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【Objective】 To evaluate the predictive value of isoform [-2] proprostate-specific antigen, p2 PSA (p2PSA) and its derived indexes for prostate cancer in a Chinese cohort with PSA 4-20 ng/mL. 【Methods】 A total of 139 males scheduled for biopsy were enrolled in the prospective study from Nov.2021 to Jun.2022. The total PSA (tPSA), free PSA (fPSA), fPSA/tPSA (f/t) and p2PSA were collected, and the percentage of p2PSA(%p2PSA) and prostate health index(PHI) were calculated. The predictive value of p2PSA and its derived indexes were compared with traditional indexes with receiver operating characteristic (ROC) curve and Logistic analysis. 【Results】 Prostate cancer was found in 54 cases (38.8%). There were significant statistical differences in tPSA(10.68 vs.8.14, P=0.021), f/t(0.13 vs.0.16, P=0.006), p2PSA(30.25 vs.19.81, P<0.001), %p2PSA(21.52 vs.13.15, P<0.001) and PHI(64.3vs.38.2, P<0.001) between prostate cancer patients and non-prostate cancer patients. The area under the ROC curve (AUC) of tPSA, fPSA, %fPSA, p2PSA, %p2PSA and PHI were 0.63, 0.51, 0.63, 0.71, 0.73, and 0.80, respectively. The inclusion of %p2PSA and PHI significantly increased the prediction efficiency of the basic prediction model (AUCbase+PHI=0.81, AUCbase+%p2PSA=0.78, AUCbase=0.67). With 35 as the recommended cut-off value of PHI, the incidence of meaningless puncture was reduced by 25.8%(36/139). 【Conclusion】 The application of p2PSA and its derived indexes have good predictive value for patients with PSA 4-20 ng/mL. The combined detection of %p2PSA and PHI can significantly increase the detection efficiency of prostate cancer and reduce the incidence of meaningless prostate puncture by 25.8%.
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【Objective】 To explore the expressions of PBRM1 and PD-L1 in renal cell carcinoma (RCC), and the molecular mechanism of PBRM1 regulating PD-L1, in order to provide experimental results for clinical immunotherapy. 【Methods】 The protein expressions of PBRM1 and PD-L1 were detected with immunohistochemistry, and their mRNA expressions were determined by analyzing TCGA database. Meanwhile, the relationship between overall survival and mRNA expressions of PBRM1 and PD-L1 were analyzed in TCGA database. The exosomes were extracted with exoEasy Maxi Kit. Expressions of exosomal biomarkers CD63 and CD9 were detected with Western blotting, and their morphology was observed with transmission electron microscope. PD-L1 expression after IFN-γ, IL-6 and TNF-α treatment was detected with Western blotting. 【Results】 The expression of PBRM1 was significantly lower in canver tissue than in paracancerous tissue (P<0.001). The loss rate of PBRM1 was up to 76.4%. PBRM1 expression was not correlated with PD-L1 expression. PBRM1 deletion activated TNF-α/exosome signaling pathway, leading to increase of PD-L1 secretion in exosomes, which was then transported to the outside of cells. 【Conclusion】 There is no relationship between PBRM1 and PD-L1 protein expressions in RCC. However, PBRM1 mutation can lead to inflammatory signaling pathway activation, inducing PD-L1 secretion, which is encapsulated in exosomes and transported to the outside of cells, and affects the response of immunotherapy.
