Standardized IETA criteria enhance accuracy of junior and intermediate ultrasound radiologists in diagnosing malignant endometrial and intrauterine lesions.

OBJECTIVES: To transform the standardized descriptions of the ultrasound characteristics of endometrial and intrauterine lesions devised by the International Endometrial Tumor Analysis (IETA) group into a practical scoring method and to investigate whether application of this method enhances the diagnostic accuracy of ultrasound radiologists with different levels of experience in detecting malignancy compared with subjective assessment. METHODS: This was a retrospective study of 855 patients with endometrial and/or intrauterine lesions, who were divided into a training (n = 600) and a validation (n = 255) set. Ultrasound radiologists with varying levels of experience (expert, intermediate and junior) evaluated all lesions by subjective assessment and according to IETA rules. Using IETA rules, the experts identified signs of malignancy in the training set, assigned scores for each indicator and validated the scoring method in the validation set. The intermediate-level and junior ultrasound radiologists reassessed the malignancy of the lesions using the IETA scoring method and compared their classifications with those made previously by subjective assessment. Postsurgical pathological evaluation was used as the reference standard. RESULTS: Using subjective assessment, the experts demonstrated the highest level of diagnostic accuracy, with a sensitivity of 85.0%, specificity of 94.3% and an area under the receiver-operating-characteristics curve (AUC) of 0.897. Applying the IETA scoring method (comprising eight ultrasound characteristics that contributed to the total score) with a threshold of > 25 points for the diagnosis of malignancy achieved a sensitivity of 84.7%, specificity of 94.7% and AUC of 0.9533 in the training set, with similar performance in the validation set, when performed by experts. Using the IETA scoring method, both junior and intermediate ultrasound radiologists showed improvement in sensitivity (from 55.5% to 74.8% and from 70.2% to 77.1%, respectively), specificity (from 88.4% to 91.5% and from 87.4% to 92.2%, respectively) and AUC (from 0.704 to 0.827 and from 0.793 to 0.841, respectively) for diagnosing malignant lesions. CONCLUSIONS: The IETA scoring method exhibits high diagnostic efficacy for malignant endometrial and intrauterine lesions. This method compensates for the lack of experience among junior and intermediate-level ultrasound radiologists, enhancing their diagnostic skill to a level nearing that of experienced senior ultrasound radiologists. Further research is essential to validate the practicality of implementing this method and to confirm its clinical value. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Precise Measurement of Born Cross Sections for e

Using data samples collected with the BESIII detector at the BEPCII collider at center-of-mass energies ranging from 3.80 to 4.95 GeV, corresponding to an integrated luminosity of 20 fb^{-1}, a measurement of Born cross sections for the e^{+}e^{-}→D^{0}D[over ¯]^{0} and D^{+}D^{-} processes is presented with unprecedented precision. Many clear peaks in the line shape of e^{+}e^{-}→D^{0}D[over ¯]^{0} and D^{+}D^{-} around the mass range of G(3900), ψ(4040), ψ(4160), Y(4260), and ψ(4415), etc., are foreseen. These results offer crucial experimental insights into the nature of hadron production in the open-charm region.

[Huangqin Qingrechubi Capsule alleviates inflammation and uric acid and lipid metabolism imbalance in rats with gouty arthritis by inhibiting the PTEN/PI3K/AKT signaling pathway].

