ABSTRACT
OBJECTIVE: To explore the mechanism of Lingze Tablets (LZT) acting on BPH in rats based on the VEGFA/TNF/IL-6 signaling pathway. METHODS: We equally randomized 30 SPF SD male rats into five groups, normal control, BPH model control, low-dose LZT, medium-dose LZT and high-dose LZT, and established a BPH model in the latter four groups by induction with non-castrate testosterone propionate. After the modeling, we treated the rats in the normal and model groups by intragastrical administration of physiological saline, and those in the latter three groups with low-, medium-, and high-dose LZT respectively, all for 28 successive days. Then we collected the prostate tissue from the animals for observation of the changes in the prostatic indexes and histomorphology, detected the expressions of the proteins related to the VEGFA/TNF/IL-6 signaling pathway, and compared the data obtained among different groups. RESULTS: Compared with the normal controls, the rats in the model control group showed significant prostatic hyperplasia, markedly increased prostatic index (ï¼»0.84 ± 0.01ï¼½ g, P<0.05), thickness of the prostatic epithelia and infiltration of the luminal area, and dramatically up-regulated protein expressions of VEGFA (0.60 ± 0.02, P< 0.05), TNF (0.76 ± 0.02, P< 0.05) and IL-6 (0.64 ± 0.02, P< 0.05). In comparison with the model controls, the rats in the low-, medium- and high-dose LZT groups exhibited significantly decreased prostatic indexes (ï¼»0.76 ± 0.02ï¼½ g, ï¼»0.58 ± 0.02ï¼½ g and ï¼»0.52 0.01ï¼½ g, all P< 0.05), improved prostatic histomorphology, and down-regulated expressions of VEGFA (0.45 ± 0.01, 0.35 ± 0.01 and 0.31 ± 0.02, all P< 0.05), TNF (0.45 ± 0.01, 0.33 ± 0.01 and 0.27 ± 0.01, all P< 0.01) and IL-6 (0.44 ± 0.01, 0.36 ± 0.01 and 0.30 ± 0.01, all P< 0.01) in a dose-dependent manner. CONCLUSION: LZT produces therapeutic effect on BPH by negatively regulating the VEGFA/TNF/IL-6 signaling pathway, reducing the expression levels of VEGFA, TNF and IL-6 proteins, and regulating cell proliferation, apoptosis and inflammatory response.
Subject(s)
Drugs, Chinese Herbal , Interleukin-6 , Prostatic Hyperplasia , Rats, Sprague-Dawley , Signal Transduction , Tumor Necrosis Factor-alpha , Vascular Endothelial Growth Factor A , Male , Animals , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/metabolism , Rats , Vascular Endothelial Growth Factor A/metabolism , Interleukin-6/metabolism , Signal Transduction/drug effects , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Tumor Necrosis Factor-alpha/metabolism , Prostate/metabolism , Prostate/drug effects , Prostate/pathology , Tablets , Disease Models, AnimalABSTRACT
RATIONALE AND OBJECTIVES: To assess the efficacy of a preoperative contrast-enhanced CT (CECT)-based deep learning radiomics nomogram (DLRN) for predicting murine double minute 2 (MDM2) gene amplification as a means of distinguishing between retroperitoneal well-differentiated liposarcomas (WDLPS) and lipomas. METHODS: This retrospective multi-center study included 167 patients (training/external test cohort, 104/63) with MDM2-positive WDLPS or MDM2-negative lipomas. Clinical data and CECT features were independently measured and analyzed by two radiologists. A clinico-radiological model, radiomics signature (RS), deep learning and radiomics signature (DLRS), and a DLRN incorporating radiomics and deep learning features were developed to differentiate between WDLPS and lipoma. The model utility was evaluated based on the area under the receiver operating characteristic curve (AUC), accuracy, calibration curve, and decision curve analysis (DCA). RESULTS: The DLRN showed good performance for distinguishing retroperitoneal lipomas and WDLPS in the training (AUC, 0.981; accuracy, 0.933) and external validation group (AUC, 0.861; accuracy, 0.810). The DeLong test revealed the DLRN was noticeably better than clinico-radiological and RS models (training: 0.981 vs. 0.890 vs. 0.751; validation: 0.861 vs. 0.724 vs. 0.700; both P < 0.05); however, no discernible difference in performance was seen between the DLRN and DLRS (training: 0.981 vs. 0.969; validation: 0.861 vs. 0.837; both P > 0.05). The calibration curve analysis and DCA demonstrated that the nomogram exhibited good calibration and offered substantial clinical advantages. CONCLUSION: The DLRN exhibited strong predictive capability in predicting WDLPS and retroperitoneal lipomas preoperatively, making it a promising imaging biomarker that can facilitate personalized management and precision medicine.
