Initial [18F]DCFPyL PET/CT in treatment-naïve prostate cancer: correlation with post-ADT PSA outcomes and recurrence.

PURPOSE: Positron emission tomography (PET) with prostate-specific membrane antigen (PSMA) targeting tracers has emerged as a valuable diagnostic tool for prostate cancer (PCa), androgen deprivation therapy (ADT) stands as the cornerstone treatment for advanced PCa, yet forecasting the response to hormonal therapy poses a significant clinical hurdle. METHODS: In a prospective cohort of 86 PCa patients undergoing short-term ADT, this study evaluated the prognostic potential of [18F]DCFPyL PET/CT scans. Comprehensive data encompassing clinical profiles, baseline prostate-specific antigen (PSA) levels, and imaging metrics were assessed. We developed predictive models for assessing decreases in PSA levels (PSA50 and PSA70) based on a combination of PET-related parameters and clinical factors. Kaplan-Meier survival analysis was utilized to ascertain the prognostic value of PET-based metrics. RESULTS: In this study, elevated [18F]DCFPyL uptake within the primary tumor, as indicated by a SUV ≥ 6.78 (p = 0.0024), and a reduction in the tumor volume (TV) of primary PSMA-avid tumor with PSMA-TV < 41.96 cm3 (p = 0.038), as well as an increased burden of metastatic PSMA-avid tumor, with PSMA-TV (PSMA-TV ≥ 71.39 cm3) (p = 0.012) were identified in association with diminished progression-free survival (PFS). PET and clinical parameters demonstrated constrained predictive capacity for PSA50 response as indicated by an area under the curve (AUC) of 0.442. CONCLUSION: Our study revealed that pretreatment [18F]DCFPyL uptake in primary or metastatic tumor sites is prognostically relevant in high-risk PCa patients undergoing ADT. Further research is needed to develop robust predictive models in this multifaceted landscape of PCa management.

Distribution of 50-layer corneal densitometry values and related factors.

PURPOSE: To investigate the distribution of 50 layers of corneal densitometry and related factors. METHODS: Clinical data, including age, sex, central corneal thickness, corneal keratometry, and diopters, were collected from 102 healthy participants (102 eyes) in this retrospective study. The cornea was divided into 50 layers, and densitometry of each layer at 19 points was measured by the Pentacam. The value versus the depth curve was plotted. Paired-sample t test and one-way analysis of variance were used to compare densitometry in different regions or depth. Statistical significance was defined as P < .05. RESULTS: The densitometry values of the Bowman membrane (10-14% depth), anterior stroma (14-30% depth), epithelium (0-10% depth), and Descemet membrane (94-98% depth) decreased sequentially, and the densitometry values of the middle and posterior stroma (30-94% depth) and endothelium (98-100% depth) were the lowest. The higher the degree of astigmatism, the higher the second densitometry peak (R = 0.277, P < .001). The densitometry values of the vertex and superior parts of the cornea were higher than those in the periphery and inferior parts, respectively (all P < .001). In the Bowman membrane, the densitometry is lowest in the inferior nasal part, while in the Descemet membrane, it is lowest in the inferior temporal part. CONCLUSION: Two densitometry peaks appeared near the Bowman membrane and Descemet membrane. For different depths, the distribution of densitometry within a layer is different. We provide a methodological reference and data basis for corneal research based on local changes in densitometry, and help understand the details of corneal structure from an optical perspective through detailed layering and zoning analysis of densitometry.

Synovial Fluid α-MSH Levels are Inversely Correlated with Articular Cartilage Degeneration in Anterior Cruciate Ligament Deficient Knees.

BACKGROUND: Secondary osteoarthritis after ligament or meniscus injury generally causes great burdens to patients. Alpha-melanocyte-stimulating hormone (α-MSH ), a 13 amino acid neuropeptide produced by intracellular cleavage of the proopiomelanocortin (POMC) hormone, has been proven to suppress inflammation and protect cartilage from damage. The present study was carried out to explore the relationship between synovial fluid α-MSH levels and articular cartilage degeneration in patients with anterior cruciate ligament (ACL) deficiency. METHODS: 51 patients with ACL deficiency admitted to our hospital were enrolled. The Noyes score method was used to assess articular cartilage damage arthroscopically. Synovial fluid α-MSH levels were examined using a double antibody radioimmunoassay method. Inflammation markers such as IL-6, MMP-3, and degradation biomarker of collagen type II (CTX-II) were also explored by enzyme-linked immunosorbent assay (ELISA). RESULTS: The articular cartilage in ACL deficiency patients deteriorated significantly with time after injury (r = 0.673, p < 0.001). Synovial fluid α-MSH levels are inversely associated with Noyes scores (r = -0.682, p < 0.001), levels of inflammation markers IL-6 (r = -0.302, p = 0.035), MMP-3 (r = -0.652, p < 0.001) and degradation biomarker CTX-II (r = -0.584, p < 0.001). CONCLUSIONS: Synovial fluid α-MSH levels showed an independent and negative correlation with articular cartilage degeneration in patients with knee ACL deficiency. Supplementing with a-MSH may serve as a possible adjuvant therapy for delaying cartilage degeneration after ACL injury.

