Booster vaccinations are highly recommended in combating the SARS-CoV-2 Omicron variant and its subvariants. However, the optimal booster vaccination strategies and related immune mechanisms with different prior vaccinations are under-revealed. In this study, we systematically evaluated the immune responses in mice and hamsters with different prime-boost regimens before their protective efficacies against Omicron were detected. We found that boosting with Ad5-nCoV, S_WT-2P or S_Omicron-6P induced significantly higher levels of neutralization activities against Omicron variants than CoronaVac and ZF2001 by eliciting stronger germinal center (GC) responses. Specifically, S_Omicron-6P induced even stronger antibody responses against Omicron variants in CoronaVac and Ad5-nCoV-primed animals than non-Omicron-specific vaccines but with limited differences as compared to Ad5-nCoV and S_WT-2P. In addition, boosting with a specific vaccine has the potential to remodel the existing immune profiles. These findings indicated that adenovirus-vectored vaccines and mRNA vaccines would be more effective than other types of vaccines as booster shots in combating Omicron infections. Moreover, the protective efficacies of the vaccines in booster vaccinations are highly related to GC reactions in secondary lymphatic organs. In summary, these findings provide timely important information on prime-boost regimens and future vaccine design.

Lumbar disc (LD) herniation and aging are prevalent conditions that can result in substantial morbidity. This study aimed to clarify the mechanisms connecting the LD aging and herniation, particularly focusing on cellular senescence and molecular alterations in the nucleus pulposus (NP). We performed a detailed analysis of NP samples from a diverse cohort, including individuals of varying ages and those with diagnosed LD herniation. Our methodology combined histological assessments with single-nucleus RNA sequencing to identify phenotypic and molecular changes related to NP aging and herniation. We discovered that cellular senescence and a decrease in nucleus pulposus progenitor cells (NPPCs) are central to both processes. Additionally, we found an age-related increase in NFAT1 expression that promotes NPPC senescence and contributes to both aging and herniation of LD. This research offers fresh insights into LD aging and its associated pathologies, potentially guiding the development of new therapeutic strategies to target the root causes of LD herniation and aging.
Intervertebral Disc Displacement/metabolism* ; Humans ; Aging/pathology* ; Nucleus Pulposus/pathology* ; Male ; Female ; Transcriptome ; Middle Aged ; Lumbar Vertebrae/pathology* ; Adult ; Cellular Senescence ; Stem Cells/pathology* ; Aged ; Intervertebral Disc Degeneration/metabolism*

Immune-mediated inflammatory diseases (IMIDs) represent a heterogeneous group of disorders characterized by chronic inflammation. Their long disease duration and relapsing nature often necessitate long-term, sometimes lifelong, pharmacotherapy. However, the adverse effects associated with these medications cannot be overlooked, with particular attention warranted for the potential risk of malignancy. This article reviews the current evidence regarding the oncogenic risk of major therapeutic agents used for IMIDs, aiming to enhance clinicians' comprehensive understanding of these drugs. For IMIDs patients with a history of malignancy or those possessing other risk factors for cancer, this knowledge may encourage more deliberate deliberation and a more thorough assessment when selecting appropriate treatment options, thereby facilitating better management of drug-associated malignancy risks.