ABSTRACT
Objective: To detect the continuous blood purification (CBP)'s application value in patients with urosepsis caused by ureteral calculi and heart failure after catheterization. Methods: This is a clinical comparative study. Sixty patients with ureteral calculi complicated with heart failure and urosepsis were admitted at Affiliated Hospital of Hebei University from January 2021 to March 2023 randomly split into control and experimental group(n=30). Based on conventional treatment after indwelling the DJ tube, the experimental group was treated with CBP therapy. The control group dealt with conventional anti-inflammatory, oxygen inhalation and other treatments only. Compared and analyzed in terms of alterations in blood inflammatory factors, cardiac function, BNP prior to and after therapy, blood pressure, blood WBC recovery time, and so on. Results: TNF-a, CRP, and PCT levels in the control and experimental groups were substantially more prominent than the average reference value prior to treatment. They decreased considerably at distinct time points after therapy, with substantial distinctions (p< 0.05). A more meaningful decrease was noticed in the experimental group in comparison with the control group (p< 0.05). BNP and cardiac function were improved in both groups prior to and after therapy, and the amelioration of indexes in the experimental group was more substantial than that in the control group after therapy, with statistically considerable distinctions. The improvement time in experimental group was earlier than in the control group, with statistically substantial differences. Conclusion: Patients with urosepsis complicated with heart failure after indwelling DJ tube have their inflammatory factors improved significantly, with more thorough excretion by using conventional treatment combined with CBP therapy.
ABSTRACT
BACKGROUND AND AIM: Diabetes and Urinary Tract Infections (UTIs) are both common and serious health problems. Shuangdong capsule, a Chinese patent medicine, has been used to treat these conditions. This study assesses its efficacy and mechanism in treating diabetes combined with UTIs. METHODS: We induced diabetes in rats using streptozotocin and UTIs with Escherichia coli, dividing the rats into five groups: control, model, levofloxacin, Shuangdong capsule, and levofloxacin + Shuangdong capsule. After two weeks, we measured blood glucose, insulin, infection indicators, and bladder histology. We also detected the expression of insulin receptor substrate 1 (IRS1)-phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt)-C-X-C motif chemokine ligand 2 (CXCL2) signaling pathway by Western Blot and the myeloperoxidase (MPO) levels by Enzyme-Linked Immunosorbent Assay (ELISA). Additionally, we conducted a Mendelian randomization study using genetic variants of the insulin receptor to assess its causal effect on UTI risk. RESULTS: Shuangdong capsule improved bladder pathology and infection indicators, similar to levofloxacin. It did not affect blood glucose or insulin levels. Moreover, it reversed the suppression of the IRS1-PI3K-Akt-CXCL2 pathway and MPO levels caused by UTI in diabetic rats. The Mendelian randomization study showed that increased insulin receptor expression reduced UTI risk, which was consistent with the results of the animal experiments. CONCLUSION: The Shuangdong capsule was effective in treating diabetes with UTIs. It may function by activating the IRS1-PI3K-Akt signaling pathway, thereby increasing CXCL2 and MPO levels, enhancing innate immunity, and promoting bacterial clearance. The Mendelian randomization study provided further evidence supporting the causal role of the insulin receptor in UTI prevention.
