ObjectiveTo investigate the effect and mechanism of Yijingtang （YJT） in treating diminished ovarian reserve （DOR） in rats by regulating the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway. MethodsFifty female SD rats with normal estrous cycles were randomly allocated into blank， model， low- and high-dose （12.579 and 25.158 g·kg^-1， respectively） YJT， and dehydroepiandrosterone （7.487 5 mg·kg^-1） groups， with 10 rats in each group. The rats in other groups except the blank group were administrated with the tripterygium glycosides tablet suspension （5 mg·kg^-1） by gavage for 14 days for the modeling of DOR. The rats in the drug treatment groups were administrated with corresponding drugs by gavage from day 15 for 30 consecutive days， and those in the blank and model groups received equal volumes of distilled water. The vaginal exfoliated cell smears were observed to assess the changes in the estrous cycle. The wet weight of bilateral ovaries was weighed for calculation of the ovarian index. Hematoxylin-eosin staining was performed to observe the histopathological changes in the ovaries and the proportions of follicles at various levels were calculated. The serum levels of sex hormones ［follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， and anti-Müllerian hormone （AMH）］ and inflammatory factors ［tumor necrosis factor-alpha （TNF-α）， interleukin-1beta （IL-1β）， and interleukin-10 （IL-10）］ were determined by enzyme-linked immunosorbent assay. Real-time quantitative polymerase chain reaction（Real-time PCR） was conducted to determine the mRNA levels of TLR4， MyD88， NF-κB profilin α （IκBα）， NF-κB and inflammatory factors in the ovarian tissue. Western blot was employed to measure the protein levels of factors related to the TLR4/MyD88/NF-κB signaling pathway in the ovarian tissue. Immunofluorescence （IF） was used to detect the nuclear translocation of NF-κB p65 in the ovarian tissue. ResultsCompared with the blank group， the model group showed disturbed estrous cycles， increased inflammatory infiltration in the ovarian tissue， decreases in ovarian index and proportion of presinusoidal follicles， and an increase in the proportion of atretic follicles （P<0.05， P<0.01）. In addition， the model group showed elevated serum levels of FSH， LH， TNF-α， and IL-1β， up-regulated mRNA levels of TLR4， MyD88， IκBα， NF-κB， TNF-α， and IL-1β and protein levels of TLR4， MyD88， p-IκBα， and p-NF-κB p65 （P<0.01）， lowered serum levels of AMH， E₂， and IL-10， down-regulated mRNA level of IL-10 （P<0.01）， and massive nuclear translocation of NF-κB p65 in the ovarian tissue. Compared with the model group， dehydroepiandrosterone and low and high doses of YJT restored the disturbed estrous cycle， reduced inflammatory infiltration in the ovarian tissue， increased the ovarian index （P<0.01）， and changed the follicular composition ratio （P<0.01）. Furthermore， the drugs lowered the serum levels of FSH， LH， TNF-α， and IL-1β， down-regulated the mRNA levels of TLR4， MyD88， IκBα， NF-κB， TNF-α， and IL-1β and the protein levels of TLR4， MyD88， p-IκBα， and p-NF-κB p65 （P<0.05， P<0.01）， raised the serum levels of AMH， E₂， and IL-10， up-regulated the mRNA level of IL-10 （P<0.05， P<0.01）， and reduced the nuclear translocation of NF-κB p65 in the ovarian tissue. ConclusionYJT may inhibit the release and expression of inflammatory factors by regulating the TLR4/MyD88/NF-κB signaling pathway to attenuate the inflammatory responses in the ovarian tissue， thereby improving the ovarian function in DOR rats.