OBJECTIVE: To investigate the effects of Huangqin Qingrechubi Capsule (HQC) on inflammation and uric acid and lipid metabolism in rats with gouty arthritis (GA) and its mechanism. METHODS: SD rat models of GA established by injecting monosodium urate into the right ankle joint were treated with saline, colchicine and HQC at low, medium and high doses (n=10) by gavage for 7 days. Toe swelling of the rats was detected at 4, 8, 24, 48 and 72 h after modeling, and synovial histological changes were observed with HE staining. Serum levels of interleukin-10 (IL-10), IL-18, tumor necrosis factor-α (TNF-α), transforming growth factor-ß1 (TGF-ß1), adiponectin, leptin, resistin and visfatin were measured by ELISA, and the levels of high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), total cholesterol (TC), and uric acid (BUA) were detected. RTqPCR and Western blotting were used to detect the mRNA expressions of phosphatase and tensin homolog (PTEN), phosphatidylinositol-3-kinase (PI3K) and protein kinase B (AKT) and the protein expressions of PTEN, PI3K, p-PI3K, AKT and p-AKT. RESULTS: The rat models of GA showed obvious toe swelling, which reached the peak level at 48 h. HE staining revealed massive inflammatory cell infiltration and synovial tissue hyperplasia. The rat models showed significantly increased expressions of TNF-α, TGF-ß1, IL-18, TC, TG, leptin, resistin and visfatin, BUA, p-PI3K, and p-AKT and lowered levels of IL-10, APN, HDL-C, and PTEN. Treatment with HQC and colchicine obviously improved these changes and alleviated synovial pathologies and toe swelling in the rat models. CONCLUSION: HQC can improve inflammation and correct the imbalance of uric acid and lipid metabolism in GA rats possibly by inhibiting the PTEN/PI3K/AKT signaling pathway.

[Analysis of core functional components in Yinchenhao Decoction and their pathways for treating liver fibrosis].

OBJECTIVE: To analyze the core functional component groups (CFCG) in Yinchenhao Decoction (YCHD) and their possible pathways for treating hepatic fibrosis based on network pharmacology. METHODS: PPI data were extracted from DisGeNET, Genecards, CMGRN and PTHGRN to construct a weighted network using Cytoscape 3.9.1. The data of the chemical components in YCHD were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the potential active components and targets were selected using PreADMET Web server and SwissTargetPrediction. A fusion model was constructed to obtain the functional effect space and evaluate the effective proteins to identify the CFCG followed by GO and KEGG pathway enrichment analyses for all the targets. In cultured human hepatic stellate cells (LX-2 cells), the cytotoxicity of different compounds in YCHD was tested using CCK-8 assay; the effects of these compounds on collagen α1 (Col1a1) mRNA expression and the pathways in 20 ng/mL TGF-ß1-stimulated cells were analyzed using RT-qPCR and Western blotting. RESULTS: A total of 1005 pathogenic genes, 226 potential active components and 1529 potential targets in YCHD and 52 potential targets of CFCG were obtained. Benzyl acetate, vanillic acid, clorius, polydatin, lauric acid and ferulic acid were selected for CCK-8 verification, and they all showed minimal cytotoxicity below the concentration of 200 µmol/L. Clorius, polydatin, lauric acid and ferulic acid all effectively inhibited TGF-ß1-induced LX-2 cell activation. At the concentration of 200 µmol/L, all these 4 components inhibited PI3K, p-PI3K, AKT, p-AKT, ERK, p-ERK, P38 MAPK and p-P38 MAPK expressions in TGF-ß1-induced LX-2 cells. CONCLUSION: The therapeutic effect of YCHD on hepatic fibrosis is probably mediated by its core functional components including benzyl acetate, vanillic acid, clorius, polydatin, lauric acid and ferulic acid, which inhibit the PI3K-AKT and MAPK pathways in hepatic stellate cells.

[Establishment of Nano-ITO induced rat model of indium lung disease and exploration of its pathological characteristics].

