Therapeutic mechanism of Qingre Tonglin capsules (QRTL) in CNP via inflammasome suppression.

Objectives: Transperineal (TP) prostate biopsy is increasingly used because of its lower complication rates compared with the transrectal approach. However, prospective data regarding its effects on erectile and ejaculatory function remain limited. This study prospectively evaluated short-term sexual function outcomes after TP prostate biopsy in sexually active men. Methods: This single-center prospective observational cohort study included men undergoing TP prostate biopsy between 15 April 2025 and 1 September 2025. Indications for biopsy were prostate-specific antigen levels >4 ng/mL, abnormal digital rectal examination findings, or suspicious lesions (PI-RADS ≥ 3) on multiparametric prostate MRI. Sexual function was assessed at baseline and at 1 and 3 months after biopsy using the International Index of Erectile Function (IIEF-5), the Premature Ejaculation Diagnostic Tool (PEDT), and the Male Sexual Health Questionnaire–Ejaculatory Dysfunction Short Form (MSHQ-EjD-SF). Results: Overall, 249 sexually active men were analyzed. No significant changes in erectile or ejaculatory function were observed in the overall cohort at either follow-up point. In contrast, among 132 men diagnosed with prostate cancer, significant declines were observed in IIEF-5, PEDT, and MSHQ-EjD-SF scores at both 1 and 3 months compared to baseline (all p < 0.001). Conclusions: Transperineal prostate biopsy minimally affects sexual function in the general population. However, prostate cancer patients experience notable deterioration in erectile and ejaculatory outcomes, which may be a transient decline, and long-term follow-up is necessary for this subgroup.

Expression levels of human leukocyte antigen (HLA) are associated with susceptibility to various diseases and outcomes after allogeneic hematopoietic cell transplantation (allo-HCT). However, there has been no comprehensive analysis of the effect of the expression levels of the HLA-A, -B, -C, and -DRB1 alleles in unrelated (UR)-HCT. Using the Capture RNA-Seq method, we analyzed the gene expression of HLA alleles in 443 healthy donors and determined the allele-specific transcription levels (AST levels). We assigned median (M)-AST levels to HLA typing data of patients who received a transplant from HLA-A, -B, -C, and -DRB1-matched unrelated donors using transplant registry data. All 6,084 patients were divided into low, middle, and high tertile groups according to the distribution of the sum of the two alleles of the M-AST level for each HLA locus and the sum of the eight alleles of the M-AST level for all four loci. The risk of grade II-IV acute graft-versus-host disease (GVHD) was significantly higher in the middle group (hazard ratio, 1.11; P = 0.044) and high group (hazard ratio, 1.20; P < 0.001) than in the low group for the sum of the HLA-A, -B, -C, and -DRB1 loci. Similar results were observed at the HLA-A, -B, -C, and -DRB1 loci. Higher transcription levels were also associated with a lower risk of relapse at the HLA-B, -C, and -DRB1 loci. Our data suggest that a high transcription level of patient and/or donor HLA may evoke strong alloimmune responses and affect UR-HCT outcomes.

Peginterferon α-2b Enhances HBsAg Loss in NA-Suppressed Low-HBsAg Chronic Hepatitis B Patients: Everest Study in China.

Human leukocyte antigen-C*08 increases the risk of BK virus viremia in kidney transplant recipients.

Thromboelastography-based screening and diagnosis of Factor XIII inhibitor: A case report.

CAR-modified marrow infiltrating lymphocytes efficiently target malignant plasma cells with very low antigen density.

An optimized sandwich ELISA for quantitative detection of fowl adenovirus serotype 4 (FAdV-4) in chickens.

