Objective:To investigate the risk factors for detecting clinically significant prostate cancer (CSPCa) in patients with Prostate Imaging Reporting and Data System (PI-RADS) score≤3 on multi-parameter magnetic resonance imaging (mpMRI).Methods:Retrospective analysis was performed on the case data of 335 patients with suspected prostate cancer and PI-RADS score ≤3 who were admitted to Beijing Friendship Hospital, Capital Medical University from January 2013 to October 2022. All patients underwent 24-needle prostate biopsy. Clinical data such as age, body mass index, past medical history, serological laboratory indicators, and mpMRI imaging data were collected. The patients were grouped according to whether the puncture pathology was CSPCa or not, and the differences in clinical data between the two groups were analyzed by t-test, rank sum test and Chi-test. Multivariate Logistic regression analysis was further used to determine independent risk factors for MRI invisible prostate cancer, and receiver operating characteristics (ROC) curves were drawn. At the same time, further subgroup analysis was conducted based on whether prostate-specific antigen (PSA) was positive before puncture and PI-RADS score, respectively, and the same statistical method was used to further determine the influence of different serological indicators and PI-RADS score on the analysis results of risk factors. Results:Among all patients, 81 were CSPCa patients and 254 were non-CSPCa patients. Multivariate Logistic regression analysis showed that prostate-specific antigen density (PSAD) and PI-RADS score of 3 were independent risk factors for MRI invisible prostate cancer. At the same time, compared with suspected lesions located only in the transitional zone, the incidence of CSPCa in patients with suspected lesions located in the peripheral zone would increase, and the incidence of CSPCa would further increase when suspected lesions were found in both the transitional zone and the peripheral zone. In PSA-negative patients, only suspected lesion location was an independent risk factor for MRI invisible prostate cancer, while in PSA-positive patients, prostate volume, PSAD, and PI-RADS scores were independent risk factors. In subgroup analysis with different PI-RADS scores, suspicious lesions in both the transitional zone and peripheral zone indicate a higher likelihood of CSPCa. For patients with PI-RADS scores of 1 to 2, suspicious lesions in the peripheral zone alone may also indicated CSPCa, while for patients with PI-RADS scores of 3, the lower free prostate-specific antigen/total prostate-specific anti-principle was more accurate in predicting CSPCa.Conclusions:For patients who are clinically suspected of prostate cancer but whose PI-RADS score is less than or equal to 3 points indicated by mpMRI, it is necessary to further focus on the results of different serological indicators according to whether their PSA is positive and PI-RADS score respectively to judge whether patients should receive systemic prostate puncture, instead of using PSA level as a single indication for puncture. At the same time, clinicians should also pay full attention to the location of suspected lesions, when they are located in the peripheral zone, or there are suspected lesions in both the peripheral zone and the transitional zone, the possibility of CSPCa should be fully considered.