Objective: To study the dynamic pathological characteristics of lung tissue in a Nano-ITO induced rat model of indium lung disease and to guide clinical and basic scientific research to further explore the mechanisms of pulmonary interstitial injury and pulmonary alveolar proteinosis (PAP). Methods: Dose-response (three divided doses) and time-course studies (six exposure periods) were performed to investigate the pulmonary toxicity induced by Nano-ITO. At the end of the experiment, cytokine levels and oxidative stress were analyzed in the bronchoalveolar lavage fluid. Rat lung tissues were also collected for staining with H&E, PAS, Masson's, Oil Red O, and Sirius Red. Ultrastructure of lung tissue cells was observed by transmission electron microscopy. Expression of IL-1ß, HO-1, SP-A was observed by immunohistochemistry, and the expression of α-SMA was observed by immunofluorescence. Results: Nano-ITO intratracheal instillation caused pulmonary toxicity by inducing acute inflammation at 3 days, granuloma (nodule) formation and collagen hyperplasia at 14 days, and alveolar proteinosis at 56 days post-exposure. Pathological features of lung tissue included typical alveolar exudates, cellular fibrous nodules, enlarged alveolar fat droplet fusion, cholesterol crystal granuloma and pulmonary alveolar proteinosis. The intra-alveolar eosinophilic material (multilamellated, lattice-shaped, and myelin-like structure) showed abnormal lamellar bodies (features of alveolar type Ⅱ epithelial cells) and abundant rough endoplasmic reticulum and mitochondria (features of fibroblasts) on transmission electron microscopy of the lung tissue from rats exposed to Nano-ITO on the 84th day. Cellular pathology revealed that a large amount of amorphous PAS stain-positive substances appear in BALF at 28 days post-exposure, and pink granular protein-like substances can be seen in alveolar macrophages. Conclusions: There are three characteristic developmental stages in Nano-ITO induced pulmonary injury in rats, acute inflammation, granuloma (nodule) formation and collagen proliferation, and pulmonary alveolar proteinosis, which provide a reference feature model for the pathogenesis of indium lung disease.

[Primary ciliary dyskinesia associated with a novel DNAH11 genetic variant: a case report].

Primary ciliary dyskinesia (PCD) is a heterogeneous genetic disorder associated with abnormalities in ciliary structure and function. Here, we report A 22-year-old non-smoking Chinese man with recurrent episodes of respiratory tract infections and sinusitis since high school period. The diagnosis is more complicated by the atypical symptoms and the late age of onset. We summarized the clinical characteristics of this case and literature review. This report aimed to improve the clinical understanding of primary ciliary dyskinesia.

[Research advances in mechanistic signaling in pulmonary fibrosis].

Pulmonary fibrosis is a complex and intractable disease characterized by extracellular matrix accumulation and altered mechanical properties of lung tissue. Biomechanical properties are closely related to the development, progression, and treatment of tissue fibrosis. In this review, we summarized the changes in the pulmonary biomechanical microenvironment, highlight the role of mechanotransduction in pulmonary fibrosis, and describe recent clinical advances targeting mechanical signals to alleviate pulmonary fibrosis.

Vitamin D Prevents Gestational Diabetes Mellitus via Modulating Glucose Metabolism in a Mouse Model.

Gestational diabetes mellitus (GDM) is a common disease during pregnancy that has adverse effects on both the mother and fetus. There are currently rare researches on the effect of vitamin supplementation on GDM pregnant mother and their offspring on animal and cell levels systematically. This work supplemented the GDM pregnant mouse model with vitamin D and found that vitamin D can effectively alleviate the hyperglycemia in GDM pregnant mice, increase blood insulin and adiponectin concentrations, and improve GTT and ITT in pregnant mice. In addition, vitamin D can reduce the incidence of death and high birth weight of offspring caused by GDM. The offspring of GDM pregnant mice had higher blood glucose levels in the first 5 weeks after birth compared to the normal group, and then returned to normal levels. Vitamin D can alleviate abnormal glucose metabolism in newborn mice. The therapeutic effect exhibited by vitamin D may be due to their anti-inflammatory effects, as vitamin D supplementation significantly reduces the levels of TFN-?, MCP-1, IL-1? and IL-8 in the blood. Vitamin D also regulates liver lipid metabolism, resulting in a decrease in liver lipid accumulation and a decrease in blood triglycerides (TG) and cholesterol (CHO). The results of this study demonstrate that vitamin D supplementation can serve as an effective treatment strategy for alleviating GDM symptoms. Keywords: Gestational diabetes mellitus, Vitamin D, Glucose metabolism, Anti-inflammatory.

Saccharomycetaceae: delineation of fungal genera based on phylogenomic analyses, genomic relatedness indices and genomics-based synapomorphies.

