We propose a strategy to reduce unnecessary prostate biopsies in Chinese patients with total prostate-specific antigen (tPSA) >10 ng ml -1 and Prostate Imaging Reporting and Data System (PI-RADS) scores between 1 and 3. Clinical data derived from 517 patients of The First Affiliated Hospital of USTC (Hefei, China) from January 2020 to December 2023 who met the screening criteria for the study were retrospectively collected. Independent predictors were identified via univariate and multivariate logistic regression analysis. The diagnostic capacity of clinical variables was evaluated using the receiver operating characteristic (ROC) curves and area under the curve (AUC). A prostate biopsy strategy was developed via risk stratification. Of the 517 patients, 17/348 (4.9%) with PI-RADS 1-2 were diagnosed with clinically significant prostate cancer (csPCa), and 27/169 (16.0%) patients with PI-RADS 3 were diagnosed with csPCa. The appropriate prostate-specific antigen density (PSAD) cut-off values were 0.45 ng ml -2 for PI-RADS 1-2 patients and 0.3 ng ml -2 for PI-RADS 3 patients. The appropriate prostate volume (PV) cut-off values were 40 ml for PI-RADS 1-2 patients and 50 ml for PI-RADS 3 patients. The prostate biopsy strategy based on PSAD and PV developed in this study can reduce unnecessary prostate biopsies in patients with tPSA >10 ng ml -1 and PI-RADS 1-3. In the study, 66.5% (344/517) patients did not need to undergo prostate biopsy, at the expense of missing only 1.7% (6/344) patients with csPCa.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Prostate-Specific Antigen/blood* ; Aged ; Middle Aged ; Retrospective Studies ; Prostate/diagnostic imaging* ; Unnecessary Procedures/statistics & numerical data* ; Biopsy/statistics & numerical data* ; China ; ROC Curve

BACKGROUND: The association of systemic inflammatory response index (SIRI) with prognosis of coronary artery disease (CAD) patients has never been investigated in a large sample with long-term follow-up. This study aimed to explore the association of SIRI with all-cause and cause-specific mortality in a nationally representative sample of CAD patients from United States. METHODS: A total of 3386 participants with CAD from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included in this study. Cox proportional hazards model, restricted cubic spline (RCS), and receiver operating characteristic curve (ROC) were performed to investigate the association of SIRI with all-cause and cause-specific mortality. Piece-wise linear regression and sensitivity analyses were also performed. RESULTS: During a median follow-up of 7.7 years, 1454 all-cause mortality occurred. After adjusting for confounding factors, higher lnSIRI was significantly associated with higher risk of all-cause (HR = 1.16, 95% CI: 1.09-1.23) and CVD mortality (HR = 1.17, 95% CI: 1.05-1.30) but not cancer mortality (HR = 1.17, 95% CI: 0.99-1.38). The associations of SIRI with all-cause and CVD mortality were detected as J-shaped with threshold values of 1.05935 and 1.122946 for SIRI, respectively. ROC curves showed that lnSIRI had robust predictive effect both in short and long terms. CONCLUSIONS SIRI was independently associated with all-cause and CVD mortality, and the dose-response relationship was J-shaped. SIRI might serve as a valid predictor for all-cause and CVD mortality both in the short and long terms.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Objective To analyze the sensitivity of ARHGAP8 in predicting the efficacy of neoadjuvant chemotherapy in the patients with locally advanced mid-low colorectal cancer and provide accurate evidence for the treatment of advanced colorectal cancer.Methods The differentially expressed gene ARHGAP8 was screened out by bioinformatics analysis.Cancer tissue and rectal tissue of 68 patients with primary rectal cancer were select-ed.The rectal cancer tissue samples and the rectal tissue samples were collected for clinical validation of ARH-GAP8 expression by quantitative real-time PCR,Western blotting,and immunohistochemistry.The clinical and pathological features such as gender,age,tumor stage,differentiation degree,and pathological type of the pa-tients were collected for functional validation.Forty-four patients with locally advanced mid-low rectal cancer who received neoadjuvant chemotherapy were selected for immunohistochemical examination of ARHGAP8 expres-sion.The expression level of ARHGAP8 was compared between before and after chemotherapy and among different efficacy groups.Results The bioinformatics analysis revealed differences in the expression level of ARHGAP8 between the cancer tissue and rectal tissue(P＜0.001).The expression level of ARHGAP8 was correlated with tumor stage(P=0.024),lymph node metastasis(P=0.007),and age(P=0.005).Quantitative real-time PCR results showed that the mRNA level of ARHGAP8 in the cancer tissue was higher than that in the rectal tis-sue(P＜0.001).Western blotting and immunohistochemistry results demonstrated that the protein level of ARH-GAP8 in the cancer tissue was higher than that in the rectal tissue(P=0.011).The expression of ARHGAP8 was correlated with tumor size(P=0.010)and pathological stage(P=0.005),while it showed no significant association with tumor differentiation degree,lymph node metastasis,liver metastasis,Ki-67,or microsatellite instability expression level.The 44 patients receiving neoadjuvant chemotherapy included 13,8,8,and 15 pa-tients of tumor regression grades 0,1,2,and 3,respectively.Among them,65.91％(29/44)patients showed responses to the treatment.After neoadjuvant chemotherapy,the expression of ARHGAP8 in the cancer tissue was down-regulated in the patients who responded to the chemotherapy(P＜0.001).The response rate in the patients with low protein level of ARHGAP8 was 92.86％,which was higher than that(53.33％)in the patients with high pro-tein level of ARHGAP8(P=0.033).Conclusions ARHGAP8 is highly expressed in the rectal cancer tissue.The pa-tients with locally advanced mid-low rectal cancer and low ARHGAP8 expression are more sensitive to neoadjuvant chemotherapy with the XELOX protocol.ARHGAP8 can serve as a potential biomarker for the occurrence and develop-ment of rectal cancer and an important index for evaluating the efficacy of neoadjuvant chemotherapy with the XELOX protocol in the patients with locally advanced mid-low rectal cancer.

