ObjectiveTo investigate the effect of mitochondrial calcium uniporter （MCU） on the cytoskeleton of pancreatic ductal epithelial cells in a mouse model of acute pancreatitis （AP） induced by caerulein （CAE）， to analyze the role of MCU in the development of AP， and to provide a theoretical basis for clinical treatment. MethodsIn the in vivo experiment， wild-type male C57BL6/J mice， aged 4 weeks， were randomly divided into control group and AP group， with 6 mice in each group. The mice in the AP group were given intraperitoneal injection of CAE to establish a model of AP， and those in the control group were given intraperitoneal injection of an equal volume of normal saline. Serum and pancreatic tissue samples were collected after 24 hours of modeling. HE staining was used to observe pancreatic histopathological changes； Western Blot was used to measure the expression levels of MCU， glutathione peroxidase 4 （GPX4）， and acyl-CoA synthetase long chain family member 4 （ASCL4）； kits were used to measure the serum level of amylase. In the in vitro experiment， the human pancreatic ductal epithelial cell line HPDE6-C7 was co-cultured with CAE for 24 hours to establish an in vitro AP model， and the cells were divided into control group， CAE group， RR （an MCU activity inhibitor） group， CAE+RR group， Fer-1 （an ferroptosis inhibitor） group， CAE+Fer-1 group， Erastin （an ferroptosis inducer） group， and CAE+Erastin group. CCK-8 assay was used to observe the influence of different agents on cell viability； Western Blot was used to measure the expression levels of MCU， GPX4， and ASCL4； immunofluorescence assay was used to measure reactive oxygen species （ROS）， actin cytoskeleton， and monolayer permeability； kits were used to measure the concentrations of malondialdehyde （MDA）， glutathione （GSH）， Fe²⁺， and total iron. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for comparison between two groups. ResultsIn the in vivo experiment， compared with the control group， the AP group had significant increases in pancreatic histopathological score， the serum level of amylase， and the expression levels of MCU and ASCL4， as well as a significant reduction in the expression of GPX4 （all P<0.05）. In the in vitro experiment， compared with the control group， the CAE group had significant increases in the expression levels of MCU and ASCL4， a significant reduction in the expression of GPX4， and significant increases in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability， as well as a significant reduction in the concentration of GSH （all P<0.05）， with the presence of actin cytoskeleton disruption. Compared with the CAE group， the CAE+RR group had a significant increase in the expression level of GPX4， a significant reduction in the expression level of ASCL4， and significant reductions in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability and a significant increase in the concentration of GSH （all P<0.05）， with alleviation of actin cytoskeleton disruption. Compared with the CAE group， the CAE+Fer-1 group had significant reductions in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability and a significant increase in the concentration of GSH （all P<0.05）， with alleviation of actin cytoskeleton disruption. Compared with the CAE group， the CAE+Erastin group had significant increases in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability and a significant reduction in the concentration of GSH （all P<0.05）， with aggravation of actin cytoskeleton disruption. ConclusionDuring the onset of AP， MCU mediates oxidative stress-induced ferroptosis and leads to the disruption of the pancreatic ductal epithelial barrier， which may be one of the possible pathogeneses of AP.

Objective: To explore the correlation between Candida albicans and the development of oral leukoplakia (OLK), and to provide a basis for improving the pathogenic mechanism of the malignant transformation of OLK. Methods: Oral microbiome data were obtained from public databases (NCBI BioProject, PRJNA788378; GEO, GSE227919), and bioinformatic methods were employed to evaluate the correlation between Candida albicans infection and OLK. Approval was obtained from the institutional Medical Ethics Committee. A tissue microarray was constructed using samples collected from an OLK clinical cohort. Hematoxylin and eosin (H&E) staining and periodic acid-Schiff (PAS) staining were performed to analyze the relationship between the Candida albicans detection rate and clinicopathological features. Approval was obtained from the institutional Animal Ethics Committee. A mouse model was established by combining 4-nitroquinoline-1-oxide (4NQO) in drinking water with oral inoculation of Candida albicans (4NQO + Candida albicans group), while mice treated with 4NQO in drinking water and PBS served as the control group (4NQO + PBS group). The degree of epithelial dysplasia was compared between the two groups to assess the impact of Candida albicans infection on lesion progression (defined in this study as the progression from mild/moderate epithelial dysplasia to severe dysplasia/carcinoma in situ or invasive squamous cell carcinoma). Results: Bioinformatic analysis revealed that the detection rate of Candida albicans in OPMDs and OLK tissues was significantly higher than that in the healthy control group. Staining results of clinical samples demonstrated that Candida albicans colonized OLK lesions; compared with Candida albicans-negative patients, positive patients exhibited a state of high-grade progression. Animal experiments indicated that, compared with the 4NQO + PBS group, the degree of oral epithelial dysplasia in the 4NQO + Candida albicans group was significantly exacerbated, and the malignant transformation rate was higher, suggesting that Candida albicans promotes the high-grade progression of OLK. Conclusion Candida albicans exhibits a increasing trend during the malignant progression of the OLK. It aggravates the degree of epithelial dysplasia in OLK and promotes its transformation into high-grade lesions, suggesting that Candida albicans plays a crucial promoting role in the high-grade progression of OLK.