ABSTRACT
BACKGROUND: Saccharomyces cerevisiae is an important microorganism in ethanol synthesis, and with sugarcane molasses as the feedstock, ethanol is being synthesized sustainably to meet growing demands. However, high-concentration ethanol fermentation based on high-concentration sugarcane molasses-which is needed for reduced energy consumption of ethanol distillation at industrial scale-is yet to be achieved. RESULTS: In the present study, to identify the main limiting factors of this process, adaptive laboratory evolution and high-throughput screening (Py-Fe3+) based on ARTP (atmospheric and room-temperature plasma) mutagenesis were applied. We identified high osmotic pressure, high temperature, high alcohol levels, and high concentrations of K+, Ca2+, K+ and Ca2+ (K+&Ca2+), and sugarcane molasses as the main limiting factors. The robust S. cerevisiae strains of NGT-F1, NGW-F1, NGC-F1, NGK+, NGCa2+ NGK+&Ca2+-F1, and NGTM-F1 exhibited high tolerance to the respective limiting factor and exhibited increased yield. Subsequently, ethanol synthesis, cell morphology, comparative genomics, and gene ontology (GO) enrichment analysis were performed in a molasses broth containing 250 g/L total fermentable sugars (TFS). Additionally, S. cerevisiae NGTM-F1 was used with 250 g/L (TFS) sugarcane molasses to synthesize ethanol in a 5-L fermenter, giving a yield of 111.65 g/L, the conversion of sugar to alcohol reached 95.53%. It is the highest level of physical mutagenesis yield at present. CONCLUSION: Our results showed that K+ and Ca2+ ions primarily limited the efficient production of ethanol. Then, subsequent comparative transcriptomic GO and pathway analyses showed that the co-presence of K+ and Ca2+ exerted the most prominent limitation on efficient ethanol production. The results of this study might prove useful by promoting the development and utilization of green fuel bio-manufactured from molasses.
Subject(s)
Calcium , Ethanol , Fermentation , Molasses , Potassium , Saccharomyces cerevisiae , Saccharum , Ethanol/metabolism , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae/genetics , Saccharum/metabolism , Calcium/metabolism , Potassium/metabolismABSTRACT
Haploid cells are a kind of cells with only one set of chromosomes. Compared with traditional diploid cells, haploid cells have unique advantages in gene screening and drug-targeted therapy, due to their phenotype being equal to the genotype. Embryonic stem cells are a kind of cells with strong differentiation potential that can differentiate into various types of cells under specific conditions in vitro. Therefore, haploid embryonic stem cells have the characteristics of both haploid cells and embryonic stem cells, which makes them have significant advantages in many aspects, such as reproductive developmental mechanism research, genetic screening, and drug-targeted therapy. Consequently, establishing haploid embryonic stem cell lines is of great significance. This paper reviews the progress of haploid embryonic stem cell research and briefly discusses the applications of haploid embryonic stem cells.
Subject(s)
Embryonic Stem Cells , Haploidy , Humans , Embryonic Stem Cells/metabolism , Embryonic Stem Cells/cytology , Animals , Cell DifferentiationABSTRACT
Ajaniaflavida, a new species from western Sichuan and eastern Xizang, China, is described and illustrated. It is readily assigned to A.sect.Ajania owing to its straw-colored, glossy involucres and marginally whitish scarious phyllaries. Within the section, it is distinct in being a shrub of 1-2 m in height, and in having creamy yellow florets. It is superficially similar to A.ramosa in A.sect.Phaeoscyphus, but can easily be distinguished by, among other characters, the plant height, color of the florets and margins of the phyllaries. In addition, we provide a distribution map of the new species.
ABSTRACT
Ligularialushuiensis, a new species from northwestern Yunnan, China, is described and illustrated. It was tentatively placed in L.sect.Ligulariaser.Ligularia on the basis of the pinnate-palmate leaf venation, racemose synflorescence and pappus which is as long as tubular corolla. Within the series, it appeared somewhat close to both L.lamarum and L.pseudolamarum. However, L.lushuiensis can be easily distinguished from the latter two species by, among other characters, the leaf margin, bract size, involucre shape and size, and number and width of ray florets. Morphologically, L.lushuiensis is also superficially similar to L.secunda but differs readily by having distally shortly yellowish and brownish puberulent stems, palmately-pinnately veined leaves regularly dentate at margin, scarious, brown and larger bracts, and larger ray laminae. In addition, a distribution map and a diagnostic key to Chinese species of L.ser.Ligularia are also provided.