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OBJECTIVE：To study the effec ts of Tibetan Codonopsis tralictrifolia extract （called“ZDS”for short ） on collagen-induced arthritis （CIA）model rats and its mechanism. METHODS ：Eight of 48 rats were randomly selected as normal control group （normal saline ），and the remaining 40 rats were used to establish CIA model. After successful modeling ，the rats were randomly divided into model group （normal saline ），ZDS low-dose ，medium-dose and high-dose groups （0.44，0.88，1.76 g/kg，by crude drug ），dexamethasone group （positive control ，0.002 5 g/kg），with 8 rats in each group. They were given relevant medicine intragastrically ，the volume of 400 μL，once a day ，for consecutive 28 days. The body weight of rats were weighed before medication （0 d），7，14，21 and 28 days after medication ；and arthritis indexes were scored. The pathological changes of the knee joint synoviual tissue were observed after last medication. The thymus index ，spleen index ，the levels of serum inflammatory factors （IL-1β，TNF-α，IL-6），protein expressions of NF-κB p65，p-NF-κB p65，IκB and p-IκB in synovial tissue were detected. RESULTS ：Compared with normal control group ，the body weight （14，21，28 days after administration ）of rats in model group was significantly reduced （P＜0.05）；the arthritis index score （before administration and different administration time）was significantly increased （P＜0.05）；the joint synovial tissue was pathologically damaged ；the thymus and spleen index ， inflammation factor level ，the protein expression of p-NF-κB p65 and p-IκB were increased significantly（P＜0.05），while the protein expression of IκB was decreased significantly（P＜0.05）. Compared with model group ，the level of IL- 1β was decreased significantly in ZDS low-dose group （P＜0.05）. Body weight of rats （21，28 days after administration ）were increased significantly in ZDS medium-dose and high-dose groups ，dexamethasone group （P＜0.05），while arthritis index score （14，21，28 days after administration ） was decreased significantly （P＜0.05）. The pathological damage of joint synovial tissue was significantly relieved ；thymus and spleen index ，inflammation factor level ，the protein expression of p-NF-κB p65 and p-IκB were significantly reduced，while the protein expression of IκB was significantly increased （P＜0.05）. CONCLUSIONS ：ZDS can improve CIA model rats to some extent ，and its mechanism may be related to the inhibition of NF-κB signaling pathway.
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OBJECTIVE：To study the anti-oxidation and an ti-hypoxia effect of Yuanshen granule on normal mice. METHODS ： Totally 800 mice were randomly divided into blank control group ，Yuanshen granule low-dose ，middle-dose and high-dose groups （10，20，40 g/kg）and Hongjingtian oral liquid group （positive control ，2 mL/kg），with 160 mice in each group. Administration groups were given relevant medicine intragastrically ，once a day ，for consecutive 30 d. Blank control group was given constant volume of normal saline by the same method. At 1st，3rd，7th，14th and 30th day after administration ，8 mice in each group at each time point were randomly selected for anoxia tolerance test under normobaric pressure and decompression ；the contents of MDA and SOD in myocardium and cerebral tissue were measured ；the hemolysis effect of red blood cell induced by H 2O2 was investigated. RESULTS ：Compared with blank control group ，the survival time of anoxia tolerance under normobaric pressure and under decompression （after 7 days of administration ）were prolonged significantly in Yuanshen granule groups （P＜0.05）. The contents of MDA in myocardium and cerebral tissue （after 3 or 7 days of administration ；after 3，7 or 14 days of administration ） were significantly decreased （P＜0.05），and the contents of SOD （after 7，14 or 30 days of administration ；after 7 days of administration）were increased significantly （P＜0.05）；the erythrocyte hemolysis rate （after 3 or 7 days of administration ）was significantly decreased （P＜0.05）. At some time points ，the improvement effect of the above indexes in the Yuanshen granule middle-dose and high-dose groups was significantly better than that of Hongjingtian oral liquid group （P＜0.05）. CONCLUSIONS ： Yuanshen granule can effectively prolong the hypoxia tolerance survival time of normal mice ，it has anti-oxidant and anti-hypoxia effects on normal mice ，and the effect of Yuanshen granule middle-dose and high-dose groups is better than that of Hongjingtian oral liquid group.
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OBJECTIVE： To study the efficacy enhancing effect of compatibility of Aconitum carmichaeli liposoluble alkaloids and total glucosides of peony in the treatment of wind-cold-dampness type bi-syndrome model rats. METHODS： Totally 100 SD male rats were randomly divided into blank group （water）， model group （water）， rotundine group [positive control， 10.0 mg/（kg·d）]， dexamethasone group [positive control， 0.3 mg/（kg·d）]，A. carmichaeli alkaloids low-dose and high-dose groups [A. carmichaeli liposoluble alkaloid extract 12.5， 25.0 mg/（kg·d）]， total glucosides of peony low-dose and high-dose groups [total glucosides of peony powder 200.0，400.0 mg/（kg·d）]， compatibility low-dose and high-dose groups [A. carmichaeli liposoluble alkaloid+total glucosides of peony powder were 12.5 mg/（kg·d）+400.0 mg/（kg·d）， 25.0 mg/（kg·d）+800.0 mg/（kg·d） respectively]， with 10 rats in each group. Except for blank group， other groups were given complete Freund’s adjuvant 0.1 mL on the right hind paw and wind-cold-dampness stimulation to induce wind-cold-dampness type bi-syndrome model. Nineteen days after modeling， they were given relevant medicine or water intragastrically， once a day， for consecutive 14 d. The joint tenderness threshold （except for dexamethasone group） and joint swelling index （except for rotundine group） were measured at 0 （before medication）， 3rd and 6th day after administration respectively. HE staining was used to observe the pathological changes of synovial membrane of ankle joint in rats （except for rotundine group）. ELISA assay was used to determine anti-cyclic citrullinated peptide （CCP） antibody in serum of rats （except for rotundine group）， and compatibility index （CI） were calculated. RESULTS： Compared with blank group， joint tenderness threshold of rats were decreased significantly in model group at different time points， while joint swelling index was increased significantly （P＜0.01）. Inflammatory lesions in synovial tissue were obvious， and the content of anti-CCP antibody in serum was significantly increased （P＜0.01）. Compared with model group， the joint tenderness threshold， joint swelling index， synovial tissue pathological changes and anti-CCP antibody content in serum of rats in medication groups were improved in varying degrees， most of the indicators had significant difference （P＜0.05 or P＜0.01）， and the improvement effect of the compatibility groups was better than single component treatment groups. CI value calculated based on anti-CCP antibody content was 0.213，suggesting that the compatibility of the two components had synergistic effect. CONCLUSIONS： The compatibility of A. carmichaeli liposoluble alkaloids and total glucosides of peony in the treatment of wind-cold-dampness type bi-syndrome model rats has analgesia，anti-inflammation and synovial tissue protection， with synergistic efficacy-enhancing effect.