Objective To investigate the setup error in patients with spinal bone metastasis who underwent radiotherapy under the guidance of kilovoltage cone-beam CT (KV-CBCT). Methods A total of 118 patients with spinal metastasis who underwent radiotherapy, including 17 cases of cervical spine, 62 cases of thoracic spine, and 39 cases of lumbar spine, were collected. KV-CBCT scans were performed using the linear accelerators from Elekta and Varian’s EDGE system. CBCT images were registered with reference CT images in the bone window mode. A total of 973 data were collected, and 3D linear errors were recorded. Results The patients with spinal bone metastasis were grouped by site, height, weight, and BMI. The P value of the patients grouped only by site was P<0.05, which was statistically significant. Conclusion When grouped by site in the 3D direction, the positioning effect of cervical spine is better than that of thoracic and lumbar spine. The positioning effect of the thoracic spine is better in the head and foot direction but worse in the left and right direction compared with that of the lumbar spine. Instead of extending or narrowing the margin according to the BMI of patients with spinal metastasis, the margin must be changed according to the site of spinal bone metastasis.

Toxoplasma gondii is an obligate intracellular parasite that can invade the central nervous system(CNS)and cause complications such as encephalitis and schizophrenia.To migrate into the brain,T.gondii must cross restrictive cell barriers(blood-brain barrier,blood-cerebrospinal fluid barrier,and meninges).T.gondii migrates into the brain through transcellular or/and paracel-lular invasion and"Trojan horse"mechanisms,alone or in combination.The excessive inflammatory response after T.gondii infection destroys the blood-brain barrier and increases its permeability,thus further promoting the migration of T.gondii into the brain and causing persistent infection of the central nervous system.This review focuses on the mechanisms through which T.gondii migrates into the brain and the anti-T.gondii responses of brain parenchymal cells,to provide a deeper understanding of the pathogenic mecha-nisms of T.gondii and to offer insights for the development of novel therapeutic strategies.

Objective To evaluate the frailty status and risk factors among hospitalized elderly patients after percutaneous coronary intervention(PCI),and to provide a reference for improving and delaying their frailty.Methods From March to August 2024,using convenience sampling,patients aged over 75 years who underwent PCI in a tertiary cardiovascular disease specialist hospital in Beijing were selected as the survey participants.Patient-related informations were collected through a self-designed general information questionnaire.The Fried Phenotype Frailty Scale,the Katz Activities of Daily Living,Lawton Instrumental Activities of Daily Living(IADL)scale,the Charlson Comorbidity Index,the Morse Fall Scale,the Mini Nutritional Assessment-Short Form(MNA-SF),and the 15-item Geriatric Depression Scale(GDS-15)were evaluated postoperatively until discharge.Univariate and multivariate logistic analyses were conducted to identify factors associated with frailty among patients after PCI.Results A total of 278 patients were included.The incidence of frailty after PCI was 52.16％.Based on Fried Phenotype scores,patients were divided into a non-frail group and a frail group.Univariate analysis showed statistically significant differences between the 2 groups in terms of age,gender,hemoglobin,NT-ProBNP,LVEF,IADL scores,living alone status,nutrition status,falls risk,and depression level(P＜0.05).Multivariate logistic regression analysis revealed that age,Lawton IADL scores,falls risk,nutrition status,depression level were factors influencing frailty,with odds ratios of 1.167,0.575,1.597,0.399,and 3.610,respectively(P＜0.05).Conclusion The incidence of frailty is high among patients aged over 75 years after PCI,and there are multiple risk factors affecting their frailty status.Clinical healthcare providers should prioritize long-term management of these patients and implement comprehensive interventions with the consideration of their physiological,psychological,and social conditions.

