Objective:Exploring the toxic effects of aspartame (APM) exposure on mice intestine and its potential mechanisms.Methods:Animal experimental research was conducted from July 2023 to May 2024 on the exposure omics platform of the School of Public Health at Capital Medical University. Using a random number table method, 6-8-week-old male C57BL/6J mice were divided into three groups: 0 mg/kg (control group), 150 mg/kg aspartame exposure group, and 500 mg/kg aspartame exposure group, once a day. After 8 weeks of gavage, intestinal permeability tests were performed, and serum was collected from the mice for biochemistry tests. Hematoxylin-eosin staining was used to evaluate the pathological phenotype of the mice′s major organs and colorectal tissues. Transmission electron microscopy (TEM) was used to observe changes in the microscopic structure of the tight junctions in the colorectal epithelium. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunofluorescence (IF) were used to analyze the mRNA levels of tight junction-related genes ( Claudin-1, Occludin, and Tjp-1) and the protein expression levels of tight junction-related proteins (Claudin-1, Occludin, and Tjp-1) in the colorectal tissues of the mice. Comparisons between data were performed using one-way analysis of variance (ANOVA). Results:There were no statistically significant differences in the serum blood biochemistry indicators of mice in the 150 mg/kg and 500 mg/kg aspartame exposure groups compared to the control group. H&E staining showed no significant pathological changes in the major organs and colorectal tissues of mice in the aspartame exposure groups. The results of the intestinal permeability assay showed statistically significant differences in serum FITC-dextran content between groups. The serum FITC-dextran content of mice in the control group and aspartame low and high dose exposure groups were (286.9±33.26), (354.9±78.88) and (350.9±37.87) ng/ml, respectively, with statistically significant differences ( F=4.486, P<0.05). Two-by-two comparisons revealed that the differences between the low or high dose groups and the control group were significant ( q=3.78,3.50, P<0.05), but there was no statistically significant difference between the low and high dose groups ( q=0.23, P>0.05).Transmission electron microscopy revealed disruption and blurred structure of tight junctions in the colorectal epithelium of mice in the low and high-dose aspartame exposure groups. The qRT-PCR results showed that the relative mRNA expression of Claudin-1 and Occludin in mice colon was significantly lower in 150 mg/kg and 500 mg/kg exposed mice, but there was no significantly difference in the expression of the mRNA between the low and high dose groups. The qRT-PCR results showed that the relative mRNA expression levels of Claudin-1 and Occludin in the colon of mice from the control group, 150 mg/kg, and 500 mg/kg aspartame exposure groups were (1.06±0.39, 0.44±0.16, 0.51±0.15) and (1.01±0.10, 0.32±0.17, 0.58±0.17), respectively. The differences were statistically significant ( F=10.26, 31.26, P<0.05). The Tukey test results indicated that the mRNA levels of Claudin-1 and Occludin in the colon of mice in the 150 mg/kg and 500 mg/kg aspartame exposure groups were significantly lower than those in the control group ( q=5.86, 5.18, 11.09, 6.78, P<0.05), but there was no statistically significant difference between the low-dose and high-dose exposure groups ( q=0.68, 4.31, P>0.05). There was no significantly difference in the mRNA expression of Tjp-1 gene in the colon of mice in all groups ( F=1.18, P>0.05). The protein levels of Claudin-1 and Occludin in the colorectal tissues of mice in the 150 mg/kg ( q=7.25, 5.62, P<0.05) and 500 mg/kg ( q=5.35, 5.66, P<0.05) aspartame exposure groups were significantly downregulated, however, there was no significantly difference in the 500 mg/kg compared to 150 mg/kg aspartame exposure group ( q=0.30, 1.64, P>0.05). And the protein level of ZO-1 showed no significant differences between groups ( F=0.43, P>0.05). Conclusion:Aspartame exposure may leads to decreased expression of colorectal tight junction genes Claudin-1 and Occludin and intestinal mechanical barrier damage in mice.

Oral squamous cell carcinoma is a common malignant tumor of the head and neck.Early surgery can achieve good results,but most patients have cervical lymph node metastasis at the time of initial diagnosis.Although surgery combined with radiotherapy or chemotherapy can delay the progression of the disease,the overall prognosis is still not ideal.Especially in patients at stage Ⅲ/Ⅳ,the long-term survival rate has not improved.As a key microbubble in intercellular communication,exosomes contain a large number of biological molecules such as nucleic acids,proteins and lipids.Tumor-derived exosomes play a key role in regulating the tumor micro-environment.This article reviews the effects of tumor-derived exosomes on tumor proliferation,metastasis,immune regulation,diagnosis and treatment in oral squamous cell carcinoma,in order to provide new ideas for early diagnosis and treatment of oral cancer.

