Ischemic stroke (IS) is a prevalent neurological disorder often resulting in significant disability or mortality. Resveratrol, extracted from Polygonum cuspidatum Sieb. et Zucc. (commonly known as Japanese knotweed), has been recognized for its potent neuroprotective properties. However, the neuroprotective efficacy of its derivative, (E)-4-(3,5-dimethoxystyryl) quinoline (RV02), against ischemic stroke remains inadequately explored. This study aimed to evaluate the protective effects of RV02 on neuronal ischemia-reperfusion injury both in vitro and in vivo. The research utilized an animal model of middle cerebral artery occlusion/reperfusion and SH-SY5Y cells subjected to oxygen-glucose deprivation and reperfusion to simulate ischemic conditions. The findings demonstrate that RV02 attenuates neuronal mitochondrial damage and scavenges reactive oxygen species (ROS) through mitophagy activation. Furthermore, Parkin knockdown was found to abolish RV02's ability to activate mitophagy and neuroprotection in vitro. These results suggest that RV02 shows promise as a neuroprotective agent, with the activation of Parkin-mediated mitophagy potentially serving as the primary mechanism underlying its neuroprotective effects.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Mitophagy/drug effects* ; Resveratrol/analogs & derivatives* ; Neuroprotective Agents/pharmacology* ; Humans ; Neurons/metabolism* ; Reactive Oxygen Species/metabolism* ; Ischemic Stroke/genetics* ; Male ; Quinolines/pharmacology* ; Mice ; Fallopia japonica/chemistry* ; Mitochondria/metabolism* ; Reperfusion Injury/metabolism* ; Rats ; Mice, Inbred C57BL ; Disease Models, Animal

Objective:To observe the clinical characteristics of elderly patients with demyelinating optic neuritis (DON), and preliminarily analyze the related factors affecting their visual prognosis.Methods:A observational clinical case-control study. A total of 107 patients with DON who were diagnosed and hospitalized in Beijing Tongren Hospital and its medical alliance Department of Ophthalmology, Beijing Puren Hospital from March 2019 to October 2023 were included in this study. Detailed medical histories were recorded, including time of onset, presence of ocular pain, treatment modalities, and follow-up status. All affected eyes underwent best-corrected visual acuity (BCVA) testing, orbital magnetic resonance imaging (MRI), and laboratory tests, including erythrocyte sedimentation rate (ESR), antinuclear antibodies (ANA), extractable nuclear antigens (ENA), aquaporin-4 (AQP4) antibodies, and myelin oligodendrocyte glycoprotein (MOG) antibodies in peripheral blood. Based on age, patients were categorized into the elderly DON group (≥50 years) and the young and middle-aged DON group (<50 years), comprising 50 and 57 cases, respectively. Furthermore, the elderly DON group was subdivided by serum-specific antibody status into the AQP4 antibody-positive ON group (AQP4-ON group), the MOG antibody-positive ON group (MOG-ON group), and the double-negative ON group (DN-ON group), with 18, 10, and 22 cases respectively. The median follow-up duration was 36 months. Follow-up assessments were conducted using the same equipment, methods, and relevant examinations as those applied at baseline. Binary logistic regression analysis was performed to identify factors associated with visual prognosis in elderly DON patients.Results:Compared with the DON group of young and middle-aged people, the incidence of binocular disease, accelerated ESR, MRI imaging score, the incidence of combined cardiovascular and cerebrovascular diseases, diabetes, tumors, and the proportion of adverse reactions of glucocorticoids in the elderly group were higher, and the proportion of ocular pain was lower. The differences were statistically significant ( P<0.05). Six months after the treatment, the number of cases with BCVA> 0.3 in the affected eyes in the elderly DON group and the young and middle-aged DON group was 28 (56.0%, 28/50) and 42 (73.7%, 42/57), respectively. The number of patients with BCVA> 0.3 in the elderly DON group was significantly lower than that in the young and middle-aged DON group, and the difference was statistically significant ( P=0.034). Moreover, with the increase of age, the degree of improvement in visual acuity showed a decreasing trend. The proportion of females in the AQP4-ON group, the proportion of optic chiasm and posterior optic pathway involvement in acute MRI, and the positive rate of ANA/ENA were significantly higher than those in the MOG-ON group and the DN-ON group, and the differences were statistically significant ( P<0.05). The rate of optic disc edema in the MOG-ON group was significantly higher than that in the AQP4-ON group, and the difference was statistically significant ( P=0.031). One and six months after treatment, the BCVA in the MOG-ON group was significantly better than that in the AQP4-ON group and the DN-ON group, and the difference was statistically significant ( P<0.05). The results of binary logistic regression analysis showed that at the onset of the disease, BCVA <0.01 [odds ratio ( OR) =2.60, 95% confidence interval ( CI) 1.23-5.52, P=0.013] and accelerated ESR ( OR=4.68, 95% CI 1.08-20.18, P=0.039) was an independent risk factor affecting the prognosis of BCVA in elderly patients with DON. Conclusions:There are different clinical characteristics between elderly DON patients and young and middle-aged patients. The risk of combined systemic diseases and side effects of glucocorticoids is higher, and the visual prognosis is worse. There are also differences in clinical characteristics and visual prognosis among subgroups of different serological antibodies in elderly DON. Advanced age, the lowest visual acuity at onset and immune inflammatory indicators are all factors affecting the visual prognosis of DON.

