Purpose This study aimed to explore the mucinous phenotype characteristics,key points of differenti-al diagnosis and prognosis of invasive non-mucinous adenocarcinoma(INMA)and invasive mucinous adenocarcinoma(IMA)under the WHO(2021)lung adenocarcinoma classification.Methods We retrospectively collected clinico-pathological data from 522 cases of lung adenocarcinoma,including 425 INMA(66 with mucin secretion,259 without mucin secretion)and 97 IMA.Immunohistochemical(IHC)staining using the EnVision method was performed on the mucin-secreting adenocarcinoma to assess expression of TTF-1,HNF4α,MUC1,MUC4,MUC5AC,MUC5B,and MUC6.Unsupervised clustering analysis was conducted to explore phenotypic subgroups.Results 522 patients with lung adenocarcinoma ranged from 32 to 83 years old(median:61).251 cases(48.1％)were male and 271 cases(51.9％)were female.Clustering analysis divided lung adenocarcinomas into two major groups:one characterized by TTF-1-/HNF4α+and gastric-type mucins MUC5AC+/MUC6+,predominantly IMA;the other,TTF-1+/HNF4α-/MUC4+,largely INMA.A three-marker IHC panel(TTF-1,HNF4α,MUC6)distinguished IMA from mucinous IN-MA with an area under the ROC curve(AUC)of 0.957(95％CI:0.928-0.986)and a Youden's index of 0.860.Further cluster analysis of INMA cases identified four phenotypic subgroups.Prognostic analysis demonstrated that pa-tients with advanced-stage mucin-secreting INMA had significantly shorter overall survival(OS)and progression-free survival(PFS)than those without mucin secretion(5-year OS:57.1％ vs 81.8％,P=0.004;3-year PFS:40.9％ vs 62.4％,P=0.004).No significant survival differences were noted among INMA subgroups stratified by varying mucin proportions.Multivariate analysis identified pathological stage,tumor necrosis,KRAS mutation,and TTF-1 negativity as independent adverse prognostic factors for both OS and PFS in mucinous INMA.Conclusion A three-marker im-munohistochemical panel of TTF-1,HNF4α,and MUC6 is recommended to distinguish IMA from mucinous INMA.Mucus component portends a worse prognosis in advanced INMA,with necrosis,KRAS mutations,and TTF-1 negativi-ty serving as independent adverse prognostic factors in mucinous INMA.

