Objective:To investigate the value of biparametric-MRI (bpMRI) based peritumoral radiomics for preoperative prediction of extraprostatic extension (EPE) in prostate cancer (PCa).Methods:In this cross-sectional study, consecutive bpMRI of patients undergoing prostatectomy for PCa were retrospectively collected from the First Medical Center (center 1) and the Third Medical Center (center 2) of Chinese PLA General Hospital. A total of 274 patients were finally enrolled. Patients at center 1 from January 2020 to December 2022 were randomly divided into a training set (149 cases) and an internal validation set (63 cases) by stratified random sampling. Patients at center 2 from January 2023 to March 2024 were assigned to the external test set (62 cases). Patients were categorized into EPE-positive group and EPE-negative group according to pathological assessment postoperatively. In the training set, there were 49 cases in EPE-positive group and 100 cases in EPE-negative group. In the internal validation set, there were 26 cases in EPE-positive group and 37 cases in EPE-negative group. In the external test set, there were 22 cases in EPE-positive group and 40 cases in EPE-negative group. Axial T 2WI and apparent diffusion coefficient (ADC) images were manually annotated to obtain index lesion regions of interest (ROIs), with the peritumoral ROIs subsequently delineated by semi-automatic segmentation technique. Radiomics features were extracted from intra-tumoral, peri-tumoral, and intra-tumoral plus peri-tumoral ROIs. The training set data was employed to select and optimize features to build the radiomics models. The logistic regression analysis was used to develop radiomics, clinical, and integrated models. The predictive performance was assessed by the area under the receiver operating characteristic curve (AUC) in the external test set, and compared by the DeLong test. The sensitivity and specificity were compared by the exact McNemar test. Results:In the external test set, the peri-tumoral radiomics model based on bpMRI showed the highest performance in evaluating EPE, with an AUC of 0.739 (95% CI 0.611-0.842), which was identified as the optimal radiomics model. EPE grade ( OR=6.151, 95% CI 3.371-11.226, P<0.001) was incorporated into the clinical model, with an AUC of 0.780 (95% CI 0.657-0.875) in the external test set. The integrated model had an AUC of 0.817 (95% CI 0.698-0.904) in the external test set. There was no statistically significant difference in comparisons of AUCs among the three models (all P>0.05). The sensitivity of the integrated model (68.2%) showed no significant difference from those of the clinical model and the optimal radiomics model (77.3% and 86.4%, respectively; P=0.500 and P=0.289). However, the specificity of the integrated model (85.0%) was significantly higher than those of the clinical model (67.5%, P=0.016) and the optimal radiomics model (50.0%, P<0.001). Conclusion:A bpMRI-based peritumoral radiomics integrating clinical model demonstrates high performance for preoperative prediction of EPE in PCa.

Objective To investigate the effects of high-altitude hypoxic environment on the pharmacokinetic characteristics and brain tissue distribution of phenytoin sodium in epileptic rats.Methods A total of 70 male SPF-grade Wistar rats aged 2 months and weighing(200±20)g were used in the study.An epilepsy model was induced in the rats using the lithium chloride-pilocarpine method.The successfully modeled rats were randomly assigned to a normoxic treatment group and a high-altitude hypoxic treatment group.Phenytoin sodium was administered via intragastric gavage at a dose of 50 mg/kg in both groups.Blood samples were collected from the orbital venous plexus before treatment and 0.5,1,2,3,4,6,8,10,and 24 h post treatment.The animals were euthanized after the final blood collection,and samples of the liver and the whole brain tissue were collected.In the brain tissue distribution experiment,brain tissue samples were collected at 0.5,1,2,and 4 h after drug administration.The concentration of phenytoin sodium in rat plasma and brain tissue was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS),and the pharmacokinetic parameters were calculated using WinNolin 8.1 software.The expression levels of CYP2C9 in liver tissue and those of P-gp in brain tissue of epileptic rats were determined by Western blot.Results Compared with those in the normoxia group,the peak concentration,peak time,and half-life of phenytoin sodium in the high-altitude hypoxia group were significantly decreased by 46.0%,42.3%,and 55.5%,respectively(all P<0.05);the clearance rate was significantly increased by 162.0%(P<0.05);and the area under the curve of plasma concentration-time curve was decreased by 45.6%(P<0.01).At 0.5,1,and 2 hours after administration,compared with that in the normoxia treatment group,the concentration of phenytoin sodium in the brain tissue of the high-altitude hypoxia treatment group was significantly decreased by 78.1%,63.5%,and 32.5%,respectively(all P<0.05).Western blot results showed that the expression levels of CYP2C9 in the liver tissue and P-gp in the brain tissue of rats in the high-altitude hypoxia group were approximately 1.78 and 1.65 times higher than those in the normoxia group,respectively(both P<0.05).Conclusion The hypoxic environment at high altitudes can promote the metabolism of phenytoin sodium,reduce its absorption efficiency,and change the characteristics its distribution in the brain,which may be related to the up-regulation of the expression of CYP2C9 in the liver and that of P-gp in the brain.

