ObjectiveTo explore the material basis of the "interaction of blood stasis and toxin" mechanism in cerebral ischemia-reperfusion injury， as well as the protective role of Huoxue Huayu Jiedu prescription （HXHYJDF） against ferroptosis. MethodsSixty SPF-grade male SD rats were randomly divided into six groups： sham group， model group， deferoxamine （DFO） group （100 mg·kg^-1）， low-dose HXHYJDF group （4.52 g·kg^-1）， medium-dose HXHYJDF group （9.04 g·kg^-1）， and high-dose HXHYJDF group （18.07 g·kg^-1）， with ten rats in each group. Except for the sham group， the other groups were used to replicate the model of focal cerebral ischemia-reperfusion in the middle cerebral artery of rats by the reforming Longa method. Neurological function was assessed at 1^st， 3^rd， 5^th， and 7^th days post-reperfusion using the modified neurological severity scores （m-NSS）. Brain tissue pathology and the morphology of mitochondria were observed using hematoxylin-eosin （HE） staining and transmission electron microscopy. The contents of malondialdehyde （MDA）， glutathione （GSH）， divalent iron ions （Fe²⁺）， and reactive oxygen species （ROS） in the ischemic cerebral tissue were detected using enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry and Western blot （WB） were used to detect the expression of iron death marker proteins glutathione peroxidase 4 （GPX4）， ferroportin-1 （FPN1）， transferrin receptor protein 1 （TfR1）， and ferritin mitochondrial （FtMt） in brain tissue. ResultsCompared with the sham group， the mNSS score of the model group was significantly increased （P<0.01）. HE staining showed that the number of neurons in the cortex of brain tissue was seriously reduced， and the intercellular space was widened. The nucleus was fragmented， and the cytoplasm was vacuolated. The results of transmission electron microscopy showed that the mitochondria in the cytoplasm contracted and rounded， and the mitochondrial cristae decreased. The matrix was lost and vacuolated， and the density of the mitochondrial bilayer membrane increased. The results of ELISA showed that the content of GSH decreased significantly （P<0.01）， and the contents of MDA， Fe²⁺， and ROS increased significantly （P<0.01）. The results of immunohistochemistry and WB showed that the expression of GPX4 and FPN1 proteins was significantly decreased （P<0.01）， and the expression of FtMt and TfR1 proteins was significantly increased （P<0.01）. Compared with those of the model group， the m-NSS scores of the high-dose and medium-dose HXHYJDF groups began to decrease on the 3^rd and 5^th days， respectively （P<0.05， P<0.01）. The results of HE and transmission electron microscopy showed that the intervention of HXHYJDF improved the pathological changes of neurons and mitochondria. The results of ELISA showed that the content of GSH in the medium-dose and high-dose HXHYJDF groups increased significantly （P<0.01）， and the contents of MDA， Fe²⁺， and ROS decreased significantly （P<0.05， P<0.01）. The content of GSH in the low-dose HXHYJDF group increased significantly （P<0.01）， and the contents of MDA and ROS decreased significantly （P<0.01）. The results of immunohistochemistry showed that the expression of GPX4 and FPN1 in the high-dose HXHYJDF group increased significantly （P<0.01）， and the expression of FtMt and TfR1 decreased significantly （P<0.01）. The expression of GPX4 and FPN1 in the medium-dose HXHYJDF group increased significantly （P<0.05）， and the expression of TfR1 decreased significantly （P<0.01）. WB results showed that the expression levels of FPN1 and GPX4 proteins in the high-dose， medium-dose， and low-dose HXHYJDF groups were significantly up-regulated （P<0.01）， and the expression levels of FtMt and TfR1 proteins were significantly down-regulated （P<0.01）. ConclusionHXHYJDF can significantly improve neurological dysfunction symptoms in rats with cerebral ischemia-reperfusion injury， improve the pathological morphology of the infarcted brain tissue， and protect the brain tissue of rats with cerebral ischemia-reperfusion injury to a certain extent. Neuronal ferroptosis is involved in cerebral ischemia-reperfusion injury， with increased levels of MDA， Fe²⁺， ROS， and TfR1 and decreased levels of FtMt， FPN1， GPX4， and GSH potentially constituting the material basis of the interaction of blood stasis and toxin mechanism in cerebral ischemia-reperfusion injury. HXHYJDF may exert brain-protective effects by regulating iron metabolism-related proteins， promoting the discharge of free iron， reducing brain iron deposition， alleviating oxidative stress， and inhibiting ferroptosis.

