This study explored a new model of Prostate Imaging Reporting and Data System (PIRADS) and adjusted prostate-specific antigen density of peripheral zone (aPSADPZ) for predicting the occurrence of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). The demographic and clinical characteristics of 853 patients were recorded. Prostate-specific antigen (PSA), PSA density (PSAD), PSAD of peripheral zone (PSADPZ), aPSADPZ, and peripheral zone volume ratio (PZ-ratio) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The calibration and discrimination abilities of new nomograms were verified with the calibration curve and area under the ROC curve (AUC). The clinical benefits of these models were evaluated by decision curve analysis and clinical impact curves. The AUCs of PSA, PSAD, PSADPZ, aPSADPZ, and PZ-ratio were 0.669, 0.762, 0.659, 0.812, and 0.748 for PCa diagnosis, while 0.713, 0.788, 0.694, 0.828, and 0.735 for csPCa diagnosis, respectively. All nomograms displayed higher net benefit and better overall calibration than the scenarios for predicting the occurrence of PCa or csPCa. The new model significantly improved the diagnostic accuracy of PCa (0.945 vs 0.830, P < 0.01) and csPCa (0.937 vs 0.845, P < 0.01) compared with the base model. In addition, the number of patients with PCa and csPCa predicted by the new model was in good agreement with the actual number of patients with PCa and csPCa in high-risk threshold. This study demonstrates that aPSADPZ has a higher predictive accuracy for PCa diagnosis than the conventional indicators. Combining aPSADPZ with PIRADS can improve PCa diagnosis and avoid unnecessary biopsies.
Male ; Humans ; Prostate/pathology* ; Prostate-Specific Antigen/analysis* ; Prostatic Neoplasms/diagnostic imaging* ; Biopsy ; Nomograms ; Retrospective Studies

Genetic risk factors have been shown to contribute to the development of sexual dysfunction. However, the role of methylenetetrahydrofolate reductase (MTHFR) gene variants in the risk of erectile dysfunction (ED) remains unclear. In this study, we recruited 1254 participants who underwent ED assessed by the International Index of Erectile Function-5. The MTHFR c.677C>T variant was also measured by fluorescence polymerase chain reaction (PCR). No significant difference in the genotypic frequency of the MTHFR C677T polymorphism (CC, CT, and TT) was observed between men from the ED and non-ED groups. In addition, on binary logistic regression analysis, both crude and adjusted models showed that the risk of ED was not significantly associated with the C677T polymorphism. Interestingly, a significantly higher frequency of the 677TT polymorphism was found in severe and moderate ED (P = 0.02). The positive correlation between the MTHFR 677TT polymorphism and severe ED was confirmed by logistic regression analysis, even after adjusting for potential confounders (odds ratio [OR] = 2.46, 95% confidence interval [CI]: 1.15-5.50, P = 0.02). These findings suggest a positive correlation between the MTHFR 677TT polymorphism and the risk of severe ED. Identification of MTHFR gene polymorphisms may provide complementary information for ED patients during routine clinical diagnosis.

Objective Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9％) were men. Among them, nearly two-thirds (62.5％) of the survivors were moderate, three (9.4％) were severe, and more than half (59.4％) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6％ at 3 months to 15.8％ at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1％) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