Objective:To investigate the value of biparametric-MRI (bpMRI) based peritumoral radiomics for preoperative prediction of extraprostatic extension (EPE) in prostate cancer (PCa).Methods:In this cross-sectional study, consecutive bpMRI of patients undergoing prostatectomy for PCa were retrospectively collected from the First Medical Center (center 1) and the Third Medical Center (center 2) of Chinese PLA General Hospital. A total of 274 patients were finally enrolled. Patients at center 1 from January 2020 to December 2022 were randomly divided into a training set (149 cases) and an internal validation set (63 cases) by stratified random sampling. Patients at center 2 from January 2023 to March 2024 were assigned to the external test set (62 cases). Patients were categorized into EPE-positive group and EPE-negative group according to pathological assessment postoperatively. In the training set, there were 49 cases in EPE-positive group and 100 cases in EPE-negative group. In the internal validation set, there were 26 cases in EPE-positive group and 37 cases in EPE-negative group. In the external test set, there were 22 cases in EPE-positive group and 40 cases in EPE-negative group. Axial T 2WI and apparent diffusion coefficient (ADC) images were manually annotated to obtain index lesion regions of interest (ROIs), with the peritumoral ROIs subsequently delineated by semi-automatic segmentation technique. Radiomics features were extracted from intra-tumoral, peri-tumoral, and intra-tumoral plus peri-tumoral ROIs. The training set data was employed to select and optimize features to build the radiomics models. The logistic regression analysis was used to develop radiomics, clinical, and integrated models. The predictive performance was assessed by the area under the receiver operating characteristic curve (AUC) in the external test set, and compared by the DeLong test. The sensitivity and specificity were compared by the exact McNemar test. Results:In the external test set, the peri-tumoral radiomics model based on bpMRI showed the highest performance in evaluating EPE, with an AUC of 0.739 (95% CI 0.611-0.842), which was identified as the optimal radiomics model. EPE grade ( OR=6.151, 95% CI 3.371-11.226, P<0.001) was incorporated into the clinical model, with an AUC of 0.780 (95% CI 0.657-0.875) in the external test set. The integrated model had an AUC of 0.817 (95% CI 0.698-0.904) in the external test set. There was no statistically significant difference in comparisons of AUCs among the three models (all P>0.05). The sensitivity of the integrated model (68.2%) showed no significant difference from those of the clinical model and the optimal radiomics model (77.3% and 86.4%, respectively; P=0.500 and P=0.289). However, the specificity of the integrated model (85.0%) was significantly higher than those of the clinical model (67.5%, P=0.016) and the optimal radiomics model (50.0%, P<0.001). Conclusion:A bpMRI-based peritumoral radiomics integrating clinical model demonstrates high performance for preoperative prediction of EPE in PCa.