ObjectiveTo investigate the accuracy of risk prediction models and scores for diagnosing ovarian cancer in premenopausal women presenting to secondary care with symptoms and abnormal test results.DesignProspective cohort study.SettingSecondary care in 23 hospitals in the UK between June 2015 and March 2023.ParticipantsPremenopausal women presenting with non-specific symptoms, and raised serum levels of cancer antigen 125 or abnormal imaging results, were prospectively recruited, predominantly referred through the NHS urgent suspected cancer pathway from primary care. A head-to-head comparison of the accuracy of the six risk prediction models and scores was conducted using donated blood and ultrasound scans performed by NHS staff trained in the use of International Ovarian Tumour Analysis (IOTA) imaging terminology. The index tests used were Risk of Malignancy Index 1 (with pre-stated thresholds of 200, 250), Risk of Malignancy Algorithm (7.4%, 11.4%, 12.5%, 13.1%), IOTA Assessment of Different Neoplasias in the adnEXa (ADNEX) (3%, 10%), IOTA simple rules risk model (3%, 10%), IOTA simple rules, and cancer antigen 125 (CA 125, 87 IU/mL). Participants were classified as having primary invasive ovarian cancer versus having benign or normal pathology according to the reference standard determined from surgical specimens or biopsies by histology or cytology, if undertaken, or else at 12 month follow-up. After June 2018, because of covid restrictions and concerns about sample size, recruitment was restricted to only women undergoing surgery within three months of presentation to clinic (in whom ovarian cancer was more likely).Main outcome measuresDiagnostic accuracy at predicting primary invasive ovarian cancer versus benign or normal histology, assessed by analysing the sensitivity, specificity, C index, area under receiver operating characteristic curve, positive and negative predictive values, and calibration plots in participants with conclusive reference standard results and available index test data.Results88 of 1211 premenopausal women received diagnoses of primary ovarian cancer: 49 of 857 women in the pre-June 2018 cohort (prevalence of 5.7%) and 39 of 354 women in the post-June 2018 cohort (11.0%). For the diagnosis of primary ovarian cancer (n=799 women, after exclusion of 58 other diagnoses), Risk of Malignancy Index 1 at the 250 threshold had a sensitivity of 42.6% (95% confidence interval (CI) 28.3 to 57.8; specificity 96.5%, 94.7 to 97.8). Compared with Risk of Malignancy Index 1 at the 250 threshold, CA 125 and all other tests had higher sensitivity (CA 125 at 87 IU/mL threshold: 55.1%, 40.2 to 69.3, P=0.06; Risk of Malignancy Algorithm at 11.4% threshold: 79.2%, 65.0 to 89.5, P<0.001; IOTA ADNEX at 10% threshold: 89.1%, 76.4 to 96.4, P<0.001; IOTA simple rules risk at 10% threshold: 83.0%, 69.2 to 92.4, P<0.001; IOTA simple rules: 75.0%, 56.6 to 88.5, P=0.01) and lower specificity (CA 125 at 87 IU/mL threshold: 89.0%, 86.5 to 91.2, P<0.001; Risk of Malignancy Algorithm at 11.4% threshold: 73.1%, 69.6 to 76.3, P<0.001; IOTA ADNEX at 10% threshold: 75.1%, 71.4 to 78.6, P<0.001; IOTA simple rules risk at 10% threshold: 76.0%, 72.4 to 79.3, P<0.001; IOTA simple rules: 95.2%, 93.0 to 96.9, P=0.06). Results for IOTA simple rules were inconclusive in 120 of 799 participants. Analysis of the complete cohort (n=1211), including the 354 premenopausal women with a higher likelihood of developing ovarian cancer, yielded similar results.ConclusionsCompared to Risk of Malignancy Index 1 at 250 threshold—the test currently used in NHS secondary care to triage women to tertiary care—most tests improve sensitivity but reduce specificity. Ultrasound triage with the IOTA ADNEX model at 10% in secondary care demonstrated the highest sensitivity gain, with a comparable decline in specificity to other comparator tests. Ultrasound with the IOTA ADNEX model at 10% should be considered the new standard of care test for triaging premenopausal women in secondary care. Implementation should incorporate staff training and quality assurance.Trial registrationISRCTN17160843.

