Objective:To explore the value of non-invasive habitat imaging (HI) multi-parametric MRI (mpMRI) in predicting the risk of prostate cancer (PCa).Methods:In this cross-sectional study, 220 patients with PCa confirmed by radical prostatectomy (RP) who underwent multi-parametric MRI (mpMRI) scanning at Xijing Hospital, Air Force Military Medical University from January 2018 to May 2024 were retrospectively collected. Patients were divided into a training set (154 cases) and a test set (66 cases) by simple random sampling in a 7∶3 ratio. Based on mpMRI imaging, the apparent diffusion coefficient (ADC), perfusion fraction (f), and mean kurtosis (MK) of each voxel were integrated. The K-means clustering algorithm was used to divide the PCa target lesions into habitat subregions, generate habitat maps, and calculate the proportion of each habitat subregion in the entire lesion. According to the 2019 International Society of Urological Pathology (ISUP) guidelines, patients were categorized into a low-risk group (ISUP≤2, 65 cases) and a high-risk group (ISUP≥3, 155 cases). The RP specimens were matched with the habitat map to identify corresponding habitat subregions, and the ISUP grade of each subregion was individually evaluated to calculate the detection rate of high-risk PCa patients. The logistic regression analysis was applied to identify the independent risk factors associated with PCa risk, and the HI-clinical imaging model and clinical imaging model were constructed. The efficacy of the models was assessed using receiver operating characteristic curve.Results:Based on the optimal cluster number, the habitat was divided into three subregions. Habitat 1 had lower ADC and f values and higher MK values, while habitat 2 had the opposite characteristics, and habitat 3 was intermediate. The proportion of habitat 1 in the high-risk group was 28.8%, in the low-risk group was 8.9%. In the training set, the comparison of habitat subregions with pathological results showed that the detection rate of high-risk lesions was 66.9% (103/154) in habitat 1, 25.3% (39/154) in habitat 2, and 47.4% (73/154) in habitat 3. The logistic regression analysis indicated that the proportion of habitat 1 ( OR=3.03, 95% CI 1.77-5.18, P<0.001), prostate-specific antigen ( OR=1.66, 95% CI 1.04-2.66, P=0.034), and the prostate imaging reporting and data system score ( OR=1.65, 95% CI 1.00-2.70, P=0.048) as independent risk factors for high-risk PCa. In the training set, the area under the curve (AUC) for predicting PCa risk was 0.854 (95% CI 0.789-0.920) for the HI-clinical imaging model and 0.779 (95% CI 0.701-0.856) for the clinical imaging model. In the test set, the AUC values were 0.809 (95% CI 0.693-0.895) and 0.738 (95% CI 0.619-0.856), respectively. Conclusion:HI based on mpMRI can effectively predict the risk of PCa.

Protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in liver cancer, yet its roles and in-depth molecular mechanisms within the liver cancer immune microenvironment remain mostly undefined. Here, we demonstrated that disruption of tumor-intrinsic PRMT5 enhances CD8⁺ T-cell-mediated antitumor immunity both in vivo and in vitro. Further experiments verified that this effect is achieved through downregulation of the inhibitory immune checkpoint molecule, fibrinogen-like protein 1 (FGL1). Mechanistically, PRMT5 catalyzed symmetric dimethylation of transcription factor 12 (TCF12) at arginine 554 (R554), prompting the binding of TCF12 to FGL1 promoter region, which transcriptionally activated FGL1 in tumor cells. Methylation deficiency at TCF12-R554 residue downregulated FGL1 expression, which promoted CD8⁺ T-cell-mediated antitumor immunity. Notably, combining the PRMT5 methyltransferase inhibitor GSK591 with PD-L1 blockade efficiently inhibited liver cancer growth and improved overall survival in mice. Collectively, our findings reveal the immunosuppressive role and mechanism of PRMT5 in liver cancer and highlight that targeting PRMT5 could boost checkpoint immunotherapy efficacy.

