[Objective] To analyze the clinicopathological characteristics of treatment-naive patients with highly suspected prostate cancer (PCa) with prostate-specific antigen (PSA) level ≥20 ng/mL, to provide reference for promoting early screening of PCa. [Methods] A retrospective analysis was conducted on the clinical data of treatment-naive patients with PSA level ≥20 ng/mL, undergoing prostate biopsy for highly suspected PCa at the Department of Urology, Tianjin Medical University Second Hospital during Jan.2013 and Jun.2023. The correlation between patients' age, body mass index (BMI), PSA, prostate volume (PV), prostate cancer-specific antigen density (PSAD), prostate imaging reporting and data system (PI-RADS) score, and International Society of Urological Pathology (ISUP) grade with highly suspected PCa metastasis and PSA stratification were analyzed. [Results] A total of 1778 suspected patients were enrolled. Pathological findings confirmed PCa in 1465 cases (82.4%), with 487(33.2%) diagnosed as metastatic PCa. Over the past decade, the number of patients undergoing prostate biopsy for highly suspected PCa and being confirmed has been increasing annually, with the proportion of metastatic cases remaining at around 30%. Compared with those with PSA level being 20-50 ng/mL, patients with PSA level >50 ng/mL had older age, lower BMI, higher PSAD, higher PI-RADS, higher ISUP, more diverse pathological types, and a higher incidence of metastasis (P<0.05) with lower proportion of urban residents. Additionally, analysis of metastatic PCa cases showed that 46.8%(228/487) had oligometastasis (≤5 metastatic lesions), including 99.0% bone metastasis, 4.1% extraregional lymph node metastasis, and 4.3% other organ metastasis. [Conclusion] Over the past 10 years, there has been a continuous increase in the number of treatment-naive biopsied cases and newly diagnosed cases of highly suspicious PCa with PSA level ≥20 ng/mL, while the proportion of metastatic cases remains high. Therefore, proactive efforts should be made to promote early screening of high-risk suspected cases.

BACKGROUND: T cell dysfunction, which includes exhaustion, anergy, and senescence, is a distinct T cell differentiation state that occurs after antigen exposure. Although T cell dysfunction has been a cornerstone of cancer immunotherapy, its potential in transplant research, while not yet as extensively explored, is attracting growing interest. Interferon regulatory factor 4 (IRF4) has been shown to play a pivotal role in inducing T cell dysfunction. METHODS: A novel ultra-low-dose combination of Trametinib and Rapamycin, targeting IRF4 inhibition, was employed to investigate T cell proliferation, apoptosis, cytokine secretion, expression of T-cell dysfunction-associated molecules, effects of mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling pathways, and allograft survival in both in vitro and BALB/c to C57BL/6 mouse cardiac transplantation models. RESULTS: In vitro , blockade of IRF4 in T cells effectively inhibited T cell proliferation, increased apoptosis, and significantly upregulated the expression of programmed cell death protein 1 (PD-1), Helios, CD160, and cytotoxic T lymphocyte-associated antigen (CTLA-4), markers of T cell dysfunction. Furthermore, it suppressed the secretion of pro-inflammatory cytokines interferon (IFN)-γ and interleukin (IL)-17. Combining ultra-low-dose Trametinib (0.1 mg·kg -1 ·day -1 ) and Rapamycin (0.1 mg·kg -1 ·day -1 ) demonstrably extended graft survival, with 4 out of 5 mice exceeding 100 days post-transplantation. Moreover, analysis of grafts at day 7 confirmed sustained IFN regulatory factor 4 (IRF4) inhibition, enhanced PD-1 expression, and suppressed IFN-γ secretion, reinforcing the in vivo efficacy of this IRF4-targeting approach. The combination of Trametinib and Rapamycin synergistically inhibited the MAPK and mTOR signaling network, leading to a more pronounced suppression of IRF4 expression. CONCLUSIONS Targeting IRF4, a key regulator of T cell dysfunction, presents a promising avenue for inducing transplant immune tolerance. In this study, we demonstrate that a novel ultra-low-dose combination of Trametinib and Rapamycin synergistically suppresses the MAPK and mTOR signaling network, leading to profound IRF4 inhibition, promoting allograft acceptance, and offering a potential new therapeutic strategy for improved transplant outcomes. However, further research is necessary to elucidate the underlying pharmacological mechanisms and facilitate translation to clinical practice.
Animals ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Interferon Regulatory Factors/metabolism* ; Heart Transplantation/methods* ; T-Lymphocytes/immunology* ; Sirolimus/therapeutic use* ; Pyridones/therapeutic use* ; Graft Survival/drug effects* ; Pyrimidinones/therapeutic use* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Male ; Signal Transduction/drug effects*