To investigate clinical outcomes, treatment, and survival rates of men aged ≥75 years with prostate cancer in Japan. The study used data from the Prostate Cancer Research International: Active Surveillance (PRIAS)-JAPAN, a nationwide, multicentre prospective cohort study of men with clinically localised prostate cancer managed with active surveillance (AS). The original eligibility criteria were clinical stage T1c-T2 disease, prostate-specific antigen (PSA) level ≤10 ng/mL, PSA density (PSAD) <0.20 ng/mL/mL, and Gleason Score ≤3 + 3 with two or fewer positive biopsy cores. In 2021, magnetic resonance imaging use expanded eligibility to include patients with a PSA level ≤20 ng/mL, PSAD <0.25 ng/mL/mL, and Gleason Score ≤3 + 4 with <50% of biopsy cores positive. PSA was monitored every 3-6 months, and biopsies were scheduled at 1, 4, 7, and 10 years, and every 5 years thereafter. The outcomes in those aged ≥75 years (older group) were compared with those aged <75 years (younger group). Of the 1274 eligible patients enrolled by 29 February 2024, 231 were in the older group and 1043 were in the younger group. In the older group, the median age at enrolment was 77 years. At diagnosis, patients in the older group had significantly larger prostate volumes, higher proportion of Gleason Score 3 + 4, and more T2 disease than those in the younger group. The protocol biopsy acceptance rate decreased over time (first: 82.9%, second: 63.6%, third: 42.2%, fourth: 22.4%), with no significant difference between age groups. The 10-year AS persistence rate in the older group was 8.8%. The overall survival was significantly lower in the older group than in the younger group (hazard ratio: 0.32, 95% confidence interval 0.14-0.74); however, the 10-year metastasis-free survival and cancer-specific survival rates in the older group were both 100%. In some patients aged ≥75 years an observation-focused management approach may be appropriate, in which AS is initiated as a structured monitoring phase with planned de-intensification and transition to watchful waiting, to prevent overtreatment while maintaining excellent cancer-specific outcomes.

To determine the short-term oncological results and safety of the ProFocal Laser Therapy for Prostate Tissue Ablation (PFLT-PC) trial, the first phase II clinical trial of ProFocal® (Medlogical Innovations, Sydney, Australia), a novel, cooled laser focal therapy (cLFT) device for prostate cancer (PCa) treatment. Men with localised PCa, prostate-specific antigen (PSA) level ≤15 ng/mL, T stage ≤T2c, International Society of Urological Pathology (ISUP) score 2-3 concordant with multiparametric magnetic resonance imaging (mpMRI) visibledisease were recruited for this trial (Australian and New Zealand Clinical Trial Registry [ACTRN]12618001774213p) at Nepean Hospital, Australia. The cLFT was performed under general anaesthesia as a day procedure. Primary outcome was adequacy of tissue ablation assessed by mpMRI within 72 h and biopsy at 3 months. Secondary outcomes of functional measures were assessed using validated questionnaires (International Prostate Symptom Score, Sexual Health Inventory for Men [SHIM], Expanded Prostate cancer Index Composite [EPIC], 12-item Short-Form Health Survey). Complications and adverse events within 90 days were reported using Clavien-Dindo classification grading. A total of 100 patients were recruited. The median (interquartile range [IQR]) age was 66 (60-72) years, PSA level 5.9 (3.9-7.6) ng/mL, prostate volume 39 (30-51) mL and MRI lesion volume 0.84 (0.57-1.2) mL. The median (IQR) treatment time was 60 (47-70) min. In all, 84% had no ISUP Grade Group ≥2 PCa in their 3-month treatment zone biopsies. Erectile dysfunction was reported in 12% of the men, with a 15% mean decline in the SHIM and EPIC-sexual domains scores. There was a 4.5% decrease on EPIC-urinary domain scores. There was no decline in anyother functional measures. This study's main limitations were the absence of a control group and the short follow-up. The PFLT-PC trial demonstrates that at 3 months, cLFT using the ProFocal device provides an 84% treatment success with low morbidity.

To evaluate the diagnostic performance of combined biomarkers for colorectal cancer (CRC), this prospective observational study enrolled 188 CRC patients and 693 non-CRC controls from Hunan Provincial People's Hospital. Binary logistic regression was used to establish a predictive model for CRC risk factors, and receiver operating characteristic (ROC) curve analysis was performed to assess diagnostic efficacy. Results showed that the positive rates of plasma methylated SEPT9 (mSEPT9) and fecal occult blood test (FOBT) in the CRC group were significantly higher than those in the non-CRC group (both P < 0.001). Additionally, levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), red blood cell distribution width-coefficient of variation (RDW-CV), red blood cell distribution width-standard deviation (RDW-SD), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were markedly elevated in CRC patients (all P < 0.001). Multivariate regression identified mSEPT9, CEA, CA19-9, FOBT, RDW-CV, and PLR as independent CRC-related factors. Notably, their combined model achieved an area under the curve (AUC) of 0.939, with a sensitivity of 0.920 and specificity of 0.839, offering a valuable non-invasive strategy to enhance CRC diagnosis.

