OBJECTIVES: To identify potential plasma lipidomic biomarkers that distinguish non-metastatic medulloblastoma (nmMB) from metastatic medulloblastoma (mMB) in children. METHODS: In this prospective study, 17 children with mMB and 20 matched children with nmMB were enrolled. Plasma samples were analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Lipid metabolites were evaluated for their associations and diagnostic performance. RESULTS: Orthogonal partial least squares discriminant analysis based on lipid profiles clearly separated nmMB from mMB, and 14 differential lipids were identified, including DG(18:2/20:4/0:0) and SM(d18:1/20:0). Receiver operating characteristic analysis showed nine metabolites with area under the curve greater than 0.7. Differential lipids were enriched in sphingolipid, glycerophospholipid, and arachidonic acid metabolism, suggesting an association with the metastatic phenotype. CONCLUSIONS Plasma lipidomics provides a new approach to identify mMB, and the identified lipid metabolites may support early diagnosis and treatment, prognostic assessment, and selection of therapeutic targets for metastatic medulloblastoma.
Humans ; Medulloblastoma/diagnosis* ; Lipidomics ; Child ; Male ; Female ; Child, Preschool ; Cerebellar Neoplasms/blood* ; Biomarkers, Tumor/blood* ; Neoplasm Metastasis ; Prospective Studies ; Adolescent ; Lipids/blood*

OBJECTIVE: Cancer remains a significant global health challenge, necessitating the development of effective treatment approaches. Developing synergistic therapy can provide a highly promising strategy for anti-cancer treatment through combining the benefits of various mechanisms. METHODS: In this study, we developed a synergistic strategy for chemo-photothermal therapy by constructing nanocomposites using gold nanorods (GNRs) and tetrahedral framework nucleic acids (tFNA) loaded with the anti-tumor drug doxorubicin (DOX). RESULTS: Our in vitro studies have systematically clarified the anti-cancer behaviors of tFNA-DOX@GNR nanocomposites, characterized by their enhanced cellular uptake and proficient lysosomal escape capabilities. It was found that the key role of tFNA-DOX@GNR nanocomposites in tumor ablation is primarily due to their capacity to induce cytotoxicity in tumor cells via a photothermal effect, which generates instantaneous high temperatures. This mechanism introduces various responses in tumor cells, facilitated by the thermal effect and the integrated chemotherapeutic action of DOX. These reactions include the induction of endoplasmic reticulum stress, characterized by elevated reactive oxygen species levels, the promotion of apoptotic cell death, and the suppression of tumor cell proliferation. CONCLUSION This work exhibits the potential of synergistic therapy utilizing nanocomposites for cancer treatment and offers a promising avenue for future therapeutic strategies.
Doxorubicin/chemistry* ; Gold/chemistry* ; Nanotubes/chemistry* ; Humans ; Nanocomposites/chemistry* ; Cell Line, Tumor ; Nucleic Acids/chemistry* ; Antibiotics, Antineoplastic/pharmacology* ; Antineoplastic Agents/administration & dosage*

Objective:To investigate the differences in clinical outcomes of septic children with varying serum zinc levels,and to analyze the relationship between reduced serum zinc levels and organ dysfunction as well as 28-day mortality in septic children.Methods:This study conducted a retrospective analysis of clinical data from pediatric patients diagnosed with sepsis or septic shock in the Department of critical care medicine of the children's Hospital of Soochow University between January 2017 and December 2022.Clinical characteristics,organ dysfunction,and prognosis were compared between two groups:children with low serum zinc levels and those with normal zinc levels.Results:The serum zinc level of septic children within 24 hours of admission was 9.60(5.52,13.80)μmol/L,with 50.54%(94/186)of the children exhibiting low serum zinc levels(<10.07 μmol/L).Compared to the normal serum zinc group,the low serum zinc group had a significantly lower Pediatric Critical Illness Score(PCIS)[(78.71±9.35)vs.(85.12±8.51),P=0.005]and higher 28-day mortality(46.80%vs.14.13%,P<0.001).The low serum zinc group also had a higher proportion of invasive mechanical ventilation(64.89%vs.47.82%,P=0.019),renal replacement therapy(15.59%vs.3.26%,P=0.003),and use of vasoactive drugs(56.38%vs.30.43%,P<0.001).The rate of underlying conditions in the low serum zinc group was significantly higher than that in the normal serum zinc group(57.44%vs.36.95%,P=0.005).Additionally,the low serum zinc group had a higher incidence of disseminated intravascular coagulation(DIC),respiratory failure,acute kidney injury,shock,and multiple organ dysfunction syndrome(MODS)compared to the normal serum zinc group(P<0.05).Serum zinc levels had predictive value for 28-day mortality in septic children(AUC=0.813;95%CI:0.725～0.902;P<0.001).A serum zinc level of less than 6.950 μmol/L predicted the death of septic children with a sensitivity of 0.618 and a specificity of 0.902.Conclusion:Sepsis in children is commonly associated with low serum zinc levels,especially in those with underlying conditions such as hematologic and oncologic disorders.Sepsis patients hypozincemia with a higher incidence of DIC,respiratory failure,acute kidney injury,shock,and MODS.A serum zinc level below 6.95 μmol/L serves as a significant predictor of 28-day mortality in children with severe sepsis.