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

OBJECTIVE: To investigate the clinical efficacy and safety of single Kirschner wire assisted poking and closed reduction in the treatment of Gartland type Ⅲ supracondylar humeral fractures in children. METHODS: A retrospective analysis was performed on patients diagnosed with Gravland type Ⅲ supracondylar humeral fractures between January 2022 and June 2023. A total of 46 patients were treated with closed reduction assisted by Kirschner wires and percutaneous Kirschner wire internal fixation.There were 25 males and 21 females. The age ranged from 5 to 10 years old, with an average of (5.8±1.8) years old. The left side was involved in 28 patients and the right side in 18 patients. Record the operative duration for patients, the number of fluoroscopic exposures, fracture healing time, postoperative carrying angle, Baumann angle, elbow joint function score at three months post-operation, and any associated complications. RESULTS: All 46 patients were followed up for a period of 12 to 16 weeks, with an average of (13.74±1.44 )weeks. The operation duration was (30.7±5.1) minutes, the fluoroscopy count was (10.2±2.7) times, the postoperative carrying angle of the elbow joint was (8.7±2.2) degrees, and the Baumann angle was (71.5±2.9) degrees. All fractures achieved successful union in all patients, with a mean healing time of (25.5±1.7) days.At the final follow-up, elbow joint function was assessed using the Flynn criteria, with 43 patients rated as excellent and 3 patients rated as good. No complications were observed, including cubitus varus, nerve injury, or local infection. CONCLUSION The use of a single Kirschner wire assisted prying reduction for treating Gartland type Ⅲ supracondylar humeral fractures in children demonstrates excellent clinical efficacy and safety.
Humans ; Male ; Female ; Child ; Bone Wires ; Child, Preschool ; Humeral Fractures/physiopathology* ; Retrospective Studies ; Fracture Fixation, Internal/instrumentation* ; Treatment Outcome ; Fracture Healing

OBJECTIVES: To evaluate the efficacy and safety of avatrombopag in promoting platelet engraftment after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children, compared with recombinant human thrombopoietin (rhTPO). METHODS: A retrospective analysis was conducted on 53 pediatric patients who underwent allo-HSCT at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from April 2023 to August 2024. Based on medications used during the periengraftment period, patients were divided into two groups: the avatrombopag group (n=15) and the rhTPO group (n=38). RESULTS: At days 14, 30, and 60 post-transplant, platelet engraftment was achieved in 20% (3/15), 60% (9/15), and 93% (14/15) of patients in the avatrombopag group, and in 39% (15/38), 82% (31/38), and 97% (37/38) in the rhTPO group, respectively. There were no significant differences between the two groups in platelet engraftment rates at each time point, cumulative incidence of platelet engraftment, overall survival, and relapse-free survival (all P>0.05). Multivariable Cox proportional hazards analysis indicated that acute graft-versus-host disease was an independent risk factor for delayed platelet engraftment (P=0.043). CONCLUSIONS In children undergoing allo-HSCT, avatrombopag effectively promotes platelet engraftment, with efficacy and safety comparable to rhTPO, and represents a viable therapeutic option.
Humans ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child ; Child, Preschool ; Infant ; Adolescent ; Transplantation, Homologous ; Blood Platelets/drug effects* ; Thiazoles/therapeutic use* ; Thrombopoietin/therapeutic use* ; Thiophenes