Objective To compare the effects of three nickel-titanium file systems,ProTaper Next,TruNatomy,and VDW.RO-TATE,on the morphology of the Danger Zone of the mesial buccal root of mandibular first molar after root canal preparation using Mi-cro-CT and 3D printing technology.Methods 3D-printed mandibular first molars were selected and designed for purpose.They were randomly divided into three groups according to the used NiTi files(n=20).Micro-CT was used to scan the cross-sectional images of the Danger Zone 2 mm below the furcation of the mesial buccal root before and after root canal preparation.The changes in the root ca-nal wall thickness,root canal volume,surface area,cross-sectional area,and root canal transportation in the Danger Zone were ob-served.Statistical analysis was performed using one-way ANOVA(P＜0.05).Results Statistically significant differences were observed before and after root canal preparation in the Danger Zone among the three groups(P＜0.05).Among the three groups,the PTN files caused the largest change before and after preparation,followed by VDW files,and the TRU files had the smallest change.Conclusion The study highlights TruNatomy's conservative shaping capacity,advocating its use in minimally invasive endodontics,whereas Pro-Taper Next may be reserved for cases requiring aggressive canal preparation.

Linxian County in Henan Province, Northern China is known as the region with the highest incidence and mortality rate of esophageal cancer worldwide. Since 1959, the Henan medical team has conducted field work on esophageal cancer prevention and treatment in Linxian. Through three generations of effort exerted by oncologists over 65 years of research on esophageal cancer prevention and treatment in Linxian, the incidence rate of esophageal squamous cell carcinoma in this area has dropped by nearly 50%, and the 5-year survival rate has increased to 40%, reaching the international leading level. This article aims to summarize the history, present opportunities and new challenges, and explore the experience of esophageal cancer prevention and treatment in Linxian (referred to as the “Linxian experience”), providing reference and guidance to cancer prevention and treatment research in China.

Meropenem （MEM） is one of the important drugs for the treatment of severe infections， but the standard dose is often difficult to achieve an effective therapeutic concentration target. This article reviews the related studies on the population pharmacokinetics of MEM in patients with severe infection. It is found that the apparent volume of distribution （Vd） and clearance rate are the most important factors affecting the dose adjustment， and the factors affecting Vd include serum albumin， age， overall weight， shock status， and chest/abdomen/cerebrospinal fluid drainage. The main factors affecting the clearance rate were renal function， renal replacement therapy treatment mode and combination therapy. For adult patients with severe infections in China， MEM is recommended to be administered in an individualized manner based on glomerular filtration rate， with a dosage range of 500 to 1 500 mg given every 4 to 6 hours， and prolonged infusion is preferred. When the minimum inhibitory concentration （MIC） of the pathogenic bacteria reaches 64 mg/L， therapeutic drug monitoring is required. For therapeutic efficacy， it is essential to ensure that the trough concentration remains above the MIC； to prevent drug resistance， it should be maintained above 4×MIC. Regarding safety， it is recommended that the upper limit of the trough concentration be 32 mg/L， and blood sampling for monitoring can be conducted as early as after 1 to 2 doses of administration.

The pathogenesis of chronic sinusitis is complex, involving a variety of inflammatory cells and inflammatory mediators, and neutrophils play a key role in the pathological process of chronic sinusitis. Understanding the molecular basis of the pathogenesis of CRS is helpful for the precise diagnosis and treatment of chronic sinusitis. This article will systematically review the mechanism of neutrophils in the inflammatory response of the body, their role in the pathogenesis and treatment progress in CRS, and look forward to future research directions.
Humans ; Neutrophils ; Sinusitis/immunology* ; Chronic Disease

This article provides a comprehensive review of the progress in the application of transoral robotic surgery（TORS） in the field of head and neck surgery. It elaborates on its developmental background and technical principles as a subset of natural orifice endoscopic surgery and highlights the technical characteristics and optimization trends of both general-purpose and specialized surgical robotic platforms. The review emphasizes the key advantages of TORS in addressing the limitations of traditional transoral surgery, improving surgical precision, and expanding the scope of surgical indications. This in-depth analysis serves as a valuable reference for the future development and wider adoption of TORS technology in head and neck surgery.
Humans ; Robotic Surgical Procedures/methods* ; Natural Orifice Endoscopic Surgery/methods* ; Mouth/surgery*