Objective: To explore the relationship between beverage dependence and sleep quality among college students, providing empirical evidence for improving their sleep quality. Methods: From December 2024 to January 2025, a convenience sampling method was used to conduct a questionnaire survey among 3 974 college students from four universities in Anhui Province. The Beverage Addiction Scale for College Students (BASCS) was used to assess beverage dependence, and the Self rating Scale of Sleep(SRSS) was used to evaluate sleep quality. A multivariate Logistic regression model was employed to analyze the relationship between beverage dependence and sleep quality, and a restricted cubic spline model was used to examine the dose response relationship between the two. Results: The positive rate of beverage dependence symptoms among college students was 7.6%, with positive rates of 9.6%, 13.8%, and 7.4% for the withdrawal symptoms, health effects, and dependence symptoms dimensions, respectively. The detection rate of sleep disorders was 23.6%. Multivariate Logistic regression analysis showed that after adjusting for covariates such as grade, gender, and body mass index, compared with the no beverage dependence group, students with positive beverage dependence symptoms had a higher risk of sleep disorders( OR =3.71, 95% CI =2.87-4.80, P <0.01). The OR (95% CI ) for sleep disorders among students with positive symptoms in the withdrawal symptoms, health effects, and dependence symptoms dimensions were 2.80(2.22-3.53), 2.38(1.95-2.91), and 2.45(1.89-3.18)(all P <0.01). Further analysis using a restricted cubic spline model revealed that the overall beverage dependence score and its three dimensional scores were approximately linearly related to the risk of sleep disorders among college students (all nonlinear P >0.05). Conclusions Beverage dependence is associated with sleep quality among college students. Schools should take multiple approaches, such as health education on beverage awareness, to improve students sleep quality.

Cardiac arrest (CA) is a critical condition in the field of cardiovascular medicine. Despite successful resuscitation, patients continue to have a high mortality rate, largely due to post CA syndrome (PCAS). However, the injury and pathophysiological mechanisms underlying PCAS remain unclear. Experimental animal models are valuable tools for exploring the etiology, pathogenesis, and potential interventions for CA and PCAS. Current CA animal models include electrical induction of ventricular fibrillation (VF), myocardial infarction, high potassium, asphyxia, and hemorrhagic shock. Although these models do not fully replicate the complexity of clinical CA, the mechanistic insights they provide remain highly relevant, including post-CA brain injury (PCABI), post-CA myocardial dysfunction (PAMD), systemic ischaemia/reperfusion injury (IRI), and the persistent precipitating pathology. Summarizing the methods of establishing CA models, the challenges encountered in the modeling process, and the mechanisms of PCAS can provide a foundation for developing standardized CA modeling protocols.
Animals ; Disease Models, Animal ; Post-Cardiac Arrest Syndrome/physiopathology* ; Heart Arrest/physiopathology* ; Humans ; Ventricular Fibrillation/complications*

Autoimmune hepatitis （AIH） is an inflammatory disease caused by immune dysfunction， and its pathogenic mechanism remains unclear. In recent years， a large number of studies have shown that iron homeostasis imbalance and ferroptosis are closely associated with the pathogenesis and progression of AIH. This article reviews the pathological mechanism and impact of iron overload and ferroptosis in AIH， in order to provide new insights and theoretical bases for research on the mechanism and clinical treatment of AIH.