Tumor-associated macrophages(TAMs)are the predominant cell group in the tumor microenvironment(TME)and are the most important regulatory cells of immune system suppression and tumor cell proliferation in TIME.Src homology-2 domain-containing protein tyrosine phosphatase 2(SHP-2)is a non-receptor protein tyrosine phosphatase that plays an important role in the transmission of signals from the cell surface to the nucleus.SHP-2 is a key intracellular regulatory factor mediating cell proliferation and differentiation and is involved in a variety of growth factor and cytokine signaling pathways linking the cell surface to the nucleus.Recent studies have shown that SHP-2 is a key enzyme in determining the function of TAMs,but because of its variable function,it plays different or even opposite roles in different solid TMEs.This paper reviews the function of SHP-2 in TAMs and related solid tumors to provide a comprehensive reference for tumor immunity and targeted therapy research.

Objective:To analyze the efficacy and safety of daratumumab plus dexamethasone in the treatment of renal injury patients with light chain amyloidosis, and to provide clinical reference.Methods:It was a single center retrospective observational study. The clinical data before and after daratumumab treatment of renal injury patients with light chain amyloidosis treated with daratumumab plus dexamethasone from December 2021 to August 2022 were retrospectively collected. The hematologic response, kidney response, prognosis, and adverse events were analyzed. The treatment regimen was 16 mg/kg intravenous infusion of daratumumab on day 1 + 20 mg intravenous push of dexamethasone on day 1-2, once every 2 weeks. The follow-up was up to February 28, 2023.Results:The study included 18 patients, with age of (58.4±7.7) years old, and a male to female ratio of 11∶7. Eleven patients were newly diagnosed and 7 patients were retreated. There were 7, 5, 5 and 1 patients, respectively at the stage Ⅰ, Ⅱ, Ⅲ and Ⅳ of light chain amyloidosis according to 2012 Mayo stage criteria. The median course of disease before onset was 2.5 (1.0, 8.0) months and the follow-up time was (8.7±2.8) months. The patients received (10±3) times of treatment. The overall hematologic response rates were 9/13, 11/13 and 13/13 at 1 month, 3 months, and 6 months respectively after treatment, meanwhile 8/13, 10/13 and 12/13 achieved at least very good partial response at 1 month, 3 months, and 6 months respectively (the other 5 patients did not undergo detailed evaluation due to baseline difference of serum free κ and λ light chain <20 mg/L). The median duration of hematologic response was 16 (13, 40) days. At 3 months, 6 months and the end of follow-up, 10, 13 and 13 of 18 patients respectively achieved renal response, and the median duration of response was 66 (26, 182) days. During follow-up, the median difference of serum free κ and λ light chain decreased by 93% (72%, 97%). Until the last follow-up, one patient died of organ hemorrhage. Other infusion reactions, leukopenia, neutropenia and infection all improved after symptomatic treatments.Conclusion:Daratumumab plus dexamethasone treatment is effective for light chain amyloidosis nephropathy in inducing hematologic remission and kidney remission, with good safety.