A correct classification of fungi, including yeasts, is of prime importance to understand fungal biodiversity and to communicate about this diversity. Fungal genera are mainly defined based on phenotypic characteristics and the results of single or multigene-based phylogenetic analyses. However, because yeasts often have less phenotypic characters, their classification experienced a strong move towards DNA-based data, from short ribosomal sequences to multigene phylogenies and more recently to phylogenomics. Here, we explore the usefulness of various genomics-based parameters to circumscribe fungal genera more correctly taking the yeast domain as an example. Therefore, we compared the results of a phylogenomic analysis, average amino acid identity (AAI) values, the presence of conserved signature indels (CSIs), the percentage of conserved proteins (POCP) and the presence-absence patterns of orthologs (PAPO). These genome-based metrics were used to investigate their usefulness in demarcating 13 hitherto relatively well accepted genera in Saccharomycetaceae, namely Eremothecium, Grigorovia, Kazachstania, Kluyveromyces, Lachancea, Nakaseomyces, Naumovozyma, Saccharomyces, Tetrapisispora, Torulaspora, Vanderwaltozyma, Zygosaccharomyces and Zygotorulaspora. As a result, most of these genera are supported by the genomics-based metrics, but the genera Kazachstania, Nakaseomyces and Tetrapisispora were shown to be genetically highly diverse based on the above listed analyses. Considering the results obtained for the presently recognized genera, a range of 80-92 % POCP values and a range of 60-70 % AAI values might be valuable thresholds to discriminate genera in Saccharomycetaceae. Furthermore, the genus-specific genes identified in the PAPO analysis and the CSIs were found to be useful as synapomorphies to characterize and define genera in Saccharomycetaceae. Our results indicate that the combined monophyly-based phylogenomic analysis together with genomic relatedness indices and synapomorphies provide promising approaches to delineating yeast genera and likely those of filamentous fungi as well. The genera Kazachstania, Nakaseomyces and Tetrapisispora are revised and we propose eight new genera and 41 new combinations. Citation: Liu F, Hu Z-D, Yurkov A, et al. 2024. Saccharomycetaceae: delinaeation of fungal genera based on phylogenomic analyses, genomic relatedness indices and genomics-based synapomorphies. Persoonia 52: 1-21. https://doi.org/10.3767/persoonia.2024.52.01.

[A normative study of speech development in Mandarin-speaking infants and children].

Objective: The aim of this study is to analyze the development of speech ability in Mandarin-speaking infants and children with normal hearing using MUSS and to provide a normal value control for the evaluation of speech ability in children with hearing loss. Methods: From September 2012 to January 2023, a total of 256 infants and children aged 1-60 months in Mandarin language environment participated in this study. 200 infants and children aged from 1 to 60 months were finally included, whose hearing was considered normal according to the history collection, high-risk registers for hearing loss and hearing screening. All infants and children were divided into 10 groups with 20 infants or children in each group. They were: 1 month, 2-3 months, 4-6 months, 7-9 months, 10-12 months, 13-18 months, 19-24 months, 25-36 months, 37-48 months, and 49-60 months. Using SPSS 19.0 software for data analysis, we calculated regression equations based on fitting curves. Results: The language ability of infants and children with normal hearing increased with age and reached ceiling at 56.5months.The regression equation was: score=-0.009 3×(age) 2+2.179×(age)+6.718 6, r2=0.85; age=0.003 9×(score) 2+0.148 4×(score)+2.708, r2=0.85. Conclusions: The speech ability of infants and children with normal hearing shows an increasing trend with age. Scores of different speech skills can be predicted according to their age. Age can also be predicted according to their scores of different speech skills.

[Effect of RDN on long-term blood pressure in refractory hypertensive patients with different cardiovascular risk stratification].