Metabolic reprogramming plays a central role in tumors. However, the key drivers modulating reprogramming of gluconeogenesis/lipogenesis are poorly understood. Here, we try to identify the mechanism by which histone acetyltransferase 1 (HAT1) confers reprogramming of gluconeogenesis/lipogenesis in liver cancer. Diethylnitrosamine (DEN)/carbon tetrachloride (CCl₄)-induced hepatocarcinogenesis was hardly observed in HAT1-knockout mice. Multi-omics identified that HAT1 modulated gluconeogenesis and lipogenesis in liver. Protein phosphatase 2 scaffold subunit alpha (PPP2R1A) promoted gluconeogenesis and inhibited lipogenesis by phosphoenolpyruvate carboxykinase 1 (PCK1) serine 90 dephosphorylation to suppress the tumor growth. HAT1 succinylated PPP2R1A at lysine 541 (K541) to block the assembly of protein phosphatase 2A (PP2A) holoenzyme and interaction with PCK1, resulting in the depression of dephosphorylation of PCK1. HAT1-succinylated PPP2R1A contributed to the remodeling of gluconeogenesis/lipogenesis by PCK1 serine 90 phosphorylation, leading to the inhibition of gluconeogenic enzyme activity and activating sterol regulatory element-binding protein 1 (SREBP1) nuclear accumulation-induced lipogenesis gene expression, which enhanced the tumor growth. In conclusion, succinylation of PPP2R1A lysine 541 by HAT1 converses the role in modulation of gluconeogenesis/lipogenesis remodeling through PCK1 S90 phosphorylation to support liver cancer. Our finding provides new insights into the mechanism by which post-translational modifications (PTMs) confer the conversion of tumor suppressor function to oncogene.

Temporomandibular joint osteoarthritis (TMJ-OA) is a common disease often accompanied by pain, seriously affecting physical and mental health of patients. Abnormal innervation at the osteochondral junction has been considered as a predominant origin of arthralgia, while the specific mechanism mediating pain remains unclear. To investigate the underlying mechanism of TMJ-OA pain, an abnormal joint loading model was used to induce TMJ-OA pain. We found that during the development of TMJ-OA, the increased innervation of sympathetic nerve of subchondral bone precedes that of sensory nerves. Furthermore, these two types of nerves are spatially closely associated. Additionally, it was discovered that activation of sympathetic neural signals promotes osteoarthritic pain in mice, whereas blocking these signals effectively alleviates pain. In vitro experiments also confirmed that norepinephrine released by sympathetic neurons promotes the activation and axonal growth of sensory neurons. Moreover, we also discovered that through releasing norepinephrine, regional sympathetic nerves of subchondral bone were found to regulate growth and activation of local sensory nerves synergistically with other pain regulators. This study identified the role of regional sympathetic nerves in mediating pain in TMJ-OA. It sheds light on a new mechanism of abnormal innervation at the osteochondral junction and the regional crosstalk between peripheral nerves, providing a potential target for treating TMJ-OA pain.
Animals ; Osteoarthritis/physiopathology* ; Mice ; Sympathetic Nervous System/physiopathology* ; Temporomandibular Joint Disorders/physiopathology* ; Arthralgia ; Sensory Receptor Cells ; Disease Models, Animal ; Norepinephrine ; Male ; Temporomandibular Joint/physiopathology* ; Pain Measurement

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

Objective To evaluate the clinical value of a modified Cancer and Aging Research Group(CARG)model in guiding anticancer drug dose adjustments for elderly cancer patients in China.Methods This prospective study enrolled patients aged≥65 years with solid tumors at the Department of Oncology,Peking Union Medical College Hospital from September 1,2022 to October 29,2023.All patients underwent comprehensive geriatric assessment(CGA)and CARG risk scoring,and were stratified into low-,intermediate-,and high-risk groups.Anti-cancer drug doses(including chemotherapy,targeted therapy or immunotherapy)were reduced proportionally based on CARG risk stratification and treatment intent(curative vs.palliative).Treatment outcomes and adverse events(AEs)were recorded regularly.Fisher's Exact Test compared AE incidence between the CARG-guided dose adjust-ment group(experimental)and the physician-experience-guided dose adjustment group(control).Receiver operating characteristic(ROC)curve analysis was used to assess the predictive value of the CARG model for severe toxicity.Results Among 166 enrolled patients(median age:71 years[range:65-90];78.3%were male;68.7%had gastro-intestinal cancers;69.3%had stageⅣ),95 were assigned to the experimental group(CARG low-risk:24[25.3%],intermediate-risk:51[53.7%],high-risk:20[21.0%])and 71 were included into the control group.By December 31,2024,81 patients experienced disease progression and 10 patients died.Overall AE rates was 92.6%in the ex-perimental group and 94.4%in the control group,while grade≥3 AEs were recorded in 45.3%vs.43.7%,respec-tively(both P＞0.05).Conclusions The modified CARG model-guided dose adjustment strategy achieved comparable safety to empirical dose adjustment,which is in line with the individualized treatment paradigm for elderly cancer pa-tients,representing a structured framework for optimizing therapeutic decision-making in geriatric oncology.