Objective To investigate the protective effect of Lycium barbarum polysaccharide(LBP)on reproductive system damage induced by exposure to high-altitude hypoxic environment in female rats,and to explore the mechanisms involved.Methods After undergoing physiological synchronization,30 female Wistar rats were randomly and evenly assigned to 3 groups,including a plain control(C)group,a high-altitude hypoxia(H)group,and a high-altitude hypoxia+LBP(H-LBP)group.The C group was placed in a region at an altitude of 1500 m above sea level(with an oxygen volume fraction of 18.55％),while the H group and the H-LBP group were placed in a region at an altitude of 4 010 m above sea level(with an oxygen volume fraction of 12.70％).Rats in the H-LBP group were fed with LBP at 75 mg/kg via gastric gavage,while the C and H groups received normal saline once a day for 14 days in a row.Changes in estrous cycles were documented throughout the experiment.At the end of the experiment,the serum levels of reproductive hormones and the levels of oxidative stress in the ovarian and uterine tissues were measured.Morphological changes in the ovarian and uterine tissues were assessed using hematoxylin-eosin(HE)staining.A component-target-pathway network diagram was constructed using network pharmacology methods to analyze the key targets and pathways.Results Compared with the C group,rats in the H group had disrupted estrous cycles and significantly lower serum levels of reproductive hormones(all P＜0.05).In addition,rats in the H group had increased oxidative stress damage and experienced pathological damage in the ovarian and uterine tissues.However,compared with those of the H group,the estrous cycle in the H-LBP group became normalized after the administration of LBP and the serum levels of estradiol(E2),progesterone(P),luteinizing hormone(LH),and anti-Müllerian hormone(AMH)were significantly increased in H-LBP group(all P＜0.05).In the ovarian tissue,the malondialdehyde(MDA)content was significantly reduced,superoxide dismutase(SOD)activity was increased,and the content of reduced glutathione(GSH)was increased.In addition,in the uterine tissue,the MDA content was reduced and SOD activity was increased(all P＜0.05),with LBP significantly improving the pathological damage to the reproductive organs of female rats caused by high-altitude hypoxic environment.Through network pharmacology analysis,we identified 76 potential targets for the protective effect of LBP against high-altitude hypoxia-induced reproductive injury,and the targets were mainly involved in the signaling pathways such as calcium channels,PI3K-Akt,MAPK,and HIF-1.Conclusion LBP can ameliorate high-altitude hypoxia-induced reproductive damage in female rats.The mechanisms involved may be associated with the regulation of PI3K-Akt,MAPK,and HIF-1 pathways.

Receptors, Purinergic ; Signal Transduction/physiology*

To reveal the pharmacological mechanism of 3-arylcoumarin derivative 3-(4′-hydroxyphenyl)-6-hydroxycoumarin (SJ-6) against vascular calcification, advanced glycation end products (AGEs) were used to induce the calcification of human aortic vascular smooth muscle cells (HCASMCs), and calcification was identified by alizarin red staining and quantification.The effects of SJ-6 on alkaline phosphatase (ALP) activity, cell proliferation rate, calcium content, and total reactive oxygen species (ROS), superoxide dismutase (SOD), AGEs, and tetra methylethlene diamine proteinase factor-α (TNF-α), interleukin-6 (1L-6), interleukin-β (1L-β), runt-related transcription factor 2 mRNA (Runx2 mRNA), the receptor of advanced glycation endproducts (RAGE), nuclear factor kappa-B (NF-κB), napdh oxidase-1 (NoX-1), protein kinase C(PKC), protein kinase b(AKT), p38 mitogen-activated protein kinase (p38 MAPK), and smooth muscle actin-α (SMA-α) protein expression were determined.According to our results, SJ-6 significantly decreased AGEs content, ALP activity, intracellular calcium content, ROS content, Runx2 mRNA and inflammatory factors TNF-α, 1L-6 and 1L-β (P < 0.05) and increased SOD content (P < 0.01), with similar to those of the positive control drug aminoguanidine hydrochloride (AGH).Therefore, we investigated the pharmacological mechanism of compound SJ-6, which was found to significantly inhibit the expression of RAGE, NF-κB, NoX-1, PKC, Akt, p-p38 and other essential signaling proteins in the calcified cell model (P < 0.01) and increas the expression of smooth actin SMA-α (P < 0.01).SJ-6 inhibits vascular calcification by inhibiting oxidative stress and the expression of AGEs/RAGE, Akt/PKC and NF-κB signaling pathways, suggesting that it may be a novel drug for the treatment of vascular calcification.