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Objective To evaluate the effect of 131 iodine(131I) therapy in medium and large goiter with hyperthyroidism in order to investigate the influence of pretreatment with antithyroid drugs (ATD) methimazole(MMI) and propylthiouracide (PTU) on 131I therapy.Methods A total of 338 hyperthyroidism patients (136 cases for male,202 cases for female) with thyroid mass greater than 40 grams were treated with 131I in the People's Hospital of Sichuan Province.Thyroid function,thyroid 131I uptake ratio and thyroid imaging were measured before treatment were measured 1-3 months later after administration of 131I,and they were followed up for 6 months to 4 years.Results There were statistical difference between pretreatment and 3 months later of 131I therapy in terms of free triiodothyronine (FT3),(Free thyroxine) FT4.The level of FT3 decreased from (31.9 ± 16.2) pmol/L to (7.8 ±8.5) pmol/L(t =23.9,P =0.000) and level of FT4 decreased from (58.8 ± 22.2) pmol/L to (19.4 ± 16.9) pmol/L(t =25.4,P =0.000).Among 338 patients,109 patients (32.2％) were developed hypothyroidism,and 91 patients (26.9％) were cured,91patients (26.9％) with improved state,20 patients(5.9％) with ineffective and 27 patients(8.0％) with relapse after administration of 131I.The total effective rate was 94.1％ (318/338).Thyroid weight,levels of FT3,FT4,thyroglobulin antibody(TGA),thyroid microsomal antibody(MCA) in effective group were (49.8 ± 9.97) g,(32.5 ± 16.3) pmol/L,(59.5 ± 22.2) pmol/L,(43.6 ± 35.3) ％,(30.1 ± 22.6) ％ respectively,and were (56.9±15.7) g,(22.8 ± 12.8) pmol/L,(47.9 ±20.3) pmol/L,(22.8±30.0)％,(15.3 ±20.5)％ respectively in ineffective group.There were statistically significant differences between the ineffective group and effective group (t =2.932,2.602,2.287,2.501,2.766 ; P =0.000,0.010,0.023,0.013,0.006).Logistic regression analysis was showed that weight of thyroid and serum FT3 were the most important factors in affecting 1131 therapy.Conclusion 131 I therapy for medium and large-sized goiter with hyperthyroidism is safe and effective.ATD may not reduce the effectiveness of subsequent 131I of hyperthyroidism.Thyroid weight and FT3 are the key influential factors in affecting 131I.
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Objective: To observe the effectiveness of neltimicin sulfate in treating the infections of lower respiratory tract. Methods: 41 cases of lower respiratory tract infections served as observation subjects (treated with netilmicin sulfate 200 mg*d-1, iv drip) while the other 30 cases as control subjects (treated with penicillin 8×109 U*d-1 and ampicillin 8.0 g*d-1, iv drip). Results: The therapeutic effectiveness was significantly higher in the observation group than that in the control group (P＜0.01). The sensitivity tests of isolates from the sputum showed that 71.1% of the isolates were highly sensitive to netilmicin sulfate, 28.9% moderately sensitive to netilmicin sulfate. The total effectiveness rate was 97.6%. Conclusion: Netilmicin sulfate is effective in treating the lower respiratory tract infections and causes less side effects.