Objective： The aim of this study is to explore the predictive value of biparametric magnetic resonance imaging(bpMRI)for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L and establish a nomogram. Methods： The imaging data and clinical data of 363 patients undergoing radical prostatectomy and pelvic lymph node dissection in the First Affiliated Hospital of Nanjing Medical University from July 2018 to December 2023 were retrospectively analyzed. Univariate analysis and multivariate logistic regression were used to screen independent risk factors for pelvic lymph node metastasis in prostate cancer, and a nomogram of the clinical prediction model was established. Calibration curves were drawn to evaluate the accuracy of the model. Results： Multivariate logistic regression analysis showed extrocapusular extension (OR=8.08,95%CI=2.62－24.97, P<0.01), enlargement of pelvic lymph nodes (OR=4.45,95%CI=1.16－17.11,P=0.030), and biopsy ISUP grade(OR=1.97,95%CI=1.12－3.46, P=0.018)were independent risk factors for pelvic lymph node metastasis. The C-index of the prediction model was 0.834, which indicated that the model had a good prediction ability. The actual value of the model calibration curve and the prediction probability of the model fitted well, indicating that the model had a good accuracy. Further analysis of DCA curve showed that the model had good clinical application value when the risk threshold ranged from 0.05 to 0.70.Conclusion： For prostate cancer patients with PSA≤20 μg/L, bpMRI has a good predictive value for the pelvic lymph node metastasis of prostate cancer with extrocapusular extension, enlargement of pelvic lymph nodes and ISUP grade≥4.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Lymphatic Metastasis ; Retrospective Studies ; Nomograms ; Prostate-Specific Antigen/blood* ; Lymph Nodes/pathology* ; Pelvis ; Predictive Value of Tests ; Prostatectomy ; Lymph Node Excision ; Risk Factors ; Magnetic Resonance Imaging ; Logistic Models ; Middle Aged ; Aged

The development of anticancer drugs to treat triple-negative breast cancer (TNBC) is an ongoing challenge. Immunogenic cell death (ICD) has garnered considerable interest worldwide as a promising synergistic modality for cancer chemoimmunotherapy. However, only few drugs or treatment modalities can trigger an ICD response and none of them exert a considerable clinical effect against TNBC. Therefore, new agents with potentially effective chemoimmunotherapeutic response are required. In this study, five new cyclometalated Ir(III) complexes containing isoquinoline alkaloid CˆN ligands were designed and synthesized. Among them, Ir-1 exhibited the highest in vitro cytotoxicity. Mechanistically, Ir-1 could trigger autophagy-dependent ferroptosis and a subsequent ferroptosis-dependent ICD response as well as indoleamine 2,3-dioxygenase (IDO) inhibition via reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress in MDA-MB-231 cells. When immunocompetent BALB/c mice were vaccinated with Ir-1-treated dying TNBC cells, antitumor CD8⁺ T-cell response and Foxp3⁺ T-cell depletion were induced, resulting in long-lasting antitumor immunity in TNBC cells. Moreover, combination therapy with Ir-1 and anti-PD1 could substantially augment in vivo therapeutic effects. Based on these results, Ir-1 is a promising candidate for chemoimmunotherapy against TNBC and its effects are mediated synergistically via ICD induction and IDO blockage.

AIM:To investigate the preventive and therapeutic effects of sesamin(SES)on fatty liver disease in rats with hypertension combined with dyslipidemia,and to explore the potential mecha-nisms based on mRNA-seq.METHODS:Spontane-ously hypertensive rats(SHRs)were fed a high-fat,high-cholesterol diet to establish a rat model of hy-pertension combined with dyslipidemia,and then treated with SES for 16 weeks continuously.The ex-periment was divided into four groups:WKY,SHR,Model,and Model+SES(160 mg·kg-1·d-1).Blood pressure was measured using the tail-cuff method.Body weight was monitored,and body mass index was calculated.Liver morphology was detected by ultrasound,and liver thickness was measured.Liver wet weight was weighed,and liver index was calcu-lated.Liver volume was detected by the water dis-placement method.Serum triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),alanine aminotransferase(ALT),aspartate amino-transferase(AST),and total bile acids(TBA)were de-tected by ELISA.Liver sequencing analysis was per-formed using mRNA-seq.Liver histomorphological changes were observed by HE staining.The degree of hepatic steatosis was observed by Oil Red O stain-ing,and the degree of hepatic fibrosis was observed by MASSON staining.The mRNA expression of Al-dh1a7,Nnmt,Irs2,Pltp,and Scd was detected by q-PCR.The protein expression of Scd,Nnmt,AMPK,p-AMPK,PPARα,and PPARγ was detected by Western blotting.RESULTS:After 16 weeks of continuous SES administration to rats with hypertension combined with dyslipidemia,blood pressure was significantly reduced(P＜0.01),and body weight was decreased.Serum TG,TC,and LDL-C levels were decreased,while HDL-C levels were increased.Serum ALT and AST levels were decreased.Liver weight,organ in-dex,liver thickness,and liver volume were de-creased.The degree of hepatic steatosis and hepat-ic fibrosis was improved.A total of 545 differentially expressed mRNAs were identified in the livers of rats in each group,of which 278 were upregulated and 267 were downregulated.Among the 27 com-monly differentially expressed mRNAs,five mRNAs related to lipid metabolism were screened,namely Aldh1a7,Nnmt,Irs2,Pltp,and Scd.KEGG enrich-ment analysis showed that the enriched pathways were AMPK and PPAR.Further validation revealed that in the SES-treated group,the mRNA expression of Scd in the liver was decreased,while the mRNA expression of Nnmt was increased.The protein ex-pression of Scd was decreased,while the protein ex-pression of Nnmt,AMPK,p-AMPK,PPARα,and PPARγ was increased.CONCLUSION:SES has preven-tive and therapeutic effects on fatty liver disease in rats with hypertension combined with dyslipidemia,and its mechanism of action may be related to the reduction of Scd expression levels in the liver and the increase in the expression of Nnmt,AMPK,p-AMPK,PPARα,and PPARγ.