Objective To analyze the effects of tactile vibration feedback training combined with 1 Hz repetitive tran-scranial magnetic stimulation on limb balance and walking ability of stroke patients with hemiplegia.Methods From August 2021 to August 2023,98 patients with stroke and hemiplegia who were diagnosed and treated in Daxing District People's Hospital were selected and divided into training group and stimulation group according to different treatment schemes with 49 in each.The training group was given tactile vibration feedback training,and the stimula-tion group was given tactile vibration feedback training combined with 1 Hz repetitive trans-cranial magnetic stimula-tion.The clinical symptoms,ability of keeping balance and walk,life situation and curative effect of the two groups were analyzed.Results After 8 weeks of treatment,the scores of mouth and drooling points,language impairment points,and hemiparalysis points in the two groups were all lower than those before treatment(P<0.05),and the above indexes in the stimulation group were even lower than those in the training group(P<0.05).After 8 weeks of treatment,the scores of Lindmark Balance Reaction,Berg Balance scale(BBS),stride length,10-meters maximum walking speed(10 mMWS),Barthel index(BI)and Functional Independence Measure(FIM)in both groups were higher than those before treatment(P<0.05),and the above indexes in the stimulation group were higher than those in the training group(P<0.05).After 8 weeks of treatment,the total effective rate in the stimulation group(91.84％)was higher than that in the training group(69.39％)(P<0.05).Conclusions Tactile vibration feedback training plus 1 Hz repetitive trans-cranial magnetic stimulation can significantly alleviate the clinical symptoms of stroke patients with hemiplegia and can improve their ability of keeping balance,walking and management of daily life.

Diabetic retinopathy(DR)is a kind of microvascular disease caused by the long-term influence of diabetes mellitus(DM),and it is one of the main cause of global visual impairment and blindness.Its typical characteristics include microaneurysms,hard exudates,macular edema(DME)and neovascularization.Its pathogenesis is diverse,and the root cause is oxidative stress and advanced glycosylation end products.The nuclear red blood cell related factor 2(Nrf2)signa-ling pathway plays an important role in preventing various diseases.As one of the characteristics of DM,hyperglycemia will activate the generation of reactive oxygen species(ROS)in mitochondria.These oxidative stress factors activate the nucle-ar transcription factor κB pathway,becoming the main inducement of various complications of DM.This pathway will in-duce increased transcription of proinflammatory cytokines,including tumor necrosis factor-alpha,transforming growth fac-tor-beta and interleukin-1.The active ingredients of traditional Chinese medicine have significant antioxidant,anti-inflam-matory,anti-apoptotic and angiogenesis-promoting effects,and can block the progression of DR through various mecha-nisms.In this article,the research status of traditional Chinese medicine targeting the Nrf2 signaling pathway in the preven-tion and treatment of DR is reviewed to guide clinical and scientific research.

