Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, functional impairment, and neuropsychiatric symptoms. It represents the most prevalent form of dementia among the elderly population. Accumulating evidence indicates that oxidative stress plays a pivotal role in the pathogenesis of AD. Notably, elevated levels of oxidative stress have been observed in the brains of AD patients, where excessive reactive oxygen species (ROS) can cause extensive damage to lipids, proteins, and DNA, ultimately compromising neuronal structure and function. Amyloid β‑protein (Aβ) has been shown to induce mitochondrial dysfunction and calcium overload, thereby promoting the generation of ROS. This, in turn, exacerbates Aβ aggregation and enhances tau phosphorylation, leading to the formation of two pathological features of AD: extracellular Aβ plaque deposition and intracellular neurofibrillary tangles (NFTs). These events ultimately culminate in neuronal death, forming a vicious cycle. The interplay between oxidative stress and these pathological processes constitutes a core link in the pathogenesis of AD. The signaling pathways mediating oxidative stress in AD include Nrf2, RCAN1, PP2A, CREB, Notch1, NF‑κB, ApoE, and ferroptosis. Nrf2 signaling pathway serves as a key regulator of cellular redox homeostasis, exerts important antioxidant capacity and protective effects in AD. RCAN1 signaling pathway, as a calcineurin inhibitor, and modulates AD progression through multiple mechanisms. PP2A signaling pathway is involved in regulating tau phosphorylation and neuroinflammation processes. CREB signaling pathway contributes to neuroplasticity and memory formation; activation of CREB improves cognitive function and reduce oxidative stress. Notch1 signaling pathway regulates neuronal development and memory, participates in modulation of Aβ production, and interacts with Nrf2 toco-regulate antioxidant activity. NF‑κB signaling pathway governs immune and inflammatory responses; sustained activation of this pathway forms “inflammatory memory”, thereby exacerbating AD pathology. ApoE signaling pathway is associated with lipid metabolism; among its isoforms, ApoE-ε4 significantly increases the risk of AD, leading to elevated oxidative stress, abnormal lipid metabolism, and neuroinflammation. The ferroptosis signaling pathway is driven by iron-dependent lipid peroxidation, and the subsequent release of lipid peroxidation products and ROS exacerbate oxidative stress and neuronal damage. These interconnected pathways form a complex regulatory network that regulates the progression of AD through oxidative stress and related pathological cascades. In terms of therapeutic strategies targeting oxidative stress, among the drugs currently used in clinical practice for AD treatment, memantine and donepezil demonstrate significant therapeutic efficacy and can improve the level of oxidative stress in AD patients. Some compounds with antioxidant effects (such asα-lipoic acid and melatonin) have shown certain potential in AD treatment research and can be used as dietary supplements to ameliorate AD symptoms. In addition, non-drug interventions such as calorie restriction and exercise have been proven to exerted neuroprotective effects and have a positive effect on the treatment of AD. By comprehensively utilizing the therapeutic characteristics of different signaling pathways, it is expected that more comprehensive multi-target combination therapy regimens and combined nanomolecular delivery systems will be developed in the future to bypass the blood-brain barrier, providing more effective therapeutic strategies for AD.

OBJECTIVE: To explore the accuracy of human-computer interaction software in identifying and locating type C1 distal radius fractures. METHODS: Based on relevant inclusion and exclusion criteria, 14 cases of type C1 distal radius fractures between September 2023 and March 2024 were retrospectively analyzed, comprising 3 males and 11 females(aged from 27 to 82 years). The data were assigned randomized identifiers. A senior orthopedic physician reviewed the films and measured the ulnar deviation angle, radial height, palmar inclination angle, intra-articular step, and intra-articular gap for each case on the hospital's imaging system. Based on the reduction standard for distal radius fractures, cases were divided into reduction group and non-reduction group. Then, the data were sequentially imported into a human-computer interaction intelligent software, where a junior orthopedic physician analyzed the same radiological parameters, categorized cases, and measured fracture details. The categorization results from the software were consistent with manual classifications (6 reduction cases and 8 non-reduction cases). For non-reduction cases, the software performed further analyses, including bone segmentation and fracture recognition, generating 8 diagnostic reports containing fracture recognition information. For the 6 reduction cases, the senior and junior orthopedic physicians independently analyzed the data on the hospital's imaging system and the AI software, respectively. Bone segments requiring reduction were identified, verified by two senior physicians, and measured for displacement and rotation along the X (inward and outward), Z (front and back), and Y (up and down) axes. The AI software generated comprehensive diagnostic reports for these cases, which included all measurements and fracture recognition details. RESULTS: Both the manual and AI software methods consistently categorized the 14 cases into 6 reduction and 8 non-reduction groups, with identical data distributions. A paired sample t-test revealed no statistically significant differences (P>0.05) between the manual and software-based measurements for ulnar deviation angle, radial ulnar bone height, palmar inclination angle, intra-articular step, and joint space. In fracture recognition, the AI software correctly identified 10 C-type fractures and 4 B-type fractures. For the 6 reduction cases, a total of 24 bone fragments were analyzed across both methods. After verification, it was found that the bone fragments identified by the two methods were consistent. A paired sample t-tests revealed that the identified bone fragments and measured displacement and rotation angles along the X, Y, and Z axes were consistent between the two methods. No statistically significant differences(P>0.05) were found between manual and software measurements for these parameters. CONCLUSION Human-computer interaction software employing AI technology demonstrated comparable accuracy to manual measurement in identifying and locating type C1 distal radius fractures on CT imaging.
Humans ; Male ; Female ; Radius Fractures/surgery* ; Middle Aged ; Adult ; Aged ; Aged, 80 and over ; Tomography, X-Ray Computed/methods* ; Retrospective Studies ; Software ; Wrist Fractures