Corneal Biomechanical Properties to Predict Prognosis of Abnormal Tomographic Corneas: A Prospective Cohort Study.

PURPOSE: To analyze the corneal biomechanical properties in patients with abnormal corneal tomography (ACT) and predict their stability using the biomechanical stability index (BSI). DESIGN: Prospective cohort study. METHODS: Setting: Multicenter study. STUDY POPULATION: This study included 385 eyes of 278 patients with stable ACT (n = 70), subclinical keratoconus (SKC, n = 65), keratoconus (n = 65), normal controls (NL, n = 142). Forty-three eyes with first-visit ACT were included in a separate cohort (follow-up ACT group). OBSERVATION PROCEDURE: Tomographical and biomechanical parameters (Pentacam and Corvis ST) were recorded. MAIN OUTCOME MEASURES: Nonparametric tests were used for comparison. Logistic regression was employed to introduce BSI to separate stable ACT and SKC accurately. An independent dataset of 43 first-visit ACT eyes was followed up for 1 year to validate BSI's accuracy and positive and negative predictive values (PPV, NPV). RESULTS: The tomographical and biomechanical parameters in patients with Stable ACT remained stable over the follow-up period (12.73 ± 2.57 months, P > .05). Stable ACT had 12/14 biomechanical parameters different (P < .05) from SKC but not different from NL (P > .05). With a cut-off value of 0.585, BSI demonstrated the strongest ability to distinguish between stable ACT and SKC (area under the receiver operating characteristic curve = 0.991), with 93.85% sensitivity and 97.14% specificity. During the 1-year follow-up of 43 eyes (follow-up ACT group), 30 remained stable. The accuracy, PPV, and NPV of the BSI were 95.35%, 100%, and 93.75%, respectively. CONCLUSIONS: Biomechanical properties of patients with stable abnormal tomography corneas were stronger than SKC and close to normal corneas, which may explain the reason for tomographic stability. The BSI may be useful for predicting disease progression in patients with ACT and the possible management of corneal cross-linking at the first visit.

The effectiveness of web-based interventions on non-alcoholic fatty liver disease (NAFLD) in obese children: A study protocol for a randomized controlled trial.

Aim: Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent liver disease in the world, increasing the risk of cirrhosis and hepatocellular carcinoma, and contributing to the development of type 2 diabetes, cardiovascular disease, and chronic kidney disease. This study aims to carry out a web-based continuum of a care intervention model to provide comprehensive care interventions for obese children with NAFLD, to improve the effectiveness of treatment of children with NAFLD. Design: A 1-year single-blinded randomized clinical trial in hospital in Zhejiang Province. Methods: Eighty subjects will implement the program in a randomized order. The interventions for the control group mainly consisted of the routine distribution of health education materials and health education by holding health-themed lectures, and the preliminary proposed interventions including establishing management teams, regularly delivering related health knowledge, daily uploading of health intervention records, regular supervision and mutual encouragement, home visiting and psychological guidance. The primary outcomes are serum biomarkers such as alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), aspartate aminotransferase, and imaging (liver ultrasound and magnetic resonance imaging). Second outcomes are: BMI, waist-to-hip ratio and quality of life. In addition, socio-demographic characteristics such as age, gender and ethnicity will be recorded. Children aged 7-18 years old and diagnosed with NAFLD will be included, patients will be not eligible if they do not agree to participate or are participating in other health intervention programs. This study was registered on ClinicalTrials.gov (NCT05527938). Results: Over the past 30 years, NAFLD has been recognized as one of the most common liver diseases in adults and children. The current studies have focused on promoting lifestyle changes in children with NASH by providing some education and advice to children and their families to improve the histological features of NASH and lose weight. Because of the convenience and efficiency of the internet can provide some new strategies and ways for lifestyle interventions for children with NAFLD. In addition, we have designed a high-quality RCT based on the SPIRIT guidelines, which also provides strong evidence in this area.

Circulating antibodies against M-type phospholipase A2 receptor and thrombospondin type-1 domain-containing 7A in Chinese patients with membranous nephropathy.