OBJECTIVE: To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A (SV2A) influences the distribution of amyloid precursor protein (APP) in the trans-Golgi network (TGN), endolysosomal system, and cell membranes and to reveal the effects of SV2A on APP amyloid degradation. METHODS: Colocalization analysis of APP with specific tagged proteins in the TGN, ensolysosomal system, and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP. APP, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) expressions, and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing. RESULTS: APP localization was reduced in the TGN, early endosomes, late endosomes, and lysosomes, whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons. Moreover, Arl5b (ADP-ribosylation factor 5b), a protein responsible for transporting APP from the TGN to early endosomes, was upregulated by SV2A. SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis. In addition, products of APP amyloid degradation, including sAPPβ, Aβ _1-42, and Aβ _1-40, were decreased in SV2A-overexpressed cells. CONCLUSION These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway, which slows APP amyloid degradation.
Amyloid beta-Protein Precursor/genetics* ; Membrane Glycoproteins/genetics* ; Animals ; Protein Transport ; Nerve Tissue Proteins/genetics* ; Humans ; Mice ; Endosomes/metabolism* ; trans-Golgi Network/metabolism*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective To compare the effects of different doses of budesonide and formoterol fumarate powder for inhalation combined with montelukast sodium tablet in the treatment of cough variant asthma(CVA)and the improvement of airway function and inflammatory factors.Methods Elderly patients with cough variant asthma were randomly divided into group A and group B.Both groups of patients received budesonide and formoterol fumarate powder for inhalation combined with montelukast sodium tablet.Group A was given budesonide and formoterol fumarate powder for inhalation(Ⅱ),2 inhalation per time,twice a day;Group B was given budesonide and formoterol fumarate powder for inhalation,4 inhalation per time,twice a day;budesonide fumatrol inhalation powder mist for continuous treatment for 6 months,and montelukast sodium tablet 10 mg once a day for at least 3 months.The nighttime cough scores of the two groups were compared before treatment and after treatment.The percentage of forced expiratory volume in one second(FEV1)in the predicted value,the maximum mid expiratory flow(MMEF),the fractional exhaled nitric oxide(FeNO),interleukin-5(IL-5)and eosinophils were compared between the two groups.The incidence of adverse drug reactions and the recurrence rate within 1 year were compared between the two groups.Results A total of 45 cases were enrolled in both the group A and the group B.At 9 months after treatment,the nocturnal cough scores of the group A and the group B were(0.93±0.42)and(0.65±0.29)points,respectively;the percentage of FEV1 in the predicted value were(97.75±9.67)％and(100.93±11.06)％,respectively;the MMEF values were(2.81±1.04)and(3.08±1.09)L·s-1,respectively;the FeNO values were(18.94±9.75)and(15.94±7.96)ppb,respectively;the IL-5 levels were(10.88±7.06)and(8.11±5.56)pg·mL-1,respectively.The above indicators in group B showed statistically significant differences compared to group A(all P＜0.05).The total incidence of adverse drug reactions in group A and group B were 8.89％(5 cases/45 cases)and 13.33％(6 cases/45 cases),respectively.The recurrence rates was 15.56％(7 cases/45 cases)and 13.33％(6 cases/45 cases),respectively.There was no statistically significant difference in the above indicators between group B and group A(all P＞0.05).Conclusion For elderly patients with CVA,higher dose of budesonide and formoterol fumarate powder for inhalation combined with montelukast sodium tablet can better improve cough symptoms,reduce the level of airway hyperresponsiveness and inflammatory factors,reduce the recurrence rate,and the patients are well tolerated.

Objective To compare the effects of different doses of budesonide and formoterol fumarate powder for inhalation combined with montelukast sodium tablet in the treatment of cough variant asthma(CVA)and the improvement of airway function and inflammatory factors.Methods Elderly patients with cough variant asthma were randomly divided into group A and group B.Both groups of patients received budesonide and formoterol fumarate powder for inhalation combined with montelukast sodium tablet.Group A was given budesonide and formoterol fumarate powder for inhalation(Ⅱ),2 inhalation per time,twice a day;Group B was given budesonide and formoterol fumarate powder for inhalation,4 inhalation per time,twice a day;budesonide fumatrol inhalation powder mist for continuous treatment for 6 months,and montelukast sodium tablet 10 mg once a day for at least 3 months.The nighttime cough scores of the two groups were compared before treatment and after treatment.The percentage of forced expiratory volume in one second(FEV1)in the predicted value,the maximum mid expiratory flow(MMEF),the fractional exhaled nitric oxide(FeNO),interleukin-5(IL-5)and eosinophils were compared between the two groups.The incidence of adverse drug reactions and the recurrence rate within 1 year were compared between the two groups.Results A total of 45 cases were enrolled in both the group A and the group B.At 9 months after treatment,the nocturnal cough scores of the group A and the group B were(0.93±0.42)and(0.65±0.29)points,respectively;the percentage of FEV1 in the predicted value were(97.75±9.67)％and(100.93±11.06)％,respectively;the MMEF values were(2.81±1.04)and(3.08±1.09)L·s-1,respectively;the FeNO values were(18.94±9.75)and(15.94±7.96)ppb,respectively;the IL-5 levels were(10.88±7.06)and(8.11±5.56)pg·mL-1,respectively.The above indicators in group B showed statistically significant differences compared to group A(all P＜0.05).The total incidence of adverse drug reactions in group A and group B were 8.89％(5 cases/45 cases)and 13.33％(6 cases/45 cases),respectively.The recurrence rates was 15.56％(7 cases/45 cases)and 13.33％(6 cases/45 cases),respectively.There was no statistically significant difference in the above indicators between group B and group A(all P＞0.05).Conclusion For elderly patients with CVA,higher dose of budesonide and formoterol fumarate powder for inhalation combined with montelukast sodium tablet can better improve cough symptoms,reduce the level of airway hyperresponsiveness and inflammatory factors,reduce the recurrence rate,and the patients are well tolerated.