ABSTRACT
To study the species of lanthanum (III) nitrate (La[NO3]3) dispersed in cell media and the effect on the osteoblast differentiation of bone marrow stroma cells (BMSCs). Different La-containing precipitations were obtained by adding various concentrations of La(NO3)3 solutions to Dulbecco's modified Eagle medium (DMEM) or DMEM with fetal bovine serum (FBS). A series of characterisation methods, including dynamic light scattering, scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, and protein quantification were employed to clarify the species of the different La-containing precipitations. The primary BMSCs were isolated, and the cell viability, alkaline phosphatase activity, and the formation of a mineralised nodule of BMSCs were tested when treated with different La-containing precipitations. The La(NO3)3 solutions in DMEM could form LaPO4, which exits in the particle formation, while the La(NO3)3 solutions in DMEM with FBS could form a La-PO4-protein compound. When treated with La(NO3)3 solutions in DMEM, the cell viability of the BMSCs was inhibited at the concentrations of 1, 10, and 100 µM at 1 day and 3 days. Meanwhile, the supernatant derived from the La(NO3)3 solutions in DMEM did not affect the cell viability of the BMSCs. In addition, the precipitate derived from the La(NO3)3 solutions in DMEM added to the complete medium inhibited the cell viability of the BMSCs at concentrations of 10 µM and 100 µM. When treated with La(NO3)3 solutions in DMEM with FBS, the derived precipitate and supernatant did not affect the cell viability of the BMSCs, except for the concentration of 100 µM La(NO3)3. The La-PO4-protein formed from the La(NO3)3 solutions in DMEM with FBS inhibited the osteoblast differentiation of BMSCs at the concentration of 1 µM La(NO3)3 (P < 0.05) but had no effect on either the osteoblast differentiation at the concentrations of 0.001 and 0.1 µM or on the formation of a mineralised nodule at all tested concentrations of La(NO3)3. Overall, La(NO3)3 solutions in different cell culture media could form different La-containing compounds: La-PO4 particles (in DMEM) and a La-PO4-protein compound (in DMEM with FBS). The different La-containing compounds caused different effects on the cell viability, osteoblast differentiation, and the formation of a mineralised nodule of the BMSCs. The La-containing precipitation inhibited the osteoblast differentiation by inhibiting the expression of osteoblast-related genes and proteins, providing a theoretical basis for clinical doctors to apply phosphorus-lowering drugs such as lanthanum carbon.
Subject(s)
Mesenchymal Stem Cells , Nitrates , Mice , Animals , Nitrates/pharmacology , Nitrates/metabolism , Lanthanum/pharmacology , Lanthanum/metabolism , Osteogenesis , Cells, Cultured , Cell Differentiation , Bone Marrow Cells , Cell Proliferation , Stromal CellsABSTRACT
Based on the literature study,the thoughts and possible therapeutic mechanism in treating male infertility from the perspective of spleen and kidney by regulating intestinal flora were explored.Disturbance of intestinal flora is one of the important factors leading to the development of male infertility,and the spleen and kidney have certain similarities to intestinal flora in the physiological function and pathological changes.Moreover,tonifying the kidney and strengthening the spleen can regulate the intestinal flora by fostering the growth of beneficial bacteria,inhibiting the reproduction of pathogenic bacteria,and protecting the barrier of the intestinal mucosa.Therefore,the possible therapeutic mechanisms in treating male infertility with the prescriptions for tonifying the kidney and strengthening the spleen to regulate intestinal flora are as follows:inhibiting the expression of inflammatory factors to reduce the inflammatory reaction of testicular tissues;improving the antioxidant capacity to alleviate the damage of spermatozoa caused by oxidative stress,and improving the bad mood to alleviate the impact of psychological stress on the reproductive system.The exploration of the thoughts for treating male infertility from the perspective of spleen and kidney by regulating intestinal flora may provide a new entry point for modern Chinese medicine clinical treatment of male infertility.
ABSTRACT
Negative association was found between the frontal theta/beta ratio and mind wandering in participants with high schizotypal traits, while no such association was found in participants with low schizotypal traits. These findings provide insights into the neural mechanism of mind wandering in individuals with high schizotypal traits.