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 objective characteristics of tongue manifestation in different stages of damp-heat syndrome in diabetic kidney disease (DKD). Methods: A cross-sectional study enrolled 134 patients with DKD G3-5 stages who met the diagnostic criteria for damp-heat syndrome in DKD. The patients were treated at Dongzhimen Hospital, Beijing University of Chinese Medicine, from May 2023 to January 2024. The patients were divided into three groups: DKD G3, DKD G4, and DKD G5 stage, with 53, 33, and 48 patients in each group, respectively. Clinical general data (gender, age, and body mass index) and damp-heat syndrome scores were collected from the patients. The YZAI-02 traditional Chinese medicine (TCM) AI Tongue Image Acquisition Device was used to capture tongue images from these patients. The accompanying AI Open Platform for TCM Tongue Diagnosis of the device was used to analyze and extract tongue manifestation features, including objective data on tongue color, tongue quality, coating color, and coating texture. Clinical data and objective tongue manifestation characteristics were compared among patients with DKD G3-5 based on their DKD damp-heat syndrome status. Results: No statistically significant difference in gender or body mass index was observed among the three patient groups. The DKD G3 stage group had the highest age (P<0.05). The DKD G3 stage group had a lower score for symptoms of poor appetite and anorexia(P<0.05) than the DKD G5 group. No statistically significant difference was observed in damp-heat syndrome scores among the three groups. Compared with the DKD G5 stage group, the DKD G3 stage group showed a decreased proportion of pale color at the tip and edges of the tongue (P<0.05). The DKD G4 stage group exhibited an increased proportion of crimson at the root of the tongue, a decreased proportion of thick white tongue coating at the root, a decreased proportion of pale color at the tip and edges of the tongue, an increased hue value (indicating color tone) of the tongue color in the middle, an increased brightness value (indicating color lightness) of the tongue coating color in the middle, and an increased thickness of the tongue coating (P<0.05). No statistically significant difference was observed in other tongue color proportions, color chroma values, body characteristics, coating color proportions, coating color chroma values, and coating texture characteristics among the three groups. Conclusion Tongue features differ in different stages of DKD damp-heat syndrome in multiple dimensions, enabling the inference that during the DKD G5 stage, the degree of qi and blood deficiency in the kidneys, heart, lungs, liver, gallbladder, spleen, and stomach is prominent. Dampness is more likely to accumulate in the lower jiao, particularly in the kidneys, whereas heat evil in the spleen and stomach is the most severe. These insights provide novel ideas for the clinical treatment of DKD.

Objective:To construct classification models of traumatic brain injury (TBI) based on the injury data collected at the scene of the accidents and validate its efficacy.Methods:A retrospective cohort study was conducted to analyze the pre-hospital treatment data of 368 TBI patients admitted to the Second Affiliated Hospital of Army Military Medical University from January 2019 to December 2023, including 243 males and 125 females, aged 18-82 years [(48.1±20.8)years]. The patients′ Glasgow coma scale (GCS) scores were 3-15 points [11.0(3.0, 15.0)points] at emergency medical service arrival. The patients were randomly assigned to the training set ( n=257) and test set ( n=111) at a ratio of 7∶3. According to the admission diagnosis, the patients fell into the mild TBI group ( n=62), medium TBI group ( n=137), severe TBI group ( n=120), and extremely severe TBI group ( n=49). In the training set, 44 patients fell into mild TBI group, 98 into medium TBI group, 82 into severe TBI group and 33 into extremely severe TBI group, while in the test set, 18 patients fell into mild TBI group, 39 into medium TBI group, 38 into severe TBI group and 16 into extremely severe TBI group. The following 12 kinds of injury data, including MARCH [massive hemorrhage (M), airway obstruction (A), respiratory failure (R), circulatory failure (C) and hypothermia (H)], GCS, pre-hospital index (PHI), shock index (SI), reverse SI multiplied by GCS (rSIG), optic nerve sheath diameter (ONSD) measured by ultrasound, scalp and skull injuries were collected at the scene of the accidents. Three machine algorithm including random forest (RF), support vector machine (SVM) and logistic regression (LR) were used to construct scene data-based TBI classification models. The accuracy rate, precision rate, recall rate, F1 value and area under receiver operating characteristic (ROC) curve (AUC) of the 3 models were used to verify the efficiency of the models for TBI classification. Shapley additive explanations (SHAP) method was used to interpret the results of the optimal model. The 12 kinds of injury data in the models were sorted according to their contribution to the TBI classification and the injury data with greater contribution were selected. Results:In the test set, the accuracy rate of the RF, SVM and LR models was 0.93, 0.92 and 0.87, respectively; the precision rate was 0.93, 0.92 and 0.89, respectively; the recall rate was 0.93, 0.92 and 0.87, respectively; the F1 value was 0.93, 0.92 and 0.87, respectively. In the mild, medium, severe and extremely severe TBI groups in the test set, the AUC of the RF model was 0.96 (95% CI 0.92, 0.98), 0.98 (95% CI 0.94, 0.99), 0.97 (95% CI 0.95, 0.98), and 0.97 (95% CI 0.96, 0.98), respectively; the AUC of the SVM model was 0.90 (95% CI 0.88, 0.94), 0.95 (95% CI 0.92, 0.97), 0.96 (95% CI 0.94, 0.98), and 0.95 (95% CI 0.92, 0.99), respectively; the AUC of the LR model was 0.90 (95% CI 0.83, 0.96), 0.90 (95% CI 0.84, 0.95), 0.96 (95% CI 0.95, 0.98), and 0.95 (95% CI 0.94, 0.97), respectively. The RF model demonstrated optimal discriminative performance for TBI classification. As the SHAP′s interpretation of the RF model indicated, among the 12 kinds of injury data, those with greater contributions to the TBI classification were GCS, rSIG, SI, PHI, respiratory failure, ONSD, and circulatory failure in sequence. Conclusions:Of the scene data-based TBI classification models, the RF model achieves good predictive performance for TBI classification when compared with the SVM model and LR model. Besides, GCS, rSIG, SI, PHI, respiratory failure, ONSD and circulatory failure contribute significantly to the classification of TBI in the RF model, which may assist emergency medical personnel in field triage and management of TBI at accident scenes.