Objective Taking a tertiary hospital in Beijing as an example,to investigate patients'continuous use inclination towards utilizing Internet diagnosis and treatment,dissect the influential factors and elucidate the pathway through which these factors exert their impact,and propose recommendations for optimizing internet diagnosis and treatment services in the hospital.Methods Based on the model of continuous use of information system and the model of success of information system,it constructed a structural equation model of the willingness to use Internet diagnosis and treatment service continuously and put forward the hypotheses,conducted a questionnaire survey.Descriptive analysis,reliability and validity tests,structural model analysis and hypothesis testing were conducted using Excel and SmartPLS 4.0 software to validate the research hypotheses.Results The information quality,service quality,and system quality of Internet diagnosis and treatment services have a positive effect on patients'willingness to continue to use them,with perceived usefulness and user satisfaction playing a major mediating role.Conclusion Internet hospitals should establish skill training and medical record review mechanisms,improve service processes and communication norms,optimize system design and user experience,enhance interactivity and personalized services,to promote the sustainable development of Internet diagnosis and treatment services in entity medical institutions.

[Purpose]To analyze the incidence and mortality of oral and pharyngeal cancer in can-cer registration areas of Hunan Province in 2021 and the trend changes from 2012 to 2021.[Methods]Data on oral and pharyngeal cancer incidence and mortality from 2012 to 2021 were collected from 78 quality-controlled cancer registries in Hunan Province,with population data sourced from household registration statistics provided by public security authorities.Indicators such as crude incidence and mortality rates,age-standardized incidence and mortality rates by Chinese standard population(ASIRC/ASMRC),and world standard population(ASIRW,ASMRW)in 2021 were calculated.The Chinese standard population(2000 national census)and Segi's world standard population were used for standardization.Joinpoint Regression Program 4.9.0.0 software was used to fit a Log-linear regression model,and the average annual percentage change(AAPC)of ASIRC/ASMRC of oral and pharyngeal cancer from 2012 to 2021 was calculated to analyze the changing trends.[Results]In 2021,the crude incidence rate of oral and pharyngeal cancer in cancer registration areas of Hunan Province was 9.28/105(15.14/105 for males and 3.07/105 for fe-males),with an ASIRC of 6.10/105;the crude mortality rate was 3.75/105(6.19/105 for males and 1.16/105 for females),with an ASMRC of 2.16/105.Both the incidence and mortality rates in male were significantly higher than those in female.Age distribution analysis showed that the incidence rate of oral and pharyngeal cancer increased with age after 30 years old,peaking in the age group of 60～64 years old(22.29/105);the mortality rate continued to rise after 35 years old,reaching the peak in the population aged ≥85 years old(14.52/105).Trend analysis from 2012 to 2021 indicated that the crude incidence rate and ASIRC of oral and pharyngeal cancer increased from 3.50/105 and 2.63/105 in 2012 to 9.28/105 and 6.10/105 in 2021,with AAPC of 12.33％and 10.80％,re-spectively;the crude mortality rate and ASMRC also showed upward trends(AAPC of 9.87％and 7.21％,respectively);all trend changes were statistically significant(all P＜0.05).Sex stratification revealed that the AAPC of ASIRC and ASMRC of oral and pharyngeal cancer in male were higher than those in female(AAPC of ASIRC:12.65％for males vs 4.28％for females;AAPC of ASMRC:8.79％for males vs 4.13％for females).Age-specific trend analysis found that the ASIRC of oral and pharyngeal cancer in the population aged ≤ 44 years old showed an upward trend(AAPC=11.73％,P＜0.001),with the AAPC of male in this group reaching 14.57％;the AAPC of ASIRC for the age groups of 45～64 years old and ≥65 years old were 11.03％and 9.74％,respectively,and the AAPC of ASMRC for these two groups were 10.05％and 8.19％,respectively,with all trend changes being statistically significant(all P＜0.05);there was no statistically significant change in the ASMRC of the population aged ≤44 years old(AAPC=5.66％,P=0.087).[Conclusion]The incidence and mortality rates of oral and pharyngeal cancer in cancer registration areas of Hunan Province remain high and show an upward trend,with a tendency of younger onset.Males and middle-aged and elderly populations are the key focuses of prevention and control.

