Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective:To investigate the clinical characteristics and independent risk factors of severe disease in patients with anti-nuclear matrix protein (NXP) 2 antibody-positive juvenile dermatomyositis (JDM).Methods:A retrospective cohort study was conducted, including 219 anti-NXP2 antibody-positive JDM patients admitted to 23 children′s hospitals across China from July 2011 to July 2023. Patients were classified into severe and non-severe groups based on classification criteria for severe dermatomyositis. Demographic characteristics, clinical manifestations, and laboratory parameters were compared between the 2 groups using independent sample t-test, Mann-Whitney U test, or χ2 test. Univariate and multivariate Logistic regression analyses were performed to identify risk factors for severe disease. The receiver operating characteristic curve was employed to calculate optimal cut-off values. Results:Among the 219 patients, 108 were male and 111 were female, with an age at onset of 6.3 (3.5, 9.4) years. The severe group comprised 69 patients, and the non-severe group 150 patients. The severe group had significantly higher rates of fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, as well as elevated levels of ferritin-to-albumin ratio (FAR), creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (all P<0.05). Multivariate analysis identified anti-Ro52 antibody positivity ( OR=13.26, 95% CI 1.37-128.29) and elevated FAR ( OR=1.90, 95% CI 1.09-2.31) as independent risk factors for severe anti-NXP2 antibody-positive JDM (both P<0.05). Receiver operating characteristic curve analysis revealed that a FAR cutoff value of 6.82 predicted severe disease with an area under the curve of 0.87 (95% CI 0.81-0.94, P<0.001), sensitivity of 0.85, and specificity of 0.70. All patients received glucocorticoid therapy, and the severe group received higher proportions of steroid pulse therapy, cyclophosphamide, mycophenolate mofetil, intravenous immunoglobulin, biologics, and adjuvant treatments compared to the non-severe group (all P<0.05). In terms of outcomes, 2 patients (2.9%) in the severe group died (due to neurological involvement and intestinal perforation, respectively), while the remaining patients achieved complete clinical response or remission. All patients in the non-severe group achieved remission. Conclusions:The primary clinical features of anti-NXP2 antibody-positive JDM included fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, and elevated levels of CK, AST, LDH, and FAR. Furthermore, anti-Ro52 antibody positivity and a FAR>6.82 were identified as independent risk factors.

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective:To investigate the clinical characteristics and independent risk factors of severe disease in patients with anti-nuclear matrix protein (NXP) 2 antibody-positive juvenile dermatomyositis (JDM).Methods:A retrospective cohort study was conducted, including 219 anti-NXP2 antibody-positive JDM patients admitted to 23 children′s hospitals across China from July 2011 to July 2023. Patients were classified into severe and non-severe groups based on classification criteria for severe dermatomyositis. Demographic characteristics, clinical manifestations, and laboratory parameters were compared between the 2 groups using independent sample t-test, Mann-Whitney U test, or χ2 test. Univariate and multivariate Logistic regression analyses were performed to identify risk factors for severe disease. The receiver operating characteristic curve was employed to calculate optimal cut-off values. Results:Among the 219 patients, 108 were male and 111 were female, with an age at onset of 6.3 (3.5, 9.4) years. The severe group comprised 69 patients, and the non-severe group 150 patients. The severe group had significantly higher rates of fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, as well as elevated levels of ferritin-to-albumin ratio (FAR), creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (all P<0.05). Multivariate analysis identified anti-Ro52 antibody positivity ( OR=13.26, 95% CI 1.37-128.29) and elevated FAR ( OR=1.90, 95% CI 1.09-2.31) as independent risk factors for severe anti-NXP2 antibody-positive JDM (both P<0.05). Receiver operating characteristic curve analysis revealed that a FAR cutoff value of 6.82 predicted severe disease with an area under the curve of 0.87 (95% CI 0.81-0.94, P<0.001), sensitivity of 0.85, and specificity of 0.70. All patients received glucocorticoid therapy, and the severe group received higher proportions of steroid pulse therapy, cyclophosphamide, mycophenolate mofetil, intravenous immunoglobulin, biologics, and adjuvant treatments compared to the non-severe group (all P<0.05). In terms of outcomes, 2 patients (2.9%) in the severe group died (due to neurological involvement and intestinal perforation, respectively), while the remaining patients achieved complete clinical response or remission. All patients in the non-severe group achieved remission. Conclusions:The primary clinical features of anti-NXP2 antibody-positive JDM included fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, and elevated levels of CK, AST, LDH, and FAR. Furthermore, anti-Ro52 antibody positivity and a FAR>6.82 were identified as independent risk factors.

