Objective To investigate the effect of ubiquitin specific peptidase 22 (USP22) on the occurrence and development of esophageal squamous cell carcinoma (ESCC) under hypoxic conditions, and its regulatory relationship with hypoxia-inducible factor-1α (HIF-1α). Methods Western blotting and quantitative polymerase chain reaction were used to detect the differences in USP22 protein and mRNA expression between normal esophageal epithelial cells HEEC and ESCC cell lines KYSE30, KYSE150, EC9706, and TE-1 under normoxic (5% CO2, 20% O2, 75% N2) and hypoxic (5% CO2, 1% O2, 94% N2) conditions. By transfecting USP22 plasmid or siUSP22, ESCC cells were divided into a normoxia control group, a normoxia+USP22 group, a normoxia+siUSP22 group, a hypoxia control group, a hypoxia+USP22 group, and a hypoxia+siUSP22 group. The proliferation and migration abilities of cells in each group were detected. The expression of USP22 and HIF-1α under hypoxic conditions after up-regulating or down-regulating USP22 was detected, and their regulatory relationship was verified. The interaction between USP22 and HIF-1α was verified by co-immunoprecipitation (Co-IP) technique. Results Compared with HEEC cells, the expression of USP22 in ESCC cells was significantly increased (P<0.05). Up-regulation of USP22 expression promoted the proliferation and migration of ESCC cells, while silencing USP22 inhibited the proliferation and migration of ESCC cells (P<0.05). Under hypoxic conditions, the expression of USP22 and HIF-1α increased, and with the up-regulation of USP22 expression, the expression of HIF-1α also significantly increased (P<0.05). Co-IP experiment confirmed the binding between USP22 and HIF-1α. Conclusion Up-regulation of USP22 expression promotes the proliferation and migration of ESCC cells. Hypoxia microenvironment can induce the increase of USP22 expression in ESCC. USP22 may participate in the regulation of the occurrence and development of ESCC by directly binding to HIF-1α.

With the rapid development of artificial intelligence, computational pathology has been seamlessly integrated into the entire clinical workflow, which encompasses diagnosis, treatment, prognosis, and biomarker discovery. This integration has significantly enhanced clinical accuracy and efficiency while reducing the workload for clinicians. Traditionally, research in this field has depended on the collection and labeling of large datasets for specific tasks, followed by the development of task-specific computational pathology models. However, this approach is labor intensive and does not scale efficiently for open-set identification or rare diseases. Given the diversity of clinical tasks, training individual models from scratch to address the whole spectrum of clinical tasks in the pathology workflow is impractical, which highlights the urgent need to transition from task-specific models to foundation models (FMs). In recent years, pathological FMs have proliferated. These FMs can be classified into three categories, namely, pathology image FMs, pathology image-text FMs, and pathology image-gene FMs, each of which results in distinct functionalities and application scenarios. This review provides an overview of the latest research advancements in pathological FMs, with a particular emphasis on their applications in oncology. The key challenges and opportunities presented by pathological FMs in precision oncology are also explored.
Humans ; Precision Medicine/methods* ; Medical Oncology/methods* ; Artificial Intelligence ; Neoplasms/pathology* ; Computational Biology/methods*

Objective To evaluate the efficacy and safety of modified pelvic floor reconstruction in non-nerve-sparing robot-assisted radical prostatectomy (NNS RARP) for improving postoperative urinary control. Methods A retrospective analysis was conducted on the clinical data of 79 prostate cancer patients who underwent NNS RARP at Tangdu Hospital during Jan.2020 and Dec.2023, including 29 in the reconstruction group, and 50 in the non-reconstruction group. The baseline characteristics including age, body mass index, prostate-specific antigen (PSA) level, clinical stage, prostate volume, and biopsy Gleason score, and perioperative indexes including operation time, intraoperative blood loss, catheter indwelling time, complication rate, and positive rate of surgical margins were compared between the two groups. Additionally, urinary continence function was assessed before operation and 1,3,6, and 12 months after operation using the international consultation on incontinence questionnaire-short form (ICIQ-SF) and the incontinence quality of life questionnaire score (I-QoL). Results No statistically significant differences were observed in the baseline characteristics between the two groups (P>0.05). The operation time was significantly longer in the reconstruction group than in the non-reconstruction group [ (110.24±15.08) min vs. (101.80±9.89) min, P=0.010]. There were no significant differences in intraoperative blood loss, catheter indwelling time, complication rate, and positive rate of surgical margins between the two groups (P>0.05). The reconstruction group demonstrated significantly lower ICIQ-SF scores at 1 month [ (10.17±2.16) vs. (11.56±1.66), P=0.002],3 months [ (7.62±1.29) vs. (9.52±1.80), P<0.001], and 6 months postoperatively [ (4.93±1.22) vs. (6.18± 1.67), P=0.001]compared to the non-reconstruction group (adjusted P<0.0125). Conversely, the I-QoL scores were significantly higher in the reconstruction group at 1 month [ (73.32±10.30) vs. (63.88±9.55), P<0.001]and 3 months postoperatively [ (78.91±4.82) vs. (75.66±5.17), P=0.007] (adjusted P<0.0125). However, no significant differences were found in ICIQ-SF or I-QoL scores between the two groups preoperatively and 12 months postoperatively (adjusted P>0.0125). Conclusion The application of modified pelvic floor reconstruction technique in NNS RARP is safe and feasible. Although it slightly prolongs the operation time, it does not increase surgical risks; instead, it effectively promotes early recovery of postoperative urinary continence, thereby significantly enhancing patients'quality of life.