Objective:To explore the value of non-invasive habitat imaging (HI) multi-parametric MRI (mpMRI) in predicting the risk of prostate cancer (PCa).Methods:In this cross-sectional study, 220 patients with PCa confirmed by radical prostatectomy (RP) who underwent multi-parametric MRI (mpMRI) scanning at Xijing Hospital, Air Force Military Medical University from January 2018 to May 2024 were retrospectively collected. Patients were divided into a training set (154 cases) and a test set (66 cases) by simple random sampling in a 7∶3 ratio. Based on mpMRI imaging, the apparent diffusion coefficient (ADC), perfusion fraction (f), and mean kurtosis (MK) of each voxel were integrated. The K-means clustering algorithm was used to divide the PCa target lesions into habitat subregions, generate habitat maps, and calculate the proportion of each habitat subregion in the entire lesion. According to the 2019 International Society of Urological Pathology (ISUP) guidelines, patients were categorized into a low-risk group (ISUP≤2, 65 cases) and a high-risk group (ISUP≥3, 155 cases). The RP specimens were matched with the habitat map to identify corresponding habitat subregions, and the ISUP grade of each subregion was individually evaluated to calculate the detection rate of high-risk PCa patients. The logistic regression analysis was applied to identify the independent risk factors associated with PCa risk, and the HI-clinical imaging model and clinical imaging model were constructed. The efficacy of the models was assessed using receiver operating characteristic curve.Results:Based on the optimal cluster number, the habitat was divided into three subregions. Habitat 1 had lower ADC and f values and higher MK values, while habitat 2 had the opposite characteristics, and habitat 3 was intermediate. The proportion of habitat 1 in the high-risk group was 28.8%, in the low-risk group was 8.9%. In the training set, the comparison of habitat subregions with pathological results showed that the detection rate of high-risk lesions was 66.9% (103/154) in habitat 1, 25.3% (39/154) in habitat 2, and 47.4% (73/154) in habitat 3. The logistic regression analysis indicated that the proportion of habitat 1 ( OR=3.03, 95% CI 1.77-5.18, P<0.001), prostate-specific antigen ( OR=1.66, 95% CI 1.04-2.66, P=0.034), and the prostate imaging reporting and data system score ( OR=1.65, 95% CI 1.00-2.70, P=0.048) as independent risk factors for high-risk PCa. In the training set, the area under the curve (AUC) for predicting PCa risk was 0.854 (95% CI 0.789-0.920) for the HI-clinical imaging model and 0.779 (95% CI 0.701-0.856) for the clinical imaging model. In the test set, the AUC values were 0.809 (95% CI 0.693-0.895) and 0.738 (95% CI 0.619-0.856), respectively. Conclusion:HI based on mpMRI can effectively predict the risk of PCa.

Objective:To explore the effects of different electrical stimulations on cerebral cortex excitability, upper limb motor function, left-right coordination and counterbalance mechanisms among stroke survivors.Methods:Thirty stroke survivors with hemiplegia were randomly divided into a neuromuscular electrical stimulation (NMES) group and a contralateral control functional electrical stimulation (CCFES) group, each of 15. In addition to conventional rehabilitation treatment, the NMES group was additionally given daily 20-minute NMES to promote elbow extension and wrist extension 5 days a week for 4 weeks, while the CCFES group was given CCFES, instead. Before and after the treatment, the bilateral resting motor thresholds (RMTs), motor evoked potential (MEPs) cortical latency, MEP amplitude and inter-hemisphere asymmetry (IHA) index were measured. The Fugl-Meyer upper extremity assessment (FMA-UE) and the Hong Kong version of the functional test for hemiplegic upper extremities (FTHUE-HK) were employed to evaluate the subjects′ motor functioning. Pearson correlation coefficients relating cortical excitability with upper extremity function were computed.Results:After the treatments, significant improvement was observed in both groups in the latency and amplitude of the RMT and MEP of the affected hemisphere, the IHA value, as well as the FMA-UE and FTHUE-HK scores. The CCFES group then had scores significantly superior to those in the NMES group, on average. The improvements in the FMA-UE and FTHUE-HK scores were significantly positively correlated with the gap in IHA values and the MEP amplitude of the affected hemisphere.Conclusions:Both NMES and CCFES can improve the excitability of the affected motor cortex after a stroke. They help to restore the dynamic balance between the brain hemispheres for better motor functioning of the upper limbs. CCFES has a better therapeutic effect than NMES. The improvement in upper limb motor function is positively correlated with the increase in cortical excitability of the affected hemisphere and the normalization of inter-hemisphere asymmetry.