Objective:The association between air pollutants and the risk of sudden cardiac death (SCD) remains controversial. This study aimed to investigate the relationship between five air pollutants—PM 2.5, PM 2.5–10, PM 10, NO 2, and NO?—and the risk of SCD. Methods:We analyzed data from 460 862 participants in the UK Biobank cohort, all enrolled between 2006 and 2010, with no baseline SCD. Follow-up continued until the study endpoint. Annual average concentrations of the five pollutants were assessed. Associations between pollutants and SCD were evaluated using Cox proportional hazards models, followed by Mendelian randomization (MR) to assess causality.Results:Over a mean follow-up of 12.4 years, 2 662 SCD cases were recorded. After adjusting for confounders, no significant associations were found between air pollutants and SCD risk: PM 2.5 ( HR 1.03, 95% CI 0.99–1.07, P = 0.14), PM 2.5–10 ( HR 1.04, 95% CI 1.00–1.08, P = 0.08), PM 10 ( HR 1.01, 95% CI 0.99–1.03, P = 0.26), NO? ( HR 1.00, 95% CI 0.99–1.00, P = 0.26), and NO x ( HR 1.00, 95% CI 1.00–1.01, P = 0.19). MR analysis further supported the absence of causal relationships: PM 2.5 ( β = -0.149, P = 0.90), PM 2.5–10 ( β = 0.387, P = 0.62), PM 10 ( β = -0.994, P = 0.62), NO? ( β = –0.005, P = 0.99), and NO 2 ( β = –0.827, P = 0.25). Conclusions:This study found no evidence linking PM 2.5, PM 2.5–10, PM 10, NO?, or NO 2 to an increased risk of SCD. Mendelian randomization confirmed the lack of causal associations between these pollutants and SCD.

Child safety seats have been proven to be one of the most effective tools for protecting child passengers. However, the widespread phenomenon of safety seats being "unavailable," "owned but not used," or "used incorrectly" is prevalent globally. This paper aims to summarize the obstacles to the use of child safety seats from four aspects: Individual, society, environment and policy, in order to provide a basis for follow-up comprehensive intervention to ensure the safety of children.

AIM: To explore the clinical features, diagnosis and treatment experience and the distribution characteristics of pathogenic microorganisms of primary canaliculitis, and provide reference for its diagnosis and treatment. METHODS: Retrospective clinical study. A total of 119 cases(120 eyes)diagnosed as primary canaliculitis in the department of ophthalmology of Wuxi No.2 People's Hospital from June 2019 to February 2023 were included. The treatment methods were mainly divided into conservative treatment(removing canaliculus stones through lacrimal punctum combined with injecting antibiotic eye ointment into the tube)and surgical treatment. The inspection methods of pathogenic microorganisms included secretion smear microscopy and microbial culture.RESULTS: Primary canaliculitis was more common in middle-aged and older female, mainly manifested by long-term red eye and increased secretion; however, the majority was not accompanied by tearing. Totally, 118 cases(99.2%)had monocular disease, while 63 cases(63 eyes; 52.5%)had inferior lacrimal canaliculus disease. Laboratory examination: Among 119 cases(120 eyes), 4 cases(4 eyes)did not undergo laboratory examination, and the other 115 cases(116 eyes)were as follows: Gram staining microscopy of secretion smear showed that Actinomyces were detected in 102 cases(103 eyes; 88.8%), while no fungus was detected; Microbial culture: 85 cases(86 eyes; 74.1%)were positive for bacterial culture. A total of 111 bacterial strains were cultured, which contained 26 types of bacteria. Among them, 32 strains were aerobic(28.8%); 26 strains were anaerobic(23.4%); and 53 strains were facultative anaerobic(47.7%). The most common bacteria were streptococcus(20 strains), staphylococcus(13 strains), Propionibacterium(10 strains), and capnocytophaga(10 strains). Only 4 cases(4 eyes; 3.4%)of microbial cultures were positive for Actinomyces. Fungus was negative in all microbial cultures. Treatment: Of the 119 cases(120 eyes), 114 cases(115 eyes; 95.8%)were cured by conservative treatment of removing lacrimal canaliculus stones through lacrimal punctum and intracanalicular ointment infiltration(IOI), while 5 cases(5 eyes)were not effective in conservative treatment; however, all of them were cured after surgical treatment, and the cure rate for primary canaliculitis was 100.0%.CONCLUSION: The incidence of primary canaliculitis is low, and it is prevalent in middle-aged and older female. Single lacrimal canaliculus is more common, which could be missed and misdiagnosed in clinic. Actinomyces is the major pathogen observed mostly in mixed infections, with heterogeneous strains, mainly anaerobic or facultative anaerobic bacteria. Streptococcus and Staphylococcus are the most common whereas fungal canaliculitis is rare. The cure rate of primary canaliculitis is high after diagnosis, and IOI method is recommended as the initial treatment of canaliculitis.

