ObjectiveTo develop and preliminarily validate a prediction model for brace treatment failure risk in patients with adolescent idiopathic scoliosis (AIS), based on information obtained before brace treatment and during initial brace fitting. MethodsA total of 191 patients with AIS who initiated thoracolumbosacral orthosis treatment at Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from March, 2015 to August, 2024 and had determinable outcomes were retrospectively included. Patients were divided according to a prespecified scheme into a training set (n = 133) and a validation set (n = 58). Brace treatment failure was defined as progression of the major-curve Cobb angle by ≥ 5° from baseline during follow-up or at brace weaning, or a final major-curve Cobb angle > 45°. Logistic regression, random forest, support vector machine with radial basis function kernel, and extreme gradient boosting (XGBoost) models were developed using routinely available clinical and radiographic variables before brace treatment and during initial brace fitting. Stratified five-fold cross-validation was used for hyperparameter tuning in the training set. Model performance was evaluated in the validation set using the area under the receiver operating characteristic curve (AUC), area under the precision-recall curve (AUPRC), Brier score, calibration curves, and decision curve analysis (DCA). SHapley Additive exPlanations (SHAP) was used to interpret the main explanatory model. ResultsIn cross-validation of the training set, both random forest and XGBoost showed good discriminative performance, with cross-validation-AUC values of 0.871 and 0.880, respectively. In the validation set, the AUC values of random forest and XGBoost were 0.888 and 0.899, the AUPRC values were 0.678 and 0.830, and the Brier scores were 0.086 and 0.076, respectively. Random forest was selected as the primary model for interpretation, with a calibration intercept of 0.091 and a calibration slope of 0.995. SHAP analysis indicated that the in-brace correction rate and the major-curve Cobb angle measured in the brace contributed most to the model predictions. ConclusionThe random forest model developed using routinely available pretreatment and initial-fitting variables shows preliminary predictive value for brace treatment failure risk in AIS, and may provide quantitative support for follow-up scheduling, brace-fit reassessment and early adherence-oriented management.

For HCQ retinopathy with CME, acupuncture combined with periocular injection can be used to improve the CME and protect the central vision. Subsequent research endeavors involving a more extensive cohort and extended observation periods are warranted to evaluate the effectiveness and safety profile of the intervention.
Humans ; Macular Edema/drug therapy* ; Acupuncture Therapy/methods* ; Hydroxychloroquine/therapeutic use* ; Female ; Retinal Diseases/chemically induced* ; Middle Aged ; Combined Modality Therapy ; Male

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Photodynamic immunotherapy is a promising strategy for cancer treatment. However, the dysfunctional tumor vasculature results in tumor hypoxia and the low efficiency of drug delivery, which in turn restricts the anticancer effect of photodynamic immunotherapy. In this study, we designed photosensitive lipid nanoparticles. The synthesized PFBT@Rox Lip nanoparticles could produce type I/II reactive oxygen species (ROS) by electron or energy transfer through PFBT under light irradiation. Moreover, this nanosystem could alleviate tumor hypoxia and promote vascular normalization through Roxadustat. Upon irradiation with white light, the ROS produced by PFBT@Rox Lip nanoparticles in situ dysregulated calcium homeostasis and triggered endoplasmic reticulum stress, which further promoted the release of damage-associated molecular patterns, enhanced antigen presentation, and stimulated an effective adaptive immune response, ultimately priming the tumor microenvironment (TME) together with the hypoxia alleviation and vessel normalization by Roxadustat. Indeed, in vivo results indicated that PFBT@Rox Lip nanoparticles promoted M1 polarization of tumor-associated macrophages, recruited more natural killer cells, and augmented infiltration of T cells, thereby leading to efficient photodynamic immunotherapy and potentiating the anti-primary and metastatic tumor efficacy of PD-1 antibody. Collectively, photodynamic immunotherapy with PFBT@Rox Lip nanoparticles efficiently program TME through the induction of immunogenicity and oxygenation, and effectively suppress tumor growth through immunogenic cell death and enhanced anti-tumor immunity.

Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.

Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.