BACKGROUND Postoperative recurrence remains a major challenge in gastric cancer management. Monitoring serum biomarkers such as carcinoembryonic antigen (CEA) may enable earlier detection of recurrence and improve patient outcomes. AIM To evaluate postoperative serum CEA expression and its efficacy in predicting gastric cancer recurrence. METHODS This retrospective study analyzed clinical data from 120 patients with primary gastric cancer treated between January 2022 and January 2023. Patients were categorized into recurrence and non-recurrence groups. Serum levels of CEA, alpha-fetoprotein (AFP), and carbohydrate antigen 19-9 (CA19-9) were measured at one week, three months, and six months postoperatively. Logistic regression identified independent risk factors for recurrence, Pearson correlation assessed the association with recurrence timing, and receiver operating characteristic (ROC) curves evaluated the predictive performance of combined CEA and AFP levels. RESULTS During 24 months of follow-up, 39 patients (32.50%) experienced recurrence. No significant baseline differences were observed between groups (P &gt; 0.05). CEA, AFP, and CA19-9 levels at one week were comparable between groups (P &gt; 0.05), whereas levels at three and six months were significantly higher in the recurrence group (P &lt; 0.05). Logistic regression identified postoperative CEA and AFP as independent risk factors for recurrence (P &lt; 0.05). Pearson correlation showed a negative association between CEA and AFP levels and recurrence interval (P &lt; 0.05). ROC curve analysis demonstrated that combined CEA and AFP yielded an area under the curve of 0.826, with specificity of 94.36% and sensitivity of 90.50%, outperforming either marker alone (P &lt; 0.05). CONCLUSION Dynamic postoperative monitoring of serum CEA and AFP enables early prediction and detection of gastric cancer recurrence.

Differentiating prostate cancer (PCa) in the transition zone (TZ) from benign prostate hyperplasia based on MRI findings has often been challenging. This study aims to evaluate the utility of a quantitative analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using time-resolved angiography with stochastic trajectories‒volumetric interpolated breath-hold examination (TWIST-VIBE) in cases of PCa in the TZ. In this retrospective study, we examined the biopsy findings of 23 patients with elevated prostate-specific antigen (PSA) levels (>4 ng/mL) who underwent DCE-MRI using TWIST-VIBE. The parameters analyzed included Ktrans (the transfer constant), Kep (the reflux constant), Ve (the extravascular extracellular volume fraction), and the initial area under the curve on the Tissue 4D platform (Siemens). The quantitative analysis revealed no significant differences in any of the examined parameters between positive and negative PCa in the TZ. Additionally, there were no significant differences among the histological grades of PCa in the TZ. A quantitative analysis of findings obtained by DCE-MRI using TWIST-VIBE did not yield statistically significant results for differentiating the status of PCa in the TZ. However, DCE-MRI using TWIST-VIBE, an ultrafast DCE-MRI technique, may be useful for evaluating tumor hemodynamics and assessing the size dependence of prostate cancer lesions in the transition zone.

RNA interference (RNAi) therapeutics targeting hepatitis B virus (HBV) RNAs and monoclonal antibodies (mAbs) targeting HBV surface antigen (HBsAg) represent potential strategies for enabling functional cure in chronic HBV patients. Tobevibart (VIR-3434) is an investigational, Fc-engineered human mAb that targets HBsAg with pan-genotypic neutralizing activity. Elebsiran (VIR-2218) is an investigational small interfering RNA targeting a conserved region of the HBV genome. The in vitro antiviral activity of elebsiran was assessed in HBV-infected primary human hepatocytes and hepatoma cells and showed potent inhibition of viral markers HBeAg (EC50 of 2.5 nM and 53.7 pM, respectively) and HBsAg (EC50 of 1.4 nM and 66.5 pM, respectively). Tobevibart and elebsiran activity in vivo was determined using two well-established HBV mouse models: AAV-HBV transduced C57BL/6 mice and human liver-chimeric mice. Mice were treated with a monotherapy or a combination of muHBC34 (the murinized parental mAb of tobevibart) and elebsiran at different doses. In both models, the mouse surrogate of tobevibart or elebsiran monotherapy was effective in reducing blood HBsAg levels. Combined treatment improved suppression of HBsAg (maximum mean reductions of 2.81 log in the AAV-HBV model and 2.51 log in human liver-chimeric mice) and HBV DNA over monotherapy. Tobevibart and elebsiran have been tested in clinical trials for the treatment of chronic hepatitis B and chronic hepatitis Delta.