Subject(s)
Attention , Schizotypal Personality Disorder , HumansABSTRACT
Exosomes are nanoscale small vesicles (EVs) secreted by cells that carry important bio information, including proteins, miRNAs, and more. Exosome contents are readily present in body fluids, including blood, and urine of humans and animals, and thereby act as markers of diseases. In patients with Parkinson's disease (PD), exosomes may spread alpha-synuclein and miR-184 between the cells contributing to dopaminergic neuronal loss. In this study, we detected the levels of miR-184 in urine-excreted neuronal exosomes between PD patients and age-matched healthy subjects by qRT-PCR analysis. Transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) were also used to determine the ultracellular structures of exosomes nanoparticles. MPP + and MPTP were used to construct the cell and animal PD model. Behavioral tests were used to detect motor performance. Furthermore, the cytological experiments were measured to examine the relationship between miR-184 and ZNF865. We found that the levels of miR-184 in urine-derived neuronal exosomes from PD patients were higher, compared to aged-matched normal people. The exosomes from PD patients were larger with greater numbers than those from the age-matched healthy subjects. The difference in miR-184 in urinary exosomes between PD patients and normal people may provide a novel perspective for early diagnosis of PD. However, no difference in CD63 level was observed in Exo-control and Exo-PD groups (exosome from control or PD groups). Moreover, ZNF865 was detected as the targeted gene of miR-184. In addition, miR-184 ASO (miR-184 antisense oligodeoxynucleotide, miR-184 ASO) could rescue the damage of neuronal apoptosis and motor performance in PD mice. Our results showed the miR-184 potential to function as a diagnostic marker of PD.
ABSTRACT
Rotavirus remains a major cause of diarrhea among 5-y-old children, and vaccination is currently the most effective and economical measure. We conducted a randomized, double-blind, placebo-controlled phase II clinical trial designed to determine the dosage, immunogenicity, and safety profile of a novel hexavalent rotavirus vaccine. In total, 480 eligible healthy infants, who were 6-12 weeks of age at the time of randomization were randomly allocated (1:1:1) to receive 105.5 focus-forming unit (FFU) or 106.5FFU of vaccine or placebo on a 0, 28 and 56-d schedule. Blood samples were collected 28 d after the third dose to assess rotavirus immunoglobulin A (IgA) antibody levels. Adverse events (AEs) up to 28 d after each dose and serious adverse events (SAEs) up to 6 months after the third dose were recorded as safety measurements. The anti-rotavirus IgA seroconversion rate of the vaccine groups reached more than 70.00%, ranging from 74.63% to 76.87%. The postdose 3 (PD3) geometric mean concentrations (GMCs) of anti-rotavirus IgA among vaccine recipients ranged from 76.97 U/ml to 84.46 U/ml. At least one solicited AE was recorded in 114 infants (71.25%) in the high-dose vaccine group, 106 infants (66.25%) in the low-dose vaccine group and 104 infants (65.00%) in the placebo group. The most frequently solicited AE was fever. The novel oral hexavalent rotavirus vaccine was safe and immunogenic in infants support the conclusion to advance the candidate vaccine for phase 3 efficacy trials.