BACKGROUND: M-type phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) have recently been identified as target antigens for patients with idiopathic membranous nephropathy (IMN). The prevalence of PLA2R and THSD7A in the serum of MN patients deserves further investigation. METHODS: Here, we studied the presence of anti-PLA2R and anti-THSD7A antibodies in patients with biopsy-proven IMN (n = 212), secondary membranous nephropathy (SMN, n = 118), and other kidney diseases (n = 84). The progress of 49 IMN patients [anti-PLA2R(+), n = 27; anti-THSD7A(+), n = 6; anti-PLA2R(-) and anti-THSD7A(-) dual negative, n = 16] who received immunosuppressive therapy was observed for 12 months. Serum concentrations of antibodies against PLA2R and THSD7A were detected using an indirect immunofluorescent assay. RESULTS: One hundred fifty-two (71.7%) IMN patients and 11 (9.3%) SMN patients were identified as anti-PLA2R(+) anti-THSD7A(-). Five (2.4%) IMN patients and two (1.7%) SMN patients were identified as anti-THSD7A(+) anti-PLA2R(-). One of the IMN patients was identified as anti-PLA2R(+) and anti-THSD7A(+). The rate of partial remission was lower in anti-PLA2R(+) patients than in anti-PLA2R(-) patients 3 months (P = 0.045) and 6 months (P = 0.006) after immunosuppressive therapy. The rate of complete remission was lower in anti-PLA2R(+) patients than in anti-PLA2R(-) patients 12 months (P = 0.037) after immunosuppressive therapy. CONCLUSIONS: The serum concentration of anti-PLA2R antibodies may be used as a sensitive and specific marker for diagnosing IMN. Immunosuppressive therapy is more effective for IMN patients who are anti-PLA2R(-) than for those who are anti-PLA2R(+).

[Association between inflammatory cytokine CD40 gene polymorphism and risk of acute coronary syndrome].

OBJECTIVE: To investigate the expression levels of CD40, sCD40L, hs-CRP, WBC in acute coronary syndrome (ACS) patients and the association between CD40-1C/T single nucleotide polymorphism and risk of ACS in Han Chinese, moreover, the regulatory effects of IFN-gamma and fluvastatin on the expression of CD40 in peripheral blood mononuclear cell (PBMNC) were also observed. METHODS: (1) 160 ACS patients and 92 control patients diagnosed by coronary angiography were recruited. Enzyme linked immunosorbent assay, particle enhanced immunoturbidimetric assay, flow cytometry were used to detect the levels of soluble CD40L, hs-CRP, and WBC count. (2) The CD40 genotype and allele frequency were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing technology. (3) PBMNC were separated by density gradient centrifugation heparinized venous blood from 40 ACS patients, cultured for 24 h with or without 100 ng/ml IFN-gamma in the absence or present of 10 micromol/L fluvastatin. The CD40 expression levels were then detected by flow cytometry. RESULTS: Inflammatory cytokine CD40, sCD40L, hs-CRP levels were significantly higher in ACS patients than in controls. The CD40-1C allele frequency was 0.606 in ACS group and 0.489 in controls, while T allele frequency was 0.394 in ACS group and 0.511 in controls. The frequency of CC genotype was significantly higher in ACS group than in controls (P < 0.01). C allele carriers had significantly higher risk of ACS (OR = 1.608, 95%CI: 1.12 - 2.32, P = 0.011). CD40 production increased after 24 h culturing and the CD40 levels were significantly higher in subjects with CC genotype than that in subjects with CT or TT genotype [CC: (14.78 +/- 4.56) MFI, CT: (11.98 +/- 4.12) MFI, TT: (9.86 +/- 3.83) MFI, P < 0.05]. IFN-gamma further increased PBMNC CD40 expressions in all subjects after culturing for 24 h and fluvastatin equally inhibited IFN-gamma induced PBMNC CD40 expression from various genotypes (CC, CT, TT was 30.3%, 26.3%, 29.3% respectively, all P > 0.05). CONCLUSION: Inflammatory cytokines were increased in ACS patients and CD40-1C/T polymorphism is associated with higher risk for ACS in Han Chinese.

[Correlation of CD40 gene polymorphisms with acute coronary syndrome, hypertension and diabetes].