Objective: To investigate the long-term therapeutic effects and safety of renal denervation (RDN) on hypertensive patients with different cardiovascular risks, as well as its impact on adverse events, cardiovascular death and all-cause mortality. Methods: This was a single-center, single-arm, real-world retrospective study. Patients with refractory hypertension who underwent RDN at Tianjin First Central Hospital from July 6, 2011 to December 23, 2015 were enrolled and divided into either a high or intermediate-low risk group based on baseline cardiovascular risk. The treatment responsiveness of hypertensive patients with different cardiovascular stratification to RDN was assessed by comparing the results of office blood pressure, home blood pressure, and 24-h ambulatory blood pressure monitoring at 1, 5, and 11 years after RDN. Long-term safety of RDN was assessed by creatinine, and estimated glomerular filtration rate (eGFR) at 1 and 11 years after RDN. In addition, the total defined daily dose (DDD) of antihypertensive medications and the incidence of long-term adverse events, cardiovascular deaths, and all-cause deaths after RDN were followed up 11 years after RDN in person or by telephone. Results: A total of 62 patients with refractory hypertension, aged (50.2±15.0) years, of whom 35 (56.5%) were male, were included. There were 35 cases in high-risk group and 27 cases in low and medium risk group. The decrease in clinic systolic blood pressure (high risk vs. low-medium risk: (-38.0±15.1) mmHg vs. (-25.0±16.6) mmHg(1 mmHg=0.133kPa),P=0.002), home self-measured systolic blood pressure ((-28.4±12.7) mmHg vs. (-19.7±13.1) mmHg,P=0.011) and clinic systolic blood pressure 11 years after RDN ((-43.0±18.4) mmHg vs. (-27.8±17.9) mmHg,P=0.003) in the high-risk group was significantly higher than that in the low-medium risk group. The differences in heart rate and the decrease in total DDD number of antihypertensive drugs between the two groups were not statistically significant (all P>0.05). Creatinine and eGFR levels in the two groups at 1 and 11 years after RDN were not statistically significant when compared with the baseline values (all P>0.05). The cumulative cardiovascular mortality rate was 1.6% (1/62) and 8.1% (5/62), and the cumulative all-cause mortality rate was 3.2% (2/62) and 11.3% (7/62) at 5 and 11 years after RDN, respectively. The differences in the incidence rate of adverse events, cardiovascular mortality, and all-cause mortality rate between the two groups were not statistically significant (all P>0.05). Conclusions: RDN has long-term antihypertensive effect and good safety. Hypertensive patients who belong to the high-risk stratification of cardiovascular risk may respond better to RDN treatment.

Neuroprotection of low dose carbon monoxide in Parkinson's disease models commensurate with the reduced risk of Parkinson's among smokers.

Paradoxically, cigarette smoking is associated with a reduced risk of Parkinson's Disease (PD). This led us to hypothesize that carbon monoxide (CO) levels, which are constitutively but modestly elevated in smokers, might contribute to neuroprotection. Using rodent models of PD based on α-synuclein (αSyn) accumulation and oxidative stress, we show that low-dose CO mitigates neurodegeneration and reduces αSyn pathology. Oral CO administration activated signaling cascades mediated by heme oxygenase-1 (HO-1), which have been implicated in limiting oxidative stress, and in promoting αSyn degradation, thereby conferring neuroprotection. Consistent with the neuroprotective effect of smoking, HO-1 levels in cerebrospinal fluid were higher in human smokers compared to nonsmokers. Moreover, in PD brain samples, HO-1 levels were higher in neurons without αSyn pathology. Thus, CO in rodent PD models reduces pathology and increases oxidative stress responses, phenocopying possible protective effects of smoking evident in PD patients. These data highlight the potential for low-dose CO-modulated pathways to slow symptom onset and limit pathology in PD patients.

Whole genome sequencing reveals that five genes are related to BW trait in sheep.

BW is an important economic trait in sheep that influences growth and development. Currently, most studies have used a single approach to screen genes associated with BW traits in sheep. To address this limitation, we conducted a genome-wide association study (GWAS) covering four different BW periods: birth, weaning, 6 months, and 12 months. Five new candidate genes: MAP3K1, ANKRD55, ABCB1, MEF2C and TRNAW-CCA-87 were screened using a combination of GWAS and quantitative trait loci analysis in sheep. Additionally, five genes were subjected to Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. These genes were primarily enriched in pathways related to growth hormone and energy metabolism. The results demonstrated that the above genes potentially influenced the growth and development of sheep. The five new candidate genes are closely related to the BW trait in sheep, which will be valuable for understanding the genetic mechanisms underlying BW traits and for guiding sheep breeding.

A phase I trial of LHC165 single agent and in combination with spartalizumab in patients with advanced solid malignancies.