Objective:To investigate the diagnostic efficacy of differentially expressed proteins in the plasma of prostate cancer patients.Methods:Plasma samples were collected from patients who visited the Department of Urology at the Second Affiliated Hospital of Soochow University from January to March 2023. Among them，there were 30 patients with prostate cancer，aged（75.10 ± 9.33）years，with a median serum PSA value of 24.60（5.38，516.00）ng/ml，and 30 patients with benign prostatic hyperplasia，aged（72.90 ± 7.30）years，with a median serum PSA value of 2.21（0.44，4.38）ng/ml Label-free quantitative proteomic technology was used to detect differentially expressed proteins in the plasma. Combined with TCGA transcriptome changes and relevant literature，the differentially expressed candidate proteins with the most significant up-regulation were selected.In addition，prostate biopsy tissue samples were collected from another 14 patients who visited the Department of Urology at the Second Affiliated Hospital of Soochow University from September to November 2023. Among them，there were 8 patients with prostate cancer，aged（72.25 ± 6.52）years，with a median serum PSA value of 74.65（5.63，151.00）ng/ml，and 6 patients with benign prostatic hyperplasia，aged（70.83 ± 5.04）years，with a median serum PSA value of 5.06（3.34，28.70）ng/ml. Immunohistochemical staining was performed using antibodies corresponding to the candidate proteins to analyze the expression differences of the candidate proteins between the 8 prostate cancer cases and the 6 benign prostatic hyperplasia cases.Plasma samples were collected from 44 patients with prostate diseases who visited the Department of Urology at the Second Affiliated Hospital of Soochow University from March to September 2023. Among them，there were 30 patients with prostate cancer，aged（71.58 ± 7.99）years，with a median serum PSA value of 29.85（1.25，108.00）ng/ml，and 14 patients with benign prostatic hyperplasia，aged（69.00 ± 8.94）years，with a median serum PSA value of 1.78（0.61，12.40）ng/ml. Area under the curve（AUC）was calculated to analyze the diagnostic efficacy of each protein for prostate cancer. Detect the expression levels of candidate proteins in plasma by ELISA，draw the ROC curve，calculate the area under the curve（AUC），and analyze the diagnostic efficacy of each protein for prostate cancer.Results:A total of 34 most significant upregulated proteins and 72 downregulated proteins were detected by proteomics and eight proteins were detected by referring to TCGA data and literatures. Percentage of positive cells of SPON2，FGB，PCSK6，ORM1，ORM2，HP，SND1，and SUSD2 in prostate cancer tissues（51.97 ± 10.81，42.97 ± 6.76，49.83 ± 12.46，53.85 ± 11.52，50.46 ± 11.13，39.69 ± 10.96，52.01 ± 13.03，45.92 ± 9.55）were significantly higher than in BPH（36.31 ± 19.87，21.85 ± 10.99，21.59 ± 5.61，20.36 ± 4.75，24.38 ± 11.55，20.75 ± 3.75，23.60 ± 6.51，19.69 ± 8.45）（ P < 0.05）. FGB，HP，and ORM1 were significantly increased in plasma of prostate cancer patients compared to BPH patients（ng/ml）［（689.9 ± 659.7）ng/ml vs.（200.0 ± 127.1）ng/ml，（1.819 ± 0.833）ng/ml vs.（1.126 ± 0.362）ng/ml，（733.5 ± 385.0）ng/ml vs.（344.7 ± 214.6）ng/ml， P < 0.05］，with AUC values 0.803，0.781，and 0.832，respectively. The combined diagnostic efficacy of the three proteins FGB，HP，and ORM1 for prostate cancer is significantly better than that of any single protein（AUC = 0.953），with higher sensitivity（81.48%）and specificity（100.0%）. Conclusions:FGB，HP，ORM1 were significantly increased in plasma of prostate cancer patients compared to BPH patients，indicating higher diagnostic efficacy. The combined diagnostic efficacy FGB，HP，and ORM1 for prostate cancer is significantly better than that of any single protein，and they exhibit higher sensitivity and specificity.

Purpose This study aimed to explore the mucinous phenotype characteristics,key points of differenti-al diagnosis and prognosis of invasive non-mucinous adenocarcinoma(INMA)and invasive mucinous adenocarcinoma(IMA)under the WHO(2021)lung adenocarcinoma classification.Methods We retrospectively collected clinico-pathological data from 522 cases of lung adenocarcinoma,including 425 INMA(66 with mucin secretion,259 without mucin secretion)and 97 IMA.Immunohistochemical(IHC)staining using the EnVision method was performed on the mucin-secreting adenocarcinoma to assess expression of TTF-1,HNF4α,MUC1,MUC4,MUC5AC,MUC5B,and MUC6.Unsupervised clustering analysis was conducted to explore phenotypic subgroups.Results 522 patients with lung adenocarcinoma ranged from 32 to 83 years old(median:61).251 cases(48.1％)were male and 271 cases(51.9％)were female.Clustering analysis divided lung adenocarcinomas into two major groups:one characterized by TTF-1-/HNF4α+and gastric-type mucins MUC5AC+/MUC6+,predominantly IMA;the other,TTF-1+/HNF4α-/MUC4+,largely INMA.A three-marker IHC panel(TTF-1,HNF4α,MUC6)distinguished IMA from mucinous IN-MA with an area under the ROC curve(AUC)of 0.957(95％CI:0.928-0.986)and a Youden's index of 0.860.Further cluster analysis of INMA cases identified four phenotypic subgroups.Prognostic analysis demonstrated that pa-tients with advanced-stage mucin-secreting INMA had significantly shorter overall survival(OS)and progression-free survival(PFS)than those without mucin secretion(5-year OS:57.1％ vs 81.8％,P=0.004;3-year PFS:40.9％ vs 62.4％,P=0.004).No significant survival differences were noted among INMA subgroups stratified by varying mucin proportions.Multivariate analysis identified pathological stage,tumor necrosis,KRAS mutation,and TTF-1 negativity as independent adverse prognostic factors for both OS and PFS in mucinous INMA.Conclusion A three-marker im-munohistochemical panel of TTF-1,HNF4α,and MUC6 is recommended to distinguish IMA from mucinous INMA.Mucus component portends a worse prognosis in advanced INMA,with necrosis,KRAS mutations,and TTF-1 negativi-ty serving as independent adverse prognostic factors in mucinous INMA.