The role of WNT10B expression in the prognosis of colorectal cancer: A retrospective study based on TCGA database and clinical data.

BACKGROUNDIn the treatment of nasopharyngeal carcinoma (NPC), there is a lack of effective assessment of the long-term effects on patients. Searching for an effective evaluation scheme and screening a reliable index for various therapeutic regimens is an urgent clinical issue that needs to be resolved.AIMTo establish an effective evaluation scheme and screen a reliable index for NPC patients across various therapeutic regimens.METHODSThis population-based retrospective cohort study included NPC survivors (n = 1142; weighted population, 100984) from the OB database of the Hunan Cancer Hospital, spanning from 2011 to 2023. The software DT Health (V 6.8) and I Medical software were utilized to extract the data. By leveraging the aforementioned database, the survival and mortality rates of NPC patients across various therapeutic regimens were analyzed. Three Cox regression models were formulated to explore the independent association of the Ferritin index with 3- and 5-year mortality risk. We used restricted cubic spline analysis to assess the potential nonlinear relationships between Ferritin-related indices and 3- and 5-year mortality. We also assessed the association between the Ferritin index and mortality using Cox proportional hazards regression models. All NPC patients were randomly divided into training and validation sets in a 3:7 ratio. Receiver operating characteristic (ROC), decision curve analysis (DCA), and calibration curves were plotted simultaneously for both training and validation sets.RESULTSNPC patients were divided into two groups: Survivors (615, 53.85%) and non-survivors (527, 46.15%) based on their 5-year mortality. The 5-year mortality rate of males (71.35%) was higher than that of females (28.65%). The tumor stage of the non-survivors converged to TNM stages III and IV. Non-survivors displayed significantly higher levels of Ferritin, lactate dehydrogenase, and carcinoembryonic antigen than the survivors (P < 0.05). Follow-up analysis revealed that nidaplatin plus 5-fluorouracil (NF), docetaxel plus nidaplatin (TN), and docetaxel plus cisplatin (TP) regimens were associated with imporved 5-year survival in NPC patients. The 3- and 5-year rates showed a significant association with Ferritin level. When patients were stratified by Ferritin index quartiles, the tumor stages were predominantly skewed towards TNM stages III and IVa. Thus, Ferritin serves as a key novel biomarker for assessing NPC treatment efficacy. The Ferritin index was significantly associated with 3- and 5-year mortality risk. This correlation was evident in both the unadjusted and fully adjusted models. There was a minor level, S-shaped correlation between the Ferritin index and 3-year mortality. NPC patients with the Ferritin index in quartiles 1 and 3 had a higher 5-year mortality risk. Kaplan-Meier curves demonstrated that there were significant differences in mortality rates among different Ferritin quartiles. NPC patients with the Ferritin index in quartile 4 exhibited the highest 5-year survival rates. ROC curve analysis based on logistic regression predictive model revealed that the Ferritin index predicted 5-year mortality in the validation set. Additionally, the DCA curves of both the training and validation sets indicated that the Ferritin index optimized the predictive performance of the basic risk model for 5-year mortality.CONCLUSIONThe chemotherapy regimens of NF, TN, and TP for NPC are associated with the prognosis of NPC. The Ferritin index is an important indicator for predicting NPC survival.