ObjectiveTo observe the effect of natural moxibustion at "Feishu （BL 13）" on immune balance of T helper cell 17 （Th17） / regulatory T cell （Treg） in healthy rats. MethodsForty-eight rats were randomly divided into 10 rats in the sham moxibustion group and 38 rats in natural moxibustion group. The rats in the sham moxibustion group applied blank acupoint stickers to bilateral "Feishu （BL 13）"， and the rats in natural moxibustion group applied acupoint stickers filled with Compound Banmao Ointment （复方斑蝥膏） to bilateral "Feishu （BL 13）" for a period of 8 h. Thirty rats in natural moxibustion group were successfully blistered after 8 h， and then were randomly divided into 1-day， 3-day and 7-day groups with 10 rats in each group. The general condition of rats was recorded during the experiment； different time groups of natural moxibustion were sampled at the corresponding time， and HE staining was used to observe the pathological changes of the skin in the area of application； flow cytometry was used to detect the subpopulations of Th17 and Treg in peripheral blood， and the value of Th17/Treg was calculated； and ELISA was used to detect the serum interleukin 17A （IL-17A） and interleukin 6 （IL-6）， interleukin 10 （IL-10） levels. ResultsCompared with sham moxibustion group， blisters can be seen in the application area of rats in 1-day natural moxibustion group， and the rats often scratched the skin of the moxibustion area， which showed loose stratum corneum， thickening of the stratum spinosum and stratum granulosum， absence of cells in the basal layer， inflammatory cell infiltration， and elevation of Treg in peripheral blood， and serum IL-17A， IL-6； in 3-day natural moxibustion group， the moxibustion area of the rats was scabbed and partially detached， with the most obvious dermatopathological changes， and elevated peripheral blood Th17 and Treg， and serum IL-17A， IL-6， IL-10； in 7-day natural moxibustion group， skin damage and pathological changes in the area of moxibustion were basically restored； Th17/Treg values were reduced in 1-， 3- and 7-day moxibustion groups after blistering （P＜0.05 or P＜0.01）. Compared with the 1-day moxibustion group， peripheral blood Th17， Treg， and serum IL-17A elevated in the 3-day moxibustion group； peripheral blood Treg， serum IL-17A， and IL-6 decreased， and Th17/Treg values elevated in the 7-day moxibustion group （P＜0.05 or P＜0.01）. Compared with the 3-day moxibustion group， the 7-day moxibustion group had lower peripheral blood Th17 and Treg， serum IL-17A， IL-6， and IL-10， and higher Th17/Treg values （P＜0.05 or P＜0.01）. ConclusionNatural moxibustion at "Feishu （BL 13）" can shift the Th17/Treg balance towards Treg of healthy rats， which will gradually lead to immune homeostasis， and regulate the relevant inflammatory factors in the serum to prevent inflammation from occurring and developing.

Objectives:To investigate the relationship between total ischemic time(TIT)and the risk of major adverse cardiovascular events(MACE,including all-cause death,non-fatal myocardial infarction,non-fatal ischemic stroke)within 1 year after primary percutaneous coronary intervention(PPCI)in patients with ST segment elevation myocardial infarction(STEMI)with TIT≤720 minutes. Methods:A total of 1 812 STEMI patients who underwent PPCI and had a TIT≤720 minutes in the Chest Pain Center of the General Hospital of the Southern Theatre Command of PLA from January 1,2011 to December 31,2021 were selected as the research subjects.Logistic regression and Cox regression models were used to analyze the association between TIT and the risk of MACE in the hospital and within 1 year after discharge.The restricted cubic spline(RCS)analysis was used to analyze the dose-response relationship between TIT and the risk of MACE. Results:Among 1 812 patients,the incidence of MACE during hospitalization was 3.26%,and the incidence of MACE within 1 year after discharge was 6.84%in 1 651 patients who survived.RCS analysis showed that TIT had an approximate logarithmic linear relationship with the risk of MACE during hospitalization and within 1 year after discharge,and the risk of MACE increased with longer TIT.Multivariate logistic regression analysis showed that compared with the group with a TIT of≤480 minutes,the risk of MACE during hospitalization increased by 77.7%(OR=1.777,95%CI:1.020-2.929,P=0.038)in the group with a TIT of more than 480 minutes.Multivariate Cox proportional hazards regression analysis showed that compared with the group with a TIT of≤280 minutes,the risk of MACE within 1 year after discharge increased by 106.7%(HR=2.067,95%CI:1.384-3.089,P<0.001)in the group with a TIT of more than 280 minutes. Conclusions:In STEMI patients after PPCI,the risk of MACE during hospitalization significantly increases when TIT exceeds 480 minutes,and the risk of MACE within 1 year after discharge significantly increases when TIT exceeds 280 minutes.

Objective To observe the value of Zero-Shot Noise2Noise(ZS-N2N)based on Z-axis correlation for reducing noise of low dose CT(LDCT)images.Methods CT data of the cancer imaging archive were enrolled,including normal dose CT(NDCT)images and LDCT images,with 3 sets of chest and 3 sets of abdominal images.Noise on LDCT images were reduced with ZS-N2N method based on Z-axis correlation,and the peak signal-to-noise ratio(PSNR),structural similarity(SSIM)and time-consuming of reducing noise were compared with those of Self2Self,simple ZS-N2N and traditional Block-matching and 3D filtering(BM3D).Results After reducing noise,noise on Self2Self denoised images remained significant,the structure edges on BM3D denoised images were blurry with some details lost,while simple ZS-N2N and ZS-N2N based on Z-axis correlation denoised images preserved more details and had better quality.PSNR and SSIM of Self2Self denoised images were poor and the time-consuming were longer.PSNR,SSIM and time-consuming of the other 3 methods were similar,among which PSNR of ZS-N2N based on Z-axis correlation were slightly higher than BM3D and simple ZS-N2N,but the time-consuming were also slightly longer.Conclusion ZS-N2N based on Z-axis correlation had high value for reducing noise of LDCT images.