OBJECTIVE: To evaluate the efficacy and safety of dupilumab in the treatment of atopic dermatitis in the elderly. METHODS: In this study, elderly patients with atopic dermatitis treated with dupilumab for at least 16 weeks in the Department of Dermatology and Venereology of Beijing Anzhen Hospital from January 2021 to October 2023 were retrospectively collected. Clinical indicators were compared before, during and after treatment, including pruritus numerical rating score (PNRS), eczema area and severity index (EASI), dermatology life quality index (DLQI) score, and the incidence of adverse events was recorded. The expression of interferon γ (IFN-γ), interleukin-4 (IL-4) and interleukin-6 (IL-6) in peripheral blood were compared before treatment and after 16 weeks of treatment. RESULTS: A total of 90 elder patients with atopic dermatitis were included, EASI, PNRS and DLQI scores all showed a gradual downward trend during the treatment period, which was manifested as a rapid decline in the first 4 weeks after starting treatment, and then the decline gradually leveled off. The results of point-to-point comparison showed that EASI, PNRS and DLQI scores in 4 weeks after treatment were significantly lower than those before treatment (P < 0.001); In the 16th week after treatment, the scores of the above therapeutic indicators were further reduced, and the difference was statistically significant compared with the 4th week (P < 0.01); The EASI score was significantly lower at each time point than the previous time point, indicating that the patients' skin lesions continued to improve significantly. The overall efficacy of dupliumab was evaluated. After 4 weeks of treatment, 62.89% of patients achieved EASI-50 (EASI score decreased by ≥50%), and 74.4% of patients' DLQI score decreased by ≥4 points. After 16 weeks of treatment, 57.8% of the patients achieved EASI-75, 32.2% achieved EASI-90, and the PNRS and DLQI scores of all the patients decreased by ≥4 points. After 16 weeks of treatment, the expression levels of IL-4 and IL-6 were (31.62±6.23) ng/L and (14.36±2.25) ng/L, respectively, which were significantly lower than those before treatment (P < 0.001), and the expression level of IFN-γ was (15.37±3.14) ng/L, which was higher than before treatment (P < 0.001).The main adverse reactions were conjunctivitis (2 cases), injection site reaction (3 cases) and multiple bacterial folliculitis of the back (2 cases), which could be alleviated by symptomatic treatment, and no serious adverse reactions occurred. CONCLUSION Dupilumab has shown good efficacy in the treatment of elderly atopic dermatitis, which can effectively improve clinical symptoms such as itching and skin lesions, improve the quality of life of patients, and no serious adverse reactions occurred during treatment, so it is safe and worthy of clinical promotion.
Humans ; Dermatitis, Atopic/blood* ; Antibodies, Monoclonal, Humanized/adverse effects* ; Aged ; Male ; Female ; Interleukin-4/blood* ; Retrospective Studies ; Quality of Life ; Interleukin-6/blood* ; Interferon-gamma/blood* ; Middle Aged ; Treatment Outcome ; Severity of Illness Index

Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

The gut microbiota is an indispensable symbiotic entity within the human holobiont, serving as a critical regulator of host lipid metabolism homeostasis. Therefore, it has emerged as a central subject of research in the pathophysiology of metabolic disorders. This microbial consortium orchestrates key aspects of host lipid dynamics-including absorption, metabolism, and storage-through multifaceted mechanisms such as the enzymatic processing of dietary polysaccharides, the facilitation of long-chain fatty acid uptake by intestinal epithelial cells (IECs), and the bidirectional modulation of adipose tissue functionality. Mounting evidence underscores that gut microbiota-derived metabolites not only directly mediate canonical lipid metabolic pathways but also interface with host immune pathways, epigenetic machinery, and circadian regulatory systems, thereby establishing an intricate crosstalk that coordinates systemic metabolic outputs. Perturbations in microbial composition (dysbiosis) drive pathological disruptions to lipid homeostasis, serving as a pathogenic driver for conditions such as obesity, hyperlipidemia, and non-alcoholic fatty liver disease (NAFLD). This review systematically examines the emerging mechanistic insights into the gut microbiota-mediated regulation of intestinal lipid metabolism, while it elucidates its translational implications for understanding metabolic disease pathogenesis and developing targeted therapies.
Humans ; Gastrointestinal Microbiome/physiology* ; Lipid Metabolism ; Animals ; Intestinal Mucosa/metabolism* ; Homeostasis ; Dysbiosis ; Obesity/metabolism* ; Intestines/microbiology* ; Non-alcoholic Fatty Liver Disease/metabolism* ; Metabolic Diseases/metabolism*

Objective To explore the diagnostic value of endoscopic grading of gastric intestinal metaplasia (EGGIM) score under acetic acid-enhanced narrow band imaging (AA-NBI) observation mode for gastric intestinal metaplasia (GIM). Methods A total of 120 patients who underwent gastroscopy at Jinshan Hospital of Fudan University from February 2022 to February 2023 were selected. All patients underwent both white light and AA-NBI endoscopy, with photographic records of intestinal metaplasia in five areas: greater curvature of antrum, lesser curvature of antrum, greater curvature of corpus, lesser curvature of corpus and incisura. EGGIM score was performed: 0 for no intestinal metaplasia, 1 point for focal intestinal metaplasia (GIM area ratio≤30%), 2 points for extensive intestinal metaplasia (GIM area ratio＞30%), with a total score of 10 points. Targeted biopsies were performed on suspicious GIM lesions found during endoscopy. If no suspicious GIM lesions were observed, random biopsies were performed according to the updated Sydney system. The pathological histological examination results were staged based on the operative link on gastric intestinal metaplasia assessment (OLGIM) system. The diagnostic value of EGGIM score for OLGIM stage Ⅲ-Ⅳ patients was evaluated using receiver operating characteristic (ROC) curves. Results The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of AA-NBI in detecting GIM were 96.3%, 91.6%, 94.5%, 95.0%, and 93.6%, respectively. The area under the ROC curve for EGGIM diagnosing OLGIM stage Ⅲ-Ⅳ was 0.952 (95%CI 0.914-0.990). The optimal cut-off value for EGGIM was 5 points, with a sensitivity of 96.7% (95%CI 87.6%-99.4%) and specificity of 88.1% (95%CI 76.5%-94.7%). Conclusions EGGIM score (≥5 points) under AA-NBI mode has good diagnostic capability for patients with OLGIM stage Ⅲ-Ⅳ.

Objective: To examine the reciprocal relationships of anxiety and depressive symptoms,uncertainty stress with academic buoyancy among college students, providing evidence for mental health promotion and academic resilience enhancement. Methods: A multi stage cluster random sampling method was used to selected 741 undergraduates from grade 1 to 2 of a university in Xuzhou, Jiangsu Province. Participants completed two waves of surveys (T1: October 2022; T2: October 2023) using the Uncertainty Stress Scale, Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Academic Buoyancy Scale. Cross lagged models analyzed bidirectional relationships between three mental health variables and academic buoyancy, followed by latent variable modeling integrating all mental health dimensions. Results: Cross lagged model results revealed that T1 uncertainty stress negatively predicted T2 academic buoyancy ( β =-0.14), while T1 academic buoyancy negatively predicted T2 uncertainty stress ( β =-0.11); T1 depressive symptom negatively predicted T2 academic buoyancy ( β =-0.08), while T1 academic buoyancy negatively predicted T2 depressive symptom ( β =-0.09); furthermore, T1 academic buoyancy negatively predicted T2 anxiety symptom( β =-0.10) ( P <0.05). Results from the latent variable cross lagged model of psychological problems (constructed from the three mental health variables) indicated that T1 psychological problems negatively predicted T2 academic buoyancy ( β =-0.09), while T1 academic buoyancy negatively predicted T2 psychological problems ( β =-0.09) ( P <0.05). Conclusions Longitudinal bidirectional relationships exist between mental health status and academic buoyancy in college students. Better mental health facilitates higher academic buoyancy.