CD200 and its receptor CD200R constitute an endogenous inhibitory signal. The binding of CD200 and CD200R can regulate the immune response to pathogenic stimuli, which has received much attention in recent years. It has been found that CD200-CD200R is involved in the regulation of many kinds of pathological inflammation, including autoimmune diseases, cardiac cerebrovascular disease, infection and tumor. This paper reviews the protein structure, distribution, expression, biological function of CD200-CD200R and the correlation with diseases, and analyses the current status and development ideas of CD200-CD200R as drug targets. It aims to provide theoretical support for new drug research and development based on this target.

Objective:To investigate the current situation of fall fear in elderly patients after operation of intertrochanteric fracture, analyze the influencing factors and build a prediction model.Methods:A prospective cohort study and convenient sampling method were used to select 303 elderly patients with intertrochanteric fracture after surgery in the Department of Orthopedics, Affiliated Hospital of Jining Medical University from January 2021 to December 2022 as the modeling group. According to the scores of fall fear when getting out of bed for the first time, they were divided into 211 cases in the fall fear group and 92 cases in the non-fall fear group. Multivariate Logistic regression was used to analyze the influencing factors of fall fear after operation of femoral intertrochanteric fracture in elderly patients, and a risk prediction score model was established. ROC curve was used to evaluate the differentiation of the model, calibration chart was used to evaluate the calibration degree of the model, and Bootstrap method was used for internal verification. Data of 81 elderly patients with intertrochanteric fracture treated from January to May 2023 were collected as a validation set for external verification of the model.Results:A total of 6 influencing factors were included in the prediction of fall fear risk model for elderly patients after operation of intertrochanteric fracture: gender ( OR = 3.229, 95% CI 1.672 - 6.401), number of co-existing diseases ( OR = 9.578, 95% CI 4.532 - 20.245), pain ( OR = 1.684, 95% CI 1.074 - 2.463), depression ( OR = 1.719, 95% CI 1.371 - 2.155), social support ( OR = 0.859, 95% CI 0.784 - 0.942), and ability to perform activities of daily living ( OR = 0.960, 95% CI 0.932 - 0.989) (all P<0.05). The area under ROC curve of the prediction model was 0.853, the sensitivity was 0.896, and the specificity was 0.663. The area under the externally verified ROC curve was 0.766, the sensitivity was 0.800, and the specificity was 0.645. The calibration curve was close to the reference curve in the model prediction, indicating that the model hasd a good prediction effect. Conclusions:The prediction effect of this model is good, and it can quickly predict the risk of fall fear in elderly patients after operation of intertrochanteric fracture, and provide a basis for medical personnel to provide timely intervention measures.

Aim To explore the efficacy of levosimendan on hypoxia pulmonary hypertension through animal experiments, and to further explore the potential mechanism of action using network pharmacological methods and molecular docking technique. Methods The rat model of hypoxia pulmonary hypertension was constructed to detect right heart systolic pressure and right heart remodeling index. HE , Masson, and VG staining were core targets were screened out. GO and KEGG pathway enrichment analysis were performed using the DAVID database. Molecular docking of the core targets was performed with the AutoDock software. Results The results of animal experiments showed that levosimendan had obvious therapeutic effect on hypoxia pulmonary hypertension. The network pharmacology results showed that SRC, HSP90AA1, MAPK1, PIK3R1, AKT1, HRAS, MAPK14, LCK, EGFR and ESR1 used to analyze the changes of rat lung histopathology. Search the Swiss Target Prediction, DrugBank Online, BatMan, Targetnet, SEA, and PharmMapper databases were used to screen for drug targets. Disease targets were retrieved from the GeneCards, OMIM databases. The "drug-target-disease" network was constructed after identification of the two intersection targets. The protein interaction network was constructed and the were the key targets to play a therapeutic role. Molecular docking showed good docking of levosimendan with all the top five core targets with degree values. Conclusions Levosimendan may exert a therapeutic effect on hypoxia-induced pulmonary hypertension through multiple targets.