Objective : To evaluate the prognostic value of a radiomics model based on the peritumoral region of gli- oma． Methods : 138 patients with glioma were retrospectively analyzed ，medical imaging interaction toolkit ( MITK) software was used to obtain the magnetic resonance imaging (MRI) images of peritumoral area 5 mm，10 mm and 20 mm from the tumor edge and extract texture features．The texture features were screened the radiomics model was established and the radiomic score was calculated．A clinical prediction model and a combined predic- tion model along with Rad-score and clinical risk factors were established．The combined prediction model was dis- played as a nomogram，and the predictive performance of the model for survival in glioma patients was evaluated. Results : In the validation set，the C-index value of the radiomics model based on the peritumoral region 10 mm a- way from the tumor edge based on T2 weighted image (T2WI) images was 0. 663 (95% CI = 0. 72－0. 78) ，resul- ting in the best prediction performance．On the training set and validation set，the C-index of the nomogram was 0. 770 and 0. 730，respectively，indicating that the prediction performance of nomogram was better than those of the radiomics model and clinical prediction model．The model had the highest prediction effect on the 3-year survival rate of glioma patients (training set area under curve (AUC) = 0. 93，95% CI = 0. 83 － 0. 98 ; validation set AUC = 0. 88，95% CI = 0. 76 －0. 99) ．The calibration curve showed that the joint prediction nomogram in both the training set and the validation set had good performance． Conclusion The combined prediction model based on the preoperative T2WI images in the peritumoral region 10 mm from the tumor edge and the clinicopathological risk factors can accurately predict the prognosis of glioma，providing the best effect of prediction on the 3-year survival rate of glioma.

Neovascular age-related macular degeneration (nAMD) is one of the main causes of visual impairment in middle-aged and elderly people,and the incidence of this disease is rising in our country.The imbalance of vascular endothelial growth factor (VEGF) is the main cause of nAMD.In addition,various growth factors other than VEGF,complement system activation,inflammatory factors,autophagy,and many other factors are involved in the pathogenesis of nAMD.Currently,intravitreal injection of anti-VEGF drugs has become the first-line regimen for the treatment of nAMD,but there are still many shortcomings of the current anti-VEGF drugs,such as multiple potential risks of frequent injections,insensitive responses in some patients,and low compliance of the patients,etc.Therefore,the search for novel therapeutic agents has become urgent.This article provides a review of new developments in the study of novel drugs newly marketed and undergoing clinical trials for the treatment of nAMD,with the aim of seeking longer-lasting and better-acting therapeutic regimens,as well as exploring new therapeutic targets,to further inform the advancement of innovation and development of therapeutic strategies for nAMD.

Objective To observe the effects of budesonide,glycopyrronium bromide and formoterol fumarate inhalation aerosol on lung function,inflammatory markers,and exercise tolerance in stable chronic obstructive pulmonary disease(COPD)patients.Methods Stable COPD patients were randomly divided into control group and treatment group.The treatment group inhaled budesonide,glycopyrronium bromide and formoterol fumarate inhalation aerosol,1 shovel per time,twice a day,once in the morning and once in the evening;respiratory function exercise for 15 minutes each time,bid.The control group was given budesonide and formoterol fumarate powder for inhalation(Ⅱ),1 shovel each time,bid.The respiratory function exercise method was the same as that of the treatment group.Both groups of patients were treated continuously for 3 months.Compare the clinical efficacy of two groups of patients after treatment,and compare the lung function[forced expiratory volume in one second(FEV1),percentage of FEV1 to expected value(FEV,％),FEV1/forced vital capacity(FVC)],inflammatory indicators[interleukin-6(IL-6),IL-10],immune function indicators[T lymphocyte subsets(CD3+CD4+,CD8+),CD4+/CD8+],exercise tolerance[6-minute walking distance(6MWD),peak oxygen uptake(VO2 peak),maximum metabolic equivalents(METs)],and safety evaluation.Results Fifty cases were enrolled in the treatment group,2 cases were dropped out,and ultimately 48 cases were included in the statistical analysis;50 cases were enrolled in the control group,2 cases were dropped out,and ultimately 48 cases were included in the statistical analysis.The total effective rates of the treatment group and the control group were 91.67％(44 cases/48 cases)and 75.00％(36 cases/48 cases),with significant difference(P＜0.05).After treatment,the FEV1 of the treatment group and the control group were(1.99±0.19)and(1.79±0.21)L,the FEV1％were(64.18±5.85)％and(59.81±5.02)％,the FEV1/FVC were 61.82±5.37 and 53.45±6.11,the IL-6 levels were(19.53±4.08)and(27.82±4.57)ng·L-1,the IL-10 levels were(22.49±3.71)and(17.69±3.05)ng·L-1,the CD3+levels were(67.11±5.09)％and(64.20±4.26)％,the CD4+levels were(38.76±2.89)％and(36.15±3.04)％,the CD8+levels were(27.28±2.35)％and(28.76±2.59)％,the CD4+/CD8+were 1.49±0.28and 1.30±0.22,the 6MWD were(421.07±31.46)and(391.89±30.44)m,the VO2peak were(20.22±1.47)and(17.66±1.41)mL·min-1·kg-1,the METs were 5.61±1.02 and 4.86±1.04,respectively,the differences were statistically significant(all P＜0.05).The adverse drug reactions in the treatment group included palpitations and headache;the adverse drug reactions in the control group included palpitations,headache and hoarseness.The total incidences of adverse drug reactions in the treatment group and the control group were 6.25％(3 cases/48 cases)and 6.25％(3 cases/48 cases),without statistically significant difference(P＞0.05).Conclusion Budesonide,glycopyrronium bromide and formoterol fumarate inhalation aerosol combined with respiratory function exercise has significant therapeutic effects and good safety in stable COPD patients.