Objective:To investigate the diagnostic efficacy of differentially expressed proteins in the plasma of prostate cancer patients.Methods:Plasma samples were collected from patients who visited the Department of Urology at the Second Affiliated Hospital of Soochow University from January to March 2023. Among them，there were 30 patients with prostate cancer，aged（75.10 ± 9.33）years，with a median serum PSA value of 24.60（5.38，516.00）ng/ml，and 30 patients with benign prostatic hyperplasia，aged（72.90 ± 7.30）years，with a median serum PSA value of 2.21（0.44，4.38）ng/ml Label-free quantitative proteomic technology was used to detect differentially expressed proteins in the plasma. Combined with TCGA transcriptome changes and relevant literature，the differentially expressed candidate proteins with the most significant up-regulation were selected.In addition，prostate biopsy tissue samples were collected from another 14 patients who visited the Department of Urology at the Second Affiliated Hospital of Soochow University from September to November 2023. Among them，there were 8 patients with prostate cancer，aged（72.25 ± 6.52）years，with a median serum PSA value of 74.65（5.63，151.00）ng/ml，and 6 patients with benign prostatic hyperplasia，aged（70.83 ± 5.04）years，with a median serum PSA value of 5.06（3.34，28.70）ng/ml. Immunohistochemical staining was performed using antibodies corresponding to the candidate proteins to analyze the expression differences of the candidate proteins between the 8 prostate cancer cases and the 6 benign prostatic hyperplasia cases.Plasma samples were collected from 44 patients with prostate diseases who visited the Department of Urology at the Second Affiliated Hospital of Soochow University from March to September 2023. Among them，there were 30 patients with prostate cancer，aged（71.58 ± 7.99）years，with a median serum PSA value of 29.85（1.25，108.00）ng/ml，and 14 patients with benign prostatic hyperplasia，aged（69.00 ± 8.94）years，with a median serum PSA value of 1.78（0.61，12.40）ng/ml. Area under the curve（AUC）was calculated to analyze the diagnostic efficacy of each protein for prostate cancer. Detect the expression levels of candidate proteins in plasma by ELISA，draw the ROC curve，calculate the area under the curve（AUC），and analyze the diagnostic efficacy of each protein for prostate cancer.Results:A total of 34 most significant upregulated proteins and 72 downregulated proteins were detected by proteomics and eight proteins were detected by referring to TCGA data and literatures. Percentage of positive cells of SPON2，FGB，PCSK6，ORM1，ORM2，HP，SND1，and SUSD2 in prostate cancer tissues（51.97 ± 10.81，42.97 ± 6.76，49.83 ± 12.46，53.85 ± 11.52，50.46 ± 11.13，39.69 ± 10.96，52.01 ± 13.03，45.92 ± 9.55）were significantly higher than in BPH（36.31 ± 19.87，21.85 ± 10.99，21.59 ± 5.61，20.36 ± 4.75，24.38 ± 11.55，20.75 ± 3.75，23.60 ± 6.51，19.69 ± 8.45）（ P < 0.05）. FGB，HP，and ORM1 were significantly increased in plasma of prostate cancer patients compared to BPH patients（ng/ml）［（689.9 ± 659.7）ng/ml vs.（200.0 ± 127.1）ng/ml，（1.819 ± 0.833）ng/ml vs.（1.126 ± 0.362）ng/ml，（733.5 ± 385.0）ng/ml vs.（344.7 ± 214.6）ng/ml， P < 0.05］，with AUC values 0.803，0.781，and 0.832，respectively. The combined diagnostic efficacy of the three proteins FGB，HP，and ORM1 for prostate cancer is significantly better than that of any single protein（AUC = 0.953），with higher sensitivity（81.48%）and specificity（100.0%）. Conclusions:FGB，HP，ORM1 were significantly increased in plasma of prostate cancer patients compared to BPH patients，indicating higher diagnostic efficacy. The combined diagnostic efficacy FGB，HP，and ORM1 for prostate cancer is significantly better than that of any single protein，and they exhibit higher sensitivity and specificity.