Subject(s)
Rotavirus Infections , Rotavirus Vaccines , Rotavirus , Humans , Infant , Antibodies, Viral , Double-Blind Method , East Asian People , Immunogenicity, Vaccine , Immunoglobulin A , Rotavirus Infections/prevention & control , Rotavirus Vaccines/adverse effects , Rotavirus Vaccines/therapeutic use , Vaccines, Attenuated , Vaccines, CombinedABSTRACT
BACKGROUND: Urinary sepsis is frequently seen in patients with diabetes mellitus (DM) complicated with upper urinary tract calculi (UUTCs). Currently, the known risk factors of urinary sepsis are not uniform. AIM: To analyze the risk factors of concurrent urinary sepsis in patients with DM complicated with UUTCs by logistic regression. METHODS: We retrospectively analyzed 384 patients with DM complicated with UUTCs treated in People's Hospital of Jincheng between February 2018 and May 2022. The patients were screened according to the inclusion and exclusion criteria, and 204 patients were enrolled. The patients were assigned to an occurrence group (n = 78) and a nonoccurrence group (n = 126). Logistic regression was adopted to analyze the risk factors for urinary sepsis, and a risk prediction model was established. RESULTS: Gender, age, history of lumbago and abdominal pain, operation time, urine leukocytes (U-LEU) and urine glucose (U-GLU) were independent risk factors for patients with concurrent urinary sepsis (P < 0.05). Risk score = 0.794 × gender + 0.941 × age + 0.901 × history of lumbago and abdominal pain - 1.071 × operation time + 1.972 × U-LEU + 1.541 × U-GLU. The occurrence group had notably higher risk scores than the nonoccurrence group (P < 0.0001). The area under the curve of risk score for forecasting concurrent urinary sepsis in patients was 0.801, with specificity of 73.07%, sensitivity of 79.36% and Youden index of 52.44%. CONCLUSION: Sex, age, history of lumbar and abdominal pain, operation time, ULEU and UGLU are independent risk factors for urogenic sepsis in diabetic patients with UUTC.
ABSTRACT
Introduction: Patients with schizophrenia exhibit prospective memory (PM) impairment. Intraindividual reaction time variability (IIRTV) is an index of attentional control that is required for PM. This study examined the differences in IIRTV between patients with schizophrenia and healthy controls and the relationship between IIRTV and PM performance.Method: Thirty-nine patients with schizophrenia and forty-two healthy controls were recruited to complete a PM task and the Sustained Attention to Response Task. IIRTV was calculated as the coefficient of variation (mean/SD) of reaction time over correctly responded trials in these tasks.Results: Patients with schizophrenia showed lower PM accuracy and increased IIRTV, while the associations between PM accuracy and IIRTV were significant in healthy controls but not in patients with schizophrenia.Conclusion: These findings suggest impaired PM and relationship between PM and attentional control in patients with schizophrenia.
Subject(s)
Memory, Episodic , Schizophrenia , Humans , Reaction Time/physiology , Cognition , Memory DisordersABSTRACT
BACKGROUND: Haploid embryonic stem cells (haESCs) have been established in many species. Differentiated haploid cell line types in mammals are lacking due to spontaneous diploidization during differentiation that compromises lineage-specific screens. AIM: To derive human haploid neural stem cells (haNSCs) to carry out lineage-specific screens. METHODS: Human haNSCs were differentiated from human extended haESCs with the help of Y27632 (ROCK signaling pathway inhibitor) and a series of cytokines to reduce diploidization. Neuronal differentiation of haNSCs was performed to examine their neural differentiation potency. Global gene expression analysis was con-ducted to compare haNSCs with diploid NSCs and haESCs. Fluorescence activated cell sorting was performed to assess the diploidization rate of extended haESCs and haNSCs. Genetic manipulation and screening were utilized to evaluate the significance of human haNSCs as genetic screening tools. RESULTS: Human haESCs in extended pluripotent culture medium showed more compact and smaller colonies, a higher efficiency in neural differentiation, a higher cell survival ratio and higher stability in haploidy maintenance. These characteristics effectively facilitated the derivation of human haNSCs. These human haNSCs can be generated by differentiation and maintain haploidy and multipotency to neurons and glia in the long term in vitro. After PiggyBac transfection, there were multiple insertion sites in the human haNSCs' genome, and the insertion sites were evenly spread across all chromosomes. In addition, after the cells were treated with manganese, we were able to generate a list of manganese-induced toxicity genes, demonstrating their utility as genetic screening tools. CONCLUSION: This is the first report of a generated human haploid somatic cell line with a complete genome, proliferative ability and neural differentiation potential that provides cell resources for recessive inheritance and drug targeted screening.
ABSTRACT
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.
