Objective To explore the causal relationship between immune cells and heart failure (HF), and the mediating role of serum metabolites, in order to identify potential biomarkers and therapeutic targets. Methods We employed a two-sample Mendelian randomization (MR) analysis method based on genome-wide association study (GWAS) data, analyzing the direct and indirect effects of 731 types of immune cells and 1 400 metabolites on HF. We selected valid instrumental variables and conducted statistical analyses using R software. The primary analysis was performed using the inverse variance weighted method, supplemented by MR-Egger analysis and weighted median method. The stability of the results was assessed through tests such as Cochran’s Q test. Results Our research found a negative causal relationship between PD-L1 on CD14−CD16+ and HF. Sensitivity analysis supported this result. The reverse MR analysis did not find an effect of HF on PD-L1 on CD14−CD16+, indicating that PD-L1 on CD14−CD16+ might play a unidirectional role in reducing the risk of HF. Further mediation MR analysis showed that PD-L1 on CD14−CD16+ might influence the risk of HF onset by regulating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), with a mediation effect ratio of 6.7%. Conclusion PD-L1 on CD14−CD16+ may reduce the risk of HF by elevating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), which provides a new perspective for understanding the pathogenesis of HF.

Objective:To investigate the reference intervals of serum uric acid levels in normal-weight children and analyze the factors influencing these levels.Methods:In this cross-sectional study, clinical data were collected from 7 910 normal-weight children, aged 1 month to 15 years, who underwent health check-ups at the Children′s Hospital of Zhejiang University School of Medicine between August 2013 and August 2023. Data included sex, age, pubertal signs, blood pressure, and serum uric acid levels. The participants were categorized into 4 age groups: 1-<12 months, 1-<6 years, 6-<11 years, and 11-<16 years, and were further analyzed by sex. The P5 and P95 percentiles of uric acid values were defined as the lower and upper limits of the reference interval, respectively. Correlation analysis and partial correlation analysis were used to assess the relationship between uric acid and other variables such as age, body mass index Z value, and Tanner stage. Multivariate linear regression was used to compare uric acid levels across gender and age groups, respectively. Results:Among the 7 910 children, the distribution across age groups was as follows: 562 (317 boys) in 1-<12 months, 4 120 (2 366 boys) in 1-<6 years, 2 357 (1 432 boys) in 6-<11 years, and 871 (536 boys) in 11-<16 years, the uric acid levels in boys were significantly higher than those in girls ( P<0.05). Uric acid levels exhibited a positive correlation with age ( r=0.47 , 0.20, both P<0.001), and a weak positive correlation with BMI Z-scores(both r=0.11, P<0.001). Among participants aged 6-<11 years and 11-<16 years, uric acid levels in boys were positively correlated with Tanner stage ( r=0.10, 0.27, both P<0.05), but no significant correlation was observed in girls (all P>0.05). The uric acid levels were significantly higher in boys than in girls in the 1-<12 months, 1-<6 years and 11-<16 years age groups (all P<0.05), but no significant gender difference was found in the 6-<11 years groups ( P>0.05). Uric acid levels exhibited statistically significant variations among age groups ( P<0.001). The reference intervals of uric acid values were as follows in 1-<12 months age group, 157-335 μmol/L for boys and 160-315 μmol/L for girls; in 1-<6 years age group, 180-359 μmol/L for boys and 180-355 μmol/L for girls; in 6-<11 years group, 190-375 μmol/L; in 11-<16 years age group, 237-480 μmol/L for boys and 218-410 μmol/L for girls. Conclusions:Reference intervals for uric acid varying significantly across different pediatric age groups. Sex, and pubertal development status are closely related to uric acid levels.

Objective To explore the mediating role of intolerance of uncertainty(IU)and moderating role of the negative emotion differentiation in the influence of perceived stress on anxiety among college students from a cognitive perspective.Methods A total of 271 participants were surveyed using the perceived stress scale,intolerance of uncertainty scale,depression anxiety and stress scale(Chinese version),and the test on negative emotional differentiation.SPSS 22.0 was used to perform descriptive statistics and correlation analyses and to test the moderated mediation model.Results Perceived stress affected anxiety and IU played a mediating role-perceived stress could affect anxiety through influencing IU.At the same time,the influence of IU on anxiety could be adjusted through the negative emotion differentiation.The higher the degree of negative emotion differentiation,the lower the degree of anxiety increase(β=0.17,t=5.70,P＜0.01).Conclusion It may be effective to develop training programs to reduce anxiety by regulating perceived stress,increasing acceptance of uncertainty,and improving the negative emotion differentiation,which can help individuals reduce anxiety by perceiving and adjusting anxiety-related emotional or cognitive factors in a timely manner.