Objective:To observe the clinical effect of aripiprazole combined with non-convulsive electroshock(MECT)for children and adolescents with first episode schizophrenia.Methods:94 children and adolescents with first episode schizophrenia who were admitted to Yiling Kangning Mental Hospital of Yichang from August 2022 to August 2024 were divided into control group(received aripiprazole,n=47)and study group(received aripiprazole combined with MECT,n=47)by using random number table method.The clinical efficacy,dysfunction scale[Positive and Negative Symptom Scale(PANSS),Montreal Cognitive Assessment Scale(MoCA),Wechsler Memory Scale(WMS)],glucose and lipid metabolism indexes[low density lipoprotein cholesterol(LDL-C),glycated hemoglobin(HbAlc),total cholesterol(TC),fasting blood glucose(FBG),High density lipoprotein cholesterol(HDL-C),inflammatory factor indexes[interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)],neurocytokine levels[serum brain-derived neurotrophic factor(BDNF),s100βprotein(s100β),homocysteine(Hcy)]and the occurrence of adverse reactions were compared between the two groups.Results:Compared with the control group after treatment,the clinical total effective rate,MoCA,WMS score,HDL-C,BDNF were higher,PANSS score,HbAlc,FBG,TC,LDL-C,TNF-α,IL-1β,IL-6,s100β and Hcy were lower in the study group(P＜0.05).There was no difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion:Aripiprazole combined with MECT in the treatment of in children and adolescents with first episode schizophrenia can reduce the degree of inflammation,regulate glucose and lipid metabolism,improve clinical symptoms and neurological function of children,with good safety.

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*

Objective:To explore the predictive value of hepatitis B surface antibody (HBsAb) quantitative level for achieving hepatitis B surface antigen (HBsAg) seroclearance and serological conversion in patients with chronic hepatitis B (CHB) treated with nucleos(t)ide analogs (NAs) or interferon (IFN).Methods:A two-center prospective cohort study was conducted, including CHB patients from Nanfang Hospital Southern Medical University and Eastern Theater General Hospital treated with NAs and IFN. All patients were followed up once every three to six months. Basic clinical information and test results were collected at each follow-up. The presence or absence of HBsAg seroclearance and serological conversion rate was evaluated. HBsAg serological conversion was defined as HBsAg quantification continuously below the detection limit (<0.05 IU/mL) at two detection time points at least six months apart. HBsAg serological conversion was defined as HBsAb positivity (≥10 IU/L) at the same time as the first HBsAg seroclearance. The Kruskal-Wallis test was used to compare the quantitative data of multiple groups, and the Wilcoxon rank-sum test was used to compare the data between groups. The chi-square test was used for the count data, and the Fisher exact test was used when the chi-square test was not met. Univariate and multivariate Cox analysis was used to determine the predictors of the study endpoints, and stepwise regression was used for variable screening.Results:A total of 2 266 CHB cases were included, of which 86.5% (1 959/2 266) were NA antiviral-received population. The median treatment duration before baseline was 10.5 (2.5, 37.6) months, and the baseline HBsAg quantification was 3.1 (2.6, 3.5) log 10 IU/mL. A total of 68 cases (3.0%) had HBsAg seroclearance, and 44 cases (1.9%) achieved serological conversion after 85.0 (62.7, 97.3) months of prospective follow-up. The level and positivity rate of HBsAb showed a progressive increase 36 months before and significantly after HBsAg seroclearance. Cox regression analysis results showed that baseline HBsAb level was an independent predictor of HBsAg serological conversion ( HR=2.26, P=0.002) in the overall population, especially in the subgroup with HBsAg between 100 and 1 000 IU/mL, suggesting HBsAb level had important predictive value. In addition, the serological conversion development rate was significantly higher in the GOLDEN model favourable patients than in the unfavourable patients (11.5% vs. 0, P<0.001). Conclusion:The baseline HBsAb quantitative level can predict HBsAg seroclearance and serological conversion for patients with CHB receiving antiviral treatment, which is of significant value in long-term treatment monitoring.