BACKGROUND: LHC165 is a Toll-like receptor (TLR)-7 agonist that generates an effective tumor antigen-specific T-cell adaptive immune response as well as durable antitumor responses. We aimed to evaluate the safety, tolerability, efficacy, dose-limiting toxicities, and pharmacokinetics (PK) of LHC165 single agent (SA) ± spartalizumab [PDR001; anti-programmed cell death protein 1 (PD-1)] in adult patients with advanced solid tumors. MATERIALS AND METHODS: In this phase I/Ib, open-label, dose-escalation/expansion study, patients received LHC165 SA 100-600 µg biweekly through intratumoral (IT) injection and LHC165 600 µg biweekly + spartalizumab 400 mg Q4W through intravenous (IV) infusion. RESULTS: Forty-five patients were enrolled: 21 patients received LHC165 SA, and 24 patients received LHC165 + spartalizumab. The median duration of exposure was 8 weeks (range 2-129 weeks). No maximum tolerated dose was reached. Recommended dose expansion was established as LHC165 600 µg biweekly as SA and in combination with spartalizumab 400 mg Q4W. The most common drug-related adverse events (AEs) were pyrexia (22.2%), pruritus (13.3%), chills (11.1%), and asthenia (4.4%). The only serious AE (SAE) suspected to be related to the study drug was grade 3 pancreatitis (n = 1). Across all tumor types, overall response rate and disease control were 6.7% and 17.8%, respectively. Overall median progression-free survival (PFS) and immune-related PFS was 1.7 months. LHC165 serum PK demonstrated an initial rapid release followed by a slower release due to continued release of LHC165 from the injection site. CONCLUSIONS: LHC165 demonstrated acceptable safety and tolerability both as SA and in combination with spartalizumab, and evidence of limited antitumor activity was seen in adult patients with relapsed/refractory or metastatic solid tumors.

Association between non-alcoholic fatty liver disease and metabolic abnormalities in children with different weight statuses.

OBJECTIVES: Both obesity and non-alcoholic fatty liver disease (NAFLD) increase the risk of metabolic abnormalities. However, the metabolic status of children suffering from NAFLD and exhibiting various subtypes of obesity is currently unclear. We aimed to explore the association between NAFLD and metabolic abnormalities in children with different weight statuses. METHODS: We included 6086 participants aged 6-18 years from the China Child and Adolescent NAFLD Study (CCANS), all of whom had undergone ultrasonography or magnetic resonance imaging-proton density fat fraction (MRI-PDFF) to identify NAFLD and metabolic abnormalities, including hyperglycemia, high triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C), high low-density lipoprotein cholesterol, high total cholesterol, and hyperuricemia. RESULTS: Among the participants, there were 2408 children with obesity and NAFLD, 174 with NAFLD, 2396 with obesity, and 1108 without obesity and NAFLD. The odds ratios (ORs) of suffering from individual metabolic abnormalities were significantly greater in children with obesity and NAFLD than in children without obesity and NAFLD, with ORs ranging from 6.23 (95% CI: 4.56, 8.53) to 1.77 (95% CI: 1.06, 2.94). The ORs of metabolic abnormalities, except for low HDL-C, were greater in children with NAFLD alone than in children without obesity or NAFLD, with ORs ranging from 4.36 (95% CI: 2.77, 6.84) to 2.08 (95% CI: 1.14, 3.78). Notably, obesity and NAFLD had a multiplicative effect on overall metabolic abnormalities, high TG levels, and low HDL-C levels. CONCLUSIONS: Children with obesity and NAFLD could be at a significantly increased risk of metabolic abnormalities. Even for children without obesity, NAFLD appears to be associated with an increased risk of experiencing a worsened metabolic status.

[Prostate cancer with BRCA2 pathogenic mutation: a clinicopathological analysis].