Objective: To explore the feasibility of synthetic magnetic resonance imaging (syMRI) combined with clinicopathological characteristics for the pre-treatment prediction of chemoradiotherapy (CRT) response in advanced nasopharyngeal carcinoma (ANPC). Materials and Methods: Patients with ANPC treated with CRT between September 2020 and June 2022 were retrospectively enrolled and categorized into response group (RG, n = 95) and non RGs (NRG, n = 32) based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The quantitative parameters from pre-treatment syMRI (longitudinal [T1] and transverse [T2] relaxation times and proton density [PD]), diffusion-weighted imaging (apparent diffusion coefficient [ADC]), and clinicopathological characteristics were compared between RG and NRG. Logistic regression analysis was applied to identify parameters independently associated with CRT response and to construct a multivariable model. The areas under the receiveroperating characteristic curve (AUC) for various diagnostic approaches were compared using the DeLong test. Results: The T1, T2, and PD values in the NRG were significantly lower than those in the RG (all P < 0.05), whereas no significant difference was observed in the ADC values between these two groups. Clinicopathological characteristics (Epstein–Barr virus [EBV]-DNA level, lymph node extranodal extension, clinical stage, and Ki-67 expression) exhibited significant differences between the two groups. Logistic regression analysis showed that T1, PD, EBV-DNA level, clinical stage, and Ki-67 expression had significant independent relationships with CRT response (all P < 0.05). The multivariable model incorporating these five variables yielded AUC, sensitivity, and specificity values of 0.974, 93.8% (30/32), and 91.6% (87/95), respectively. Conclusion SyMRI may be used for the pretreatment prediction of CRT response in ANPC. The multivariable model incorporating syMRI quantitative parameters and clinicopathological characteristics, which were independently associated with CRT response, may be a new tool for the pretreatment prediction of CRT response.

This study employed 16S r RNA gene high-throughput sequencing and metabolomics to explore the mechanism of Angelicae Dahuricae Radix polysaccharides(RP) in the treatment of ulcerative colitis(UC). A mouse model of UC was induced with 2. 5% dextran sulfate sodium. The therapeutic effects of RP on UC in mice were evaluated based on changes in body weight, disease activity index( DAI), and colon length, as well as pathological changes. RT-qPCR was performed to assess the m RNA levels of interleukin(IL)-6, IL-1β, tumor necrosis factor(TNF)-α, myeloperoxidase(MPO), mucin 2(Muc2), Occludin, Claudin2, and ZO-1 in the mouse colon tissue. ELISA was employed to measure the expression of IL-1β and TNF-α in the colon tissue. The intestinal permeability of mice was evaluated by the fluorescent dye permeability assay. Immunohistochemistry was employed to detect the expression of Muc2 and occludin in the colon tissue. Changes in gut microbiota and metabolites were analyzed by 16S r RNA sequencing and ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry( UPLC-Q-Exactive Plus Orbitrap MS), respectively. The results indicated that low-dose RP alleviated general symptoms, reduced colonic inflammation and intestinal permeability, and promoted Muc2 secretion and tight junction protein expression in UC mice. In addition, low-dose RP increased gut microbiota diversity in UC mice and decreased the relative abundance of harmful bacteria such as Ochrobactrum and Streptococcus. Twenty-seven differential metabolites were identified in feces, and low-dose RP restored the levels of disturbed metabolites. Notably, arginine and proline metabolism were the most significantly altered amino acid metabolic pathways following lowdose RP intervention. In conclusion, RP can ameliorate general symptoms, inhibit colonic inflammation, and maintain intestinal mucosal barrier integrity in UC mice by modulating gut microbiota composition and arginine and proline metabolism.
Animals ; Gastrointestinal Microbiome/drug effects* ; Colitis, Ulcerative/genetics* ; Mice ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Polysaccharides/administration & dosage* ; Angelica/chemistry* ; Humans ; Colon/metabolism* ; Disease Models, Animal ; Mucin-2/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*