Objective:To explore the clinical characteristics of neonatal necrotizing enterocolitis（NEC）and analyze the risk factors for early-onset NEC.Methods:A total of 220 children with NEC admitted to the Department of Pediatrics，Tianjin Medical University General Hospital from January 1st，2018 to February 29th，2024 were retrospectively selected as the research objects. According to the time of onset，the early-onset group（ n=120）and the late-onset group（ n=100）were established，and the clinical characteristics of the two groups were compared. Another 150 cases of normal healthy newborns born in this hospital in the same period were selected as the control group，and the clinical data of the control group were collected. The clinical characteristics of the early-onset group and the control group were compared，and the risk factors of early-onset NEC were analyzed by multivariate Logistic regression. Results:Compared with the late-onset group，the early-onset group had fever［50.0%（60/120）vs. 40%（40/100）， χ2=7.333， P=0.007］，apnea［39.17%（47/120）vs. 28%（28/100）， χ2=7.568， P=0.006］，no rise in body temperature［56.67%（68/120）vs. 39%（39/100）， χ2=6.815， P=0.009］，abdominal distension［25%（30/120）vs. 40%（40/100）， χ2=13.200， P<0.001］，vomiting［30.83%（37/120）vs. 45%（45/100）， χ2=12.797， P<0.001］was significantly different（all P<0.05）；Multivariate Logistic regression analysis：weight<1 500 g（ OR=5.871，95% CI：3.153～9.673， P<0.001），gestational age<30 weeks（ OR=4.256，95% CI：2.641～7.896， P=0.007），hemodynamically significant patent ductus arteriosus（hs-PDA）（ OR=3.113，95% CI：1.865～5.133， P=0.033），severe anemia（ OR=3.057，95% CI：2.165～4.802， P=0.001），feeding intolerance（ OR=4.215，95% CI：1.579～10.802， P=0.005），amniotic fluid pollution（ OR=2.452，95% CI：1.579～3.111， P<0.001）were the independent risk factors for early-onset NEC（all P<0.05）. Conclusion:Weight<1 500 g，gestational age<30 weeks，hs-PDA，severe anemia，feeding intolerance，and amniotic fluid contamination are independent risk factors for early-onset NEC. In clinical practice，more attention should be paid to these factors for disease prevention，early identification，and timely intervention in newborns to reduce the occurrence of NEC.

BACKGROUND: Without timely and effective rehabilitation, hearing loss may profoundly affect human life quality. China has a large population of hearing-impaired individuals, which imposes a heavy health burden on society. Moreover, this population is projected to increase rapidly owing to China's aging society. METHODS: We used data from a population-representative epidemiological investigation of hearing loss and ear diseases in four Chinese provinces. We estimated the national prevalence using multiple linear regression of the age-group proportions and prevalence in 31 provinces with clustering analysis. We used years lived with disability (YLDs) to analyze the disease burden and forecasted the prevalence of hearing loss by 2060 in China. RESULTS: An estimated 115 million people had moderate-to-complete hearing loss in 2015 across the 31 provinces of China (8.4% of 1.37 billion people). Of these, 85.7% were older than age 50 years (99 million people) and 2.4% were younger than 20 years old (2.8 million people). Of all YLDs attributable to hearing loss, 68.9% were attributable to moderate-to-complete cases. By 2060, a projected 242 million people in China will have moderate-to-complete hearing loss, a 110.0% increase from 2015. CONCLUSIONS The hearing loss prevalence in China is high. Population aging and socioeconomic factors substantially affect the prevalence and severity of hearing loss and the disease burden. The prevalence and severity of hearing loss are unevenly distributed across different provinces. Future public health policies should take these trends and regional variations into account.
Humans ; China/epidemiology* ; Hearing Loss/epidemiology* ; Prevalence ; Middle Aged ; Male ; Female ; Adult ; Aged ; Adolescent ; Young Adult ; Child ; Child, Preschool ; Infant ; Aged, 80 and over ; Cost of Illness