ABSTRACT
BACKGROUND: Norovirus is a leading cause of acute gastroenteritis among children. Previous studies based on symptomatic infections indicated that mutations, rather than recombination drove the evolution of the norovirus ORF2. These characteristics were found in hospital-based symptomatic infections, whereas, asymptomatic infections are frequent and contribute significantly to transmission. METHODS: We conducted the first norovirus molecular epidemiology analysis covering both symptomatic and asymptomatic infections derived from a birth cohort study in the northern China. RESULTS: During the study, 14 symptomatic and 20 asymptomatic norovirus infections were detected in 32 infants. Out of the 14 strains that caused symptomatic infections, 12 strains were identified as GII.3[P12], and others were GII.4[P31]. Conversely, 17 asymptomatic infections were caused by GII.4[P31], two by GII.2[P16], and one by GII.4[P16]. Regardless of symptomatic and asymptomatic infections, the mutations were detected frequently in the ORF2 region, and almost all recombination were identified in the RdRp-ORF2 region. The majority of the mutations were located around the predefined epitope regions of P2 subdomain indicating a potential for immune evasion. CONCLUSION: The role of symptomatic as well as asymptomatic infections in the evolution of norovirus needs to be evaluated continuously.
Subject(s)
Caliciviridae Infections , Norovirus , Humans , Infant , Asymptomatic Infections/epidemiology , Caliciviridae Infections/epidemiology , Cohort Studies , East Asian People , Feces , Genotype , Molecular Epidemiology , Norovirus/genetics , PhylogenyABSTRACT
Aquaculture wetlands, particularly those located within urban areas, are fragile ecosystems due to urban and aquaculture impacts. However, to date, there are no reports on the combined toxicity of heavy metal mixtures in aquatic biota in sediments from aquaculture wetlands in metropolitan areas. Thus, the characterization, bioavailability, and ecological probability risk of heavy metals were studied in the riverine/estuarine sediments of the Rongjiang River in an aquaculture wetland in Chaoshan metropolis, South China. In the study area, the average total concentrations (mg/kg) were 2.38 (Cd), 113.40 (Pb), 88.27 (Cr), 148.25 (Ni), 62.08 (Cu), 125.18 (Zn), 45,636.44 (Fe), and 797.18 (Mn), with the Cd pollution being regarded as extremely serious based on the enrichment factor (EF). There are two main sources of heavy metals in the study area; Ni, Pb, Zn, Fe and Mn are mainly from domestic waste, while Cr, Cd and Cu are possibly associated with industrial production activities. The bioavailability of most heavy metals accounted for more than 20% of the total concentration. The combined toxicity of heavy metal mixtures based on probabilistic risk assessment suggests that the surface sediments of the Rongjiang River and its estuary had a 15.71% probability of toxic effects on aquatic biota.
Subject(s)
Metals, Heavy , Water Pollutants, Chemical , Wetlands , Ecosystem , Cadmium , Biological Availability , Lead , Water Pollutants, Chemical/analysis , Environmental Monitoring , Metals, Heavy/analysis , Aquaculture , China , Rivers , Geologic Sediments , Risk AssessmentABSTRACT
BACKGROUND: Mental time travel (MTT) is the ability to re-experience past events (autobiographic memory, AM) and pre-experience possible future events (episodic future thinking, EFT) through mental simulation. Empirical findings suggest that individuals with high level of schizotypy exhibit MTT impairment. However, the neural correlates of this impairment remain unclear. METHOD: Thirty-eight individuals with high level of schizotypy and 35 low level of schizotypy were recruited to complete an MTT imaging paradigm. Participants were required to recall past events (AM condition), imagine possible future events (EFT condition) related to cue words, or generate exemplars related to category words (control condition) while undergoing functional Magnetic Resonance Imaging (fMRI). RESULTS: AM showed greater activation in precuneus, bilateral posterior cingulate cortex, thalamus, and middle frontal gyrus than EFT. Individuals with high level of schizotypy exhibited reduced activation in the left anterior cingulate cortex during AM (vs. Control) and in the medial frontal gyrus during EFT (vs. Control) compared to individuals with low level of schizotypy. Although psychophysiological interaction analyses did not show any significant group difference, individuals with high level of schizotypy exhibited functional connectivity between left anterior cingulate cortex (seed) and right thalamus, between medial frontal gyrus (seed) and left cerebellum during MTT, whereas individuals with low level of schizotypy did not exhibit these functional connectivities. CONCLUSION: These findings suggest that decreased brain activations may underlie MTT deficits in individuals with high level of schizotypy.