OBJECTIVE: To investigate lymph node metastasis (LNM) in the prostatic anterior fat pad (PAFP) of PCa patients after robot-assisted radical prostatectomy (RARP), and analyze the clinicopathological features and prognosis of LNM in the PAFP. METHODS: We retrospectively analyzed the clinicopathological data on 1 003 cases of PCa treated by RARP in the Department of Urology of PLA General Hospital from January 2017 to December 2022. All the patients underwent routine removal of the PAFP during RARP and pathological examination, with the results of all the specimens examined and reported by pathologists. Based on the presence and locations of LNM, we grouped the patients for statistical analysis, compared the clinicopathological features between different groups using the Student's t, Mann-Whitney U and Chi-square tests, and conducted survival analyses using the Kaplan-Meier and Log-rank methods and survival curves generated by Rstudio. RESULTS: Lymph nodes were detected in 77 (7.7%) of the 1 003 PAFP samples, and LNM in 11 (14.3%) of the 77 cases, with a positive rate of 1.1% (11/1 003). Of the 11 positive cases, 9 were found in the upgraded pathological N stage, and the other 2 complicated by pelvic LNM. The patients with postoperative pathological stage≥T3 constituted a significantly higher proportion in the PAFP LNM than in the non-PAFP LNM group (81.8% ［9/11］ vs 36.2% ［359/992］, P = 0.005), and so did the cases with Gleason score ≥8 (87.5% ［7/8］ vs 35.5% ［279/786］, P = 0.009). No statistically significant differences were observed in the clinicopathological features and biochemical recurrence-free survival between the patients with PAFP LNM only and those with pelvic LNM only. CONCLUSION The PAFP is a potential route to LNM, and patients with LNM in the PAFP are characterized by poor pathological features. There is no statistically significant difference in biochemical recurrence-free survival between the patients with PAFP LNM only and those with pelvic LNM only. Routine removal of the PAFP and independent pathological examination of the specimen during RARP is of great clinical significance.
Humans ; Male ; Prostatectomy/methods* ; Robotic Surgical Procedures ; Lymphatic Metastasis ; Retrospective Studies ; Prognosis ; Prostatic Neoplasms/pathology* ; Adipose Tissue/pathology* ; Prostate/pathology* ; Lymph Nodes/pathology* ; Middle Aged ; Aged