This study investigated the effects and underlying mechanisms of the luteolin-naringenin combination(LN)on liver injury induced by acetaminophen(APAP).Forty-eight Kunming mice were randomly allocated into six groups:a normal control group,an APAP-induced liver injury model group,a positive drug treatment group,and three LN treatment groups with low,medium,and high doses.After the final drug administration,the mice were fasted for 12 hours prior to eu-thanasia for sample collection.Serum transaminase activity,oxidative stress indices,and hematoxy-lin-eosin(HE)staining were assessed to evaluate the effects of LN on APAP-induced hepatic inju-ry.Additionally,Western blot analysis was conducted to examine the expression levels of sphingo-sine kinase 1(SPHK1)and endoplasmic reticulum stress(ERS)-related proteins,thereby elucida-ting the potential mechanisms by which LN mitigates APAP-induced liver injury.The results dem-onstrated that varying concentrations of LN effectively ameliorated serum aminotransferase activi-ty and oxidative stress levels induced by APAP in a dose-dependent manner.Histopathological ex-amination via HE staining revealed significant improvement in APAP-induced liver tissue injury following treatment with different concentrations of LN.Furthermore,Western blot analysis indi-cated that the protein expressions of SPHK1,CHOP,p-IRE1α,ATF6,p-PERK,p-eIF2α,and ATF4 were markedly reduced after administration of various concentrations of LN.The results demonstrate that LN exhibits a significant protective effect against APAP-induced liver injury by inhibiting the SPHK1-mediated aberrant expression of ERS-related molecules.This study high-lights the importance of targeting SPHK1 in the treatment of APAP liver injury and provides a no-vel therapeutic approach through the multi-target and multi-pathway combination of monomers.

Objective To compare the efficacy of artificial intelligence(AI)diagnostic group and artificial reading group in the diagnosis for osteoporotic vertebral compression fractures.Methods From January 2023 to December 2023,80 patients with osteoporotic vertebral compression fractures and 20 patients without fractures but with nonspecific low back pain were included in the study.According to the patient's computed tomography(CT)image,the AI software diagnosis and physicians of different seniority(one senior physician,one intermediate physician and one junior physician)diagnosis were performed.The diagnostic efficacy of different detection methods was compared.Results The sensitivity,specificity,positive predictive value,negative predictive value and area under the receiver operating characteristic(ROC)curve(AUC)and Kappa value of each group were as follows:AI image interpretation:0.975,0.900,0.975,0.900,0.938,0.875;senior physician:0.950,0.900,0.974,0.818,0.925,0.819;intermediate physician:0.825,0.850,0.957,0.548,0.837,0.560;and junior physician:0.750,0.750,0.923,0.429,0.751,0.390.Conclusion The diagnostic performance of AI was comparable to that of senior physician,and significantly higher than that of intermediate and primary physicians.

Objective To establish an online gel permeation chromatography-gas chromatography/mass spectrometry(GPC-GCMS)method for the determination of etomidate in blood.Methods Blood samples were extracted with acetonitrile,dehydrated with anhydrous sodium sulfate,purified with an online GPC system,and then analyzed by GCMS using large volume injection.The external standard curve method was used for quantification.Results The detection limit of etomidate was 0.002 μg/mL,with good linearity in the concentration range of 0.01～5 μg/mL and a correlation coefficient of 0.9992.The extraction recovery rates ranged between 90%and 120%.In an actual case,the content of etomidate detected in the blood sample was 0.024 μg/mL.Conclusion This method is fast,simple,accurate,and stable,providing a reliable basis for the determination of etomidate content in blood.