Objective:To compare clinical features, esophageal motility, and reflux characteristics in elderly patients with gastroesophageal reflux disease(GERD)with and without extraesophageal symptoms.Methods:This study was conducted as a cross-sectional analysis involving 75 patients aged 60 years and older, who visited the outpatient department of gastroenterology at China-Japan Friendship Hospital between January and December 2023.Among these, 43 patients exhibited extraesophageal symptoms [23 males, 20 females; median age 69(66, 75)], while 32 patients did not present with such symptoms [12 males, 20 females; median age 69(66, 73.75)].We collected data regarding the patients' demographic characteristics, lifestyle habits, and comorbidities via a questionnaire, and analyzed the range of extraesophageal symptoms.The presence of reflux esophagitis was assessed according to the Los Angeles classification, and the status of the gastroesophageal valve was evaluated through gastroscopy.Additionally, we measured esophageal motility and reflux characteristics using high-resolution manometry and 24-hour pH-impedance monitoring.Results:The smoking rate was significantly higher in patients with extraesophageal symptoms compared to those without extraesophageal symptoms[39.53%(17/43) vs.15.63%(5/32), P=0.039].Conversely, the prevalence of hypertension was significantly higher in patients without extraesophageal symptoms compared to those with extraesophageal symptoms[41.86%(18/43) vs.65.63%(21/32), χ2=4.151, P=0.042].Among patients with extraesophageal symptoms, the proportion experiencing pharyngeal symptoms was the highest at 83.72% (36/43), followed by oral symptoms at 32.56%(14/43), while the lowest proportion was for respiratory symptoms at 16.28%(7/43).The esophageal body peristaltic contraction rate was significantly higher in patients without extraesophageal symptoms compared to those with extraesophageal symptoms[100%(100%, 100%) vs.100%(80%, 100%), Z=-2.671, P=0.008].The number of non-acid reflux episodes was significantly higher in patients with extraesophageal symptoms compared to those without[5.00(1.00, 5.00) vs.1.00(1.00, 2.00), Z=-3.842, P<0.001].Additionally, the proportion of proximal reflux was significantly higher in patients with extraesophageal symptoms compared to those without[83.8%(65.6%, 95.4%) vs.68.5%(59.8%, 77.35%), Z=-2.037, P=0.042]. Conclusions:Patients with GERD and extraesophageal symptoms exhibit a higher prevalence of smoking, diminished peristaltic function in the esophageal body, an increased incidence of proximal esophageal reflux, and a greater number of non-acid reflux episodes.

Objective:To explore the role and molecular mechanisms of S100A6 protein in neonatal meningitis caused by Streptococcus agalactiae. Methods:Human brain microvascular endothelial cells (HBMECs) were used as an in vitro experimental model, and siRNA was employed to construct S100A6 gene knockdown HBMECs strain. The S100A6 gene overexpression cell line was established by lentiviral transfection method. Western blot was used to detect the expression level of S100A6 protein in HBMECs after Streptococcus agalactiae infection, and the change in intracellular inflammatory cytokine protein levels after S100A6 gene knockdown or overexpression. A neonatal bacterial meningitis model was established by injecting Streptococcus agalactiae suspension into the cisterna magna of neonatal Sprague-Dawley (SD) rats. HE staining was used to observe pathological changes in brain tissue; immunohistochemistry was used to detect the expression and distribution of S100A6 protein in brain tissue; Western blot and ELISA were used to measure S100A6 protein levels in cerebrospinal fluid (CSF). Results:Compared with the control group, the intracellular S100A6 protein level in HBMECs increased significantly following Streptococcus cgalactiae infection. After S100A6 gene knockdown, the invasion rate of Streptococcus agalactiae into the HBMECs was significantly reduced ( P<0.01), while intracellular TNF-α and IL-6 protein levels were elevated markedly ( P<0.01). In contrast, overexpression of S100A6 gene increased the invasion rate ( P<0.01) and notably decreased TNF-α and IL-6 protein levels ( P<0.001). In the neonatal SD rat bacterial meningitis model, HE staining revealed substantial neutrophil infiltration in brain tissue after Streptococcus agalactiae infection. Immunohistochemistry showed extensive deposition of S100A6 protein around the meninges, and significant expression of S100A6 protein was also detected in CSF. Conclusions:S100A6 protein is crucial in mediating neonatal meningitis caused by Streptococcus agalactiae infection. S100A6 gene knockdown promotes the production of intracellular inflammatory cytokines and reduces Streptococcus agalactiae invasion into cells, thereby alleviating bacteria-induced cellular damage. Additionally, the increased expression of S100A6 protein in brain tissue and CSF after Streptococcus agalactiae infection suggests its potential as a diagnostic biomarker for bacterial meningitis.

Children with cancer represent a distinct patient population, and decisions regarding hospice care preferences are primarily made by their parents. This article examines parental preferences concerning the location and goals of hospice care for their children with cancer, discusses the advantages and disadvantages associated with these choices, and identifies factors influencing parental preferences for hospice care. The aim is to provide a reference for clinical healthcare professionals in delivering high-quality hospice care services for children with cancer that align with parental preferences.