The liver regenerative capacity is crucial for patients with end-stage liver disease following partial hepatectomy (PHx). The specific bacteria and mechanisms regulating liver regeneration post-PHx remain unclear. This study demonstrated dynamic changes in the abundance of Parabacteroides distasonis (P. distasonis) post-PHx, correlating with hepatocyte proliferation. Treatment with live P. distasonis significantly promoted hepatocyte proliferation and liver regeneration after PHx. Targeted metabolomics revealed a significant positive correlation between P. distasonis and β-hydroxybutyric acid (BHB), as well as hyodeoxycholic acid and 3-hydroxyphenylacetic acid in the gut after PHx. Notably, treatment with BHB, but not hyodeoxycholic acid or 3-hydroxyphenylacetic acid, significantly promoted hepatocyte proliferation and liver regeneration in mice after PHx. Moreover, STAT3 inhibitor Stattic attenuated the promotive effects of BHB on cell proliferation and liver regeneration both in vitro and in vivo. Mechanistically, P. distasonis upregulated the expression of fatty acid oxidation-related proteins, and increased BHB levels in the liver, and then BHB activated the STAT3 signaling pathway to promote liver regeneration. This study, for the first time, identifies the involvement of P. distasonis and its associated metabolite BHB in promoting liver regeneration after PHx, providing new insights for considering P. distasonis and BHB as potential strategies for promoting hepatic regeneration.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Objective To explore clinical efficacy of osteoplasty combined with percutaneous vertebroplasty(PVP)and percutaneous kyphoplasty(PKP)alone in treating osteoporosis vertebral compression fractures(OVCFs).Methods The clini-cal data of 80 patients with single-level OVCFs treated from January 2021 to June 2022 were retrospectively analyzed,and were divided into treatment group and control group according to different surgical methods,40 patients in each group.In treatment group,there were 24 males and 16 females,aged from 60 to 83 years old with an average of(70.43±7.31)years old;bone min-eral density ranged from-3.30 to-2.50 SD with an average of(-2.84±0.24)SD;1 patient with T10,4 patients with T11,11 pa-tients with T12,7 patients with L1,7 patients with L2,5 patients with L3,3 patients with L4,2 patients with L5;bone setting tech-nique combined with PVP were performed.In control group,there were 27 males and 13 females,aged from 60 to 82 years old with an average of(68.98±6.94)years old;bone mineral density ranged from-3.40 to-2.50 SD with an average of(-2.76±0.23)SD;2 patients with T10,3 patients with T11,13 patients with T12,11 patients with L1,5 patients with L2,3 patients with L3,2 patients with L4,1 patient with L5;simple PKP were peformed.Visual analogue scale(VAS)and lumbar Oswestry disability in-dex(ODI)were compared between two groups before operation,3 days,3 and 12 months after operation.The changes of local kyphotic angle,vertebral wedge angle and vertebral anterior margin height ratio were compared between two groups before op-eration,3 days and 12 months after operation.Results All patients were successfully completed operation.Treatment group were followed up from 13 to 22 months with an average of(16.82±2.14)months,and control group were followed up from 13 to 23 months with an average of(16.45±2.56)months.Three patients were occurred bone cement leakage in treatment group,while 1 patient were occurred bone cement leakage and 1 patient occurred sensory disturbance of lower limb skin in control group;there were no significant difference in complications between two groups(P＞0.05).There were no significant difference in preoperative VAS and ODI between two groups(P＞0.05).At 3 days after operation,VAS of treatment group 3.68±0.62 was significantly higher than that of control group 4.00±0.72(P＜0.05).There were no significant difference in VAS and ODI be-tween two groups at 3 and 12 months after operation(P＞0.05).There were no significant difference in local kyphotic angle,vertebral wedge angle and vertebral anterior margin height between two groups at 3 days and 12 months after operation(P＞0.05).Conclusion Compared with PKP,bone setting manipulation combined with PVP for the treatment of OVCFs has advan-tages in early postoperative pain relief.In terms of vertebral height recovery,bone setting manipulation combined with PVP and PKP alone have similar clinical effects.

Objective To construct an artificial intelligence assisted diagnosis model based on deep learning for dynamically recognizing gastric lesions and their locations under gastroscopy in real time,and to evaluate its ability to detect and recognize gastric lesions and their locations.Methods The gastroscopy videos of 104 patients in our hospital was retrospectively analyzed,and the video frames were manually annotated.The annotated picture frames of lesion category were divided into the training set and the validation set according to the ratio of 8∶2,and the annotated picture frames of location category were divided into the training set and the validation set according to the patient sources at the ratio of 8∶2.These sets were utilized for training and validating the respective models.YoloV4 model was used for the training of lesion recognition,and ResNet152 model was used for the training of location recognition.The accuracy,sensitivity,specificity,positive predictive value,negative predictive value and location recognition accuracy of the auxiliary diagnostic model were evaluated.Results A total of 68 351 image frames were annotated,with 54 872 frames used as the training set,including 41 692 frames for lesion categories and 13 180 frames for location categories.The validation set consisted of 13 479 frames,comprising 10 422 frames for lesion categories and 3 057 frames for location categories.The lesion recognition model achieved an overall accuracy of 98.8%,with a sensitivity of 96.6%,specificity of 99.3%,positive predictive value of 96.3%,and negative predictive value of 99.3% in validation set.Meanwhile,the location recognition model demonstrated an top-5 accuracy of 87.1% .Conclusion The artificial intelligence assisted diagnosis model based on deep learning for real-time dynamic recognition of gastric lesions and their locations under gastroscopy has good ability in lesion detection and location recognition,and has great clinical application prospects.