Renal tumor scoring systems can describe the anatomical characteristics of renal tumors. It is an important standard to evaluate the surgical complexity and to evaluate the surgical complexity and feasibility of partial nephrectomy. Scholars at home and abroad have established various scoring systems based on different anatomical parameters，such as R.E.N.A.L.，PADUA，C-Index，which are used to guide the clinical selection of surgical modalities，and predict perioperative complications and prognosis. In this paper，various scoring systems are grouped into three major categories according to their functions：prediction of surgical complexity，prediction of complications，and prediction of prognosis. The contents，characteristics and clinical application value of various renal tumor scoring systems are introduced in detail to guide urologists，enhance their surgical decision-making ability，and improve the clinical outcomes.

Objective To explore the behavioral characteristics of using cognitive reappraisal(CR)and expressive suppression(ES)in high trait anxiety individuals under both explicit and implicit conditions.Methods A total of 57 non-psychology undergraduates and postgraduates were recruited in a military medical university from June to July in 2023.All the participants were surveyed with Trait Form of Spielberger's State-Trait Anxiety Inventory(STAI-T)and Emotion Regulation Questionnaire(ERQ)to investigate their level of anxiety and usage habits of CR and ES strategies.According to the STAI-T results,they were divided to a high trait anxiety(HTA)group(n=28)and a low trait anxiety(LTA)group(n=29).Then the implicit and explicit emotion regulation(ER)tasks were used to analyze and compare 2 strategies on improving negative emotional pleasure and arousal,and the differences in difficulty and success of using CR and ES under the explicit condition.Results ① Both the HTA and LTA individuals showed a higher use of CR and less use of ES[t(27)=3.94,P<0.001;t(28)=11.33,P<0.001],while the HTA individuals used more ES[t(55)=3.02,P<0.01]and less CR than the LTA individuals[t(55)=-2.20,P=0.02].②Compared with implicit neutral priming,both implicit CR(Pleasure:2.56±0.11 vs 2.73±0.12,P<0.01;Arousal:6.68±0.18 vs 6.51±0.20,P<0.05)and implicit ES priming(Pleasure:2.56±0.11 vs 2.86±0.11,P<0.001;Arousal:6.68±0.18 vs 6.30±0.20,P<0.001)improved the negative emotional experiences of both HTA and LTA groups,and ES showed better effect(Pleasure:P<0.001;Arousal:P<0.001).③ Explicit CR(Pleasure:2.92±0.12 vs 5.09±0.09,P<0.001;Arousal:6.43±0.20 vs 4.33±0.21,P<0.001)and explicit ES(Pleasure:2.92±0.12 vs 4.34±0.09,P<0.001;Arousal:6.43±0.20 vs 4.22±0.22,P<0.001)ameliorated the negative feelings in the HTA and LTA individuals,and the effect of explicit CR on improving pleasure was superior than that of explicit ES(P<0.001).For the HTA individuals,it is more difficult to implement CR and ES[CR:t(55)=2.16,P=0.02;ES:t(55)=2.92,P<0.01],and ES was less successful in emotion regulation when compared with the LTA individuals[t(55)=-1.88,P=0.03];the difficulty of using ES was significantly higher than that of CR[4.00±1.81 vs 5.00±1.80,t(27)=-2.78,P<0.01],and the success rate was also lower[7.04±1.00 vs 6.64±1.13,t(27)=2.09,P=0.02].④ Comparing the effects of emotion regulation under implicit and explicit conditions,it was presented that explicit CR and ES were better than implicit CR and ES for both HTA and LTA individuals(Pleasure:explicit CR vs implicit CR:5.09±0.09 vs 2.73±0.12,P<0.001;explicit ES vs implicit ES:4.34±0.09 vs 2.86±0.11,P<0.001;Arousal:explicit CR vs implicit CR:4.33±0.21 vs 6.51±0.20,P<0.001;explicit ES vs implicit ES:4.22±0.22 vs 6.30±0.20,P<0.001).Conclusion In terms of usage habits of ER strategies,HTA individuals tend to use ES more and CR less than LTA individuals.Under the implicit/explicit conditions,HTA individuals can both employ CR and ES to improve negative emotional experience,and the effect of explicit ER is significantly better than implicit condition.