PURPOSE: The study aimed to examine the pattern of motorization and the mortality rate related to road traffic crashes in Zunyi (a city in northern Guizhou province of China) from 2013 to 2022, and to identify the epidemiological characteristics of these crashes with to provide insights that could help improve road safety. METHODS: Data were obtained from the Zunyi traffic management data platform, and the mortality rates were calculated. We deployed various analytical methods, including descriptive analysis, Chi-square test or Fisher's exact test for categorical variables, circular distribution map analysis, and Rayleigh test to characterize the traits of road traffic crashes in the region. RESULTS: During the 10-year study period, 7488 people died due to road traffic accidents, with males accounting for 70.4% and females 29.6% (χ² = 101.97, p < 0.001). The mortality rate increased from 7.80 deaths per 100,000 people in 2013 to 10.70 deaths per 100,000 people in 2016, but then decreased to 9.54 deaths per 100,000 people in 2019. A notable finding was that the death rate per 10,000 vehicles declined from 16.09 deaths per 10,000 vehicles in 2013 to 5.48 deaths per 10,000 vehicles in 2022. The study also found that vulnerable road users represented nearly half (48.76%) of all accident fatalities, and unlicensed or inexperienced driving contributed significantly to the occurrence of road traffic accidents. CONCLUSION Although the number of road traffic accidents in Zunyi has decreased, there are still some critical issues that need to be addressed, particularly for vulnerable road users and unlicensed drivers. Our results highlight the need for targeted interventions to address the specific risk factors of road traffic crashes, particularly those affecting vulnerable road users and drivers without sufficient experience or license.
Humans ; Accidents, Traffic/statistics & numerical data* ; China/epidemiology* ; Male ; Female ; Adult ; Middle Aged ; Aged ; Adolescent ; Young Adult ; Child

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

OBJECTIVE: To explore the expression and clinical significance of XPO1 in newly diagnosed adult diffuse large B-cell lymphoma (DLBCL), and further investigate its functional mechanism. METHODS: Immunohistochemical testing was conducted for XPO1 expression in 93 cases of DLBCL and 30 cases of reactive lymphoid hyperplasia. A risk model was construed to find survival related genes in DLBCL patients. Cell proliferation, apoptosis, and cell cycle assays were performed to explore the effect of XPO1 inhibitor (KPT-8602) and XPO1 knockdown. Differential expression gene (DEG) was examined based on the transcriptomes. RESULTS The expression of XPO1 in DLBCL patients was higher than that of the controls. Compared with XPO1 low-expression group, XPO1 high-expression group had a worse prognosis. The constructed risk model indicated that XPO1 and 14 genes in nucleocytoplasmic transport pathway (NTP) might be potential prediction marker of adverse outcome in DLBCL. Moreover, KPT-8602 as well as the XPO1 knockdown could inhibit cell proliferation, promote apoptosis, and induce cell cycle arrest in two DLBCL cell lines, Farage and SU-DHL-4. Based on the gene expression profiling in the datasets of DLBCL, patients were classified into XPO1 high and XPO1 low expression groups, and the MYBL1 was identified as the down-stream effector of XPO1. Inhibiting the function of XPO1 or reducing its expression can significantly decrease the expression of MYBL1 Conclusion: XPO1 is highly expressed in DLBCL, which is associated with poor prognosis. The oncogenic roles of the new XPO1/MYBL1 signaling are identified in DLBCL and XPO1 inhibitor may be a potential option for newly-diagnosed DLBCL patients.
Humans ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Exportin 1 Protein ; Karyopherins/metabolism* ; Receptors, Cytoplasmic and Nuclear/metabolism* ; Cell Proliferation ; Apoptosis ; Prognosis ; Cell Line, Tumor ; Clinical Relevance

Objective: To explore the feasibility of synthetic magnetic resonance imaging (syMRI) combined with clinicopathological characteristics for the pre-treatment prediction of chemoradiotherapy (CRT) response in advanced nasopharyngeal carcinoma (ANPC). Materials and Methods: Patients with ANPC treated with CRT between September 2020 and June 2022 were retrospectively enrolled and categorized into response group (RG, n = 95) and non RGs (NRG, n = 32) based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The quantitative parameters from pre-treatment syMRI (longitudinal [T1] and transverse [T2] relaxation times and proton density [PD]), diffusion-weighted imaging (apparent diffusion coefficient [ADC]), and clinicopathological characteristics were compared between RG and NRG. Logistic regression analysis was applied to identify parameters independently associated with CRT response and to construct a multivariable model. The areas under the receiveroperating characteristic curve (AUC) for various diagnostic approaches were compared using the DeLong test. Results: The T1, T2, and PD values in the NRG were significantly lower than those in the RG (all P < 0.05), whereas no significant difference was observed in the ADC values between these two groups. Clinicopathological characteristics (Epstein–Barr virus [EBV]-DNA level, lymph node extranodal extension, clinical stage, and Ki-67 expression) exhibited significant differences between the two groups. Logistic regression analysis showed that T1, PD, EBV-DNA level, clinical stage, and Ki-67 expression had significant independent relationships with CRT response (all P < 0.05). The multivariable model incorporating these five variables yielded AUC, sensitivity, and specificity values of 0.974, 93.8% (30/32), and 91.6% (87/95), respectively. Conclusion SyMRI may be used for the pretreatment prediction of CRT response in ANPC. The multivariable model incorporating syMRI quantitative parameters and clinicopathological characteristics, which were independently associated with CRT response, may be a new tool for the pretreatment prediction of CRT response.