Objective:To investigate the expression level of NME3 in gastric cancer and its correlation with clinicopathological characteristics and prognosis.Methods:A retrospective case series study was conducted. The clinicopathological data of 156 patients with gastric cancer who received radical gastrectomy in Zhejiang Cancer Hospital between January 2013 and December 2017 were collected. The samples of cancer tissues and paracancerous tissues were taken and partial paracancerous tissues were not meet the standard. Finally, immunohistochemical staining was conducted on both cancer tissues (156 cases) and paracancerous tissues (139 cases) to detect the expression of NME3 protein; H scoring system was used to score the expression of NME3 protein and the patients were divided into NME3 high expression group (H score ≥ 6 points) and NME3 low expression group (H score < 6 points). The clinicopathological characteristics of the 2 groups were analyzed. Kaplan-Meier method was used for overall survival (OS) analysis of the 2 groups, and log-rank test was used for comparison. Univariate and multivariate Cox proportional risk models were used to determine the poor independent factors affecting the poor OS in patients with gastric cancer.Results:The median age of the 156 patients was 61 years (53 years, 68 years), including 110 males (70.5%) and 46 females (29.5%). The proportion of patients with NME3 high expression in cancer tissues was lower than that in paracancerous tissues [51.9% (81/156) vs. 75.5% (105/139)], and the difference was statistically significant ( χ2 = 17.60, P < 0.001). The proportion of patients with NME3 high expression in moderate-low differentiation and moderate differentiation group was lower than that of those in low-differentiation group [63.3% (50/79) vs. 39.4% (28/71)], the proportion of patients with NME3 high expression in pTNM staging group Ⅲ-Ⅳ was higher than that of those in pTNM staging group Ⅰ-Ⅱ [55.5% (76/137) vs. 26.3% (5/19)], and the difference was statistically significant (both P < 0.05). The proportion of patients with NME3 high expression was 62.2% (46/74), 52.0% (13/25), 39.3% (22/56), respectively in patients with Lauran intestinal type, mixed type and diffused type, and the differences were statistically significant ( χ2 = 6.69, P = 0.035). In addition, OS of patients with the NME3 high expression group was better than that of those with the NME3 low expression group, and the difference was statistically significant ( P < 0.001). The further analysis of gender subgroup showed that OS of male patients with the NME3 high expression group was better than that of those with the NME3 low expression group, and OS of female patients with the NME3 high expression group was better than that of those with the NME3 low expression group, and the differences was statistically significant (all P < 0.05). Univariate and multivariate Cox regression analysis showed that the expression of NME3 in cancer tissues (high expression vs. low expression: HR = 0.342, 95% CI: 0.207-0.564, P < 0.001), family history (yes vs. no: HR = 2.240, 95% CI: 1.285-3.907, P = 0.004), pN staging (N 2-3vs. N 0-1: HR = 2.133, 95% CI: 1.114-4.083, P = 0.022), pM staging (M 1vs. M 0: HR = 2.761, 95% CI: 1.386-5.500, P = 0.004), carcinoma embryonic antigen (CEA) level (CEA > 5 ng/ml vs. CEA ≤ 5 ng/ml: HR = 1.688, 95% CI: 1.018-2.798, P = 0.042), carbohydrate antigen 125 (CA125) level (CA125 > 35 U/ml vs. CA125 ≤ 35 U/ml: HR = 2.913, 95% CI: 1.403-6.047, P = 0.004) were independent factors influencing OS in patients with gastric cancer. Conclusions:NME3 is lowly expressed in gastric cancer tissues, and it is highly expressed in higher-differentially, late staged and intestinal type gastric cancer. NME3 low expression is an independent risk factor for the poor prognosis of gastric cancer. It is speculated that NME3 may play a inhibitory role in gastric cancer.