Objective:To investigate optimal treatment strategy for pT3N0 laryngeal squamous cell carcinoma（SCC）. Methods:A retrospective study of 150 patients with pT3N0 laryngeal SCC treated in the First Affiliated Hospital of Chongqing Medical University was performed. The efficacies of partial laryngectomy and total laryngectomy, as well as surgery alone and postoperative radiotherapy were evaluated. The overall survival（OS）, disease specific survival（DSS） and disease-free survival（DFS） were analyzed with statistical package from SPSS. Results:Among the 108 patients with glottic laryngeal SCC, there were no significant differences in OS, DSS and DFS between the partial laryngectomy group and the total laryngectomy group（Log-rank=0.184, 0.010 and 0.051, P>0.05）. Similarly, there were no significant differences in OS, DSS and DFS between the surgery-alone group and postoperative radiotherapy group（Log-rank=0.214, 0.251 and 0.003, P>0.05）. Among the 38 patients with supraglottic laryngeal SCC, the OS in the total laryngectomy group was significantly higher than that in the partial laryngectomy group（Log-rank=7.338, P=0.007）. The DSS and DFS in the total laryngectomy group were higher than in the partial laryngectomy group, but the differences were not statistically significant（Log-rank=0.895 and 1.792; P>0.05）. The DFS in the postoperative radiotherapy group was significantly higher than in the surgery-alone group（Log-rank=7.172, P=0.007）, but there were no significant differences in OS and DSS between these two groups（Log-rank=0.010 and 0.876, P>0.05）. Conclusion:For pT3N0 glottic laryngeal cancer patients, the efficacy of partial laryngectomy is comparable to total laryngectomy, same as surgery alone and postoperative radiotherapy. For pT3N0 supraglottic laryngeal cancer patients, total laryngectomy could improve the overall survival, and postoperative radiotherapy could reduce the recurrence. Prospectively randomized study with large samples is still needed.
Humans ; Laryngeal Neoplasms/therapy* ; Laryngectomy/methods* ; Retrospective Studies ; Carcinoma, Squamous Cell/surgery* ; Male ; Female ; Middle Aged ; Disease-Free Survival ; Neoplasm Staging ; Aged ; Survival Rate ; Treatment Outcome

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.

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Objective To analyze the differences in bone serum protein between patients with osteoporosis accompanied by obstructive sleep apnea syndrome(OSAS)and those with osteoporosis only using proteomics.Methods A total of 80 osteoporosis patients who attended our hospital between June 2022 and June 2024 were enrolled.Based on their polysomnography results,the participants were divided into an OSAS and osteoporosis comorbidity(OSAS-osteoporosis)group(n=42)and an osteoporosis only group(n=38).Propensity score matching was applied to incorporate covariates in logistic regression so that the individual characteristics of the two groups of patients were generally balanced.Following the matching procedure,a final cohort of 20 matched pairs was obtained and subsequently utilized for further analysis.The mass spectrum was obtained using laser desorption ionization mass spectrometry.Principal component analysis(PCA)was performed to assess differences in metabolic patterns between groups.Partial least squares discriminant analysis(PLS-DA)and orthogonal PLS-DA(OPLS-DA)were employed for further data analysis.Variable importance in projection(VIP)scores of each substance were calculated with OPLS-DA to screen the metabolites showing inter-group differences.Heatmaps were generated to visualize metabolic profile differences between the OSAS-osteoporosis group and the osteoporosis group.Enrichment pathway analysis was conducted on the differential identified metabolites.Results After propensity score matching,individual characteristics between the groups were well balanced.Mass spectrometry revealed significant differences between the OSAS-osteoporosis and osteoporosis groups.In the PCA score plot,the separation trend of the two groups was not significant.The PLS-DA score plot showed a discernible separation trend,with R2 and Q2 lower than those of the corresponding results of the real model,confirming the reliability of the model.OPLS-DA showed that the total R2X of the model was 0.635,R2Y was 0.879,and O2Y was 0.728,showing obvious separation trends between the two groups.A total of 16 differential metabolites were identified,including stearyl-oleyl-glycerol phosphate choline,phosphate choline,L-histidine,erucamide,2'-deoxyuridine,1-palmitoyl glycerol,thymine,tyramine,L-pyroglutamic acid,L-glutamic acid,myristate,glycerol-3-phosphate,caprylic acid,pregnenolone,L-arginine,D-4-hydroxyphenylglycine,and isobutyric acid.Heatmaps showed significant differences in metabolic profiles between the OSAS-osteoporosis group and the osteoporosis group.Pathway enrichment analysis showed that 27 metabolic pathways were involved.27 metabolic pathways.Under the conditions of P<0.05 and pathway impact>0.2,the three most significant metabolic pathways identified included mainly alanine,aspartate,and glutamate metabolism,arginine biosynthesis,and histidine metabolism.Conclusion Significant differences were observed in the metabolic profiles between patients with both OSAS and osteoporosis and those with osteoporosis alone.