Objective To explore the effect of Qingre Xiaoyanning tablets on chronic toxicity in SD rats.Methods A total of 120 SD rats were randomly divided into blank group(water)and experimental-L,-M,-H groups(2.63,5.25 and 10.50 g·kg 1 Qingre Xiaoyanning dry paste powder),with 30 rats per group.Four groups were administered continuously for 4 weeks with a recovery period of 4 weeks.SD rats were dissected as planned.The general condition,weight gain,hematological and biochemical indexes,major organ coefficients,macroscopic and microscopic tissue morphology were observed.Results There were no significant differences in the general condition,body mass growth,coagulation index and histopathology of rats between the experimental-L,-M,-H groups and the blank group.End of administration,the mean hemoglobin concentrations of experimental-H and blank groups were(370.70±3.78)and(365.90±5.77)g·L-1,glucose were(5.98±0.63)and(6.61±0.93)mmol·L-1,blood urea nitrogen(BUN)were(4.72±1.01)and(5.78±1.64)mmol·L-1,liver coefficients were 3.05±0.17 and 2.89±0.19,and the differences were statistically significant(P≤0.05,P≤0.01).Resumption of the final,direct bilirubin of experimental-L and blank groups were(0.38±0.18)and(0.19±0.18)pmol·L 1,BUN of experimental-M and blank groups were(4.45±0.56)and(5.65±1.16)mmol·L-1,and the differences were statistically significant(all P≤0.05).Conclusion Repeated administration of Qingre Xiaoyanning tablets showed no significant toxicity in SD rats.

Hepatocellular carcinoma(HCC)accounts for more than 80％of primary liver cancer,and the prognosis of patients is very poor due to factors such as untimely diagnosis,failure of chemotherapy and frequent recurrence.MicroRNA is a kind of endogenous noncoding RNA,which can inhibit the translation of messenger RNA in liver malignant tumors,regulate the proliferation,apoptosis,migration and invasion of HCC cells,and play an important role in the development of HCC.Therefore,the mechanism of miRNAs in the development of HCC and its research progress in diagnosis and treatment are deeply discussed.

Objective This study aimed to explore the relationships between residential greenness and cardiometabolic risk factors among rural adults in Xinjiang Uygur Autonomous Region(Xinjiang)and thus provide a theoretical basis and data support for improving the health of residents in this region. Methods We recruited 9,723 adult rural residents from the 51st Regiment of the Third Division of the Xinjiang Production and Construction Corps in September 2016.The normalized difference vegetation index(NDVI)was used to estimate residential greenness.The generalized linear mixed model(GLMM)was used to examine the association between residential greenness and cardiometabolic risk factors. Results Higher residential greenness was associated with lower cardiometabolic risk factor prevalence.After adjustments were made for age,sex,education,and marital status,for each interquartile range(IQR)increase of NDVI500-m,the risk of hypertension was reduced by 10.3%(OR=0.897,95%CI=0.836-0.962),the risk of obesity by 20.5%(OR=0.795,95%CI=0.695-0.910),the risk of type 2 diabetes by 15.1%(OR=0.849,95%CI=0.740-0.974),and the risk of dyslipidemia by 10.5%(OR=0.895,95%CI=0.825-0.971).Risk factor aggregation was reduced by 20.4%(OR=0.796,95%CI=0.716-0.885)for the same.Stratified analysis showed that NDVI500-m was associated more strongly with hypertension,dyslipidemia,and risk factor aggregation among male participants.The association of NDVI500-m with type 2 diabetes was stronger among participants with a higher education level.PM10 and physical activity mediated 1.9%-9.2%of the associations between NDVI500-m and obesity,dyslipidemia,and risk factor aggregation. Conclusion Higher residential greenness has a protective effect against cardiometabolic risk factors among rural residents in Xinjiang.Increasing the area of green space around residences is an effective measure to reduce the burden of cardiometabolic-related diseases among rural residents in Xinjiang.