Objective:To establish and validate a lipid parameter-based prognostic model for predicting recurrence free survival (RFS) in pancreatic cancer patients receiving postoperative adjuvant chemotherapy.Methods:A retrospective analysis was conducted on the clinical and pathological data of 155 patients who underwent pancreatic cancer resection followed by adjuvant chemotherapy at Affiliated Hospital of Qingdao University between January 2019 and December 2022. The patients were randomly divided into a training set ( n=108) and a validation set ( n=47) in a 7∶3 ratio. X-tile software was used to determine cutoff values for lipid parameters. Univariate and multivariate Cox regression analyses were performed to construct a model predicting RFS, which was then visualized using a nomogram. The model's predictive performance, accuracy and stability, and clinical application value were evaluated using the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA), respectively. Individual risk scores for recurrence were calculated based on the nomogram model, and X-tile software was employed to identify optimal cutoff values for risk stratification, which was used to divide patients into low-risk and high-risk groups. Survival differences between two groups were analyzed using survival curves. Results:Among lipid parameters, patients with higher apolipoprotein A1 level had obviously longer RFS than those with low apolipoprotein A1 level (10.17 months vs 8.92 months, HR=0.397, 95% CI 0.237~0.664); patients with high total cholesterol level had obviously shorter RFS than those with low total cholesterol level (8.33 months vs 16.27months, HR=3.382, 95% CI 1.901~5.824) ; patients with high low-density lipoprotein level had obviously shorter RFS than those with low low-density lipoprotein level (8.53 months vs 11.43 months, HR=1.617, 95% CI 1.013~2.582) ; patients with high lipoprotein(a) had shorter RFS than those with low lipoprotein(a) (8.53 months vs 14.43 months, HR=2.640, 95% CI 1.514-4.604) ; and all the differences were statistical significant (all P value <0.05). Univariate Cox regression analysis identified advanced T stage, advanced N stage, high total cholesterol level, high low-density lipoprotein level, low apolipoprotein A1 level, high apolipoprotein B level, and high lipoprotein(a) level as risk factors for RFS. Multivariate Cox regression analysis revealed that tumors located in the pancreatic body or tail ( HR=0.63, 95% CI 0.36-0.86, P=0.042), advanced T stage ( HR=4.85, 95% CI 1.47-16.04, P=0.010), advanced N stage ( HR=0.48, 95% CI 0.26-0.87, P=0.015), elevated total cholesterol levels ( HR=3.61, 95% CI 1.46-8.91, P=0.005), high density lipoprotein levels ( HR=0.48, 95% CI 0.26-0.87, P=0.015), and elevated lipoprotein(a) levels ( HR=3.17, 95% CI 1.61-6.24, P<0.001) were independent risk factors for RFS. The nomogram model incorporating these six factors above demonstrated an AUC of 0.78 (95% CI 0.70-0.87) in the training set and 0.75 (95% CI 0.59-0.91) in the validation set. Calibration curves indicated a high degree of agreement between predicted and observed outcomes. DCA suggested that the model provides substantial clinical benefit. Kaplan-Meier survival curve analysis showed that patients in the high-recurrence risk group from training set and validation set both had significantly shorter RFS compared to those in the low-recurrence risk group (6.93 months vs 12.13 months, HR=4.024, 95% CI 2.594-6.243; 6.85 months vs 11.93 months, HR=2.314, 95% CI 1.227-4.362); and all the differences were statistical significant (all P value <0.05). Conclusions:The nomogram model based on lipid parameters can effectively predict recurrence free survival in patients undergoing adjuvant chemotherapy after pancreatic cancer surgery.

Objective To compare the efficacy of artificial intelligence(AI)diagnostic group and artificial reading group in the diagnosis for osteoporotic vertebral compression fractures.Methods From January 2023 to December 2023,80 patients with osteoporotic vertebral compression fractures and 20 patients without fractures but with nonspecific low back pain were included in the study.According to the patient's computed tomography(CT)image,the AI software diagnosis and physicians of different seniority(one senior physician,one intermediate physician and one junior physician)diagnosis were performed.The diagnostic efficacy of different detection methods was compared.Results The sensitivity,specificity,positive predictive value,negative predictive value and area under the receiver operating characteristic(ROC)curve(AUC)and Kappa value of each group were as follows:AI image interpretation:0.975,0.900,0.975,0.900,0.938,0.875;senior physician:0.950,0.900,0.974,0.818,0.925,0.819;intermediate physician:0.825,0.850,0.957,0.548,0.837,0.560;and junior physician:0.750,0.750,0.923,0.429,0.751,0.390.Conclusion The diagnostic performance of AI was comparable to that of senior physician,and significantly higher than that of intermediate and primary physicians.

Diabetic retinopathy(DR)is a kind of microvascular disease caused by the long-term influence of diabetes mellitus(DM),and it is one of the main cause of global visual impairment and blindness.Its typical characteristics include microaneurysms,hard exudates,macular edema(DME)and neovascularization.Its pathogenesis is diverse,and the root cause is oxidative stress and advanced glycosylation end products.The nuclear red blood cell related factor 2(Nrf2)signa-ling pathway plays an important role in preventing various diseases.As one of the characteristics of DM,hyperglycemia will activate the generation of reactive oxygen species(ROS)in mitochondria.These oxidative stress factors activate the nucle-ar transcription factor κB pathway,becoming the main inducement of various complications of DM.This pathway will in-duce increased transcription of proinflammatory cytokines,including tumor necrosis factor-alpha,transforming growth fac-tor-beta and interleukin-1.The active ingredients of traditional Chinese medicine have significant antioxidant,anti-inflam-matory,anti-apoptotic and angiogenesis-promoting effects,and can block the progression of DR through various mecha-nisms.In this article,the research status of traditional Chinese medicine targeting the Nrf2 signaling pathway in the preven-tion and treatment of DR is reviewed to guide clinical and scientific research.