Objective To analyze the risk factors of heart failure in patients with coronary heart disease(CHD),and to construct and verify a nomogram prediction model for the risk of heart failure in patients with CHD.Methods The clinical data of 453 patients with CHD who were hospitalized in the Second Affiliated Hospital of Shenyang Medical College from January to December 2022 were retrospectively analyzed,including 278 patients with CHD combined with heart failure and 175 patients without heart failure.The patients were divided into training group(318 cases)and validation group(135 cases)according to the ratio of 7:3.R software was applied to perform LASSO regression to screen the risk factors,and Logistic regression to establish a prediction model and construct a nomogram.The calibration curve and receiver operating characteristic(ROC)curve were used to evaluate the calibration and discrimination of the model.Results LASSO regression analysis ultimately screened five risk factors from 22 variables,and Logistic regression results showed that age,smoking,history of myocardial infarction,New York Heart Association(NYHA)cardiac function class Ⅳ,and left ventricular ejection fraction(LVEF)were all independent risk factors for heart failure in CHD patients(P＜0.05).The model formula was Z=-2.927+0.045 × age+0.886 × smoking+0.808 × history of myocardial infarction-2.829 × NYHA cardiac function class Ⅳ+0.037×LVFF.Internal validation of the model showed that area under the curve was 0.727(95％CI:0.588-0.752),the sensitivity was 40.4％,the specificity was 84.3％,and the Youden index was 0.247.According to the calibration curve,the predicted value of the calibration curve was highly consistent with the actual value,and the Brier score was 0.106.Conclusion The risk prediction model for heart failure in patients with CHD based on LASSO regression has good discrimination and prediction efficiency,which can be used as an evaluation tool for medical staff to predict the risk of patients.

Objective To explore the clinical value of methylation at promoter sites of urine protein kinase Y-linked(PRKY)gene in the early diagnosis of prostate cancer(PCa).Methods Urine samples were collected from 50 suspected PCa patients.After extracting DNA,the methylation levels of the PRKY gene promoter sites cg05163709,cg08045599,and cg05618150 were detected using quantitative methylation-specific PCR(qMSP).Simultaneously,the patients were divided into the benign prostatic hyperplasia(BPH)group and the PCa group.The differences in clinical indicators between the two groups were analyzed,as well as the methylation status of the PRKY gene promoter sites in the urine of the two groups of patients.The receiver operating charac-teristic(ROC)curve of PRKY promoter sites methylation was established,and the area under the curve(AUC)was calculated to analyze the diagnostic value of PRKY promoter sites methylation in PCa,and to perform com-bined diagnosis with clinical indicators.Results The methylation rates of cg05163709 and cg05618150 in urine specimens of PCa patients were significantly higher than those of BPH patients.The AUC for cg05163709 methyla-tion in diagnosing PCa was 0.762,with a sensitivity of 86.70%.It showed better performance in early screening for PCa compared to total prostate specific antigen(tPSA),percentage free prostate specific antigen(f/tPSA)and prostate specific antigen density(PSAD)index.We found that the AUC for cg05618150 methylation in conjunc-tion with PSAD in diagnosing PCa was 0.787,with a sensitivity of 86.70%.The AUC of cg05163709 methylation and PSAD in the joint diagnosis of PCa was 0.855,and the specificity could reach 95.00%.Conclusion The methylation of urine PRKY gene promoter sites cg05163709 and cg05618150 shows high sensitivity and specificity in diagnosing PCa,making them promising biomarkers for early detection of PCa.

Opioid analgesics are currently known as the best analgesics. However， toxicity and side effects such as constipation， tolerance and addiction severely limit their clinical application. With the in-depth understanding of the signal transduction mechanism of opioid receptors and the continuous advancement of drug design technology， researchers have managed to develop many promising new methods to get low-toxic and more efficient opioid analgesics， which are different from the traditional morphine skeleton structure modifications. This article focuses on three new research strategies of G-protein biased activation，“ one drug-multiple targets” and peripheral activation. The basic principles of relative separation of analgesic activity and adverse drug reaction by each strategy are introduced， and the latest research progress of representative drugs is briefly reviewed. Among them， the recently approved novel opioid analgesics oliceridine and tegileridine are G-protein biased μ-opioid receptor agonists， Cebranopadol is a typical “one drug-multiple targets” analgesic， and NFEPP is a representative drug of peripheral opioid receptor agonists. The above several strategies complement each other and provide reference for the development of new opioid analgesic drugs.