Objective:To explore the effects of different electrical stimulations on cerebral cortex excitability, upper limb motor function, left-right coordination and counterbalance mechanisms among stroke survivors.Methods:Thirty stroke survivors with hemiplegia were randomly divided into a neuromuscular electrical stimulation (NMES) group and a contralateral control functional electrical stimulation (CCFES) group, each of 15. In addition to conventional rehabilitation treatment, the NMES group was additionally given daily 20-minute NMES to promote elbow extension and wrist extension 5 days a week for 4 weeks, while the CCFES group was given CCFES, instead. Before and after the treatment, the bilateral resting motor thresholds (RMTs), motor evoked potential (MEPs) cortical latency, MEP amplitude and inter-hemisphere asymmetry (IHA) index were measured. The Fugl-Meyer upper extremity assessment (FMA-UE) and the Hong Kong version of the functional test for hemiplegic upper extremities (FTHUE-HK) were employed to evaluate the subjects′ motor functioning. Pearson correlation coefficients relating cortical excitability with upper extremity function were computed.Results:After the treatments, significant improvement was observed in both groups in the latency and amplitude of the RMT and MEP of the affected hemisphere, the IHA value, as well as the FMA-UE and FTHUE-HK scores. The CCFES group then had scores significantly superior to those in the NMES group, on average. The improvements in the FMA-UE and FTHUE-HK scores were significantly positively correlated with the gap in IHA values and the MEP amplitude of the affected hemisphere.Conclusions:Both NMES and CCFES can improve the excitability of the affected motor cortex after a stroke. They help to restore the dynamic balance between the brain hemispheres for better motor functioning of the upper limbs. CCFES has a better therapeutic effect than NMES. The improvement in upper limb motor function is positively correlated with the increase in cortical excitability of the affected hemisphere and the normalization of inter-hemisphere asymmetry.

Objective:To explore the value of multi-gene copy number variation (CNV) analysis in the clinical prognostic prediction of patients with multiple myeloma (MM).Methods:A retrospective case series study was conducted. The clinical data of 79 MM patients who were admitted to the Affiliated Cancer Hospital of Zhengzhou University from June 2016 to March 2023 were collected. The whole-genome CNV status was obtained by using whole-genome low depth sequencing (sWGS) of bone marrow blood cells. The outcomes of remission, minimal residual disease (MRD) turning negative, progression-free survival (PFS) and overall survival (OS) in patients with and without CNV were compared. The Cox proportional hazards model was used to analyze the influencing factors of PFS and OS.Results:Among the 79 patients with MM, 43 were males and 36 were females. The median age [ M ( Q1, Q3)] was 65 years old (55 years old, 71 years old). In the revised international staging system, there were 20, 51 and 8 cases in stage Ⅰ, Ⅱ and Ⅲ, respectively. The results of fluorescence in situ hybridization (FISH) were abnormal in 17 cases. CNV was detected in 55 patients (69.6%), and the abnormality of chromosome 1q (27 cases, 49.1%) was the most frequently detected, followed by the abnormality of chromosome 13 (26 cases, 47.3%), chromosome 6 (22 cases, 40.0%), chromosome 11 (19 cases, 34.5%), chromosome 8 (18 cases, 32.7%), chromosome 14 (14 cases, 25.5%), and chromosome 17 (11 cases, 20.0%). The ≥ very good partial remission rate in the detected CNV group was lower than that in the undetected CNV group [29.1% (16/55) vs. 45.8% (11/24)], but the difference was not statistically significant ( χ2 = 2.08, P = 0.149). The MRD negative conversion rate of detected CNV group was lower than that of undetected CNV group [21.8% (12/55) vs. 58.3% (14/24)], and the difference was statistically significant ( χ2 = 10.09, P = 0.001). Survival analysis showed that PFS in the detected CNV group was worse than in the undetected CNV group [median PFS time: 36.7 months (95% CI: 6.1-67.4 months) vs. not reached], and the difference between the two groups was statistically significant ( χ2 = 6.61, P = 0.010), while the difference in OS between the two groups was not statistically significant ( χ2 = 1.84, P = 0.175). There was no significant difference in PFS and OS between patients with 1 and ≥2 abnormal copy sequences (both P > 0.05). PFS of patients with CNV on chromosomes 1q, 17, 8, 11 and 13 was worse than that of patients without CNV at these sites (all P < 0.05), while there was no statistical difference in OS (all P > 0.05). Results of univariate analysis showed that lactate dehydrogenase (LDH) level was correlated with PFS and OS of patients (both P < 0.05), and CNV was correlated with PFS of patients (P = 0.010). Results of multivariate analysis showed that LDH > 250 U/L was an independent factor for poor PFS and OS of patients ( HR = 0.135, 95% CI: 0.019-0.983, P = 0.048; HR = 0.132, 95% CI: 0.018-0.951, P = 0.045). Conclusions:Multi-gene CNV analysis can assist in predicting the prognosis of MM patients, and it is more sensitive than traditional CNV detection methods such as FISH. Patients with CNV on chromosomes 1q, 17, 8, 11, and 13 have poor prognosis.