Objective:To explore the predictive value of serum interleukin-6(IL-6)combined with Montreal Cognitive Assessment(MoCA)score and CHANGE risk score for post-stroke cognitive impairment(PSCI),and to provide a basis for early identification and intervention of high-risk patients.Methods:The general data of 200 patients with acute stroke who were admitted to our hospital from October 2022 to September 2024 were retrospectively analyzed,they were divided into PSCI group(49 cases)and non PSCI group(151 cases)based on whether PSCI occurred 3 months after acute stroke.The general data of two groups were compared,multiple logistic regression was used to analyze the influencing factors of PSCI,and receiver operating characteristic(ROC)curves were used to evaluate predictive efficiency of serum IL-6,MoCA score and CHANGE risk score for of PSCI.Results:There was a statistically significant difference in age and education level between the two groups(P＜0.05).The serum IL-6 level and CHANGE risk score in the PSCI group were higher than those in the non PSCI group,while the MoCA score was lower than that in the non PSCI group(P＜0.05).Multivariate logistic regression showed that elevated IL-6 levels(OR=1.851,P=0.001)and elevated CHANGE risk scores(OR=1.076,P=0.016)were independent risk factors of the occurrence of PSCI,while elevated in MoCA score(OR=0.806,P=0.001)was a protective factor(P＜0.05).IL-6 levels,MoCA scores and CHANGE risk scores have high predictive efficiency for the occurrence of PSCI,the area under the curve(AUC)for predicting occurrence of PSCI by the three alone were 0.783,0.825 and 0.857 respectively,the AUC for the combined detection of the three indicators was 0.912,significantly higher than that of each indicator detected separately.Conclusion:Elevated serum IL-6,decreased MoCA score and increased CHANGE risk score are risk factors for PSCI,the combined detection model of the three has the highest predictive efficiency for occurrence of PSCI and can provide scientific basis for early clinical intervention.

Cardiovascular disease has become the main cause of death worldwide,seriously threatening human life and health.Some studies have shown that cluster of differentiation 74(CD74)is involved in the pathology and inflammatory pathways of cardiovascular diseases,which has attracted wide attention from scholars.CD74 is a major histocompatibility complex(MHC)Ⅱ chaperone and macrophage migration inhibitory fac-tor(MIF)receptor.It activates a variety of signaling pathways and plays a biological role in the occurrence and progression of cardiovascular diseases.This article summarizes the relevant lit-erature advances of CD74 in cardiovascular diseases,to explore the pathogenesis from the perspective of CD74 and seek disease protection and more effective therapeutic targets.

Objective:To explore the predictive value of serum interleukin-6(IL-6)combined with Montreal Cognitive Assessment(MoCA)score and CHANGE risk score for post-stroke cognitive impairment(PSCI),and to provide a basis for early identification and intervention of high-risk patients.Methods:The general data of 200 patients with acute stroke who were admitted to our hospital from October 2022 to September 2024 were retrospectively analyzed,they were divided into PSCI group(49 cases)and non PSCI group(151 cases)based on whether PSCI occurred 3 months after acute stroke.The general data of two groups were compared,multiple logistic regression was used to analyze the influencing factors of PSCI,and receiver operating characteristic(ROC)curves were used to evaluate predictive efficiency of serum IL-6,MoCA score and CHANGE risk score for of PSCI.Results:There was a statistically significant difference in age and education level between the two groups(P＜0.05).The serum IL-6 level and CHANGE risk score in the PSCI group were higher than those in the non PSCI group,while the MoCA score was lower than that in the non PSCI group(P＜0.05).Multivariate logistic regression showed that elevated IL-6 levels(OR=1.851,P=0.001)and elevated CHANGE risk scores(OR=1.076,P=0.016)were independent risk factors of the occurrence of PSCI,while elevated in MoCA score(OR=0.806,P=0.001)was a protective factor(P＜0.05).IL-6 levels,MoCA scores and CHANGE risk scores have high predictive efficiency for the occurrence of PSCI,the area under the curve(AUC)for predicting occurrence of PSCI by the three alone were 0.783,0.825 and 0.857 respectively,the AUC for the combined detection of the three indicators was 0.912,significantly higher than that of each indicator detected separately.Conclusion:Elevated serum IL-6,decreased MoCA score and increased CHANGE risk score are risk factors for PSCI,the combined detection model of the three has the highest predictive efficiency for occurrence of PSCI and can provide scientific basis for early clinical intervention.

Cardiovascular disease has become the main cause of death worldwide,seriously threatening human life and health.Some studies have shown that cluster of differentiation 74(CD74)is involved in the pathology and inflammatory pathways of cardiovascular diseases,which has attracted wide attention from scholars.CD74 is a major histocompatibility complex(MHC)Ⅱ chaperone and macrophage migration inhibitory fac-tor(MIF)receptor.It activates a variety of signaling pathways and plays a biological role in the occurrence and progression of cardiovascular diseases.This article summarizes the relevant lit-erature advances of CD74 in cardiovascular diseases,to explore the pathogenesis from the perspective of CD74 and seek disease protection and more effective therapeutic targets.