Objective:To understand the current status of gastroscopy in diagnosing gastric lesions in general population, and to recommend the optimal age for the first gastroscopy and intervals for repeated gastroscopy.Methods:The gastroscopy records of residents aged 18-80 years in Yinzhou District of Ningbo, Zhejiang Province, between April 2010 and December 2021 were analyzed retrospectively. The detections of gastric lesions across different years, age and genders were described. Goodness of fit tests were applied to compare the differences in detection rates of different lesions in first-time endoscopy in different age groups and different populations. Generalized additive models were used to fit the trend of age specific gastric lesion detection rate explore the optimal age for gastroscopy. The appropriate gastroscopy intervals were determined according to the progress of the gastric lesions detected in repeated gastroscopy.Results:A total of 237 751 participants with 344 398 gastroscopy records were included in analyses. A total of 5 597 cases of chronic atrophic gastritis (CAG), 9 796 cases of intestinal metaplasia (IM), 165 cases of low-grade intraepithelial neoplasia (LGIN), 52 cases of high-grade intraepithelial neoplasia (HGIN) and 435 cases of gastric cancer were detected by the first gastroscopy. The overall detection rate of gastric lesions increased significantly in age group 45-70 years, and remained stable after 70 years old, with LGIN and HGIN showing notable increases at 50 and 55 years old, respectively. Repeated gastroscopy detected CAG, IM, LGIN, and HGIN at a higher rate compared with the first gastroscopy. Normal/superficial gastritis progressed in 3-5 years, whereas CAG or more severe lesions progressed in 1-6 years.Conclusion:Gastroscopy is recommended for general population aged 45 years and above. Furthermore, gastroscopy can be performed every 3-5 years for individuals with normal endoscopy results and once a year for patients with CAG or more severe gastric lesions.

BACKGROUND:Recently,regenerative endodontic therapy is a promising alternative to the maturation of tissue engineering.Inflammatory microenvironment plays a key role in regulating pulp regeneration. OBJECTIVE:To focus on the change in the inflammatory pulp microenvironment,the balance between inflammation and regeneration,and the research advances in tissue-engineered regenerative endodontic therapy within the context of the inflammatory microenvironment to provide a reference for future investigations into regenerative endodontic therapy. METHODS:We conducted a literature search on PubMed and CNKI using search terms"pulp regeneration,inflammation,regenerative endodontic therapy,tissue engineering"in Chinese and English for articles published between 2013 and 2023.The review finally included 61 relevant articles. RESULTS AND CONCLUSION:(1)The changes in the microenvironment of pulpitis involve a complex interplay of cellular and molecular reactions,which,as inflammation progresses,ultimately the microenvironment hinders tissue repair more than facilitates it.(2)Inflammation can promote dental pulp regeneration through stem cell recruitment and activate the complement system,but it can also hinder the regenerative process through immunosuppression and fibrosis.(3)Tissue engineering's three components(stem cells,growth factors,scaffold materials)collaborate to balance inflammation and regeneration,for example,by using interleukin-6 to regulate dental pulp stem cells and foster a regenerative environment.(4)Current research has been largely silent on infection and inflammation issues.The mechanisms underlying changes in the microenvironment of pulpitis are still not fully understood.One promising avenue for improving the clinical applicability of regenerative dental pulp therapy is to achieve precise regulation of the inflammatory-regeneration balance and create a regenerative microenvironment by synergistically leveraging the three elements of tissue engineering.However,this field of investigation still exhibits significant gaps in understanding,necessitating further exploration into innovative strategies for facilitating dental pulp regeneration under inflammation.As such,additional animal experimentation and randomized clinical trials are required to establish a robust foundation for the clinical practice of tissue engineering-based regenerative dental pulp therapy.

Anterior diastema is a common esthetic defect in China.The general treatment for a patient with diastema-ta,including orthodontics and direct and indirect restorations,is a multidisciplinary clinical procedure covering the ortho-dontics,operative dentistry,general dentistry,and prosthodontics department.Given the diversity of departments and the complex etiology of this defect,decision-making regarding the closing methods and time selection is undefined and unin-tegrated,which makes the long-term stability of closure unpredictable.This article proposed an etiology-based decision tree with actual measurement of diastemata width for diastemata closure.The decisional steps include classifying the eti-ological factors based on patients'medical history and clinical manifestation to evaluate the stability of diastemata.After maintaining the stability of diastemata,contemporary and multidisciplinary treatment plans were selected in accordance with the measured width of diastemata and patients'cosmetic psychology,economics,and available time.These decision trees focus on the challenges of collaboration among dental departments,propose an objective and efficient ways for con-nections,and promote efficient and effective diastemata closure.

Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.
Male ; Humans ; Middle Aged ; Atorvastatin/therapeutic use* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Hypercholesterolemia/drug therapy* ; Cholesterol, LDL/therapeutic use* ; Anticholesteremic Agents/therapeutic use* ; Treatment Outcome ; Triglycerides ; Apolipoproteins B/therapeutic use* ; Double-Blind Method ; Pyrroles/therapeutic use*