Objective To study the acupoint selection and medication rules of acupoint application as an advantageous therapy in treating stroke.Methods The clinical literature from CNKI,Wanfang,CBMdisc,and other databases were searched,and Excel 2013 was used to count the frequency of disease,acupoint selection,and medication,and to analyze the acupoint selection rules using SPSS 25.0 and SPSS Modeler.Results Finally,523 articles were included in the literature,among which,the literature on the treatment of post-stroke constipation with acupoint patch was the most,and the related literature was further screened to analyze the acupoint selection and medication rules,and it was concluded that the most frequently applied acupoints of acupoint application for the treatment of post-stroke constipation were Shenque(RN8),Tianshu(ST25),Zhongwan(RN12),Zusanli(ST36),and the acupoints were mainly taken from conception vessel,stomach meridian and gallbladder meridian,and the core prescriptions were Shenque,Tianshu,Zhongwan,Qihai(RN6),Guanyuan(RN4),Zusanli.For the treatment of post-stroke constipation,acupoint application is often used with Rhei Radix et Rhizoma,Aurantii Fructus Immaturus,Cortex Magnoliae Officinalis,Natrii Sulfas Exsiccatus and Borneolum Syntheticum,among which,warm and cold nature drugs are mainly used,and bitter drugs are most frequently used among five flavors,and most frequently enter to the spleen meridian;and the core prescription is Rhei Radix et Rhizoma,Aurantii Fructus Immaturus,Cortex Magnoliae Officinalis,Natrii Sulfas Exsiccatus and Borneolum Syntheticum.Conclusion Acupoint application is an advantageous treatment for treating post-stroke constipation.The selection of acupoints was based on the conception vessel and stomach meridian,and the medication used were mainly focusing on those with functions of unblocking the bowels and directing qi downward,supplemented by strengthening the spleen and benefiting qi,warming the meridians and nourishing the blood.

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Acute liver injury (ALI) is one of the common severe diseases in clinic, which is characterized by redox imbalance and inflammatory storm. Untimely treatment can easily lead to liver failure and even death. Rosmarinic acid (RA) has been proved to have anti-inflammatory and antioxidant activity, but it is not clear how to protect ALI through antioxidation and inhibition of inflammation. Therefore, this study explored the therapeutic effect and molecular mechanism of RA on ALI through in vitro and in vivo experiments. In the mouse ALI model, the effects of RA on liver function and inflammatory indexes were studied, the pathological changes of liver were observed by HE, the effect of RA on reactive oxygen species in liver was detected by fluorescence method, and the level of F4/80 in liver tissue was detected by immunohistochemical method. The levels of thioredoxin interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3) and cysteinyl aspartate specific proteinase-1 (CASPASE-1) in liver tissue were measured by Western blot. All animal welfare and experimental procedures follow the rules of the Animal Ethics Committee of Southwest Minzu University. In vitro, human hepatoma cell line HepG2 was used to establish the model of oxidative damage induced by H₂O₂. The cell viability was detected by CCK-8 method. The level of interleukin-1β (IL-1β) in the supernatant was detected by enzyme linked immunosorbent assay (ELISA), the activity of lactatede hydrogenase (LDH) was detected by LDH kit, and the level of ROS was detected by fluorescence probe DCFH-DA labeling. The mRNA expression of Txnip, Nlrp3, Caspase 1, Il1β was detected by real-time fluorescence quantitative PCR (qPCR), and the protein levels of nuclear factor erythroid-2 related factor 2 (NRF2), TXNIP, NLRP3 and CASPASE-1 were measured by Western blot. The results showed that compared with the model group, the degree of liver swelling, tissue injury, liver function index in RA group were significantly lower than those in model group. And RA significantly attenuated the increases of ROS in liver tissue. The expression levels of TXNIP, NLRP3 and CASPASE-1 in liver tissue were significantly lower than those in model group. Additionally, RA inhibited the expressions of F4/80 and IL-1β. In vitro experiment, compared with model group, RA effectively inhibited the secretion of IL-1β and LDH. The level of ROS also decreased significantly. RA inhibited the mRNA expressions of Txnip, Caspase 1, Il1β. Furthermore, RA significantly increased the expression level of NRF2 protein in nucleus, and decreased the expression level of TXNIP and NLRP3 protein. Specifically, with the addition of ML385, the effect of RA on NRF2, TXNIP, NLRP3, CASPASE-1 protein expression was reversed. Collectively, these findings suggested that RA may inhibit the production of ROS by promoting NRF2 nuclear transfer, and then reduce the activation of NLRP3 inflammatory bodies by TXNIP, reduce cell death and inflammatory response to prevent the liver injury.

