effect on patients with diabetic erectile dysfunction (DIED). The main function of Huoxue Tongluo Qiwei Decoction is to stimulate the blood circulation and dredge collaterals, remove blood stasis, and calm wind. RATIONALE: To further explore the mechanism of Huoxue Tongluo Qiwei Decoction in the treatment of DIED, related animal experiments were designed. MATERIALS AND METHODS: The chemical constituents of Huoxue Tongluo Qiwei Decoction were identified with the help of high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). A rat model was induced by streptozotocin (STZ) and screened by apomorphine (APO). Serum sE-selectin, lysyl oxidase-1 (LOX-1), malondialdehyde (MDA) and other markers of vascular endothelial injury and related indicators of oxidative stress were studied through enzyme-linked immunosorbent assay (ELISA). The endothelial cells and ultrastructure of the corpus cavernosum were examined by electron microscopy and HE staining. The expression of protein and mRNA was detected by western blotting (WB) and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The results of the study revealed that the sE-selectin, LOX-1, intercellular adhesion molecule-1 (sICAM-1), endothelial microparticles (EMPs), P-selectin (CD62P), and MDA levels in the serum of group M rats were considerably higher than rats of group K, while the superoxide dismutase (SOD) level showed a significant decrease. In addition, the PKC pathway was activated, and the expression of related proteins and mRNA was increased. After 8 weeks of intervention with Huoxue Tongluo Qiwei Decoction and LY333531, serum level of sE-selectin, LOX-1, sICAM-1, EMPs, CD62P and MDA in L, D and G groups were remarkably lower than group M while SOD level increased significantly, protein kinase C (PKC) pathway was inhibited with the improved erectile function of rats. CONCLUSION: Huoxue Tongluo Qiwei Decoction can inhibit the expression of protein and mRNA of the PKCß signaling pathway related molecules in DIED rats to cure the injury of vascular endothelial, enhance antioxidant capacity, and prevent the activation of platelet, thus improving erectile function in rats with DIED.

MicroRNA differential expression spectrum and microRNA-125a-5p inhibition of laryngeal cancer cell proliferation.

[This retracts the article DOI: 10.3892/etm.2017.4685.].

Mechanism of Huoxue Tongluo Decoction in treatment of erectile dysfunction caused by ischemic stroke based on network pharmacology.

Objective: To study the therapeutic effect of Huoxue Tongluo Decoction (HXTLD) on erectile dysfunction caused by ischemic stroke and identify the mechanisms involved. Methods: Network pharmacology was used to predict the key active ingredients and targets of HXTLD. Surgical methods were used to create a rat model of ischemic stroke. The rats were then given a suspension of HXTLD by ig administration. Erectile function was evaluated by Apomorphine (APO) induction. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (Real-time PCR) and Western blotting were used to detect the expression of related mRNAs and proteins in rat penile corpus cavernous tissue and brain tissue. Hematoxylin & Eosin (HE) staining was used to investigate structural changes in the penile cavernous tissue. Results: Network pharmacology showed that tumor necrosis factor (TNF), nitric oxide synthase 3 (eNOS), and vascular endothelial growth factor (VEGF) were the key targets of HXTLD in the treatment of erectile dysfunction caused by ischemic stroke. Experimental studies showed that HXTLD improved erectile dysfunction caused by ischemic stroke. HE results showed that HXTLD improved the structure of the corpus cavernosa. HXTLD also inhibited the expression of TNF and VEGF proteins in penile tissue (P < 0.05) and enhanced the expression of eNOS protein in penile tissue (P < 0.05). Conclusion: HXTLD improved the erectile function of rats with erectile dysfunction caused by ischemic stroke by regulating the mRNA and protein levels of TNF, eNOS and VEGF.

A Bioinformatic Investigation of the Mechanism Underlying Migraine-Induced Erectile Dysfunction.

BACKGROUND: Over recent years, an increasing body of literature has focused on the relationship between erectile dysfunction (ED) and migraine. However, the specific mechanism is unclear. MATERIALS AND METHODS: We used a bioinformatic database to predict the targets and pathways associated with migraine and ED. Twenty male SD rats were randomly divided into a blank group (Group A, n = 10) and a migraine model group (Group B, n = 10). The rats in Group A were subcutaneously injected with normal saline (2 ml/kg) into the back of the neck. Rats in Group B were subcutaneously injected with nitroglycerin 10 mg/kg (5 mg/ml) into the back of the neck in order to create an animal model of migraine. Next, we carried out the measurement of erectile function. We used hematoxylin and eosin (HE) to compare the tissue structure of the cavernous body of the penis. Western blotting was used to determine the expression levels of PI3K, p-AKT, and p-mTOR in the protein; Reverse Transcription-Polymerase Chain Reaction (RT-qPCR) was used to determine the expression levels of PI3K, AKT, and mTOR in the messenger ribonucleic acid (mRNA). RESULTS: There are 117 intersection targets of migraine and ED, involving 188 cell biological processes (BP), 21 cellular components (CC), 31 molecular functions (MF), and 65 signaling pathways. HE staining results show that there were no significant differences between Group A and Group B with regard to any of the parameters. Compared with Group A, the levels of the PI3K, p-AKT, and p-mTOR proteins and PI3K, AKT, and mTOR mRNAs in Group B decreased (P < 0.01). CONCLUSIONS: The decline of erectile function in a rat model of migraine was associated with the PI3K/Akt/mTOR signaling pathway.