Objective:To explore the impacts of different frequencies of orthogonal image-guided verification on set-up error correction and the reference values of planning target volume (PTV) margins in postoperative radiotherapy for breast cancer, in order to provide recommendations of the verification frequency in clinical practice.Methods:A total of 80 breast cancer patients who received postoperative intensity-modulated radiotherapy for breast cancer at the Affiliated Union Hospital of Fujian Medical University from January 2021 to January 2022 were enrolled. Orthogonal image-guided verification was conducted before each radiation treatment to determine initial and residual set-up errors. The error data were statistically analyzed by categorizing patients into groups A, B, C, D, E, and F, based on assumed verification frequencies (daily, every 2, 3, 4, and 5 d, and no correction). The magnitude, distribution, and differences of set-up errors of various groups were analyzed, and the PTV margins were calculated using a reference formula.Results:The collected initial set-up errors of the 80 patients were (3.49±3.43), (2.87±2.88), and (2.75±2.35) mm, in x, y, and z directions, respectively. The residual set-up errors decreased gradually with increasing verification frequency. In the case of daily image-guided verification, the residual set-up errors in x, y, and z directions decreased to (1.63±0.90), (1.63±0.93), and (1.55±0.90)mm, respectively. The reference values of PTV margins calculated under different verification frequencies decreased with an increase in the verification frequency. Under daily verification, the reference values of PTV margins calculated based on set-up errors decreased from initial 6.60, 6.29, and 4.22 mm (without correction) to 1.27, 1.37, and 1.28 mm, respectively. Differences in the reference values under verification frequencies every 3, 4, and 5 d were less than 0.81 mm. Conclusions:Daily image-guided verification (including correction) can effectively reduce set-up errors in image-guided radiotherapy for breast cancer. The set-up errors differ under varying verification frequencies, with a higher frequency corresponding to better correction effects and smaller PTV margins required.

OBJECTIVE To provide reference for the establishment and optimization of add-on payment policy in China. METHODS The two-party evolutionary game model was constructed， involving medical insurance and medical institutions，and simulation experiments were conducted. The effects of factors such as whether the establishment of add-on payment policy by the medical insurance department， the compensation ratio， and the cost and incremental utility of new technology on the adoption of innovative technologies by medical institutions were analyzed under the backdrop of the reform of the diagnosis-related groups （DRG） payment system. RESULTS & CONCLUSIONS The add-on payment policy can effectively incentivize the utilization of innovative technologies， but it also carries the risk of overuse or misuse of new technologies. The compensation ratio， unit price of new technology， and cost savings derived from the improved effectiveness of new technologies， as well as the incremental utility of new technology， will all affect the equilibrium state of the evolutionary game， potentially even reversing it. It is recommended to optimize the selection criteria for the scope of add-on payment， so as to incentivize the use of innovative technologies while controlling the risk of their misuse. Additionally， a reasonable approach should be taken to adopt either standalone payment or supplementary payment models based on the surplus level of medical insurance funds in the coordinated regions. Meanwhile， a regular adjustment mechanism should be established to ensure smooth integration between the add-on payment and the DRG payment system.