In this study, Andrographis paniculata seedlings were used as experimental materials to study the effects of salicylic acid(SA) on the growth and effective component accumulation of A. paniculata under NaCl stress. The results showed that with the increase of NaCl concentration, the growth of A. paniculata seedlings was significantly inhibited, and the content of carotene and carotenoid decreased. The activity of antioxidant enzyme was enhanced. At the same time, the contents of proline, proline and soluble protein were on the rise. The contents of andrographolide, new andrographolide and deoxyandrographolide showed an upward trend, while deoxyandrographolide showed a downward trend. Treatment with 100 mmol·L~(-1) NaCl+5 mg·L~(-1) SA showed a significant increase in antioxidant enzyme activity in A. paniculata leaves. Treatment with 100 mmol·L~(-1) NaCl+10 mg·L~(-1) SA showed significant changes in soluble protein and proline content in A. paniculata leaves, while MDA content in A. paniculata leaves significantly decreased. 10 mg·L~(-1) SA had the best effect on the growth of A. paniculata seedlings under salt stress. Under the treatment of 50 mmol·L~(-1) NaCl+10 mg·L~(-1) SA, fresh weight, dry weight and leaf dry weight of A. paniculata seedlings reached the highest level, which were 1.02, 1.09 and 1.11 times of those in the control group, respectively. The concentrations of NaCl and 10 mg·L~(-1) SA were significantly higher than those of the control group. Four key enzyme genes of A. paniculata diterpene lactone synthesis pathway were selected to explore the molecular mechanism of salicylic acid to alleviate salt stress. With the increase of salt stress, the relative expressions of HMGR, GGPS and ApCPS were up-regulated, indicating that salt stress may enhance the synthesis of A. paniculata diterpene lactone through MVA pathway. SA can effectively promote the growth and development of A. paniculata under salt stress, improve its osmotic regulation and antioxidant capacity, improve its salt tolerance, and alleviate the effects of salt stress on A. paniculata.
Andrographis ; Plant Leaves ; Salicylic Acid ; Salt Tolerance ; Seedlings/genetics*

Salvia miltiorrhiza(Sm) and Salvia castanea f. tomentosa(Sc) hairy roots were used as experimental materials to study the effects of six different carbon sources, galactose, fructose, lactose, glucose, arabinose and sucrose(control), on fresh weight, dry weight, contents and yields of salvianolic acids and tanshinones. The results showed that galactose was most beneficial to the growth of two kinds of hairy roots, while lactose and arabinose were not conducive to their growth. As for Sm hairy roots, fructose significantly promoted the accumulation of salvianolic acid B, and the content increased by 5.801 times and 10.151 times compared with the control group, respectively. Glucose significantly promoted the accumulation of salvianolic acids. The content and yield of rosmarinic acid were 7.674 times and 9.260 times of that of the control group, and the content and yield of salvianolic acid B were 5.532 times and 6.675 times of the control group. For the hairy roots of Sc, galactose significantly increased the content and yield of rosmarinic acid, reaching 7.820 times and 9.944 times of the control group, respectively. Fructose promoted the increase of the content and yield of cryptotanshinone, reaching 9.242 times and 6.609 times of the control group, respectively. The study confirmed the optimal carbon source for the hairy root culture of Sm and Sc, and provided theoretical guidance for large-scale production of Sm drug-derived components and the utilization of Sc.
Carbon ; Plant Roots ; Salvia ; Salvia miltiorrhiza

Objective: In order to explore natural active ingredients of Scutellariae Radix and alleviate the pressure of traditional medicinal resources,this research aimmed to screen endophytic fungus strains from Scutellariae Radix which could transform baicalin into some active ingredients.Method: Taking fresh plants of Scutellariae Radix as strain resource,endophytic fungus strains were isolated by potato dextrose agar (PDA) plate separation,Scutellariae Radix powder selective culture and HPLC detection.Result: An endophytic fungus strain R3 was isolated and it can transform baicalin to baicalein and oroxylin A simultaneously in potato dextrose broth (PDB) contained 0.1% baicalin and the conversion rate reached 61.09% in 5 d cultured at 28℃ and 150 r·min^-1,molar ratio of baicalein and oroxylin A was 3:5.With the method of morphological analysis,microscopic identification and 18SrDNA sequence analysis,the bacterium was identified as Penicillium sp.R3. Conclusion: Penicillium sp.R3 can transform baicalin to baicalein and oroxylin A with certain research value and application value.

Adult ; Connexin 43 ; genetics ; Erythrokeratodermia Variabilis ; genetics ; Female ; Heterozygote ; Humans ; Male ; Mutation ; genetics ; Mutation, Missense ; genetics ; Pedigree

Next-generation sequencing has allowed identification of millions of somatic mutations in human cancer cells. A key challenge in interpreting cancer genomes is to distinguish drivers of cancer development among available genetic mutations. To address this issue, we present the first web-based application, consensus cancer driver gene caller (C), to identify the consensus driver genes using six different complementary strategies, i.e., frequency-based, machine learning-based, functional bias-based, clustering-based, statistics model-based, and network-based strategies. This application allows users to specify customized operations when calling driver genes, and provides solid statistical evaluations and interpretable visualizations on the integration results. C is implemented in Python and is freely available for public use at http://drivergene.rwebox.com/c3.