Objective: To analyze the clinicopathological features of prostate cancers with BRCA2 pathogenic mutations, and the association between BRCA2 pathogenic mutation and clinicopathological characteristics. Patient survivals were also examined. Methods: Clinicopathological data of 249 prostate cancer patients who underwent genetic testing in West China Hospital of Sichuan University, Chengdu, China from June 2014 to August 2021 were collected. A retrospective analysis of histopathological morphology, clinicopathological characteristics, and patient survivals was conducted. Results: The genetic testing in the 249 prostate cancer patients showed a pathogenic mutation of DNA damage repair gene (DRG) in 73 cases (73/249, 29.3%), including 22 cases (8.8%) with BRCA2 pathogenic mutation and 51 cases with pathogenic mutations of other DRG. Among the 22 patients with BRCA2 pathogenic mutation, 14 patients (5.6%) harbored germline mutations and 8 patients (3.2%) somatic mutations. Their ages ranged from 48 to 91 years, with a median of 67 years. Seventeen patients (77.3%) had distant metastasis, including 16 cases with bone metastasis and 1 case with multiple metastases. Thirteen patients (59.1%) were castration-resistant prostate cancer. The histological type was mainly classical prostatic acinar adenocarcinoma, including 16 cases (72.7%) with intraductal carcinoma of the prostate (IDC-P). Six cases (27.3%) showed focal neuroendocrine differentiation. Perineural/vascular invasion and extraprostatic extension were seen in 11 cases (50.0%) and 8 cases (36.4%), respectively. The Gleason scores of 19 patients (86.4%) were≥8. IDC-P was more commonly found in patients with BRCA2 germline pathogenic mutation than those with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation (P=0.002). With a total follow-up time of 189 months, the median overall survival (OS) was 132.3 months. Patients with DRG pathogenic mutation had shorter OS than those with no-DRG pathogenic mutation (P=0.040). The OS of patients with BRCA2 germline pathogenic mutation did not significantly differ from that of patients with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation (P=0.216). Conclusions: The presence of BRCA2 gene pathogenic mutation is common in the prostate cancers with high Gleason grade, advanced clinical stage, and castration resistance. IDC-P is more commonly noted in cases with BRCA2 germline pathogenic mutation than those without. Patients with DRG pathogenic mutation have shorter OS than those with no-DRG pathogenic mutation, but there is no significant association between BRCA2 pathogenic mutations and OS.

[Study on the application value of fecal SDC2 gene methylation detection in colorectal cancer screening of urban residents in Zengcheng District in Guangzhou City].

Objective: To investigate the application value of fecal Syndecan-2 (SDC2) gene methylated SDC2 (mSDC2) detection in colorectal cancer (CRC) screening among urban residents in Guangzhou City. Methods: A cross-sectional study was conducted in Shitan Town, Zengcheng District, Guangzhou City from July to December 2022. A community-based screening program for CRC was conducted among residents aged 40-74 years old. mSDC2 detection was employed in the participants, and those with positive results should be recommended to receive colonoscopy examination. The positive rate of mSDC2 detection, colonoscopy compliance rate, detection rate of intestinal lesions and clinicopathological characteristics were observed. The relationship between cycle threshold (CT) value of mSDC2 and intestinal lesions was explored. Further, the cost-effectiveness of screening was evaluated. Results: A total of 8 189 fecal samples were collected from 8 877 participants with the recovery rate of 92.25%. 8 048 qualified samples were enrolled in this study, consisted of 3 182 males (39.54%) and 4 866 females (60.46%), with the average age of 56 years old (40-74 years). The positive rate of mSDC2 detection was 7.99% (643/8 048), and the compliance rate of colonoscopy was 73.10% (470/643). 20 cases (4.25%) of colorectal cancer, 109 cases (23.19%) of advanced adenoma, 145 cases (30.85%) of non-advanced adenoma, 79 cases (16.81%) of polyps were detected. The detection rate of intestinal lesions was 75.11% and indicated significant differences in gender and age. 20 CRCs included 15 of stage 0-I, 4 of stage Ⅱ-Ⅲ and 1 of unknown stage. The CT value of mSDC2 was negatively correlated with the proportion of advanced colorectal neoplasms (χ2=16.063, P<0.001). The total cost of the screening was 4.339 5 million yuan, the screening benefit was 28.506 2 million yuan, and the benefit-cost ratio was 6.57. Conclusion: The CRC screening strategy of fecal mSDC2 detection combined with colonoscopy has high colonoscopy compliance and detection rate of intestinal lesions, which is conducive to the detection of early CRCs, and has good cost-effectiveness. This study suggests that this method may be applied to the general CRC screening in China and contribute to the prevention of CRC. The CT value of mSDC2 may have a certain suggestion on the malignant degree of intestinal tumors.