Background::Urticaria is a common skin disease characterized by episodes of wheals, and it has a negative effect on patients’ quality of life. Large-scale population-based epidemiological studies of urticaria are scarce in China. The aim of this survey was to determine the prevalence, clinical forms, and risk factors of urticaria in the Chinese population.Methods::This survey was conducted in 35 cities from 31 provinces, autonomous regions, and municipalities of China. Two to three communities in each city were selected in this investigation. Participants completed questionnaires and received dermatological examinations. We analyzed the prevalence, clinical forms, and risk factors of urticaria.Results::In total, 44,875 questionnaires were distributed and 41,041 valid questionnaires were collected (17,563 male and 23,478 female participants). The lifetime prevalence of urticaria was 7.30%, with 8.26% in female and 6.34% in male individuals ( P < 0.05). The point prevalence of urticaria was 0.75%, with 0.79% in female and 0.71% in male individuals ( P < 0.05). Concomitant angioedema was found in 6.16% of patients. Adults had a higher prevalence of urticaria than adolescents and children. Living in urban areas, exposure to pollutants, an anxious or depressed psychological status, a personal and family history of allergy, thyroid diseases, and Helicobacter pylori infection were associated with a higher prevalence of urticaria. Smoking was correlated with a reduced risk of urticaria. Conclusion::This study demonstrated that the lifetime prevalence of urticaria was 7.30% and the point prevalence was 0.75% in the Chinese population; women had a higher prevalence of urticaria than men. Various factors were correlated with urticaria.

Objective:Tumor-treating fields (TTFields) is a kind of non-invasive anti-mitotic tumor therapy, which has been approved for patients with newly diagnosed and recurrent glioblastoma. This study aims to explore the efficacy and safety of TTFields in high-grade gliomas in clinical practice settings.Methods:The clinical data of 15 patients with recurrent glioma and 9 patients with newly diagnosed high-grade glioma admitted to our center from April 2019 to January 2021 were retrospectively analyzed. All patients accepted TTFields≥1 month. Follow-up was performed for 5.3 months (ranged from 2.3 to 10.7 months); Response Assessment in Neuro-Oncology Working Group (RANO) criteria was used to evaluate the glioma responses. The progression-free survival (PFS) and overall survival (OS) were calculated according to Kaplan-Meier method. Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0) and TTFields related skin adverse reaction (dAE) criteria were used to evaluate the adverse events. Quality of life questionnaire-core 30 (QLQ-C30) and QLQ-brain cancer module (QLQ-BN20) questionnaires were used to evaluate the health-related quality of life (HRQoL). Treatment compliance was evaluated by data on the use of NovoTTF-200A devices, and calculated as a percentage of daily TTFields usage.Results:The median duration of TTFields was 4.2 months (ranged from 1.0 to 10.7 months), with a median compliance rate of 91.5% (67.0%-97.0%). TTFields was used alone in 2 patients and used with combination of chemotherapy in 22 patients. From follow-up to April 2021, 14 patients had stable symptoms and 10 had disease progression (8 died). The median PFS and OS of recurrent patients were 5.9 months ( 95%CI: 3.3-8.6 months) and 8.5 months ( 95%CI: 3.2-13.8 months), respectively; and the median PFS and OS of newly diagnosed patients were both 10.7 months (without 95%CI). The common adverse events included grading 1 dAE (58.3%) and grading 2 dAE (12.5%), without grading 3 or 4 dAE, manifested as contact or allergic dermatitis, erosion, folliculitis and ulcers. And 87.5% patients had stable HRQoL. Conclusions:The preliminary results showed that the survival of recurrent high-grade glioma patients treated by TTFields is similar to that reported in foreign literature; and the newly diagnosed patients need further survival follow-up. The patients' treatment compliance and safety are good. The dAE incidence (grading 1-2) is higher than that reported in the literature, and the toxicity was acceptable.