Objective:To elucidate the molecular mechanisms through which high-dose dexamethasone exerts long-term effects on bone marrow mesenchymal stem cells (BMSCs), specifically its role in suppressing osteogenic differentiation, accelerating cellular senescence, triggering the senescence-associated secretory phenotype (SASP), and inducing apoptosis.Methods:Primary rat BMSCs were isolated and treated with high-dose dexamethasone (1×10 -4 mol/L) to establish the experimental group, while untreated cells served as the control. The gene and protein expression levels of osteogenic markers, bone alkaline phosphatase (bALP) and Runt-related transcription factor 2 (Runx2), were analyzed in both groups. Cellular senescence was evaluated using senescence-associated β-galactosidase (SA-β-gal) staining. The expression of senescence-related markers (P16 and P21), components of the senescence-associated secretory phenotype (SASP), including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and interferon (IFN)-γ, as well as apoptosis-related proteins (Bcl-2, Bax, and Cleaved-Caspase-3), and key factors of the Nrf2/HO-1 signaling pathway were assessed at both transcriptional and protein levels using qRT-PCR, immunofluorescence, and Western-blot analyses. These comprehensive evaluations aimed to determine the senescent state, apoptotic features, and alterations in osteogenic differentiation of BMSCs. Results:Following treatment with dexamethasone and subsequent withdrawal, both qRT-PCR and Western blot analyses indicated a significant reduction in the expression of the osteogenic markers bALP and Runx2 at both mRNA and protein levels. The proportion of SA-β-gal positive cells was markedly higher in the dexamethasone group (74.33%±6.89%) than in the control group (20.30%±1.57%, t=17.300, P<0.001). qRT-PCR analysis revealed upregulated mRNA expression of the senescence-related genes P16 and P21 after dexamethasone treatment, which was further supported at the protein level by immunofluorescence showing increased P21 expression. Western-blot results confirmed that protein expression levels of P16 and P21 were significantly elevated in the dexamethasone group (7.025±0.255 and 6.362±0.456, respectively) compared with the control group (1.016±0.115 and 0.816±0.172; both P<0.05). Furthermore, gene expression levels of the senescence-associated secretory phenotype (SASP) factors TNF-α and IL-1β were significantly increased (TNF-α: 3.539±0.599 vs. 0.742±0.095; IL-1β: 4.469±0.331 vs. 0.799±0.175; both P<0.05), and their protein expression was consistently upregulated as validated by Western-blot. Additionally, protein expression levels of TNF-α, IL-1β, and IFN-γ were significantly higher in the dexamethasone-treated group (3.476±0.932 vs. 0.945±0.095; 4.111±0.220 vs. 0.762±0.105; 2.155±0.240 vs. 0.656±0.104; all P<0.05).Western-blot analysis also demonstrated that protein expression of Nrf2 and HO-1 was significantly suppressed in the dexamethasone group (0.21±0.07 and 0.19±0.06, respectively) compared with the control group (1.13±0.15 and 0.92±0.21; P<0.05). Moreover, Western-blot analysis revealed that the expression levels of the pro-apoptotic proteins Bax and Cleaved-Caspase-3 were significantly up, regulated in the dexamethasone, treated BMSCs (Bax: 3.673±0.397 vs. 0.453±0.111; Cleaved-Caspase-3: 3.863±0.399 vs. 0.465±0.057), while the expression of the anti-apoptotic protein Bcl-2 was markedly down, regulated (0.959±0.073 vs. 2.126±0.195), with all differences being statistically significant ( P<0.05). Conclusions:High-dose dexamethasone treatment of BMSCs, followed by withdrawal of dexamethasone, induces cellular senescence and enhances the expression of the senescence-associated secretory phenotype (SASP) through suppression of the Nrf2/HO-1 signaling pathway. Concurrently, it promotes apoptosis by activating the mitochondrial apoptotic pathway, collectively leading to impaired osteogenic differentiation of BMSCs.

Objective:To investigate clinical characteristics, treatment approaches, and prognosis of drug-induced hypersensitivity syndrome (DIHS) in children.Methods:A retrospective analysis was performed on clinical data from pediatric inpatients with DIHS in Department of Dermatology, Beijing Children's Hospital from 2009 to 2023. The clinical data included demographic characteristics, clinical manifestations, laboratory findings, treatment regimens, and outcomes.Results:A total of 103 children with DIHS were included, comprising 54 males (52.4%) and 49 females (47.6%), with ages ( M [ Q1, Q3]) of 2.3 (1.2, 4.5) years. Primary causative drugs were antibiotics (52 cases, 45.2%), antiepileptic drugs (41 cases, 35.7%), and nonsteroidal anti-inflammatory drugs (19 cases, 16.5%), with a median latency period of 12 days. All patients presented with rashes, including 72 (69.9%) with maculopapular rashes, 69 (67.0%) with edema (including 46 with facial edema). Lip involvement occurred in 25 cases (24.3%), and mucosal involvement was noted in 11 cases (10.7%). Additionally, 102 (99.0%) patients had fever, and 79 (76.7%) presented with lymphadenectasis. Eosinophilia was present in 64 cases (62.1%). Among 84 patients tested for atypical lymphocytes, 51 (60.7%) showed elevated percentages of atypical lymphocytes. Liver involvement was noted in 94 cases (91.3%), followed by pulmonary involvement in 31 (30.1%), gastrointestinal symptoms in 25 (24.3%), cardiac involvement in 14 (13.6%), renal involvement in 10 (9.7%), and pancreatic involvement in 7 cases (6.8%). Among 82 patients tested for blood immunocytes, 49 (59.8%) showed decreased percentages of B lymphocytes, and 69 (84.1%) showed decreased percentages of natural killer cells. Of 88 patients tested for serum immunoglobulins, 40 (45.5%) showed decreased IgA levels. Among 20 patients tested for serum cytokines, 15 (75.0%), 15 (75.0%), 13 (65.0%), and 12 (60.0%) showed elevated levels of interleukin (IL) -5, IL-6, IL-10, and interferon-γ, respectively. All patients received systemic glucocorticoid therapy, among whom 86 additionally received intravenous immunoglobulin therapy, 4 received Janus kinase inhibitors, and 3 received dupilumab. Five patients died, 9 developed hemophagocytic lymphohistiocytosis, 6 developed bronchiolitis obliterans, and 5 experienced long-term immune-related sequelae. Conclusions:Among these children with DIHS, antibiotics were the most common causative drugs, and the latency period could be shorter than 2 weeks. In addition to the common involvement of the liver and lungs, gastrointestinal and cardiac impairments were relatively frequent, while renal involvement was rare. Immunological features included decreased percentages of B lymphocytes and natural killer cells, reduced IgA levels, and elevated levels of cytokines such as IL-5, IL-6, IL-10, and interferon-γ.