Objective CT scans combined with Mimics software were used to measure femoral offset(FO),rotation center height(RCH)and lower leg length discrepancy(LLD)following total hip arthroplasty(THA),and the relationship between FO,RCH and LLD after THA is discussed.Methods Retrospective analysis was performed on 40 patients with unilateral THA who met standard cases from October 2020 to June 2022.There were 21 males and 19 females,18 patients on the left side and 22 patients on the right side,aged range from 30 to 81 years old,with an average age of(58.90±14.13)years old,BMI ranged from 17.3 to 31.5 kg·m-2withan average of(25.3±3.4)kg·m-2.There were 30 cases of femoral head necrosis(Ficattype Ⅳ),2 cases of hip osteoarthritis(Tonnis type Ⅲ),2 cases of developmental hip dislocation combined with end-stage osteoarthritis(Crowe type Ⅲ),and 6 cases of femoral neck fracture(Garden type Ⅳ).Three-dimensional CT reconstruction of pelvis was taken preoperative and postoperative,and three-dimensional reconstruction model was established after processing by Mimics software.FO,RCH and LLD were measured on the model.The criteria for FO reconstruction were as follows:postoperative bi-lateral FO difference less than 5 mm;the standard for equal length of both lower limbs was as follows:postoperative LLD differ-ence less than 5 mm.Results Bilateral FO difference was positively correlated with LLD(r=0.744,P＜0.00l).Chi-square test was performed between the FO reconstructed group and the non-reconstructed eccentricity group:The results showed that the i-sometric ratio of lower limbs in the FO reconstructed group was significantly higher than that in the FO reconstructed group(x2=6.320,P=0.012).The bilateral RCH difference was significantly negatively correlated with LLD(r=-0.877,P＜0.001).There is a linear relationship between bilateral FO difference and bilateral RCH difference and postoperative LLD,and the lin-ear regression equation is satisfied:postoperative LLD=0.038x-0.099y+0.257(x:postoperative bilateral FO difference,y:post-operative bilateral RCH difference;Unit:cm),F=77.993,R2=0.808,P=0.009.Conclusion After THA,LLD increased with the increase of FO and decreased with the increase of RCH.The effect of lower limb isometric length can be obtained more easily by reconstruction of FO.There is a linear relationship between the bilateral FO difference and the bilateral RCH difference after THA and LLD,and the regression equation can provide a theoretical reference forjudging LLD.

Objective To analyze the hip joint biomechanies of the acetabular anatomical reconstruction and nonanatomi-cal reconstruction in total hip arthroplasty(THA)for Crowe type Ⅲ developmental dysplasia of the hip(DDH)by finite ele-ment method,which provided theoretical foundation and experimental basis for the anatomical acetabular reconstruction dur-ing THA in clinical practice.Methods One patient with left end-stage hip arthritis secondary to Crowe type Ⅲ DDH was se-lected in this study,who underwent total hip arthroplasty in the orthopedic department of the First Affiliated Hospital of Bengbu Medical College in April 2020.This patient was female,57 years old.The preoperative and postoperative three dimentional CT scan of the patient's pelvis were performed.Fourteen acetabular cup models with different anteversion,inclination and rotation center height were established in Mimics and 3-Matic software.The boundary and load conditions were set in Abaqus software.The Von Mises and stress distribution of the hip joint were calculated and observed.Results In the Crowe type Ⅲ DDH THA,if the hip rotation center was restored anatomically and the acetabular cup's inclination was set as 40°,the cup's anteversion var-ied from 5° to 25°,the lowest Von Mises value of acetabular cup and polyethylene liner occured in 20°anteversioin;if the hip rotation center was restored anatomically and the acetabular cup's anteversion was set as 15°,the cup's inclination varied from 35° to 55°,the lowest Von Mises value of acetabular cup and polyethylene liner occured in 35° inclination;if the acetabular cup's anteversion and inclination were set as 15°and 40°respectively,the up migration of hip rotaion center varied from 0 mm to 20 mm,the lowest Von Mises value of acetabular cup and polyethylene liner occured in 10 mm up migration.In all fourteen models,the Von Mises value of the acetabulum,acetabulum cup and polyethylene liner were lowest when the acetabular cup's anteversion and inlcination were 15°,35° respectively,as well as the rotation center was restored anatomically.Conclusion In total hip arthroplasty for Crowe type Ⅲ DDH,the anatomical restoration of hip rotation center with 15° anteversion and 35° in-clination of the acetabular cup are suggested,bone graft above the acetabular cup and additional screws are recommended si-multaneously to further reduce the Von Mises of hip joint.