Objective:To evaluate the diagnostic performance of fecal calprotectin (FC) in predicting endoscopic activity of ulcerative colitis (UC), and to compare it with high-sensitivity C reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR) .Methods:A cross-sectional stydy was conducted. UC patients diagnosed at Peking Union Medical College Hospital between May 2023 and July 2025 were retrospective enrolled. Patients were divided into the endoscopically active group and endoscopic remission group according to endoscopic activity. FC levels were measured using latex-enhanced turbidimetric immunoassay (LETIA). Receiver operating characteristic (ROC) curves and logistic regression models were used to assess diagnostic efficacy. Subgroup analyses were conducted according to disease extent.Results:A total of 166 UC patients were enrolled, including 92 males and 74 females with the age of 40.00 (32.00, 52.00) years old and disease course 5.00 (2.00, 10.75) years. Forty-six patients were assigned to the active group, while the remaining 120 were assigned to the remission group. FC levels were significantly higher in the active group than in the remission group (620.72 μg/g vs. 29.00 μg/g, P < 0.001), with an AUC of 0.894 at a cutoff value of 122.54 μg/g. hsCRP and ESR had lower AUC (0.712 and 0.736, respectively). The combination of FC, hsCRP, and ESR slightly improved specificity (AUC 0.898). FC was strongly correlated with the endoscopic activity ( r =0.669, P < 0.001) but not with disease extent. Conclusions:FC measured by latex-enhanced turbidimetric immunoassay had comparable diagnostic accuracy to ELISA-based methods commonly used abroad, and provided a reference cutoff value of 122.54 μg/g. FC outperforms hsCRP and ESR in assessing intestinal inflammation in UC and it is less affected by disease extent, making it a reliable non-invasive biomarker for UC monitoring.

Objective:To evaluate the predictive efficacy of fecal calprotectin (FC) for endoscopic activity in patients with Crohn's disease (CD) .Methods:A cross-sectional study was conducted and patients diagnosed as CD at Peking Union Medical College Hospital from June 2023 to September 2025 were enrolled consecutively. Data was collected including general information, laboratory tests [hemoglobin (HGB), platelet (PLT), FC, high-sensitivity C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR) and so on], and endoscopic results. FC levels were measured by latex-enhanced turbidimetric immunoassay (LETIA). Endoscopic activity was defined as the simplified endoscopic score for Crohn's disease (SES-CD) > 2. Patients were divided into the endoscopically active group and endoscopic remission group according to endoscopic activity, and the differences in clinical data between the two groups were compared. Spearman correlation analysis was used to assess the correlation between FC and endoscopic activity, and receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of FC, hsCRP and ESR for endoscopic activity, and the differences were compared.Results:A total of 90 CD patients were enrolled, including 65 males and 25 females with the age of 30 (22, 41) years old and disease course 4.0 (0.5, 8.0) years. Seventy-one patients (78.9%) had ileocolonic disease involvement (L3), and 55 patients (61.1%) were using biologics. Sixty-nine patients in endoscopic active phase were assigned to the endoscopically active group, while the remaining 21 were assigned to the endoscopic remission group. There were no statistically significant differences in general characteristics such as age and gender between the two groups (all P > 0.05). Compared with endoscopic remission group, HGB was significantly lower in the endoscopically active group, while PLT, hsCRP, ESR, and FC were moderataly higher (all P < 0.05). Among the 90 CD patients, FC levels were moderatly correlated with endoscopic activity (ρ = 0.494). ROC curve analysis indicated that the area under the curve for FC in predicting endoscopic activity was 0.836 (95% CI: 0.737-0.935), with a sensitivity of 0.725, specificity of 0.952, and accuracy of 0.778 at the optimal FC cutoff value of 153.8 μg/g. FC outperformed hsCRP and ESR. Conclusion:FC measured by LETIA demonstrates certain efficacy in predicting endoscopic activity in CD and will assist in efficient clinical monitoring of CD patients.