Objective: To explore the feasibility of synthetic magnetic resonance imaging (syMRI) combined with clinicopathological characteristics for the pre-treatment prediction of chemoradiotherapy (CRT) response in advanced nasopharyngeal carcinoma (ANPC). Materials and Methods: Patients with ANPC treated with CRT between September 2020 and June 2022 were retrospectively enrolled and categorized into response group (RG, n = 95) and non RGs (NRG, n = 32) based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The quantitative parameters from pre-treatment syMRI (longitudinal [T1] and transverse [T2] relaxation times and proton density [PD]), diffusion-weighted imaging (apparent diffusion coefficient [ADC]), and clinicopathological characteristics were compared between RG and NRG. Logistic regression analysis was applied to identify parameters independently associated with CRT response and to construct a multivariable model. The areas under the receiveroperating characteristic curve (AUC) for various diagnostic approaches were compared using the DeLong test. Results: The T1, T2, and PD values in the NRG were significantly lower than those in the RG (all P < 0.05), whereas no significant difference was observed in the ADC values between these two groups. Clinicopathological characteristics (Epstein–Barr virus [EBV]-DNA level, lymph node extranodal extension, clinical stage, and Ki-67 expression) exhibited significant differences between the two groups. Logistic regression analysis showed that T1, PD, EBV-DNA level, clinical stage, and Ki-67 expression had significant independent relationships with CRT response (all P < 0.05). The multivariable model incorporating these five variables yielded AUC, sensitivity, and specificity values of 0.974, 93.8% (30/32), and 91.6% (87/95), respectively. Conclusion SyMRI may be used for the pretreatment prediction of CRT response in ANPC. The multivariable model incorporating syMRI quantitative parameters and clinicopathological characteristics, which were independently associated with CRT response, may be a new tool for the pretreatment prediction of CRT response.

Objective: To explore the feasibility of synthetic magnetic resonance imaging (syMRI) combined with clinicopathological characteristics for the pre-treatment prediction of chemoradiotherapy (CRT) response in advanced nasopharyngeal carcinoma (ANPC). Materials and Methods: Patients with ANPC treated with CRT between September 2020 and June 2022 were retrospectively enrolled and categorized into response group (RG, n = 95) and non RGs (NRG, n = 32) based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The quantitative parameters from pre-treatment syMRI (longitudinal [T1] and transverse [T2] relaxation times and proton density [PD]), diffusion-weighted imaging (apparent diffusion coefficient [ADC]), and clinicopathological characteristics were compared between RG and NRG. Logistic regression analysis was applied to identify parameters independently associated with CRT response and to construct a multivariable model. The areas under the receiveroperating characteristic curve (AUC) for various diagnostic approaches were compared using the DeLong test. Results: The T1, T2, and PD values in the NRG were significantly lower than those in the RG (all P < 0.05), whereas no significant difference was observed in the ADC values between these two groups. Clinicopathological characteristics (Epstein–Barr virus [EBV]-DNA level, lymph node extranodal extension, clinical stage, and Ki-67 expression) exhibited significant differences between the two groups. Logistic regression analysis showed that T1, PD, EBV-DNA level, clinical stage, and Ki-67 expression had significant independent relationships with CRT response (all P < 0.05). The multivariable model incorporating these five variables yielded AUC, sensitivity, and specificity values of 0.974, 93.8% (30/32), and 91.6% (87/95), respectively. Conclusion SyMRI may be used for the pretreatment prediction of CRT response in ANPC. The multivariable model incorporating syMRI quantitative parameters and clinicopathological characteristics, which were independently associated with CRT response, may be a new tool for the pretreatment prediction of CRT response.