Jembrana disease, caused by the Jembrana virus, leads to high mortality (30%) and abortion (49%) in cattle, making vaccination essential. In this study, a multiepitope vaccine was designed using immunogenic TM and CA proteins. Predicted cytotoxic T lymphocyte, helper T lymphocyte, and linear B-cell epitopes were linked with flexible linkers, and the 50S L7/L12 ribosomal protein was added as a TLR4 agonist. In silico analysis confirmed the construct as non-allergenic, antigenic, and thermostable (aliphatic index 85.44), with 94.2% of residues in favored Ramachandran regions. Docking analysis revealed strong binding to TLR4 (−66 kcal/mol), and molecular dynamics simulations validated the structural stability. Immune simulations revealed increased antigen and antibody levels (IgM early, IgG1/IgG2 after day 15), progressive CD4+ T-helper expansion, transient CD8+ T-cell peaks, elevated IFN-γ and IL-2, and strong dendritic cell activation through MHC I and II pathways. These findings indicate the vaccine effectively stimulates humoral and cellular responses, supporting its potential as a promising candidate against the Jembrana virus.

Background and Objectives: The introduction of total neoadjuvant therapy (TNT) in the preoperative stage has been associated with improved oncological outcomes. However, TNT may lead to tissue fibrosis and be accompanied by increased difficulty during surgery. Additionally, predicting tumor response to neoadjuvant therapy is crucial for identifying patients who may achieve a complete pathological response (pCR) or qualify for organ-preserving strategies. The aim of this study is to evaluate the effect of TNT versus conventional chemoradiotherapy (CRT) on tumor regression grade (TRG) and the association between preoperative carcinoembryonic antigen (CEA) levels and good tumor response. A secondary endpoint is to investigate the effect of TNT on surgical difficulty, using indirect indicators like the quality of total mesorectal excision (TME), circumferential resection margin (CRM), and achievement of R0 resection. Materials and Methods: This is a retrospective, single-center study including 93 patients with locally advanced rectal cancer who received either TNT (n = 43) or CRT (n = 50). Results: The TNT group, compared to the CRT group, demonstrated a significantly higher rate of pCR (TRG0) (37.2% vs. 18%, p = 0.038) and good tumor regression (TRG 0–1) (53.5% vs. 28%, p = 0.019). Furthermore, patients with CEA < 5 ng/mL showed significantly higher rates of good tumor response (TRG 0–1) compared to those with CEA ≥ 5 ng/mL (45.3% vs. 16.7%, p = 0.032). When further categorized by treatment type, CEA levels did not demonstrate statistically significant differences Lastly, increased surgical difficulty could not be established, as no significant differences were observed in terms of positive CRM rates, R0 resection, and TME quality between groups. Conclusions: TNT was associated with improved TRG scores compared to CRT without increasing surgical difficulty. Lower pre-treatment CEAs were linked to better tumor response, irrespective of the type of treatment. These findings support the oncological benefit of TNT and suggest that CEA may have some predictive value for treatment response.

Plant-derived polynucleotides (PNs) have emerged as promising regenerative biomolecules; however, their mechanisms remain less defined than those of salmon-derived polydeoxyribonucleotides (S-PDRNs). Here, we extracted polynucleotides from Paeonia lactiflora callus (PL-PN) and evaluated their biological effects on human dermal fibroblasts. PL-PN treatment increased cell viability and pro-collagen I α1 secretion. PL-PN enhanced adenosine A2A receptor expression and activated the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP response element-binding protein (CREB) pathway, accompanied by increased Cyclin D1 levels, retinoblastoma protein (Rb) phosphorylation, and nuclear proliferating cell nuclear antigen (PCNA) levels, indicating an accelerated G1/S transition. PL-PN also significantly reduced nuclear NF-κB localization and downregulated MMP1, MMP3, MMP9, and MMP13, suggesting attenuation of inflammatory and catabolic signaling. Furthermore, PL-PN increased TGF-β maturation, Smad2/3 phosphorylation, and the transcription of COL1A1, COL3A1, and elastin, resulting in enhanced collagen and elastin deposition. These effects are comparable to those of S-PDRN. Although the pathway specificity and in vivo relevance require further studies, our findings provide evidence that PL-PN promotes extracellular matrix regeneration via coordinated proliferative, anabolic, and anti-inflammatory actions. Thus, PL-PN represents a potential sustainable plant-based alternative to S-PDRN for dermatological regeneration.