Retrograde intrarenal surgery（RIRS）has become a first-line therapeutic option for upper urinary tract stones ≤2 cm. Although conventional ureteral access sheaths enable smooth ureteroscope insertion and reduce intrarenal pressure，but the stone-free rate（SFR）remains limited. Recently，a novel flexible and navigable suction ureteral access sheath（FANS）has improved the stone clearance efficiency，therapeutic effect，and safety of RIRS. The advent of FANS is progressively reshaping the role of RIRS within urological endoscopic surgery. This review aims to summarize the current research on FANS in the management of urolithiasis and discuss potential directions for its future development.

We report a 30-year-old woman who presented with intermittent gross hematuria and left flank pain，and CT revealed a left staghorn stones. The initial percutaneous nephrolithotomy（PCNL）left a 6 mm fragment，and both stone and urine cultures yielded extended-spectrum β-lactamase（ESBL）-producing Escherichia coli. Seven months later，the stone increased to 6 cm and urine culture revealed Proteus mirabilis. Endoscopic combined intrarenal surgery（ECIRS）achieved complete clearance. At 6-month follow-up，the patient remained asymptomatic，culture-negative，and stone-free. This case highlights that small residual fragments after PCNL may rapidly enlarge with secondary urease-producing infection，underscoring the need for early re-intervention and standard follow-up.

Objective:To evaluate the diagnostic efficacy of conventional ultrasound combined with contrast-enhanced ultrasound (CEUS) for detecting cervical lymph node metastasis in head and neck squamous cell carcinoma (HNSCC).Methods:This retrospective case control study included 259 patients (249 males and 10 females,aged 40-88 years with a median age of 63 years) who were pathologically diagnosed with HNSCC at the First Affiliated Hospital of Chongqing Medical University from April 2022 to August 2024. A total of 259 lymph nodes were assessed(78 pathologically positive nodes and 181 pathologically negative ones). Receiver operating characteristic (ROC) curves were plotted to compare the diagnostic efficacies of conventional ultrasound combined with CEUS and CT, MRI, or conventional ultrasound for cervical lymph node metastasis. Patients were randomly assigned to a training group ( n=208) and a validation group ( n=51) (8∶2). Univariate and multivariate Logistic regression were used to analyze the independent risk factors for lymph node metastasis prediction. A nomogram model was constructed based on independent risk factors. The model predictive efficacy was assessed by ROC curve, and model′s fit was evaluated by Hosmer-Lemeshow test. Results:The area under the curve (AUC) for conventional ultrasound combined with CEUS in predicting cervical lymph node metastasis in HNSCC was 0.923 (95% CI: 0.880-0.965), which was significantly higher than those for enhanced CT, cervical enhanced MRI, and conventional ultrasound [AUC were 0.820 (95% CI: 0.753-0.886), 0.802 (95% CI: 0.737-0.866), and0.836 (95% CI: 0.774-0.899), respectively].There were no statistically significant differences in clinical data between the two groups (all P>0.05). Univariate Logistic regression analysis showed that, among contrast-enhanced ultrasound features, the centripetal perfusion pattern, irregular perfusion defect type, and uneven distribution of contrast agent were significantly associated with cervical lymph node metastasis (all P<0.05). Among conventional ultrasound features, L/S ratio≤1.5, heterogeneous internal echoes, uneven cortex thickening, blurred corticomedullary boundary, loss of lymphatic gate structure, and peripheral or mixed type on color Doppler flow imaging were significantly associated with cervical lymph node metastasis (all P<0.05). Multivariate Logistic regression analysis indicated that the centripetal perfusion pattern, heterogeneous internal echoes, and uneven cortical thickening were independent risk factors for cervical lymph node metastasis (all P<0.05). A nomogram model was constructed based on the above independent risk factors, and offered an AUC of 0.933 (95% CI:0.890-0.976) in the training group, which was significantly higher than that for enhanced CT, enhanced MRI, conventional ultrasound, and conventional ultrasound combined with CEUS [AUC were 0.818 (95% CI:0.747-0.890), 0.807 (95% CI:0.739-0.875), 0.842 (95% CI: 0.777-0.908), and 0.921 (95% CI:0.876-0.967), respectively]. In the validation group, the AUC was 0.866 (95% CI:0.703-1.000), which was higher than that for cervical enhanced CT, enhanced MRI, and conventional ultrasound [AUC were 0.820 (95% CI:0.613-1.000), 0.711 (95% CI:0.478-0.943), and 0.748 (95% CI:0.515-0.982), respectively]. Conclusion:The combination of conventional ultrasound and CEUS has significant clinical application value in predicting cervical lymph node metastasis in HNSCC.