The aim of this paper was to observe the effect of triptolide( TP) on cardiovascular function and its possible mechanism by intraperitoneal injection of bacterial lipopolysaccharide in rats with endotoxemia. Sixty male Sprague-Dawley rats were randomly divided intonormal group( NC group),endotoxemia model group( LPS group),TP low concentration intervention group( LPS + TP-L group,25 μg·kg~(-1)),TP middle concentration intervention group( LPS+TP-M group,50 μg·kg~(-1)),TP high concentration intervention group( LPS+TP-H group,100 μg·kg~(-1)) and polymyxin B group( LPS+PMX-B group,0. 2 mg·kg~(-1)). 10 mg·kg~(-1) LPS was injected intraperitoneally for 6 h to replicate the endotoxemia rat model. The rats in TP intervention groups were pre-treated 15 min before intraperitoneal injection of LPS. Rats in each group underwent total arterial intubation to measure hemodynamic parameters: heart rate( HR),left ventricular diastolic pressure( LVDP),the maximum rate of the increase/decrease of left ventricular pressure( ±dp/dtmax). The levels of BNP,CK-MB and c Tn-Ⅰ in serum and levels of TNF-α and IL-6 in plasma were detected by ELISA. The contents of p65 protein in myocardium and contents of p65,TLR4,i NOS and e NOS protein in thoracic aorta were detected by Western blot. As compared with NC group,the hemodynamic indexes in LPS group were significantly decreased; the contents of BNP,CK-MB and c Tn-Ⅰ in serum,TNF-α and IL-6 in plasma,p65 in myocardium,i NOS,e NOS,TLR4 and p65 in vascular tissues were significantly increased. As compared with LPS group,the hemodynamic indexes were significantly improved in LPS+TP-M group,LPS+TP-H group and LPS+PMX-B group; the contents of BNP,CK-MB and c Tn-Ⅰ in serum,TNF-α and IL-6 in plasma,p65 in myocardium,i NOS,e NOS,TLR4 and p65 in vascular tissues were significantly decreased in each treatment group. Triptolide has a protective effect on cardiovascular damage in a dose-dependent manner in endotoxemia rats,probably through TLR4/NF-κB p65 signaling pathway to improve endothelial function.
Animals ; Diterpenes/pharmacology* ; Endothelium ; Endotoxemia ; Epoxy Compounds/pharmacology* ; Lipopolysaccharides ; Male ; NF-kappa B ; Phenanthrenes/pharmacology* ; Protective Agents/pharmacology* ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Toll-Like Receptor 4/metabolism* ; Tumor Necrosis Factor-alpha

Objective: To evaluate the clinical outcomes of a series of patients who have undergone reconstruction of craniofacial defects after resection of intracranial tumors or craniofacial trauma with free composite anterolateral thigh flaps. Methods: Retrospective analyses the clinical cases from September 2007 to September 2016. Data included flap survival rate, complication, satisfaction survey was reviewed to evaluate the efficacy and safety of this surgical strategy. Results: Totally 10 free anterolateral thigh flaps including 3 cases of fasciocutaneous flaps, 2 case of adipofascial flaps, 4 cases of myocutaneous flaps, 1 case of chimeric flap, were adopted to reconstruct craniofacial defects. Follow-up ranged from 3 to 17 months (average, 12 months). All flaps were transferred successfully. There were no cranial spinal fluid(CSF) leaks, intracranial infections or donor site complications. All patients were satisfied. Conclusions Because of its abundance of tissue, matched vessels to recipient site, versatility of muscular flaps to fill irregularly intracranial defects, reliable blood supply, feasibility of simultaneous fascia lata harvesting, free composite anterolateral thigh flap is the reconstructive method of choice for craniofacial defects reconstruction after resection of intracranial tumors or craniofacial trauma. The use of ALT flap was reliable in the decrease of CSF leak and infection rate and dependable according to long time follow-up.