Objective To investigate the relationship between CYP 2C19 gene polymorphisms and clopidogrel efficacy in coronary heart disease patients after percutaneous coronary intervention (PCI).Methods From January 2016 to December 2017,62 patients with acute coronary syndromes and treated with PCI in Guizhou Aerospace Hospital were recruited, CYP2C19 genotype, ADP －induced platelet aggregation rate and myocardial enzymes and other indicators were detected before operation .The myocardial enzymes were measured 24 hours after PCI.According to different metabolic types,the patients were grouped,the above indicators were compared.Results The CYP2C19*1/*1 was 37.10%,CYP2C19*1/*2 was 35.48%,CYP2C19*1/*3 was 11.29%,CYP2C19*2/*2 was 12.90%,CYP2C19*2/*3 was 3.23% and CYP2C19*3/*3 was 0.00%.The LDH,AST,CK,CK－MB and α－HBDH in the PCI patients after operation were significantly higher than those before operation (t＝0.019,0.040, 0.044,0.022,0.014,all P＜0.05).But ADP induced platelet aggregation rate and myocardial enzymes and other indicators among fast metabolism group,intermediate metabolic group and slow metabolic group had no statistically significant differences (all P ＞0.05).Conclusion CYP2C19 mutation frequency in the Chinese population is relatively large,the sample size of this study is less ,the relationship between clopidogrel resistance and the specific genotype can not be obtained ,it need to increase the sample size and comprehensive multi －factor consideration .

Objective To explore the clinical characteristics of patients with thyrotropin-secreting pituitary adenomas ( TSHomas) in China. Methods All the articles related to TSHomas were retrieved from the Chinese journal databases up to July 2017. All reported cases were assessed. Results TSHomas have been diagnosed in all ages (range:12-81 years old, average 41.9 ± 13.8 years old) with no gender difference (male : female=84: 69). The rate of misdiagnosis fell from 84.6％(11/13) to 50.6％(39/77) in the last 10 years. In 92 cases (60.1％), the level of TSH was elevated [median 1.57×ULN (upper limits of normal)]. The most common elevated hormones associated with TSHomas were growth hormone ( GH) and prolactin ( PRL;11.1％and 9.7％, respectively) . 37 cases underwent octreotide suppression test, of which the inhibitory rates ranged from 26. 2％ to 94. 9％ ( median 71.79％). The detection rate of micro-adenoma was 7.7％(1/13)before year 2000, 11.4％(4/35)from 2000 to 2006, and 26.7％(28/105) after 2006. Although TSHomas usually invade surrounding tissues, they hardly cause pituitary apoplexy. Surgery orγ-knife was performed in 132 cases ( 86. 3％) . Immunohistochemistry of tumors showed that 87 (52.9％) of 46 were pure TSH adenomas and 32 (36.8％) cases were mixed ones, while GH and PRL were most common (75.0％and 56.3％respectively) in the mixed adenomas. Negative immunohistochemistry for TSH was found in 9 cases (10.3％). In the follow-up, the restoring rates of thyroid hormone and TSH level were 77.0％(87/113) and 80.0％( 36/45) respectively. Conclusion TSHoma is diagnosed at an earlier age in China than that reported in Europe and America, while at similar age compared with Japan. Macro-adenomas were more common in spite of the increasing detection rate of micro-adenomas. Macro-adenomas are often invasive but less likely to induce pituitary apoplexy. Immunostaining for TSH could be negative. The most common positive immunostaining in mixed adenoma is GH and/or PRL. However, a positive immunostaining for one pituitary hormone does not necessarily correlates with its hypersecretion of that hormone.