Objective To observe the effects of budesonide,glycopyrronium bromide and formoterol fumarate inhalation aerosol on lung function,inflammatory markers,and exercise tolerance in stable chronic obstructive pulmonary disease(COPD)patients.Methods Stable COPD patients were randomly divided into control group and treatment group.The treatment group inhaled budesonide,glycopyrronium bromide and formoterol fumarate inhalation aerosol,1 shovel per time,twice a day,once in the morning and once in the evening;respiratory function exercise for 15 minutes each time,bid.The control group was given budesonide and formoterol fumarate powder for inhalation(Ⅱ),1 shovel each time,bid.The respiratory function exercise method was the same as that of the treatment group.Both groups of patients were treated continuously for 3 months.Compare the clinical efficacy of two groups of patients after treatment,and compare the lung function[forced expiratory volume in one second(FEV1),percentage of FEV1 to expected value(FEV,％),FEV1/forced vital capacity(FVC)],inflammatory indicators[interleukin-6(IL-6),IL-10],immune function indicators[T lymphocyte subsets(CD3+CD4+,CD8+),CD4+/CD8+],exercise tolerance[6-minute walking distance(6MWD),peak oxygen uptake(VO2 peak),maximum metabolic equivalents(METs)],and safety evaluation.Results Fifty cases were enrolled in the treatment group,2 cases were dropped out,and ultimately 48 cases were included in the statistical analysis;50 cases were enrolled in the control group,2 cases were dropped out,and ultimately 48 cases were included in the statistical analysis.The total effective rates of the treatment group and the control group were 91.67％(44 cases/48 cases)and 75.00％(36 cases/48 cases),with significant difference(P＜0.05).After treatment,the FEV1 of the treatment group and the control group were(1.99±0.19)and(1.79±0.21)L,the FEV1％were(64.18±5.85)％and(59.81±5.02)％,the FEV1/FVC were 61.82±5.37 and 53.45±6.11,the IL-6 levels were(19.53±4.08)and(27.82±4.57)ng·L-1,the IL-10 levels were(22.49±3.71)and(17.69±3.05)ng·L-1,the CD3+levels were(67.11±5.09)％and(64.20±4.26)％,the CD4+levels were(38.76±2.89)％and(36.15±3.04)％,the CD8+levels were(27.28±2.35)％and(28.76±2.59)％,the CD4+/CD8+were 1.49±0.28and 1.30±0.22,the 6MWD were(421.07±31.46)and(391.89±30.44)m,the VO2peak were(20.22±1.47)and(17.66±1.41)mL·min-1·kg-1,the METs were 5.61±1.02 and 4.86±1.04,respectively,the differences were statistically significant(all P＜0.05).The adverse drug reactions in the treatment group included palpitations and headache;the adverse drug reactions in the control group included palpitations,headache and hoarseness.The total incidences of adverse drug reactions in the treatment group and the control group were 6.25％(3 cases/48 cases)and 6.25％(3 cases/48 cases),without statistically significant difference(P＞0.05).Conclusion Budesonide,glycopyrronium bromide and formoterol fumarate inhalation aerosol combined with respiratory function exercise has significant therapeutic effects and good safety in stable COPD patients.

Public exposure to radon has attracted increasing public concern. The newly issued "Standards for indoor air quality (GB/T 18883-2022)" has revised the radiological parameters of radon. This study analyzed and discussed the relevant technical contents about the derivation of radon limit, including the distribution level for indoor radon, exposure pathway, health effects, and the process for establishing the standard limits. Specific implementation and evaluation suggestions are also proposed.
Humans ; Radon/analysis* ; Air Pollution, Indoor ; China ; Housing