OBJECTIVES: To evaluate the protective effect of Schistosoma japonicum cystatin (rSj-Cystatin) in a mouse mode of "two-hit" sepsis. METHODS: Sixty male C57BL/6 mice randomized equally into sham-operated group, protein group, "two-hit" modeling group, and protein intervention group. In the former two groups, the mice received an intraperitoneal injection of 100 μL PBS followed by exposure of the cecum and then by intraperitoneal injection of 100 μL PBS or 25 μg rSj-Cystatin 30 min later; In the latter two groups, 100 μL PBS containing LPS (5 mg/kg) was injected intraperitoneally 24 h before cecal ligation and puncture (CLP), and 100 μL PBS or 25 μg rSj-Cystatin were injected 30 min after CLP. At 12 h after rSj-Cystatin treatment, 6 mice from each group were sacrificed for detection of TNF-α, IL-6, IL-10, TGF-β, iNOS and Arg-1 in the serum, spleen, liver, lung and kidney tissues using ELISA, for examinations of liver, lung and kidney pathologies with HE staining, and for analysis of CD3⁺CD4⁺CD25⁺Foxp3⁺ T cell percentage in the spleen using flow cytometry. The remaining mice were observed for general condition and 72-h survival. RESULTS: The 72-h survival rates in the 4 groups were 100%, 100%, 0% and 20%, respectively, showing significant differences between the latter two groups. The mouse models of "two-hit" sepsis exhibited obvious tissue pathologies and significant elevations of TNF-α and IL-6 in both the serum and tissue homogenate, which were significantly ameliorated by rSj-Cystatin treatment. Treatment with rSj-Cystatin also increased IL-10 and TGF-β levels and spleen CD3⁺CD4⁺CD25⁺Foxp3⁺ T cell percentage. The septic mouse models also showed increased iNOS levels in all the detected tissues and a decreased Arg-1 level in the kidney, and these changes were obviously improved by rSj-Cystatin treatment. CONCLUSIONS rSj-Cystatin has a protective effect against "two-hit" sepsis in mice by regulating the inflammatory microenvironment.
Animals ; Mice ; Sepsis/drug therapy* ; Male ; Schistosoma japonicum/chemistry* ; Mice, Inbred C57BL ; Cystatins/therapeutic use* ; Interleukin-10/metabolism* ; Interleukin-6/blood* ; Tumor Necrosis Factor-alpha/blood* ; Disease Models, Animal ; Transforming Growth Factor beta/metabolism*

Chronic cerebral hypoperfusion leads to white matter injury (WMI), which plays a significant role in contributing to vascular cognitive impairment. While 13-docosenamide is a type of fatty acid amide, it remains unclear whether it has therapeutic effects on chronic cerebral hypoperfusion. In this study, we conducted bilateral common carotid artery stenosis (BCAS) surgery to simulate chronic cerebral hypoperfusion-induced WMI and cognitive impairment. Our findings showed that 13-docosenamide alleviates WMI and cognitive impairment in BCAS mice. Mechanistically, 13-docosenamide specifically binds to cannabinoid receptor 1 (CNR1) in oligodendrocyte precursor cells (OPCs). This interaction results in an upregulation of ubiquitin-specific peptidase 33 (USP33)-mediated CNR1 deubiquitination, subsequently increasing CNR1 protein expression, activating the phosphorylation of the AKT/mTOR pathway, and promoting the differentiation of OPCs. In conclusion, our study suggests that 13-docosenamide can ameliorate chronic cerebral hypoperfusion-induced WMI and cognitive impairment by enhancing OPC differentiation and could serve as a potential therapeutic drug.
Animals ; Oligodendrocyte Precursor Cells/metabolism* ; Mice ; Cell Differentiation/drug effects* ; Male ; Receptor, Cannabinoid, CB1/metabolism* ; Mice, Inbred C57BL ; Ubiquitin Thiolesterase/metabolism* ; Ubiquitination/drug effects* ; Carotid Stenosis/complications* ; Cognitive Dysfunction/drug therapy*