In Vivo Dosimetry ; Radiotherapy Dosage ; Radiometry/methods* ; Electronics ; Radiotherapy, Intensity-Modulated/methods* ; Phantoms, Imaging ; Algorithms

Objective:To explore MRI T 2-mapping and blood oxygenation level dependent (BOLD) to evaluate the functional changes of paraspinal muscle in rats with discogenic low back pain (DLBP) after swimming. Methods:Totally 54 female 1-month-old SD rats were selected, which were divided into 3 groups by random number table method, sham operation (Sham) group, DLBP non-swimming group and DLBP swimming group, with 18 rats in each group. Under the guidance of X-ray fluoroscopy, the L4/5 and L5/6 intervertebral discs of the rats in the DLBP non-swimming group and DLBP swimming group were punctured by the posterior approach, and establishment of DLBP rat model by destroying nucleus pulposus, and only paraspinal muscles at the same level were punctured in the Sham group. After modeling, the DLBP swimming group received swimming exercise intervention for 5 consecutive days (30 min/d), while the DLBP non-swimming group and Sham group did not receive any rehabilitation exercise intervention. Each group was divided into 3 time point subgroups on average, the T 2-mapping and BOLD sequences were scanned at 30, 90 and 180 days after modeling to obtain the T 2 value, R 2* value of the paraspinal muscles, and the paraspinal muscles at the modeling level were taken for immunofluorescence staining, and the fluorescence intensity of myosin heavy chain (MYH)1 (type Ⅱ muscle fiber) and MYH7 (type I muscle fiber) was analyzed. One-way analysis of variance was used for comparison among the 3 groups, and the Bonferroni method was used for multiple comparisons, and Pearson correlation coefficient was used to evaluate the correlation between quantitative MRI parameters T 2 value, R 2* value and MYH1, MYH7 immunofluorescence intensity of rat paraspinal muscles at 180 days after modeling. Results:At 30 days after modeling, there was no significant difference in T 2 value and R 2* value among the 3 groups (all P>0.05). At 90 days after modeling, the T 2 value of the DLBP swimming group was higher than that of the DLBP non-swimming group, and the T 2 value of the DLBP non-swimming group was lower than that of the Sham group (all P<0.05), and there was no significant difference in the R 2* value among the 3 groups ( P>0.05). At 180 days after modeling, the T 2 value of the DLBP swimming group was higher than that of the DLBP non-swimming group, and the R 2* value was lower than that of the DLBP non-swimming group; the T 2 value of the DLBP non-swimming group was lower than that of the Sham group, and the R 2* value was higher than that of the Sham group (all P<0.05). At 30 and 90 days after modeling, there was no significant difference in the expressions of MYH1 and MYH7 among the 3 groups (all P>0.05). At 180 days after modeling, the expression of MYH1 decreased and the expression of MYH7 increased in the DLBP swimming group compared with the DLBP non-swimming group; the expression of MYH1 increased and the expression of MYH7 decreased in the DLBP non-swimming group compared with the Sham group (all P<0.05). At 180 days after modeling, the T 2 value had a moderate negative correlation with the fluorescence intensity of MYH1 ( r=-0.511, P=0.043), and a moderate positive correlation with the fluorescence intensity of MYH7 ( r=0.564, P=0.023); R 2* value was moderate positive correlated with the fluorescence intensity of MYH1 ( r=0.625, P=0.010), and moderate negative correlated with the fluorescence intensity of MYH7 ( r=-0.653, P=0.006). Conclusions:Swimming exercise can improve the reduction of water content and perfusion in the paraspinal muscles of DLBP rats, and reduce the transformation of muscle fibers from type Ⅰ to type Ⅱ, the changes of T 2 and R 2* value can reflect the transformation of paraspinal muscle fiber types to a certain extent.

Long non-coding RNA (lncRNA) is a class of highly conserved transcript with a length of more than 200 nucleotides, which is of great significance for the occurrence, development, diagnosis and treatment of malignant tumors. The abnormal expression of linc01410 in malignant tumors can affect the occurrence and development of malignant tumors by regulating the biological processes such as proliferation, migration and epithelial-mesenchymal transformation of malignant tumor cells, acting on related signaling pathways such as nuclear factor-κB and Notch or through exosome pathways.