OBJECTIVE: To investigate the correlation of CD40-E1SNP (-1C/T) and CD40-E4SNP with acute coronary syndrome (ACS), hypertension and diabetes in Chinese Han population. METHODS: The allele frequencies of CD40-E1SNP (-1C/T) and CD40-E4SNP were assayed by polymerase chain reaction-restriction fragment length polymorphism and DNA sequence technology in 160 definite ACS patients and 92 controls with negatively coronary arteriography. Multivariate logistic regression models were used to analyzed the interaction between the CD40 gene polymorphisms and hypertension and diabetes. RESULTS: CD40-1C allele frequency of the ACS group was 0.606, significantly higher than that of the control group (0.489, P < 0.01), while the T allele frequency of the ACS group was 0.394, significantly lower than that of the control group (0.511, P < 0.01). The frequency of CC genotype was much higher in the ACS group than in the control group (P < 0.01). C allele increased the risk of ACS (OR = 1.608, 95% CI: 1.12 - 2.32, P = 0.011). After adjustment of confounding variables, such as age, sex, and body mass index, the binary logistic analysis showed a significant gene-environment interaction (P < 0.05). The OR value were: 1.608 for C allele (95% CI: 1.12 - 2.32, P < 0.05), 5.71 for C allele-with hypertension (95% CI: 1.12 - 29.08, P < 0.05), 1.44 for C allele-without diabetes (95% CI: 1.12 - 5.13, P < 0.01), and 2.35 for C allele-with diabetes (95% CI: 1.47 - 4.82, P < 0.01). Expression of CD40-E4SNP was not found in these subjects. CONCLUSION: CD40-1C/T polymorphism is associated with ACS in Chinese people. The -1C allele carriers have higher risk of ACS if they get hypertension or diabetes; CD40-E4SNP may not exist in Chinese people.

A common polymorphism in CD40 Kozak sequence (-1C/T) is associated with acute coronary syndrome.

OBJECTIVE: Evidence suggests the CD40-CD40L pathway as a key process in the development, progression, and outcome of acute coronary syndrome (ACS). We hypothesized that the -1C/T polymorphism of the CD40 gene would be associated with ACS and influence the CD40 expression. METHODS: The genotype distribution and allele frequency of CD40-1C/T polymorphism in 248 ACS patients and 206 controls were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Monocytes from 90 healthy volunteers were incubated with IFN-gamma. CD40 expression was detected by flow cytometry. RESULT: Patients with ACS showed a significant increase of CD40 expression compared with controls (P<0.001). The frequency of the CC genotype in the ACS group was significantly higher than that of the controls (P<0.001). Frequency of the C allele was higher among ACS patients compared with controls (P<0.001). Case control association analysis of the CD40 -1C/T SNP showed an association between the C allele and ACS (OR=1.991, 95%CI: 1.526 approximately 2.596, P<0.001). -1C/C carriers presented significantly higher CD40 expression levels than -1C/T and -1T/T subjects, both in ACS group and controls (P<0.001). When stimulated by IFN-gamma, CD40 expression levels on monocytes in individuals with CC, CT and TT genotypes were increased by 9.16, 3.83 and 1.53 fold, respectively, compared with the levels absent with IFN-gamma. CONCLUSIONS: These results suggest that the -1C allele of the CD40 (-1C/T) gene polymorphism is a genetic factor that may determine an individual's susceptibility by ACS in Chinese. The CD40 -1C/T polymorphism is a novel regulator of CD40 expression.

[Expression of WT1 gene and its isomer ratio changes during phorbol ester induced differentiation of K562 cell line].

OBJECTIVE: To explore the changes in expression of WT1 gene and ration of its isomers during phorbol ester (TPA) induced differentiation of leukemia cell line K562 by fluorescence quantitative RT-PCR and analysis the relationship between different isomers and hematogenic cell differentiation. METHODS: The degree of cellular maturation were verified by NBT reduction test and immunophenotyping. Expression of WT1 gene was determined by fluorescence quantitative RT-PCR during differentiation of K562 cell line. The relative ratio of the four splicing variants WT1 ( + / + ), WT1 ( + / - ), WT1 ( - / + ), WT1 ( - / - ) were calculated. RESULTS: During the differentiation of K562 cell, the NBT reduction rate and the CD9 positive rate both increased significantly (P < 0. 05). The expression of WT1 gene decreased immediately to (1.67 +/- 0.45) x 10(-3) from (4.67 +/- 1.11) x 10(-3), and then increased again to (4.64 +/- 1.53) x 10(-3) at 96 hours. The ratio of WT1 ( + / + ) was decreased gradually, from 0 hour (39.65 +/- 19.46)% to 96 hour (15.25 +/- 7.27)%. While the ratio of WT1( - / - ) was increased, from 0 hour (15.38 +/- 11.34)%, to 96 hour (37.60 +/- 11.90)%. The other two isomers ratios did not change significantly. CONCLUSION: During the TPA induced differentiation of K562 cell, there are two high expression levels of WT1 gene. Before differentiation, the majority is WT1 ( + / + ), and after differentiation, is WT1 ( - / - ). It indicates that WT1 gene may activate or inhibit cell differentiation by regulating the ratio of its four splicing variants.