This experiment aims to study the taste-masking effects of different kinds of corrigent used individually and in combination on ibuprofen oral solution, in order to optimize the taste-masking formulation. Firstly, a wide range of corrigent and the mass fractions were extensively screened using electronic tongue technology. Subsequently, a combination of sensory evaluation, analytic hierarchy process (AHP)-fuzzy mathematics evaluation, and Box-Behnken experimental design were employed to comprehensively assess the taste-masking effects of different combinations of corrigent on ibuprofen oral solution, optimize the taste-masking formulation, and validate the results. The study received ethical approval from the Review Committee of the Beijing University of Chinese Medicine (ethical code: 2024BZYLL0102). The results showed that corrigent fractions and types were screened separately through single-factor experiments. Subsequently, a Box-Behnken response surface design combined with AHP and fuzzy mathematics evaluation was used to fit a functional model: Z = 688.310 11 - 3 023.722 22X₁ - 11.477 00X₂ + 62.721 67X₃ + 14.600 00X₁X₂ - 179.666 67X₁X₃ - 3.152 00X₂X₃ + 4 031.111 11X₁² + 0.525 28X₂² + 9.772 00X₃². This model is stable and reliable, determining the optimal taste-masking formulation to be 3.9 g·L^-1 of stevioside, 100 g L^-1 of xylitol, and 30 g L^-1 of methyl-β-cyclodextrin. The comprehensive score of the verification test is 88.14, with a relative RSD of 0.39%, indicating the feasibility of this model. This study achieved the improvement of the taste of ibuprofen oral solution through a combination of objective and subjective methods. Three types of corrigent were identified for enhancing drug taste, leading to the selection of the optimal taste-masking formulation for ibuprofen oral solution. This significantly enhanced the taste of the original formulation, improved patient compliance, and offered a new approach to mitigating the undesirable taste of formulations.

Microplastics(MPs)and nanoplastics(NPs)have become hazardous materials due to the massive amount of plastic waste and disposable masks,but their specific health effects remain uncertain.In this study,fluorescence-labeled polystyrene NPs(PS-NPs)were injected into the circulatory systems of mice to determine the distribution and potential toxic effects of NPs in vivo.Interestingly,whole-body imaging found that PS-NPs accumulated in the testes of mice.Therefore,the toxic effects of PS-NPs on the reproduction systems and the spermatocytes cell line of male mice,and their mechanisms,were investigated.After oral exposure to PS-NPs,their spermatogenesis was affected and the spermatogenic cells were damaged.The spermatocyte cell line GC-2 was exposed to PS-NPs and analyzed using RNA sequencing(RNA-seq)to determine the toxic mechanisms;a ferroptosis pathway was found after PS-NP exposure.The phenomena and indicators of ferroptosis were then determined and verified by ferroptosis inhibitor ferrostatin-1(Fer-1),and it was also found that nuclear factor erythroid 2-related factor 2(Nrf2)played an important role in spermatogenic cell ferroptosis induced by PS-NPs.Finally,it was confirmed in vivo that this mechanism of Nrf2 played a protective role in PS-NPs-induced male reproductive toxicity.This study demonstrated that PS-NPs induce male reproductive dysfunction in mice by causing spermatogenic cell ferroptosis dependent on Nrf2.

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of liquiritin apioside,alibiflorin,swertiamarin,methyl gallate,benzoylpaeoniflorin,sweroside,6′-O-β-D-glucosylgentiopicroside,isoliquiritigenin,loganic acid,liquiritigenin,gallic acid,paeoniflorin,oxypaeoniflorin,gentiopicroside,glycyrrhizic acid,isoliquiritoside and liquiritin in Yangxue Ruanjian Capsules.METHODS The analysis was performed on a 40℃thermostatic Waters BEH C18column(2.1 mm×100 mm,1.7 μm),with the mobile phase comprising of 2 mmol/L ammonium acetate(containing 0.1%formic acid)-acetonitrile flowing at 0.3 mL/min in a gradient elution manner,and electron spray ionization source was adopted in negative ion scanning with multiple reaction monitoring mode.RESULTS Seventeen constituents showed good linear relationships within their own ranges(r>0.999 6),whose average recoveries were 91.33%-104.03%with the RSDs of 1.58%-3.50%.CONCLUSION This rapid,accurate and stable method can be used for the quality control of Yangxue Ruanjian Capsules.