OBJECTIVE: To investigate the current status of methotrexate (MTX) application in rheumatoid arthritis (RA) patients. METHODS: The clinical and laboratory data of RA patients who attended in the Department of Rheumatology and Immunology of Peking University Third Hospital from January 1, 2022 to November 31, 2023 were collected retrospectively. In order to figure out the relationship between MTX use and RA disease control, we recorded information including the starting dose, maximum dose, current dose, reasons of discontinuation of MTX, etc. The t test, Mann-Whitney U test, Chi-square test, Fisher' s exact probability and multivariable Logistic regression were used for analysis. RESULTS: A total of 239 RA patients were enrolled, including 201 females and 38 males with a mean age of (54.5±14.3) years. Among them, 101 patients reached the therapeutic target [clinical remission or low disease activity assessed by 28-joint disease activity score (DAS28)-erythrocyte sedimentation rate (ESR)], accounting for 42.2% of the RA patients. Twenty-six patients met the European League Against Rheumatism (EULAR) definition of difficult-to-treat (D2T) RA, accounting for 10.9% of RA patients. The proportion of the RA patients who had ever used MTX was 84. 1%, and those who were currently on it accounted for only 39.7%. The MTX dose was generally low, with a starting dose of (9.5±3.0) mg/week, the maximum dose of 15.0 (10.0, 15.0) mg/week, and the current dose being (12.4±2.7) mg/week. The most common reasons for MTX dose reduction or discontinuation were adverse reactions, mainly including abnormalities of hepatic function, gastrointestinal discomfort, leucopenia, etc. Those who were currently on MTX had a higher rate of treatment to target (52.6% vs. 35.4%, P>0.05), lower disease activity score (DAS28-ESR, 3.6±1.8 vs. 4.2±1.8, P < 0.05), and fewer tender joint counts (4.8±8.3 vs. 8.6±10.4, P < 0.05) as compared with those who were not taking the drug, while swollen joint count, pain visual analog score and patient' s global score, C-reactive protein (CRP) level and ESR level were not significantly different between the two groups. Compared with those who did not reach the target of treatment, those who did had a higher rate of current MTX application (48.5% vs. 33.3%, P < 0.05), but the history of MTX did not differ between the two groups (84.2% vs. 84.1%, P>0.05). The maximum dose of MTX (median 15.0 mg/week vs. 13.7 mg/week, P>0.05) and the current dose [(12.9±2.5) mg/week vs. (11.8±2.8) mg/week, P>0.05] was higher in those who achieved the target, while the starting dose [(9.6±2.8) mg/week vs. (9.5±3.1) mg/week, P>0.05] and the rate of prior MTX (84.2% vs. 83.3%, P>0.05) was comparable between the two groups. The D2T RA patients had a higher rate of previous MTX use (96.2% vs. 82.6%, P < 0.05) and a higher starting dose [(11.6±4.3) mg/week vs. (9.8±2.7) mg/week, P>0.05], while the maximum dose (median 12.5 mg/week vs. 15.0 mg/week, P>0.05) and the current dose were both lower [(11.6±3.2) mg/week vs. (12.5±2.6) mg/week, P>0.05] than the non-D2T RA patients. CONCLUSION The proportion of regular use of MTX among RA patients was low and the dose was generally small. The RA patients with regular use of MTX had a higher rate of achieving treatment target and lower disease activity. Those who achieved the target had a higher rate of current MTX use, higher maximum and current doses than those who did not. The D2T RA patients had lower maximum and current doses of MTX than the non-D2T RA patients. Therefore, increasing the usage and dosage of MTX in RA patients may help to improve the rate of achieving treatment targets.
Humans ; Arthritis, Rheumatoid/drug therapy* ; Methotrexate/therapeutic use* ; Male ; Female ; Middle Aged ; Retrospective Studies ; Antirheumatic Agents/therapeutic use* ; Aged ; Adult ; Blood Sedimentation ; Severity of Illness Index ; Remission Induction

【Objective】 To establish and verify a nomogram model of overall survival (OS) of prostate cancer patients based on the SEER data. 【Methods】 A total of 12 642 patients diagnosed with prostate cancer during 2010 and 2015 were extracted from the SEER database. Patients were randomly divided into the model group (n=8 850) and validation group (n=3 792). The independent risk factors for OS were analyzed with univariate Cox proportional risk regression, lasso regression and multivariate Cox proportional risk regression. A nomogram was constructed to predict the 1-year, 3-year and 5-year OS. The prediction potential of the model was evaluated with the consistency index (C-index), calibration curve and receiver operating characteristic (ROC) curve. 【Results】 Multivariate Cox regression analysis showed that age, T stage, N stage, M stage, bone metastasis, liver metastasis and regional lymphadenectomy were independent risk factors for OS (P<0.05). The seven factors were used to construct an OS nomogram model. The C-index of the modeling set was 0.750, and the area under the ROC curve (AUC) at 1, 3 and 5 years were 0.77, 0.77 and 0.76, respectively;the C-index of the validation set was 0.765, and the AUC at 1, 3 and 5 years were 0.83, 0.79 and 0.76, respectively. The calibration curves of the modelling set and validation set showed a good agreement with the actual survival prediction rate. Risk stratification of patients based on the nomogram model showed that the OS of patients in the high-risk group was significantly lower than that in the low-risk group (P<0.001). 【Conclusion】 The nomogram can be used to predict the prognosis of prostate cancer patients, and is important for individualized treatment plans.